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BACKGROUND Chronic musculoskeletal pain ( CMP ) is a major health problem , accounting for approximately one-quarter of general practice ( GP ) consultations in the United Kingdom ( UK ) . Exercise and physical activity is beneficial for the most common types of CMP , such as back and knee pain . However , poor adherence to exercise and physical activity may limit long-term effectiveness . OBJECTIVES To assess the effects of interventions to improve adherence to exercise and physical activity for people with chronic musculoskeletal pain . SEARCH STRATEGY We search ed the trials registers of relevant Cochrane Review Groups . In addition , we search ed the Cochrane Central Register of Controlled Trials , MEDLINE , EMBASE , CINAHL , AMED , PsycINFO , Science Citation Index and Social Science Citation Index and reference lists of articles to October 2007 . We consulted experts for unpublished trials . SELECTION CRITERIA R and omised or quasi-r and omised trials evaluating interventions that aim ed to improve adherence to exercise and physical activity in adults with pain for three months and over in the axial skeleton or large peripheral joints . DATA COLLECTION AND ANALYSIS Two of the four authors independently assessed the quality of each included trial and extracted data . We contacted study authors for missing information . MAIN RESULTS We included 42 trials with 8243 participants , mainly with osteoarthritis and spinal pain . Methods used for improving and measuring adherence in the included trials were inconsistent . Two of the 17 trials that compared different types of exercise showed positive effects , suggesting that the type of exercise is not an important factor in improving exercise adherence . Six trials studied different methods of delivering exercise , such as supervising exercise sessions , refresher sessions and audio or videotapes of the exercises to take home . Of these , five trials found interventions improved exercise adherence . Four trials evaluated specific interventions targeting exercise adherence ; three of these showed a positive effect on exercise adherence . In eight trials study ing self-management programmes , six improved adherence measures . One trial found grade d activity was more effective than usual care for improving exercise adherence . Cognitive behavioural therapy was effective in a trial in people with whiplash-associated disorder , but not in trials of people with other CMP . In the trials that showed a positive effect on adherence , association between clinical outcomes and exercise adherence was conflicting . AUTHORS ' CONCLUSIONS Interventions such as supervised or individualised exercise therapy and self-management techniques may enhance exercise adherence . However , high- quality , r and omised trials with long-term follow up that explicitly address adherence to exercises and physical activity are needed . A st and ard vali date d measure of exercise adherence should be used consistently in future studies
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"Abstract Objective To estimate the effect of adding exercise classes , spinal manipulation delivered in NHS or private premises , or manipulation followed by exercise to “ best care ” in general practice for patients consulting with back pain . Fig 1 Progress of the UK BEAM trial Design Pragmatic r and omised trial with factorial design . Setting 181 general practice s in Medical Research Council General Practice Research Framework ; 63 community setting s around 14 centres across the United Kingdom . Participants 1334 patients consulting their general practice s about low back pain . Main outcome measures Scores on the Rol and Morris disability question naire at three and 12 months , adjusted for centre and baseline scores . Results All groups improved over time . Exercise improved mean disability question naire scores at three months by 1.4 ( 95 % confidence interval 0.6 to 2.1 ) more than “ best care . ” For manipulation the additional improvement was 1.6 ( 0.8 to 2.3 ) at three months and 1.0 ( 0.2 to 1.8 ) at 12 months . For manipulation followed by exercise the additional improvement was 1.9 ( 1.2 to 2.6 ) at three months and 1.3 ( 0.5 to 2.1 ) at 12 months . No significant differences in outcome occurred between manipulation in NHS premises and in private premises . No serious adverse events occurred . Conclusions Relative to “ best care ” in general practice , manipulation followed by exercise achieved a moderate benefit at three months and a small benefit at 12 months ; spinal manipulation achieved a small to moderate benefit at three months and a small benefit at 12 months ; and exercise achieved a small benefit at three months but not 12 months",
"OBJECTIVE To compare short-term and long-term effectiveness of the Arthritis Self-Help Course ( ASHC ) and the Chronic Disease Self-Management Program ( CDSMP ) for persons with arthritis concerning health care use , health-related quality of life , health behaviors , and arthritis self-efficacy . METHODS Forty-eight workshops were r and omized to the ASHC ( n = 26 ) or CDSMP ( n = 22 ) . A total of 416 individuals , including 365 African Americans , participated . The mean age for each group was 64 years , mean years of education was 11.7 , mean number of chronic conditions was 4 , and 75 - 80 % of participants in each group were female . Multivariate statistical tests were used to assess effectiveness within and between programs for all workshop participants and African Americans . RESULTS At 4 months all ASHC participants including African Americans , had significant improvements ( P self-efficacy , stretching and strengthening exercises , aerobic exercises , and general health . All CDSMP participants had statistically significant improvements in self-efficacy , disability , pain , and general health . African American CDSMP participants showed statistically significant improvements in general health . Trends toward improvement ( P = 0.051 - 0.100 ) were shown in 5 variables among African American CDSMP participants and in 4 variables among all CDSMP participants . Statistically significant differences between the 2 programs at 4 months were seen in pain and disability in both groups . The CDSMP produced stronger results . Significant results at 1 year within and between programs were minimal for both groups . CONCLUSION When population s with arthritis and multiple comorbid conditions are targeted , the CDSMP may be most cost effective",
"AIM This paper is a report of a study to assess the effect of an adapted arthritis self-management programme with an added focus on exercise practice among osteoarthritic knee sufferers . BACKGROUND Osteoarthritis of the knee is a major source of loss of function in older people . Previous studies have found self-management programmes to be effective in increasing arthritis self-efficacy and in mastery of self-management practice . METHOD A r and omized control trial was carried out from December 2002 to May 2003 and 120 participants ( 65.9 % , including 67 in intervention group and 53 in control group ) completed the 16-week postintervention assessment s. Outcome measures included arthritis self-efficacy , use of self-management techniques , pain intensity and daily activity . FINDINGS At 16 weeks , there was a ' statistically ' significant improvement in the arthritis self-efficacy level ( P self-management skills , i.e. use of cold and hot compresses , in two of three joint protective practice s ( P duration of light exercise practice ( P current arthritis pain ( P ability to perform daily activities ( P sufferers of chronic conditions to live with their illness",
"In a prospect i ve trial , 222 adults with low-back pain of at least 2 weeks ' duration in a Health Maintenance Organization ( HMO ) were r and omly assigned to usual care ( UC ) , a 4-hour back school psychoeducational session ( LBS ) , or the same back school plus a 1-year “ compliance package ” program design ed to encourage appropriate self-management for back pain ( CP ) . Sixty-four percent of LBS and CP subjects attended their back school sessions . Follow-up measurement of pain level ( using the Visual Analogue Scale ) , functional status ( using the Sickness Impact Profile ) , and various other indicators of health status showed no measurable effect of either treatment condition ( LBS or CP ) compared with UC at 3 , 6 , 12 , and 18 months after entry into the study . Initial disability resolved by 3 months in most patients , and a minority of subjects ( 10–15 % ) showed residual or recurrent functional Impairment 1 year after entry . Health care utilization tended to be slightly higher after intervention In the CP group . With or without follow-up encouragement , back school instructions given in a single 4-hour session had no measurable impact on the comfort or functional status of the majority of patients with new onset back pain in this HMO",
"OBJECTIVE To determine whether high exercise adherence improved physical function among older adults with knee osteoarthritis ( OA ) who were overweight or obese . METHODS Associations between exercise adherence , changes in 6-minute walking distance in meters , and self-reported disability ( Western Ontario and McMaster Universities Osteoarthritis Index function subscale ) after 6 and 18 months were examined among an Arthritis , Diet , and Activity Promotion Trial sub sample ( n = 134 ) using multiple linear regression models . RESULTS Higher exercise adherence was associated with greater improvements in 6-minute walking distance after 6 and 18 months and in disability after 6 months . Pain and body mass index ( BMI ) contributed , to some extent , to explaining the link between exercise adherence and changes in physical performance and self-reported disability . CONCLUSION Higher exercise adherence is associated with improved physical function in overweight and obese older adults with knee OA . This indicates that promoting adherence is clinical ly relevant when prescribing exercise regimens that also focus on decreasing pain and BMI",
"Background This study examined the impact of a home-based self-management intervention for housebound older adults with arthritis on the adoption of health behaviors . The moderating role of socio-demographic , psychological , and physical characteristics in the process of behavior change was also investigated . Methods Participants were 113 older adult women ( n = 102 ) and men ( n = 11 ) with osteoarthritis ( OA ) or rheumatoid arthritis ( RA ) who were r and omly assigned to experimental ( n = 68 ) or wait list control ( n = 45 ) groups . Participants were interviewed using st and ardized question naires at baseline , pre-intervention , and post-intervention . Results Adjusted multilevel modeling analyses indicated that from pre to post intervention , experimental participants significantly increased their weekly frequency of exercise and relaxation activities . Socioeconomic status and depression played a moderating role in this change for exercise with larger effects occurring among more privileged , non-depressed participants . Conclusion We conclude that a self-management intervention can successfully improve involvement in exercise and relaxation among housebound older adults with arthritis",
"PURPOSE Tai Chi exercise , an ancient Chinese martial art , has drawn more and more attention for its health benefits . The purpose of the study was to identify the effects of a Sun-style Tai Chi exercise on arthritic symptoms ( joint pain and stiffness ) , motivation for performing health behaviors , and the performance of health behaviors among older women with osteoarthritis . METHODS Total of 72 women with the mean age of 63 years old were recruited from out patients clinic or public health centers according to the inclusion criteria and assigned r and omly to either the Tai Chi exercise group or the control . A Sun-style Tai Chi exercise has been provided three times a week for the first two weeks , and then once a week for another 10 weeks . In 12 weeks of study period , 22 subjects in the Tai Chi exercise group and 21 subjects in the control group completed the posttest measure with the dropout rate of 41 % . Outcome variables included arthritic symptoms measured by K-WOMAC , motivation for health behavior , and health behaviors . RESULTS At the completion of the 12 week Tai Chi exercise , the Tai Chi group perceived significantly less joint pain ( t=-2.19 , p=0.03 ) and stiffness ( t=-2.24 , p=0.03 ) , perceived more health benefits ( t=2.67 , p=0.01 ) , and performed better health behaviors ( t=2.35 , p=0.02 ) , specifically for diet behavior ( t=2.06 , p=0.04 ) and stress management ( t=2.97 , p=0.005 ) . CONCLUSION A Sun-style Tai Chi exercise was found as beneficial for women with osteoarthritis to reduce their perceived arthritic symptoms , improve their perception of health benefits to perform better health behaviors",
"Abstract Practice guidelines recommend various types of exercise and manipulative therapy for chronic back pain but there have been few head‐to‐head comparisons of these interventions . We conducted a r and omized controlled trial to compare effects of general exercise , motor control exercise and manipulative therapy on function and perceived effect of intervention in patients with chronic back pain . Two hundred and forty adults with non‐specific low back pain ⩾3 months were allocated to groups that received 8 weeks of general exercise , motor control exercise or spinal manipulative therapy . General exercise included strengthening , stretching and aerobic exercises . Motor control exercise involved retraining specific trunk muscles using ultrasound feedback . Spinal manipulative therapy included joint mobilization and manipulation . Primary outcomes were patient‐specific function ( PSFS , 3–30 ) and global perceived effect ( GPE , −5 to 5 ) at 8 weeks . These outcomes were also measured at 6 and 12 months . Follow‐up was 93 % at 8 weeks and 88 % at 6 and 12 months . The motor control exercise group had slightly better outcomes than the general exercise group at 8 weeks ( between‐group difference : PSFS 2.9 , 95 % CI : 0.9–4.8 ; GPE 1.7 , 95 % CI : 0.9–2.4 ) , as did the spinal manipulative therapy group ( PSFS 2.3 , 95 % CI : 0.4–4.2 ; GPE 1.2 , 95 % CI : 0.4–2.0 ) . The groups had similar outcomes at 6 and 12 months . Motor control exercise and spinal manipulative therapy produce slightly better short‐term function and perceptions of effect than general exercise , but not better medium or long‐term effects , in patients with chronic non‐specific back pain",
"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",
"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",
"Background The treatment of non-specific chronic low back pain is often based on three different models regarding the development and maintenance of pain and especially functional limitations : the deconditioning model , the cognitive behavioral model and the biopsychosocial model . There is evidence that rehabilitation of patients with chronic low back pain is more effective than no treatment , but information is lacking about the differential effectiveness of different kinds of rehabilitation . A direct comparison of a physical , a cognitive-behavioral treatment and a combination of both has never been carried out so far . Methods The effectiveness of active physical , cognitive-behavioral and combined treatment for chronic non-specific low back pain compared with a waiting list control group was determined by performing a r and omized controlled trial in three rehabilitation centers . Two hundred and twenty three patients were r and omized , using concealed block r and omization to one of the following treatments , which they attended three times a week for 10 weeks : Active Physical Treatment ( APT ) , Cognitive-Behavioral Treatment ( CBT ) , Combined Treatment of APT and CBT ( CT ) , or Waiting List ( WL ) . The outcome variables were self-reported functional limitations , patient 's main complaints , pain , mood , self-rated treatment effectiveness , treatment satisfaction and physical performance including walking , st and ing up , reaching forward , stair climbing and lifting . Assessment s were carried out by blinded research assistants at baseline and immediately post-treatment . The data were analyzed using the intention-to-treat principle . Results For 212 patients , data were available for analysis . After treatment , significant reductions were observed in functional limitations , patient 's main complaints and pain intensity for all three active treatments compared to the WL . Also , the self-rated treatment effectiveness and satisfaction appeared to be higher in the three active treatments . Several physical performance tasks improved in APT and CT but not in CBT . No clinical ly relevant differences were found between the CT and APT , or between CT and CBT . Conclusion All three active treatments were effective in comparison to no treatment , but no clinical ly relevant differences between the combined and the single component treatments were found",
"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",
"BACKGROUND Diary recording of pain and disabling activities in osteoarthritis ( OA ) is widely recommended , but , to our knowledge , its impact on symptoms has not been investigated . Exercise programmes have been shown to be effective when patients are closely supervised by nurses or physiotherapists ; however , data are lacking on the efficacy of an unsupervised home based exercise regimen in patients with OA . OBJECTIVES To evaluate the clinical efficacy of patient administered assessment tools and an unsupervised home based exercise programme alone or in combination in patients with OA . METHODS The study was a 24 week , open cluster r and omised controlled trial with a factorial design . Rheumatologists ( n = 867 ) were assigned to four groups according to the treatment given : st and ardised tools ( ST ; n = 220 ) , exercises ( EX ; n = 213 ) , both tools and exercises ( ST+EX ; n = 213 ) , or usual care ( n = 221 ) . Each rheumatologist was to enroll four patients who met the American College of Rheumatology criteria for OA ( three with knee OA , one with hip OA ) . \" Tools \" consisted of weekly recording of pain and disabling activities in a diary . A home based exercise programme was performed daily at least four times per week with the aid of videotape and booklet . In addition to exercise and assessment , all patients received 12.5 mg or 25 mg of the non-steroidal anti-inflammatory drug rofecoxib once daily . Outcome variables were : pain ( measured on a visual analogue scale , 0 - 100 ) ; Western Ontario and McMaster Universities Osteoarthritis Index , function subscale ( 0 - 100 ) ; and patient assessment of the quality of care ( 0 - 100 ) . RESULTS Overall , 2957 patients with OA ( 2216 knee , 741 hip ) were included . After 24 weeks , both pain and function improved in the ST , EX , ST+EX , and usual care groups ( mean ( SD ) -17 ( 27 ) , -20 ( 29 ) , -15 ( 27 ) , -19 ( 29 ) ; and -11 ( 19 ) , -12 ( 19 ) , -10 ( 19 ) , -11 ( 20 ) , respectively ) , without significant differences between groups . However , patients in the EX and ST+EX groups were more likely to agree that their rheumatologist had done his best to preserve their functional and physical activities . CONCLUSION Although patients ' assessment s favoured the exercise programme , results from this study failed to demonstrate a short term symptomatic effect of the two non-pharmacological treatments ( weekly recording of condition and exercise ) in patients with OA concurrently receiving nonsteroidal anti-inflammatory drugs",
"BACKGROUND Chronic pain is recognised as an important problem in the community but our underst and ing of the epidemiology of chronic pain remains limited . We undertook a study design ed to quantify and describe the prevalence and distribution of chronic pain in the community . METHODS A r and om sample of 5036 patients , aged 25 and over , was drawn from 29 general practice s in the Grampian region of the UK and surveyed by a postal self-completion question naire . The question naire included case-screening questions , a question on the cause of the pain , the chronic pain grade question naire , the level of expressed needs question naire , and sociodemographic questions . FINDINGS 3605 question naires were returned completed . 1817 ( 50.4 % ) of patients self reported chronic pain , equivalent to 46.5 % of the general population . 576 reported back pain and 570 reported arthritis ; these were the most common complaints and accounted for a third of all complaints . Backward stepwise logistic-regression modelling identified age , sex , housing tenure , and employment status as significant predictors of the presence of chronic pain in the community . 703 ( 48.7 % ) individuals with chronic pain had the least severe grade of pain , and 228 ( 15.8 % ) the most severe grade . Of those who reported chronic pain , 312 ( 17.2 % ) reported no expressed need , and 509 ( 28.0 % ) reported the highest expressed need . INTERPRETATION Chronic pain is a major problem in the community and certain groups within the population are more likely to have chronic pain . A detailed underst and ing of the epidemiology of chronic pain is essential for efficient management of chronic pain in primary care",
"Background Chronic pain is a common and frequently disabling problem in older adults . Clinical guidelines emphasize the need to use multimodal therapies to manage persistent pain in this population . Pain self-management training is a multimodal therapy that has been found to be effective in young to middle-aged adult sample s. This training includes education about pain as well as instruction and practice in several management techniques , including relaxation , physical exercise , modification of negative thoughts , and goal setting . Few studies have examined the effectiveness of this therapy in older adult sample s. Methods / Design This is a r and omized , controlled trial to assess the effectiveness of a pain self-management training group intervention , as compared with an education-only control condition . Participants are recruited from retirement communities in the Pacific Northwest of the United States and must be 65 years or older and experience persistent , noncancer pain that limits their activities . The primary outcome is physical disability , as measured by the Rol and -Morris Disability Question naire . Secondary outcomes are depression ( Geriatric Depression Scale ) , pain intensity ( Brief Pain Inventory ) , and pain-related interference with activities ( Brief Pain Inventory ) . R and omization occurs by facility to minimize cross-contamination between groups . The target sample size is 273 enrolled , which assuming a 20 % attrition rate at 12 months , will provide us with 84 % power to detect a moderate effect size of .50 for the primary outcome . Discussion Few studies have investigated the effects of multimodal pain self-management training among older adults . This r and omized controlled trial is design ed to assess the efficacy of a pain self-management program that incorporates physical and psychosocial pain coping skills among adults in the mid-old to old-old range",
"Study Design . The study was carried out as an open , r and omized , multicenter , parallel‐group study with an observation period of 12 months . Four Norwegian physiotherapy institutes took part . Patients were subsequently followed for 12 months of home exercise on their own , without the supervision of a physiotherapist . Objectives . 1 ) To investigate and compare the effects of two different exercise programs on low back problems in patients after a 1‐year training program under the supervision of a physiotherapist . 2 ) To investigate the effect supervision by , and motivation from , physiotherapists has on training compliance and efficacy . Summary of Background Data . After ordinary physiotherapy treatment for low back problems , patients were r and omly allocated either to a conventional training program design ed by physiotherapists or to a training program using a new Norwegian‐developed training apparatus called the TerapiMaster . The study included 153 patients with low back problems , all of whom had been referred to physiotherapy by their general practitioners . One hundred twenty‐six patients were followed for an additional 12 months when performing home exercise programs on their own . Methods . Monitoring patient satisfaction with the training program , compliance with the program , and absenteeism from work during the training period . Results . Patient satisfaction with both training programs was high , with about 83 % of participating patients completing the study in accordance with the protocol . Mean absenteeism ( SD ) during the preceding year totaled 82.5 days ( 19.8 ) in the conventional training group and 61.6 days ( 14.7 ) in the TerapiMaster group . Significant reductions to 17.2 days ( 6.0 ) and 15.4 days ( 5.3 ) in the two groups , respectively , were recorded during the training period , corresponding to a 75 % to 80 % reduction compared with the preceding 1‐year period . Mean absenteeism showed a further significant decline during the 12‐month period without supervised training . The average values were 9.9 days ( 3.2 ) for conventional training and 9.3 days ( 3.1 ) for the TerapiMaster , respectively . Conclusions . Both exercise programs reduced absenteeism significantly ( 75‐80 % ) . No difference in the effects of the two different programs was discernible . Regular follow‐up through encouragement and variation in the training programs appear to be important factors for motivating patients to adhere to regular exercise programs for low back problems . This thesis was corroborated by the 12‐month study of unsupervised exercise",
"Abstract Objective To determine the effectiveness of dynamic muscle training and relaxation training for chronic neck pain . Design R and omised controlled trial . Setting Five occupational healthcare centres , Tampere , Finl and . Participants 393 female office workers ( mean age 45 years ) with chronic non-specific neck pain r and omly assigned to 12 weeks of dynamic muscle training ( n = 135 ) or relaxation training ( n = 128 ) , plus one week of reinforcement training six months after baseline ; or ordinary activity ( control group ; n = 130 ) . Main outcome measure Change in intensity of neck pain at three , six , and 12 months . Results No significant difference was found in neck pain between the groups at follow up . However , the range of motion for cervical rotation and lateral flexion increased more in the training groups than in the control group . Conclusions Dynamic muscle training and relaxation training do not lead to better improvements in neck pain compared with ordinary activity",
"Context Yoga combines exercise with achieving a state of mental focus through breathing . In the United States , 1 million people practice yoga for low back pain . Contribution The authors recruited patients who had a recent primary care visit for low back pain and r and omly assigned 101 to yoga or conventional exercise or a self-care book . Patients in the yoga and exercise groups reported good adherence at 26 weeks . Compared with self-care , symptoms were milder and function was better with yoga . The exercise group had intermediate outcomes . Symptoms improved between 12 and 26 weeks only with yoga . Implication s Yoga was a more effective treatment for low back pain than a self-care book . The Editors Most treatments for chronic low back pain have modest efficacy at best ( 1 ) . Exercise is one of the few proven treatments for chronic low back pain ; however , its effects are often small , and no form has been shown to be clearly better than another ( 2 - 5 ) . Yoga , which often couples physical exercise with breathing , is a popular alternative form of mindbody therapy . An estimated 14 million Americans practice d yoga in 2002 ( 6 ) , including more than 1 million who used it as a treatment for back pain ( 7 , 8) . Yoga may benefit patients with back pain simply because it involves exercise or because of its effects on mental focus . We found no published studies in western biomedical literature that evaluated yoga for chronic low back pain ; therefore , we design ed a clinical trial to evaluate its effectiveness and safety for this condition . Methods Study Design and Setting This r and omized , controlled trial compared the effects of yoga classes with conventional exercise classes and with a self-care book in patients with low back pain that persisted for at least 12 weeks . The study was conducted at Group Health Cooperative , a nonprofit , integrated health care system with approximately 500000 enrollees in Washington State and Idaho . The Group Health Cooperative institutional review board approved the study protocol , and all study participants gave oral informed consent before the eligibility screening and written consent before the baseline interview and r and omization . Patients Patients from Group Health Cooperative were recruited for 12-week sessions of classes that were conducted between June and December 2003 . We mailed letters describing the study to 6913 patients between 20 and 64 years of age who had visited a primary care provider for treatment of back pain 3 to 15 months before the study ( according to electronic visit records ) . We also advertised the study in the health plan 's consumer magazine . Patients were informed that we were comparing 3 approaches for the relief of back pain and that each was design ed to help reduce the negative effects of low back pain on people 's lives . A research assistant telephoned patients who returned statements of interest to assess their eligibility . After we received their signed informed consent forms , eligible patients were telephoned again for collection of baseline data and r and omization to treatment . We excluded individuals whose back pain was complicated ( for example , sciatica , previous back surgery , or diagnosed spinal stenosis ) , potentially attributable to specific underlying diseases or conditions ( for example , pregnancy , metastatic cancer , spondylolisthesis , fractured bones , or dislocated joints ) , or minimal ( rating of less than 3 on a bothersomeness scale of 0 to 10 ) . We also excluded individuals who were currently receiving other back pain treatments or had participated in yoga or exercise training for back pain in the past year , those with a possible disincentive to improve ( such as patients receiving workers ' compensation or those involved in litigation ) , and those with unstable medical or severe psychiatric conditions or dementia . Patients who had contraindications ( for example , symptoms consistent with severe disk disease ) or schedules that precluded class participation , those who were unwilling to practice at home , or those who could not speak or underst and English were also excluded . R and omization Protocol Participants were r and omly assigned to participate in yoga or exercise classes or to receive the self-care book . We r and omly generated treatment assignments for each class series by using a computer program with block sizes of 6 or 9 . A research er who was not involved in patient recruitment or r and omization placed the assignments in opaque , sequentially numbered envelopes , which were stored in a locked filing cabinet until needed for r and omization . Interventions The yoga and exercise classes developed specifically for this study consisted of 12 weekly 75-minute classes design ed to benefit people with chronic low back pain . In addition to attending classes held at Group Health facilities , participants were asked to practice daily at home . Participants received h and outs that described home practice s , and yoga participants received auditory compact discs to guide them through the sequence of postures with the appropriate mental focus ( examples of postures are shown in the Appendix Figure ) . Study participants retained access to all medical care provided by their insurance plan . Appendix Figure . Yoga postures Yoga We chose to use viniyoga , a therapeutically oriented style of yoga that emphasizes safety and is relatively easy to learn . Our class instructor and a senior teacher of viniyoga , who has + written a book about its therapeutic uses ( 9 ) , design ed the yoga intervention for patients with back pain who did not have previous yoga experience . Although all the sessions emphasized use of postures and breathing for managing low back symptoms , each had a specific focus : relaxation ; strength-building , flexibility , and large-muscle movement ; asymmetric poses ; strengthening the hip muscles ; lateral bending ; integration ; and customizing a personal practice . The postures were selected from a core of 17 relatively simple postures , some with adaptations ( Appendix Table ) , and the sequence of the postures in each class was performed according to the rudiments of viniyoga ( 9 ) . Each class included a question - and -answer period , an initial and final breathing exercise , 5 to 12 postures , and a guided deep relaxation . Most postures were not held but were repeated 3 or 6 times . Exercise Because we could not identify a clearly superior form of therapeutic exercise for low back pain from the literature , a physical therapist design ed a 12-session class series that was 1 ) different from what most participants would have probably experienced in previous physical therapy sessions ( to maximize adherence ) and 2 ) similar to the yoga classes in number and length . We included a short educational talk that provided information on proper body mechanics , the benefits of exercise and realistic goal setting , and overcoming common barriers to developing an exercise routine ( for example , fear ) . Each session began with the educational talk ; feedback from the previous week ; simple warm-ups to increase heart rate ; and repetitions of a series of 7 aerobic exercises and 10 strengthening exercises that emphasized leg , hip , abdominal , and back muscles . Over the course of the 12-week series , the number of repetitions of each aerobic and strength exercise increased from 8 to 30 in increments of 2 . The strengthening exercises were followed by 12 stretches for the same muscle groups ; each stretch was held for 30 seconds . Classes ended with a short , unguided period of deep , slow breathing . Self-Care Book Participants were mailed a copy of The Back Pain Helpbook ( 10 ) , an evidence -based book that emphasized such self-care strategies as adoption of a comprehensive fitness and strength program , appropriate lifestyle modification , and guidelines for managing flare-ups . Although we did not provide any instructions for using the book , many of the chapters concluded with specific action items . Outcome Measures Interviewers who were masked to the treatment assignments conducted telephone interviews at baseline and at 6 , 12 , and 26 weeks after r and omization . The baseline interview collected information regarding sociodemographic characteristics , back pain history , and the participant 's level of knowledge about yoga and exercise . Participants were asked to describe their current pain and to rate their expectations for each intervention . The primary outcomes were back-related dysfunction and symptoms , and the primary time point of interest was 12 weeks . We used the modified Rol and Disability Scale ( 11 ) to measure patient dysfunction by totaling the number of positive responses to 23 questions about limitations of daily activities that might arise from back pain . This scale has been found to be valid , reliable , and sensitive to change ( 12 - 14 ) ; research ers estimate that the minimum clinical ly significant difference on the Rol and scale ranges from 2 to 3 points ( 13 , 15 ) . Participants rated how bothersome their back pain had been during the previous week on an 11-point scale , in which 0 represented not at all bothersome and 10 represented extremely bothersome ; a similar measure demonstrated substantial construct validity in earlier research ( 13 ) . Estimates of the minimum clinical ly significant difference on the bothersomeness scale were approximately 1.5 points ( 16 , 17 ) . Secondary outcome measures were general health status , which we assessed by conducting the Short Form-36 Health Survey ( 18 ) ; degree of restricted activity as determined by patient responses to 3 questions ( 19 ) ; and medication use . After all outcomes data were collected , we asked questions related to specific interventions ( for example , Did you practice at home ? ) . At the 12-week interview , we asked class participants about any pain or substantial discomfort they experienced as a result of the classes . We assessed adherence to the home practice recommendations by asking class participants to complete weekly home practice logs and by asking about home practice during the follow-up",
"We conducted a pilot study to evaluate a practical exercise program for elderly people with chronic musculo-skeletal pain . Thirty-three subjects ( mean age , 73 years ; 69 % back pain ; 24 % knee pain ; 9 % hip pain ) were r and omly assigned to one of three groups . Group 1 received a 6-week supervised program of walking . Group 2 received a pain education program that included instruction and demonstration of use of heat , cold , massage , relaxation and distraction . Group 3 received usual care . Outcomes including pain , self-reported health and functional status , and performance-based measures of functional status were evaluated at baseline , at two weeks and at eight weeks ( end of study ) . Attendance was 100 % for the education sessions and 93 % for walking sessions . No injuries were sustained . Both intervention groups demonstrated significant improvements in pain ( p performance-based measures of functional status ( p patient education and fitness walking can improve overall pain management and related functional limitations among elderly people with chronic musculo-skeletal pain",
"Conducted a treatment- outcome study to investigate the effectiveness of behavioral ( BT ) or physical therapy ( PT ) for treating chronic low back pain ( CLBP ) . Thirteen patients received BT ; 12 patients received PT . All patients had at least a 6-month history of seeking treatment of CLBP . Prior to treatment patients were assessed in four principal areas of functioning : ( 1 ) physical abilities ; ( 2 ) current physical functioning ; ( 3 ) psychological and psychosocial functioning ; and ( 4 ) pain intensity and pain perception . Treatments were conducted in a group ( 5 - 8 patients ) outpatient setting . Both BT and PT met for 10 weekly 2-hour sessions . BT was design ed to address the environmental , social , and emotional influences of the pain experience , depression , and decreased activity from CLBP . PT was based upon traditional rehabilitation theory and was design ed to improve low back function . The posttreatment results showed general improvement for patients in both groups , but few treatment-specific differences in outcome measures ",
"Background Neck and upper limb symptoms are frequently reported by computer workers . Work style interventions are most commonly used to reduce work-related neck and upper limb symptoms but lifestyle physical activity interventions are becoming more popular to enhance workers health and reduce work-related symptoms . A combined approach targeting work style and lifestyle physical activity seems promising , but little is known on the effectiveness of such combined interventions . Methods / design The RSI@Work study is a r and omised controlled trial that aims to assess the added value of a lifestyle physical activity intervention in addition to a work style intervention to reduce neck and upper limb symptoms in computer workers . Computer workers from seven Dutch companies with frequent or long-term neck and upper limb symptoms in the preceding six months and /or the last two weeks are r and omised into three groups : ( 1 ) work style group , ( 2 ) work style and physical activity group , or ( 3 ) control group . The work style intervention consists of six group meetings in a six month period that take place at the workplace , during work time , and under the supervision of a specially trained counsellor . The goal of this intervention is to stimulate workplace adjustment and to improve body posture , the number and quality of breaks and coping behaviour with regard to high work dem and s. In the combined ( work style and physical activity ) intervention the additional goal is to increase moderate to heavy physical activity . The control group receives usual care . Primary outcome measures are degree of recovery , pain intensity , disability , number of days with neck and upper limb symptoms , and number of months without neck and upper limb symptoms . Outcome measures will be assessed at baseline and six and 12 months after r and omisation . Cost-effectiveness of the group meetings will be assessed using an employer 's perspective . Discussion This study will be one of the first to assess the added value of a lifestyle physical activity intervention in addition to a work style intervention in reducing neck and upper limb symptoms of computer workers . The results of the study are expected in 2007",
"BACKGROUND People with osteoarthritis ( OA ) of the knee experience pain and deconditioning that lead to disability . This study challenged the clinical belief that repetitive lower extremity exercise is not indicated in persons with knee OA . The effects of high-intensity and low-intensity stationary cycling on functional status , gait , overall and acute pain , and aerobic capacity were examined . METHODS Thirty-nine adults ( 71+/-6.9 years old ) with complaints of knee pain and diagnosis of OA were r and omized to either a high-intensity ( 70 % heart rate reserve [ HRR ] ) or low-intensity ( 40 % HRR ) exercise group for 10 weeks of stationary cycling . Participants cycled for 25 minutes , 3 times per week . Before and after the exercise intervention they completed the Arthritis Impact Measurement Scale 2 for overall pain assessment , underwent timed chair rise , 6-minute walk test , gait , and grade d exercise treadmill tests . Acute pain was reported daily with a visual analog scale and the Western Ontario and McMaster Universities Osteoarthritis Index scale . RESULTS Analysis of variance revealed that participants in both groups significantly improved in the timed chair rise , in the 6-minute walk test , in the range of walking speeds , in the amount of overall pain relief , and in aerobic capacity . No differences between groups were found . Daily pain reports suggested that cycling did not increase acute pain in either group . CONCLUSIONS Cycling may be considered as an alternative exercise modality for patients with knee OA . Low-intensity cycling was as effective as high-intensity cycling in improving function and gait , decreasing pain , and increasing aerobic capacity",
"We conducted a pilot study of a nurse-run telephone self-management programme for elderly people with osteoarthritis ( OA ) . Thirty-two subjects , aged 60 years or more , with a diagnosis of OA were recruited from two hospital rheumatology clinics and were r and omized to a control or intervention group . The intervention group received six weekly mailings of OA health education modules , a relaxation audio-tape and six weekly 45 min follow-up telephone self-management sessions . There was a 100 % compliance rate in the intervention group , and all subjects completed baseline and three-month interviews ; one subject in each group was lost to six-month follow-up . There were no significant differences in self-management between the control and intervention groups . However , at three months there were improvements in the intervention group ( relative to baseline ) on some outcome measures . The results suggest that the telephone may be a useful tool for reinforcing health-promoting activities for patients",
"BACKGROUND The prescription of exercise as a conservative treatment for lumbar pain is frequent and seems effective for the chronic cases of nonspecific low back pain . However , there is no evidence favoring one type of exercise over another . Often , exercise programs are prescribed without adequate evaluation of the individual characteristics like posture , muscular force , and extensibility . Patients with totally different causes of low back pain will often be given the same type of exercises . OBJECTIVE Our objective was to compare the effectiveness of 2 home exercise programs in decreasing disability and pain related to subacute and chronic nonspecific low back pain . To do so we compared a specific ( individualized ) exercise program with a program of commonly prescribed exercises for low back pain . METHOD In a control group study , 20 patients with chronic or subacute nonspecific low back pain participated after giving their informed consent . All subjects were evaluated ( physical evaluation of lumbar and pelvic muscles [ 1 ] force and [ 2 ] extensibility , [ 3 ] trunk range of motion ) and then divided in 2 groups : 10 patients received specific exercises ( experimental group ) based on their evaluation , and 10 patients received a commonly prescribed exercise program for low back pain ( control group ) . Six weeks later a second physical evaluation was conducted . Pain ( visual analog pain scale ) and disability ( modified Oswestry ) question naires were also completed by each subject at both evaluations . DESIGN This was a r and omized experimental study . RESULTS Both groups had similar age , weight , and sex characteristics . The experimental group showed significant improvements for some components targeted by the program . The control group significantly had improvement of some physical characteristics not related to their initial deficits . Even if both groups showed some improvements in muscular force and extensibility , only the members of the group who received specific exercises significantly reduced their level of pain and disability . Both groups showed a similar rate of participation in the program . CONCLUSION The results of this study suggest that applying a specific physical evaluation and exercise prescription is an appropriate treatment for people having subacute or chronic nonspecific pain . Thus clinicians should prescribe exercise programs based on individual muscular deficits rather than most commonly prescribed exercise programs",
"Abstract Objectives : To determine whether a home based exercise programme can improve outcomes in patients with knee pain . Design : Pragmatic , factorial r and omised controlled trial of two years ' duration . Setting : Two general practice s in Nottingham . Participants : 786 men and women aged—45 years with self reported knee pain . Interventions : Participants were r and omised to four groups to receive exercise therapy , monthly telephone contact , exercise therapy plus telephone contact , or no intervention . Patients in the no intervention and combined exercise and telephone groups were r and omised to receive or not receive a placebo health food tablet . Main outcome measures : Primary outcome was self reported score for knee pain on the Western Ontario and McMaster universities ( WOMAC ) osteoarthritis index at two years . Secondary outcomes included knee specific physical function and stiffness ( scored on WOMAC index ) , general physical function ( scored on SF-36 question naire ) , psychological outlook ( scored on hospital anxiety and depression scale ) , and isometric muscle strength . Results : 600 ( 76.3 % ) participants completed the study . At 24 months , highly significant reductions in knee pain were apparent for the pooled exercise groups compared with the non-exercise groups ( mean difference -0.82 , 95 % confidence interval -1.3 to -0.3 ) . Similar improvements were observed at 6 , 12 , and 18 months . Regular telephone contact alone did not reduce pain . The reduction in pain was greater the closer patients adhered to the exercise plan . Conclusions : A simple home based exercise programme can significantly reduce knee pain . The lack of improvement in patients who received only telephone contact suggests that improvements are not just due to psychosocial effects because of contact with the therapist",
"The objective of this study was to determine whether the Arthritis Self-Management Programme ( ASMP ) improves perceptions of control , health behaviours and health status , and changes use of health care re sources . The design was a pragmatic r and omized controlled study ; participants were allocated to ASMP ( Intervention Group ) or a 4-month waiting-list Control Group . The Intervention Group completed a 12-month follow-up . In total , 544 people with arthritis were recruited from the community--311 in the Intervention Group and 233 in the Control Group . Main outcome measures included : arthritis self-efficacy , health behaviours ( exercise , cognitive symptom management , diet and relaxation ) and health status ( pain , fatigue , anxiety , depression and positive affect ) . At 4 months follow-up , the ASMP had a significant effect on arthritis self-efficacy for other symptoms and pain subscales . Performance of a range of health behaviours ( cognitive symptom management , communication with physicians , dietary habit , exercise and relaxation ) was significantly greater among the Intervention Group . The Intervention Group were significantly less depressed and had greater positive mood . In addition , trends towards decreases on fatigue and anxiety were noted . Physical functioning , pain and GP visits remained stable at 4 months . A similar pattern of findings was found at 12 months follow-up for the Intervention Group . Furthermore , a significant improvement was found on pain and visits to GPs had decreased . Apart from a small improvement on physical functioning among the Intervention Group participants with osteoarthritis 12 months , all effects were independent of the type of arthritis . The findings suggest that the ASMP is effective in promoting improvements in perception of control , health behaviours and health status , when delivered in UK setting ",
"Objective Chronic knee pain is a major cause of disability and health care expenditure , but there are concerns about efficacy , cost , and side effects associated with usual primary care . Conservative rehabilitation may offer a safe , effective , affordable alternative . We compared the effectiveness of a rehabilitation program integrating exercise , self-management , and active coping strategies ( Enabling Self-management and Coping with Arthritic Knee Pain through Exercise [ ESCAPE-knee pain ] ) with usual primary care in improving functioning in persons with chronic knee pain . Methods We conducted a single-blind , pragmatic , cluster r and omized controlled trial . Participants age ≥50 years , reporting knee pain for > 6 months , were recruited from 54 inner-city primary care practice s. Primary care practice s were r and omized to continued usual primary care ( i.e. , whatever intervention a participant 's primary care physician deemed appropriate ) , usual primary care plus the rehabilitation program delivered to individual participants , or usual primary care plus the rehabilitation program delivered to groups of 8 participants . The primary outcome was self-reported functioning ( Western Ontario and McMaster Universities Osteoarthritis Index physical functioning [ WOMAC-func ] ) 6 months after completing rehabilitation . Results A total of 418 participants were recruited ; 76 ( 18 % ) withdrew , only 5 ( 1 % ) due to adverse events . Rehabilitated participants had better functioning than participants continuing usual primary care ( −3.33 difference in WOMAC-func score ; 95 % confidence interval [ 95 % CI ] −5.88 , −0.78 ; P = 0.01 ) . Improvements were similar whether participants received individual rehabilitation ( −3.53 ; 95 % CI −6.52 , −0.55 ) or group rehabilitation ( −3.16 ; 95 % CI −6.55 , −0.12 ) . Conclusion ESCAPE-knee pain provides a safe , relatively brief intervention for chronic knee pain that is equally effective whether delivered to individuals or groups of participants",
"Behavioral and health status outcomes of an unreinforced , self-help education program for arthritis patients taught by lay persons were examined in 2 ways : a 4-month r and omized experiment and a 20-month longitudinal study . At 4 months , experimental subjects significantly exceeded control subjects in knowledge , recommended behaviors , and in lessened pain . These changes remained significant at 20 months . The course was inexpensive and well-accepted by patients , physicians , and other health professionals",
"This study evaluated a novel intervention for older osteoarthritis ( OA ) patients and their spousal caregivers that consisted of st and ard patient education supplemented by information related to effectively managing arthritis as a couple . Twenty-four female OA patients and their husb and s were r and omly assigned to either an educational intervention that was targeted at both patient and spouse or to a patient education intervention that was targeted at only the patient . Findings revealed that both interventions were evaluated favorably but the couple intervention was better attended than the patient intervention . In addition , patients in the couple intervention experienced greater increased efficacy in managing arthritis pain and other symptoms . The findings of this pilot study point to the utility of a dyadic intervention approach to management of OA in late life",
"OBJECTIVE To determine the effectiveness of a behavioral grade d activity program ( BGA ) compared with usual care ( UC ; exercise therapy and advice ) according to the Dutch guidelines for physiotherapy in patients with osteoarthritis ( OA ) of the hip and /or knee . The BGA intervention is intended to increase activity in the long term and consists of an exercise program with booster sessions , using operant treatment principles . METHODS We conducted a cluster r and omized trial involving 200 patients with hip and /or knee OA . Primary outcome measures were pain ( visual analog scale [ VAS ] and Western Ontario and McMaster Universities Osteoarthritis Index [ WOMAC ] ) , physical function ( WOMAC ) , and patient global assessment , assessed at weeks 0 , 13 , 39 , and 65 . Secondary outcome measures comprised tiredness ( VAS ) , patient-oriented physical function ( McMaster Toronto Arthritis Patient Preference Disability Question naire [ MACTAR ] ) , 5-meter walking time , muscle strength , and range of motion . Data were analyzed according to intent-to-treat principle . RESULTS Both treatments showed short-term and long-term beneficial within-group effects . The mean differences between the 2 groups for pain and functional status were not statistically significant . Significant differences in favor of BGA were found for the MACTAR functional scale and 5-meter walking test at week 65 . CONCLUSION Because both interventions result ed in beneficial long-term effects , the superiority of BGA over UC has not been demonstrated . Therefore , BGA seems to be an acceptable method to treat patients with hip and /or knee OA , with equivalent results compared with UC",
"OBJECTIVE The purpose of this study is to determine whether patient activation is a changing or changeable characteristic and to assess whether changes in activation also are accompanied by changes in health behavior . STUDY METHODS To obtain variability in activation and self-management behavior , a controlled trial with chronic disease patients r and omized into either intervention or control conditions was employed . In addition , changes in activation that occurred in the total sample were also examined for the study period . Using Mplus growth models , activation latent growth classes were identified and used in the analysis to predict changes in health behaviors and health outcomes . DATA SOURCES Survey data from the 479 participants were collected at baseline , 6 weeks , and 6 months . PRINCIPAL FINDINGS Positive change in activation is related to positive change in a variety of self-management behaviors . This is true even when the behavior in question is not being performed at baseline . When the behavior is already being performed at baseline , an increase in activation is related to maintaining a relatively high level of the behavior over time . The impact of the intervention , however , was less clear , as the increase in activation in the intervention group was matched by nearly equal increases in the control group . CONCLUSIONS Results suggest that if activation is increased , a variety of improved behaviors will follow . The question still remains , however , as to what interventions will improve activation",
"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",
"Abstract This study assessed the effectiveness of a single intervention targeting work style and a combined intervention targeting work style and physical activity on the recovery from neck and upper limb symptoms . Computer workers with frequent or long‐term neck and upper limb symptoms were r and omised into the work style group ( WS , n = 152 ) , work style and physical activity group ( WSPA , n = 156 ) , or usual care group ( n = 158 ) . The WS and WSPA group attended six group meetings . All meetings focused on behavioural change with regard to body posture , workplace adjustment , breaks and coping with high work dem and s ( WS and WSPA group ) and physical activity ( WSPA group ) . Pain , disability at work , days with symptoms and months without symptoms were measured at baseline and after 6 ( T1 ) and 12 months ( T2 ) . Self‐reported recovery was assessed at T1/T2 . Both interventions were ineffective in improving recovery . The work style intervention but not the combined intervention was effective in reducing all pain measures . These effects were present in the neck/shoulder , not in the arm/wrist/h and . For the neck/shoulder , the work style intervention group also showed an increased recovery‐rate . Total physical activity increased in all study groups but no differences between groups were observed . To conclude , a group‐based work style intervention focused on behavioural change was effective in improving recovery from neck/shoulder symptoms and reducing pain on the long‐term . The combined intervention was ineffective in increasing total physical activity . Therefore we can not draw conclusions on the effect of increasing physical activity on the recovery from neck and upper limb symptoms",
"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",
"& NA ; Chronic pain is a common , disabling problem in older adults . Pain self‐management training is a multimodal therapy that has been found to be effective in young to middle‐aged adult sample s ; however , few studies have examined the effectiveness of this therapy in older adults . In this r and omized , controlled trial , we evaluated a pain self‐management training group ( SMG ) intervention as compared with an education‐only ( BOOK ) control condition . Participants , 65 years of age or older who experienced persistent , noncancer pain that limited their activities , were recruited from 43 retirement communities in the Pacific Northwest of the United States . The primary outcome was physical disability , as measured by the Rol and ‐Morris Disability Question naire . Secondary outcomes were depression ( Geriatric Depression Scale ) , pain intensity ( Brief Pain Inventory ) , and pain‐related interference with activities ( Brief Pain Inventory ) . R and omization occurred by facility to minimize cross‐contamination between groups . Two‐hundred and fifty‐six individuals , mean age = 81.8 ( SD : 6.5 ) , enrolled and 218 completed the study . No significant differences in outcomes were found between groups at post‐intervention , 6‐month follow‐up , or 12‐month follow‐up . The SMG group showed a significantly greater increase over time , relative to the BOOK group , in two process measures , as measured by the Chronic Pain Coping Inventory : use of relaxation and use of exercise/stretching . In both cases , the increase was greatest from baseline to the post‐intervention assessment . Study findings indicate that additional research is needed to determine the most effective content and delivery methods for self‐management therapies targeted at older adults with chronic pain",
"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",
"UNLABELLED The aim of this study was to examine whether treatments based on different theories change pain catastrophizing and internal control of pain , and whether changes in these factors mediate treatment outcome . Participants were 211 patients with nonspecific chronic low back pain ( CLBP ) participating in a r and omized controlled trial , attending active physical treatment ( APT , n = 52 ) , cognitive-behavioral treatment ( CBT , n = 55 ) , treatment combining the APT and CBT ( CT , n = 55 ) , or waiting list ( WL , n = 49 ) . Pain catastrophizing decreased in all 3 active treatment groups and not in the WL . There was no difference in the change in internal control across all 4 groups . In all the active treatment groups , patients improved regarding perceived disability , main complaints , and current pain at post-treatment , and no changes were observed in the WL group . Depression only changed significantly in the APT group . Change in pain catastrophizing mediated the reduction of disability , main complaints , and pain intensity . In the APT condition , pain catastrophizing also mediated the reduction of depression . Not only cognitive-behavioral treatments but also a physical treatment produced changes in pain catastrophizing that seemed to mediate the outcome of the treatment significantly . The implication s and limitations of these results are discussed . PERSPECTIVE This article shows that treatment elements that do not deliberately target cognitive factors can reduce pain catastrophizing . Reduction in pain catastrophizing seemed to mediate the improvement of functioning in patients with chronic low back pain . The results might contribute to the development of more effective interventions",
"OBJECTIVE The purpose s of this pilot study were to determine if a combined dietary and exercise intervention would result in significant weight loss in older obese adults with knee osteoarthritis , and to compare the effects of exercise plus dietary therapy with exercise alone on gait , strength , knee pain , biomarkers of cartilage degradation , and physical function . DESIGN Single-blind , two-arm , r and omized clinical trial conducted for 24 weeks . SETTING A university health and exercise science center . PARTICIPANTS Twenty-four community-dwelling obese older adults aged > or = 60 years , body mass index > or = 28 , knee pain , radiographic evidence of knee osteoarthritis , and self-reported physical disability . INTERVENTION R and omization into two groups : exercise and diet ( E&D ) and exercise alone ( E ) . Exercise consisted of a combined weight training and walking program for 1 hour three times per week . The dietary intervention included weekly sessions with a nutritionist utilizing cognitive-behavior modification to change dietary habits to reach a group goal of an average weight loss of 15 lb ( 6.8 kg ) over 6 months . MEASUREMENTS All measurements were conducted at baseline and 3 and 6 months , except for synovial fluid analysis , which was obtained only at baseline and 6 months . In addition , weight was measured weekly in the E&D group . Physical disability and knee pain were measured by self-report and physical performance was measured using the 6-minute walk and stair climb tasks . Biomechanical testing included kinetic and kinematic analysis of gait and isokinetic strength testing . Synovial fluid was analyzed for levels of total proteoglycan , keratan sulfate , and interleukin-1 beta . RESULTS Twenty-one of the 24 participants completed the study , with one dropout in the E&D group and two in the E group . The E&D group lost a mean of 18.8 lb ( 8.5 kg ) at 6 months compared with 4.0 lb ( 1.8 kg ) in the E group ( P = .01 ) . Significant improvements were noted in both groups in self-reported disability and knee pain intensity and frequency as well as in physical performance measures . However , no statistical differences were found between the two groups at 6 months in knee pain scores or self-reported performance measures of physical function . There was no difference in knee strength between the groups , with both groups showing modest improvements from baseline to 6 months . At 6 months , the E&D group had a significantly greater loading rate ( P = .03 ) and maximum braking force ( P = .01 ) during gait . There were no significant between-group differences in the other biomechanical measures . Synovial fluid sample s were obtainable at both baseline and 6 months in eight participants ( four per group ) . The level of keratan sulfate decreased similarly in both groups from an average baseline of 96.8 + /- 37.1 to 71.5 + /- 23 ng/microg total proteoglycan . The level of IL-1 decreased from 25.3 + /- 9.8 at baseline to 8.3 + /- 6.1 pg/mL. The decrease in IL-1 correlated with the change in pain frequency ( r = -0.77 , P = .043 ) . CONCLUSIONS Weight loss can be achieved and sustained over a 6-month period in a cohort of older obese persons with osteoarthritis of the knee through a dietary and exercise intervention . Both exercise and combined weight loss and exercise regimens lead to improvements in pain , disability , and performance . Moreover , the trends in the biomechanical data suggest that exercise combined with diet may have an additional benefit in improved gait compared with exercise alone . A larger study is indicated to determine if weight loss provides additional benefits to exercise alone in this patient population",
"& NA ; An outpatient multimodal cognitive‐behavioural treatment program ( MMCBT ) for chronic spinal pain was evaluated during an 18‐month follow‐up period . The treatment included a 1‐day course for the patients ’ work supervisors . The aim of the study was to evaluate the long‐term effect of the treatment program as well as the effect of a work supervisor‐training program on the patients ’ return to work . The design was a matched cohort study with four repeated measures . Two groups of subjects suffering from non‐specific spinal pain ( treatment group n=67 , no treatment control group n=29 ) were assessed with regard to pain intensity , sick‐leave , pain coping ability and behavioural changes at work and in personal life . Recordings on supervisors attending the course and changes of supervisory behaviour were also obtained . The results show a significant between group difference in pain intensity and perceived pain coping ability at work , favouring the MMCBT group . Further , the MMCBT intervention enhances self‐reported behavioural changes in areas within the subjects ’ own control . There is not sufficient statistical support to accept the assumption of MMCBT being superior in reducing sick‐leave , either with or without the education of supervisors . Even when supervisors changed their behaviour as reported by the patient , no significant effect was found on patients ’ return to work . In conclusion , the MMCBT do not seem to be effective in reducing sick‐leave compared to no treatment , but the MMCBT program is superior in decreasing pain intensity , enhancing self‐reported behavioural changes in personal life and improving pain coping ability at work",
"OBJECTIVE To evaluate the effectiveness of a community-based arthritis education program conducted in a number of locations throughout the Sydney , Australia , metropolitan area . METHODS The program , based on earlier work , comprised 6 weekly sessions of 2.5 hours ' duration . The study sample included 175 men and women with different types of arthritis , divided into intervention ( n = 104 ) and control ( n = 71 ) groups . Five outcome measures were selected to evaluate effectiveness of the program : pain perception , knowledge level , self-efficacy , disability index , and self-management behavior . RESULTS The results indicated that the program was effective in increasing knowledge level ( F[1,222 ] = 10.3 , P = 0.001 at 6 weeks ; F[1,108 ] = 7.8 , P = 0.006 at 6 months ) , and a statistically significant difference was found in disability satisfaction 6 months after intervention ( F[1,98 ] = 5.9 , P = 0.01 ] , but no statistically significant difference was found in pain perception , self-efficacy , and disability index . CONCLUSION This research supports some of the successful outcomes which follow an arthritis education program : increased knowledge level and increased disability satisfaction",
"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",
"STUDY DESIGN A prospect i ve , r and omized , controlled trial with a stratification block design in which a Mensendieck exercise program was compared with the experience of a control group . OBJECTIVE To evaluate the effect of a Mensendieck program on the incidence of recurrent episodes of low back pain in patients with a history of the condition who currently are working . SUMMARY OF BACKGROUND DATA One episode of low back pain increases the risk of further episodes of the condition . The Mensendieck approach combines education and exercise . This approach has been used for many years in Sc and inavia and the Netherl and s. However , the effects on low back pain have not been evaluated previously in a r and omized , controlled trial . METHODS A total of 77 men and women , mean age 39.6 years ( range , 21.2 - 49.8 years ) , who had finished treatment for a low back pain episode , were stratified according to incidence of low back pain episodes and symptoms of sciatica over the preceding 3 years . The patients were assigned at r and om to either the Mensendieck program or a control group . The Mensendieck group received 20 group sessions of exercises and ergonomic education in 13 weeks . At 5- and 12-month follow-up examinations , the patients were assessed for recurrence of low back pain , days of sick leave , low back pain , and functional scores . RESULTS After 12 months , there was a significant reduction in recurrent low back pain episodes in the Mensendieck group compared with the control group ( P days of sick leave because of low back pain in the Mensendieck group , but no significant differences between the groups . There was reduction in pain and improvement in function in both groups , with no significant differences between the groups . CONCLUSIONS A secondary prophylaxis Mensendieck exercise program of 20 group sessions significantly reduced the incidence of low back pain recurrences in a population with history of the condition . However , there were no differences between the groups with regard to days of sick leave , low back pain , and function",
"OBJECTIVE To investigate the therapeutic effects of different muscle-strengthening exercises on the functional status of patients with knee osteoarthritis ( OA ) . METHODS One hundred thirty-two patients with bilateral knee OA ( Altman Grade II ) were sequentially divided into 4 r and om groups ( GI to GIV ) . The patients in group I received isokinetic muscle-strengthening exercise , group II received isotonic muscle-strengthening exercise , group III received isometric muscle-strengthening exercise , and group IV acted as controls . The changes of muscle power of leg flexion and extension were measured with a Kinetic Communicator dynamometer , and patients ' functional status was evaluated by visual analogue scale , ambulation speed , and Lequesne index before and after treatment , and at the follow-up 1 year later . RESULTS The results showed that the patients with OA in each treated group had significant improvement in pain reduction , disability reduction , and in walking speed after treatment and at follow-up when compared with their initial status . Isotonic exercise had the greatest effect on pain reduction after treatment , and fewer participants discontinued the treatment because of exercise knee pain . Isokinetic exercise caused the greatest increase of walking speed and decrease of disability after treatment and at follow-up . The greatest muscle-strength gain in 60 degrees /second angular velocity peak torques was found in the isokinetic and isotonic exercise groups . A significant muscle-strength gain in 180 degrees /second angular velocity peak torques was found only in the isokinetic group after treatment . CONCLUSION AND RELEVANCE Isotonic exercise is suggested for initial strengthening in patients with OA with exercise knee pain , and isokinetic exercise is suggested for improving joint stability or walking endurance at a later time",
"OBJECTIVES To determine whether a home-based pedometer-driven walking program with arthritis self-management education ( Walk + ) would increase physical activity , muscle strength , and functional performance in older adults with osteoarthritis ( OA ) of the knee as opposed to arthritis self-management education alone ( EDU ) . DESIGN A r and omized two-by-three ( group-by-time ) design with participants assigned to Walk + ( n = 17 , mean age + /- st and ard deviation = 69.6 + /- 6.7 ) or EDU ( n = 17 , age = 70.8 + /- 4.7 ) . SETTING Community located in the Baltimore-Washington area . PARTICIPANTS Thirty-four community-dwelling adults , aged 60 and older with symptomatic knee OA and self-reported functional impairment . INTERVENTIONS Both groups received 12 hours of the Arthritis Self-Management program over 12 weeks and were followed for an additional 12 weeks . In addition , the Walk + group received individualized instruction in the use of a pedometer , with the goal of increasing their step count by 30 % of their baseline step count . MEASUREMENTS The outcome measures were physical activity ( daily step counts and total activity vector magnitude as measured by a pedometer and Tritrac-R3D accelerometer ) , quadriceps femoris strength ( isometric peak torque ) , and functional performance tasks ( 100-foot walk-turn-walk , timed stair climb , timed chair rise , and pain status ) . RESULTS Daily steps walked showed a significant group-by-time interaction ( P = .04 ) after controlling for age . From baseline to completion of training , a 23 % increase in daily steps occurred in the Walk + group and a 15 % decrease in the EDU group . Although steps increased in the Walk + group , total activity vector magnitude was maintained , suggesting a more efficient gait . The Walk + group became quicker than the EDU group in the normal-pace walk-turn-walk ( P = .04 ) . An isometric strength gain of 21 % postintervention was seen in the Walk + group , compared with a loss of 3.5 % in the EDU group . CONCLUSION In older adults with symptomatic knee OA , Walk + appears to increase walking , with improvements in muscle strength and walking performance . The use of a home-based pedometer-driven program to increase physical activity , strength , and function in this population warrants further research",
"The long-term outcome results of inpatient and outpatient treatment of low back pain ( LBP ) were studied in 476 subjects ( aged 35 - 54 , 63 % men ) r and omly assigned to three study groups : in patients ( n = 157 ) , out patients ( n = 159 ) , and controls ( n = 160 ) . The study included changes in the severity of low back pain , grade and disability , compliance with self-care , data on disability pensions , and days of sickness allowance during a 2.5-year follow-up period . These variables were used as outcome criteria . Pain and disability had decreased significantly in the two treated groups up to the 3-month follow-up . LBP was still a little slighter in the in patients at the 1.5-year and 22-month follow-ups , but there were no significant differences between the groups in disability caused by LBP . The refresher programme carried out 1.5 years after the first one did not bring about as clear short-term improvement in pain and disability as the first treatment . During the whole 2.5-year follow-up compliance with self-care was better in the two treated groups , especially in the in patients . Days of sickness allowance had increased somewhat more in the controls than in the in patients during the follow-up . No differences between the groups were found in the number of disability pensions granted",
"OBJECTIVE Self-management courses in arthritis have been shown to improve outcomes and to decrease medical re source utilization . We studied the effectiveness of a mail-delivered arthritis self-management program with the potential for extending these effects more broadly . METHODS R and omized controlled trial of 375 program participants and 434 controls over a 6 month period . Baseline and 6 month data were analyzed for each group and between groups by paired 2 sample t test . The intervention consists of health assessment question naires at 3 month intervals , with computer processed recommendation letters and reports individualized to age , diagnosis , education level , disability , pain , medication , and other patient-specific variables . RESULTS At 6 months , outcomes of function ( 4.7 % ; 95 % confidence limits 2.7 , 6.7 ) , decreased pain ( 9 % ; 2.8 , 15.2 ) , global vitality ( 7 % ; 2.8 , 11.2 ) , and joint count ( 28 % ; 20 , 36 ) were improved in the program group compared with controls ( p Exercise ( 35 % ; 26 , 44 ) and self-efficacy ( 14.7 % ; 9 , 20 ) were increased in the program group but not controls ( p Doctor visits/year were decreased by 16 % ( 3 , 29 ) in the program group compared with controls ( p days missed work or confined to home decreased by 52 % ( -3 , 107 ) in the program group compared with controls ( p = 0.06 ) . At one year , patients in the original program group continued to improve , and the control group , provided with the program in the second 6 months , showed improvement similar to the first 6 months of the original program group . CONCLUSION A mail-delivered arthritis self-management program can positively affect patient outcomes and can decrease medical re source utilization",
"OBJECTIVE To determine whether manual therapy or pulsed shortwave diathermy , in addition to advice and exercise , provide better clinical outcome at 6 months than advice and exercise alone in primary care patients with nonspecific neck disorders . METHODS This was a multicenter , 3-arm r and omized controlled trial in 15 physical therapy departments . Of the 735 screened patients , 350 were recruited to the study ( mean age 51 years ) from July 2000 to June 2002 . Participants were r and omized to advice and exercise plus manual therapy , advice and exercise plus pulsed shortwave , or advice and exercise alone . Assessment s were undertaken at baseline , 6 weeks , and 6 months . The primary outcome was the Northwick Park Neck Pain Question naire . Analysis was by intention to treat . RESULTS Of the participants , 115 were allocated to advice and exercise , 114 to advice and exercise plus manual therapy , and 121 to advice and exercise plus pulsed shortwave ; 98 % received the allocated treatment . There was 93 % followup at 6 months . The mean + /- SD fall in Northwick Park score at 6 months was 11.5 + /- 15.7 for advice and exercise alone , 10.2 + /- 14.1 for advice and exercise plus manual therapy , and 10.3 + /- 15.0 for advice and exercise plus pulsed shortwave . There were no statistically significant differences in mean changes between groups . CONCLUSION The addition of pulsed shortwave or manual therapy to advice and exercise did not provide any additional benefits in the physical therapy treatment of neck disorders",
"BACKGROUND Determination of the mode of action of new exercise techniques in different back pain population s is lacking . The effectiveness of supplementing an exercise programme with stabilisation exercises concerning physiological and functional parameters in non-specific back pain patients is unknown . METHODS R and omised controlled trial , comparing a general trunk muscle endurance exercise approach enhanced with specific muscle stabilisation exercises ( S&G group ) with a general exercise approach only ( G group ) . 55 patients with recurrent back pain were r and omised in S&G group ( n=29 ) and G group ( n=26 ) . Both groups received an 8-week exercise intervention and written advice . Paraspinal muscle strength and electromyographic fatigue of the erector spinae and multifidus were measured . Additionally , 3 functional speed tests were assessed . Outcomes were collected pre- and post-intervention . FINDINGS No differences were detected for any of the paraspinal fatigue characteristics either within or between groups , apart from a significant decrease in normalised median frequency slope of the erector spinae for the G group . Paraspinal muscle strength and all functional tests have demonstrated significant within-group improvements for both groups , without any between-group differences . INTERPRETATION An 8-week stabilisation exercise-enhanced approach presented equal benefits to a general endurance-based exercise programme for patients with recurrent non-specific back pain . A slightly steeper slope for the erector spinae in the G group was the only electromyographic fatigue alteration noted . Concomitant strength improvement probably reflects neural input changes rather than histochemical muscle changes . Physical exercise alone and not the exercise type was the key determinant for improvement in this patient group",
"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 This study examined , in a group of older patients , ( a ) the effectiveness of an invitation to participate in a program providing individualized physical activity advice in a primary care setting and ( b ) the changes in self-reported physical activity and symptoms in patients with osteoarthritis ( OA ) . METHODS Healthy , sedentary community-dwelling men and women aged 60 years or more were invited to participate . Following r and om allocation , the intervention group received individualized physical activity advice at baseline and at 3 , 6 , and 12 months followup . RESULTS Of the 299 people who satisfied the study 's inclusion criteria , a subgroup of 69 people reported pain and stiffness of the hip or knee at baseline . These patients reported increases in frequency and time of walking and vigorous exercise ( all P OA symptom scores ( pain and stiffness ) , and a small decline in physical functioning was reported at 12 months followup in the control group only ( P = 0.027 ) . At the 12-month followup more intervention participants than control participants ( P = 0.013 ) reported a greater intention to exercise . CONCLUSIONS An offer of primary care-based physical activity advice , with an emphasis on the benefits for general health ( rather than \" treatment \" for OA ) , will attract individuals with OA symptoms . Although the present study was unable to demonstrate intervention-control group differences for the majority of outcomes , intention to exercise did appear to be positively influenced",
"This study was design ed to evaluate , by means of a r and omized controlled trial , the effects of a physical activity program incorporating aerobic , strength , and stretching exercises in individuals with osteoarthritis of the knee . We r and omly assigned 137 volunteers ages > /=50 to an experimental group or a control group . The experimental group participated in three 1-hour sessions of supervised exercises per week over a 3-month period . The control participants were instructed to continue their usual daily activities , and they attended 1-hour education sessions twice a month . The effectiveness of the program was evaluated using repeated measurements of parameters related to self-reported health status , physical capacity , and joint tenderness . After 3 months , significantly greater improvements were observed in the experimental group than the control group in terms of : arthritis pain ( p = 0.02 ) , ability to walk and bend ( p = 0.03 ) , aerobic capacity ( p hamstring and low back flexibility ( p = 0.003 ) , quadriceps and hamstring strength ( p perception of changes relating to osteoarthritis of the knee and general condition ( p isokinetic strength of the quadriceps ( all p 's > = = 0.05 ) , joint tenderness ( p = 0.18 ) , and health perception ( p = 0.7 ) . The overall results suggest that this program is effective for older persons with osteoarthritis of the knee and that it could contribute to maintaining their independence and improving their quality of life",
"UNLABELLED This study compares the outcomes of an individually tailored behavioral medicine intervention ( experimental ) with physical exercise therapy ( control ) . The experimental intervention was systematic ally individualized according to each participant 's behavioral treatment goals and functional behavioral analyses . One hundred twenty-two patients seeking care at 3 primary health care clinics because of musculoskeletal pain were r and omized . Ninety-seven completed the trial . Data were collected at baseline , immediately after treatment , and at a 3-month follow-up . Analyses of data from completers , as well as intention-to-treat analyses , showed that the experimental group experienced lower levels of disability ( P = .01 ) , lower maximum pain intensity ( P = .02 ) , higher levels of pain control ( P = .001 ) , and lower fear of movement ( P = .022 ) as a result of treatment condition . Self-efficacy ( P = .0001 ) and physical performance ( P = .0001 ) increased over time for both groups . Participants in the experimental group generally reported more positive effects after treatment . Treatment fidelity was maintained during the course of the study . Activity can be resumed and pain might be managed by the patients themselves if treatment incorporates the biopsychosocial explanatory model of pain and strategies are tailored according to individual 's priorities of everyday life activities and empirically derived determinants of pain-related disability . PERSPECTIVE This study shows that the biomedical and the psychosocial perspectives of the experiences and consequences of pain complement rather than contradict each other . Primary health care patients with persistent musculoskeletal pain benefit more from a systematic tailoring of treatments according to biopsychosocial factors than from a physically based exercise intervention",
"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",
"In a r and omized , observer-blinded trial , the effectiveness of 3-month high-intensity training ( HIT ) of the isolated lumbar extensors was compared to low-intensity training ( LIT ) . Eighty-one workers with nonspecific low back pain longer than 12 weeks were r and omly assigned to either of the two training programs . Training sessions were performed on a modified training device that isolated the lower back extensors . Total intervention time was limited to 5–10 min ( one or two training sessions ) per week . Training effects were assessed in terms of changes in self-rated degree of back complaints , functional disability , and general , physical and mental health . Secondary outcomes in this study were muscle strength and fear of moving the back ( kinesiophobia ) . Outcomes were evaluated at 1,2 , 3 , 6 , and 9 months after r and omization . The results showed that the two treatment programs led to comparable improvements in all outcome measures , except for mean isometric strength at 1 , 2 , 3 , 6 , and 9 months and kinesiophobia score at 2 and 9 months of follow-up . The high-intensity training group showed a higher strength gain ( 24 to 48 Nm ) but a smaller decline in kinesiophobia ( 2.5 and 3.4 points , respectively ) , compared to the low-intensity training group . It can be concluded that high-intensity training of the isolated back extensors was not superior to a non-progressive , low-intensity variant in restoring back function in nonspecific ( chronic ) low back pain . In further research , emphasis should be put on identifying subgroups of patients that will have the highest success rate with either of these training approaches",
"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",
"OBJECTIVE To determine whether Tai Chi or hydrotherapy classes for individuals with chronic symptomatic hip or knee osteoarthritis ( OA ) result in measurable clinical benefits . METHODS A r and omized controlled trial was conducted among 152 older persons with chronic symptomatic hip or knee OA . Participants were r and omly allocated for 12 weeks to hydrotherapy classes ( n = 55 ) , Tai Chi classes ( n = 56 ) , or a waiting list control group ( n = 41 ) . Outcomes were assessed 12 and 24 weeks after r and omization and included pain and physical function ( Western Ontario and McMaster Universities Osteoarthritis Index ) , general health status ( Medical Outcomes Study Short Form 12 Health Survey [ SF-12 ] , version 2 ) , psychological well-being , and physical performance ( Up and Go test , 50-foot walk time , timed stair climb ) . RESULTS At 12 weeks , compared with controls , participants allocated to hydrotherapy classes demonstrated mean improvements ( 95 % confidence interval ) of 6.5 ( 0.4 , 12.7 ) and 10.5 ( 3.6 , 14.5 ) for pain and physical function scores ( range 0 - 100 ) , respectively , whereas participants allocated to Tai Chi classes demonstrated improvements of 5.2 ( -0.8 , 11.1 ) and 9.7 ( 2.8 , 16.7 ) , respectively . Both class allocations achieved significant improvements in the SF-12 physical component summary score , but only allocation to hydrotherapy achieved significant improvements in the physical performance measures . All significant improvements were sustained at 24 weeks . In this almost exclusively white sample , class attendance was higher for hydrotherapy , with 81 % attending at least half of the available 24 classes , compared with 61 % for Tai Chi . CONCLUSION Access to either hydrotherapy or Tai Chi classes can provide large and sustained improvements in physical function for many older , sedentary individuals with chronic hip or knee OA",
"BACKGROUND AND PURPOSE Exercise and education is a common physiotherapy approach in the prevention of low back pain . A Mensendieck exercise programme consisting of exercises and ergonomical education has , in a previous study , been shown to be effective in preventing recurrent low back pain during one-year follow-up . The purpose of the present study was to evaluate the long-term effect of the Mensendieck exercise programme on people with recurrent episodes of low back pain who , when entering the study , had finished treatment for their last episode of low back pain . METHOD A r and omized controlled clinical trial in which 41 women and 36 men were allocated to either a Mensendieck or control group . The Mensendieck subjects received 20 group sessions of exercises and ergonomical education over 13 weeks . The control subjects were not offered any prophylactic therapy , but were free to receive treatment or exercises . Outcome measures were the number of recurrences of low back pain , sick leave , low back function and general functional status . RESULTS At three-year follow-up , 11 subjects had been lost to the study . Survival analysis showed a significant reduction ( p = 0.02 ) in subjects experiencing recurrent low back pain in the Mensendieck group compared to the control group . Significant improvements in pain and function scores were reported in both groups . There was no significant difference between the groups in pain , function or sick leave . CONCLUSION A Mensendieck exercise programme seems efficient in reducing recurrent episodes of low back pain at three-year follow-up , but it did not influence sick leave , pain or function scores",
"& NA ; The aim of the present study was to evaluate the long‐term outcome of a behavioural medicine rehabilitation programme and the outcome of its two main components , compared to a ‘ treatment‐as‐usual ’ control group . The study employed a 4 × 5 repeated‐ measures design with four groups and five assessment periods during a 3‐year follow‐up . The group studied consisted of blue‐collar and service/care workers on sick leave , identified in a nationwide health insurance scheme in Sweden . After inclusion , the subjects were r and omised to one of the four conditions : behaviour‐oriented physiotherapy ( PT ) , cognitive behavioural therapy ( CBT ) , behavioural medicine rehabilitation consisting of PT+CBT ( BM ) and a ‘ treatment‐as‐usual ’ control group ( CG ) . Outcome variables were sick leave , early retirement and health‐related quality of life . A cost‐effectiveness analysis , comparing the programmes , was made . The results showed , consistently , the full‐time behavioural medicine programme being superior to the three other conditions . The strongest effect was found on females . Regarding sick leave , the mean difference in the per‐ protocol analysis between the BM programme and the control group was 201 days , thus reducing sick leave by about two‐thirds of a working year . Rehabilitating women has a substantial impact on costs for production losses , whereas rehabilitating men seem to be effortless with no significant effect on either health or costs . In conclusion , a full‐time behavioural medicine programme is a cost‐effective method for improving health and increasing return to work in women working in blue‐collar or service/care occupations and suffering from back/neck pain",
"OBJECTIVE Twelve forms of Sun-style tai chi exercise have been developed specifically to reduce the symptoms and improve the physical functioning of arthritic patients , and this r and omized study examined the changes in symptoms and physical characteristics in older women with osteoarthritis ( OA ) at the completion of a 12-week tai chi exercise program . METHODS Seventy-two patients with OA were r and omly assigned into 2 groups . Due to a 41 % overall dropout rate , 22 experimental subjects and 21 controls completed pre- and post-test measures over a 12 week interval . Outcome variables were physical symptoms and fitness , body mass index , cardiovascular functioning , and perceived difficulties in physical functioning . The independent t test was used to examine group differences . RESULTS The homogeneity test confirmed that there were no significant group differences in demographic data and pretest measures . Mean comparisons of the change scores revealed that the experimental group perceived significantly less pain ( t = -2.19 , p = 0.034 ) and stiffness ( t = -2.13 , p = 0.039 ) in their joints , and reported fewer perceived difficulties in physical functioning ( t = -2.81 , p = 0.008 ) , while the control group showed no change or even deterioration in physical functioning after 12 weeks . In the physical fitness test , there were significant improvements in balance ( t = 3.34 , p = 0.002 ) and abdominal muscle strength ( t = 2.74 , p = 0.009 ) for the tai chi exercise group . No significant group differences were found in flexibility and upper-body or knee muscle strength in the post-test scores . CONCLUSION Older women with OA were able to safely perform the 12 forms of Sun-style tai chi exercise for 12 weeks , and this was effective in improving their arthritic symptoms , balance , and physical functioning . A longitudinal study with a larger sample size is now needed to confirm the potential use of tai chi exercise in arthritis management",
"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",
"Study Design . Multicentered r and omized controlled trial . Objectives . To determine if previously vali date d low back pain ( LBP ) subgroups respond differently to contrasting exercise prescriptions . Summary of Background Data . The role of “ patient-specific ” exercises in managing LBP is controversial . Methods . A total of 312 acute , subacute , and chronic patients , including LBP-only and sciatica , underwent a st and ardized mechanical assessment classifying them by their pain response , specifically eliciting either a “ directional preference ” ( DP ) ( i.e. , an immediate , lasting improvement in pain from performing either repeated lumbar flexion , extension , or sideglide/rotation tests ) , or no DP . Only DP subjects were r and omized to : 1 ) directional exercises “ matching ” their preferred direction ( DP ) , 2 ) exercises directionally “ opposite ” their DP , or 3 ) “ nondirectional ” exercises . Outcome measures included pain intensity , location , disability , medication use , degree of recovery , depression , and work interference . Results . A DP was elicited in 74 % ( 230 ) of subjects . One third of both the opposite and non-directionally treated subjects withdrew within 2 weeks because of no improvement or worsening ( no matched subject withdrew ) . Significantly greater improvements occurred in matched subjects compared with both other treatment groups in every outcome ( P values medication use . Conclusions . Consistent with prior evidence , a st and ardized mechanical assessment identified a large subgroup of LBP patients with a DP . Regardless of subjects ’ direction of preference , the response to contrasting exercise prescriptions was significantly different : exercises matching subjects ’ DP significantly and rapidly decreased pain and medication use and improved in all other outcomes . If repeatable , such subgroup validation has important implication s for LBP management",
"CONTEXT Active physical training is commonly recommended for patients with chronic neck pain ; however , its efficacy has not been demonstrated in r and omized studies . OBJECTIVE To evaluate the efficacy of intensive isometric neck strength training and lighter endurance training of neck muscles on pain and disability in women with chronic , nonspecific neck pain . DESIGN Examiner-blinded r and omized controlled trial conducted between February 2000 and March 2002 . SETTING Participants were recruited from occupational health care systems in southern and eastern Finl and . PATIENTS A total of 180 female office workers between the ages of 25 and 53 years with chronic , nonspecific neck pain . INTERVENTIONS Patients were r and omly assigned to either 2 training groups or to a control group , with 60 patients in each group . The endurance training group performed dynamic neck exercises , which included lifting the head up from the supine and prone positions . The strength training group performed high-intensity isometric neck strengthening and stabilization exercises with an elastic b and . Both training groups performed dynamic exercises for the shoulders and upper extremities with dumbbells . All groups were advised to do aerobic and stretching exercises regularly 3 times a week . MAIN OUTCOME MEASURES Neck pain and disability were assessed by a visual analog scale , the neck and shoulder pain and disability index , and the Vernon neck disability index . Intermediate outcome measures included mood assessed by a short depression inventory and by maximal isometric neck strength and range of motion measures . RESULTS At the 12-month follow-up visit , both neck pain and disability had decreased in both training groups compared with the control group ( P Maximal isometric neck strength had improved flexion by 110 % , rotation by 76 % , and extension by 69 % in the strength training group . The respective improvements in the endurance training group were 28 % , 29 % , and 16 % and in the control group were 10 % , 10 % , and 7 % . Range of motion had also improved statistically significantly in both training groups compared with the control group in rotation , but only the strength training group had statistically significant improvements in lateral flexion and in flexion and extension . CONCLUSIONS Both strength and endurance training for 12 months were effective methods for decreasing pain and disability in women with chronic , nonspecific neck pain . Stretching and fitness training are commonly advised for patients with chronic neck pain , but stretching and aerobic exercising alone proved to be a much less effective form of training than strength training",
"An intervention design ed to enhance preaction self-efficacy beliefs ( i.e. , beliefs about ability to initiate behavior despite anticipated barriers during the initiation period ) was tested in patients with spondylosis in relation to initiation of exercises recommended by a consultant in orthopedic rehabilitation . Sixty patients ( age 28 - 83 years ; 44 % men ) with spondylosis who had not previously performed exercises recommended for degenerative spine diseases were r and omly assigned to a control ( education session ) or intervention group . Three weeks later , intervention patients performed recommended exercises more frequently than controls . Regression analysis for all patients showed that preintervention , preaction self-efficacy predicted exercise . Age and preintervention self-efficacy moderated the intervention effects . Among older patients , only those with weak preintervention , preaction self-efficacy beliefs benefited from the intervention , whereas among younger patients , only those with strong preintervention , preaction self-efficacy beliefs benefited from the intervention",
"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",
"A treatment- outcome study was conducted to study the impact of behavior and physical therapy on components of the chronic low back pain syndrome . Eighteen patients received behavior therapy and 15 patients received physical therapy . All patients had at least a 6-month history of seeking treatment for chronic low back pain . Prior to treatment patients were assessed in four principal areas of functioning : ( 1 ) physical abilities ; ( 2 ) current physical functioning ; ( 3 ) psychological and psychosocial functioning ; and ( 4 ) pain intensity and pain perception . Treatments were conducted in a group ( five to eight patients ) outpatient setting . Both behavior therapy and physical therapy groups met for 10-weekly sessions , each lasting 2 hr . Behavior therapy was design ed to address the environmental , social , and emotional components of the low back pain syndrome as well as the depression and decreased activity that result from chronic low back pain . Physical therapy was based upon traditional rehabilitation theory and was design ed to improve low back function . Patients were reevaluated at posttreatment , 6 months , and 1 year . The results showed a general improvement for patients in both groups and a few treatment-specific differences in outcome measures",
"Study Design . A r and omized comparative study with single-blind outcome assessment s. Objectives . To compare the efficacy of a multimodal treatment emphasizing proprioceptive training ( ACTIVE ) with activated home exercises ( HOME ) and recommendation of exercise ( CONTROL ) in patients with nonspecific chronic neck pain . Summary of Background Data . The efficacy of active exercises and passive physiotherapy for neck trouble has been somewhat disappointing in the previous few studies . Methods . Seventy-six patients ( 22 men , 54 women ) with chronic , nonspecific neck pain participated . Sixty-two participated the 1-year follow-up . Subjective pain and disability , cervical ranges of motion , and pressure pain threshold in the shoulder region were measured at baseline , at 3 months , and at 12 months . The ACTIVE treatment consisted of 24 sessions of proprioceptive exercises , relaxation , and behavioral support . The HOME regimen included a neck lecture and two sessions of practical training for home exercises and instructions for maintaining a diary of progress . The CONTROL treatment included a lecture regarding care of the neck with a recommendation to exercise . Results . The average self-experienced total benefit was highest in the ACTIVE group , and the HOME group rated over the CONTROL group ( P reduction of neck symptoms and improvements in general health and self-experienced working ability ( P measures of mobility and pressure pain threshold were minor . Conclusions . Regarding self-experienced benefit , the multimodal treatment was more efficacious than activated home exercises that were clearly more efficacious than just advising . No major differences were noted in objective measurements of cervical function between the groups , but the content validity of these assessment s in chronic neck trouble can be question ed",
"OBJECTIVE The study aim ed to compare the relative effectiveness of providing a home-based exercise programme versus home-based exercise supplemented with an 8-week class-based exercise programme in reducing pain and improving function in patients with knee osteoarthritis . METHODS Patients ( n = 214 ) with radiologically confirmed knee osteoarthritis were selected . Patients were r and omly allocated to either home or home supplemented with class-based exercise programmes . Both groups were given a home exercise programme whilst the supplemented group also attended for 8 weeks of twice weekly knee classes . Assessment s of locomotor function , walking pain and Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) scores were made . Assessment s were made pre- and post-treatment and also at 6- and 12-month follow-ups . Statistical analysis involved the use of a longitudinal linear model ANCOVA with baseline values entered as a covariate . RESULTS Patients from the class-based group demonstrated significantly greater improvement in locomotor function ( -3.7 seconds ; 95 % C.I. -4.9 to -2.5 ) and decrease in walking pain ( -15 mm ; 95 % C.I. -20 to -11 ) than the home-based group , at 12-months follow-up . CONCLUSIONS The supplementation of a home based exercise programme with a class-based exercise programme led to clinical ly significant superior improvement . These improvements were still evident at 12-month review . This is the first trial to evaluate this common physiotherapeutic practice , and based on this evidence , supplementation of home exercises with a class-based exercise programme can be recommended to patients , clinicians and service providers",
"Purpose : Arthritis self‐efficacy ( ASE ) characterizes individuals ' confidence in managing their arthritis . This study 's purpose was to examine the effects of a telephone intervention on ASE , depression , pain , and fatigue in older adults with arthritis . Methods : Eighty‐five elders with arthritis were r and omly assigned to the intervention or control group . Participants in both groups : ( a ) completed baseline assessment s of ASE , depression , pain , and fatigue ; ( b ) received written information on arthritis management ; and ( c ) received individualized action plans for achieving their own arthritis management goal over the 6‐week study . Participants in the intervention group received a telephone intervention including instruction on managing arthritis and encouragement to pursue their goal . In the sixth week the assessment tools were re‐administered . Quantitative and qualitative data analysis methods were employed . Results : Quantitative analyses showed a significant increase in ASE and a significant reduction in depression and pain over time for both groups . Qualitative analyses revealed several themes related to benefits of telephone intervention . Conclusion : Study results suggest that minimal intervention ( ie , written information , goal ‐ setting , and action plans ) may produce positive changes in ASE , depression , and pain in some older adults with arthritis . Furthermore , telephone intervention may assist older patients in managing their arthritis",
"OBJECTIVE To investigate the effects of ultrasound ( US ) in isokinetic muscle strengthening exercises on functional status of patients with knee osteoarthritis ( OA ) . DESIGN Effectiveness of isokinetic muscle strengthening exercises for treatment of periarticular soft tissue disorders was compared with and without pulsed and continuous US . SETTING Outpatient exercise program in a Taiwan medical university hospital . PARTICIPANTS One hundred twenty subjects with bilateral knee OA ( Altman grade II ) . INTERVENTION Subjects were r and omized sequentially into 1 of 4 groups . Group I received isokinetic muscular strengthening exercises , group II received isokinetic exercise and continuous US , group III received isokinetic exercise and pulsed US treatment , and group IV was the control group . MAIN OUTCOME MEASURES Therapeutic effects of isokinetic exercise were evaluated by changes in ambulation speed and the Lequesne index . In addition , changes in knee range of motion ( ROM ) , visual analog scale for pain , and muscle peak torques during knee flexion and extension were compared . Compliance in each group was recorded . RESULTS Each treated group had increased muscle peak torques and significantly reduced pain and disability after treatment and at follow-up . However , only patients in groups II and III had significant improvement in ROM and ambulation speed after treatment . Fewer participants in group III discontinued treatment due to knee pain during exercise . Patients in group III also showed the greatest increase in walking speed and decrease in disability after treatment and at follow-up . Gains in muscular strength in 60 degrees /s angular velocity peak torques were also noted in groups II and III . However , group III showed the greatest muscular strength gains with 180 degrees /s angular velocity peak torques after treatment and follow-up . CONCLUSIONS US treatment could increase the effectiveness of isokinetic exercise for functional improvement of knee OA , and pulsed ultrasound has a greater effect than continuous US",
"Purpose . To compare a group exercise programme known as the Back to Fitness programme with individual physiotherapy for patients with non-specific low back pain from a material ly deprived area . Method . This was a r and omized controlled trial including 237 physiotherapy patients with back pain lasting more than six weeks . Participants were allocated to either the Back to Fitness programme or to individual physiotherapy , and followed up at three months and 12 months after r and omization . The main outcome measure was the Rol and Disability Question naire . Secondary measures were : SF12 , EQ5D , Pain Self-Efficacy Scale . Health care diaries recording patients ' use of health care re sources were also collected over a 12-month period . Results . There were no statistically significant differences in change scores between groups on the primary outcome measure at three months ( CI − 2.24 to 0.49 ) and at 12 months ( CI − 1.68 to 1.39 ) . Only minor improvements in disability scores were observed in the Back to Fitness group at three months and 12 months respectively ( mean change scores ; − 0.89 , − 0.77 ) and in the individual physiotherapy arm ( mean change scores ; − 0.02 , − 0.63 ) . Further analysis showed that patients from the most severely deprived areas were marginally worse at three month follow-up whereas those from more affluent areas tended to improve ( CI 0.43 to 3.15 )",
"BACKGROUND AND PURPOSE The purpose of this r and omized controlled trial was to examine the usefulness of the addition of specific stabilization exercises to a general back and abdominal muscle exercise approach for patients with subacute or chronic nonspecific back pain by comparing a specific muscle stabilization-enhanced general exercise approach with a general exercise-only approach . SUBJECTS Fifty-five patients with recurrent , nonspecific back pain ( stabilization-enhanced exercise group : n=29 , general exercise-only group : n=26 ) and no clinical signs suggesting spinal instability were recruited . METHODS Both groups received an 8-week exercise intervention and written advice ( The Back Book ) . Outcome was based on self-reported pain ( Short-Form McGill Pain Question naire ) , disability ( Rol and -Morris Disability Question naire ) , and cognitive status ( Pain Self-Efficacy Question naire , Tampa Scale of Kinesiophobia , Pain Locus of Control Scale ) measured immediately before and after intervention and 3 months after the end of the intervention period . RESULTS Outcome measures for both groups improved . Furthermore , self-reported disability improved more in the general exercise-only group immediately after intervention but not at the 3-month follow-up . There were generally no differences between the 2 exercise approaches for any of the other outcomes . DISCUSSION AND CONCLUSION A general exercise program reduced disability in the short term to a greater extent than a stabilization-enhanced exercise approach in patients with recurrent nonspecific low back pain . Stabilization exercises do not appear to provide additional benefit to patients with subacute or chronic low back pain who have no clinical signs suggesting the presence of spinal instability",
"AIMS The present study examines the outcome of counselling in physiotherapy based on the Transtheoretical Model ( TTM ) in a sample of elderly individuals with chronic low back pain . METHODS In a prospect i ve r and omised trial with concealed assignment , elderly individuals with chronic low back pain were allocated to two treatment conditions . Both contained 10 sessions of physiotherapy , each of 20min duration . In addition , the experimental group ( EG ) received 10min counselling prior to every session based on the TTM , also provided by the physiotherapist , and the control group ( CG ) underwent a placebo ultrasound treatment with an inactivated device to control for the additional attention given to the EG . Assessment s took place prior to the treatment ( t1 ) , immediately after termination of the treatment ( t2 ) , and at a 6-months follow-up . Outcome measures were physical activity calculated from one-week activity diaries , self-reported functional capacity , and range of motion measured by ultrasound topometry . RESULTS A total of 170 individuals ( 64 % female ) with a mean age of 70.3 years ( SD=4.4 , range 65 - 84 ) participated in the study . The retention rate was 90 % . At t3 , both EG and CG showed increased physical activity and functional capacity , but no change in range of motion . Effect sizes were large . Contrary to our hypothesis , however , motivational training did not result in a better outcome compared with placebo treatment . CONCLUSION The study does not provide evidence that a short TTM-based motivation programme is superior to placebo treatment regarding adherence to activity recommendations",
"& NA ; The aim of the present study was to evaluate the outcome of a behavioral medicine ( BM ) rehabilitation program and the outcome of its two main components , compared to a ‘ treatment‐as‐usual ’ control group ( CG ) . The study employed a 4 × 4 repeated‐ measures design with four groups and four assessment periods ( pre‐treatment , post‐treatment , 6‐month follow‐up , and 18‐month follow‐up ) . The group studied consisted of subjects on sick leave identified in a nationwide health insurance scheme in Sweden . After inclusion , the subjects were r and omized to one of four conditions , which were : ( 1 ) behavior‐oriented physical therapy ( PT ) ; ( 2 ) cognitive behavioral therapy ( CBT ) ; ( 3 ) BM rehabilitation consisting of PT+CBT ( BM ) ; ( 4 ) a ‘ treatment‐as‐usual ’ CG . The treatments were given over a period of 4 weeks , PT and CBT on a part‐time basis and BM on a full‐time basis . Outcome variables were sick leave , early retirement , and health‐related quality of life ( measured using the Short Form Health Survey , SF‐36 ) . The results showed that the risk of being granted full‐time early retirement was significantly lower for females in PT and CBT compared to the CG during the 18‐month follow‐up period . However , the total absence from work ( sick listing plus early retirement ) in days over the 18‐month follow‐up period was not significantly different in the CG compared to the treatments . On the SF‐36 , women in CBT and BM reported a significantly better health‐related quality of life than women in the CG at the 18‐month follow‐up . No significant differences for men were found on the SF‐36 scales . In conclusion , the results revealed gender differences in the outcome of the treatments and that the components of this BM program yielded as good results as the whole program",
"BACKGROUND AND PURPOSE The purpose of this study was to investigate whether the mode of teaching exercises ( use of brochures versus therapist teaching ) affects whether patients correctly perform the exercises and whether it affects changes in impairment . SUBJECTS Eighty-seven patients ( 33 women , 54 men ) with neck pain and low back pain were examined . The average age was 48 years ( SD = 12.7 , range = 21 - 67 ) . METHODS Two groups of patients were analyzed . The supervised ( physical therapist-instructed ) group ( n = 47 ) exercised under the supervision of a physical therapist , whereas the brochure group ( n = 40 ) received their instructions only from one of three brochures . A rating scale was used to assess the correctness of exercise performance . Muscle status was registered using a st and ardized procedure for determination of muscle force and length . Pain severity was determined by means of a visual analogue scale . RESULTS On the rating scale evaluating the correctness of exercise performance at follow-up , the patients in the supervised group performed better than the patients in the brochure group . In addition , there was a strong correlation between the quality of exercise performance and decrease in pain . CONCLUSION AND DISCUSSION Exercises learned only from a brochure without being monitored by a physical therapist were done properly by only about half of the patients and appeared to result in fewer improvements in impairments",
"Study Design . A r and omized clinical trial with blinded assessment . Objectives . To investigate the clinical efficacy of 2 active interventions for patients with chronic low back pain . Summary of Background Data . Manual therapy and exercise prescription are treatments frequently prescribed for patients with chronic low back pain . The evidence for the relative benefit of these treatments is limited , and questions concerning the most appropriate type of intervention remain unanswered . Methods . Eighty patients with chronic low back pain ( > 3 months ) were r and omized to one of the following treatments , involving 8 treatments over 8 weeks ; 1 ) one-to-one treatment involving 30 minutes of manual therapy ( mobilizations to the spine ) and spinal stabilization exercises , and 2 ) a 10 station exercise class involving aerobic exercises , spinal stabilization exercises , and manual therapy . Three physiotherapists led the hour long group with a maximum of 10 patients . Question naires were completed , and physical measurements were taken by a blinded observer before r and omization , at the completion of treatment , and at 6 months and 12 months after the completion of treatment . The intention-to-treat principle was used in data analysis . Results . Eleven patients dropped out of the individual treatment sessions and 7 dropped out of the exercise group . There was a significant reduction ( reduced disability ) in the question naire score in both groups , and there were significant increases in range for all the physical movements tested in both groups . The exercise group was 40 % more cost effective than the individual treatments . Conclusion . Both forms of intervention were associated with significant improvement . On-going clinical research is necessary to provide guidance as to the clinical efficacy of various forms of intervention",
"OBJECTIVE To determine the effectiveness of exercise therapy in patients with osteoarthritis ( OA ) of the hip or knee . METHODS A r and omized single blind , clinical trial was conducted in a primary care setting . Patients with hip or knee OA by American College of Rheumatology criteria were selected . Two intervention groups were compared . Both groups received treatment from the patients ' general practitioner , including patient education and medication if necessary . The experimental group also received exercise therapy from a physiotherapist in primary care . The treatment period was 12 weeks . The main outcome measures were pain , medication use ( nonsteroidal antiinflammatory drugs , NSAID ) and observed disability . RESULTS A total of 201 patients were r and omized . Exercise therapy was associated with a reduction of pain in the past week ( difference in change -17.0 ; 95 % CI -23.6 , -10.4 ) and observed disability ( -0.19 ; 95 % CI -0.38 ; -0.01 ) . Effect sizes were medium ( 0.58 ) and small ( 0.28 ) , respectively . No effect of exercise therapy was found for the use of NSAID . Additional beneficial effects ( p = 0.05 ) were found for the use of paracetamol ( effect size 0.33 ) , global effect as perceived by the patient ( effect size 0.68 ) , and muscle strength of the hip ( effect size 0.34 ) . CONCLUSION After 12 weeks , exercise therapy is effective in reducing pain and disability . The size of the effects is medium and small , respectively",
"OBJECTIVES To study whether isometric shoulder endurance was more advantageous than isometric shoulder strength training in reducing pain and perceived exertion and to increase shoulder function through improved muscle endurance and strength . DESIGN R and omized trial . SETTING Three occupational health care centers . PARTICIPANTS Women industrial workers with nonspecific neck-shoulder pain . The International Classification of Diseases , 10th Revision ( ICD-10 ) diagnosis was \" cervicobrachial syndrome \" ( M53.1 ) . Thirty-eight patients completed the isometric shoulder endurance training and 31 patients completed the isometric shoulder strength training . INTERVENTION Twelve weeks of training . MAIN OUTCOME MEASURES Self-reported pain and rating of perceived exertion ( RPE ) , arm motion performance test , shoulder muscle strength , shoulder muscle endurance , and shoulder functional tests , as well as follow-up after supervised training had ended . RESULTS The isometric shoulder strength training result ed in an almost one-scale step decrease in RPE at work and a 5 % to 15 % improvement of arm motion performance compared with the endurance training . The isometric shoulder strength training more effectively improved left side shoulder abduction strength ( p isometric shoulder endurance training was not more successful than the strength training in the endurance test ( p .51 to .81 ) . CONCLUSIONS Physical training programs for neck-shoulder pain may include isometric shoulder muscular strength exercise in addition to isometric shoulder endurance training , rather than endurance training only",
"This study investigated factors related to an initial exercise experience to explain exercise maintenance in 120 adults with rheumatoid arthritis or osteoarthritis . Integral secondary analysis was used to incorporate data from a prospect i ve , controlled trial of exercise ( Minor et al. : Arthritis Rheum 32:1396 , 1989 ) with data collected at 18 months follow-up . The dependent variable was self-directed exercise ( min/wk ) reported at 3 , 9 , and 18 or more months after exercise class participation . Predictor variables included physical , psychosocial , disease , and programmatic factors . The all possible regressions search procedure result ed in three explanatory models ( p = .0001 ) . At 3 months the model ( R2 = .45 ) included initial aerobic capacity , depression , and anxiety ; and changes in depression and social activity . The 9-month model ( R 2 = .35 ) consisted of initial anxiety and physical activity , change in depression , support of friends for exercise , and exercise behavior at prior assessment . At 18 or more months ( R2 = .42 ) , model variables were initial aerobic capacity , change in pain , and exercise behavior at the two prior assessment s. Neither disease nor program factors appeared as significant . This limited study indicates that factors associated with exercise behavior in this sample are similar to those in the general population ; explanatory factors change over time , and changes ascribed to a trial behavior may influence subsequent decision making",
"OBJECTIVE To assess the effect of a combined exercise and motivation program on the compliance and level of disability of patients with chronic and recurrent low back pain . DESIGN A double-blind prospect i ve r and omized controlled trial . SETTING Physical therapy outpatient department , tertiary care . PATIENTS Ninety-three low back pain patients were r and omly assigned to either a st and ard exercise program ( n = 49 ) or a combined exercise and motivation program ( n = 44 ) . INTERVENTIONS Patients were prescribed 10 physical therapy sessions and were advised to continue exercising after treatment termination . The motivation program consisted of five compliance-enhancing interventions . Follow-up assessment s were performed at 3 1/2 weeks , 4 months , and 12 months . MAIN OUTCOME MEASURES Disability ( low back outcome score ) , pain intensity , physical impairment ( modified Waddell score , fingertip-to-floor distance , abdominal muscle strength ) , working ability , motivation , and compliance . RESULTS The patients in the motivation group were significantly more likely to attend their exercise therapy appointments ( p = .0005 ) . Four and 12 months after study entry there was a significant difference in favor of the motivation group with regard to the disability score ( p = .004 ) and pain intensity ( p fingertip-to-floor distance ( p = .01 ) and in abdominal muscle strength ( p = .018 ) . No significant differences were found in motivation scores , self-reported compliance with long-term exercise , and modified Waddell score . In terms of working ability , there was a trend favoring the combined exercise and motivation program . CONCLUSION The combined exercise and motivation program increased the rate of attendance at scheduled physical therapy sessions , ie , short-term compliance , and reduced disability and pain levels by the 12-month follow-up . However , there was no difference between the motivation and control groups with regard to long-term exercise compliance",
"This investigation examined predictors of compliance with exercise therapy in a clinical trial involving older adults with knee osteoarthritis ( OA ) . The study sample was partitioned into tertiles by level of compliance to determine its effect on several clinical outcome measures in the trial ( i.e. , knee pain , difficulty with activities of daily living , and performance-related disability ) . The participants ( N = 439 ) first completed all baseline assessment s and were then r and omly assigned to one of three treatment conditions : health education control , aerobic exercise , or resistance exercise . The two exercise treatments involved a 3-month center-based phase and a 15-month home-based phase . Variables in five categories ( i.e. , demographic , fitness , health-related quality of life , performance-related disability , and prior exercise behavior ) were entered as predictors of attendance and time spent exercising during each session for three different periods of time across the course of the study . Results of these analyses revealed that it was possible to explain more variance for time spent exercising ( approximately 40 % ) during the first 3 months than for attendance ( approximately 10 % ) . Furthermore , once participants completed the first 3 months of their training , prior behavior was the strongest predictor of exercise compliance . In most cases , the regression models accounted anywhere from 26 to 46 % of the variance in attendance or time spent exercising ( 7 of the 8 P values demographic , fitness , psychosocial , and disability-related measures did not predict compliance with any consistency across the various phases of the trial . Analysis of the dose-response data suggest that , in the use of aerobic exercise to deter disability in older people with knee OA , consideration should be given to prescribing frequent bouts of activity ( at least 3 times each week ) of moderate duration ( approximately 35 min )",
"The effect of \" neck school \" on neck and shoulder disorders was studied in medical secretaries . A neck school reinforced with compliance enhancing measures ( group B ) was compared with a traditional neck school ( group A ) and a control group ( group C ) . The results show that ergonomical knowledge was good even before the secretaries attended the neck schools and that compliance was significantly higher for group B. When comparisons were made within groups some improvements on neck and shoulder fatigue and pain were noted , particularly for group B. When workload was controlled no significant group differences were found . No differences were noted for range of neck motion , or sick leave in any group . Our conclusion is that neck schools , despite good compliance , appear to be of limited clinical value for prevention of neck and shoulder disorders"
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HIGHLIGHTSPreterm birth is associated with an elevated risk for neurodevelopmental deficits . Auditory event‐related potentials can be used to assess early cognitive functioning . This paper represents the first systematic review investigating the predictive power of AERPs on cognition in preterms . According to our findings , auditory event‐related potentials can help to predict neurodevelopmental outcome in preterms . More evidence ‐based studies are needed before clinical ly applying this method . ABSTRACT Prematurity is a known risk factor for later cognitive deficits . At present there are neither behavioral nor neurological tests available to detect those preterm infants who would benefit most from early interventions . Neurophysiologic methods , and more specifically , auditory event‐related potentials ( AERPs ) are convenient tools to investigate early cognitive functioning . However , the capability of AERPs as a prognostic factor for mental development in preterm infants remains unclear . The present systematic search of the literature yielded 1016 articles , out of which 13were included . Both prospect i ve and cross‐sectional studies reported a relationship between AERPs and cognitive outcome . Our results show that larger amplitudes and shorter latencies of late AERPs are related to better cognitive outcomes . Additional studies are needed to corroborate our findings regarding this potential use of AERPs in the individual evaluation of preterm born infants
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"In this study , the diagnostic and predictive value of brainstem , middle latency , and cortical auditory evoked responses ( BMC -AERs ) obtained in the neonatal period in 81 preterm infants was assessed in relation to neurodevelopmental outcome . The preterm infants were neonatally classified according to risk category and gestational age . The BMC -AERs were analyzed with respect to detectability , latencies , and amplitudes as well as derived latency and amplitude measures . At 5 y of age the neurodevelopmental outcome was assessed from neurologic and neuropsychologic evaluations . The results showed that BMC -AER differences mainly correlated with risk category ( low risk/high risk ) and to some extent with degree of prematurity . In view of these findings the degree of prematurity and the effect of risk category have to be taken into account , when BMC -AERs are applied in the preterm period to predict neurodevelopmental outcome . In this study the BMC -AERs for infants with abnormal neurodevelopmental outcome were scarcely distinguishable from the BMC -AERs for infants with normal neurodevelopmental outcome . Thus far , this and previous reports have indicated that BMC -AERs in preterm infants are useful in maturational studies and with infants showing symptoms related to lesions or dysfunction of the peripheral and /or central auditory system . For predicting neurodevelopmental outcome in preterm infants , BMC -AERs are of limited clinical value",
"The mismatch negativity ( MMN ) component of the auditory event-related potential ( ERP ) is elicited by infrequent , physically deviant stimuli in a sequence of frequent homogeneous stimuli ( st and ards ) . It has been suggested that the MMN is generated by an automatic ( attention-independent ) neural mismatch process with a memory trace that encodes the physical features of the st and ard stimulus . The proposed MMN independence of attention was addressed in the present study . St and ard stimuli and two types of deviant stimuli , differing from st and ards either in frequency or intensity , were dichotically presented in r and om order and at a rapid rate . The subject attended either to left- or right-ear stimuli , counting the number of a design ated type of deviants in that ear . In the present conditions of very strongly focused attention , the MMN was elicited even by frequency change in the ignored input stream , and its amplitude was very similar to that of the MMN elicited by equivalent deviant stimuli ( targets ) in the attended input stream . In contrast , the MMN to intensity deviation was clearly attenuated in the absence of attention . This effect is , however , probably due to the attention effect on the MMN generator itself rather than the antecedent sensory- analysis and -storing functions",
"Background : Auditory event-related potentials ( AERP ) are neurophysiological correlates of sound perception and cognitive processes . Our aim was to study in very preterm born children at preschool age if AERP correlate with cognitive outcome . Methods : Seventy children ( mean ± SD gestational age 27.4 ± 1.9 wk , birth weight 996 ± 288 g ) were investigated at age 4.3–5.3 y with psychological testing ( WPPSI-R , four subtests of NEPSY ) . Electroencephalogram was recorded while they listened to a repeated st and ard tone , r and omly replaced by one of three deviants . Latencies and amplitudes for AERP components and mean amplitudes in successive 50-ms AERP time windows were measured . Results : Better cognitive test results and higher gestational age correlated with shorter P1 latencies and more positive mean amplitudes 150–500 ms after stimulus change onset . Neonatal brain damage was associated with a negative displacement of AERP curves . Neonatal morbidity had an impact on earlier time windows while gestational age and brain damage on both early and later time windows . Conclusion : AERP measures were associated with cognitive outcome . Neonatal morbidity mainly affects early cortical auditory encoding , while immaturity and brain damage additionally influence higher cortical functions of auditory perception and distraction . Perinatal auditory environment might play a role in development of auditory processing",
"OBJECTIVE The aim of this follow-up study was to evaluate the development of object naming ability and auditory processing in prematurely born children . Furthermore , we investigated whether the mismatch negativity ( MMN ) parameters at the age of 4 years correlate with the MMN parameters and naming ability at the age of 6 years . METHODS Twelve very low birth weight ( VLBW ) preterm children ( mean age 5 years 7 months ) and matched controls were studied . Object naming was measured by the Boston naming test . Auditory event-related potentials ( ERPs ) , especially the MMN , were recorded for Finnish syllables ( st and ard /taa/ ; deviants /ta/ and /kaa/ ) in an oddball paradigm . RESULTS VLBW preterm children scored significantly lower in the object naming test than their controls . The MMN amplitude for consonant change was significantly smaller in the preterm group compared to the controls . The MMN amplitude at the age of 4 years correlated with the MMN amplitude at the age of 6 years . Furthermore , absence of the MMN at the age of 4 years predicted naming difficulties at the age of 6 years . CONCLUSIONS VLBW preterm children with a difficulty to preattentively discriminate changes in syllables , as indexed by the diminished change detection response , MMN , seem to have sustained naming difficulty . Therefore , it is reasonable to record the MMN along with the language development from infancy , in order to identify the children at risk for language deficiencies and to provide appropriate rehabilitation",
"The aim of this prospect i ve pilot study was to evaluate the predictive value of discrimination and habituation , which was measured by mismatch negativity in 17 healthy very preterm ( mean gestational age 27.4 weeks ; range 25.0 - 31.3 ) and 16 term ( mean gestational age 40.3 weeks ; range 37.9 - 41.7 ) born infants at term equivalent age . Developmental outcome was measured by Bayley Scales of Infant Development – I in 13 preterm and 13 term-born children at a mean age of 21.7 months ( ±2.18 ) and 18.5 months ( ±1.9 ) , respectively . No differences in amplitude and latency of the mismatch negativity were found between both groups at term equivalent age . Within the preterm group habituation capacity was positively correlated with the Mental Developmental Index ( r = .654 , P = .008 ) and Performance Developmental Index ( r = .482 , P = .048 ) at 21 months . Early learning capability , as measured by habituation , may be associated with a better prognosis for early mental development in healthy preterm infants",
"Neurodevelopmental delays in intensive care neonates are common but difficult to predict . In children , hemisphere differences in cortical processing of speech are predictive of cognitive performance . We hypothesized that hemisphere differences in auditory event-related potentials in intensive care neonates are predictive of neurodevelopment in infancy , even in those born preterm . Event-related potentials to speech sounds were prospect ively recorded in 57 infants ( gestational age 24 - 40 weeks ) prior to discharge . The Developmental Assessment of Young Children was performed at 6 and 12 months . Hemisphere differences in mean amplitudes increased with postnatal age ( P hemisphere differences were associated with improved communication and cognitive scores at 6 and 12 months , but decreased in significance at 12 months after adjusting for socioeconomic and clinical factors . Auditory cortical responses can be used in intensive care neonates to help identify infants at higher risk for delays in infancy",
"The mismatch negativity ( MMN ) component of event-related potentials ( ERPs ) , a measure of passive change detection , is suggested to develop early in comparison to other ERP components , and an MMN-like response has been measured even from preterm infants . The MMN response in adults is negative in polarity at about 150 - 200 ms . However , the response measured in a typical MMN paradigm can also be markedly different in newborns , even opposite in polarity . This has been suggested to be related to maturational factors . To verify that suggestion , we measured ERPs of 21 newborns during quiet sleep to rarely occurring deviant tones of 1100 Hz ( probability 12 % ) embedded among repeated st and ard tones of 1000 Hz in an oddball sequence . Gestational age ( GA ) and two cardiac measures , vagal tone ( V ) and heart period ( HP ) , were used as measures of maturation . GA and HP explained between 36 % and 42 % of the total variance of the individual ERP peak amplitude ( the largest deflection of the difference wave at a time window of 150 - 375 ms ) at different scalp locations . In the discriminant function analyses , GA and HP as classifying variables differentiated infants in whom the peak of the difference wave had positive polarity from those with a negative polarity at an accuracy level ranging from 72 % to 91 % . These results demonstrate that during quiet sleep , maturational factors explain a significant portion of the ERP difference wave amplitude in terms of its polarity , indicating that the more mature the ERPs are , the more positive the amplitude . The present study suggests that maturational effects should be taken into account in ERP measurements using MMN paradigms with young infants"
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BACKGROUND Autism spectrum disorder ( ASD ) has an estimated prevalence of around 1.7 % of the population . People with ASD often also have language difficulties , and about 25 % to 30 % of children with ASD either fail to develop functional language or are minimally verbal . The ability to communicate effectively is an essential life skill , and difficulties with communication can have a range of adverse outcomes , including poorer academic achievement , behavioural difficulties and reduced quality of life . Historically , most studies have investigated communication interventions for ASD in verbal children . We can not assume the same interventions will work for minimally verbal children with ASD . OBJECTIVES To assess the effects of communication interventions for ASD in minimally verbal children . SEARCH METHODS We search ed CENTRAL , MEDLINE and Embase as well as 12 other data bases and three trials registers in November 2017 . We also checked the reference lists of all included studies and relevant review s , contacting experts in the field as well as authors of identified studies about other potentially relevant ongoing and unpublished studies . SELECTION CRITERIA R and omised controlled trials ( RCTs ) of communication-focused interventions for children ( under 12 years of age ) diagnosed with ASD and who are minimally verbal ( fewer than 30 functional words or unable to use speech alone to communicate ) , compared with no treatment , wait-list control or treatment as usual . DATA COLLECTION AND ANALYSIS We used st and ard Cochrane method ological procedures . MAIN RESULTS This review includes two RCTs ( 154 children aged 32 months to 11 years ) of communication interventions for ASD in minimally verbal children compared with a control group ( treatment as usual ) . One RCT used a verbally based intervention ( focused playtime intervention ; FPI ) administered by parents in the home , whereas the other used an alternative and augmentative communication ( AAC ) intervention ( Picture Exchange Communication System ; PECS ) administered by teachers in a school setting .The FPI study took place in the USA and included 70 participants ( 64 boys ) aged 32 to 82 months who were minimally verbal and had received a diagnosis of ASD . This intervention focused on developing coordinated toy play between child and parent . Participants received 12 in-home parent training sessions for 90 minutes per session for 12 weeks , and they were also invited to attend parent advocacy coaching sessions . This study was funded by the National Institute of Child Health and Human Development , the MIND Institute Research Program and a Professional Staff Congress-City University of New York grant . The PECS study included 84 minimally verbal participants ( 73 boys ) aged 4 to 11 years who had a formal diagnosis of ASD and who were not using PECS beyond phase 1 at baseline . All children attended autism-specific classes or units , and most classes had a child to adult ratio of 2:1 . Teachers and parents received PECS training ( two-day workshop ) . PECS consultants also conducted six half-day consultations with each class once per month over five months . This study took place in the UK and was funded by the Three Guineas Trust . Both included studies had high or unclear risk of bias in at least four of the seven ' Risk of bias ' categories , with a lack of blinding for participants and personnel being the most problematic area . Using the GRADE approach , we rated the overall quality of the evidence as very low due to risk of bias , imprecision ( small sample sizes and wide confidence intervals ) and because there was only one trial identified per type of intervention ( i.e. verbally based or AAC).Both studies focused primarily on communication outcomes ( verbal and non-verbal ) . One of the studies also collected information on social communication . The FPI study found no significant improvement in spoken communication , measured using the expressive language domain of the Mullen Scale of Early Learning expressive language , at postintervention . However , this study found that children with lower expressive language at baseline ( less than 11.3 months age-equivalent ) improved more than children with better expressive language and that the intervention produced expressive language gains in some children . The PECS study found that children enrolled in the AAC intervention were significantly more likely to use verbal initiations and PECS symbols immediately postintervention ; however , gains were not maintained 10 months later . There was no evidence that AAC improved frequency of speech , verbal expressive vocabulary or children 's social communication or pragmatic language immediately postintervention . Overall , neither of the interventions ( PECS or FPI ) result ed in maintained improvements in spoken or non-verbal communication in most children . Neither study collected information on adverse events , other communication skills , quality of life or behavioural outcomes . AUTHORS ' CONCLUSIONS There is limited evidence that verbally based and ACC interventions improve spoken and non-verbal communication in minimally verbal children with ASD . A substantial number of studies have investigated communication interventions for minimally verbal children with ASD , yet only two studies met inclusion criteria for this review , and we considered the overall quality of the evidence to be very low . In the study that used an AAC intervention , there were significant gains in frequency of PECS use and verbal and non-verbal initiations , but not in expressive vocabulary or social communication immediately postintervention . In the study that investigated a verbally based intervention , there were no significant gains in expressive language postintervention , but children with lower expressive language at the beginning of the study improved more than those with better expressive language at baseline . Neither study investigated adverse events , other communication skills , quality of life or behavioural outcomes . Future RCTs that compare two interventions and include a control group will allow us to better underst and treatment effects in the context of spontaneous maturation and will allow further comparison of different interventions as well as the investigation of moderating factors
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"A r and omized control trial comparing two social-communication interventions in young children with autism examined far-transfer of the use of picture exchange to communicate . Thirty-six children were r and omly assigned to one of two treatment conditions , one of which was the Picture Exchange Communication System ( PECS ) . All children had access to picture symbols during assessment s. Post-treatment measurement of the number of picture exchanges in a far-transfer , assessment context favored the PECS intervention . These findings were interpreted as support for the hypothesis that the PECS curriculum can successfully teach a generalized means of showing coordinated attention to object and person without requiring eye contact to children with ASD",
"BACKGROUND Delays and deficits in joint attention and symbolic play constitute two important developmental problems in young children with autism . These areas of deficit have been well studied in autism but have rarely been the focus of treatment efforts ( see Kasari , Freeman , & Paparella , 2001 ) . In this study , we examine the efficacy of targeted interventions of joint attention and symbolic play . METHODS Participants were 58 children with autism aged 3 and 4 years ( 46 boys ) . Children were r and omized to a joint attention intervention , a symbolic play intervention , or control group . Interventions were conducted 30 minutes daily for 5 - 6 weeks . Both structured assessment s of joint attention and play skills and mother-child interactions were collected pre and post intervention by independent assessors . RESULTS Results indicate that both intervention groups improved significantly over the control group on certain behaviors . Children in the joint attention intervention initiated significantly more showing and responsiveness to joint attention on the structured joint attention assessment and more child-initiated joint attention in the mother-child interaction . The children in the play group showed more diverse types of symbolic play in interaction with their mothers and higher play levels on both the play assessment and in interaction with their mothers . CONCLUSIONS This r and omized controlled trial provides promising data on the specificity and generalizability of joint attention and play interventions for young children with autism . Future studies need to examine the long-term effects of these early interventions on children 's development",
"PURPOSE The purpose of this study was to compare the effects of enhanced milieu teaching ( EMT ) implemented by parents and therapists versus therapists only on the language skills of preschool children with intellectual disabilities ( IDs ) , including children with Down syndrome and children with autism spectrum disorders . METHOD Seventy-seven children were r and omly assigned to 2 treatments ( parent + therapist EMT or therapist-only EMT ) and received 36 intervention sessions . Children were assessed before , immediately after , 6 months after , and 12 months after intervention . Separate linear regressions were conducted for each st and ardized and observational measure at each time point . RESULTS Parents in the parent + therapist group demonstrated greater use of EMT strategies at home than untrained parents in the therapist-only group , and these effects maintained over time . Effect sizes for observational measures ranged from d = 0.10 to d = 1.32 favoring the parent + therapist group , with the largest effect sizes found 12 months after intervention . CONCLUSION Findings from this study indicate generally that there are benefits to training parents to implement naturalistic language intervention strategies with preschool children who have ID and significant language impairments",
"OBJECTIVE This study reports 12-month follow-up data from a r and omized controlled trial of preschool-based social communication treatment for young children with autism . METHOD A total of 61 children ( 48 males ) with autism , 29 to 60 months of age , had earlier been r and omized either to 8 weeks of preschool-based social communication treatment in addition to st and ard preschool program ( n = 34 ) or to st and ard preschool program only ( n = 27 ) . Significant short-term effects on targeted social communication skills have previously been published . Long-term gains in social communication , language and global social functioning and communication were assessed from video-taped preschool teacher-child and mother-child interactions , Early Social Communication Scales , Reynell Developmental Language Scale , and Social Communication Question naire . RESULTS Compared with those in the control group , the treated children achieved significantly larger improvements in joint attention and joint engagement from baseline to 12-month follow-up . However , no effects were detected on language and global ratings of social functioning and communication . The treatment effect on child initiation of joint attention increased with increasing level of sociability at baseline , whereas nonverbal IQ and expressive language had no moderating effect . CONCLUSIONS This study is the first to show that , similar to specialist-delivered treatment , preschool-based treatment may produce small but possibly clinical ly important long-term changes in social communication in young children with autism . The treatment did not affect language and global ratings of social functioning and communication . More studies are needed to better underst and whether treatment effects may be improved by increasing the intensity and duration of the treatment . Clinical trial registration information -- Joint Attention Intervention and Young Children With Autism ; http:// clinical trials.gov/ ; NCT00378157",
"The current study is a r and omized clinical trial evaluating the efficacy of Focused Playtime Intervention ( FPI ) in a sample of 70 children with Autism Spectrum Disorder . This parent-mediated intervention has previously been shown to significantly increase responsive parental communication ( Siller et al. in J Autism Dev Disord 43:540–555 , 2013a ) . The current analyses focus on children ’s attachment related outcomes . Results revealed that children who were r and omly assigned to FPI showed bigger increases in attachment-related behaviors , compared to children assigned to the control condition . Significant treatment effects of FPI were found for both an observational measure of attachment-related behaviors elicited during a brief separation-reunion episode and a question naire measure evaluating parental perceptions of child attachment . The theoretical and clinical implication s of these findings are discussed",
"This single subject design study examined two models of intervention : Denver Model ( which merges behavioral , developmental , and relationship-oriented intervention ) , and PROMPT ( a neuro-developmental approach for speech production disorders ) . Ten young , nonverbal children with autism were matched in pairs and r and omized to treatment . They received 12 1-h weekly sessions of therapy and daily 1-h home intervention delivered by parents . Fidelity criteria were maintained throughout . Eight of the ten children used five or more novel , functional words spontaneously and spoke multiple times per hour by the conclusion of treatment . There were no differences in acquired language skills by intervention group . Initial characteristics of the best responders were mild to moderate symptoms of autism , better motor imitation skills , and emerging joint attention skills",
"We piloted a 2-week “ Autism-1 - 2 - 3 ” early intervention for children with autism and their parents immediately after diagnosis that targeted at ( 1 ) eye contact , ( 2 ) gesture and ( 3 ) vocalization/words . Seventeen children were r and omized into the Intervention ( n = 9 ) and Control ( n = 8) groups . Outcome measures included the Autism Diagnostic Observation Schedule , Ritvo-Freeman Real Life Rating Scale , Symbolic Play Test , and Parenting Stress Index . Children with autism improved in language /communication , reciprocal social interaction , and symbolic play . Parents perceived significant improvement in their children ’s language , social interaction , and their own stress level . This intervention can serve as short-term training on communication and social interaction for children with autism , and reduce the stress of their parents during the long waiting time for public health services",
"OBJECTIVE : To conduct a r and omized , controlled trial to evaluate the efficacy of the Early Start Denver Model ( ESDM ) , a comprehensive developmental behavioral intervention , for improving outcomes of toddlers diagnosed with autism spectrum disorder ( ASD ) . METHODS : Forty-eight children diagnosed with ASD between 18 and 30 months of age were r and omly assigned to 1 of 2 groups : ( 1 ) ESDM intervention , which is based on developmental and applied behavioral analytic principles and delivered by trained therapists and parents for 2 years ; or ( 2 ) referral to community providers for intervention commonly available in the community . RESULTS : Compared with children who received community-intervention , children who received ESDM showed significant improvements in IQ , adaptive behavior , and autism diagnosis . Two years after entering intervention , the ESDM group on average improved 17.6 st and ard score points ( 1 SD : 15 points ) compared with 7.0 points in the comparison group relative to baseline scores . The ESDM group maintained its rate of growth in adaptive behavior compared with a normative sample of typically developing children . In contrast , over the 2-year span , the comparison group showed greater delays in adaptive behavior . Children who received ESDM also were more likely to experience a change in diagnosis from autism to pervasive developmental disorder , not otherwise specified , than the comparison group . CONCLUSIONS : This is the first r and omized , controlled trial to demonstrate the efficacy of a comprehensive developmental behavioral intervention for toddlers with ASD for improving cognitive and adaptive behavior and reducing severity of ASD diagnosis . Results of this study underscore the importance of early detection of and intervention in autism",
"PURPOSE This r and omized group experiment compared the efficacy of 2 communication interventions ( Responsive Education and Prelinguistic Milieu Teaching [ RPMT ] and the Picture Exchange Communication System [ PECS ] ) on spoken communication in 36 preschoolers with autism spectrum disorders ( ASD ) . METHOD Each treatment was delivered to children for a maximum total of 24 hr over a 6-month period . Spoken communication was assessed in a rigorous test of generalization at pretreatment , posttreatment , and 6-month follow-up periods . RESULTS PECS was more successful than RPMT in increasing the number of nonimitative spoken communication acts and the number of different nonimitative words used at the posttreatment period . Considering growth over all 3 measurement periods , an exploratory analysis showed that growth rate of the number of different nonimitative words was faster in the PECS group than in the RPMT group for children who began treatment with relatively high object exploration . In contrast , analogous slopes were steeper in the RPMT group than in the PECS group for children who began treatment with relatively low object exploration",
"Objective : To evaluate the effectiveness of the Play and Language for Autistic Youngsters ( PLAY ) Project Home Consultation model , in combination with usual community services ( CS ) , to improve parent-child interaction , child development , and autism symptomatology in young children with autism spectrum disorders ( ASDs ) compared with CS only . Methods : Children ( N = 128 ) with autism or PDD-NOS ( DSM-4 criteria ) aged 2 years 8 months to 5 years 11 months and recruited from 5 disability agencies in 4 US states were r and omized in two 1-year cohorts . Using videotape and written feedback within a developmental framework , PLAY consultants coached caregivers monthly for 12 months to improve caregiver-child interaction . CS included speech/ language and occupational therapy and public education services . Primary outcomes included change in parent-child interactions , language and development , and autism-related diagnostic category/symptoms . Secondary outcomes included parent stress and depression and home consultant fidelity . Data were collected pre- and post-intervention . Results : Using intent-to-treat analysis ( ITT ) , large treatment effects were evident for parent and child interactional behaviors on the Maternal and Child Behavior Rating Scales . Child language and developmental quotient did not differ over time by group , although functional development improved significantly . PLAY children improved in diagnostic categories on the Autism Diagnostic Observation Schedule ( ADOS ) . PLAY caregivers ' stress did not increase , and depressive symptomatology decreased . Home consultants administered the intervention with fidelity . Conclusions : PLAY intervention demonstrated substantial changes in parent-child interaction without increasing parents ' stress/depression . ADOS findings must be interpreted cautiously because results do not align with clinical experience . PLAY offers communities a relatively inexpensive effective intervention for children with ASD and their parents",
"The purpose of this study was to compare the efficacy of Melodic Based Communication Therapy ( MBCT ) to traditional speech and language therapy for eliciting speech in nonverbal children with autism . Participants were 12 nonverbal children with autism ages 5 through 7 r and omly assigned to either treatment group . Both groups made significant progress after treatment . The MBCT group progressed significantly in number of verbal attempts after weeks 1 through 4 and number of correct words after weeks 1 and 3 , while the traditional group progressed significantly after weeks 4 and 5 . No significant differences in number of verbal attempts or number of correct words were noted between groups following treatment . A significant number of new words were heard in the home environment for the MBCT group ( p = .04 ) . Participants in the MBCT group had more imitative attempts ( p = .03 ) . MBCT appears to be a valid form of intervention for children with autism",
"Summary Background Results of small trials suggest that early interventions for social communication are effective for the treatment of autism in children . We therefore investigated the efficacy of such an intervention in a larger trial . Methods Children with core autism ( aged 2 years to 4 years and 11 months ) were r and omly assigned in a one-to-one ratio to a parent-mediated communication-focused ( Preschool Autism Communication Trial [ PACT ] ) intervention or treatment as usual at three specialist centres in the UK . Those assigned to PACT were also given treatment as usual . R and omisation was by use of minimisation of probability in the marginal distribution of treatment centre , age ( ≤42 months or > 42 months ) , and autism severity ( Autism Diagnostic Observation Schedule-Generic [ ADOS-G ] algorithm score 12–17 or 18–24 ) . Primary outcome was severity of autism symptoms ( a total score of social communication algorithm items from ADOS-G , higher score indicating greater severity ) at 13 months . Complementary secondary outcomes were measures of parent-child interaction , child language , and adaptive functioning in school . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N58133827 . Results 152 children were recruited . 77 were assigned to PACT ( London [ n=26 ] , Manchester [ n=26 ] , and Newcastle [ n=25 ] ) ; and 75 to treatment as usual ( London [ n=26 ] , Manchester [ n=26 ] , and Newcastle [ n=23 ] ) . At the 13-month endpoint , the severity of symptoms was reduced by 3·9 points ( SD 4·7 ) on the ADOS-G algorithm in the group assigned to PACT , and 2·9 ( 3·9 ) in the group assigned to treatment as usual , representing a between-group effect size of −0·24 ( 95 % CI −0·59 to 0·11 ) , after adjustment for centre , sex , socioeconomic status , age , and verbal and non-verbal abilities . Treatment effect was positive for parental synchronous response to child ( 1·22 , 0·85 to 1·59 ) , child initiations with parent ( 0·41 , 0·08 to 0·74 ) , and for parent-child shared attention ( 0·33 , −0·02 to 0·68 ) . Effects on directly assessed language and adaptive functioning in school were small . Interpretation On the basis of our findings , we can not recommend the addition of the PACT intervention to treatment as usual for the reduction of autism symptoms ; however , a clear benefit was noted for parent-child dyadic social communication . Funding UK Medical Research Council , and UK Department for Children , Schools and Families",
"BACKGROUND With rates of autism diagnosis continuing to rise , there is an urgent need for effective and efficient service delivery models . Pivotal Response Treatment ( PRT ) is considered an established treatment for autism spectrum disorder ( ASD ) ; however , there have been few well-controlled studies with adequate sample size . The aim of this study was to conduct a r and omized controlled trial to evaluate PRT parent training group ( PRTG ) for targeting language deficits in young children with ASD . METHODS Fifty-three children with autism and significant language delay between 2 and 6 years old were r and omized to PRTG ( N = 27 ) or psychoeducation group ( PEG ; N = 26 ) for 12 weeks . The PRTG taught parents behavioral techniques to facilitate language development . The PEG taught general information about ASD ( clinical trial NCT01881750 ; http://www . clinical trials.gov ) . RESULTS Analysis of child utterances during the structured laboratory observation ( primary outcome ) indicated that , compared with children in the PEG , children in the PRTG demonstrated greater improvement in frequency of utterances ( F(2 , 43 ) = 3.53 , p = .038 , d = 0.42 ) . Results indicated that parents were able to learn PRT in a group format , as the majority of parents in the PRTG ( 84 % ) met fidelity of implementation criteria after 12 weeks . Children also demonstrated greater improvement in adaptive communication skills ( Vinel and -II ) following PRTG and baseline Mullen visual reception scores predicted treatment response to PRTG . CONCLUSIONS This is the first r and omized controlled trial of group-delivered PRT and one of the largest experimental investigations of the PRT model to date . The findings suggest that specific instruction in PRT results in greater skill acquisition for both parents and children , especially in functional and adaptive communication skills . Further research in PRT is warranted to replicate the observed results and address other core ASD symptoms",
"Children with autism exhibit deficits in their quantity and quality of joint attention . Early autism intervention studies rarely document improvement in joint attention quality . The purpose of this study was to determine whether there was a change in joint attention quality for preschoolers with autism who were r and omized to a joint attention intervention , symbolic play intervention , or a control group . Quality was defined as shared positive affect during joint attention as well as shared positive affect and utterances during joint attention . Interactions of group and time were found for both types of joint attention quality . During the follow up visits , the joint attention and symbolic play intervention groups produced more of these two types of joint attention quality than the control group",
"Twenty-four children with autism were r and omly assigned to a clinic-directed group , replicating the parameters of the early intensive behavioral treatment developed at UCLA , or to a parent-directed group that received intensive hours but less supervision by equally well-trained supervisors . Outcome after 4 years of treatment , including cognitive , language , adaptive , social , and academic measures , was similar for both groups . After combining groups , we found that 48 % of all children showed rapid learning , achieved average posttreatment scores , and at age 7 , were succeeding in regular education classrooms . Treatment outcome was best predicted by pretreatment imitation , language , and social responsiveness . These results are consistent with those reported by Lovaas and colleagues ( Lovaas , 1987 ; McEachin , Smith , & Lovaas , 1993 )",
"Imitation is an early skill thought to play a role in social development , leading some to suggest that teaching imitation to children with autism should lead to improvements in social functioning . This study used a r and omized controlled trial to evaluate the effect of a focused imitation intervention on initiation of joint attention and social-emotional functioning in 27 young children with autism . Results indicated the treatment group made significantly more gains in joint attention initiations at post-treatment and follow-up and social-emotional functioning at follow-up than the control group . Although gains in social functioning were associated with treatment , a mediation analysis did not support imitation as the mechanism of action . These findings suggest the intervention improves social functioning in children with ASD",
"This r and omized group experiment compared the efficacy of 2 communication interventions ( Responsive Education and Prelinguistic Milieu Teaching [ RPMT ] and the Picture Exchange Communication System [ PECS ] ) in 36 preschoolers with autism spectrum disorders . Each treatment was delivered 3 times per week , in 20-min sessions , for 6 months . The results revealed that the RPMT facilitated the frequency of generalized turn taking and generalized initiating joint attention more than did the PECS . The latter effect occurred only for children who began treatment with at least some initiating joint attention . In contrast , the PECS facilitated generalized requests more than the RPMT in children with very little initiating joint attention prior to treatment . These effect sizes were large",
"OBJECTIVES : To compare the effects of two 9-month parent-implemented interventions within the Early Social Interaction ( ESI ) Project . Both individual-ESI , offered 2 or 3 times per week at home or in the community , and group-ESI , offered once per week in a clinic , taught parents how to embed strategies to support social communication throughout everyday activities . METHODS : Participants in the r and omized controlled trial included 82 children diagnosed with autism spectrum disorder at 16 to 20 months . Children were matched on pretreatment nonverbal developmental level and pairs were r and omly assigned to treatment condition . Child outcomes included measures of social communication , autism symptoms , adaptive behavior , and developmental level . Child outcomes are reported from baseline to the end of the 9-month interventions . RESULTS : Children in individual-ESI showed differential change on a st and ardized examiner-administered observational measure of social communication , as they improved at a faster rate than children in group-ESI . Individual-ESI also showed differential efficacy on a parent report measure of communication , daily living , and social skills , as they showed improvement or stability , whereas group-ESI led to worsening or no significant change on these skills . Finally , individual-ESI showed differential change on examiner-administered measures of receptive language skills , as children in individual-ESI improved significantly , whereas group-ESI showed no change . CONCLUSIONS : These findings support the efficacy of individual-ESI compared with group-ESI on child outcomes , suggesting the importance of individualized parent coaching in natural environments . The efficacy of a parent-implemented intervention using little professional time has potential for community viability , which is particularly important in light of the lack of main effects on child outcomes of most other parent-implemented interventions",
"This study evaluated a technology-based early intervention for social communication skills in pre-schoolers in a r and omised controlled trial . Participants were 54 children aged under 6 years with a diagnosis of autism , assigned to either intervention or control conditions . The app engaged children , who played consistently , regardless of developmental level , and was rated highly by parents . There were no significant group differences in parent-report measures post-intervention , nor in a measure of parent – child play at follow-up . Therefore , this intervention did not have an observable impact on real-world social communication skills and caution is recommended about the potential usefulness of iPad ™ apps for amelioration of difficulties in interaction . However , positive attitudes among participants , lack of harms and the potential of apps to deliver therapeutic content at low economic cost suggest this approach is worth pursuing further , perhaps targeting other skill domains",
"This r and omized controlled trial compared results obtained after 12 months of nonintensive parent training plus care-as-usual and care-as-usual alone . The training focused on stimulating joint attention and language skills and was based on the intervention described by Drew et al. ( Eur Child Adolesc Psychiatr 11:266–272 , 2002 ) . Seventy-five toddlers with autism spectrum disorder ( 65 autism , 10 PDD-NOS , mean age = 34.4 months , SD = 6.2 ) were enrolled . Analyses were conducted on a final sample of 67 children ( lost to follow-up = 8) . No significant intervention effects were found for any of the primary ( language ) , secondary ( global clinical improvement ) , or mediating ( child engagement , early precursors of social communication , or parental skills ) outcome variables , suggesting that the ‘ Focus parent training ’ was not of additional value to the more general care-as-usual",
"OBJECTIVE The vast majority of children with an autism spectrum disorder ( ASD ) attend public preschools at some point in their childhood . Community preschool practice s often are not evidence based , and almost none target the prelinguistic core deficits of ASD . This study investigated the effectiveness of public preschool teachers implementing a vali date d intervention ( the Joint Attention and Symbolic Play/Engagement and Regulation intervention ; JASP/ER ) on a core deficit of autism , initiating joint attention . METHOD Sixteen dyads ( preschoolers with ASD and the public school teachers who worked in the child 's classroom ) were r and omly assigned to the 6-week JASP/ER intervention or a control group . RESULTS At the end of the intervention , JASP/ER teachers used more JASP/ER strategies than the control teachers , and JASP/ER preschoolers used more joint attention in their classroom than control children . Additionally , JASP/ER children spent more time in supported engagement and less time in object engagement than control preschoolers on a taped play interaction . CONCLUSIONS Findings suggest that teachers were able to improve a core deficit of children with ASD in a public preschool context ",
"PURPOSE This study compared the language performance of young children with developmental delays who were r and omly assigned to 1 of 3 parent-coached language interventions . Differences in performance on augmented and spoken word size and use , vocabulary size , and communication interaction skills were examined . METHOD Sixty-eight toddlers with fewer than 10 spoken words were r and omly assigned to augmented communication input ( AC-I ) , augmented communication output ( AC-O ) , or spoken communication ( SC ) interventions ; 62 children completed the intervention . This trial assessed the children 's symbolic language performance using communication measures from the language transcripts of the 18th and 24th intervention sessions and coding of target vocabulary use . RESULTS All children in the AC-O and AC-I intervention groups used augmented and spoken words for the target vocabulary items , whereas children in the SC intervention produced a very small number of spoken words . Vocabulary size was substantially larger for AC-O and AC-I than for SC groups . CONCLUSIONS This study found that augmented language interventions that include parent coaching have a positive communication effect on young children with developmental delays who begin with fewer than 10 spoken words . Clinical implication s suggest that augmented communication does not hinder , and actually aids , speech production abilities in young children with developmental delays",
"Young children with pervasive developmental disorder were r and omly assigned to intensive treatment or parent training . The intensive treatment group ( 7 with autism , 8 with pervasive developmental disorder not otherwise specified -- NOS ) averaged 24.52 hours per week of individual treatment for one year , gradually reducing hours over the next 1 to 2 years . The parent training group ( 7 with autism , 6 with pervasive developmental disorder NOS ) received 3 to 9 months of parent training . The groups appeared similar at intake on all measures ; however , at follow-up the intensive treatment group outperformed the parent training group on measures of intelligence , visual-spatial skills , language , and academics , though not adaptive functioning or behavior problems . Children with pervasive developmental disorder NOS may have gained more than those with autism",
"PURPOSE To assess any changes in the Functional Communicative Profile ( FCP ) and in the Social Cognitive Performance ( SCP ) of children with Autism Spectrum Disorders , based on two short periods of intervention . METHODS The study was conducted with 21 children with Autism Spectrum Disorder diagnoses , r and omly allocated into two groups , who received the same short-term intervention types ( 6 weeks with the mother and 6 weeks with the support of an educational software program ) . The intervention process was conducted by speech- language pathologists who were part of a graduate program in this area . RESULTS Sample s of 15-minute interaction sessions between the child and speech- language pathologist were used to assess the changes in the FCP and the SCP . The statistic analysis pointed out differences only in Group 1 for the variables \" percentage of communicative space used \" and \" use of the mediating object \" . CONCLUSION With the intervention sessions structured over 12 weeks , it was possible to observe a few changes in the children 's FCP and in the SCP . Therefore , we point out the need for new research studies of longer duration",
"Presently there is no consensus on the specific behavioral treatment of choice for targeting language in young nonverbal children with autism . This r and omized clinical trial compared the effectiveness of a verbally-based intervention , Pivotal Response Training ( PRT ) to a pictorially-based behavioral intervention , the Picture Exchange Communication System ( PECS ) on the acquisition of spoken language by young ( 2–4 years ) , nonverbal or minimally verbal ( ≤9 words ) children with autism . Thirty-nine children were r and omly assigned to either the PRT or PECS condition . Participants received on average 247 h of intervention across 23 weeks . Dependent measures included overall communication , expressive vocabulary , pictorial communication and parent satisfaction . Children in both intervention groups demonstrated increases in spoken language skills , with no significant difference between the two conditions . Seventy-eight percent of all children exited the program with more than 10 functional words . Parents were very satisfied with both programs but indicated PECS was more difficult to implement",
"This r and omized field trial comparing Strategies for Teaching based on Autism Research and Structured Teaching enrolled educators in 33 kindergarten-through-second- grade autism support classrooms and 119 students , aged 5–8 years in the School District of Philadelphia . Students were assessed at the beginning and end of the academic year using the Differential Ability Scales . Program fidelity was measured through video coding and use of a checklist . Outcomes were assessed using linear regression with r and om effects for classroom and student . Average fidelity was 57 % in Strategies for Teaching based on Autism Research classrooms and 48 % in Structured Teaching classrooms . There was a 9.2-point ( st and ard deviation = 9.6 ) increase in Differential Ability Scales score over the 8-month study period , but no main effect of program . There was a significant interaction between fidelity and group . In classrooms with either low or high program fidelity , students in Strategies for Teaching based on Autism Research experienced a greater gain in Differential Ability Scales score than students in Structured Teaching ( 11.2 vs 5.5 points and 11.3 vs 8.9 points , respectively ) . In classrooms with moderate fidelity , students in Structured Teaching experienced a greater gain than students in Strategies for Teaching based on Autism Research ( 10.1 vs 4.4 points ) . The results suggest significant variability in implementation of evidence -based practice s , even with supports , and also suggest the need to address challenging issues related to implementation measurement in community setting",
"Thirty-five children diagnosed with autism were r and omly assigned to either a joint attention or a symbolic play intervention . During the 5—8 week treatment , three novel probes were administered to determine mastery of joint attention skills . The probes consisted of auditory and visual stimuli , such as a loud spider crawling or a musical ball bouncing . The current study examined affect , gaze , joint attention behaviors , and verbalizations at three different time points of intervention . Results revealed that children r and omized to the joint attention group were more likely to acknowledge the probe and engage in shared interactions between intervener and probe upon termination of intervention . Additionally , the joint attention group improved in the proportion of time spent sharing coordinated joint looks between intervener and probe . These results suggest that generalization of joint attention skills to a novel probe did occur for the group targeting joint attention and provides further evidence of the effectiveness of the joint attention intervention",
"Based on earlier studies , an adult ’s imitations of the behaviors of children with autism lead to increased social behavior in the children . The present study explored the effects of repeated sessions of imitation . Twenty children were recruited from a school for children with autism to attend three sessions during which an adult either imitated all of the children ’s behaviors or simply played with the child . During the second session the children in the imitation group spent a greater proportion of time showing distal social behaviors toward the adult including : ( 1 ) looking ; ( 2 ) vocalizing ; ( 3 ) smiling ; and ( 4 ) engaging in reciprocal play . During the third session , the children in the imitation group spent a greater proportion of time showing proximal social behaviors toward the adult including : ( 1 ) being close to the adult ; ( 2 ) sitting next to the adult ; and ( 3 ) touching the adult . These data suggest the potential usefulness of adult imitative behavior as an early intervention",
"There are limited data on the effects of adaptive social communication interventions with a speech-generating device in autism . This study is the first to compare growth in communications outcomes among three adaptive interventions in school-age children with autism spectrum disorder ( ASD ) who are minimally verbal . Sixty-one children , ages 5–8 years , participated in a sequential , multiple-assignment r and omized trial ( SMART ) . All children received a developmental behavioral communication intervention : joint attention , symbolic play , engagement and regulation ( JASP ) with enhanced milieu teaching ( EMT ) . The SMART included three 2-stage , 24-week adaptive interventions with different provisions of a speech-generating device ( SGD ) in the context of JASP+EMT . The first adaptive intervention , with no SGD , initially assigned JASP+EMT alone , then intensified JASP+EMT for slow responders . In the second adaptive intervention , slow responders to JASP+EMT were assigned JASP+EMT+SGD . The third adaptive intervention initially assigned JASP+EMT+SGD ; then intensified JASP+EMT+SGD for slow responders . Analyses examined between-group differences in change in outcomes from baseline to Week 36 . Verbal outcomes included spontaneous communicative utterances and novel words . Nonlinguistic communication outcomes included initiating joint attention and behavior regulation , and play . The adaptive intervention beginning with JASP+EMT+SGD was estimated as superior . There were significant ( p in spontaneous communicative utterances and initiating joint attention . School-age children with ASD who are minimally verbal make significant gains in communication outcomes with an adaptive intervention beginning with JASP+EMT+SGD . Future research should explore mediators and moderators of the adaptive intervention effects and second-stage intervention options that further capitalize on early gains in treatment",
"Few research -developed early intervention models have been deployed to and tested in real world preschool programs . In this study , teaching staff implemented a social communication modularized intervention , JASPER , in their daily program . Sixty-six preschool children with autism in twelve classrooms ( 12 teachers ) were r and omized to receive immediate JASPER training ( IT ) or were waitlisted ( WL ) for 3 months with a 1-month follow up . Measures of core deficits ( initiations of joint engagement , joint attention gestures and language , play skills ) and st and ardized cognitive measures were improved for IT over WL children . IT teachers achieved and maintained high fidelity . Teachers can implement evidence -based interventions with significant improvements in core deficits of their children with ASD",
"BACKGROUND Psychosocial treatments are the mainstay of management of autism in the UK but there is a notable lack of a systematic evidence base for their effectiveness . R and omised controlled trial ( RCT ) studies in this area have been rare but are essential because of the developmental heterogeneity of the disorder . We aim ed to test a new theoretically based social communication intervention targeting parental communication in a r and omised design against routine care alone . METHODS The intervention was given in addition to existing care and involved regular monthly therapist contact for 6 months with a further 6 months of 2-monthly consolidation sessions . It aim ed to educate parents and train them in adapted communication tailored to their child 's individual competencies . Twenty-eight children with autism were r and omised between this treatment and routine care alone , stratified for age and baseline severity . Outcome was measured at 12 months from commencement of intervention , using st and ardised instruments . RESULTS All cases studied met full Autism Diagnostic Interview ( ADI ) criteria for classical autism . Treatment and controls had similar routine care during the study period and there were no study dropouts after treatment had started . The active treatment group showed significant improvement compared with controls on the primary outcome measure -- Autism Diagnostic Observation Schedule ( ADOS ) total score , particularly in reciprocal social interaction-- and on secondary measures of expressive language , communicative initiation and parent-child interaction . Suggestive but non-significant results were found in Vinel and Adaptive Behaviour Scales ( Communication Sub-domain ) and ADOS stereotyped and restricted behaviour domain . CONCLUSIONS A R and omised Treatment Trial design of this kind in classical autism is feasible and acceptable to patients . This pilot study suggests significant additional treatment benefits following a targeted ( but relatively non-intensive ) dyadic social communication treatment , when compared with routine care . The study needs replication on larger and independent sample s. It should encourage further RCT design s in this area",
"Aim : To determine the effect of parent education on adaptive behaviour , autism symptoms and cognitive/ language skills of young children with autistic disorder . Method : A r and omised group comparison design involving a parent education and counselling intervention and a parent education and behaviour management intervention to control for parent skills training and a control sample . Two rural and two metropolitan regions were r and omly allocated to intervention groups ( n = 70 ) or control ( n = 35 ) . Parents from autism assessment services in the intervention regions were r and omly allocated to parent education and behaviour management ( n = 35 ) or parent education and counselling ( n = 35 ) . Results : Parent education and behaviour management result ed in significant improvement in adaptive behaviour and autism symptoms at 6 months follow-up for children with greater delays in adaptive behaviour . Parent education and behaviour management was superior to parent education and counselling . We conclude that a 20-week parent education programme including skills training for parents of young children with autistic disorder provides significant improvements in child adaptive behaviour and symptoms of autism for low-functioning children",
"OBJECTIVE To assess the effectiveness of expert training and consultancy for teachers of children with autism spectrum disorder in the use of the Picture Exchange Communication System ( PECS ) . METHOD DESIGN Group r and omised , controlled trial ( 3 groups : immediate treatment , delayed treatment , no treatment ) . PARTICIPANTS 84 elementary school children , mean age 6.8 years . TREATMENT A 2-day PECS workshop for teachers plus 6 half-day , school-based training sessions with expert consultants over 5 months . OUTCOME MEASURES Rates of : communicative initiations , use of PECS , and speech in the classroom ; Autism Diagnostic Observation Schedule-Generic ( ADOS-G ) domain scores for Communication and Reciprocal Social Interaction ; scores on formal language tests . RESULTS Controlling for baseline age , developmental quotient ( DQ ) and language ; rates of initiations and PECS usage increased significantly immediately post-treatment ( Odds Ratio ( OR ) of being in a higher ordinal rate category 2.72 , 95 % confidence interval 1.22 - 6.09 , p in frequency of speech , or improvements in ADOS-G ratings or language test scores . CONCLUSIONS The results indicate modest effectiveness of PECS teacher training/consultancy . Rates of pupils ' initiations and use of symbols in the classroom increased , although there was no evidence of improvement in other areas of communication . TREATMENT effects were not maintained once active intervention ceased",
"BACKGROUND Social and communication impairments are core deficits and prognostic indicators of autism . We evaluated the impact of supplementing a comprehensive intervention with a curriculum targeting socially synchronous behavior on social outcomes of toddlers with autism spectrum disorders ( ASD ) . METHODS Fifty toddlers with ASD , ages 21 to 33 months , were r and omized to one of two six-month interventions : Interpersonal Synchrony or Non-Interpersonal Synchrony . The interventions provided identical intensity ( 10 hours per week in classroom ) , student-to-teacher ratio , schedule , home-based parent training ( 1.5 hours per month ) , parent education ( 38 hours ) , and instructional strategies , except the Interpersonal Synchrony condition provided a supplementary curriculum targeting socially engaged imitation , joint attention , and affect sharing ; measures of these were primary outcomes . Assessment s were conducted pre-intervention , immediately post-intervention , and , to assess maintenance , at six-month follow-up . R and om effects models were used to examine differences between groups over time . Secondary analyses examined gains in expressive language and nonverbal cognition , and time effects during the intervention and follow-up periods . RESULTS A significant treatment effect was found for socially engaged imitation ( p = .02 ) , with more than doubling ( 17 % to 42 % ) of imitated acts paired with eye contact in the Interpersonal Synchrony group after the intervention . This skill was generalized to unfamiliar context s and maintained through follow-up . Similar gains were observed for initiation of joint attention and shared positive affect , but between-group differences did not reach statistical significance . A significant time effect was found for all outcomes ( p toddlers to identify an active ingredient for enhancing socially engaged imitation . Adding social engagement targets to intervention improves short-term outcome at no additional cost to the intervention . The social , language , and cognitive gains in our participants provide evidence for plasticity of these developmental systems in toddlers with ASD . http://www . clinical trials.gov/ct2/show/NCT00106210?term = l and a&rank = 3",
"In this pilot study , we tested the effects of a novel intervention ( JASPER , Joint Attention Symbolic Play Engagement and Regulation ) on 3 to 5 year old , minimally verbal children with autism who were attending a non-public preschool . Participants were r and omized to a control group ( treatment as usual , 30 h of ABA-based therapy per week ) or a treatment group ( substitution of 30 min of JASPER treatment , twice weekly during their regular program ) . A baseline of 12 weeks in which no changes were noted in core deficits was followed by 12 weeks of intervention for children r and omized to the JASPER treatment . Participants in the treatment group demonstrated greater play diversity on a st and ardized assessment . Effects also generalized to the classroom , where participants in the treatment group initiated more gestures and spent less time unengaged . These results provide further support that even brief , targeted interventions on joint attention and play can improve core deficits in minimally verbal children with ASD",
"OBJECTIVE This study tested the effect of beginning treatment with a speech-generating device ( SGD ) in the context of a blended , adaptive treatment design for improving spontaneous , communicative utterances in school-aged , minimally verbal children with autism . METHOD A total of 61 minimally verbal children with autism , aged 5 to 8 years , were r and omized to a blended developmental/behavioral intervention ( JASP+EMT ) with or without the augmentation of a SGD for 6 months with a 3-month follow-up . The intervention consisted of 2 stages . In stage 1 , all children received 2 sessions per week for 3 months . Stage 2 intervention was adapted ( by increased sessions or adding the SGD ) based on the child 's early response . The primary outcome was the total number of spontaneous communicative utterances ; secondary measures were the total number of novel words and total comments from a natural language sample . RESULTS Primary aim results found improvements in spontaneous communicative utterances , novel words , and comments that all favored the blended behavioral intervention that began by including an SGD ( JASP+EMT+SGD ) as opposed to spoken words alone ( JASP+EMT ) . Secondary aim results suggest that the adaptive intervention beginning with JASP+EMT+SGD and intensifying JASP+EMT+SGD for children who were slow responders led to better posttreatment outcomes . CONCLUSION Minimally verbal school-aged children can make significant and rapid gains in spoken spontaneous language with a novel , blended intervention that focuses on joint engagement and play skills and incorporates an SGD . Future studies should further explore the tailoring design used in this study to better underst and children 's response to treatment . Clinical trial registration information-Developmental and Augmented Intervention for Facilitating Expressive Language ( CCNIA ) ; http:// clinical trials.gov/ ; NCT01013545",
"OBJECTIVE This article examines the form and function of spontaneous communication and outcome predictors in nonverbal children with autism following classroom-based intervention ( Picture Exchange Communication System [ PECS ] training ) . METHOD 84 children from 15 schools participated in a r and omized controlled trial ( RCT ) of PECS ( P. Howlin , R. K. Gordon , G. Pasco , A. Wade , & T. Charman , 2007 ) . They were aged 4 - 10 years ( 73 boys ) . Primary outcome measure was naturalistic observation of communication in the classroom . Multilevel Poisson regression was used to test for intervention effects and outcome predictors . RESULTS Spontaneous communication using picture cards , speech , or both increased significantly following training ( rate ratio [ RR ] = 1.90 , 95 % CI [ 1.46 , 2.48 ] , p Spontaneous communication to request objects significantly increased ( RR = 2.17 , 95 % CI [ 1.75 , 2.68 ] , p spontaneous speech persisted by follow-up ( 9 months later ) . Less severe baseline autism symptomatology ( lower Autism Diagnosis Observation Schedule [ ADOS ] score ; C. Lord et al. , 2000 ) was associated with greater increase in spontaneous speech ( RR = 0.90 , 95 % CI [ 0.83 , 0.98 ] , p = .011 ) and less severe baseline expressive language impairment ( lower ADOS item A1 score ) , with larger increases in spontaneous use of speech and pictures together ( RR = 0.62 , 95 % CI [ 0.44 , 0.88 ] , p = .008 ) . CONCLUSION Overall , PECS appeared to enhance children 's spontaneous communication for instrumental requesting using pictures , speech , or a combination of both . Some effects of training were moderated by baseline factors . For example , PECS appears to have increased spontaneous speech in children who could talk a little at baseline",
"Longitudinal research has demonstrated that responsive parental behaviors reliably predict subsequent language gains in children with autism spectrum disorder . To investigate the underlying causal mechanisms , we conducted a r and omized clinical trial of an experimental intervention ( Focused Playtime Intervention , FPI ) that aims to enhance responsive parental communication ( N = 70 ) . Results showed a significant treatment effect of FPI on responsive parental behaviors . Findings also revealed a conditional effect of FPI on children ’s expressive language outcomes at 12-month follow up , suggesting that children with baseline language skills below 12 months ( n = 24 ) are most likely to benefit from FPI . Parents of children with more advanced language skills may require intervention strategies that go beyond FPI ’s focus on responsive communication",
"The study evaluates a social-communication-based approach to autism intervention aim ed at improving the social interaction skills of children with autism spectrum disorder . We report preliminary results from an ongoing r and omized controlled trial of 51 children aged 2 years 0 months to 4 years 11 months . Participants were assigned to either a target treatment or community treatment group . Families in the target treatment group were given 2 hours of therapy and coaching each week in an intervention emphasizing social-interaction and the parent-child relationship . Children in the community treatment group received a variety of services averaging 3.9 hours per week . After 12 months , outcomes were measured to determine changes in the groups in social interaction and communication . In addition , a regression analysis was conducted to determine whether changes in social interaction skills were associated with language development . Results suggest that children in the treatment group made significantly greater gains in social interaction skills in comparison to the community treatment group , but no between-group differences were found for st and ard language assessment s. Initiation of joint attention , involvement , and severity of language delay were found to be significantly associated with improvement of language skills in children with autism . Finally caregiver skills targeted by the intervention were found to be significantly associated with changes in children ’s interaction skills",
"The purpose of this study was to determine ( 1 ) whether comprehension , production , and spontaneous use of language are greater following language training by sign-alone , speech-alone , simultaneous communication , or alternating between speech and sign ; ( 2 ) whether high- and low-verbal imitators benefit from the same mode of treatment ; and ( 3 ) whether retention of the language skills differs among the four training conditions . Subjects were 60 moderate to severe autistic children r and omly assigned to one of four treatment conditions . Subjects were divided into high- and low-verbal imitators based on verbal imitation performances . The results indicated that the high-verbal imitators did equally well in all four treatment conditions , while the low-verbal imitators did poorest in the speech-alone condition . The high-verbal imitators performed better than did the low-verbal imitators in all of the treatment conditions . Words or signs learned were retained for three months after treatment regardless of the treatment condition or level of imitative ability . The results were discussed in terms of the efficacy of using sign language with autistic children",
"This study was carried out to test the main and interaction effects of training condition and pretreatment-elicited verbal imitation ability when predicting spoken language use during language training of 60 minimally verbal autistic children . Subjects were r and omly assigned to Speech Alone , Sign Alone , Simultaneous Presentation of Sign and Speech , and Alternating Presentation of Sign and Speech training conditions . Speech Alone , Simultaneous Presentation , and Alternating Presentation condition facilitated more child-initiated speech during treatment than did the Sign Alone condition . Regardless of training condition , pretreatment verbal imitation ability positively predicted the size of child-initiated spoken vocabulary observed during training . Exploratory analyses indicated that , in addition to verbal imitation , pretreatment age and IQ may also predict spoken language developed during training",
"Enhancing immediate and contingent responding by caregivers to children ’s signals is an important strategy to support social interactions between caregivers and their children with autism . Yet , there has been limited examination of parents ’ responsive behaviour in association with children ’s social behaviour post caregiver-mediated intervention . Eighty-five dyads were r and omized to one of two 10-week caregiver-training interventions . Parent – child play interactions were coded for parental responsivity and children ’s joint engagement . Significant gains in responsivity and time jointly engaged were found post JASPER parent-mediated intervention over a psychoeducation intervention . Further , combining higher levels of responsive behaviour with greater adoption of intervention strategies was associated with greater time jointly engaged . Findings encourage a focus on enhancing responsive behaviour in parent-mediated intervention models",
"Abstract . Few attempts have been made to conduct r and omised control trials ( RCTs ) of interventions for pre-school children with autism . We report findings of a pilot RCT for a parent training intervention with a focus on the development of joint attention skills and joint action routines . Twenty-four children meeting ICD-10 criteria for childhood autism ( mean age = 23 months ) were identified using the CHAT screen and r and omised to the parent training group or to local services only . A follow-up was conducted 12 months later ( mean age = 35 months ) . There was some evidence that the parent training group made more progress in language development than the local services group . However , the present pilot study was compromised by several factors : a reliance on parental report to measure language , non-matching of the groups on initial IQ , and a lack of systematic checking regarding the implementation of the parent training intervention . Furthermore , three parents in the local services group commenced intensive , home-based behavioural intervention during the course of the study . The difficulties encountered in the conduct of RCTs for pre-school children with autism are discussed . Method ological challenges and strategies for future well- design ed RCTs for autism interventions are highlighted",
"OBJECTIVE This study compared effects of two parent-mediated interventions on joint engagement outcomes as augmentations of an early intervention program for toddlers with autism spectrum disorder ( ASD ) . METHOD Participants included 86 toddlers ( range 22 - 36 months ) with ASD and their primary caregiver . Caregiver-child dyads were r and omized to receive 10 weeks of h and s-on parent training in a naturalistic , developmental behavioral intervention ( joint attention , symbolic play , engagement and regulation-JASPER ) or a parent-only psychoeducational intervention ( PEI ) . Dose was controlled in terms of research er-parent contact and early intervention services received by the child . RESULTS Results yielded significant effects of the JASPER intervention on the primary outcome of joint engagement . The treatment effect was large ( Cohen 's f² = .69 ) and maintained over the 6-month follow-up . JASPER effects were also found on secondary outcomes of play diversity , highest play level achieved , and generalization to the child 's classroom for child-initiated joint engagement . The PEI intervention was found to be effective in reducing parenting stress associated with child characteristics . All secondary effects were generally small to moderate . CONCLUSIONS These data highlight the benefit of a brief , targeted , parent-mediated intervention on child outcomes . Future studies may consider the combination of JASPER and PEI treatments for optimal parent and child outcomes . Trial registry no. NCT00999778"
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41175244-06ff-11f0-808a-c43d1ab1c353
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Physical activity is recommended for people with stable heart failure ( HF ) , because it is known to improve quality of life and health outcomes . However , adherence to this recommendation has been poor in many studies . A systematic review was conducted to examine the effectiveness of strategies used to promote exercise adherence in those with HF . The following data bases were search ed for relevant literature published between January 1980 and December 2010 : British Nursing Index ; CINAHL ; Cochrane Library ; Embase ; Medline and PsycINFO . Papers with a control group focused on adults with HF that measured exercise or physical activity adherence were included . Nine r and omised controlled trials were identified , involving a total of 3,231 patients ( range 16–2,331 ) . Six of these studies were informed by specific psychological theories . Positive outcomes occurred in the short-term from interventions using approaches such as exercise prescriptions , goal setting , feedback and problem-solving . However , longer-term maintenance of exercise was less successful . There was some support for interventions underpinned by theoretical frameworks , but more research is required to make clearer recommendations . Addressing self-efficacy in relation to exercise may be a particularly useful area to consider in this respect
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"QUESTION Does exercise using a gaming console result in similar cardiovascular dem and and energy expenditure as formally prescribed exercise in adults with cystic fibrosis ? How do these patients perceive gaming console exercise ? DESIGN R and omised cross-over trial with concealed allocation and intention-to-treat analysis . PARTICIPANTS 19 adults with cystic fibrosis admitted to hospital for treatment of a pulmonary exacerbation . INTERVENTION Participants underwent two 15-minute exercise interventions on separate days ; one involving a gaming console and one a treadmill or cycle ergometer . OUTCOME MEASURES Cardiovascular dem and was measured using heart rate and rating of perceived exertion ( RPE ) . Energy expenditure was estimated using a portable activity monitor . Perception ( enjoyment , fatigue , workload , effectiveness , feasibility ) was rated using a horizontal 10-cm visual analogue scale . RESULTS There was no significant difference in average heart rate ( mean difference 3 beats/min , 95 % CI -3 to 9 ) or energy expenditure ( 0.1 MET , 95 % CI -0.3 to 0.5 ) between the two interventions . Both interventions provided a ' hard ' workout ( RPE ∼15 ) . Gaming console exercise was rated as more enjoyable ( mean difference 2.6 cm , 95 % CI 1.6 to 3.6 ) than formal exercise but they did n't differ significantly in fatigue ( -1.0 cm , 95 % CI -2.4 to 0.3 ) , perceived effectiveness ( -0.4 cm , 95 % CI -1.2 to 0.3 ) , or perceived feasibility for inclusion in routine management ( 0.2 cm , 95 % CI -0.7 to 1.1 ) . CONCLUSION Gaming console exercise provides a similar cardiovascular dem and as traditional exercise modalities . It is feasible that adults with cystic fibrosis could include gaming console exercise in their exercise program . TRIAL REGISTRATION ACTRN12610000861055",
"Objectives : To develop and test the effectiveness of an Internet-based self management program by multidisciplinary health care professionals for patients with heart failure ( HF ) . Methods : The comprehensive educational material for HF was created and posted on a website . A computer with Internet connection and computer training were provided first . A secure and simple web-based recording system of vital signs and health behaviors and a mechanism for feedback regarding each participant ’s record were developed . A r and omized controlled trial with a one-year intervention was conducted using a total of 40 patients who were assessed three times in their homes . An intention-to-treat analysis used multivariate statistics . Results : The treatment group had a high ( 85 % ) adherence to the intervention . Only the treatment group showed a significant improvement in the knowledge level ( p amount of exercise ( p = 0.001 ) , and quality of life ( p = 0.001 ) , and reduction in HF related symptoms ( dyspnea , p = 0.001 ; fatigue , p = 0.003 ; functional emotion , p blood pressure ( systolic , p = 0.002 ; diastolic , p frequency of emergency room visit , and length of hospital stay ( both p = 0.001 ) . Conclusions : An effective program to change one ’s behaviors in managing HF takes a multidisciplinary approach to create and provide feedback regarding a patient ’s daily record , which can be accomplished through Internet use",
"This study used a prospect i ve design to test a model of the relation between social cognitive variables and physical activity in a sample of 277 university students . Social support , self-efficacy , outcome expectations , and self-regulation were measured at baseline and used to predict physical activity 8 weeks later . Results of structural equation modeling indicated a good fit of the social cognitive model to the data . Within the model , self-efficacy had the greatest total effect on physical activity , mediated largely by self-regulation , which directly predicted physical activity . Social support indirectly predicted physical activity through its effect on self-efficacy . Outcome expectations had a small total effect on physical activity , which did not reach significance . The social cognitive model explained 55 % of the variance observed in physical activity",
"AIMS Supervised exercise can benefit selected patients with heart failure , however the effectiveness of home-based exercise remains uncertain . We aim ed to assess the effectiveness of a home-based exercise programme in addition to specialist heart failure nurse care . METHODS AND RESULTS This was a r and omized controlled trial of a home-based walking and resistance exercise programme plus specialist nurse care ( n=84 ) compared with specialist nurse care alone ( n=85 ) in a heart failure population in the West Midl and s , UK . PRIMARY OUTCOME Minnesota Living with Heart Failure Question naire ( MLwHFQ ) at 6 and 12 months . SECONDARY OUTCOMES composite of death , hospital admission with heart failure or myocardial infa rct ion ; psychological well-being ; generic quality of life ( EQ-5D ) ; exercise capacity . There was no statistically significant difference between groups in the MLwHFQ at 6 month ( mean , 95 % CI ) ( -2.53 , -7.87 to 2.80 ) and 12 month ( -0.55 , -5.87 to 4.76 ) follow-up or secondary outcomes with the exception of a higher EQ-5D score ( 0.11 , 0.04 to 0.18 ) at 6 months and lower Hospital Anxiety and Depression Scale score ( -1.07 , -2.00 to -0.14 ) at 12 months , in favour of the exercise group . At 6 months , the control group showed deterioration in physical activity , exercise capacity , and generic quality of life . CONCLUSION Home-based exercise training programmes may not be appropriate for community-based heart failure patients",
"The purpose of this study was to determine how an exercise adherence intervention affects the physiological , functional , and quality of life outcomes of patients with heart failure ( HF ) . Sixteen HF patients were r and omly assigned to an exercise-only group ( n = 8) or to an exercise-with-adherence group ( n = 8) . Two of the 16 people died from nonexercise related causes during the study and were not included in the analysis . The intervention was tested over a 24-week period in which patients participated in a 12-week supervised exercise program ( Phase 1 ) followed by 12 weeks of unsupervised home exercise ( Phase 2 ) . The intervention format was one of individualized graphic feedback on exercise goals and participation and problem-solving support by nurses . Results indicate that patients who received the intervention exercised more frequently and experienced improved outcomes during both phases . The adherence intervention may encourage HF patients to continue to exercise and thereby maintain the health benefits gained in both phases of an exercise program",
"BACKGROUND This study tested the effects of a multicomponent exercise training intervention called \" Heart Failure Exercise And Training Camp \" ( HEART CAMP ) . The intervention was theoretically derived from B and ura 's social cognitive theory . METHODS An experimental repeated- measures design was used . Participants were r and omized to the HEART CAMP intervention group ( n = 22 ) or the attention control group ( n = 20 ) . Participants were compared on self-efficacy for exercise , symptoms , physical function , and quality of life over 12 weeks . RESULTS The intervention group had a 31 % increase in cardiac exercise self-efficacy and significantly fewer symptoms compared with the attention control group . Quality of life increased significantly in both groups . CONCLUSION A theory-based intervention improved self-efficacy for exercise and symptoms in patients with heart failure",
"BACKGROUND Hospital-based exercise programs using a bicycle ergometer or a combination of exercise modalities have shown positive benefits in heart failure , but may not be readily accessible to many patients . Thus , we sought to evaluate the effects of a 12-week home walking exercise program on functional status and symptoms in patients with heart failure . METHODS A r and omized controlled trial comparing a 12-week progressive home walking exercise program ( n = 42 ) to a \" usual activity \" control group ( n = 37 ) was conducted in patients with heart failure ( 78 [ 99 % ] male ; mean age 62.6 + /- 10.6 years ; ejection fraction 27 % + /- 8.8 % ; 63 [ 80 % ] New York Heart Association class II ; 15[20 % ] New York Heart Association class III-IV ) from a Veterans Affairs medical center and a university-affiliated medical center . Functional status ( peak oxygen consumption via cardiopulmonary exercise testing , 6-minute walk test , the Heart Failure Functional Status Inventory ) , and symptoms ( Dyspnea-Fatigue Index score with a postglobal rating of symptoms ) were measured at baseline and 12 weeks . RESULTS No adverse events related to exercise training occurred . Overall mean compliance to training was 74 + /- 37 % . Peak oxygen consumption and the Heart Failure Functional Status Inventory were unchanged with training . Compared to the usual activity group , the training group had significantly longer walking distances measured by the 6-minute walk test ( 1264 + /- 255 vs 1337 + /- 272 feet , P = .001 ) , and improved postglobal rating of symptoms ( P = .03 ) . CONCLUSION In patients with heart failure , a progressive home walking exercise program is acceptable , increases walking distance , and decreases global rating of symptoms",
"BACKGROUND Considerable research has established that self-efficacy is a consistent correlate of physical activity . Additional factors , such as exercise-induced affect , social support , and value judgments , have also been identified as having the potential to influence adherence to activity . This study examined the utility of such variables in predicting the long-term exercise behavior of older adults . METHOD In the context of a 6-month r and omized controlled trial with an 18-month follow-up , we tested the extent to which adherence during the trial , affective responses to exercise , exercise value , and social support from the exercise group had either a direct or indirect effect through the mediation of exercise self-efficacy on physical activity levels at 6- and 18-month follow-up in a sample ( N=174 ) of older adults ( M age , 66 years ) . Structural equation modeling tested several models of exercise prediction . RESULTS The best fitting model indicated significant paths from social support , affect , and exercise frequency to efficacy at the end of the program . Efficacy , in turn , was related to physical activity at 6- and 18-month follow-up . The model accounted for 40 % of the variance in 18-month activity levels . CONCLUSION This prospect i ve study provides support for the inclusion of social cognitive variables in models of exercise adherence and highlights the pivotal role of self-efficacy in long-term exercise behavior . Subsequent trials are called for to replicate and extend these findings",
"Goals of workTo evaluate a 12-week home-based walking intervention among breast cancer survivors and to quantify changes in physical activity ( PA ) behaviors , body weight , and body composition in response to the intervention . Patients and methods Breast cancer survivors that were in the posttreatment period were r and omized to intervention ( n=23 ) or wait-list usual care ( n=13 ) . PA was assessed by self-report , and in a study sub sample ( n=23 ) , by an accelerometer . Intention to treat principles were employed to estimate the intervention effect on PA behaviors , body weight , and body composition . Intervention adherence was calculated as the proportion of exercise sessions completed relative to the number of exercise sessions recommended , as reported each week on walking logs . Main results Thirty-four of 36 women r and omized ( 94 % ) completed the study . Average intervention adherence over 12 weeks was 94 % . Intervention participants reported a significantly greater increase in walking for exercise [ + 11.9 metabolic equivalent (MET)-h/week ] over time than did usual care participants ( + 1.7 MET-h/week , p=0.01 ) . Objective measures of activity also indicated that intervention participants increased their activity levels over time as compared to usual care participants [ i.e. , counts/min/day and steps/day ( p≤0.04 ) ] . No significant changes in body weight or composition were observed . Conclusion We found that a 12-week home-based walking intervention was safe and effective for increasing short-term PA levels in breast cancer survivors . Future studies are needed to assess the ability of brief interventions to facilitate the maintenance of increased activity levels and to produce favorable quality of life and risk factor outcomes",
"AIMS Despite proven benefits of cardiac rehabilitation ( CR ) , currently proposed CR models are not acceptable for many heart failure ( HF ) patients . The purpose of this study was to evaluate a new model of home-based telemonitored cardiac rehabilitation ( HTCR ) using walking training compared with an outpatient-based st and ard cardiac rehabilitation ( SCR ) using interval training on a cycle ergometer . METHODS AND RESULTS The study included 152 HF patients ( aged 58.1 + or - 10.2 years , NYHA class II and III , ejection fraction HTCR ( n = 77 ) or SCR ( n = 75 ) . All patients underwent 8 weeks of CR . Both groups were comparable in terms of demographic and clinical characteristics and medical therapy . The effectiveness of CR was assessed by changes in NYHA class , peak oxygen consumption , 6-min walking test distance , and SF-36 score . Cardiac rehabilitation result ed in a significant improvement of all parameters in both groups . All patients in the HTCR group completed the 8 weeks of CR , whereas 15 patients in the SCR group ( 20 % ) discontinued CR . CONCLUSION In patients with HF , HTCR is equally as effective as SCR and provides a similar improvement in quality of life . Adherence to CR seems to be better for HTCR . Home-based telemonitored cardiac rehabilitation may be a useful alternative form of CR in patients with HF",
"OBJECTIVE The purpose of this study is to determine the impact of a home communication intervention ( HCI ) for ischemic heart failure Coronary Artery Bypass Graft ( CABG ) patients > /= 65 years of age on self-efficacy , coronary artery disease risk factor modification and functioning posthospitalization . DESIGN A r and omized clinical trial with repeated measures was used . SAMPLE A sub sample of ischemic heart failure CABG surgery patients ( n = 35 ) was drawn from the parent study of 180 CABG patients . RESULTS HCI participants ( n = 18 ) had significantly higher adjusted mean self-efficacy scores [ F(1 , 29 ) = 6.40 , P adjusted mean levels of functioning ( physical , general health , mental , and vitality functioning ) compared with the routine care group ( n = 17 ) , using repeated measures analysis of covariance with baseline scores as covariates . There were also significant effects of time on bodily pain and role emotional functioning . Significantly higher exercise adherence ( t = 3.09 , P reported stress ( t = 3.77 , P HCI intervention with more tailored strategies for vulnerable subgroups of CABG patients",
"AIMS The ' Chronic Disease Self-Management Programme ' ( CDSMP ) emphasizes patients ' responsibility for the day-to-day management of their condition(s ) and has shown favourable effects on health behaviour and healthcare utilization among various groups of patients with chronic conditions . However , the effects of the CDSMP among congestive heart failure ( CHF ) patients are unknown . We therefore aim ed to assess the effects of the CDSMP on health behaviour and healthcare utilization in patients with CHF . METHODS AND RESULTS This r and omized , controlled trial with 12 months of follow-up included 317 CHF patients with a slight to marked limitation of physical activity . Control patients ( n = 131 ) received usual care , consisting of regular checkups at an outpatient clinic . Intervention group patients ( n = 186 ) received usual care and participated in a 6-week self-management group programme . Favourable effects on walking for exercise and other physical activities such as aerobic , stretching , and strength exercises , sports , and gardening were reported in the intervention group immediately after completion of the programme . The effect of the programme on other physical activities extended to 6 months of follow-up . No favourable effects were found for the other outcomes . CONCLUSION The CDSMP significantly improved physical activity among CHF patients for up to 6 months after the end of the programme ; however , it did not affect other health behaviour outcomes or healthcare utilization",
"BACKGROUND Measuring adherence to exercise is important to clinicians and research ers because inadequate adherence can adversely affect the effectiveness of an exercise program and cloud the relationship between exercise and clinical outcomes . Hence , assessment strategies for adherence to exercise , as with assessment strategies for other outcomes , must have demonstrated validity if they are to be employed with confidence . We conducted this study to determine the validity of pedometers as a measure of exercise adherence to a home-based walking program in heart failure patients . METHODS AND RESULTS Exercise adherence was measured using pedometers in 38 patients ( 74 % men ) age 54.1 + /- 11.7 years who participated in a 12-month home-based walking program . A comparison of functional status as measured by the 6-minute walk distance and peak oxygen uptake ( VO2 max ) at 6 months into the exercise training program was made between 2 groups of participants who were thought to represent adherers and nonadherers : participants who demonstrated > or = 10 % change in pedometer scores ( n = 20 ) and those who showed no change in pedometer scores ( n = 18 ) from baseline to 6 months . Patients who showed improvements in their pedometer scores over 6 months had better functional status at 6 months ( 6-minute walk distance 1718 + /- 46 versus 1012 + /- 25 meters , F = 5.699 , P = .022 ; VO 2 max 17 + /- 0.7 versus 10 + /- 0.5 units , F = 7.162 , P = .011 ) when compared with patients whose pedometers reflected minimal change in distance walked ( ie , Pedometers are inexpensive and readily available to both clinicians and research ers . The results of this study suggest that they may be a valid indicator of exercise adherence in heart failure patients who participate in a home-based walking program",
"AIM This paper reports a study comparing , over a 5-month period , two different methods of increasing physical activity : a traditional exercise programme and one based on motivational interviewing . BACKGROUND Chronic heart failure is associated with poor quality of life that can be improved by increased physical activity . Patients who are directed to engage in physical activity have a record of low compliance . METHOD Sixty older aged heart failure patients were r and omly assigned to st and ard care , motivational interviewing or both treatments . The primary outcome was physical activity ( kcal/kg/day ) , with the 6-minute walk test as a secondary outcome . FINDINGS At entry , no significant differences were observed between the three groups . Following treatment , the ' motivational interviewing ' and ' both treatments ' groups reported an increase in their level and type of activities , whereas the ' st and ard care ' group did not . All groups significantly increased their 6-minute walk distance . CONCLUSIONS Motivational interviewing , which incorporates established behaviour change principles and a flexible approach to promotion of activity , increases reported physical activity in older patients with heart failure over a short period . In terms of level and type of activity , this approach gives a better outcome than st and ard care , and nurses should explore alternative strategies to promote health in this population",
"BACKGROUND Patients with chronic heart failure have a reduced quality of life due in part to their limited range of physical activity and independence . OBJECTIVES The paper examines whether a physical activity ' lifestyle ' intervention , based on motivational interviewing , will improve quality of life at five months from baseline , compared with conventional treatment . METHODS Sixty older patients with chronic heart failure were r and omly assigned to either a ' st and ard care ' , ' motivational interviewing ' or ' both ' treatment groups for five months in 2002 . The primary outcome measures were the Medical Outcomes Short Form-36 Health Survey , the disease-specific Minnesota Living with Heart Failure question naire and the Motivation Readiness for Physical Activity scale . RESULTS There were non-significant differences between the groups at baseline for age , coronary risk factors , severity of chronic heart failure , ejection fraction , specific laboratory tests , length of hospitalisation , medication and social support . Following treatment there was a significant increase ( p dimensions of the health survey in the ' motivational interviewing ' group . All groups improved their scores ( p heart failure question naire . Over the five month period there was a general trend towards improvements in self-efficacy and motivation scores . CONCLUSIONS This study has demonstrated that a ' motivational interviewing ' intervention , incorporating behaviour change principles to promote physical activity , is effective in increasing selected aspects of a general quality of life question naire and a disease-specific quality of life question naire . Thus a ' motivational interviewing ' approach is a viable option compared with traditional exercise programming . It is important to test these motivational interviewing interventions more widely , especially to match individuals to treatments"
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BACKGROUND The utility of iron fortification of food to improve iron deficiency , anemia , and biological outcomes is not proven unequivocally . OBJECTIVES The objectives were to evaluate 1 ) the effect of iron fortification on hemoglobin and serum ferritin and the prevalence of iron deficiency and anemia , 2 ) the possible predictors of a positive hemoglobin response , 3 ) the effect of iron fortification on zinc and iron status , and 4 ) the effect of iron-fortified foods on mental and motor development , anthropometric measures , and infections . DESIGN R and omized and pseudor and omized controlled trials that included food fortification or biofortification with iron were included . RESULTS Data from 60 trials showed that iron fortification of foods result ed in a significant increase in hemoglobin ( 0.42 g/dL ; 95 % CI : 0.28 , 0.56 ; P and serum ferritin ( 1.36 μg/L ; 95 % CI : 1.23 , 1.52 ; P reduced risk of anemia ( RR : 0.59 ; 95 % CI : 0.48 , 0.71 ; P and iron deficiency ( RR : 0.48 ; 95 % CI : 0.38 , 0.62 ; P in other indicators of iron nutriture , and no effect on serum zinc concentrations , infections , physical growth , and mental and motor development . Significant heterogeneity was observed for most of the evaluated outcomes . Sensitivity analyses and meta-regression for hemoglobin suggested a higher response with lower trial quality ( suboptimal allocation concealment and blinding ) , use of condiments , and sodium iron edetate and a lower response when adults were included . CONCLUSION Consumption of iron-fortified foods results in an improvement in hemoglobin , serum ferritin , and iron nutriture and a reduced risk of remaining anemic and iron deficient
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"OBJECTIVE To observe the different impacts of electrolytic iron , FeSO4 , and NaFeEDTA on body iron store of anemic school students . METHODS Four hundreds anemic students at the age of 11 - 18 years were divided into four groups . Of which , three consumed different iron fortificants from wheat flour as food vehicle for six months and one consumed non-fortified flour ( control ) . The fortification level of electrolytic iron , FeSO4 , and NaFeEDTA was 60 mg Fe/kg , 30 mg Fe/kg , and 20 mg Fe/kg , respectively . Blood sample s were collected at 0 , 2 , 4 , and 6 months and hemoglobin ( Hb ) , serum ferritin ( SF ) , and transferrin receptor ( TfR ) were measured . RESULTS The hemoglobin levels in three intervention groups increased , the increments of Hb in the NaFeEDTA group were significantly higher than that in the other groups . SF and TfR levels increased in the tested groups and body iron store in the NaFeEDTA group was higher than that in the other groups . These parameters did not show any significant changes in the control group . CONCLUSION NaFeEDTA and FeSO4 fortified wheat flour has positive impacts on iron status in anemic students and NaFeEDTA is more effective than FeSO4 , while electrolytic iron is less effective in improving iron store in anemic students",
"OBJECTIVE In many developing countries , children are at high risk for both goiter and anemia . Iron ( Fe ) deficiency adversely effects thyroid metabolism and reduces efficacy of iodine prophylaxis in areas of endemic goiter . The study aim was to determine if co-fortification of iodized salt with Fe would improve efficacy of the iodine in goitrous children with a high prevalence of anemia . DESIGN AND METHODS In a 9-month , r and omized , double-blind trial , 6 - 15 year-old children ( n=377 ) were given iodized salt ( 25 microg iodine/g salt ) or dual-fortified salt with iodine ( 25 microg iodine/g salt ) and Fe ( 1 mg Fe/g salt , as ferrous sulfate microencapsulated with partially hydrogenated vegetable oil ) . RESULTS In the dual-fortified salt group , hemoglobin and Fe status improved significantly compared with the iodized salt group ( P mean decrease in thyroid volume measured by ultrasound in the dual-fortified salt group ( -38 % ) was twice that of the iodized salt group ( -18 % ) ( P serum thyroxine was significantly increased ( P prevalence of hypothyroidism and goiter decreased ( P efficacy of iodine in goitrous children with a high prevalence of anemia",
"Background . Iron-fortified formulas are recommended throughout infancy and are frequently used beyond , yet safety aspects have been inadequately studied . Iron could theoretically increase pro-oxidant stress , with potential adverse effects , including infection risk , and some clinicians suspect that iron-fortified formulas induce gastrointestinal disturbance . Objective . A planned component of a large intervention trial has been to test the hypothesis that infants receiving iron-fortified formula do not have a higher incidence of infections ( primary outcome ) or gastrointestinal problems ( secondary outcome ) than infants on low iron-formulas or cow 's milk . Methods . Children ( n = 493 ) 9 months old receiving cow 's milk were recruited in 3 UK centers and r and omized to : 1 ) cow 's milk as before , 2 ) formula containing .9 mg/L of iron , or 3 ) an otherwise identical formula but containing 12 mg/L of iron . Children were followed at 3 monthly intervals and the episodes of infections , diarrhea and constipation , and general morbidity to 18 months old were recorded . Hematologic indices of iron status were determined at 18 months old . Results . Serum ferritin concentrations were increased in infants receiving iron-fortified formula but there were no intergroup differences in incidence of infection , gastrointestinal problems , or in general morbidity or weight gain . Conclusions . We were unable to identify adverse health effects in older infants and toddlers consuming a high iron-containing formula ( 12 mg/L ) even when used in population s with a low incidence of iron deficiency",
"OBJECTIVE Combating iron deficiency in toddlers with iron-fortified food has proved difficult in countries with phytate-rich diets . For this purpose , a new haem iron preparation was developed . The study compared changes in iron status after administration of refried beans with beans fortified with a haem iron preparation or ferrous sulphate ( FeSO4 ) . DESIGN In a masked , stratified-r and omised intervention trial , children received five 156-g cans of refried black beans per week for 10 consecutive weeks . The beans-only ( control ) , FeSO4 and haem iron groups were offered a cumulative dose of 155 mg , 1625 mg and 1700 mg of iron from the bean intervention , respectively . Haemoglobin ( Hb ) and ferritin concentrations were determined at baseline and after 5 and 10 weeks . Compliance was examined weekly . SETTING A low-income community in Guatemala City . SUBJECTS One hundred and ten children aged 12 - 36 months with initial Hb values between 100 and 115 g l(-1 ) . RESULTS The cumulative intake of beans was approximately 80 % of that offered , signifying an additional approximately 1300 mg of either haem or inorganic iron in the corresponding treatment groups over 10 weeks . Hb concentrations increased by the order of 7.3 - 11.4 g l(-1 ) during the intervention , but without significant differences across treatments . Average ferritin concentrations were unaffected by treatment assignment . However , post hoc analysis by subgroups of initial high ferritin and initial low ferritin found the Hb increments after 10 weeks in the haem iron group ( 13.1+/-7.7 g l(-1 ) ) to be significantly greater than the respective increases ( 6.8+/-11.2 and 6.4+/-8.5 g l(-1 ) ) in the inorganic iron and beans-only groups . CONCLUSIONS Canned refried beans are a c and i date vehicle for fortificant iron . Given the improved colour and organoleptic properties imparted by haem iron added to refried beans , its additional potential for benefiting the iron status of consumers with iron deficiency may recommend it over FeSO4",
"OBJECTIVE Despite public health campaigns based on Fe and folic acid supplements , Fe-deficiency anaemia remains highly prevalent among women in India . We investigated leaf concentrate as an alternative to Fe and folic acid supplements for treating anaemia in adolescent girls . DESIGN R and omised controlled two-arm trial over 3 months : one group received daily Fe and folic acid ( IFA ; 60 mg Fe , 500 microg folic acid ) ; the other daily leaf concentrate ( LC ; 5 mg Fe , 13 microg folic acid ) . Hb concentration , mean cell volume , serum Fe , serum ferritin and total Fe-binding capacity were measured pre- and post-intervention . SETTING Jaipur , India . SUBJECTS One hundred and two adolescent girls aged 14 - 18 years . RESULTS Of the 102 girls r and omized to the two arms of the trial , four ( 3.9 % ) were severely anaemic ( Hb ) , twenty-eight ( 27.5 % ) were moderately anaemic ( Hb > or = 7 g/dl , mildly anaemic ( Hb > or = 10 g/dl , side-effects , compared with one girl ( 2.1 % ) in the LC group ( P = 0.005 ) . Total losses to follow-up were 14/54 in the IFA group and 2/48 in the LC group . At the end of the trial , none of the eighty-six remaining girls were severely anaemic , nine ( 10.5 % ) were moderately anaemic and twenty-six ( 30.2 % ) were mildly anaemic ; fifty-one ( 59.3 % ) had normal Hb levels ( > or = 12 g/dl ) . After adjustment for baseline values , LC was as effective as IFA in improving serum Fe parameters and treating anaemia . CONCLUSIONS Leaf concentrate is an effective , and more palatable , alternative to Fe and folic acid supplements for treating anaemia in adolescent girls",
"Background : It has been suggested that food fortification might be an inexpensive , simple and effective way to control and prevent iron deficiency and its related anemia in many countries . Despite the advantages of this approach and the fact that it has been implemented in some provinces in Iran for more than 6 years , many scientists in the country worry about the negative aspects of the extra iron distributed among non-anemic persons in the community . Objective : This study was design ed to assess the effect of the flour fortification program on oxidative stress biomarkers and iron status among non-anemic 40- to 65-year-old adults . Study Design : This study had a special design that was implemented in 3 different parts . The main and first part was a field study . We r and omized 2 cities in 1 province . In each city , 200 volunteers ( 100 men and 100 women ) were selected using a multi-stage stratified method . Examination and interview ( filling out data collection forms ) were the methods of data gathering . In each of the 3 phases , demographic , anthropometric , blood pressure , micro- and macronutrient intakes , physical activities , and some oxidative stress biomarkers were the main data that were gathered . The results of this study can help health policy makers in design ing future interventions in the country based on food fortification ",
"How to improve iron status among infants and young children is of continued concern in low- to middle-income countries , including Brazil . In a double blind , 5-mo , home-based , r and omized trial in Brazil , we gave one group of mildly anemic 6- to 24-mo-old children ( n = 175 ) rice fortified with micronized ferric pyrophosphate using the Ultra Rice technology and a placebo solution ( URG ) and another group identical nonfortified rice and iron drops . We instructed parents on the correct dosage of iron drops and to feed their children rice as they normally would . We measured serum ferritin ( SF ) and hemoglobin ( Hb ) concentrations at baseline and at 5 mo . At baseline , the prevalences of iron deficiency and anemia in the total sample were 73.1 and 100 % , respectively . At 5 mo , SF and Hb increased in both groups , although the change in the URG was larger ( P Adult participants were unable to distinguish cooked fortified rice from unfortified rice in terms of smell , color , or taste . As rice is normally consumed at home , MPF-fortified rice increased iron stores and reduced anemia in a group of mildly anemic children 6 - 24 mo old . In population s where young children are routinely fed approximately 100 g of cooked rice daily , fortifying it with iron may improve iron status at least as well as providing free iron drops",
"Iron deficiency anaemia is a most common micronutrient deficiency affecting mostly the low socioeconomic population s of the developing world . The objective of this study was to evaluate the feasibility of iron fortification of household drinking water to prevent iron deficiency anaemia among members of the low socioeconomic families of Southern Brazil . A total of 21 low socioeconomic families representing 88 subjects including 1 - 6 years old children whose haemoglobin level was between 10 and 12 g/dl were selected to participate in this study . Nine families in the control group were supplied with placebo solution and 12 families in the experimental group were supplied iron solution with ascorbic acid to be added to their domestic drinking water over a period of 4 months . The feasibility and acceptability of iron fortified drinking water was assessed through home visits and question naires . Blood sample s were collected at the beginning and after 4 months of the study for the determination of haemoglobin and serum ferritin levels . The results of this study indicated that iron fortified drinking water was well received by the low socioeconomic families and that it was effective in improving the haemoglobin and serum ferritin levels . It can be concluded from this study that iron fortification of household drinking water is a simple and effective alternative for developing countries along with other technological approaches to iron fortification of foods",
"BACKGROUND Iron fortification of rice could be an effective strategy for reducing iron deficiency anemia in South Asia . OBJECTIVE We aim ed to determine whether extruded rice grains fortified with micronized ground ferric pyrophosphate ( MGFP ) would increase body iron stores in children . DESIGN In a double-blind , 7-mo , school-based feeding trial in Bangalore , India , iron-depleted , 6 - 13-y-old children ( n = 184 ) were r and omly assigned to receive either a rice-based lunch meal fortified with 20 mg Fe as MGFP or an identical but unfortified control meal . The meals were consumed under direct supervision , and daily leftovers were weighed . All children were dewormed at baseline and at 3.5 mo . Iron status and hemoglobin were measured at baseline , 3.5 mo , and 7 mo . RESULTS At baseline , the prevalences of iron deficiency and iron deficiency anemia in the total sample were 78 % and 29 % , respectively . After 7 mo of feeding , there was a significant increase in body iron stores in both study groups ( P interaction for iron deficiency , which fell from 78 % to 25 % in the dewormed iron group and from 79 % to 49 % in the dewormed control group . Iron deficiency anemia decreased from 30 % to 15 % ( NS ) in the iron group but remained virtually unchanged in the control group ( 28 % and 27 % ) . In sensory tests , the MGFP-fortified rice ( fortified at 3 and 5 mg Fe/100 g ) was indistinguishable from natural rice , in both cooked and uncooked form . CONCLUSIONS Extruded rice fortified with MGFP has excellent sensory characteristics . Fed in a school lunch meal , it increases iron stores and reduces the prevalence of iron deficiency in Indian children",
"In a longitudinal study from age 3 to 15 mo , 276 term , healthy , spontaneously weaned infants received a full-fat acidified milk fortified with 15 mg of elemental Fe as ferrous sulfate and 100 mg of ascorbic acid/100 g of powder and 278 control infants received milk without additives . At ages 9 and 15 mo significant differences were encountered in all measures of Fe nutriture in favor of the fortified group ( p less than 0.001 ) . Anemia ( Hg less than 110 g/L ) was present in 25.7 % of unfortified infants compared with only 2.5 % in those fortified at age 15 mo . Saturation of transferrin less than 9 % was present in 33.8 % and serum ferritin less than 10 micrograms/L in 39.1 % of the nonfortified infants . The figures for the fortified group were 7 and 8.5 % respectively . The efficiency of the fortified acidified milk in eradicating Fe deficiency in the infants while discouraging use by other family members make this milk a useful targeted product in programs of supplementary food distribution in the underdeveloped world",
"BACKGROUND Dual fortification of salt with iodine and iron could be a sustainable approach to combating iodine and iron deficiencies . OBJECTIVE We compared the efficacy of dual-fortified salt ( DFS ) made by using 2 proposed contrasting formulas-one fortifying with iron as micronized ground ferric pyrophosphate ( MGFePP ) and the other with iron as encapsulated ferrous fumarate (EFF)-with the efficacy of iodized salt ( IS ) in schoolchildren in rural southern India . DESIGN After stability and acceptability testing , a double-blind , household-based intervention was conducted in 5 - 15-y-old children ( n = 458 ) r and omly assigned into 3 groups to receive IS or DFS with iron as MGFePP or EFF , both at 2 mg/g salt . We measured hemoglobin , iron status , and urinary iodine at baseline , 5 mo , and 10 mo . RESULTS Median serum ferritin and calculated median body iron improved significantly in the 2 groups receiving iron . After 10 mo , the prevalence of anemia decreased from 16.8 % to 7.7 % in the MGFePP group ( P median urinary iodine concentration increased significantly in the IS and EFF groups ( P iodine in salt with 1.8 % moisture were high for MGFePP , whereas the EFF segregated in salt with 0.5 % moisture and caused color changes in some local foods . CONCLUSIONS Both DFSs were efficacious in reducing the prevalence of anemia and iron deficiency in school-age children . Local salt characteristics should be taken into consideration when choosing an iron fortificant for DFS to achieve optimal iodine stability and color",
"A targeted , double-blind controlled iron fortification trial using Fe(111)-EDTA in masala ( curry powder ) was directed towards an Fe-deficient Indian population for 2 y. The Fe status of the fortified group improved more than that of control subjects . Improvement reached significance over control subjects for females in hemoglobin ( p = 0.0005 ) , ferritin ( p = 0.0002 ) , and body Fe stores ( p = 0.001 ) and for males in ferritin ( p = 0.04 ) . The prevalence of Fe-deficiency anemia ( IDA ) decreased from 22 to 5 % in fortified females . Premenopausal women , multipara women , and women with prolonged menstruation or initial IDA benefitted most from fortification . The mean increase in body Fe stores in females with initial IDA was 9.0 + /- 1.3 mmol , representing an increased absorption of 12 mumol/d . Fortified subjects with normal Fe status did not accumulate excessive body Fe and there was no alteration in serum Zn concentrations . Targeted fortification is a safe and effective means of combatting Fe deficiency",
"BACKGROUND Fish sauce is consumed daily by a large proportion of the Vietnamese population and could therefore be a potentially useful food vehicle for iron-fortification programs . OBJECTIVE We evaluated the efficacy of iron-fortified fish sauce in improving the iron status of anemic women . DESIGN In a r and omized , double-masked study of 152 anemic ( hemoglobin concentration of 81 - 119 g/L ) women , a meal based on noodles or rice was served 6 d/wk with 10 mL fish sauce containing either 10 mg Fe as NaFeEDTA ( iron-fortified group ) or no added iron ( control group ) . Concentrations of hemoglobin , serum ferritin ( SF ) , and serum transferrin receptor ( TfR ) were measured at baseline and after 3 and 6 mo . RESULTS After 6 mo , hemoglobin and SF concentrations were higher and TfR concentrations were lower in the iron-fortified group than in the control group [ hemoglobin : 116.3 + /- 8.7 ( + /- SD ) compared with 107.6 + /- 11.0 g/L ( P iron deficiency ( SF 8.5 mg/L ) and iron deficiency anemia ( iron deficiency with hemoglobin iron-fortified fish sauce significantly reduced the prevalence of iron deficiency anemia in Vietnamese women during the 6-mo intervention . Fortifying fish sauce with iron by using a water-soluble , highly bioavailable compound ( NaFeEDTA ) is a promising strategy for combating iron deficiency anemia in Vietnam",
"BACKGROUND According to our current underst and ing , iron absorption with weekly iron supplements is not higher than that with daily supplements ( ie , there is no mucosal block ) . However , community-based trials have repeatedly shown that a weekly regimen is as effective as a daily one . Furthermore , when differences in absorption are found , they are commonly smaller than would be expected on the basis of differences in the amount of iron provided . The possibility of differential compliance between the regimens needs to be evaluated to explain these findings . OBJECTIVE Taking compliance into account , we compared the efficacy and trial effectiveness of weekly and daily iron supplementation during pregnancy . DESIGN In Bangladesh , 50 antenatal centers were r and omly assigned to prescribe either 2 doses of 60 mg Fe once weekly or 1 dose of 60 mg Fe/d . Compliance was monitored by using a pill bottle equipped with an electronic counting device . Hemoglobin concentrations were measured at baseline and after 4 , 8 , and 12 wk of supplementation . RESULTS There was no differential effect per iron tablet between weekly and daily regimens . A 12-wk daily regimen ( 68 % compliance ) produced a small but significantly greater hemoglobin response than did the weekly regimen ( 104 % compliance ) . The first 20 tablets consumed produced most of the effect ; after 40 tablets , there was no further response . CONCLUSIONS There was no evidence of a mucosal block in the daily regimen . Over 12 wk , 50 % of the amount of iron in a daily regimen was sufficient for maximum hemoglobin effect . The weekly regimen provided a large part of this amount , explaining the limited difference in effect . It appears that the current international recommendation for iron supplementation in pregnancy is higher than necessary",
"To evaluate the effect of introducing complementary foods before 6 mo of age , we r and omly assigned 164 infants who had been exclusively breast-fed for 4 mo to continue being exclusively breast-fed until 6 mo ( EBF group ) or to receive iron-fortified foods in addition to breast milk from 4 to 6 mo ( BF+SF group ) . At 6 mo , the BF+SF group had higher mean iron intake ( 4 mg/d compared with 0.2 mg/d in EBF infants ) and higher hemoglobin , hematocrit , and ferritin values than the EBF group ( P low hemoglobin ( low hematocrit ( with ferritin concentrations hemoglobin or hematocrit , raising questions about the validity of the cutoffs at this age . Infants at greatest risk for anemia and low ferritin were those with birth weights 3000 g had a low ferritin value at 6 mo . We conclude that the risk of iron deficiency is low among infants with birth weights > 3000 g who are exclusively breast-fed for 6 mo . Iron drops are recommended for low-birth-weight infants ; for breast-fed infants with birth weights between 2500 and 3000 g , further research is needed to determine whether iron drops are more effective than complementary foods for preventing iron deficiency before 6 mo",
"We compared iron intake and iron nutritional status of two groups of healthy term infants who received meat-containing baby foods fortified with ferrous sulphate ( 2 mg Fe/100 g ) . One group received an Fe-fortified formula ( 1.6 mg Fe/100 kcal ) and the other a nonfortified formula . Fe intake of the group fed the nonfortified formula was significantly lower ( p less than 0.0001 ) . These infants received Fe mainly from fortification Fe with beikost ( 75 - 86 % ) and less than 10 % met the recommended intake of 1 mg.kg-1.d-1 ; whereas 80 - 85 % of the infants fed the Fe-fortified formula did . Hb , Hct , FEP , and ferritin were similar in both groups with the exception of lower ferritin values at age 365 d ( p less than 0.05 ) in the group fed the nonfortified formula . No infant had hemoglobin less than 100 g/L. We conclude that regular consumption of commercially prepared Fe-fortified beikost with meat prevents most healthy term infants from Fe deficiency even if Fe intake is substantially below the recommended intake",
"A 32-mo-long , double-blind field study involving one highl and control community receiving only vitamin A-fortified sugar and three vitamin A- and FeNaEDTA-sugar-fortified communities , two in the lowl and s and one in the highl and s of Guatemala , was undertaken to test the effectiveness of this approach in controlling iron deficiency . The communities ' population ranged between 1200 and 17000 . Sugar fortified with 1 g FeNaEDTA and 15 mg retinol as retinyl palmitate/kg was stable , did not segregate , and was well accepted by the communities . The impact of fortification on iron nutrition was estimated at 8 , 20 , and 32 mo of intervention . All pregnant women and subjects with severe anemia received supplements or treatment and were excluded from the analysis . Iron stores in the fortified communities increased significantly except for women 18 - 48 y of age in one lowl and community and > 49 y in the highl and community . Iron stores in the control community remained unchanged except for a rise among adult males",
"The choice of iron fortificant usually represents a balance between bioavailability of the compound and its tendency to cause organoleptic problems . The aim of this study was to evaluate the efficacy of sodium iron EDTA ( NaFeEDTA ) and ferrous fumarate at levels compatible with South African brown bread ( 10 mg/kg flour for NaFeEDTA and 20 mg/kg flour for ferrous fumarate ) in a r and omized controlled trial ; electrolytic iron was evaluated at the level currently used in South Africa ( 35 mg/kg flour ) . Schoolchildren ( n = 361 ) , aged 6 - 11 y , from a low socioeconomic community with hemoglobin ( Hb ) were r and omly assigned to 1 of 4 groups that received 4 slices of brown bread supplying either : 1 ) no fortification iron 2 ) 2.35 mg iron as NaFeEDTA ; 3 ) 4.70 mg iron as ferrous fumarate ; and 4 ) 8.30 mg iron as electrolytic iron per intervention day . These amounts simulated a bread intake of 6 slices per day over the 34-wk study period at fortification levels of 0 , 10 , 20 , and 35 mg/kg flour , respectively . Hb concentration and iron status were assessed at baseline and after 34 wk of intervention . The iron interventions did not affect Hb concentration , transferrin saturation , or serum ferritin , iron , or transferrin receptor concentrations relative to the control group . Our results suggest that electrolytic iron at the level currently used in South Africa is not effective in improving iron or Hb status . Neither do NaFeEDTA or ferrous fumarate appear to be suitable alternatives for the fortification of wheat flour when included at levels that do not cause color changes",
"BACKGROUND Iron deficiency anemia is the most prevalent nutrition problem in young children . One possible strategy to prevent iron deficiency anemia in this population group is the fortification of affordable food . OBJECTIVE This study was design ed to assess whether iron-fortified c and ies can improve iron status and are acceptable to children aged 4 - 6 y. DESIGN A double-blind , placebo-controlled intervention study was conducted in Jakarta , INDONESIA : The children were r and omly assigned to 1 of 2 treatment groups : a fortified group ( n = 57 ) and a placebo group ( n = 60 ) . Every week for 12 wk , 30 g ( 10 pieces ) c and y was given to the children . The c and y given to the fortified group contained 1 mg elemental Fe/g and very small amounts of other vitamins and minerals . RESULTS The hemoglobin concentration of the fortified group increased by 10.2 g/L ( 95 % CI : 8.3 , 12 g/L ) whereas that of the placebo group increased by 4.0 g/L ( 2.0 , 6.0 g/L ; P Anemia prevalence decreased from 50.9 % at the start of the intervention to 8.8 % after 12 wk of intervention in the fortified group ( P serum ferritin concentration was 71 % higher than at baseline in the fortified group and 28 % higher in the placebo group ( P Acceptability of the iron-fortified c and ies was good . The per capita cost of the supplement was approximately US$ 0.96 - 1.20 for the 12 wk of intervention . CONCLUSION Iron-fortified c and ies were effective for improving the iron status of young children and might be an affordable way to combat iron deficiency in children of low-to-middle income groups",
"It has been reported that large numbers of elderly Americans are moderately anemic because of iron deficiency anemia . In the present study , information has been obtained concerning blood composition , health , and nutritional habits of 779 people over 60 years of age , institutionalized or free-living in the Boston area . This paper presents the results of their blood examinations . Two hundred twenty-one of the free-living people examined who showed hemoglobin levels between 9 and 12.9 g/dl agreed to participate in an iron fortification study . Two-thirds of them received iron-fortified grain products daily for 6 to 8 months . The rest received the same foods without added iron . At the end of the experimental period a marked increase in hemoglobin levels averaging 1.4 g/dl was observed in both groups . This appeared to be attributable to an undefined intervention effect ; no measurable effects attributable to the iron fortification were observed . Three months of daily ferrous sulfate administration to those whose hemoglobin levels remained below 13 g/dl was without effect . Examination of the data obtained suggests that the cause of the moderately low hemoglobin levels initially observed was not occult bleeding or folic acid or iron deficiency",
"BACKGROUND In many developing countries , children are at high risk of both goiter and iron deficiency anemia . OBJECTIVE In a series of studies in northern Morocco , we developed and tested a dual-fortified salt ( DFS ) containing iodine and microencapsulated iron . DESIGN To establish the DFS fortification concentration , we measured salt intake by 3-d weighed food records and estimated iron bioavailability from the local diet by using published algorithms . We then formulated a DFS containing 25 micro g iodine/g salt ( as potassium iodide ) and 1 mg iron/g salt ( as ferrous sulfate hydrate encapsulated with partially hydrogenated vegetable oil ) . After storage and acceptability trials , we compared the efficacy of the DFS to that of iodized salt in a 9-mo , r and omized , double-blind trial in iodine-deficient , 6 - 15-y-old children ( n = 377 ) . RESULTS Mean salt intake in school-age children was 7 - 12 g/d , and estimated iron bioavailability from the local diet was 0.4 - 4.3 % . After storage for 20 wk , the DFS and iodized salt were not significantly different in iodine content , and color stability was acceptable when the compounds were added to local meals . During the efficacy trial , urinary iodine concentrations and thyroid volumes improved significantly ( P mean hemoglobin concentrations in the DFS group had increased by 14 g/L ( P serum ferritin , transferrin receptor , and zinc protoporphyrin concentrations were significantly better ( P salt group . The prevalence of iron deficiency anemia in the DFS group decreased from 35 % at baseline to 8 % at 40 wk ( P < 0.001 ) . CONCLUSION A DFS containing iodine and encapsulated iron can be an effective fortification strategy",
"After 1 y of distributing a milk-based fortified weaning food provided by the Mexican social program PROGRESA , positive effects on physical growth , prevalence of anemia , and several vitamin deficiencies were observed . There was no effect on iron status , which we hypothesized was related to the poor bioavailability of the reduced iron used as a fortificant in PROGRESA . The objective of this study was to compare the iron bioavailability from different iron sources added as fortificants to the weaning food . Children ( n = 54 ) aged 2 - 4 y were r and omly assigned to receive 44 g of the weaning food fortified with ferrous sulfate , ferrous fumarate , or reduced iron + Na(2)EDTA . Iron absorption was measured using an established double-tracer isotopic methodology . Iron absorption from ferrous sulfate ( 7.9 + /- 9.8 % ) was greater than from either ferrous fumarate ( 2.43 + /- 2.3 % ) or reduced iron + Na(2)EDTA ( 1.4 + /- 1.3 % ) ( P absorption of log-(58)Fe sulfate given with the iron source correlated with serum ferritin ( s-ferritin ) concentration ( n = 13 , r = 0.63 , P = 0.01 ) and log-(57)Fe absorption ( reference dose ) ( n = 14 , r = -0.52 , P = 0.02 ) . Absorption from ferrous fumarate and reduced iron + Na2EDTA did not correlate with s-ferritin or absorption of (57)Fe . The recommended daily portion of the fortified complementary food provides an average of 0.256 , 0.096 , 0.046 mmol ( 1.44 , 0.54 , and 0.26 mg ) of absorbed iron , if fortified with sulfate , fumarate and reduced iron + Na(2)EDTA , respectively . Ferrous sulfate was more bioavailable than either ferrous fumarate or reduced iron + Na(2)EDTA when added to the milk-based fortified food and more readily met the average daily iron requirements for children 2 - 3 y of age",
"BACKGROUND Phytic acid is a strong inhibitor of iron absorption from fortified foods . In adults , this inhibitory effect can be overcome by adding ascorbic acid with the iron fortificant or by using a \" protected \" iron compound such as NaFeEDTA . In addition , the use of NaFeEDTA as an iron fortificant has been reported to increase zinc absorption in adult women . No information is available on iron bioavailability from NaFeEDTA or the influence of NaFeEDTA on minerals and trace elements in infants . OBJECTIVE We aim ed to compare iron bioavailability from a complementary food based on wheat and soy fortified with either NaFeEDTA or ferrous sulfate plus ascorbic acid . The apparent absorption of zinc , copper , calcium , and magnesium was evaluated in parallel . DESIGN Stable-isotope techniques were used in a crossover design to evaluate erythrocyte incorporation of iron 14 d after administration of labeled test meals and the apparent absorption of zinc , copper , calcium , and magnesium on the basis of fecal monitoring in 11 infants . RESULTS Geometric mean erythrocyte incorporation of iron was 3.7 % ( NaFeEDTA ) and 4.9 % ( ferrous sulfate plus ascorbic acid ) ( P = 0.08 ) . No significant differences in the apparent absorption of zinc , copper , calcium , or magnesium were observed between test meals ( n = 10 ) . CONCLUSIONS Iron bioavailability from a high-phytate , cereal-based complementary food fortified with either NaFeEDTA or ferrous sulfate plus ascorbic acid was not significantly different . NaFeEDTA did not influence the apparent absorption of zinc , copper , calcium , or magnesium . NaFeEDTA does not provide any nutritional benefit compared with the combination of a highly bioavailable iron compound and ascorbic acid",
"BACKGROUND Micronutrient deficiencies are common during infancy , and optimal approaches for their prevention need to be identified . OBJECTIVE The objective was to compare the efficacy and acceptability of Sprinkles ( SP ) , crushable Nutritabs ( NT ) , and fat-based Nutributter ( NB ; 108 kcal/d ) , which provide 6 , 16 , and 19 vitamins and minerals , respectively , when used for home fortification of complementary foods . DESIGN Ghanaian infants were r and omly assigned to receive SP ( n = 105 ) , NT ( n = 105 ) , or NB ( n = 103 ) daily from 6 to 12 mo of age . We assessed dietary intake , morbidity , and compliance weekly . Hemoglobin and plasma ferritin , TfR , C-reactive protein , and zinc were measured at 6 and 12 mo . We used an exit interview to assess acceptability . A r and omly selected control group of infants who received no intervention ( NI ; n = 96 ) were assessed at 12 mo . RESULTS All supplements were well accepted , and the mean percentage of days that supplements were consumed ( 87 % ) did not differ between groups . At 12 mo , all 3 intervention groups had significantly higher ferritin and lower TfR concentrations than did the NI control group . Mean ( + /- SD ) hemoglobin was significantly higher in NT ( 112 + /- 14 g/L ) and NB ( 114 + /- 14 g/L ) but not in SP ( 110 + /- 14 g/L ) infants than in NI infants ( 106 + /- 14 g/L ) . The prevalence of iron deficiency anemia was 31 % in the NI control group compared with 10 % in the intervention groups combined ( P < 0.0001 ) . CONCLUSION All 3 options for home fortification of complementary foods are effective for reducing the prevalence of iron deficiency in such population",
"BACKGROUND Although elemental iron powders are widely used to fortify cereal products , little data exist on their efficacy in humans . OBJECTIVE We compared the efficacy of wheat-based snacks fortified with ferrous sulfate , electrolytic iron , or hydrogen-reduced iron in Thai women with low iron stores . DESIGN A double-blind intervention was conducted in 18 - 50-y-old women ( n = 330 ) r and omly assigned into 4 groups to receive either no fortification iron or 12 mg Fe/d for 6 d/wk for 35 wk as ferrous sulfate , electrolytic iron , or hydrogen-reduced iron in a baked , wheat-flour-based snack . Snacks were not consumed with meals , and consumption was monitored . At baseline , 20 wk , and 35 wk , hemoglobin status and iron were measured and the groups were compared . RESULTS Between baseline and 35 wk , geometric mean serum ferritin ( SF ) increased significantly in all 3 groups receiving iron ( P serum transferrin receptor ( TfR ) decreased significantly in the groups receiving ferrous sulfate and electrolytic iron ( P body iron stores increased from 1.5 + /- 2.8 to 5.4 + /- 2.9 mg/kg in the ferrous sulfate group , from 1.5 + /- 3.5 to 4.4 + /- 3.6 mg/kg in the electrolytic iron group , and from 1.3 + /- 3.2 to 3.2 + /- 4.3 mg/kg in the hydrogen-reduced iron group ( P Ferrous sulfate , electrolytic iron , and hydrogen-reduced iron , fortified into wheat-based snacks , significantly improved iron status . On the basis of the change in body iron stores during the 35-wk study , the relative efficacy of the electrolytic and hydrogen-reduced iron compared with ferrous sulfate was 77 % and 49 % , respectively",
"One cost-effective strategy for controlling iron deficiency is the fortification of staple foods or condiments with iron . We evaluated the effectiveness of fortifying fish sauce with NaFeEDTA for improving iron status in women of childbearing age in Vietnam in a double-blind intervention with r and omization by village . All families in the selected villages were supplied with fish sauce that was either unfortified ( Group C , 10 villages ) or fortified with NaFeEDTA [ 9 mmol ( 500 mg ) Fe/L , Group F , 11 villages ] for 18 mo . The effect of fortification was assessed in the 576 women ( n = 288/group ) by measuring hemoglobin and serum ferritin ( SF ) at 6 , 12 , and 18 mo . Analysis of the group x time interaction using a repeated- measures test for each response demonstrated a significant effect of fortification on hemoglobin ( P = 0.039 ) and log SF ( P prevalence of iron deficiency ( SF prevalence of anemia ( hemoglobin NaFeEDTA fortification of fish sauce is an effective method for reducing the prevalence of iron deficiency in women in Vietnam",
"1 . The effect of fortification of food with iron to provide 10 mg elemental Fe/child per d was studied in preschool children maintained on a cereal diet , over a 5-month period . 2 . The absorption of 5 mg Fe as ferrous sulphate mixed in one meal was 3.3 % of the test dose and when 3.3 mg was given with each of three meals over a 2 d period the corresponding value was 4.8 % . 3 . The mean absorption of a test dose of ferrous ascorbate studied in twenty-four children midway through the trial was 42 % . 4 . The only beneficial effect of Fe fortification in this time-period in the experimental group was the prevention of the decrease in packed cell volume which occurred in the control groups",
"Objective . Survival rates for preterm infants who weigh between 501 and 1500 g at birth have continued to improve over time . In response to this continuing decrease in birth weight of surviving preterm infants , Enfamil Human Milk Fortifier has recently been reformulated to meet the nutritional requirements of these smaller , more rapidly growing infants . It now provides an increased protein level of 1.1 g/58 kJ , a decreased carbohydrate level of 0.2 g/58 kJ , and a combined linoleic and α-linolenic fatty acid content of 157 mg/58 kJ. As these very small preterm infants have an increased requirement for dietary iron , the fortifier has been supplemented with 1.44 mg/58 kJ of iron , an amount of iron similar to that provided in a typical iron-fortified term infant formula . An iron-fortified product obviates the need for administration of an iron supplement , a hyperosmolar-inducing intervention . The purpose of this prospect i ve , double-blind , r and omized , controlled study was to evaluate growth , safety , and efficacy in a population of very low birth weight ( VLBW ) preterm infants who received human milk fortified with either the reformulated iron-fortified powdered human milk fortifier test product ( HMF-T ) or a powdered commercially available human milk fortifier control product ( HMF-C ) . Methods . Infants who weighed ≤1500 g , had a gestational age ≤33 weeks postmenstrual age , and had an enteral intake of at least 100 mL/kg per day of unfortified human milk were stratified by gender and birth weight and r and omized to receive HMF-T or HMF-C product from study day 1 to study day 28 , hospital discharge , or the termination of human milk feedings , whichever came first . Unless medically indicated , investigators were not to administer iron supplements from study days 1 to 14 . Infants were assessed serially for growth ; enteral and parenteral intake ; serum chemistry and hematologic values ; clinical histories , including the administration of blood transfusions ; feeding tolerance ; respiratory outcomes ; and morbidities , including adverse events . Results . Of the 181 participating infants in this study , 96 received HMF-T and 85 received HMF-C. At r and omization , there were no significant differences in infant characteristics between the fortifier groups . The percentage of participants who remained in the study for 28 days was similar between fortifier groups ( 57 % HMF-T , 46 % HMF-C ) . For both fortifier groups , the most frequent reasons for discontinuing the study before study day 28 were unavailability of human milk and hospital discharge . Rate of weight gain was similar between the fortifier groups ( 17.5 ± 0.53 g/kg per day for HMF-T and 17.3 ± 0.59 g/kg per day for HMF-C ) . Mean achieved weight , length , and head circumference were comparable between groups across the 28-day study period . Total protein intake from enteral and parenteral nutrition was significantly greater for the HMF-T fortifier group ; however , this difference did not result in any difference in growth between the 2 fortifier groups . An analysis of the growth and energy intake data of a subset of the intent-to-treat population who adhered more strictly to the study feeding protocol yielded results similar to those seen for the intent-to-treat population . There were no clinical ly significant differences in the results of laboratory studies between the groups at study days 0 , 14 , and 28 . Anemia of prematurity was prevalent in both study groups ; by study day 28 , median hematocrit levels were 27.0 % ( interquartile range [ IQR ] : 24.0%–29.6 % ) for the HMF-T group and 26.0 % ( IQR : 24.0%–31.0 % ) for the HMF-C group . Median ferritin levels were 77.0 ng/mL ( IQR : 37 - 155 ng/ml ) for HMF-T and 92.0 ng/mL ( IQR : 33 - 110 ng/mL ) for HMF-C. There were no significant differences between the study fortifier groups in regard to the receipt of medically indicated iron supplements on or before study day 14 or in the administration of blood transfusions before study day 0 or from study days 0 through 14 . However , from study day 15 to study day 28 , fewer HMF-T infants ( n = 12 ) required a blood transfusion than did HMF-C infants ( n = 20 ) . Although the higher levels of iron in the HMF-T fortifier ( 1.44 mg vs 0.35 mg for HMF-C per 4 packets of powdered fortifier ) did not prevent anemia per se , it did reduce the frequency of one of the most serious outcomes of anemia : the need for a blood transfusion . There was no statistically significant difference between fortifier groups in regard to feeding tolerance . Rates of suspected sepsis ( 26 % HMF-T vs 31 % HMF-C ) and confirmed sepsis ( 5 % HMF-T , 7 % HMF-C ) were low as were the rates of suspected necrotizing enterocolitis ( NEC ; 6 % HMF-T and 5 % HMF-C ) and confirmed Bell 's stage 2 or more NEC ( 1 % HMF-T and 1 % HMF-C ) . There were no statistically significant differences between the study fortifier groups in regard to the incidence of confirmed and suspected sepsis and NEC . Conclusion . Both human milk fortifiers studied are safe , are well tolerated , and facilitate comparable good growth ; however , using the iron-fortified product may reduce the need for blood transfusions in VLBW infants . The similar low rates of suspected and confirmed NEC and sepsis seen in both fortifier groups in this study refutes the premise that the inclusion of iron in fortifiers will increase the incidence of sepsis and NEC . Indeed , the incidence for NEC and sepsis for both groups in this study was lower than is reported for VLBW infants and similar to that seen for infants who are fed human milk",
"Some physicians are reluctant to recommend feeding of iron-fortified formulas to infants because of a fear of adverse reactions . In crossover studies , parents ' records were compared with regard to their infant 's behavior ( fussiness , cramps , regurgitation , flatus , colic ) and stool characteristics during periods when iron-fortified formulas were fed and periods when non-iron-fortified formulas were fed . No statistically significant feeding-related difference was noted except for stool color",
"The effect of iron fortification is generally assumed to be less than iron supplementation ; however , the magnitude of difference in effects is not known . The present study aims to compare the efficacy of these two strategies on anaemia and iron status . After screening on low Hb , 425 anaemic children in six primary schools in Tam Nong district of Phu Tho province were included in a r and omized , placebo-controlled trial comparing two groups receiving iron fortified instant noodles or iron supplementation for 6 months and a control group , with children in all groups having been dewormed . Blood sample s were collected before and after intervention for haemoglobin , serum ferritin ( SF ) , serum transferrin receptor ( TfR ) , C-reactive protein ( CRP ) , and haemoglobinopathies analysis . Regression analysis was used to assess the effect of iron fortification and iron supplementation on haemoglobin concentration , SF , TfR , body iron , and anaemic status as outcome variables . The improvement of haemoglobin , SF , and body iron level in the group receiving iron fortification was 42 % ( 2.6 g/L versus 6.2 g/L ) , 20 % ( 23.5 μg/L versus 117.3 μg/L ) , and 31.3 % ( 1.4 mg/kg versus 4.4 mg/kg ) of that in the iron supplementation group . The prevalence of anaemia dropped to 15.1 % in the control group , with an additional reduction of anaemia of 8.5 % in the iron supplementation group . The additional reduction due to iron fortification was 5.4 % , which amounts to well over 50 % of the impact of supplementation . In conclusion , the efficacy of iron fortification based on reduction of prevalence of anaemia , and on the change in haemoglobin level , is about half of the maximum impact of supplementation in case of optimal compliance . Thus , in a population of anaemic children with mild iron deficiency , iron fortification should be the preferred strategy to combat anaemia",
"OBJECTIVE To evaluate the effect of two types of iron pots on haemoglobin ( Hb ) and serum ferritin ( SF ) concentrations in young children ( 6 - 24 months ) , adolescent girls ( 11 - 15 years ) and women of reproductive age ( 15 - 44 years ) , whose households were provided with iron pots for cooking food over a period of 6 months , compared with controls . DESIGN AND METHODS We r and omly assigned 161 households including 339 individuals from the three subgroups to cast iron pots , blue steel pots or oral iron supplements ( control ) . In the control group , children received micronutrient Sprinkles , and adolescent girls and women received iron tablets daily for 6 months . We measured Hb , SF and C-reactive protein concentrations at baseline and 6 months , and compared groups using regression models . RESULTS Anaemia prevalence ( Hb Hb concentrations among groups ; however , differences in SF concentrations were significant ( P SF concentrations compared with the groups using iron pots . Also , differences in the prevalence of iron-deficiency anaemia ( IDA ; anaemia plus SF iron cooking pots are effective against IDA . Further research is warranted to determine whether the iron leached from the pots is bioavailable",
"This study evaluated the effectiveness of supplementation with ferrous sulfate and iron bis-glycinate chelate on hemoglobin and serum ferritin levels among schoolchildren ( 7 - 11 years ) of both sexes . A r and omized community-based trial including 138 anemic children ( hemoglobin Children were assigned to two treatment groups on an individual basis . One group ( n = 71 ) received 40 mg iron as ferrous sulfate once weekly and the other group ( n = 67 ) received 3.8 mg of iron bis-glycinate chelate-enriched cookies , 3x/week , for 8 weeks . The interventions showed a significant increase ( p hemoglobin levels ( 1.1g/dL ) for children who received ferrous sulfate and 0.9 g/dl in those who received iron bis-glycinate chelate , although not significant in the inter-group comparison ( p > 0.05 ) . No effect was observed on body iron for either intervention ( p > 0.05 ) . Children with depleted iron stores ( ) at the beginning of interventions showed increased serum ferritin concentrations after 8 weeks ( p 0.05 ) was observed . The results confirm the effectiveness of the iron supplementation interventions and corroborate the use of iron salts or ferrous bisglycinate chelate on a weekly basis to overcome iron deficiency and anemia",
"OBJECTIVE . Chronic lead poisoning and iron deficiency are concentrated in urban children from lower socioeconomic strata , and both impair neurocognitive development . Our study objective was to determine if iron fortification reduces blood lead levels in urban , lead-exposed , iron-deficient children in Bangalore , India . DESIGN , SETTING , AND PARTICIPANTS . A r and omized , double-blind , controlled school-based feeding trial was done in 5- to 13-year-old iron-deficient children ( n = 186 ) . At baseline , a high prevalence of lead poisoning was found in the younger children . Subsequently , all 5- to 9-year-old children participating in the trial ( n = 134 ) were followed to determine if iron fortification would affect their blood lead levels . INTERVENTION . Children were dewormed and fed 6 days/week for 16 weeks either an iron-fortified rice meal ( ∼15 mg of iron per day as ferric pyrophosphate ) or an identical control meal without added iron . Feeding was directly supervised and compliance monitored . OUTCOME MEASURES . Hemoglobin , serum ferritin , C-reactive protein , transferrin receptor , zinc protoporphyrin , and blood lead concentrations were measured . RESULTS . The prevalence of iron deficiency was significantly reduced in the iron group ( from 70 % to 28 % ) compared with the control group ( 76 % to 55 % ) . There was a significant decrease in median blood lead concentration in the iron group compared with the control group . The prevalence of blood lead levels ≥10 μg/dL was significantly reduced in the iron group ( from 65 % to 29 % ) compared with the control group ( 68 % to 55 % ) . CONCLUSIONS . Our findings suggest providing iron in a fortified food to lead-exposed children may reduce chronic lead intoxication . Iron fortification may be an effective and sustainable strategy to accompany environmental lead abatement",
"Spatone Iron-Plus is a naturally occurring mineral water from Trefriw Wells Spa in Conwy County , North Wales , UK . It contains approximately 0.20 mg of iron per millilitre as ferrous sulphate and has been shown to provide iron in a highly bio-available form . A 24 ml sachet contains approximately 5 mg of iron . Iron deficiency is common in the obstetric population . However , compliance with traditional iron supplements is poor because of gastrointestinal side-effects . We design ed a r and omized , double-blind , placebo-controlled trial . A total of 102 low-risk antenatal patients , who were noncompliant with routinely prescribed ferrous sulphate tablets , were r and omized to receive 48 ml of Spatone water or placebo . The study was conducted between 22 and 28 weeks gestation . Primary outcome measures were compliance , gastrointestinal side-effects and changes in ferritin levels during the trial period . Compliance in the intervention group was 57 % compared with 67 % in the control group , P = 0.22 . Dyspepsia scores , as determined by a recognized and well-vali date d question naire , did not differ between the two groups . During the trial period , mean ferritin levels fell by 24 % in the Spatone Iron-Plus group compared with a mean fall of 51 % in ferritin levels among the control group , P = 0.016",
"Objectives : ( a ) To measure iron absorption by human subjects from citric acid stabilized fish sauce fortified with ferrous sulfate , ferric ammonium citrate or ferrous lactate and ( b ) to identify the effect of added citric acid ( 3 g/l ) on iron absorption from ferrous sulfate fortified fish sauce . Design : Iron absorption from the intrinsically labeled compounds was determined via erythrocyte incorporation of isotopic labels ( 57Fe and 58Fe ) using a r and omized crossover design . In three separate absorption studies , 10 adult women each consumed a basic test meal of rice and vegetable soup seasoned with isotopically labeled , iron fortified fish sauce . Results : Iron absorption was significantly lower from ferrous lactate and from ferric ammonium citrate fortified fish sauce than from ferrous sulfate fortified fish sauce . Fractional iron absorption ( geometric mean ; −1s.d . , + 1s.d . ) was 8.7(3.6 ; 21.4)% for ferrous lactate compared to 13.0(5.4 ; 31.4)% from ferrous sulfate , P=0.003 ( study 1 ) and 6.0(2.5 ; 14.3)% from ferric ammonium citrate relative to 11.7(4.4 ; 30.7)% from ferrous sulfate , P on iron absorption from ferrous sulfate ( study 3 ) . Iron absorption in the presence of citric acid was 14.1(6.4 ; 30.8)% compared to 12.0(5.8 ; 24.7)% in its absence ( P=0.26 ) . Conclusions : Iron absorption was 50–100 % higher from ferrous sulphate fortified fish sauce than from fish sauce fortified with ferric ammonium citrate or ferrous lactate . In the presence of citric acid as a chelator , ferrous sulfate would appear to be a useful fortificant for fish sauce . Sponsorship : International Atomic Energy Agency ( IAEA ) , Vienna ,",
"BACKGROUND Sodium iron edetic acid ( NaFeEDTA ) might be a more bioavailable source of iron than electrolytic iron , when added to maize flour . We aim ed to assess the effect , on children 's iron status , of consumption of whole maize flour fortified with iron as NaFeEDTA or electrolytic iron . METHODS 516 children , aged 3 - 8 years , from four schools in Marafa , Kenya , were r and omly assigned to four groups . All were given the same amount of porridge five times a week . The porridge for one group was made from unfortified whole maize flour ; for the other three groups it was fortified with either high-dose NaFeEDTA ( 56 mg/kg ) , low-dose NaFeEDTA ( 28 mg/kg ) , or electrolytic iron ( 56 mg/kg ) . Concentrations of haemoglobin , plasma ferritin , and transferrin receptor were analysed in sample s taken at baseline and at the end of the 5-month intervention . The primary outcome was iron-deficiency anaemia . We analysed data on an intention-to-treat basis . This trial is registered with Clinical Trials.gov , number NCT00386074 . FINDINGS The prevalence of iron-deficiency anaemia in children given unfortified flour was 10 % . Compared with placebo , the prevalence of iron-deficiency anaemia in children given flour fortified with high-dose NaFeEDTA , low-dose NaFeEDTA , and electrolytic iron changed by -89 % ( 95 % CI -97 % to -49 % ) , -48 % ( -77 % to 20 % ) , and 59 % ( -18 % to 209 % ) , respectively . Consumption of high-dose NaFeEDTA improved all measured iron-status indicators . Low-dose NaFeEDTA decreased the prevalence of iron deficiency but did not noticeably change the prevalence of anaemia . Electrolytic iron did not improve any of these iron-status indicators . Children who were iron-deficient at baseline benefited more from high-dose and low-dose NaFeEDTA than those with sufficient iron at baseline . INTERPRETATION Consumption of whole maize flour fortified with NaFeEDTA caused modest , dose-dependent improvements in children 's iron status . Fortification with electrolytic iron did not improve their iron status . Therefore , in high-phytate flours , NaFeEDTA is more suitable than electrolytic iron for supplementation of iron in the diet",
"Iron deficiency is endemic in much of the world , and food system-based approaches to eradication may be viable with new plant breeding approaches to increase the micronutrient content in staple crops . It is thought that conventional plant breeding approaches provide varieties of rice that have 400 - 500 % higher iron contents than varieties commonly consumed in much of Asia . The efficacy of consuming high-iron rice was tested during a 9-mo feeding trial with a double-blind dietary intervention in 192 religious sisters living in 10 convents around metro Manila , the Philippines . Subjects were r and omly assigned to consume either high-iron rice ( 3.21 mg/kg Fe ) or a local variety of control rice ( 0.57 mg/kg Fe ) , and daily food consumption was monitored . The high-iron rice contributed 1.79 mg Fe/d to the diet in contrast to 0.37 mg Fe/d from the control rice . The 17 % difference in total dietary iron consumption compared with controls ( 10.16 + /- 1.06 vs. 8.44 + /- 1.82 mg/d ) result ed in a modest increase in serum ferritin ( P = 0.10 ) and total body iron ( P = 0.06 ) and no increase in hemoglobin ( P = 0.59 ) . However , the response was greater in nonanemic subjects for ferritin ( P = 0.02 ) and body iron ( P = 0.05 ) , representing a 20 % increase after controlling for baseline values and daily rice consumption . The greatest improvements in iron status were seen in those nonanemic women who had the lowest baseline iron status and in those who consumed the most iron from rice . Consumption of biofortified rice , without any other changes in diet , is efficacious in improving iron stores of women with iron-poor diets in the developing world",
"BACKGROUND Iron deficiency anemia ( IDA ) in the Philippines is a serious public health problem . Fortifying rice offers a great opportunity to control IDA . However , information on other types of fortificants that can be used is scarce . OBJECTIVE To compare the effects of two types of iron fortificants in rice in improving the hematological status of schoolchildren . DESIGN 180 r and omly selected 6-to 9-year-old anemic children were r and omly allocated to three groups in a double-blinded manner : One group received iron-enriched rice ( IER ) with extruded iron premix rice ( IPR ) using ferrous sulfate as fortificant ( ExFeSO4 ) ; the second group received IER with extruded IPR using micronized dispersible ferric pyrophosphate ( ExFeP80 ) ; and the third group received non-fortified rice ( Control ) . These were administered daily for 5 days a week for 6 months . Blood sample s were collected at baseline after 3 and 6 months . RESULTS At baseline , one child in the ExFeP80 group was suffering from IDA ; at 3 months , no IDA was found in any groups ; while at 6 months , one child in the ExFeP80 developed IDA . The baseline prevalence of anemia in all groups , which was 100 % , was significantly reduced to 51 % , 54 % , and 63 % in the ExFeSO4 , ExFeP80 and Control groups respectively . After 6 months , further significant reductions were observed in the ExFeSO4 ( 38 % ) and ExFeP80 ( 33 % ) but remained at 63 % in the Control group . Greater , significant increases were also observed in plasma ferritin in the fortified groups than in the Control group from baseline to 6 months . The predictors of change in hemoglobin ( Hb ) and plasma ferritin were group allocation and basal values . CONCLUSION The consumption of rice fortified with FeP80 using extrusion technology has similar effects as that of FeSO4 in reducing the prevalence of IDA among schoolchildren",
"Preterm infants with birth weights between 1,001 and 1,600 gm were r and omly assigned at one week of age to three groups and fed a st and ard milk-based formula , the same formula with iron , or a soy-based formula with iron . Hematologic values and selenium status were then studied prospect ively for five weeks . Rates of decline in hematocrit and hemoglobin did not differ significantly among the three groups and did not correlate with red cell selenium values or glutathione peroxidase activity . Attainment of vitamin E sufficiency was variable among the infants , with no significant intergroup differences . Plasma selenium concentrations did not change significantly , but plasma glutathione peroxidase activity declined consistently in all three groups . Under the conditions of this study , iron at a concentration of 12 mg/L of infant formula did not accelerate hemolysis ; nor was there evidence of a direct association between selenium values and early anemia of prematurity",
"BACKGROUND Iron status de grade s in female soldiers during military training . Inflammation-mediated up-regulation of hepcidin , a key mediator of iron homeostasis , may be a contributing factor . OBJECTIVE We measured the efficacy of an iron-fortified food product for maintaining iron status in female soldiers during basic combat training ( BCT ) and examined relations between iron status , serum hepcidin concentrations , and inflammation . DESIGN A r and omized , double-blind , placebo-controlled trial was conducted . Volunteers received an iron-fortified food product ( total dose = 56 mg Fe/d ) or a placebo twice daily during the 9-wk BCT course . Iron-status indicators , serum hepcidin concentrations , and markers of inflammation were measured pre- and post-BCT . RESULTS BCT affected iron status ; serum ferritin concentrations decreased ( P concentrations of soluble transferrin receptor ( sTfR ) and hemoglobin and the red cell distribution width increased ( P iron-fortified food product attenuated declines in iron status in iron-deficient anemic soldiers ; a group-by-time interaction was observed for hemoglobin and sTfR concentrations ( P Serum hepcidin concentrations were not affected by BCT ; however , hepcidin concentrations were lower in iron-deficient anemic soldiers than in those with normal iron status ( P serum ferritin ( P C-reactive protein ( P iron-fortified food product improved iron status in iron-deficient anemic soldiers but not in iron-normal or iron-deficient nonanemic soldiers . Serum hepcidin concentrations were not affected by training but were associated with iron status and inflammation pre- and post-BCT . This trial was registered at clinical trials.gov as NCT01100905",
"The use of flour fortified with 66 mg/kg of electrolytic or reduced iron to reduce the prevalence of anemia was determined in a two-year , double-blind , controlled trial . The trial was conducted in Sri Lanka among preschoolers between 9 and 71 months old , primary schoolers 6 to 11 years old , and nonpregnant women . At baseline , 18.4 % of the preschoolers had low hemoglobin ( Hb ) concentrations . Neither electrolytic nor reduced iron had an effect on Hb concentration among preschoolers . Only 7 % of the primary schoolers were anemic at the start of the trial and , again , fortification had no effect on Hb concentration . Twenty-nine percent of women had a low Hb at outset and there was no evidence that fortification had an effect on Hb in this group . The findings from this study suggest that fortification of flour with electrolytic iron or reduced iron was not beneficial in reducing anemia in this population . This was probably due to the low prevalence of anemia and low bioavailability of the fortificant iron . Fortification with either iron fortificant was acceptable",
"Preschool children in developing countries are likely to have multiple , concurrent micronutrient deficiencies . This study was design ed to evaluate the effectiveness of different combinations of nutritional fortified diet to improve the blood levels of iron , vitamin A and other essential micronutrients in the preschool population of Banan District of Chongqing , China . From December 2005 to June 2006 , a total of 226 2 - 6 y old preschool children were recruited from three nurseries in the area , and they were r and omly assigned to three different fortified diet groups for 6 mo . Group I was fortified with vitamin A ; groups II and III were fortified with vitamin A plus iron and vitamin A plus iron , thiamine , riboflavin , folic acid , niacinamide , zinc and calcium , respectively . Subjects ' weight and height were measured for assessing the children 's growth and development . Blood sample s were taken at the beginning and the end of the 6-mo study period for measuring serum levels of micronutrients . Group III with the multiple micronutrient fortified diet was the most effective to improve the serum level of retinol from [ media ( P25 , P75 ) : 1.06 ( 0.89 , 1.32 ) ] micromol/L to 1.29 ( 1.04 , 1.39 ) micromol/L ( p retinol binding protein from 17.0 ( 12.6 , 25.6 ) mg/L to 31.6 ( 24.4 , 44.0 ) mg/L ( p mobilize the stored iron in the liver ( p hemoglobin levels were elevated from 117.0 ( 109.0 , 124.1 ) g/L , 114.0 ( 109.2 , 119.7 ) g/L and 115.0 ( 109.5 , 122.7 ) g/L to 125.7 ( 119.2 , 133.1 ) g/L , 126.5 ( 122.2 , 135.9 ) g/L and 125.1 ( 119.8 , 131.6 ) g/L over the 6 mo of intervention period , but there were no difference among the three groups ( p>0.05 ) . Nevertheless , unexpected results were obtained when comparing the effects on growth status among the different supplement groups . Our study has demonstrated that a multiple micronutrient fortified diet for 6 mo is more effective to improve the levels of hemoglobin , serum retinol , and RBP as well as to facilitate the mobilization of iron storage in preschool children",
"OBJECTIVE Study the efficiency of the NaFeEDTA fortified soy sauce on anemia prevention among the children from iron deficiency anemia ( IDA ) prevalence region . METHODS A double blind controlled r and om intervention in Bijie , Guizhou was conducted for 18 months . The finger hemoglobin ( Hb ) was detected at baseline and after 6 , 12 , 18 months intervention . Anthropometrics were also taken at baseline and after 12 months intervention . RESULTS The Hb level increased significantly in the intervention group [ ( 111.08 + /- 11.31 ) g/L at baseline and ( 122.99 + /- 8.43 ) g/L after 12 months ] , the anemia prevalence decreased markedly ( 58.0 % at baseline , 17.6 % after 12 months ) . After 12 months intervention , a significantly gain of the weight for age Z-score ( WAZ ) was observed in the intervention group . The abdomen and triceps skin folders were thicker in the intervention group , and the intervention group had greater gains of the abdomen and triceps skin folders than those in the control group . CONCLUSION The soy sauce fortified with NaFeEDTA can increase the Hb level and decrease the prevalence of anemia in the children , and the NaFeEDTA fortified soy sauce can enhance the weight gain and the pull up of the subcutaneous fat . It is suggested that using NaFeEDTA fortified soy sauce in high IDA prevalence population was an efficient way for IDA preventing",
"The study objective was to measure the effect of consumption of a beverage mixed with a high-iron sweetener ( evaporated sugarcane juice known as rapadura ) on hemoglobin levels in preschool children , and to compare it with the effect of consuming the same beverage sweetened with refined sugar . Research consisted of a 12-week r and omized , controlled double-blind trial conducted in 2007 at a state-run school in Sobral , Brazil , among children aged 2 - 3 years . The study sample was divided into two groups-one consuming cashew juice mixed with 25 g of rapadura and 40 mg of ascorbic acid ( per 200-mL serving ) , and another consuming the same quantity of juice and ascorbic acid sweetened with 25 g of st and ard refined sugar . A significant statistical increase in hemoglobin was observed in the group consuming the rapadura-fortified beverage . It was therefore concluded that consumption of rapadura increased hemoglobin and thus reduced iron deficiency anemia in preschool children",
"BACKGROUND Many infants are switched between multiple formula preparations early in life because of perceived abnormalities in stooling pattern as well as gastrointestinal symptoms . OBJECTIVE To investigate the relationship between the type of formula consumed and the stooling characteristics and gastrointestinal symptoms of young infants . METHODS Healthy 1-month-old infants were fed one of four commercial formula preparations ( Enfamil , Enfamil with Iron , ProSobee , and Nutramigen ) for 12 to 14 days in a prospect i ve double-blinded ( parent/physician ) fashion . Parents completed a daily diary of stool characteristics as well as severity of spitting , gas , and crying for the last 7 days of the study period . A breast-fed infant group was studied as well . RESULTS Two hundred eighty five infants were enrolled and 238 completed the study . Infants receiving breast milk or Nutramigen had twice as many stools as other formula groups ( P ProSobee had hard/firm stools more often than breast-fed or other formula-fed groups ( P Watery stools were more common in infants fed Nutramigen than other formula groups ( P Green stools were more common in 12 mg/L iron preparations ( Enfamil with iron , ProSobee , Nutramigen ) than in those with 1 mg/L ( Enfamil , breast milk ) ( P Spitting , gassiness , and crying were of equal severity in all formula groups . CONCLUSIONS The interpretation of stool frequency , color , and consistency must take into account the infant 's formula type as significant variations in normal infants occur . Parental education on the range of infant stooling characteristics as well as the common occurrence of spitting , gas , and crying may alleviate concern for formula intolerance and underlying gastrointestinal disease",
"Food fortification is an important long-term strategy for addressing micronutrient deficiencies . Finding the ideal Fe fortification compound , however , remains a challenge . In the present study the effect of ferrous bisglycinate as fortificant in brown bread was compared with that of electrolytic Fe among Fe-deficient school children in a r and omised controlled trial . Children ( n 160 ) , aged 6 - 11 years , with serum ferritin , were r and omly assigned to one of three treatment categories : ( i ) st and ard unfortified bread ; ( ii ) bread with electrolytic Fe as fortificant ; and ( iii ) bread with ferrous bisglycinate as fortificant . Each child received four slices of bread ( 120 g ) on school days , which supplied an average of 3.66 mg elemental Fe per intervention day for 137 d ( 2.52 mg/d for 75 d and 5.04 mg/d for 62 d ) over a period of 7.5 months . Hb , serum ferritin , serum Fe and transferrin saturation were measured at baseline and at the end of the intervention . Significant treatment effects were observed for Hb ( P = 0.013 ) , serum Fe ( P = 0.041 ) and transferrin saturation ( P = 0.042 ) in the ferrous bisglycinate group , but not in the electrolytic Fe group . There were no significant intervention effects for serum ferritin in either treatment group . Overall , ferrous bisglycinate as Fe fortificant in brown bread performed better than electrolytic Fe in a group of Fe-deficient school children over a period of 7.5 months",
"AIMS To prospect ively evaluate the iron nutritional status of preterm infants fed either a term ( 0.5 mg/dl iron ) or preterm ( 0.9 mg/dl ) formulas fortified with iron after hospital discharge . METHODS Healthy low birthweight preterm infants were r and omly assigned into three groups at the time of hospital discharge . Group A were fed an iron fortified preterm formula ( 0.9 mg/dl iron ) until 6 months corrected age ; group B , a fortified term formula ( 0.5 mg/l iron ) until 6 months corrected age group C , the preterm formula between hospital discharge and term , then the term formula until 6 months corrected age . RESULTS Seventy eight infants were followed up to 6 months corrected age . Iron intake from formula differed significantly between the groups ( A , 1.17 mg/kg/day ( SD 0.32 ) > C , 0.86 mg/kg/day ( SD 0.40 ) = B , 0.81 mg/kg/day ( SD 0.23 ) ; p Haemoglobin concentrations were similar to those of iron sufficient preterm infants of the same postnatal age , and term infants of the same postmenstrual age ( after 3 months of age ) . There were no significant differences in haemoglobin concentration ( p = 0.391 ) , plasma ferritin ( A vs B , p = 0.322 ) , or in the incidence of iron deficiency ( A vsB , p = 0.534 ) . CONCLUSIONS Iron fortified formulas containing between 0.5 and 0.9 mg/dl iron seem to meet the iron nutritional needs of preterm infants after hospital discharge",
"The aim of this study was to determine the iron status of infants who consumed porridge cooked in water with added ferrous sulphate . A total of 234 infants , aged 6 - 12 months , were recruited from 36 nurseries in the Democratic Peoples Republic of Korea ( DPRK North Korea ) and r and omly divided into iron ( Fe ) and placebo groups . At baseline , almost half the children had Hb no significant differences between the two groups were found with regard to hemoglobin concentration and anemia prevalence . The Fe group received rice porridge fortified with 10 mg of iron ( as ferrous sulfate ) per day , added to the water in which the rice was cooked and the placebo group non-fortified cereal for 6 months . After which , the hemoglobin ( Hb ) , serum ferritin ( SF ) and packed cell volume ( PCV ) were measured and it was found that the proportion of children with anemia ( Hb Hb levels ( 117.6 g/L v 109.8 g/L p serum ferritin were higher ( 40.7 v 26.8 mcg/L p iron deficiency anemia ( Hb Ferrous sulphate , added to the water in which rice was cooked , lowered the prevalence of iron deficiency anemia of infants in the DPRK with no adverse reactions . This simple fortification would be suitable as a nationwide program in the DPRK and other countries with large infant nurseries",
"The objective of this research was to study the effectiveness of NaFeEDTA-fortified soy sauce for controlling iron deficiency in a high-risk population . This was an 18-month , r and omized , placebo-controlled intervention trial in 14,000 residents aged three years or older in Bijie City , Guizhou Province , China , using sodium-iron ethylene diamine tetraacetate (NaFeEDTA)-fortified soy sauce ( 29.6 mg Fe/100 ml ) . The study data included measurements of food consumption , hemoglobin , serum ferritin , and serum retinol . The results showed that the diet consisted primarily of cereals , fruits , and vegetables , with very little meat . Food consumption remained unchanged during the study period and was similar in the fortified and control groups . The average daily soy sauce consumption of the group consuming the fortified product was 16.4 ml per person , which provided 4.9 mg of iron from NaFeEDTA . At the end of the trial , all age and sex subgroups receiving NaFeEDTA had significantly higher hemoglobin levels , a lower prevalence of anemia , and higher plasma ferritin levels than the controls . The effects became statistically significant after six months of intervention and were maintained throughout the study period . We conclude that NaFeEDTA-fortified soy sauce was highly effective in controlling iron deficiency and reducing the prevalence of iron-deficiency anemia in men , women , and children . NaFeEDTA-fortified soy sauce is affordable and was well accepted by the study population",
"OBJECTIVE NaFeEDTA was considered as a promising iron fortificant for controlling iron deficiency anemia . Soy sauce is a suitable food carrier for iron fortification and is a popular condiment in China . Iron absorption rates of NaFeEDTA and FeSO4 were observed and compared in adult female subjects . METHODS The stable isotope tracer method was used in Chinese females consuming a typical Chinese diet . Ten healthy young Chinese women were selected as subjects in the 15-day study . A plant-based diet was used based on the dietary pattern of adult women in the 1992 National Nutrition Survey . Six milligram of 54Fe in 54FeSO4 soy sauce and 3 mg 58Fe in Na58FeEDTA soy sauce were given to the same subjects in two days . Food sample s and fecal sample s were collected and analyzed . RESULTS Iron absorption rates of NaFeEDTA and FeSO4 were 10.51 % + /- 2.83 and 4.73 % + /- 2.15 respectively . The 58Fe ( NaFeEDTA ) absorption was significantly higher than that of 54Fe ( FeSO4 ) ( P iron absorption rate from NaFeEDTA was 1.2 times higher than that from FeSO4 in Chinese adult women consuming a typical Chinese diet . CONCLUSION The higher absorption rate of NaFeEDTA suggested that NaFeEDTA would be a better iron fortificant used in soy sauce for the controlling of iron deficiency anemia in China",
"OBJECTIVE To determine if repletion of hemoglobin was achievable in young children presenting both severe ( through fortification of liquid 3.3 % butterfat milk with a bioavailable ferrous iron amino acid chelate ( Ferrochel ) at 3 mg iron/liter/day . METHODS A group of 185 children were selected from Tupã , Brazil who presented the above two stages of iron deficiency anemia plus normalcy . Initially , 54 % had severe iron deficiency anemia , 33 % were less severely anemic and 13 % had normal hemoglobin concentrations . They received iron-fortified milk for a mean of 222+/-2 days . Hemoglobin concentrations were measured initially , at 133+/-13 days , and at 222+/-2 days . RESULTS By mean 222 days , 57 % of the childrens ' hemoglobins were normal . Highest rates of repletion were in the initially severe anemic group . Repeated measures ANOVAs demonstrated that hemoglobins at 0 , 133 and 222 days for the total group , as well as for the severe and less severe iron deficiency anemic groups , represented statistically different population s at alpha=0.0005 . Children with initially normal hemoglobin concentrations showed no change at 0 , 133 and 222 days ( alpha=0.10 ) , suggesting the possibility of absorptive regulation of this form of iron . CONCLUSIONS Low hemoglobin concentrations in young children can be increased through daily consumption of fluid milk fortified with 3 mg ferrous amino acid chelate ( Ferrochel )",
" Ninety two normal birthweight infants aged 6 months entered a double blind controlled trial which compared a follow on formula milk with no added iron against the same formula milk containing 1.2 mg of iron per 100 ml . There was no significant difference in the social class or demographic characteristics of the two treatment groups or in the proportion of each group completing the trial . There was no difference between the two groups in the quantity of milk taken but the amounts taken lessened between 6 and 18 months of age . There was no difference between the two groups with respect to mean haemoglobin and median serum ferritin at 6 , 9 , 12 , 15 , and 18 months of age . Very few infants developed iron deficiency anaemia in either group but there was a tendency for serum ferritin levels to fall between 6 and 18 months of age in both groups . The results suggest that iron added to follow on milk was not an important source of dietary iron in the infants studied",
"Aims : To compare iron fortified follow-on milk ( iron follow-on ) , iron fortified partially modified cows ’ milk ( iron milk ) , and iron medicine for the treatment of iron deficiency anaemia ( IDA ) in hospitalised infants . Methods : In a r and omised controlled trial , infants aged 9–23 months with IDA and who were hospitalised with an acute illness received iron follow-on ( 12 mg/l ferrous iron ) , iron milk ( 12.9 mg/l ferrous iron ) , or iron medicine ( ferrous gluconate at 3 mg/kg of elemental iron once daily ) . All interventions were given for three months . Changes in measures of iron status three months after hospital discharge were determined . Results : A total of 234 infants were r and omised . Iron status was measured at follow up in 59 ( 70 % ) iron medicine , 49 ( 66 % ) iron follow-on , and 54 ( 70 % ) iron milk treated infants . There was a significant ( mean , 95 % CI ) increase in haemoglobin ( 15 g/l , 13 to 16 ) and iron saturation ( 9 % , 8 to 10 ) and decrease in ferritin ( −53 μg/l , −74 to −31 ) in all three groups . Mean cell volume increased in iron follow-on ( 2 fl , 1 to 3 ) and iron milk ( 1 fl , 0.1 to 3 ) treated infants , but not in the iron medicine group ( 1 fl , −1 to 2 ) . The proportion with IDA decreased in all three groups : iron medicine 93 % to 7 % , iron follow-on 83 % to 8 % , and iron milk 96 % to 30 % . Adverse effects , primarily gastrointestinal , occurred in 23 % of the iron medicine , 14 % of the iron follow-on , and 13 % of the iron milk group . Conclusions : Iron fortified follow-on milk , iron fortified partially modified cows ’ milk , and iron medicine all effectively treat IDA in infancy",
"OBJECTIVE To test the efficacy of double-fortified salt ( DFS ) on the anaemia and iodine deficiency ( ID ) status of women and their children . DESIGN Double-blind r and omised controlled trial . SETTING Sekyere West District of Ghana . SUBJECTS In this eight-month trial , mildly anaemic or non-anaemic , non-pregnant , non-lactating women were r and omised into three groups receiving : DFS plus weekly placebo ( n = 61 ) ; iodised salt plus weekly 70 mg iron supplement ( n = 65 ) ; or iodised salt ( IS ) plus weekly placebo ( control group , n = 58 ) . Correspondingly , their mildly anaemic and non-anaemic children aged 1 - 5 years were r and omised into two groups receiving either the DFS ( n = 23 ) or IS alone ( control group , n = 59 ) . RESULTS At the end of the intervention , prevalence of anaemia in women remained unchanged in the DFS or IS plus weekly iron supplement group , but significantly increased by 19.5 % in the control group ( P = 0.039 ) . In children , prevalence of anaemia in the DFS group significantly decreased by 21.7 % ( P = 0.025 ) while no change was observed in the control group . ID decreased significantly in all groups of women ( P anaemia in children . Both the DFS and IS significantly reduced ID in women and children to a similar degree",
"BACKGROUND Although uncommon , iron deficiency ( ID ) occurs in breastfed infants . The regular provision of iron may prevent ID . OBJECTIVE The objective was to test the feasibility and effectiveness of 2 modalities of providing iron ( medicinal iron or iron-fortified cereal ) to breastfed infants . The study tested the hypothesis that regular provision of iron improves iron status of breastfed infants without adverse effects . DESIGN In this prospect i ve , r and omized , open-label trial , breastfed infants received on a regular basis either medicinal iron ( n = 48 ) or an iron-fortified fruit-cereal combination ( n = 45 ) from 4 to 9 mo or no intervention ( control group ; n = 59 ) . The interventions provided 7.0 - 7.5 mg ferrous sulfate/d . Infants were enrolled at 1 mo and were followed to 2 y. Iron-status indicators were determined periodically , stool characteristics were recorded , and growth was monitored . RESULTS The regular provision of iron led to improved iron status during and for some months after the intervention . Both sources of iron were about equally effective . Iron affected stool color but had no effect on feeding-related behavior . However , medicinal iron was associated with a small but significant reduction in length gain and a trend toward reduced weight gain . ID anemia was observed in 4 infants ( 2.3 % ) , most of whom had a low birth iron endowment . Mild ID was common in the second year of life . CONCLUSIONS Regular provision of medicinal iron or iron-fortified cereal improves the iron status of breastfed infants and may prevent ID . Both modalities are equally effective , but medicinal iron leads to somewhat reduced growth . This trial was registered at Clinical Trials.gov as NCT00760890",
"OBJECTIVES For bottle-fed babies or nursing infants who receive milk supplements , the American Academy of Pediatrics recommends the use of iron-fortified infant formula . Because these recommendations have not been universally adopted , the hematologic effects of currently available low-iron formulas need to be determined . STUDY DESIGN Healthy Chilean 6-month-old infants ( without iron-deficiency anemia , born at term weighing > or 3.0 kg ) who were totally or partially weaned from the breast were r and omly allocated in a double-blind fashion to receive high-iron ( n = 430 ) or low-iron formula ( n = 405 ) , containing an average of 12.7 mg/L or 2.3 mg/L , respectively , of elemental iron as ferrous sulfate . Iron status was determined at 12 months . RESULTS The prevalence of iron-deficiency anemia was not different in the high- and low-iron groups ( 2.8 % versus 3.8 % , p = 0.35 ) . Nevertheless , infants receiving high-iron formula had somewhat higher levels of hemoglobin and serum ferritin , greater mean cell volumes , and lower erythrocyte protoporphyrin levels ( p iron status , currently available low-iron formulas may prevent iron-deficiency anemia in selected healthy , term infant population s with otherwise poor sources of dietary iron after 6 months of life . Formulas with relatively small amounts of iron appear to prevent iron-deficiency anemia . We speculate that the optimal level of iron fortification likely lies somewhere between the current levels in high- and low-iron formulas",
"Summary Single interventions for helminthic infections and micronutrient deficiencies are effective , but it is not clear whether combined interventions will provide equal , additive or synergistic effects to improve children 's health . The study objective was to determine the impact of single and combined interventions on nutritional status and scholastic and cognitive performance of school children . A double-blind , r and omized , placebo-controlled trial in 11 rural South African primary schools r and omly allocated 579 children aged between 8 and 10 years into six study groups , half of whom received antihelminthic treatment at baseline . The de-wormed and non-de-wormed arms were further divided into three groups and given biscuits , either unfortified or fortified with vitamin A and iron or with vitamin A only , given daily for 16 weeks . The outcome measures were anthropometric , micronutrient and parasite status , and scholastic and cognitive test scores . There was a significant treatment effect of vitamin A on serum retinol ( p micronutrient status in rural primary school children ; vitamin A with de-worming had a greater impact on micronutrient status than vitamin A fortification alone and antihelminthic treatment significantly reduced the overall prevalence of parasite infection . The burden of micronutrient deficiency ( anaemia , iron and vitamin A ) and stunting in this study population was low and , coupled with the restricted duration of the intervention ( 16 weeks ) , might have limited the impact of the interventions",
"OBJECTIVE Low iron status is a well known risk factor for iron deficiency anemia in infants and young children . The aim of the present study was to evaluate the influence of an iron-fortified toddler formula on iron status in 1 - 3 year-olds . PATIENTS AND METHODS Thirty-three healthy infants and young children were assigned to two groups that received 500 mL/day of and iron-fortified toddler formula or 500 mL/day of unmodified cow 's milk for 4 months . Allocation was r and om and double-blind . Daily dietary intake was calculated by dietary evaluation , and iron nutritional status was assessed ( hemoglobin , hematocrit , mean corpuscular volume , mean corpuscular hemoglobin , mean corpuscular hemoglobin concentration , serum iron , ferritin , and transferrin ) . RESULTS At enrollment , no anemia was found in either group , although hemoglobin concentration and hematocrit were significantly lower in the toddler formula group than in the unmodified cow 's milk group . However , these differences disappeared at the end of the intervention period . After 4 months , the toddler formula group showed significantly higher serum ferritin and lower serum transferrin concentrations than the cow 's milk group . CONCLUSION Intake of iron-supplemented toddler formula for 4 months in 1 - 3 year-olds is more effective in maintaining iron nutritional status than cow 's milk",
"The present study was undertaken to determine the actual amounts of mush consumed and energy iron and zinc intakes of , and to investigate the attendance rate among , children aged 6–23 months due to an improved mush intervention . A cohort of 208 children from 27 villages was followed up for 6 months . Twice a day , 6 days/week , each mother took her child to the nutrition centre we had opened in her village to receive the mush and fed it to her child . Amounts consumed were 15 , 21 and 33 g/kg body weight/meal for children aged 6–8 , 9–11 and 12–23 months respectively . The average ( st and ard deviation ) attendance rate was 68.0 % ( 25.6 % ) . The median ( range ) daily intakes from the mush were 213 ( 25–373 ) kcal , 5.3 ( 0.6–9.3 ) mg , and 2.3 ( 0.3–4.1 ) mg for energy , iron and zinc , respectively . This flour and mush production should enter the routines of individual households , supported by a large-scale programme of nutrition education",
"Background / Objectives : Despite repeated public commitments and availability of various forms of iron supplements , rates of anaemia in developing countries remain high . A major reason for this lack of success has been poor adherence . The objective of this study was to compare the effectiveness of daily and flexible administration of micronutrient Sprinkles on adherence , acceptability and haematological status among young children in rural Bangladesh . Subjects/ Methods : A sample of 362 children ( haemoglobin (Hb)⩾70 g l−1 ) aged 6–24 months were cluster-r and omized to receive 60 sachets of Sprinkles either ( i ) daily over 2 months ; ( ii ) flexibly over 3 months ; or ( iii ) flexibly over 4 months . With a flexible regimen , mothers/caregivers decided how frequently to use Sprinkles without exceeding one sachet per day . Adherence was assessed monthly by counting the number of sachets used and acceptability was evaluated through focus group discussion s. Haemoglobin was measured at baseline , at the end of each intervention period and 6 months post-intervention . Results : Mean percent adherence was significantly higher in the flexible-4-month group ( 98 % ) compared to the flexible-3-month ( 93 % ) and daily-2-month ( 88 % ) groups ( P acceptable than daily due to perceived benefits of use . Hb at the end of intervention was significantly higher in the flexible-4-month group compared to the daily group ( P=0.03 ) . Anaemia prevalence decreased by 65 % in the flexible-4-month group compared to 54 % in the flexible-3-month and 51 % in the daily-2-month groups . Percent of cured children who maintained a non-anaemic status 6 months post-intervention was significantly higher in the flexible-4-month ( 82 % ) and flexible-3-month ( 80 % ) groups than the daily-2-month ( 53 % ) group ( P Conclusions : The adherence , acceptability and haematological response to flexible administration over 4 months were found preferable to daily",
"We tested in the field an extruded rice flour , fortified with a bovine haemoglobin concentrate ( Fe:14 mg/100 g of powder ) . This cereal has a high iron bioavailability , good protein quality and amino acid score . Healthy , term breast-fed infants were prospect ively studied . One group ( n = 92 ) received the fortified cereal ( from 4 to 12 months of age ) . As control , 96 infants received regular solid foods ( cooked vegetables and meat ) from age 4 months . At the end of the field trial , a sub sample of infants in both groups was supplemented with 45 mg Fe during 90 d. Iron nutrition status was determined at 9 , 12 and 15 months . At 12 months , iron deficiency anaemia was present in 17 per cent of controls , in 10 per cent of fortified infants as a whole , but only in 6 per cent of the babies who consumed over 30 g of cereal/d . In addition , this latter group did not show any significant changes in iron nutrition status after the supplementation trial . Results demonstrate that the consumption of a haemoglobin fortified cereal is effective in markedly reducing the incidence of iron deficiency in breast-fed infants",
"BACKGROUND Iron is essential for the growth and virulence of many pathogenic enterobacteria , whereas beneficial barrier bacteria , such as lactobacilli , do not require iron . Thus , increasing colonic iron could select gut microbiota for humans that are unfavorable to the host . OBJECTIVE The objective was to determine the effect of iron fortification on gut microbiota and gut inflammation in African children . DESIGN In a 6-mo , r and omized , double-blind , controlled trial , 6 - 14-y-old Ivorian children ( n = 139 ) received iron-fortified biscuits , which contained 20 mg Fe/d , 4 times/wk as electrolytic iron or nonfortifoed biscuits . We measured changes in hemoglobin concentrations , inflammation , iron status , helminths , diarrhea , fecal calprotectin concentrations , and microbiota diversity and composition ( n = 60 ) and the prevalence of selected enteropathogens . RESULTS At baseline , there were greater numbers of fecal enterobacteria than of lactobacilli and bifidobacteria ( P iron status , anemia , or hookworm prevalence at 6 mo . The fecal microbiota was modified by iron fortification as shown by a significant increase in profile dissimilarity ( P number of enterobacteria ( P lactobacilli ( P mean fecal calprotectin concentration ( P Anemic African children carry an unfavorable ratio of fecal enterobacteria to bifidobacteria and lactobacilli , which is increased by iron fortification . Thus , iron fortification in this population produces a potentially more pathogenic gut microbiota profile , and this profile is associated with increased gut inflammation . This trial was registered at controlled-trials.com as IS RCT N21782274",
"BACKGROUND Anemia during infancy impairs neurodevelopment . Little information has been published about the effectiveness of large-scale programs on anemia and iron-deficiency prevention . OBJECTIVE The objective was to assess the effectiveness of a large-scale program that distributes subsidized iron-fortified milk in Mexico on anemia and iron deficiency in children aged 12 - 30 mo . DESIGN A double-blinded , group-r and omized effectiveness trial was conducted in 12 milk distribution clusters assigned to consume iron-fortified ( FM ; n = 7 ) or nonfortified ( NFM ; n = 5 ) milk . A daily portion of FM contained 5.28 mg Fe ( ferrous gluconate ) and 48 mg sodium ascorbate . RESULTS Overall treatment effects were documented at 6 and 12 mo for anemia and for iron deficiency assessed by both serum ferritin ( SF ) and serum soluble transferrin receptor ( sTfR ) ( interaction : P Estimated prevalences ( EPs ) of anemia ( hemoglobin EPs of SF EPs of sTfR > 3.3 mg/L from baseline to 6 and 12 mo decreased from 16.2 % to 8.3 % and 2.0 % , respectively , in the NFM group ( n = 114 ) and from 15.5 % to 0.7 % and 1.1 % , respectively , in the FM group . CONCLUSION A large-scale iron-fortified subsidized-milk program was effective at reducing the rates of anemia and iron deficiency in Mexican children during 12 mo of implementation . This trial was registered at clinical trials.gov as NCT00508131",
"We conducted a r and omized double-blind trial of a cow 's milk infant formula with increased iron fortification in order to confirm its safety and to measure its effects on iron status and immune function . A group of full-term , well nourished and healthy infants was followed from the age of 3 months to 1 year . A control group of 74 infants was given a commercially available infant formula containing 8.3 mg Fe/100 g . The test group of 75 infants received a similar formula with 40 mg Fe/100 g. The formula with the extra iron proved to be safe and , when compared with the control group , the children in the test group had significantly improved iron status as reflected by the proportion of children classed as normal ( 25 of 61 cf . 44 of 65 ; p less than 0.003 ) , and by the mean values of the haemoglobin concentration ( 11.5 cf . 11.9 g/dl ; p = 0.04 ) , red cell distribution width ( 15.5 % cf . 14.4 % ; p = 0.0005 ) , red cell zinc protoporphyrin ( 3.4 cf . 4.0 micrograms/g Hb ; p = 0.04 ) and ferritin ( 29 cf . 17.3 micrograms/l ; p = 0.004 ) . The extra iron fortification depressed zinc concentration in plasma ( 90.6 cf . 83.5 micrograms/l ; p = 0.05 ) . There was no significant difference between the two groups for laboratory measures of immune function or for incidence of infection . No adverse effects such as infection could be attributed to the increased iron . We conclude that iron fortification of cow 's milk infant formula may be safely increased to 40 mg/100 g ( i.e. by a factor of 4.8 over the common concentration of 8.3 mg/100 g ) , but that this has less than the expected effect on iron status . Further studies are required to define ( a ) the long-term role of facilitators of iron absorption such as ascorbic acid , ( b ) the interaction of iron with absorption of divalent trace elements such as zinc , and ( c ) the effect of iron status on immune function and susceptibility to infection",
"Previous data from Vietnam show that anaemia is highly prevalent among schoolchildren , who are considered not to be iron deficient . Trichuris infection doubled the risk of anaemia . The present study aim ed to evaluate the hypothesis that de-worming is more effective than iron fortification in an anaemic , infection-prone population . In a trial with a 2 x 2 factorial design , 425 anaemic children aged 6 - 8 years were r and omly assigned to receive either iron-fortified noodles or placebo , and mebendazole or placebo . Outcomes considered were change in haematological indicators of iron status ( Hb , serum ferritin ( SF ) , serum transferrin receptor ( TfR ) and haemoglobinopathies analysis ) ; inflammations ( C-reactive protein ( CRP ) ) ; parasite infection status ( hookworm , Trichuris and Ascaris infection ) ; and IgE. ANOVA and logistic regression were used to assess the effects of iron fortification and de-worming on Hb , SF , TfR , body iron and anaemia . Hb improved in all groups after 6 months of intervention . Iron fortification significantly improved Hb , SF and body iron ( 2.6 g/l , 16.3 microg/l and 1 mg/kg , respectively ) . Prevalence of elevated IgE was very high at baseline ( 99 % ) and significantly reduced to about 75 % in all groups after intervention . De-worming unexpectedly showed no effect on Hb , iron status and IgE level . It is concluded that iron fortification slightly improved anaemia and iron status in anaemic schoolchildren in rural Vietnam that were not considered iron deficient . Chronic infection or other unidentified factors may play an important role in the seasonal reduction of anaemia seen in all treatment groups",
"In an attempt to determine whether iron-fortified infant formulas produced gastrointestinal symptoms in infants , we fed two similar formulas , one with and one without iron fortification , to a group of 93 term infants upon discharge from the nursery on the third day of life . Infants were fed the formulas for a period of 42 days while their mothers kept detailed daily records of all gastrointestinal symptoms . A total of 49 infants were fed the non-iron-fortified formula and 44 infants were fed the iron-fortified formula . Review of the records revealed no differences in the number of stools per day , the description of the stools , the number of days without stools , the incidence or frequency of colic , spitting-up , or vomiting . We conclude that the feeding of iron-fortified formulas to infants does not produce an increased incidence of gastrointestinal symptoms or signs",
"Background Universal fortification of staple foods with iron has been widely promoted as a cost-effective strategy to reduce iron deficiency in developing-country population s. Nonetheless , relatively few efficacy trials have been reported to date to demonstrate impact on iron status . The Ultra Rice technology provides a means of delivering fortificant iron via rice . Objective The objective of this study was to test the efficacy of rice fortified with microencapsulated , micronized iron pyrophosphate to improve the iron status of women in Mexico in a r and omized , controlled intervention trial . Methods Nonpregnant , nonlactating women 18 to 49 years of age were recruited from six factories . The women received a daily portion of cooked rice 5 days per week for a period of 6 months , before and after which iron status indicators were determined in venous blood sample s. Results The average intake of iron from the fortificant was 13 mg/day . Mean plasma ferritin concentration and estimated body iron stores were significantly higher , and transferrin receptors were lower , in the iron-fortified rice group following the intervention . Mean hemoglobin concentration also increased in the treatment group , but the increase was significant only when the analysis was restricted to those with baseline hemoglobin anemia and iron deficiency was 10.3 and 15.1 percentage points , respectively . Total iron intake from fortificant was a significant covariate of change in body iron stores . The overall prevalence of anemia was reduced by 80 % . Conclusions Fortification of rice with iron using this technology is an efficacious strategy for preventing iron deficiency",
"Objective : This study was undertaken to assess the feasibility and effects of consuming either meat or iron-fortified infant cereal as the first complementary food . Methods : Eighty-eight exclusively breastfed infants were enrolled at 4 months of age and r and omized to receive either pureed beef or iron-fortified infant cereal as the first complementary food , starting after 5 months and continuing until 7 months . Dietary , anthropometric , and developmental data were obtained longitudinally until 12 months , and biomarkers of zinc and iron status were measured at 9 months . Results : Mean ( ±SE ) daily zinc intake from complementary foods at 7 months for infants in the meat group was 1.9 ± 0.2 mg , whereas that of the cereal group was 0.6 ± 0.1 mg , which is approximately 25 % of the estimated average requirement . Tolerance and acceptance were comparable for the two intervention foods . Increase in head circumference from 7 to 12 months was greater for the meat group , and zinc and protein intakes were predictors of head growth . Biochemical status did not differ by feeding group , but approximately 20 % of the infants had low ( μg/dL ) plasma zinc concentrations , and 30 % to 40 % had low plasma ferritin concentrations ( μg/L ) . Motor and mental subscales did not differ between groups , but there was a trend for a higher behavior index at 12 months in the meat group . Conclusions : Introduction of meat as an early complementary food for exclusively breastfed infants is feasible and was associated with improved zinc intake and potential benefits . The high percentage of infants with biochemical evidence of marginal zinc and iron status suggests that additional investigations of optimal complementary feeding practice s for breastfed infants in the United States are warranted",
"Infants were fed cow 's milk‐based formulas containing 4 mg of iron/I from 1.5 to 6 months of age and their hematological status was compared to infants receiving the same formula but with 7 mg of iron/l and with breast‐fed infants . One formula with 4 mg of iron/l contained iron as ferrous sulfate , in another , part of the iron was provided as bovine lactoferrin . We also studied the effect of selenium ( 10 μg/l ) and copper ( 0.4 mg/l ) supplementation on selenium and copper status . There were no significant differences in hematological indices among the groups at 6 months of age ; all infants had satisfactory iron status . Serum transferrin receptor levels , a potential novel indicator of iron status , were highest in breast‐fed infants , suggesting a cellular need for iron , and lowest in infants receiving formula with 7 mg of iron/l . Selenium status , as assessed by serum glutathione peroxidase activity , was similar at 6 months of age in breast‐fed infants and infants fed formula fortified with selenium but lower in infants fed unfortified formula . The lowest levels of glutathione peroxidase activity were found in infants fed the highest concentration of iron ( 7 mg/l ) . Serum copper concentrations were similar in all groups , but the lowest levels were found in infants fed the highest concentration of iron . These results suggest that 4 mg of iron/l is adequate for infants up to 6 months of age and that higher levels may have some negative effects",
"INTRODUCTION In undeveloped countries such as Peru there is a high prevalence of ferropenic anemia . In addition , iron deficiency produces cognitive alterations that could be corrected by iron treatment . OBJECTIVE To evaluate the effect of administration of heme iron-fortified cookies on the intellectual status of preschool children . PATIENTS AND METHODS Using the Goodenough-Harris Test ( GHT ) and Wechsler Preschool and Primary Scale of Intelligence ( WPPSI ) we studied the intellectual status of 53 children who received heme iron-fortified cookies for 6 - 8 weeks and 55 controls without fortification , in 2 occasions ( before and after intervention ) . RESULTS We observed a significantly higher improvement in children who received iron respect to controls for GHT score ( p WPPSI score ( p WPPSI attention-concentration subscale ( p WPPSI pure attention subscale ( p heme iron-fortified cookies may improve the intellectual performance of low-income preschool children",
"Adverse sensory changes prevent the addition of highly bioavailable ferrous sulfate ( FeSO4 ) to most wheat flours . Poorly absorbable reduced Fe powders are commonly used . Encapsulation of FeSO4 can overcome these sensory changes , but the particle size of commercial compounds is too large to be used by flour mills . The first objective of the study was to measure the efficacy in wheat flour of two newly developed Fe compounds , an H-reduced Fe powder ( NutraFine RS ; North America Höganäs High Alloys LLC , Johnstown , PA , USA ) and small particle-sized ( 40 microm ) encapsulated FeSO4 . As a second objective , the microcapsules were evaluated as a vehicle for iodine fortification . A r and omised , double-blind controlled intervention trial was conducted in Kuwaiti women ( n 279 ; aged 18 - 35 years ) with low body Fe stores ( serum ferritin ( SF ) assigned to one of three groups ( 20 mg Fe as NutraFine RS , 10 mg Fe as encapsulated FeSO4 and 150 microg iodine , or no fortification Fe ) who consumed wheat-based biscuits 5 d per week . At baseline and 22 weeks , Hb , SF , transferrin receptor , urinary iodine and body Fe stores were measured . Relative to control , mean SF in the encapsulated FeSO4 group increased by 88 % ( P body Fe stores increased from - 0.96 to 2.24 mg/kg body weight ( P increase SF or body Fe stores . The median urinary iodine concentration increased from 140 to 213 microg/l ( P efficacious in improving Fe status . The newly developed microcapsules were highly efficacious in improving both Fe stores and iodine status",
"OBJECTIVE To determine whether low-income infants ' adherence to nutritional supplementation with ferrous fumarate sprinkles was better than that with ferrous sulfate drops . STUDY DESIGN The study was a r and omized clinical trial of healthy 6-month-old infants . Each infant received either a daily packet of sprinkles or a dropperful of liquid . Follow-up included alternating telephone and home visits biweekly for 3 months . Adherence was defined as high if the infant 's caregiver reported supplement use on 5 to 7 days during the week before assessment . Side effects and caregiver attitude about supplements were secondary outcomes . Analyses were conducted using generalized estimating equations and chi(2 ) and Wilcoxon rank-sum tests . RESULTS A total of 150 of 225 eligible infants were enrolled . Adherence to supplementation was generally poor . High adherence ranged from 32 % to 63 % at any assessment in the subjects receiving drops , compared with 30 % to 46 % in those receiving sprinkles . The drops group was more likely to have at least four assessment s with high adherence ( 22 % vs 9.5 % ; P = .03 ) . Caregivers of the drops infants were more likely to report greater than usual fussiness ( P fussiness had no consistent impact on adherence . CONCLUSIONS The use of ferrous fumarate sprinkles rather than traditional ferrous sulfate drops did not improve adherence with daily iron supplementation in low-income infants",
"The effect of chronic iron intake on diarrhoeal disease was evaluated in children in a community of low socio-economic stratum in Santiago , Chile . Children were incorporated into each of two consecutive cohorts ; each cohort was divided into two groups , one receiving iron-enriched milk ( 12 mg/l ) ( monthly average = 70 children ) and the other a control milk ( 1 mg/l ) ( monthly average = 83 children ) , and each cohort was followed up for 6 months . The incidence of diarrhoea was higher among the iron-supplemented children ( 30.4 vs 25.5 episodes/100 children/month , P 3 - 8 months of age during the summer months . Supplemented infants had more bowel movements on day 1 ( P liquid or semi-liquid stools were passed for more than 15 days more frequently ( P Shigella-associated episodes were less common among iron-supplemented infants ( P Asymptomatic shedding of enteropathogens significantly increased in infants 12 - 18 months of age receiving iron-supplemented milk . In areas with inadequate environmental sanitation , chronic iron supplementation may have negative effects on diarrhoeal morbidity , despite improving iron nutritional status",
"BACKGROUND In many developing countries , children are at high risk for both goiter and anemia . In areas of subsistence farming in rural Africa , salt is one of the few regularly purchased food items and could be a good fortification vehicle for iodine and iron , provided that a stable yet bioavailable iron fortificant is used . OBJECTIVE We tested the efficacy of salt dual-fortified with iodine and micronized ferric pyrophosphate for reducing the prevalence of iodine and iron deficiencies in children . DESIGN In rural northern Morocco , we fortified local salt with 25 microg I ( as potassium io date ) /g salt and 2 mg Fe ( as micronized ferric pyrophosphate ; mean particle size = 2.5 microm)/g salt . After storage and acceptability trials , we compared the efficacy of the dual-fortified salt ( DFS ) with that of iodized salt in a 10-mo , r and omized , double-blind trial in iodine-deficient 6 - 15-y-old children ( n = 158 ) with a high prevalence of anemia . RESULTS After storage for 6 mo , there were no significant differences in iodine content or color lightness between the DFS and iodized salt . During the efficacy trial , the DFS provided approximately 18 mg Fe/d ; iron absorption was estimated to be approximately 2 % . After 10 mo of treatment in the DFS group , mean hemoglobin increased by 16 g/L ( P iron status and body iron stores increased significantly ( P iron deficiency anemia decreased from 30 % at baseline to 5 % ( P urinary iodine ( P thyroid volume ( P < 0.01 ) improved significantly from baseline . CONCLUSION A DFS containing iodine and micronized ferric pyrophosphate can be an effective fortification strategy in rural Africa",
"AIMS Iron deficiency anaemia is associated , in observational studies , with developmental disadvantage . This study tested the hypothesis that feeding iron supplemented formula from 9 to 18 months of age would improve developmental performance . SUBJECTS AND METHODS 493 healthy children aged 9 months being fed pasteurised cows ’ milk were recruited from three UK centres . They were r and omised to : cows ’ milk as before , formula containing 0.9 mg/litre iron , or formula containing 1.2 mg/litre iron , until 18 months of age . Bayley mental and psychomotor developmental indices were measured at 18 months , as were growth and haematological indices . RESULTS Children fed iron fortified formula had higher plasma ferritin concentrations , but there were no significant intergroup differences in development or growth . CONCLUSIONS There are no developmental or growth advantages in children given iron supplemented formula , but a benefit for a minority who were anaemic , or the possibility that a benefit may emerge at a later age , can not be excluded",
"To address the hypothesis that increased infectious morbidity is associated with iron supplementation , 783 r and omly selected infants were provided with a powdered full fat cow 's milk ( non-fortified group ) and 872 with a powdered acidified full fat cow 's milk fortified with 15 mg of iron as ferrous sulfate ( fortified group ) . All infants were followed from birth to 15 months of age with a monthly home visit by a nurse who recorded morbidity occurring during the previous 30 days . At 9 months of age , 15 % of infants in each cohort were receiving breast milk only ; data for these infants were segregated to make the third group . Episodes ( mean + /- SD ) of diarrhea/infant/year were 1.06 + /- 1.29 , 1.14 + /- 1.37 , and 0.82 + /- 1.04 for the fortified , non-fortified and breast-fed groups , respectively ; the fortified and non-fortified bottle-fed groups had a very similar incidence of respiratory illness ; 2.66 + /- 2.07 and 2.74 + /- 2.24 episodes/infant/year , respectively . The incidence of respiratory illness for both bottle-fed groups was significantly higher than that for the breast-fed group ( 2.22 + /- 1.84 respiratory episodes/infant/year ) . We conclude that for the infants the tested form of iron fortified milk , which is sufficient to lower iron deficiency anemia , does not result in an increased incidence of diarrhea or respiratory illness",
"BACKGROUND Inhabitants of agrarian villages of rural Cambodia suffer from high prevalences of iron deficiency and anemia in the context of a monotonous diet . OBJECTIVE To compare the efficacy and safety of placebo Khmer fish sauce to that of 10 mL of fish sauce containing 10 mg of iron , added to daily school meals either as NaFe-EDTA or as FeSO4 + citrate . METHODS 140 students aged 6 - 21 years were enrolled in a double-blinded , placebo-controlled intervention trial . They were r and omly allocated to one of three treatment groups , and followed for 21 weeks during which 114 school meals seasoned with 10 mL of fish sauce were consumed by each participant . Changes in the concentrations of hemoglobin ( hb ) , serum ferritin ( SF ) , and C-reactive protein ( CRP ) and in body weight and st and ing height were determined . Prevalences of vomiting , diarrhea , and acute respiratory infections were monitored weekly . RESULTS Both iron-fortified fish sauces increased hb and SF concentrations significantly as compared to placebo . No significant differences were observed between FeSO4+citrate and NaFe-EDTA fortification , regarding mitigation of iron-deficiency anemia ( IDA ) or regarding CRP , growth , infections , or side-effects . CONCLUSIONS Iron-fortified Khmer fish sauce added to Khmer food is a suitable vehicle for iron fortification in children and adolescents . FeSO4+citrate and NaFe-EDTA show equivalent efficacy and safety",
"Objectives : To evaluate the effects of fortified drinking water , with different concentrations of iron added , on hemoglobin and hematocrit values in preschoolers . Methods : Double-blind , r and omized cluster clinical trial , with children aged 2 to 5 years of age , from 4 state-run schools , forming 1 group for each school . For fortification , ferrous sulphate in concentrations of 5 mg of elemental iron per liter of water ( group A ) , 7.5 mg ( group B ) , and 10 mg ( group C ) , was used during a period of 4 months . In group D , the control , a placebo ( Bixa orellana ) was added . Hemoglobin and hematocrit values were checked before and after intervention . Results : Before fortification , hemoglobin and hematocrit averages were below the reference values adopted in all groups . After fortification , the prevalence of anemia showed a reduction in the 4 groups , which was more pronounced in group B , at 48.3 % . The hemoglobin values in groups B ( 11.5 ) and C ( 11.4 ) were statistically similar . However , the average consumption of water/day/student was lower in group C. Comparison of hemoglobin values between groups A ( 11.2 ) and D ( 11.0 ) did not show a significant difference , suggesting insignificant efficacy with 5 mg Fe/L fortification . Conclusions : The consumption of drinking water fortified with 7.5 mg of elemental iron/L water result ed in greater adhesion and an increase in hemoglobin values , with a reduction in the prevalence of anemia",
"Results of research into preventing iron-deficiency anaemia in inner-city toddlers , published in full in Archives of Disease in Childhood ( 1996 ; 75 : 9 - 16 ) , are discussed by the authors . In a prospect i ve study , 100 infants already receiving pasteurised cow 's milk by six months old were r and omly divided into two groups , one to receive a follow-on formula and the other to continue on cow 's milk until aged 18 months . At 18 months one-third of the cow 's milk group were anaemic compared with 2 % of the formula group . The authors consider that if the same volume of st and ard infant formula had been given instead of a follow-on formula , substantially fewer of the children would have reached the correct reference nutrient intake for iron",
"BACKGROUND Iron deficiency continues to be a common problem among infants throughout the world . Iron-fortified formula is effective in preventing iron deficiency but the benefit of iron-fortified cereal is controversial . METHODS We compared iron-fortified rice cereal to unfortified rice cereal in infants who were exclusively breast-fed for more than 4 months and to iron-fortified formula in infants who were weaned to formula before 4 months of age . The design was double blind in respect to the presence or absence of fortification iron in the cereal or formula and included 515 infants who were followed on the protocol from 4 to 15 months of age . Rice cereal was fortified with 55 mg of electrolytic iron per 100 g of dry cereal and infant formula with 12 mg of ferrous sulfate per 100 g of dry powder , levels approximating those in use in the United States . Measures of iron status were obtained at 8 , 12 , and 15 months . Infants with hemoglobin levels of were excluded from the study and treated . RESULTS Consumption of cereal reached plateaus at means of about 30 g/d after 6 months of age in the formula-fed groups and 26 g/d after 8 months in the breast-fed groups ; these amounts are higher than the 19-g/d mean intake by the 73 % of infants who consume such cereal in the United States . Among infants weaned to formula before 4 months , the cumulative percentages of infants excluded for anemia by 15 months were 8 % , 24 % , and 4 % , respectively , in the fortified cereal , unfortified cereal and formula , and fortified formula groups ( P unfortified cereal groups ( P Mean hemoglobin level and other iron status measures were in accord with these findings . CONCLUSION Iron-fortified infant rice cereal can contribute substantially to preventing iron deficiency anemia",
"Abstract Six‐month‐old infants were recruited at 21 centres in the UK and Irel and and r and omly assigned to receive matching iron‐fortified ( 12.3 mg/l iron ) or non‐fortified ( 1.4 mg/l iron ) formula for 9 months . Infants already receiving cow 's milk continued this feed . Haematological indices and iron status were evaluated at age 6 months , 9–10 months and 15 months . Four hundred and six infants entered and 302 completed the study . There were no differences between the groups for increases in weight , head circumference or length . Significant differences between the groups were observed at 15 months for haemoglobin , serum ferritin , serum iron and total iron binding capacity . Haemoglobin levels were non‐iron‐fortified and iron‐fortified formula respectively . The corresponding figures for serum ferritin < 10 µg/l were 43 % , 22 % and 6 % . Follow‐on formula provides an acceptable vehicle for preventing iron deficiency in this vulnerable group",
"Iron deficiency anemia ( IDA ) is a significant public health problem among Canadian Aboriginal children . The objectives of this study were to determine the acceptability and safety of microencapsulated-iron sprinkles , a new powdered form of iron packaged in a single-serving sachet for prevention of IDA . A total of 102 non-anemic children aged 4 to 18 months from three communities were r and omized to receive sprinkles containing 30 mg Fe/day ( NR = 49 ) or placebo ( NR = 53 ) for six months . To assess acceptability , adherence and side effects were monitored bi-weekly . To assess safety , serum ferritin ( SF ) concentration and anthropometry were measured at baseline and end . Mean adherence was 59.6 + /- 27.7 percent . There were no differences in adherence , SF , anthropometric status or side effects between groups . Although there were no differences in hemoglobin ( Hb ) concentration and anemia prevalence from baseline to end and between groups , the Hb curve shifted to the right ( increased ) for the sprinkles group and to the left ( decreased ) for the placebo group . Sprinkles may provide a safe and acceptable option to the current st and ard of care ( i.e. ferrous sulphate drops ) for the provision of iron in Canadian Aboriginal population",
"This was a double-blind , placebo-controlled , community-based trial . For 16 weeks , children in the intervention group ( n = 180 ) received iron-fortified rice , while children in the control group ( n = 174 ) received rice with placebo . Anemia was defined as hemoglobin t-test was used to compare mean variation in hemoglobin between the groups . Hemoglobin concentration improved in both groups , with a mean increase of 0.42g/ dL in the intervention group ( 11.28+/-1.23g/dL to 11.75+/-1.16g/dL , p Anemia decreased ( p Hemoglobin increase was significantly higher in children that received total iron = 53.76 mg from fortified rice , compared to those who received less than this cut-off value ( 0.94g/dl vs. 0.39g/dl , p = 0.03 ) . The findings suggest that this type of intervention can be useful in anemia control as long as fortified food intake is adequate",
" The effects on iron absorption of a traditionally fermented Japanese soy sauce added to soy and rice meals were assessed . The addition of soy sauce to a soy flour meal could not overcome the strong inhibition of iron absorption ( geometric mean absorption 7.2 per cent with soy sauce vs. 8.7 per cent without , P = 0.5 ) . However , soy sauce added to a rice meal instead of soy flour significantly improved the geometric mean iron absorption ( 13.9 per cent with soy sauce vs. 5.2 per cent with soy flour , P = 0.002 ) and had a promotory effect on absorption from a rice meal alone ( 11.4 per cent with soy sauce vs. 3.5 per cent without , P = 0.0002 ) . Although soy sauce contains appreciable amounts of organic acids , the addition of 340 mg lactic acid to rice did not enhance iron absorption ( 3.1 per cent with lactic acid vs. 2.2 per cent without , P = 0.11 ) . The promotory effect of soy sauce on iron absorption appears to be due not only to its lack of soy protein content but may also be due to the presence of fermentation products other than organic acids",
"OBJECTIVES To investigate the effect of increased iron intakes on hematologic status and cognition in low birth weight infants . STUDY DESIGN We r and omly assigned 58 infants to receive formula with 13.4 mg iron/L ( normal iron ) or 20.7 mg iron/L ( high iron ) . At baseline , discharge , and at 3 , 6 , 9 , and 12 months ' corrected age , we assessed anthropometry ; infections ; red blood cell hemoglobin , catalase , glutathione peroxidase , red blood cell fragility ( hydrogen peroxide test ) , and superoxide dismutase values ; plasma malondialdehyde , ferritin , iron , transferrin , zinc and copper levels ; and diet intake . Griffiths ' Development Assessment was done at 3 , 6 , 9 , and 12 months only . RESULTS No statistical differences ( P weight , catalase or malondialdehyde levels , red blood cell fragility , or Griffith 's Development Assessment . Iron intakes were greater in the high iron group except at 12 months . Hemoglobin ( high iron , 123 + /- 9 ; normal iron , 118 + /- 8) was not different at 3 months ( P = .07 ) . Plasma zinc levels ( high iron , 70 + /- 14 ; normal iron , 89 + /- 27 ) and copper levels ( high iron , 115 + /- 26 ; normal iron , 132 + /- 27 ; P = .06 ) at 12 months suggested inhibition of absorption by high iron formula . Glutathione peroxidase levels were higher in the high iron group . The total number of respiratory tract infections was greater in the high iron group ( 3.3 + /- 0.9 ) than in the normal iron group ( 2.5 + /- 0.9 ) . CONCLUSION In terms of cognitive outcome , there is no advantage associated with elevated iron intake for low birth weight infants",
"The effect of Fe fortification on the absorption of Zn was studied by radioisotopic labelling of single meals , followed by measurements of whole-body retention of 65Zn at 14 d after intake . Healthy adult volunteers participated in the study . Weaning cereal , wheat bread and infant formula , foods that are all frequently Fe-fortified , were evaluated in the study . The amounts of Fe added as FeSO4 were similar to the levels in commercial products in Europe and the USA , and were 200 or 500 mg Fe/kg ( weaning cereal ) , 65 mg Fe/kg ( white wheat flour ) and 12 mg Fe/l ( infant formula ) . For comparison , Zn absorption was measured in the same subjects , from identical test meals containing no added Fe . No statistically significant differences were found when Zn absorption from the Fe-fortified test meals was compared with that from non-Fe-fortified test meals . Fractional Zn-absorption values from Fe-fortified v. non-fortified meals were 31.1 ( SD 11.9 ) v. 30.7 ( SD 7.0)% ( weaning cereal ; 200 mg Fe/kg ) , 37.7 ( SD 16.6 ) v. 30.2 ( SD 9.9)% ( weaning cereal ; 500 mg Fe/kg ) , 36.5 ( SD 14.4 ) v. 38.2 ( SD 18.1)% ( bread ; 65 mg Fe/kg flour ) and 41.6 ( SD 8.1 ) v. 38.9 ( SD 14.5)% ( infant formula ; 12 mg Fe/l ) . The addition of Fe to foods at the currently used fortification levels was thus not associated with impaired absorption of Zn and the consumption of these Fe-fortified foods would not be expected to have a negative effect on Zn nutrition",
"Iron intakes and iron status were evaluated in 36 young Swedish children given either iron‐fortified or unfortified cow 's milk . All children had good iron status and had received breast milk or ironfortified formulae during infancy . Twenty 1‐y‐old children were r and omized to a diet with iron‐fortified milk ( 7.0 or 14.9 mg Fe T−1 ) and 16 to a diet with unfortified milk . The iron intakes in the unfortified group at 15 and 18 mo ( mean ± SD 5.19 ± 2.29 and 5.84 ± 1.62 mg d−1 ) were low in relation to Nordic Nutrition Recommendations , while the intakes in the iron‐fortified group ( 10.20 ±2.60 and 10.87 ± 2.79 mg d−1 ) were normal in relation to recommendations . The gain ( increase ) from receiving fortified diet during the study period was at most [ upper limit for 95 % confidence interval ( CI ) ] 2.6 g T−1 in blood haemoglobin , 1.9 fl in mean corpuscular volume , 2.7 Limol in serum iron and 4.5 % in transferrin iron saturation , and the gain ( decrease ) was at most ( lower limit for 95 % CI ) 0.29 g T−1 in serum transferrin and 0.9 mgr−1 in serum transferrin receptor ( TfR ) . None of these differences was statistically significant . There was an almost significantly higher increase in serum ferritin ( 1.4 times higher relation of values at the end compared with the beginning , p= 0.06 ) and a significantly higher ( 1.2 ; p= 0.047 ) decrease in TfR/ log10 ferritin ratio in the fortified group ",
"The therapeutic effects of NaFeEDTA-fortified soy sauce on anaemic students were investigated . Three hundred and four iron-deficient anaemic school children ( 11 - 17 years ) were r and omly assigned to three treatment groups : control group ( consuming non-fortified soy sauce ) , low-NaFeEDTA group ( consuming fortified soy sauce , providing 5 mg Fe/day ) and high-NaFeEDTA group ( consuming fortified soy sauce , providing 20 mg Fe/day ) . Blood haemoglobin ( Hb ) levels were determined before and after 1 month , 2 months and 3 months of intervention . In addition , serum iron ( SI ) , serum ferritin ( SF ) , free erythrocytic porphyrin ( FEP ) , total iron binding capability ( TIBC ) and transferritin ( TF ) were measured before and after consumption of soy sauce for 3 months . The results obtained herein show that the parameters measured were not changed remarkably within the 3-month intervention in the control group ( P increased Hb , SI , SF and TF levels and decreased TIBC and FEP levels were observed in both the high-NaFeEDTA group ( P effectiveness of iron intervention in the low-NaFeEDTA group and high-NaFeEDTA group had no statistical significance after 3 months . It was concluded that nutritional intervention for anaemic students using NaFeEDTA-fortified soy sauce could play a positive role in the improvement of iron status and control of anaemia",
"OBJECTIVE A r and omized , double-blind study was conducted comparing high-iron content ( 15 mg/L ) with low-iron content ( 3 mg/L ) premature formula given during initial hospitalization to infants with birth weights less than 1800 g to determine the influence of these differing intakes on the iron nutritional status during the first 4 months of life . A third group of similar infants received human milk mixed with an equal volume of liquid fortifier result ing in an iron content of approximately 1.7 mg/L. PATIENTS AND METHODS Mean birth weight , gestational age , age at study entry , volume of blood removed for studies , and volume of red cells transfused were not different among the three groups . After hospitalization both formula-fed groups were given a cow milk formula with an iron content of 12 mg/L , and breast-fed infants were given an iron-containing multivitamin with a result ing iron intake of 10 mg/d . Infants were observed to 8 weeks after discharge . RESULTS There were no differences in serum iron , ferritin , transferrin , transferrin saturation , hemoglobin , hematocrit , or reticulocyte count among the three groups at study entry , although mean corpuscular hemoglobin and mean corpuscular volume were lower in infants in the low-iron formula group . Mean plasma ferritin was significantly lower in infants receiving low-iron content premature formula at the time of hospital discharge compared with the other two groups . The incidence of anemia ( hemoglobin low transferrin saturation ( low plasma ferritin ( iron intake were observed . Growth was not different among the three groups . CONCLUSIONS These data indicate that preterm infants with formula benefit from formula given during initial hospitalization containing 15 mg/L iron compared with that containing 3",
"There are few data to support the use of follow-on formulas in infants from the age of 6 months . In a prospect i ve trial in a deprived inner city area of Birmingham 100 infants who were already receiving pasteurised cows ' milk by 6 months of age were enrolled and r and omised either to receive a follow-on formula or to continue on cows ' milk from 6 months until 18 months . At 18 months of age the follow-on formula group returned to cows ' milk and both groups were followed up until 24 months . Iron status , growth , and nutritional status were analysed at intervals of six months . At enrollment , no differences in haematological status were evident . However , by 12 months of age , 31 % of the cows ' milk group were anaemic ( haemoglobin concentration formulas . At 18 months , 33 % of the cows ' milk group were anaemic compared with only 2 % of the follow-on formula group and by 24 months of age none of the follow-on formula group was anaemic , whereas 26 % in the cows ' milk group still had a haemoglobin of Mean corpuscular volume was significantly smaller and ferritin significantly lower in the cows ' milk group at 12 , 18 , and 24 months . Dietary iron intake was higher in the follow-on formula group at 12 and 18 months but not at 24 months , when both groups were back on cows ' milk . Infants and toddlers at high risk of iron deficiency are therefore unlikely to become anaemic if receiving a follow-on formula , although the relative merits of follow-on formula compared with an ordinary infant formula remain uncertain",
"1 . Two large-scale community based studies of the haematinic effect of iron added to flour used to bake bread are reported . These were design ed to simulate conditions in the community as closely as possible . 2 . Neither trial gave conclusive evidence of benefit in terms of an effect on circulating haemoglobin level , but in one trial the results suggested a small haematinic effect . 3 . The availability of an iron salt from bread eaten in a normal varied diet is clearly much lower than has been suggested from highly controlled radioactive isotope studies",
"OBJECTIVE To determine the efficacy of iron-fortified infant formula in preventing developmental delays and abnormal behavior . DESIGN Double-blind , r and omized , controlled trial . SETTING Urban hospital clinic . PARTICIPANTS A total of 283 healthy , bottle-fed infants from very low income families . Children with prematurity , low birth weight , and major anomalies and those who had received more than 2 weeks of evaporated-milk feedings were excluded . The groups were similar for sociodemographic background variables . Fifty-eight infants ( 20.5 % ) dropped out before any outcome data were gathered ; 225 , 204 , 186 , and 154 remained at 6- , 9- , 12- , and 15-month assessment s , respectively . INTERVENTION Iron-fortified formula ( 12.8 mg iron per liter ) versus regular formula ( 1.1 mg iron per liter ) . MAIN OUTCOME MEASURES Iron status was measured on venous blood by determination of hemoglobin , serum iron and iron-binding capacity , serum ferritin , and free erythrocyte protoporphyrin values . The Bayley Scales of Infant Development ( mental and psychomotor indexes ) and two factors of the Infant Behavior Record ( test affect and task orientation ) were the outcomes of interest . RESULTS All measures of iron status were significantly different between groups ( p Psychomotor development patterns differed between groups ( F3,520 , 3.4 ; p = 0.02 ) with time . Mean values were similar at 6 months but differed at 9 and 12 months of age ( p Mental development and behavior were not affected . CONCLUSIONS Iron-fortified formula significantly reduced iron deficiency in a high-risk group of infants and prevented a decline in psychomotor development quotients . This effect may be transient , and its long-term significance needs further study",
"The interactions between infections , malnutrition and poor iron nutritional status in infants at weaning ages are poorly defined . Therefore , four groups of infants from an area with a high incidence of malnutrition ( Lahore , Pakistan ) were enrolled in a prospect i ve , r and omized nutritional intervention study . Between 122 and 365 days of age , the infants from one community received either a milk cereal without iron fortification ( n= 29 ) , a milk cereal fortified with ferrous fumarate ( 7.5 mg/100 g ; n= 30 ) , or a milk cereal fortified with ferric‐pyrophosphate ( 7.5 mg/100 g ; n= 27 ) . Forty‐four infants from a neighbouring community did not receive a nutritional supplement and served as the control group . Calculated mean daily energy‐ and protein intake with the cereals was between 259–287 kcal , and 9.6–10.6 g at 12 months of age , respectively . Mean daily iron intake with the fortified cereals was between 4.1–5.1 mg at corresponding age . Nutritional supplementation result ed in significantly lower incidence of malnutrition and heigher weight gain . Incidence of acute diarrhoea was significantly ( p the iron‐fortified milk cereals had significantly higher hemoglobin ( mean 10.4 vs. 9.8 gdl‐1 ) and serum ferritin ( mean 13.3 vs. 8.5 ngml‐1 ) values than the infants fed the non‐fortified milk cereals . However , no differences in the incidence of infections were found between the supplemented groups . It is concluded that poor nutritional intake between 122 and 365 days of age substantially contributed to the high incidence of diarrhoea and malnutrition in Pakistani infants",
"Iron deficiency and iron-deficiency anemia are common in the developing world . We evaluated the feasibility of iron fortification of domestic drinking water to prevent and control iron deficiency and iron-deficiency anemia . Twenty-one families representing 88 persons , including children , were selected to participate in this study . Twelve families added an iron solution plus ascorbic acid to their domestic drinking water over a four months period and nine families added a placebo . Blood sample s were collected , before and after the four months , for hemoglobin and serum ferritin measurements . Iron-fortified drinking water increased hemoglobin ( children 10.9 ±1.1 g/dl to 11.7 ± 1.1 g/dl p .01 ) and ferritin ( children 27.6 ± 21.6 ng/dl to 33.8 ± 22.1 ng/dl , adults 74.8 ± 41.3 ng/dl to 106.2 ± 93.9 ng/dl p .05 ) . No significant changes in hemoglobin and ferritin were found in the placebo group after 4 months . Preparation , distribution , and consumption of the solutions were successful . Iron fortification of household drinking water can be a simple and effective alternative to deal with iron deficiency and iron-deficiency anemia in less developed areas",
"UNLABELLED Recent research has not only question ed the necessity of iron supplementation in human milk substitutes prior to weaning , but also suggested some potential adverse effects . This study investigated the hypothesis that infant formula need not contain added iron in the first 3 mo . Healthy term infants were recruited into a double-blind controlled trial and r and omized to receive either a new no added iron formula ( New ; a st and ard formula ( St and ard ; 0.5 mg Fe 100 ml(-1 ) ) for the first 3 mo of life . A breastfed reference group was also studied . Iron status was assessed at 3 and 12 mo from heel-prick capillary blood sample s evaluated by full blood-count analysis , including reticulocytes and serum ferritin . In total , 149 infants were entered ( 51 New , 49 St and ard , 49 breastfed ) with no differences between the groups in gender distribution , birthweight , gestation or numbers completing the study . There were no significant differences between the principal outcome measures : mean values for haemoglobin , mean cell volume and ferritin , between the two formula-fed groups , and the proportion with a haemoglobin level \" no added iron \" infant formula in place of an iron-fortified formula during the first 3 mo of life did not clinical ly affect iron status at 3 and 12 mo of age . The universal supplementation of formulae with iron during this initial period needs further consideration",
"OBJECTIVE Preventing iron deficiency has been a main target of the World Health Organization since 1992 . Difficulties to reach dietary recommended iron intakes and to enhance iron absorption should be overcome . We compared in iron-deficient women the bioavailability of iron of three meat pate products enriched with ferrous sulfate , ferric pyrophosphate encapsulated in liposomes , or ferric pyrophosphate encapsulated in liposomes plus a hemoglobin-based meat pigment . METHODS Seventeen women with low iron stores ( ferritin took part in a three-way , r and omized , crossover , double-blind postpr and ial intervention . Test meals consisted of 80 g of the three different enriched meat pate products , which were spread on two slices of white bread . The pate composition was 13.5 g of protein/100 g , 30 g of fat/100 g ( 49 % monounsaturated fatty acids , 35 % saturated fatty acids , 16 % polyunsaturated fatty acids ) , 1 g of carbohydrates/100 g , and 19 mg of total iron ( including 15 mg of iron from the test fortificants ) . Blood sample s were taken at baseline and each hour for 6 h after eating the meal and serum iron was determined . RESULTS Serum iron concentration evolution during the postpr and ial study was similar with the three meals , and maximum concentrations were obtained between hours 2 and 4 . The effect of type of fortificant was not significant . CONCLUSION Consumption of meat pate fortified with ferric pyrophosphate encapsulated in liposomes can be part of a dietary strategy for preventing iron deficiency in humans . The addition of larger amounts of a meat pigment rich in heme iron should be further studied",
"The Thriposha programme is a community-level nutrition intervention in Sri Lanka that provides a combination of energy , protein and micronutrients as a ' ready-to-eat ' cereal-based food . We measured the bioavailability of Fe and Zn from Thriposha formula at two different molar ratios of Zn : Fe in order to determine the effect on Fe and Zn absorption . Children 4 - 7 years ( n 53 ) were given a meal prepared with 50 g Thriposha containing 1.5 mg Zn as zinc sulphate and either 9 mg ( high Fe concentration ( HiFe ) ) or 4.5 mg ( low Fe concentration ( LoFe ) ) Fe as ferrous fumarate . Zn and Fe percent absorption were measured using stable isotopes by tracer : tracee ratio and by incorporation of erythrocytes , respectively . Percent Fe absorption from the two meals was similar ( 6.6 % ( 4.8 ) v. 4.8 % ( 2.6 ) ; P = 0.15 ) , but total Fe absorption was significantly higher from the HiFe meal ( 0.59 ( 0.43 ) mg ) than the LoFe meal ( 0.20 ( 0.12 ) mg ; P = 0.01 ) . There was no significant difference between the two groups in Zn absorption ( 10.7 % ( 0.9 ) v. 8.8 % ( 1.4 ) , P = 0.13 , respectively ) . Decreasing the amount of Fe in Thriposha did not cause a significant change in the percent absorption of Fe and Zn , but significantly lowered the total amount of absorbed Fe . These results demonstrate the utility of maintaining a higher Fe content in this supplement . Further studies to increase Zn content are warranted while maintaining a HiFe",
"Anemia is still the major nutritional problem among pregnant women in Southeast Asia . The objective of this study was to measure hemoglobin status and reduction of underweight in a group of pregnant women who received iron-fortified or nonfortified milk , and another group who received iron supplements ( tablets ) or placebo . The 44 women in the iron-fortified milk group received 15 mg of iron per day per 400 ml of milk , and 41 women received placebo . The 40 women in the iron supplement group received 60 mg of iron per day , and 43 women received nonfortified milk . During this intervention trial , all women were supervised from the 14th to the 18th week of gestation until delivery . Blood was sample d at 0 , 5 , 10 , and 16 weeks of intervention . After the 16th week of intervention , the changes in hemoglobin ( ΔHb ) concentrations in both treatment groups ( the iron-fortified milk and the iron tablet groups ) were not significantly different ( ΔHb : −0.5 ± 0.9 and −0.3 ± 0.9 g/L , respectively ) , but the changes were significantly greater in the nonfortified milk and placebo groups ( ΔHb : −1.2 ± 0.9 and −1.1 ± 0.8 g/L , respectively ; p .01 ) . The change in transferrin saturation ( ΔTS ) in the iron-fortified milk group ( ΔTS : 3.4 ± 12.9 % ) was greater than that in the placebo and nonfortified milk groups ( ΔTS : −10.1 ± 9.8 % and −11.6 ± 10.7 % , respectively ) ( p of the subjects during intervention did not differ significantly in the fortified and nonfortified milk groups ( Δweight : 5.0 ± 2.0 and 5.8 ± 2.1 kg , respectively ) , but was higher than in the iron tablet group ( Δweight : 4.6 ± 3.1 kg p Iron supplementation and fortification were seen to be effective in promoting weight gain in pregnant Vietnamese women . For women who are underweight , the administration of iron-fortified milk has additional benefits to those of supplementation , most likely due to additional energy and nutrient inputs",
"Summary Background Bioavailability data in humans of elemental iron powders is limited although elemental iron is a common form of iron when used as a fortificant . Aim of the study The relative bioavailability ( RBV ) of seven elemental iron powders , five commercially available and two developmental are evaluated . In addition , one commercial electrolytic iron powder given with ascorbic acid ( AA ) was examined . Methods Based on a vali date d method this double – blinded r and omized crossover study included three groups of male blood donors ( n = 3 * 16 ) who were served rolls fortified with different elemental iron powders or ferrous sulfate ( FeSO4 ) nine weeks apart . Blood sample s were drawn every hour for six hours . RBV was obtained by comparing the increase in serum iron concentration induced by the elemental iron with the increase induced by FeSO4 . Results All elemental iron powders studied were significantly less well absorbed compared to FeSO4 . The electrolytic iron given with 50–mg AA was as well absorbed as FeSO4 ( molar ratio = 1:6 , AA : Fe ) . The mean RBVs of the iron powders were : electrolytic ( A–131 , RBV = 0.65 ) ; electrolytic ( Electrolytic , RBV = 0.59 ) ; carbonyl ( Ferronyl , RBV = 0.58 ) ; H – reduced ( AC– 325 , RBV = 0.56 ) ; H – reduced ( Hi – Sol , RBV = 0.50 ) ; carbonyl ( CF , RBV = 0.37 ) ; reduced ( Atomet 95SP , RBV = 0.36 ) . The reduced iron was distinguished by having significantly lower RBV ( 0.36 ) although no significant overall ranking was possible . Conclusion Based on a vali date d method this doubleblinded cross – over study in humans showed that the evaluated elemental iron powders currently available for commercial use are significantly less well absorbed compared to FeSO4 . The results indicate that the reduced iron powder was absorbed to a lower extent compared to the other iron powders and only 36 % compared to FeSO4 . Ascorbic acid seems to improve the bioavailability of elemental iron even though a rather low molar ratio is used . Thus , if confirmed , this enhancing effect of ascorbic acid on elemental iron when used as a fortificant could be used by co – fortifying them",
"Iron nutrition in infants was studied in a double-blind trial with artificial milk formula . Statistically significant differences were observed with the iron-fortified formula . Not all haematological indices showed significant differences . The fragiligraph technique result was the only parameter showing differences not influenced by other variables examined",
"The hematinic effect of ferrous sulphateenriched flour has been examined in a long-term , community-based experiment . During a period of 20 consecutive months 17000 metric tons of iron-fortified flour were produced at Tau M@lle in Stavanger , Norway ( total iron content 6.2 mg/100 g flour ) . There were neither complaints of rancidity of the flour nor of any harmful effect on its baking qualities . The monitoring of the effect of the iron-fortification programme was performed on an experimental group of 202 women of child-bearing age living in Stavanger . A control group of 215 women was established in Bergen . Blood examinations ( Hb , Hct and MCHC ) were performed at the start of the experiment and repeated on three occasions during the study . The results failed to give conclusive evidence of the hematinic effect of the iron supplement . However , the results obtained in the few women with the lowest circulating Hlb levels ( Hb white flour should be fortified with ferrous sulphate . I mt seems reasonable to apply the same level of enrichment as was recently proposed by the US Commissioner of Food and Drug Administration ( total level of iron 9 mg/ 100 g flour ) . Food fortification is a public health measure aim ed at improving and maintaining the health of individuals in the population through the provision of adequate levels of nutrient intake ( 13 ) . Iron is one of the nutrients which requires special consideration . Based on normal values for Hb concentration and other hematological parameters , we have in previous studies estimated the prevalence of anemia in various population groups ( 18 ) . Iron-deficiency anemia is rather prevalent in Norway : it is not uncommon in schoolchildren and is frequently found in women of reproductive age and in the elderly . At present the level of iron in the average Norwegian diet is only about 4 - 5 mg/l 000 kcal ( 28 , 29 ) . Infants and small children , elderly people , patients and physically inactive individuals with a low caloric intake , as well as those with an increased iron requirement due to growth , convalescence , menstrual bleeding , pregnancy and other special needs , are likely to receive an insufficient supply of iron . The recommended daily intake for women of reproductive age is , for example , 18 mg iron , which should be provided in no more than 1850 - 2 400 kcal ( 4 ) . Thus the lowcalorie consumer ( iron/l 000 kcal in order to satisfy the iron needs . This is theoretically possible to accomplish by choosing foods with a high iron content ( blood , liver , kidneys , wholemeal bread , green vegetables ) . Apart from the fact that blood and entrails are in short supply , it is unrealistic to assume that the majority of people will change their food habits according to these suggestions . An increase in the dietary iron intake might be most easily accomplished through a fortification programme . Iron fortification of the Norwegian brown-cheese with ferrous sulphate was first performed on an experimental scale in the late 1960 's ( 26 ) . In 1972 the enriched cheese became available to the ordinary consumer . The most suitable vehicle , however , for iron fortification would probably be flour and bread . In Great Britain the Bread and Flour Regulations ( 1 ) require that either reduced iron or ferric ammonium citrate shall be added , if necessary , to restore the iron content of flour , other than wholemeal , to at least 1.65 mg/100 g flour . In Acta med . sc and . 194 464 H . Natvig and 0 . D. Vellar Denmark 3 mg iron/l00 g flour is added in the form of reduced iron to wheat and rye flour ( 12 ) . In Sweden iron enrichment of flour ( up to 7 mg iron/100 g flour as reduced iron , ferrous sulphate or ferrous fumarate ) is undertaken on a voluntary basis ( 14 ) . In the USA the level of iron in \" enriched \" flour is raised to that of wholemeal flour ( 3.5 mg Fe/100 g flour ) . However , the US Commissioner of the Food and Drug Administration has proposed an increase of the level of enrichment to ensure a level of 9 mg Fe/100 g flour ( 3 , 7 ) . Finch and Monsen ( 7 ) emphasize that such manipulation of the public diet carries with it the responsibility for monitoring its effect on the iron balance of the population and on the prevalence of iron deficiency and iron overload . Based on our previous Hb studies ( 18 ) we proposed that the possibility of iron enrichment of flour and bread should be considered also in Norway . I t would be necessary , however , to examine the biological effect of various iron preparations when baked into bread as well as the technological problems relating to the baking process . While iron fortification programmes have been in force for many years in many countries , there appear to have been few thorough attempts to evaluate their effectiveness until recently . Furthermore , the results of these studies have been controversial . Three long-term feeding trials with ferrous carbonate or ferrum-reductum-enriched bread ( 5 , 15 , 25 ) showed no effect on the Hb values . Studies reported by Stott ( 23 ) , however , are at variance with these negative results . Using prisoners , Stott fed ferrous-sulphate-enriched bread for four months and obtained a considerable increase in the Hb concentration . This work , however , has been justifiably criticized because there was no control group , and because the absorption of iron from the added ferrous sulphate would have to have been in excess of 30 % in order to account for the recorded Hb rise during the first two months of supplementation . During a long-term trial we fed ferrous-sulphate-enriched bread to 77 women inmates in a mental hospital ( 24 ) . A control group was given the same bread without fortification . After a 12week period the mean Hb level increased from 13.96 to 14.32 g/100 ml in the experimental group . This increase of 0.36 g/100 ml was statistically significant at the 5 % level . However , the Acta med . sc and . 194 mean Hb increase in the control group was almost as great , but these results were difficult to assess as so many of the controls dropped out . Thus the experiment did not provide convincing proof of the effectiveness of the supplement , In a recent long-term feeding trial by Elwood et al. ( 6 ) the effect of ferric-ammonium-citrateenriched bread was examined . Although the results were not entirely consistent , they indicated a small hematinic effect of the iron supplement . Balance studies ( 9 ) with bread enriched with ferrum reductum , ferrous sulphate of ferric orthophosphate revealed some absorption ( OR an average 3 % ) of the added iron . There was no particular difference in the amount of iron absorbed from the three preparations . In absorption studies ( 24 ) we have found that ferrous-sulphate-enriched bread gave favourable results , with an increase in serum iron values two hours after the test meal . When reduced iron was used for enrichment , the response was not so pronounced . It was also observed that the added ferrous sulphate was better absorbed from white wheaten bread than from wholemeal bread . In radioactive absorption studies Steinkamp et al. ( 22 ) examined the effect of bread enriched with radioactive ferrous sulphate , reduced iron , ferric orthophosphate , and sodium ferric pyrophosphate , and found an equal effectiveness of all four forms of iron used for enrichment . In recent studies Hoglund and Reizenstein ( 10 , ll ) , using more modern technique with a whole body counter , found that the absorption of iron from ferrous-sulphate-enriched bread was much higher than when reduced iron was used for enrichment . When fine grain-reduced iron was used to enrich flour , the absorption was 50 % lower , and when a coarser grain-reduced iron was used , it was 85 % lower , than when ferrous sulphate was used for enrichment . Animal studies performed by Fritz et al. ( 8 , 20 , 21 ) of the biological availability of iron in iron-depleted chicks and rats also indicated that ferrous sulphate has a high relative biological value compared with other iron compounds . I t was also found that ferrous sulphate added to a biscuit mix prior to baking was utilized nearly as well as the same quantity of ferrous sulphate added directly to the test diet ( 8) . When these animal repletion studies were compared with human plasma iron responses following test doses of Iron-fortified bread 465 five sources of iron ( ferrous sulphate , reduced iron , sodium iron pyrophosphate , ferric orthophosphate and ferrous carbonate ) a similar ranking with ferrous sulphate as the best compound was obtained in both experiments ( 21 ) . According to three comprehensive reports on the subject of iron fortification ( 2 , 13 , 16 ) most of the evidence suggests that ferrous sulphate is among the most effective forms . As a supplement to our previous absorption and utilization studies ( 24 ) we felt that a longterm controlled , large-scale community-based feeding trial with ferrous-sulphate-enriched flour and bread should be conducted . Ideally such a trial should evaluate the beneficial effect , if any , on representative sample s of the community in terms of a change in morbidity . However , indices of morbidity are relatively insensitive . Changes in Hb levels and other hematological data might be used , as an indirect measure of health , to assess the immediate effect of the fortification programme , The plan was to supply iron-fortified flour and bread to the entire population in one particular community and to compare the changes in certain hematological data of one group of this experimental area with those obtained in a control group from an area without fortification . MATERIAL AND METHODS Iron enrichment of flour Western Norway was chosen for the trial , as in a previous study we had observed somewhat lower Hb values in the western than in other regions of the country ( 17 ) . Furthermore , in the western region it was also possible , from a practical point",
"BACKGROUND Non-water-soluble iron compounds have been reported to be less well absorbed than ferrous sulfate in young children , and concern has been raised about their usefulness as food fortificants . OBJECTIVE The objective was to evaluate the usefulness of ferrous fumarate and ferric pyrophosphate , compared with ferrous sulfate , in maintaining hemoglobin concentrations > 105 g/L in Bangladeshi children . DESIGN Two hundred thirty-five children aged 7 - 24 mo ( hemoglobin > 105 g/L ) were r and omly assigned in a double-blind study to receive an infant cereal fortified with ferrous fumarate , ferric pyrophosphate , or ferrous sulfate . One serving of cereal ( 9.3 mg Fe ; molar ratio of ascorbic acid to iron of 3:1 ) was consumed per day , 6 d/wk , for 9 mo . Blood sample s were drawn at 4.5 and 9 mo . RESULTS Raw data were reformatted , and a \" time to event \" was calculated that corresponded to reaching the following thresholds : hemoglobin plasma ferritin plasma C-reactive protein > 10 mg/L at baseline , 4.5 mo , or 9 mo . Data were censored when children did not reach the threshold or were lost to follow-up . A Kaplan-Meier approach was used to compare the 3 groups . No statistically significant differences were observed for hemoglobin 105 g/L ( P = 0.943 ) , plasma ferritin plasma C-reactive protein > 10 mg/L ( P = 0.508 ) . CONCLUSIONS Contrary to earlier concerns , these results do not indicate differences in usefulness between water-soluble and non-water-soluble iron compounds in maintaining hemoglobin concentrations and preventing iron deficiency . These data will be important in the development of food-fortification strategies to combat anemia and iron deficiency in highly vulnerable population groups",
"The availability of iron added to dried skim milk and to maize-soya-bean-milk mixture ( CMS ) was measured by whole-body counting in thirty clinical ly healthy children and compared with the availability of Fe from ferrous ascorbate alone . The mean absorption of Fe added as ferrous sulphate to a test meal of dried skim milk was 9.5 percent when the test meal was given as a sweetened drink . When maize meal was added to the dried skim milk to produce a porridge the mean absorption of the supplementary Fe was reduced to 6.3 percent . The mean absorption of Fe given as ferrous ascorbate alone was 59.6 percent . These results differed from those reported for indirect tests done with animals in which the absorption of inorganic Fe added to milk-based feed preparations for infants was substantially greater than that of dietary Fe . The mean absorption of Fe added as ferrous fumarate to a test meal of maize-soya-bean-milk mixture was 6.0 percent , whereas that of Fe given as ferrous ascorbate alone was 63.5 percent . The amount of supplementary Fe added to maize-soya-bean-milk mixture ( USA Department of Agriculture specification ) was considered to be adequate . ( AU",
"Abstract The increase in serum iron two hours after test-meals in fasting subjects was taken as an expression of iron absorption in three series of experiments . All the individuals , most of them young , healthy , female nurses acted as their own controls . Tests were performed with white wheaten and wholemeal bread fortified with ferrous sulphate or ferrum reductum to 40 mg iron per 100 g. Some experiments with unenriched white bread were also included . It was found that ferrous sulphate gave a more pronounced increase in serum iron than ferrum reductum . The increase was higher after fortified white bread than after fortified wholemeal bread . This was probably due to the inhibitory effect , although only partial , of dietary phytate on iron absorption . Because of the relative uncertainty of the performed absorption experiments , a controlled clinical trial with ferrous-sulphate-enriched white and wholemeal bread to 8 mg iron per 100 g was conducted in 146 adult female patients of a mental hospital . The 12 weeks ' trial was completed in 77 subjects in the experimental group and in only 20 in the control group . In the experimental group the mean Hb value showed a significant increase to 14.32 g% , which is equivalent to the mean optimal value for adult Norwegian women . A concomitant rise in the mean Hct and MCHC values was recorded . The results in the control group are difficult to interpret . The mean increase in Hb concentration after 12 weeks , however , was not statistically significant . The present study indicates that ferrous sulphate baked into bread is better absorbed than ferrum reductum , and is easily available for hemoglobin synthesis . A long-term community-based feeding trial , however , may be necessary before a final conclusion regarding the future Norwegian iron-fortification policy is reached",
"Objective : To assess the efficacy of ferrous sulfate ( FS ) and ferrous gluconate ( FG ) as fortificants for a complementary baby food ( Nutrisano ) to improve the iron status and to reduce the prevalence of anemia in toddlers . Patients and Methods : Toddlers 12 to 30 months old were r and omly assigned to receive either of 3 versions of Nutrisano fortified with FS or FG or not fortified ( CG ) for 6 months . In final blood sample s , the concentrations of hemoglobin , serum ferritin , and soluble transferrin receptors ( sTfR ) were determined . The effects of treatment on final hemoglobin , ferritin , and sTfR were assessed by multivariate analysis . Results : No significant changes in hemoglobin were observed within or among treatment groups . The prevalence of high sTfR decreased 7.1 percentage points in FG , increased 13.1 percentage points in FS , and increased 0.7 percentage points in CG ( P > 0.05 ) . In an interaction between treatment and total intake of Nutrisano on the concentration of ferritin , sTfR , and total iron body stores , adjusted means of serum ferritin in the medium tertiles of intake of Nutrisano for FS ( P = 0.05 ) and in the higher and medium tertiles for FG were higher ( P = 0.001 ) , and adjusted means of sTfR were significantly lower ( P level of beneficial effect on markers of iron status . The satisfactory efficacy and other sensory data has led to the political decision to substitute hydrogen-reduced iron , used formerly as a fortificant , with FG . Studies to assess the effectiveness of the reformulated Nutrisano are in order",
"Objective : To determine the efficacy of p and esal baked from wheat flour fortified with iron , with or without vitamin A ( VA ) , in improving anemic schoolchildren 's iron and anthropometric status . Methods : Anemic 6- to 12-year-old Filipino children ( n = 250 ) received two 60 g p and esal daily for 8 months . They were r and omized into 1 of 4 groups : ( 1 ) iron-fortified ( with hydrogen-reduced iron at 80 mg/kg , electrolytic iron at 80 mg/kg , or ferrous fumarate at 40 mg/kg ) , ( 2 ) iron and VA-fortified , ( 3 ) VA-fortified ( at 490 RE/100 g ) , and ( 4 ) nonfortified flour . Hemoglobin ( Hb ) and zinc protoporphyrin ( ZnPP ) concentrations and weight and height were determined before and after intervention . Analyses of variance and chi-square and multiple regression analyses were performed . Results : Mean Hb increased by 1.3 g/dL ( p and mean ZnPP decreased by 24.4 µmol/mol ( p months . Anemia decreased to 26 % and iron deficiency decreased from 58 % to 12 % . After controls were applied for baseline concentration , age , and gender , Hb concentration at post intervention was significantly higher in the Iron + VA group than in the nonfortified group ( coefficient = 0.37 ; p = 0.034 ) . The odds of being iron deficient at post intervention were significantly lower in the Iron group than in the nonfortified group after controls were applied for age , gender , and baseline prevalence ( coefficient = 0.12 ; p = 0.006 ) . None of the 3 fortified groups had significantly different weight-for-age z-score , body mass index-for-age z-score , or height-for-age z-score compared with the nonfortified group after controls were applied for baseline z-scores , age , and gender . Conclusions : Our study shows that in a non – malaria-endemic area , iron fortification of flour significantly reduced the prevalence of iron deficiency among anemic schoolchildren , and double fortification with iron and VA significantly improved Hb status",
"BACKGROUND A number of algorithms have been developed that seek to predict the bioavailability of iron from mixed meals and diets , but their direct validity in predicting change in iron status remains question able . Throughout the course of conducting a large feeding trial in convents in Manila , we collected weighed food-intake data and have the opportunity to directly compare the performance of these prediction equations . AIMS The specific aims of this particular analysis are as follows : ( a ) to determine habitual intakes of macro- and micronutrients in religious sisters in Manila , ( b ) to determine the predicted efficiency of iron absorption from each of the published bioavailability algorithms ( Monsen , Hallberg , Reddy , Tseng , Barghava , and Du ) , and ( c ) to determine which of these equations best predicts the actual \" gain \" in iron in religious sisters over the duration of the trial . DESIGN The efficacy of consuming high-iron rice was tested during a nine-month feeding trial with a double-blinded dietary intervention ; these results have been published [ 7 ] . Religious sisters living in 10 convents around metropolitan Manila , the Philippines were r and omly assigned to consume either high-iron rice ( 3.21 mg/kg Fe ) or a local variety of control rice ( 0.57 mg/kg Fe ) within each convent . RESULTS Religious sisters in convents consumed a diet that appeared to be typical of habitual intakes of macro- and micronutrients in this part of the Philippines . The analysis of the six equations revealed highly significant differences in predicted efficiency of iron absorption . The Hallberg , Monsen , and Reddy equations all predicted similar median efficiency ( 6.88 , 7.92 , and 6.42 % ) . In contrast , Bhargava ( 4.68 % ) , Tseng ( 3.23 % ) , and Du ( 2.92 % ) were significantly lower . The correlation ( r = 0.98 ) of Monsen to Hallberg was highly significant and the slope was not different than unity . The median efficiency of absorption based on the gain in body iron in 114 subjects over nine months , combined with an estimate of daily iron requirements , was 17.2 % . Thus , none of these equations approximated the computed iron absorption based on improvement in serum ferritin and suggests alternative approaches to predicting iron accumulation from diet need to be formulated . CONCLUSIONS Inhibitory factors in the prediction equations either had little effect or had too large of an effect on apparent bioavailability as compared to median absorption over a nine-month period . The causes of the lack of agreement between computed iron gain and predicted absorption are open to discussion and will need to be resolved",
"OBJECTIVE To evaluate the effectiveness of stainless steel ( Fe alloy ) cooking pots in reducing Fe-deficiency anaemia in food aid-dependent population s. DESIGN Repeated cross-sectional surveys . Between December 2001 and January 2003 , three surveys among children aged 6 - 59 months and their mothers were conducted in 110 households r and omly selected from each camp . The primary outcomes were changes in Hb concentration and Fe status . SETTING Two long-term refugee camps in western Tanzania . SUBJECTS Children ( 6 - 59 months ) and their mothers were surveyed at 0 , 6 and 12 months post-intervention . Stainless steel pots were distributed to all households in Nduta camp ( intervention ) ; households in Mtendeli camp ( control ) continued to cook with aluminium or clay pots . RESULTS Among children , there was no change in Hb concentration at 1 year ; however , Fe status was lower in the intervention camp than the control camp ( serum transferrin receptor ( sTfR ) concentration : 6.8 v. 5.9 microg/ml ; P Hb concentration among non-pregnant mothers at 1 year . Subjects in the intervention camp had lower Fe status than those in the control camp ( sTfR concentration : 5.8 v. 4.7 microg/ml ; P = 0.003 ) . CONCLUSIONS Distribution of stainless steel pots did not increase Hb concentration or improve Fe status in children or their mothers . The use of stainless steel prevents rusting but may not provide sufficient amounts of Fe and strong educational campaigns may be required to maximize use . The distribution of stainless steel pots in refugee context s is not recommended as a strategy to control Fe deficiency",
"Pregnancy anemia and pregnancy-induced hypertension ( PIH ) are common and potentially dangerous disorder in human pregnancy , and nutritional status of pregnant women is one of the leading causes . Chlorella contains large quantities of folate , vitamin B-12 and iron , and can help improve anemia and hypertensive disorder . Our objective was to investigate the preventive effects of Chlorella supplement on pregnancy anemia and PIH in Japanese pregnant women . A total of 70 pregnant women were placed into the control group ( n = 38 ) or the Chlorella group ( n = 32 ) . The subjects in the Chlorella group were supplemented daily from 12th–18th wk of gestation until delivery with 6 g of Chlorella supplement . The proportion of anemic ( hemoglobin level Chlorella group were significantly lower compared with the control group at the second and third trimesters . Additionally , in the Chlorella group , the incidences of proteinuria and edema , signs of PIH , were significantly lower during the third trimester . These results suggest that Chlorella supplementation significantly reduces the risk of pregnancy associated anemia , proteinuria and edema . Chlorella supplement may be useful as a re source of natural folate , vitamin B-12 and iron for pregnant women",
"BACKGROUND Nonanemic iron deficiency is common in toddlers in developed countries . Food-based strategies are safe methods to control and prevent mild micronutrient deficiencies . OBJECTIVE Our objective was to determine the efficacy of an increased intake of red meat , or the consumption of iron-fortified milk , in improvement of iron status in toddlers at a population level . DESIGN In this 20-wk r and omized placebo-controlled trial , 225 healthy nonanemic 12 - 20-mo-old children were assigned to 1 of 3 groups : red meat ( toddlers encouraged to consume approximately 2.6 mg iron from red meat dishes daily ) , fortified milk [ toddlers ' regular milk replaced with iron-fortified ( 1.5 mg iron/100 g prepared milk ) cow milk ] , or control [ toddlers ' regular milk replaced with nonfortified ( 0.01 mg iron/100 g prepared milk ) cow milk ] . Blood sample s were collected at baseline and at 20 wk for hemoglobin , serum ferritin , serum transferrin receptor , and C-reactive protein . The prevalence of suboptimal iron status ( ie , depleted iron stores , iron-deficient erythropoiesis , and iron deficiency anemia ) was determined , and body iron was calculated . RESULTS No intervention effects were shown on the prevalence of suboptimal iron status . Serum ferritin increased by 44 % ( 95 % CI : 14 % , 82 % ; P = 0.002 ) in the fortified milk group , did not change ( + 10 % ) in the red meat group ( 95 % CI : -7 % , 30 % ; P = 0.241 ) , and tended to decrease ( -14 % ) in the control group ( 95 % CI : -27 % , 1 % ; P = 0.063 ) . By 20 wk , in comparison with the control group , serum ferritin and body iron were significantly higher in the fortified milk group ( both P serum ferritin was significantly higher in the red meat group ( P = 0.033 ) . CONCLUSIONS Consumption of iron-fortified milk can increase iron stores in healthy nonanemic toddlers , whereas increased intakes of red meat can prevent their decline . This trial was registered at actr.org.au as ACTRN12605000487617",
"BACKGROUND R and om serial sampling is widely used in population pharmacokinetic studies and may have advantages compared with conventional fixed time-point evaluation of iron fortification . OBJECTIVE Our objective was to vali date r and om serial sampling to judge the efficacy of iron fortification of a low-fat margarine . DESIGN We conducted a 32-wk placebo-controlled , double-blind , iron-intervention trial in 18 - 40-y-old Swiss women ( n = 142 ) with serum ferritin ( SF ) concentrations Women were r and omly assigned to 3 groups to receive 20 g margarine , with 14 mg added iron as either micronized ground ferric pyrophosphate ( MGFePP ) or sodium iron edetate ( NaFeEDTA ) , or placebo daily . We measured hemoglobin and iron status of subjects at 2 fixed time points ( at baseline and the endpoint ) plus 3 r and omly assigned time points between 4 and 28 wk . With the use of bootstrapping , the number of observations per individual was reduced to 3 and then compared with the 5-time-point data . Mixed-effects models were used to estimate iron repletion over time for r and om sampling , and analysis of covariance was used for fixed time-point sampling . RESULTS Body iron stores increased in women who received MGFePP or NaFeEDTA compared with women who received placebo ( P increase in body iron stores with NaFeEDTA fortification was 2 - 3 times the increase with MGFePP fortification ( P < 0.05 ) ; the difference was more marked in women with baseline SF concentrations < 15 μg/L ( P < 0.05 ) . R and om serial sampling reduced the required sample size per group to one-tenth of that for 2 fixed time points . Compared with the 5-time-point analysis , the 3-time-point sparse sampling generated comparable estimates of efficacy . CONCLUSIONS When used to evaluate the efficacy of iron fortificants , r and om serial sampling can reduce the sample size , invasiveness , and costs while increasing sensitivity . R and om serial sampling more clearly describes the pattern of iron repletion and may prove useful in evaluating other micronutrient interventions",
"Anemia is common among children in sub-Saharan Africa and its etiology is multifactorial . Likely causes of anemia are low bioavailability of dietary iron , malaria , and helminth infection . In this study , we aim ed to assess the effect of iron fortification , intermittent preventive treatment ( IPT ) of malaria , and anthelmintic treatment on hemoglobin concentration and anemia prevalence among school children . The study was a 6-mo , r and omized , double-blind , controlled trial enrolling 591 6- to 14-y-old school children in Côte d'Ivoire using the following : 1 ) iron-fortified biscuits providing an additional 20 mg iron/d as electrolytic iron 4 times/wk ; 2 ) IPT of malaria with sulfadoxine-pyrimethamine at 0 and 3 mo ; and 3 ) anthelmintic treatment at 0 and 3 mo as the interventions . Prevalence of anemia , iron deficiency , malaria parasitemia , and helminth infection was 70.4 , 9.3 , 57.7 , and 54.8 % , respectively . Iron fortification did not improve iron status , IPT of malaria did not affect malaria burden , and neither had an impact on anemia prevalence . Anthelmintics significantly reduced the burden of helminth infections and decreased anemia prevalence ( odds ratio : 0.4 , 95 % CI : 0.3 , 0.7 ) . The low prevalence of iron deficiency and an extended dry season that decreased malaria transmission likely reduced the potential impact of iron fortification and IPT . In this setting , anthelmintic treatment was the only intervention that modestly decreased rates of anemia",
"Precooked , instant ( dry ) infant cereals in the US are fortified with electrolytic iron , a source of low reactivity and suspected low bioavailability . Iron from ferrous fumarate is presumed to be more available . In this study , we compared a dry infant rice cereal ( Cereal L ) fortified with electrolytic iron ( 54.5 mg iron/100 g cereal ) to a similar cereal ( Cereal M ) fortified with ferrous fumarate ( 52.2 mg Fe/100 g ) for efficacy in maintaining iron status and preventing iron deficiency ( ID ) in breast-fed infants . Ascorbic acid was included in both cereals . In this prospect i ve , r and omized double-blind trial , exclusively breast-fed infants were enrolled at 1 mo and iron status was determined periodically . At 4 mo , 3 infants had ID anemia and were excluded . Ninety-five infants were r and omized at 4 mo , and 69 ( 36 Cereal L , 33 Cereal M ) completed the intervention at 9 mo . From 4 to 9 mo , they consumed daily one of the study cereals . With each cereal , 2 infants had mild ID , a prevalence of 4.2 % , but no infant developed ID anemia . There were no differences in iron status between study groups . Iron intake from the study cereals was ( mean ± SD ) 1.21 ± 0.31 mg⋅kg(-1)⋅d(-1 ) from Cereal L and 1.07 ± 0.40 mg⋅kg(-1)⋅d(-1 ) from Cereal M. Eleven infants had low birth iron endowment ( plasma ferritin had ID with or without anemia by 4 mo . We conclude that electrolytic iron and ferrous fumarate were equally efficacious as fortificants of this infant cereal"
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Evidence suggests engaging in regular physical activity ( PA ) can have beneficial outcomes for adults with type 2 diabetes ( TD2 ) , including weight loss , reduction of medication usage and improvements in hemoglobin A1c (HbA1c)/fasting glucose . While a number of clinical -based PA interventions exist , community-based approaches are limited . The objective of this study is to conduct a systematic review with meta- analysis to assess the effectiveness of community-based PA interventions for the treatment of TD2 in adult population s. A search of peer- review ed publications from 2002 to June 2012 was conducted across several electronic data bases to identify interventions evaluated in community setting s. Twenty-two studies were identified , and 11 studies reporting HbA1c as an outcome measure were pooled in the meta- analysis . Risk of bias assessment was also conducted . The findings demonstrate community-based PA interventions can be effective in producing increases in PA . Meta- analysis revealed a lowering of HbA1c levels by -0.32 % [ 95 % CI -0.65 , 0.01 ] , which approached statistical significance ( p future PA community-based interventions in adult population s diagnosed with TD2
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"OBJECTIVE To test whether a theory-based , literacy , and culturally tailored self-management intervention , Latinos en Control , improves glycemic control among low-income Latinos with type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 252 patients recruited from community health centers were r and omized to the Latinos en Control intervention or to usual care . The primarily group-based intervention consisted of 12 weekly and 8 monthly sessions and targeted knowledge , attitudes , and self-management behaviors . The primary outcome was HbA1c . Secondary outcomes included diet , physical activity , blood glucose self-monitoring , diabetes knowledge and self-efficacy , and other physiological factors ( e.g. , lipids , blood pressure , and weight ) . Measures were collected at baseline and at 4- and 12-month follow-up . Change in outcomes over time between the groups and the association between HbA1c and possible mediators were estimated using mixed-effects models and an intention-to-treat approach . RESULTS A significant difference in HbA1c change between the groups was observed at 4 months ( intervention −0.88 [ −1.15 to −0.60 ] versus control −0.35 [ −0.62 to 0.07 ] , P differences in diabetes knowledge at 12 months ( P = 0.001 ) , self-efficacy ( P = 0.001 ) , blood glucose self-monitoring ( P = 0.02 ) , and diet , including dietary quality ( P = 0.01 ) , kilocalories consumed ( P , percentage of fat ( P = 0.003 ) , and percentage of saturated fat ( P = 0.04 ) . These changes were in turn significantly associated with HbA1c change at 12 months . CONCLUSIONS Literacy-sensitive , culturally tailored interventions can improve diabetes control among low-income Latinos ; however , strategies to sustain improvements are needed",
"OBJECTIVES We sought to determine the effects of a community-based , culturally tailored diabetes lifestyle intervention on risk factors for diabetes complications among African Americans and Latinos with type 2 diabetes . METHODS One hundred fifty-one African American and Latino adults with diabetes were recruited from 3 health care systems in Detroit , Michigan , to participate in the Racial and Ethnic Approaches to Community Health ( REACH ) Detroit Partnership diabetes lifestyle intervention . The curriculum , delivered by trained community residents , was aim ed at improving dietary , physical activity , and diabetes self-care behaviors . Baseline and postintervention levels of diabetes-specific quality -of-life , diet , physical activity , self-care knowledge and behaviors , and hemoglobin A1C were assessed . RESULTS There were statistically significant improvements in postintervention dietary knowledge and behaviors and physical activity knowledge . A statistically significant improvement in A1C level was achieved among REACH Detroit program participants ( P diabetes lifestyle intervention delivered by trained community residents produced significant improvement in dietary and diabetes self-care related knowledge and behaviors as well as important metabolic improvements",
"Purpose : The purpose of this study was to investigate the impact of using a pedometer on time spent walking , in sedentary and overweight adults with type 2 diabetes participating in a coaching intervention . It was hypothesized that participants using a pedometer would spend more time walking than would nonpedometer participants . Method : A sample of 57 men and women with a mean age of 62 years participated in a r and omized controlled trial in a community setting . Participants were allocated to either a pedometer and coaching ( intervention ) group or a coaching-only ( control ) group . Coaching for both groups involved education , goal setting , and supportive/motivational strategies to increase time spent walking . The duration of the study was 6 months , with blood pressure , glycosylated hemoglobin , anthropometric , and fitness measurements assessed at baseline and at 3-month intervals . Results : A repeated- measures analysis of variance indicated that the coaching-only group spent significantly more time walking than did the pedometer group . However , when an analysis of covariance with all the other variables as covariates was performed , group membership had no influence on time spent walking . Significant reductions in waist circumference and weight were achieved for both groups from baseline to 6 months . Cardiovascular fitness also increased significantly for both groups . Conclusion : The study demonstrated that previously sedentary older adults with type 2 diabetes , supported with a coaching intervention , were able to achieve the physical activity targets known to be beneficial to health . However , using a pedometer added no further benefit . Further research on the impact of specific coaching strategies in diabetes management is warranted",
"OBJECTIVE To determine whether a culturally appropriate clinic- and community-based intervention for African-American women with type 2 diabetes will increase moderate-intensity physical activity ( PA ) . RESEARCH DESIGN AND METHODS In this r and omized controlled trial conducted at seven practice s in central North Carolina , 200 African-American women , > or = 40 years of age with type 2 diabetes , were r and omized to one of three treatment conditions : clinic and community ( group A ) , clinic only ( group B ) , or minimal intervention ( group C ) . The clinic-based intervention ( groups A and B ) consisted of four monthly visits with a nutritionist who provided counseling to enhance PA and dietary intake that was tailored to baseline practice s and attitudes ; the community-based intervention ( group A ) consisted of three group sessions and 12 monthly phone calls from a peer counselor and was design ed to provide social support and reinforce behavior change goals ; and the minimal intervention ( group C ) consisted of educational pamphlets mailed to participants . The primary study outcome was the comparison of PA levels between groups assessed at 6 and 12 months by accelerometer , which was worn while awake for 7 days . RESULTS Totals of 175 ( 88 % ) and 167 ( 84 % ) participants completed PA assessment at 6 and 12 months , respectively . For comparison of PA , the P value for overall group effect was 0.014 . Comparing group A with C , the difference in the average adjusted mean for PA was 44.1 kcal/day ( 95 % CI 13.1 - 75.1 , P = 0.0055 ) . Comparing group B with C , the difference in the average adjusted mean was 33.1 kcal/day ( 95 % CI 3.3 - 62.8 , P = 0.029 ) . The intervention was acceptable to participants : 88 % were very satisfied with clinic-based counseling to enhance PA , and 86 % indicated that the peer counselor 's role in the program was important . CONCLUSIONS The intervention was associated with a modest enhancement of PA and was acceptable to participants",
"A poor underst and ing of behaviour change mechanisms has hindered the development of effective physical activity interventions . The aim of this study was to identify potential mediators of change in a home-based resistance training ( RT ) program for obese individuals with type 2 diabetes . Obese individuals with type 2 diabetes ( N = 48 ) were r and omly allocated to either an RT intervention ( n = 27 ) or a control group ( n = 21 ) for the 16-week study period . The study sample included 16 men and 32 women and the mean age of participants was 54.4 ( ±11.7 ) years . Participants in the RT group received a multi-gym and dumbbells and home supervision from a certified personal trainer . RT behaviour was measured using a modified Godin Leisure Time Question naire . Social-cognitive constructs were measured and tested in a mediating variable framework using a product-of-coefficients test . The intervention had a significant effect on RT behaviour ( p 0.001 ) and muscular strength ( p effect on RT planning strategies ( p on RT behaviour . The home-based RT program successfully targeted participants ’ RT planning strategies which contributed to their exercise adherence",
"OBJECTIVE The prevalence of type 2 diabetes , especially in developing countries , has grown over the past decades . We performed a controlled clinical study to determine whether a community-based , group-centered public health intervention addressing nutrition and exercise can ameliorate glycemic control and associated cardiovascular risk factors in type 2 diabetic patients in rural Costa Rica . RESEARCH DESIGN AND METHODS A total of 75 adults with type 2 diabetes , mean age 59 years , were r and omly assigned to the intervention group or the control group . All participants received basic diabetes education . The subjects in the intervention group participated in 11 weekly nutrition classes ( 90 min each session ) . Subjects for whom exercise was deemed safe also participated in triweekly walking groups ( 60 min each session ) . Glycosylated hemoglobin , fasting plasma glucose , total cholesterol , triglycerides , HDL and LDL cholesterol , height , weight , BMI , and blood pressure were measured at baseline and the end of the study ( after 12 weeks ) . RESULTS The intervention group lost 1.0 + /- 2.2 kg compared with a weight gain in the control group of 0.4 + /- 2.3 kg ( P = 0.028 ) . Fasting plasma glucose decreased 19 + /- 55 mg/dl in the intervention group and increased 16 + /- 78 mg/dl in the control group ( P = 0.048 ) . Glycosylated hemoglobin decreased 1.8 + /- 2.3 % in the intervention group and 0.4 + /- 2.3 % in the control group ( P = 0.028 ) . CONCLUSIONS Glycemic control of type 2 diabetic patients can be improved through community-based , group-centered public health interventions addressing nutrition and exercise . This pilot study provides an economically feasible model for programs that aim to improve the health status of people with type 2 diabetes",
"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",
"Background Yoga is a popular therapy for diabetes but its efficacy is contested . The aim of this study was to explore the feasibility of research ing community based yoga classes in Type 2 diabetes with a view to informing the design of a definitive , multi-centre trial Methods The study design was an exploratory r and omised controlled trial with in-depth process evaluation . The setting was two multi-ethnic boroughs in London , UK ; one with average and one with low mean socio-economic deprivation score . Classes were held at a sports centre or GP surgery . Participants were 59 people with Type 2 diabetes not taking insulin , recruited from general practice lists or opportunistically by general practice staff . The intervention group were offered 12 weeks of a twice-weekly 90-minute yoga class ; the control group was a waiting list for the yoga classes . Both groups received advice and leaflets on healthy lifestyle and were encouraged to exercise . Primary outcome measure was HbA1c . Secondary outcome measures included attendance , weight , waist circumference , lipid levels , blood pressure , UKPDS cardiovascular risk score , diabetes-related quality of life ( ADDQoL ) , and self-efficacy . Process measures were attendance at yoga sessions , self-reported frequency of practice between taught sessions , and qualitative data ( interviews with patients and therapists , ethnographic observation of the yoga classes , and analysis of documents including minutes of meetings , correspondence , and exercise plans ) . Results Despite broad inclusion criteria , around two-thirds of the patients on GP diabetic registers proved ineligible , and 90 % of the remainder declined to participate . Mean age of participants was 60 + /- 10 years . Attendance at yoga classes was around 50 % . Nobody did the exercises regularly at home . Yoga teachers felt that most participants were unsuitable for ' st and ard ' yoga exercises because of limited flexibility , lack of basic fitness , co-morbidity , and lack of confidence . There was a small fall in HbA1c in the yoga group which was not statistically significant and which was not sustained six months later , and no significant change in other outcome measures . Conclusion The benefits of yoga in type 2 diabetes suggested in some previous studies were not confirmed . Possible explanations ( apart from lack of efficacy ) include recruitment challenges ; practical and motivational barriers to class attendance ; physical and motivational barriers to engaging in the exercises ; inadequate intensity and /or duration of yoga intervention ; and insufficient personalisation of exercises to individual needs . All these factors should be considered when design ing future trials . Trial registration National Research Register ( 1410 ) and Current Controlled Trials ( IS RCT N63637211 )",
"BACKGROUND Physical activity ( PA ) is a cornerstone in the management of type 2 diabetes ( T2DM ) . This pilot investigation explores the effects of a st and ard diabetes education program compared with a supplemental PA intervention on diabetes-related health outcomes . METHODS Using a prospect i ve 2-armed design , 96 adults with T2DM were r and omly assigned to either st and ard care ( diabetes education program ; n = 49 ) or st and ard care supplemented with an 8-week , individualized-counseling and community-based PA component ( n = 47 ) . Measurements were taken at baseline , 3 , 6 , and 12 months . Primary outcomes were changes in PA ( self-report ) and HbA1c . Between group changes were compared using analysis of covariance ( ANCOVA ) and changes over time using repeated- measures ANOVA . RESULTS In comparison with st and ard care , the supplemental group demonstrated an increase in PA ( Ps cardiorespiratory fitness ( Ps HbA1c levels declined ( P cholesterol-ratio ( P increase in HDL ( P ) , and reductions in blood pressure , resting heart rate and BMI ( approaching statistical significance Ps PA counseling in addition to st and ard care is effective for promoting PA behavior change and positive health-related outcomes among individuals with T2DM",
"Hispanics are at increased risk of morbidity and mortality due to their high prevalence of diabetes and poor glycemic control . Strength training is the most effective lifestyle intervention to increase muscle mass but limited data is available in older adults with diabetes . We determined the influence of strength training on muscle quality ( strength per unit of muscle mass ) , skeletal muscle fiber hypertrophy , and metabolic control including insulin resistance ( Homeostasis Model Assessment –HOMA-IR ) , C-Reactive Protein ( CRP ) , adiponectin and Free Fatty Acid ( FFA ) levels in Hispanic older adults . Sixty-two community-dwelling Hispanics ( > 55 y ) with type 2 diabetes were r and omized to 16 weeks of strength training plus st and ard care ( ST group ) or st and ard care alone ( CON group ) . Skeletal muscle biopsies and biochemical measures were taken at baseline and 16 weeks . The ST group show improved muscle quality ( mean±SE : 28±3 ) vs CON ( -4±2 , p increased type I ( 860±252µm2 ) and type II fiber cross-sectional area ( 720±285µm2 ) compared to CON ( type I : -164±290µm2 , p=0.04 ; and type II : -130±336µm2 , p=0.04 ) . This was accompanied by reduced insulin resistance [ ST : median ( interquartile range ) -0.7(3.6 ) vs CON : 0.8(3.8 ) , p=0.05 ] ; FFA ( ST : -84±30µmol/L vs CON : 149±48µmol/L , p=0.02 ) ; and CRP [ ST : -1.3(2.9)mg/L vs CON : 0.4(2.3)mg/L , p=0.05 ] . Serum adiponectin increased with ST [ 1.0(1.8)µg/mL ] compared to CON [ -1.2(2.2)µg/mL , p ] . Strength training improved muscle quality and whole-body insulin sensitivity . Decreased inflammation and increased adiponectin levels were related with improved metabolic control . Further studies are needed to underst and the mechanisms associated with these findings . However , these data show that strength training is an exercise modality to consider as an adjunct of st and ard of care in high risk population s with type 2 diabetes",
"Purpose : To investigate whether a home-based resistance training ( RT ) program that supplied high- quality equipment and qualified exercise specialists could provide benefits to obese patients with type 2 diabetes . Methods : A total of 48 obese individuals with type 2 diabetes were r and omly assigned to either an RT ( n=27 ) or a control group ( n=21 ) . Those in the RT group received a multigym and dumbbells and performed RT 3 days per week for 16 weeks at home . A qualified exercise specialist supervised training , with supervision being gradually decreased throughout the study . Primary outcome measures included strength and hemoglobin-A1C , whereas secondary outcome measures included other cardiovascular risk markers , key social-cognitive constructs and health-related quality of life . Results : Intention-to-treat analyses indicated a significant increase in upper and lower body strength for the RT group compared with controls ( 20–37 % mean increases in the RT group ) . No significant reduction in A1C levels was observed . The RT group had unchanged high-density lipoprotein cholesterol levels in comparison to declines in the control group . Significant reductions in fasting insulin , and increases in RT-related self-efficacy and intentions , were also observed in the RT group . Conclusions : Supervised home-based RT with high- quality equipment was effective for improving strength , along with other secondary outcomes in obese patients with type 2 diabetes",
"Objective To evaluate the effectiveness of a structured group education programme on biomedical , psychosocial , and lifestyle measures in people with newly diagnosed type 2 diabetes . Design Multicentre cluster r and omised controlled trial in primary care with r and omisation at practice level . Setting 207 general practice s in 13 primary care sites in the United Kingdom . Participants 824 adults ( 55 % men , mean age 59.5 years ) . Intervention A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care . Main outcome measures Haemoglobin A1c levels , blood pressure , weight , blood lipid levels , smoking status , physical activity , quality of life , beliefs about illness , depression , and emotional impact of diabetes at baseline and up to 12 months . Main results Haemoglobin A1c levels at 12 months had decreased by 1.49 % in the intervention group compared with 1.21 % in the control group . After adjusting for baseline and cluster , the difference was not significant : 0.05 % ( 95 % confidence interval −0.10 % to 0.20 % ) . The intervention group showed a greater weight loss : −2.98 kg ( 95 % confidence interval −3.54 to −2.41 ) compared with 1.86 kg ( −2.44 to −1.28 ) , P=0.027 at 12 months . The odds of not smoking were 3.56 ( 95 % confidence interval 1.11 to 11.45 ) , P=0.033 higher in the intervention group at 12 months . The intervention group showed significantly greater changes in illness belief scores ( P=0.001 ) ; directions of change were positive indicating greater underst and ing of diabetes . The intervention group had a lower depression score at 12 months : mean difference was −0.50 ( 95 % confidence interval −0.96 to −0.04 ) ; P=0.032 . A positive association was found between change in perceived personal responsibility and weight loss at 12 months ( β=0.12 ; P=0.008 ) . Conclusion A structured group education programme for patients with newly diagnosed type 2 diabetes result ed in greater improvements in weight loss and smoking cessation and positive improvements in beliefs about illness but no difference in haemoglobin A1c levels up to 12 months after diagnosis . Trial registration Current Controlled Trials IS RCT N17844016",
"BACKGROUND Prolonged sitting is considered detrimental to health , but evidence regarding the independent relationship of total sitting time with all-cause mortality is limited . This study aim ed to determine the independent relationship of sitting time with all-cause mortality . METHODS We linked prospect i ve question naire data from 222 497 individuals 45 years or older from the 45 and Up Study to mortality data from the New South Wales Registry of Births , Deaths , and Marriages ( Australia ) from February 1 , 2006 , through December 31 , 2010 . Cox proportional hazards models examined all-cause mortality in relation to sitting time , adjusting for potential confounders that included sex , age , education , urban/rural residence , physical activity , body mass index , smoking status , self-rated health , and disability . RESULTS During 621 695 person-years of follow-up ( mean follow-up , 2.8 years ) , 5405 deaths were registered . All-cause mortality hazard ratios were 1.02 ( 95 % CI , 0.95 - 1.09 ) , 1.15 ( 1.06 - 1.25 ) , and 1.40 ( 1.27 - 1.55 ) for 4 to less than 8 , 8 to less than 11 , and 11 or more h/d of sitting , respectively , compared with less than 4 h/d , adjusting for physical activity and other confounders . The population -attributable fraction for sitting was 6.9 % . The association between sitting and all-cause mortality appeared consistent across the sexes , age groups , body mass index categories , and physical activity levels and across healthy participants compared with participants with preexisting cardiovascular disease or diabetes mellitus . CONCLUSIONS Prolonged sitting is a risk factor for all-cause mortality , independent of physical activity . Public health programs should focus on reducing sitting time in addition to increasing physical activity levels",
"Background Weight-bearing exercise has been discouraged for people with diabetes mellitus and peripheral neuropathy ( DM+PN ) . However , people with diabetes mellitus and insensate feet have an increased risk of falling . Lower-extremity exercise and balance training reduce fall risk in some older adults . It is unknown whether those with neuropathy experience similar benefits . Objective As part of a study of the effects of weight-bearing exercise on foot ulceration in people with DM+PN , the effects of a lower-extremity exercise and walking intervention on balance , lower-extremity strength ( force-generating capacity ) , and fall incidence were determined . Design The study was an observer-masked , 12-month r and omized controlled trial . Setting Part 1 of the intervention took place in physical therapy offices , and part 2 took place in the community . Patients The participants were 79 people who were mostly sedentary , who had DM+PN , and who were r and omly assigned to either a control group ( n=38 ) or an intervention group ( n=41 ) . Intervention Part 1 included leg strengthening and balance exercises and a graduated , self-monitored walking program ; part 2 included motivational telephone calls . Both groups received regular foot care , foot care education , and 8 sessions with a physical therapist . Measurements The measurements collected were strength , balance , and participant-reported falls for the year after enrollment . Results There were no statistically significant differences between the groups for falls during follow-up . At 12 months , there was a small increase in the amount of time that participants in the intervention group could st and on 1 leg with their eyes closed . No other strength or balance measurements differed between the groups . Limitations The study was design ed to detect differences in physical activity , not falls . The intensity of the intervention was insufficient to improve strength and balance in this population . Conclusions The training program had a minimal effect on participants ' balance and lower-extremity strength . Increasing weight-bearing activity did not alter the rate of falling for participants in the intervention group relative to that for participants in the control group . People who are sedentary and who have DM+PN appear to be able to increase activity without increasing their rate of falling",
"OBJECTIVE The aim of this study was to evaluate the effectiveness of lay diabetes facilitators ( LDFs ) to increase knowledge and improve control among persons with diabetes . Methodology . A prospect i ve cohort study was conducted among persons with diabetes in 16 health care centres in Jamaica to evaluate the effect of LDFs on glycaemia [ haemoglobin A1c ( HbA1c ) ] and body mass index ( BMI ) . One hundred and fifty-nine persons with diabetes were recruited for the intervention from eight clinical setting s in which LDFs had been recruited and trained . A matched group of 159 were recruited as a comparison sample from eight clinical setting s without LDFs . HbA1c and BMI were measured at baseline and 6 months . RESULTS Mean HbA1c at baseline for the intervention and comparison groups were 7.9 % and 8 % , respectively . After 6 months , the intervention group showed a mean decrease of 0.6 % while the comparison group showed an increase of 0.6 % , significant after control for potential confounders ( P BMI between groups . CONCLUSION Patients educated by LDFs showed improved metabolic control over the first 6 months of observation",
"BACKGROUND This study aim ed to assess the efficacy of an intensive exercise intervention strategy in promoting physical activity ( PA ) and improving hemoglobin A(1c)(HbA(1c ) ) level and other modifiable cardiovascular risk factors in patients with type 2 diabetes mellitus ( T2DM ) . METHODS Of 691 eligible sedentary patients with T2DM and the metabolic syndrome , 606 were enrolled in 22 outpatient diabetes clinics across Italy and r and omized by center , age , and diabetes treatment to twice-a-week supervised aerobic and resistance training plus structured exercise counseling ( exercise group ) vs counseling alone ( control group ) for 12 months . End points included HbA(1c ) level ( primary ) and other cardiovascular risk factors and coronary heart disease risk scores ( secondary ) . RESULTS The mean ( SD ) volume of PA ( metabolic equivalent hours per week ) was significantly higher ( P exercise ( total PA [ nonsupervised conditioning PA + supervised PA ] , 20.0 [ 0.9 ] , and nonsupervised , 12.4 [ 7.4 ] ) vs control ( 10.0 [ 8.7 ] ) group . Compared with the control group , supervised exercise produced significant improvements ( mean difference [ 95 % confidence interval ] ) in physical fitness ; HbA(1c ) level ( -0.30 % [ -0.49 % to -0.10 % ] ; P .001 ) ; systolic ( -4.2 mm Hg [ -6.9 to -1.6 mm Hg ] ; P = .002 ) and diastolic ( -1.7 mm Hg [ -3.3 to -1.1 mm Hg ] ; P = .03 ) blood pressure ; high-density lipoprotein ( 3.7 mg/dL [ 2.2 to 5.3 mg/dL ] ; P ) and low-density lipoprotein ( -9.6 mg/dL [ -15.9 to -3.3 mg/dL ] ; P = .003 ) cholesterol level ; waist circumference ( -3.6 cm [ -4.4 to -2.9 cm ] ; P These parameters improved only marginally in controls . CONCLUSIONS This exercise intervention strategy was effective in promoting PA and improving HbA(1c ) and cardiovascular risk profile . Conversely , counseling alone , though successful in achieving the currently recommended amount of activity , was of limited efficacy on cardiovascular risk factors , suggesting the need for a larger volume of PA in these high-risk subjects . Trial Registration is rct n.org Identifier : IS RCT N04252749",
"Background : Assessing muscular strength ( force-generating capacity ) and exercise capacity in response to an intervention for people with type 2 diabetes is clinical ly important in the prevention of type 2 diabetes-related complications . Objective : The purpose of this study was to investigate the impact of physical therapist – directed exercise counseling combined with fitness center – based exercise training on muscular strength and exercise capacity in people with type 2 diabetes . Design : This study was a r and omized clinical trial . Setting : The study was conducted on a university campus , with patient recruitment from the local community . Patients : Twenty-four people with type 2 diabetes were r and omly allocated to either a group that received physical therapist – directed exercise counseling plus fitness center – based exercise training ( experimental group ) or a group that received laboratory-based , supervised exercise ( comparison group ) . Intervention : The experimental group received physical therapist – directed exercise counseling on an exercise program and was provided access to a fitness center . The comparison group received the same exercise program as the experimental group while under supervision . Measurements : For all participants , chest press , row , and leg press muscular strength ( 1-repetition maximum [ in kilograms ] ) and exercise capacity ( grade d exercise test duration [ in minutes ] ) testing were conducted at baseline and 2 months later . Results : No significant differences in improvements in muscular strength were found for the chest press ( adjusted mean difference=1.2 ; 95 % confidence interval [CI]=−5.5 to 7.8 ) , row ( adjusted mean difference=0.1 ; 95 % CI=−9.0 to 9.1 ) , or leg press ( adjusted mean difference=2.7 ; 95 % CI=−9.1 to 14.6 ) between the groups . No significant difference in improvement in exercise capacity ( adjusted mean difference=0.2 ; 95 % CI=−0.9 to 1.2 ) was found between the groups . Limitations : Lack of group allocation blinding and the small sample size were limitations of this study . Conclusions : The results suggest that physical therapist – directed exercise counseling combined with fitness center – based exercise training can improve muscular strength and exercise capacity in people with type 2 diabetes , with outcomes comparable to those of supervised exercise",
"Background Physical activity ( PA ) is associated with reduced morbidity and mortality in individuals with type 2 diabetes mellitus ( T2DM ) ; however , most T2DM adults are insufficiently active . Purpose To explore the effectiveness of two innovative/theoretically based behavioral-change strategies to increase PA and reduce hemoglobin A1c ( A1c ) in T2DM adults . Methods Participants ( n = 287 ) were r and omly assigned to a control group or an intervention group ( i.e. , print-based material s/pedometer group or print-based material s/pedometer plus telephone-counseling group ) . Changes in PA and A1c and other clinical measures were examined by Linear Mixed Model analyses over 18 months , along with moderating effects for gender and age . Results PA and A1c levels did not significantly change in intervention groups . Step counts significantly increased in the print-based material s and pedometer plus telephone counseling group , for women . Conclusions No significant effects were found for PA or A1c levels for T2DM adults . The multi-component strategy including telephone counseling may have potential for women . The trial was registered on Clinical Trials.gov identifier : NCT00221234"
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Background : Testosterone replacement therapy ( TRT ) is a widely accepted form of treatment worldwide for aging men with late-onset hypogonadism syndrome . Urologists have been concerned about the possibility of TRT causing prostate cancer . The aim of this study was to assess the relationship between TRT and prostate cancer . Methods : A literature review was performed to identify all published , r and omized controlled trials ( RCTs ) of testosterone treatment for hypogonadism . The search included the MEDLINE , Embase and the Cochrane Controlled Trials Register data bases . Fixed-effect model was chosen for homogeneous studies ; otherwise , a r and om-effect model was used . Inconsistency was quantified by using the I2 statistic , which tests the proportion of heterogeneity across studies . Results : Results of 22 RCTs involving a total of 2351 patients were analyzed . Eleven RCTs were short-term ( TRT with a placebo ; TRT was administered transdermally , orally or by injection . Respective odds ratio ( OR ) and 95 % confidence interval ( CI ) values for injection , transdermal administration and oral administration of short-term TRT were as follows : prostate cancer : 0.39 ( 0.06–2.45 ) , 1.10 ( 0.26–4.65 ) and no oral ; biopsy : 5.28 ( 0.24–113.87 ) , 2.11 ( 0.32–13.73 ) and no oral ; and prostate nodule : 1.01 ( 0.13–7.60 ) , no injection and oral . Respective OR and 95 % CI values for injection , transdermal administration and oral administration of long-term TRT were as follows : prostate cancer : 2.09 ( 0.18–24.73 ) , 3.06 ( 0.12–76.70 ) and 0.19 ( 0.01–4.03 ) ; biopsy : 2.09 ( 0.18–24.73 ) , 3.65 ( 0.88–15.20 ) and 0.97 ( 0.13–7.03 ) ; and prostate nodule : 3.13 ( 0.12–80.68 ) , 1.00 ( 0.06–16.41 ) and 0.97 ( 0.13–7.03 ) . Though for some routes of administration and some end points , the OR associated with testosterone administration were > 1 indicating increased risk , none of these reached or even approached statistical significance ( all P>0.10 ) , which was consistent with the results of subgroup analyses and sensitivity analysis . Besides , sensitivity analysis indicated that short-term TRT was more likely to increase PSA levels than treatment with placebo ( P<0.00001 ) . Conclusions : This meta- analysis shows that regardless of the administration method , TRT is the short-term safety and does not promote prostate cancer development or progression but long-term data are warranted with justifiable end points
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"Purpose . We performed a r and omised controlled study regarding the effects of and rogen replacement therapy ( ART ) on lower urinary tract symptoms ( LUTS ) in hypogonadal men with benign prostate hypertrophy ( BPH ) . Methods . Fifty-two patients with hypogonadism and BPH were r and omly assigned to receive testosterone ( ART group ) as 250 mg of testosterone enanthate every 4 weeks or to the untreated control group . We compared International Prostate Symptom Score ( IPSS ) , uroflowmetry data , post-voiding residual volume ( PVR ) and systemic muscle volume at baseline and 12 months after treatment . Results . Forty-six patients ( ART group , n = 23 ; control , n = 23 ) were included in the analysis . At the 12-month visit , IPSS showed a significant decrease compared with baseline in the ART group ( 15.7 ± 8.7 vs. 12.5 ± 9.5 ; p The ART group also showed improvement in maximum flow rate and voided volume ( p controls . PVR showed no significant changes in either group . In addition , the ART group showed significant enhancement of mean muscle volume ( p Conclusion . ART improved LUTS in hypogonadal men with mild BPH",
"BACKGROUND Combination therapy with dutasteride and tamsulosin provides significantly greater benefit than either monotherapy for various patient-reported outcomes in men with moderate-to-severe lower urinary tract symptoms ( LUTS ) due to benign prostatic hyperplasia ( BPH ) and prostatic enlargement . OBJECTIVE To investigate whether combination therapy is more effective than either monotherapy in reducing the relative risk for acute urinary retention ( AUR ) , BPH-related surgery , and BPH clinical progression over 4 yr in men at increased risk of progression . DESIGN , SETTING , AND PARTICIPANTS The Combination of Avodart and Tamsulosin ( CombAT ) study was a 4-yr , multicenter , r and omised , double-blind , parallel-group study in 4844 men > or = 50 yr of age with a clinical diagnosis of BPH , International Prostate Symptom Score > or = 12 , prostate volume > or = 30 cm(3 ) , prostate-specific antigen 1.5 - 10 ng/ml , and maximum urinary flow rate ( Q(max ) ) > 5 and or = 125 ml . INTERVENTION Oral daily tamsulosin , 0.4 mg ; dutasteride , 0.5 mg ; or a combination of both . MEASUREMENTS The 4-yr primary end point was time to first AUR or BPH-related surgery . Secondary end points included BPH clinical progression , symptoms , Q(max ) , prostate volume , safety , and tolerability . RESULTS AND LIMITATIONS Combination therapy was significantly superior to tamsulosin monotherapy but not dutasteride monotherapy at reducing the relative risk of AUR or BPH-related surgery . Combination therapy was also significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression . Combination therapy provided significantly greater symptom benefit than either monotherapy at 4 yr . Safety and tolerability of combination therapy was consistent with previous experience with dutasteride and tamsulosin monotherapies , with the exception of an imbalance in the composite term of cardiac failure among the three study arms . The lack of placebo control is a study limitation . CONCLUSIONS The 4-yr CombAT data provide support for the long-term use of dutasteride and tamsulosin combination therapy in men with moderate-to-severe LUTS due to BPH and prostatic enlargement . CLINICAL TRIALS.GOV IDENTIFIER : NCT00090103 ( http://www . clinical trials.gov/ct2/show/NCT00090103 )",
"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",
"Decreases in growth hormone ( GH ) and insulin-like growth factor I occur with age , in addition to oestrogen deficiency in women and a reduction in the levels of testosterone in men . These age-related hormonal changes may contribute to reductions in lean body mass , muscle strength and cardiac endurance , which can be partially reversed in elderly people with GH treatment , and testosterone supplements and oestrogen/progestin hormone replacement therapy in men and women , respectively . These treatments are , however , thought to have potentially serious adverse effects . We conducted a study to evaluate the separate and interactive effects of GH and sex steroids on body composition , muscle strength and cardiac endurance as well as the rate of adverse events in healthy elderly people . The results of the study showed that although there were beneficial effects with GH and sex steroid treatment , a high percentage of adverse effects occurred after 26 weeks of treatment , demonstrating a need for more research on the safety of hormonal therapy in the elderly population",
"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 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",
"CONTEXT Aging in men is associated with reduced testosterone ( T ) levels and physiological changes leading to frailty , but the benefits of T supplementation are inconclusive . OBJECTIVE We studied the effects of T supplementation with and without progressive resistance training ( PRT ) on functional performance , strength , and body composition . DESIGN , SETTING , AND PARTICIPANTS We recruited 167 generally healthy community-dwelling older men ( 66 ± 5 years ) with low-normal baseline total T levels ( 200 - 350 ng/dL ) . INTERVENTION Subjects were r and omized to placebo or transdermal T gel [ 2 doses targeting either a lower ( 400 - 550 ng/dL ) or higher ( 600 - 1000 ng/dL ) T range ] and to either PRT or no exercise for 12 months . MAIN OUTCOME MEASURE The primary outcome was functional performance , whereas secondary outcomes were strength and body composition . RESULTS A total of 143 men completed the study . At 12 months , total T was 528 ± 287 ng/dL in subjects receiving any T and 287 ± 65 ng/dL in the placebo group . In the PRT group , function and strength were not different between T- and placebo-treated subjects , despite greater improvements in fat mass ( P = .04 ) and fat-free mass ( P = .01 ) with T. In the non-PRT group , T did not improve function but improved fat mass ( P = .005 ) , fat-free mass ( P = .03 ) , and upper body strength ( P = .03 ) compared with placebo . There were fewer cardiovascular events in the T-treated groups compared with placebo . CONCLUSIONS T supplementation was well tolerated and improved body composition but had no effect on functional performance . T supplementation improved upper body strength only in nonexercisers compared with placebo",
"INTRODUCTION Male hypogonadism is a significant and growing problem that can be successfully treated with testosterone replacement therapy . A new formulation of testosterone gel ( 1.62 % ) was developed with increased viscosity , reduced volume of application , and increased skin permeation compared with other currently available testosterone gels . AIM To evaluate the efficacy and safety of titrated doses of 1.62 % testosterone gel after daily application to the skin of hypogonadal men for 182 days . METHODS This was a multicenter , r and omized , double-blind , placebo-controlled study in hypogonadal men ( 234 active ; 40 placebo ) , 18 to 80 years of age with average serum total testosterone concentrations Topical testosterone gel ( 1.62 % ) , 1.25 g , 2.5 g , 3.75 g , and 5.0 g , or placebo gel was applied once daily to either upper arms/shoulders or abdomen . Dose adjustments were made on days 14 , 28 , and 42 . Main Outcome Measures . The percentage of subjects with serum total testosterone average concentrations ( C(av ) ) within the normal range of 300 - 1,000 ng/dL on study days 14 , 56 , 112 , and 182 . RESULTS Following titration , significantly ( P testosterone C(av ) values ( range 81.6 % to 82.5 % ) within the eugonadal range compared with placebo ( range 28.6 % to 37.0 % ) on all study days . The 1.62 % gel was safe and well tolerated . CONCLUSIONS In this study , treatment with 1.62 % testosterone gel was safe and efficacious , result ing in an acceptable percentage of hypogonadal males achieving eugonadal serum testosterone levels",
"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",
"We investigated the effects of 6 mo of near-physiological testosterone administration to older men on skeletal muscle function and muscle protein metabolism . Twelve older men ( > or = 60 yr ) with serum total testosterone concentrations were r and omly assigned in double-blind manner to receive either placebo ( n = 5 ) or testosterone enanthate ( TE ; n = 7 ) injections . Weekly intramuscular injections were given for the 1st mo to establish increased blood testosterone concentrations at 1 mo and then changed to biweekly injections until the 6-mo time point . TE doses were adjusted to maintain nadir serum testosterone concentrations between 17 and 28 nmol/l . Lean body mass ( LBM ) , muscle volume , prostate size , and urinary flow were measured at baseline and at 6 mo . Protein expression of and rogen receptor ( AR ) and insulin-like growth factor I , along with muscle strength and muscle protein metabolism , were measured at baseline and at 1 and 6 mo of treatment . Hematological parameters were followed monthly throughout the study . Older men receiving testosterone increased total and leg LBM , muscle volume , and leg and arm muscle strength after 6 mo . LBM accretion result ed from an increase in muscle protein net balance , due to a decrease in muscle protein breakdown . TE treatment increased expression of AR protein at 1 mo , but expression returned to pre-TE treatment levels by 6 mo . IGF-I protein expression increased at 1 mo and remained increased throughout TE administration . We conclude that physiological and near-physiological increases of testosterone in older men will increase muscle protein anabolism and muscle strength",
"CONTEXT Prostate safety is a primary concern when aging men receive testosterone replacement therapy ( TRT ) , but little information is available regarding the effects of TRT on prostate tissue in men . OBJECTIVE To determine the effects of TRT on prostate tissue of aging men with low serum testosterone levels . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial of 44 men , aged 44 to 78 years , with screening serum testosterone levels lower than 300 ng/dL ( INTERVENTION Participants were r and omly assigned to receive 150 mg of testosterone enanthate or matching placebo intramuscularly every 2 weeks for 6 months . MAIN OUTCOME MEASURES The primary outcome measure was the 6-month change in prostate tissue and rogen levels ( testosterone and dihydrotestosterone ) . Secondary outcome measures included 6-month changes in prostate-related clinical features , histology , biomarkers , and epithelial cell gene expression . RESULTS Of the 44 men r and omized , 40 had prostate biopsies performed both at baseline and at 6 months and qualified for per- protocol analysis ( TRT , n = 21 ; placebo , n = 19 ) . Testosterone replacement therapy increased serum testosterone levels to the mid-normal range ( median at baseline , 282 ng/dL [ 9.8 nmol/L ] ; median at 6 months , 640 ng/dL [ 22.2 nmol/L ] ) with no significant change in serum testosterone levels in matched , placebo-treated men . However , median prostate tissue levels of testosterone ( 0.91 ng/g ) and dihydrotestosterone ( 6.79 ng/g ) did not change significantly in the TRT group . No treatment-related change was observed in prostate histology , tissue biomarkers ( and rogen receptor , Ki-67 , CD34 ) , gene expression ( including AR , PSA , PAP2A , VEGF , NXK3 , CLU [ Clusterin ] ) , or cancer incidence or severity . Treatment-related changes in prostate volume , serum prostate-specific antigen , voiding symptoms , and urinary flow were minor . CONCLUSIONS These preliminary data suggest that in aging men with late-onset hypogonadism , 6 months of TRT normalizes serum and rogen levels but appears to have little effect on prostate tissue and rogen levels and cellular functions . Establishment of prostate safety for large population s of older men undergoing longer duration of TRT requires further study . Trial Registration clinical trials.gov Identifier : NCT00161304",
"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",
"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",
"CONTEXT The cause of declining testosterone ( T ) in aging men and their relationships with risk factors are unclear . OBJECTIVE The objective of the study was to investigate the relationships between lifestyle and health with reproductive hormones in aging men . DESIGN This was a baseline cross-sectional survey on 3200 community-dwelling men aged 40 - 79 yr from a prospect i ve cohort study in eight European countries . RESULTS Four predictors were associated with distinct modes of altered function : 1 ) age : lower free T ( FT ; -3.12 pmol/liter.yr , P total T ( TT ; -2.32 nmol/liter ) and FT ( -17.60 pmol/liter ) for body mass index ( BMI ; > or = 25 to LH , indicating hypothalamus/pituitary dysfunction ; 3 ) comorbidity : lower TT ( -0.80 nmol/liter , P LH in younger men but higher LH in older men ; and 4 ) smoking : higher SHBG ( 5.96 nmol/liter , P TT ( 1.31 nmol/liter , P T-LH-negative feedback due to elevated SHBG . CONCLUSIONS Complex multiple alterations in the hypothalamic-pituitary-testicular axis function exist in aging men against a background of progressive age-related testicular impairment . These changes are differentially linked to specific risk factors . Some risk factors operate independently of but others interact with age , in contributing to the T decline . These potentially modifiable risk factors suggest possible preventative measures to maintain T during aging in men",
"Testosterone undecanoate ( 160 mg/day ) or placebo was given orally in a double-blind fashion for 8 months to 23 middle-aged men without urinary tract symptoms . Testosterone was found to increase the mean prostate volume by 12 % ( P serum concentrations of sex-hormone-binding globulin and follicle stimulating hormone . The observed decrease in the mean serum concentration of luteinizing hormone was not statistically significant . The serum concentrations of prostate-specific antigen did not change as measured by two different well-vali date d immunometric assays . No changes in micturition habits or urine flow charts were reported",
"Transdermal testosterone ( T ) delivery represents an effective alternative to injectable and rogens . We studied 163 hypogonadal men who applied 5 , 7.5 , or 10 g And roGel ( T gel ) 1 % CIII per day for up to 42 months . Efficacy data were presented in 123 subjects considered evaluable . Continuous And roGel treatment normalized mean serum T and free T levels . Mean serum 5alpha-dihydrotestosterone concentrations and 5alpha-dihydrotestosterone/T ratio slightly increased , mean serum estradiol/T ratio doubled , and mean serum FSH and LH levels were suppressed by T replacement . Sexual function and mood parameters improved rapidly and were maintained throughout T treatment . Lean body mass increased ( P = 0.0001 ) and fat mass decreased ( P = 0.0001 ) , and these changes were maintained with treatment but were not accompanied by significant increases in muscle strength . Increases in serum bone markers suggestive of increased bone formation were followed by gradual and progressive increases in bone mineral density more in the spine ( P = 0.0001 ) than the hip ( P = 0.0004 ) . Mild local skin irritation occurred in 12 subjects , result ing in discontinuation in only one subject . Except for the anticipated increase in hematocrit and hemoglobin , there were no clinical ly significant changes in blood counts or biochemistry . In three subjects with elevated serum prostate-specific antigen , prostate biopsies showed cancer . We conclude that continued application of And roGel result ed in beneficial effects similar to those with injectables and other transdermal preparations . This study was neither placebo controlled nor powered to determine the effects of T treatment on prostate cancer risk . Thus , monitoring for prostatic disease and assessment for erythrocytosis are strongly advised to reduce the risk of adverse events with T treatment of hypogonadal men",
"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 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",
"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 ] . )",
"CONTEXT Serum testosterone levels decline significantly with aging . Testosterone supplementation to older men might beneficially affect the aging processes . OBJECTIVE To investigate the effect of testosterone supplementation on functional mobility , cognitive function , bone mineral density , body composition , plasma lipids , quality of life , and safety parameters in older men with low normal testosterone levels . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , placebo-controlled trial of 237 healthy men between the ages of 60 and 80 years with a testosterone level lower than 13.7 nmol/L conducted from January 2004 to April 2005 at a university medical center in the Netherl and s. INTERVENTION Participants were r and omly assigned to receive 80 mg of testosterone undecenoate or a matching placebo twice daily for 6 months . MAIN OUTCOME MEASURES Functional mobility ( Stanford Health Assessment Question naire , timed get up and go test , isometric h and grip strength , isometric leg extensor strength ) , cognitive function ( 8 different cognitive instruments ) , bone mineral density of the hip and lumbar spine ( dual-energy x-ray absorptiometry scanning ) , body composition ( total body dual-energy x-ray absorptiometry and abdominal ultrasound of fat mass ) , metabolic risk factors ( fasting plasma lipids , glucose , and insulin ) , quality of life ( Short-Form Health 36 Survey and the Questions on Life Satisfaction Modules ) , and safety parameters ( serum prostate-specific antigen level , ultrasonographic prostate volume , International Prostate Symptom score , serum levels of creatinine , aspartate aminotransferase , alanine aminotransferase , gamma-glutamyltransferase , hemoglobin , and hematocrit ) . RESULTS A total of 207 men completed the study . During the study , lean body mass increased and fat mass decreased in the testosterone group compared with the placebo group but these factors were not accompanied by an increase of functional mobility or muscle strength . Cognitive function and bone mineral density did not change . Insulin sensitivity improved but high-density lipoprotein cholesterol decreased ; by the end of the study , 47.8 % in the testosterone group vs 35.5 % in the placebo group had the metabolic syndrome ( P = .07 ) . Quality -of-life measures were no different except for one hormone-related quality -of-life measure that improved . No negative effects on prostate safety were detected . CONCLUSION Testosterone supplementation during 6 months to older men with a low normal testosterone concentration did not affect functional status or cognition but increased lean body mass and had mixed metabolic effects . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N23688581"
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BACKGROUND Children with autistic spectrum disorder ( ASD ) frequently present with inattention , impulsivity and hyperactivity , which are the cardinal symptoms of attention deficit hyperactivity disorder ( ADHD ) . The effectiveness of methylpheni date , a commonly used ADHD treatment , is therefore of interest in these children . OBJECTIVES To assess the effects of methylpheni date for symptoms of ADHD ( inattention , impulsivity and hyperactivity ) and ASD ( impairments in social interaction and communication , and repetitive , restricted or stereotypical behaviours ) in children and adolescents aged 6 to 18 years with ASD . SEARCH METHODS In November 2016 , we search ed CENTRAL , MEDLINE , Embase , PsycINFO , CINAHL , 11 other data bases and two trials registers . We also checked reference lists and contacted study authors and pharmaceutical companies . SELECTION CRITERIA R and omised controlled trials ( RCTs ) that investigated the effect of methylpheni date versus placebo on the core symptoms of ASD or ADHD-like symptoms , or both , in children aged 6 to 18 years who were diagnosed with ASD or pervasive developmental disorder . The primary outcome was clinical efficacy , defined as an improvement in ADHD-like symptoms ( inattention , impulsivity and hyperactivity ) and in the core symptoms of ASD ( impaired social interaction , impaired communication , and stereotypical behaviours ) , and overall ASD . Secondary outcomes examined were : rate of adverse events ; caregiver well-being ; need for institutionalisation , special schooling or therapy to achieve learning outcomes ; and overall quality of life . DATA COLLECTION AND ANALYSIS We used st and ard Cochrane method ological procedures . We combined outcome measures that used different psychometric scales , where clinical ly appropriate . We used a coefficient of 0.6 to calculate st and ard deviations and adjust for the studies ' cross-over design . We considered a st and ardised mean difference ( SMD ) of 0.52 as the minimum clinical ly relevant inter-treatment difference . We applied the GRADE rating for strength of evidence for each outcome . MAIN RESULTS The studies : we included four cross-over studies , with a total of 113 children aged 5 to 13 years , most of whom ( 83 % ) were boys . We included two studies with five-year-old children since we were unable to obtain the disaggregated data for those aged six years and above , and all other participants were in our target age range . All participants resided in the USA . The duration of treatment in the cross-over phase was one week for each dose of methylpheni date . Studies used a range of outcome scales , rated by parents , teachers or both ; clinicians ; or programme staff . We report parent-rated outcomes separately . Risk of bias : we considered three trials to be at high risk of bias due to selective reporting and all trials to be at unclear risk of bias for blinding of participants and assessors , due to the potential for recognising the side effects of methylpheni date . We judged all trials to be at low or unclear risk of bias for other items . Primary outcomes : the meta- analysis suggested that high-dose methylpheni date ( 0.43 mg/kg/dose to 0.60 mg/kg/dose ) had a significant and clinical ly relevant benefit on hyperactivity , as rated by teachers ( SMD -0.78 , 95 % confidence interval ( CI ) -1.13 to -0.43 ; 4 studies , 73 participants ; P parents ( mean difference ( MD ) -6.61 points , 95 % CI -12.19 to -1.03 , rated on the hyperactivity subscale of the Aberrant Behviour Checklist , range 0 to 48 ; 2 studies , 71 participants ; P = 0.02 ; low- quality evidence ) . Meta- analysis also showed a significant but not clinical ly relevant benefit on teacher-rated inattention ( MD -2.72 points , 95 % CI -5.37 to -0.06 , rated on the inattention subscale of the Swanson , Nolan and Pelham , Fourth Version question naire , range 0 to 27 ; 2 studies , 51 participants ; P = 0.04 ; low- quality evidence ) . There were inadequate data to conduct a meta- analysis on the symptom of impulsivity . There was no evidence that methylpheni date worsens the core symptoms of ASD or benefits social interaction ( SMD -0.51 , 95 % CI -1.07 to 0.05 ; 3 studies , 63 participants ; P = 0.07 ; very low- quality evidence ) , stereotypical behaviours ( SMD -0.34 , 95 % CI -0.84 to 0.17 ; 3 studies , 69 participants ; P = 0.19 ; low- quality evidence ) , or overall ASD ( SMD -0.53 , 95 % CI -1.26 to 0.19 ; 2 studies , 36 participants ; P = 0.15 ; low- quality evidence ) , as rated by teachers . There were inadequate data to conduct a meta- analysis on the symptom of impaired communication . SECONDARY OUTCOMES no data were available for the secondary outcomes of caregiver well-being ; need for institutionalisation , special schooling options or therapy to achieve learning outcomes ; or overall quality of life . No trials reported serious adverse events . The only adverse effect that was significantly more likely with treatment was reduced appetite as rated by parents ( risk ratio 8.28 , 95 % CI 2.57 to 26.73 ; 2 studies , 74 participants ; P symptoms of hyperactivity and possibly inattention in children with ASD who are tolerant of the medication , although the low quality of evidence means that we can not be certain of the true magnitude of any effect . There was no evidence that methylpheni date has a negative impact on the core symptoms of ASD , or that it improves social interaction , stereotypical behaviours , or overall ASD . The evidence for adverse events is of very low quality because trials were short and excluded children intolerant of methylpheni date in the test-dose phase . Future RCTs should consider extending the duration of treatment and follow-up . The minimum clinical ly important difference also needs to be confirmed in children with ASD using outcome scales vali date d for this population
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"Neural correlates of emotional dysregulation in attention-deficit/hyperactivity disorder ( ADHD ) and persisting influence of Methylpheni date ( MPH ) still remain insufficiently understood . Decreased activation in the subgenual cingulate and the ventral striatum were found during the perception of positive and negative affective pictures in drug-naïve males with ADHD during childhood ( n=10 ) . Males with ADHD during childhood treated with MPH ( n=10 ) did not show any significant differences compared to healthy controls ( n=10 ) . Further prospect i ve studies need to clarify direct and indirect mechanisms of MPH treatment that may contribute to emotional processing , which is dysfunctional in males without pharmacological treatment in childhood",
"OBJECTIVE To determine response of low-IQ children with attention deficit hyperactivity disorder ( ADHD ) symptoms to methylpheni date ( MPH ) . METHODS An aggregated analysis was conducted in 90 children with low IQ who received the same dose regimen of MPH in three independent , placebo-controlled studies . Active drug and placebo were given from 2 to 4 weeks each . Outcome measures included teacher and parent ratings on st and ardized behavior scales ( mean n = 84 ) , performance on computer-controlled cognitive-motor tests ( n = 62 ) , and measures of cardiovascular response ( n = 85 ) . RESULTS Both teachers and parents rated the children consistently as being improved on subscales assessing attention , overactivity , and conduct problems . Some 44 % of the subjects showed at least a 30 % reduction compared with placebo on teacher ratings . MPH improved accuracy on several cognitive tests , response speed was increased on some , and seat activity declined for one of three tests ; heart rate was mildly increased ( 3.9 beats/minute ) with MPH . Analyses of IQ and mental age as moderator variables suggested that lower functional level ( especially lower IQ ) may be associated with a less favorable response to MPH . CONCLUSIONS Children with low IQ and ADHD clearly respond to MPH , but their rate of beneficial response appears to be well under that of normal-IQ children and more varied . Different attentional mechanisms may moderate response to psychostimulants",
"Sixty-nine children with attention deficit hyperactivity disorder ( ADHD ) underwent blind methylpheni date trials . 36 had ADHD alone ( with or without a learning disability ) and 33 had additional neurodevelopmental disorders . Of the children with ADHD alone , 88 per cent improved significantly on methylpheni date . This did not differ significantly from the 69 per cent response rate for children with ADHD and other neurodevelopmental disorders . The results confirm and add to the research literature indicating that ADHD children who are of preschool age and /or who have co-existing neurological disorders may benefit from methylpheni date",
"This report examined the effect of methylpheni date on social communication and self-regulation in children with pervasive developmental disorders and hyperactivity in a secondary analysis of RUPP Autism Network data . Participants were 33 children ( 29 boys ) between the ages of 5 and 13 years who participated in a four-week crossover trial of placebo and increasing doses of methylpheni date given in r and om order each for one week . Observational measures of certain aspects of children ’s social communication , self-regulation , and affective behavior were obtained each week . A significant positive effect of methylpheni date was seen on children ’s use of joint attention initiations , response to bids for joint attention , self-regulation , and regulated affective state . The results go beyond the recent literature and suggest that methylpheni date may have positive effects on social behaviors in children with PDD and hyperactivity",
"A double-blind , placebo-controlled , crossover study of methylpheni date ( 0.4 mg/kgday ) and different doses of fenfluramine ( 1.0 , 1.5 , or 2.0 mg/g/day ) in children with mental retardation or borderline IQ and ADHD was conducted . Parents , teachers , examiners , and physicians rated the children . There were relatively few significant drug effects by condition . When the optimal fenfluramine dose for each child was compared with placebo and methylpheni date , significant improvements occurred for fenfluramine on several parent and teacher subscales ; teachers rated the children as somewhat improved with methylpheni date . The highest dose of fenfluramine produced more behavior compliance but apparently at the cost of cognitive efficiency . Most side effects ( drowsiness , dizziness , anorexia ) occurred with fenfluramine . Both drugs appear to be effective treatments for children with ADHD and mental retardation , although there is a possible neurotoxic action with fenfluramine . We recommend a gradual phase-in of fenfluramine dosage , up to 1.5 mg/kg/day , for most children",
"CONTEXT Hyperactivity and inattention are common symptoms in children with autistic disorder and related pervasive developmental disorders , but studies of stimulants in these conditions have been inconclusive . OBJECTIVES To determine the efficacy and safety of methylpheni date hydrochloride in children with pervasive developmental disorders and hyperactivity . DESIGN Double-blind , placebo-controlled , crossover trial followed by open-label continuation . SETTING Five academic outpatient clinics . PARTICIPANTS Seventy-two drug-free children , aged 5 to 14 years , with pervasive developmental disorders accompanied by moderate to severe hyperactivity . INTERVENTIONS Prior to r and omization , subjects entered a 1-week test-dose phase in which each subject received placebo for 1 day followed by increasing doses of methylpheni date ( low , medium , and high doses ) that were each given for 2 days . The low , medium , and high doses of methylpheni date hydrochloride were based on weight , and they ranged from 7.5 mg/d to 50.0 mg/d in divided doses . Subjects who tolerated the test dose ( n = 66 ) were assigned to receive placebo for 1 week and then 3 methylpheni date doses in r and om order during a double-blind , crossover phase . Children responding to methylpheni date then entered 8 weeks of open-label treatment at the individually determined best dose . MAIN OUTCOME MEASURES The primary outcome measure was the teacher-rated hyperactivity subscale of the Aberrant Behavior Checklist . Response was defined as \" much improved \" or \" very much improved \" on the Clinical Global Impressions Improvement item coupled with considerable reductions in the parent-rated and /or teacher-rated Aberrant Behavior Checklist hyperactivity subscale score . RESULTS Methylpheni date was superior to placebo on the primary outcome measure , with effect sizes ranging from 0.20 to 0.54 depending on dose and rater . Thirty-five ( 49 % ) of 72 enrolled subjects were classified as methylpheni date responders . Adverse effects led to the discontinuation of study medication in 13 ( 18 % ) of 72 subjects . CONCLUSIONS Methylpheni date was often efficacious in treating hyperactivity associated with pervasive developmental disorders , but the magnitude of response was less than that seen in typically developing children with attention-deficit/hyperactivity disorder . Adverse effects were more frequent",
"BACKGROUND Methylpheni date has been shown elsewhere to improve hyperactivity in about half of treated children who have pervasive developmental disorders ( PDD ) and significant hyperactive-inattentive symptoms . We present secondary analyses to better define the scope of effects of methylpheni date on symptoms that define attention-deficit/hyperactivity disorder ( ADHD ) and oppositional defiant disorder ( ODD ) , as well as the core autistic symptom domain of repetitive behavior . METHODS Sixty-six children ( mean age 7.5 y ) with autistic disorder , Asperger 's disorder , and PDD not otherwise specified , were r and omized to varying sequences of placebo and three different doses of methylpheni date during a 4-week blinded , crossover study . Methylpheni date doses used approximated .125 , .25 , and .5 mg/kg per dose , twice daily , with an additional half-dose in the late afternoon . Outcome measures included the Swanson , Nolan , and Pelham Question naire revised for DSM-IV ( ADHD and ODD scales ) and the Children 's Yale-Brown Obsessive Compulsive Scales for PDD . RESULTS Methylpheni date was associated with significant improvement that was most evident at the .25- and .5-mg/kg doses . Hyperactivity and impulsivity improved more than inattention . There were not significant effects on ODD or stereotyped and repetitive behavior . CONCLUSIONS Convergent evidence from different assessment s and raters confirms methylpheni date 's efficacy in relieving ADHD symptoms in some children with PDD . Optimal dose analyses suggested significant interindividual variability in dose response",
"CONTEXT To our knowledge , there is no published information on the epidemiology of autism spectrum disorders ( ASDs ) in adults . If the prevalence of autism is increasing , rates in older adults would be expected to be lower than rates among younger adults . OBJECTIVE To estimate the prevalence and characteristics of adults with ASD living in the community in Engl and . DESIGN A stratified , multiphase r and om sample was used in the third national survey of psychiatric morbidity in adults in Engl and in 2007 . Survey data were weighted to take account of study design and nonresponse so that the results were representative of the household population . SETTING General community ( ie , private households ) in Engl and . PARTICIPANTS Adults ( people 16 years or older ) . MAIN OUTCOME MEASURES Autism Diagnostic Observation Schedule , Module 4 in phase 2 vali date d against the Autism Diagnostic Interview-Revised and Diagnostic Interview for Social and Communication Disorders in phase 3 . A 20-item subset of the Autism-Spectrum Quotient self-completion question naire was used in phase 1 to select respondents for phase 2 . Respondents also provided information on sociodemographics and their use of mental health services . RESULTS Of 7461 adult participants who provided a complete phase 1 interview , 618 completed phase 2 diagnostic assessment s. The weighted prevalence of ASD in adults was estimated to be 9.8 per 1000 ( 95 % confidence interval , 3.0 - 16.5 ) . Prevalence was not related to the respondent 's age . Rates were higher in men , those without educational qualifications , and those living in rented social ( government-financed ) housing . There was no evidence of increased use of services for mental health problems . CONCLUSIONS Conducting epidemiologic research on ASD in adults is feasible . The prevalence of ASD in this population is similar to that found in children . The lack of an association with age is consistent with there having been no increase in prevalence and with its causes being temporally constant . Adults with ASD living in the community are socially disadvantaged and tend to be unrecognized",
"Twenty-six children having Attention Deficit Hyperaclivity Disorder were tested before and after treatment with methylpheni date . In addition to st and ardized parent and teacher rating scales , each child was assessed on a variety of psychomotor tests with an emphasis on attentional constructs . Relatively few of the performance tests , administered prior to medication , predicted clinical response to medication . However , chronological age and performance on a memory distraction task and on the Graduated Holes Task ( Kløve , 1963 ) were moderately correlated with clinical outcome . Using stepwise multiple regression analyses to predict outcome , age and the psychomotor tasks predicted about 50 % of outcome variance . There was virtually no relationship between clinical change and change on the performance tests . Findings are discussed with respect to results from previous prediction studies , theoretical models of drug response , and clinical management",
"This study examined the effects of methylpheni date ( MPH ) on reaction time ( RT ) variability in children with attention deficit hyperactivity disorder ( ADHD ) . Using a broad battery of computerized tasks , and both conventional and ex-Gaussian indicators of RT variability , in addition to within-task manipulations of incentive and event rate ( ER ) , this study comprehensively examined the breadth , specificity , and possible moderators of effects of MPH on RT variability . A total of 93 children with ADHD completed a 4-week within-subject , r and omized , double-blind , placebo-controlled crossover trial of MPH to identify an optimal dosage . Children were then r and omly assigned to receive either their optimal MPH dose or placebo after which they completed five neuropsychological tasks , each allowing trial-by-trial assessment of RTs . Stimulant effects on RT variability were observed on both measures of the total RT distribution ( ie , coefficient of variation ) as well as on an ex-Gaussian measure examining the exponential portion of the RT distribution ( ie , τ ) . There was minimal , if any , effect of MPH on performance accuracy or RT speed . Within-task incentive and ER manipulations did not appreciably affect stimulant effects across the tasks . The pattern of significant and pervasive effects of MPH on RT variability , and few effects of MPH on accuracy and RT speed suggest that MPH primarily affects RT variability . Given the magnitude and breadth of effects of MPH on RT variability as well as the apparent specificity of these effects of MPH on RT variability indicators , future research should focus on neurophysiological correlates of effects of MPH on RT variability in an effort to better define MPH pharmacodynamics",
"OBJECTIVE The aim of this study was to investigate the short-term efficacy and safety of methylpheni date ( MPH ) to treat attention-deficit/hyperactivity disorder ( ADHD ) symptoms in an understudied population of preschoolers with pervasive developmental disorder ( PDD ) or intellectual disability ( ID ) . METHODS Fourteen preschoolers with developmental disorders ( DD , n = 14 ; PDD , n = 12 ; ID , n = 2 ) underwent MPH titration in a single-blind manner followed by a 4-week double-blind crossover phase . Each child was administered placebo for 2 weeks and \" optimal dose \" for 2 weeks . The primary outcome measure was the Diagnostic and Statistical Manual of Mental Disorders , 4(th ) edition ( DSM-IV ) ADHD subscale of the Conners ' Parent Rating Scale-Revised ( CPRS-R-DSM-IV-ADHD ) . RESULTS MPH improved parent-rated ADHD symptoms of the preschoolers ; 50 % were rated as responders . The CPRS-R-DSM-IV-ADHD subscale was significant for the PDD subgroup ( p = 0.005 , Cohen d = 0.97 ) and marginally significant for the entire DD sample ( p = 0.08 , Cohen d = 0.50 ) . Half of the preschoolers experienced side effects with MPH , including reports of increased stereotypic behavior , upset stomach , sleep-related difficulties , and emotional lability . One child discontinued during titration due to side effects . CONCLUSION The predominant direction of response in these preschoolers with both ADHD and PDD/ID favored MPH , even though the response was more subtle and variable than in older and typically developing children . Due to high rates of adverse effects , preschoolers should be monitored closely",
"OBJECTIVE The aim of this study was to investigate the effects of ongoing methylpheni date ( MPH ) on ADHD-related and autistic symptoms in Pervasive Developmental Disorders ( PDD ) in children who did not present any adverse effects to an initial acute dose administered at the clinic . METHODS Participants included 13 subjects ( 12 males , with a mean age of 7.9 years ) with PDD and moderate to severe hyperactivity/impulsivity . The severity of the symptoms assessment was based on Clinical Global Impression ( CGI ) , Childhood Autism , Child Psychiatric and Conners Parent and Teacher Rating Scales ( CPRS ) . Scores at baseline , and after 1 and 3 months of treatment , were compared to intent-to-treat analyses . RESULTS One ( 1 ) hour after a single MPH dose ( 0.4 mg/kg ) , 5 subjects exhibited increased hyperactivity , stereotypes , dysphoria , or motor tics and were rated as minimally or much worse on the CGI Global Improvement Scale . They received no further treatment with MPH . Four ( 4 ) of the remaining subjects were rated as improved , and four as unchanged ; they proceeded to a 12-week open trial of MPH . Two children remained unchanged : they discontinued treatment after 1 week on maximally tolerated doses . However , in group analyses , behavioral measures of hyperactivity and impulsivity improved significantly , while autism core symptom measures were unaffected . No significant adverse effects were observed in any of the 8 subjects . CONCLUSIONS Administering a single MPH test dose may be useful in identifying children with PDD who may benefit from prolonged therapy",
"BACKGROUND The thrice daily dosing regimen of immediate release methylpheni date ( IR-MPH ) for Attention Deficit/Hyperactivity Disorder ( ADHD ) requires in-school dosing , leading to issues surrounding dispensing and storage of controlled substances by school personnel and concerns over children?s privacy and the embarrassment associated with taking medication in public at school . OROS-methylpheni date ( OROS-MPH ) is a once-daily controlled-release formulation of methylpheni date ( MPH ) developed to overcome some of the limitations associated with IR-MPH and first-generation sustained-release formulations . R and omized , controlled trials ( RCTs ) that focus on treatment efficacy provide the best evidence for demonstrating whether an intervention works , but under ideal conditions one can not discount the importance of efficacy study results . However , the most useful information to clinicians comes from an effectiveness study design . OBJECTIVES To evaluate the effectiveness and tolerability of OROS-MPH versus usual care with IR-MPH in children aged 6 to 12 years with ADHD . METHODS This 8 week , multicentre , open-label study r and omized 147 subjects to either once-daily OROS-MPH or usual care with IR-MPH . Subjects were titrated to a clinical ly effective dose of either study medication over 4 weeks and maintained on that dose for an additional 4 weeks . The SNAP-IV parent-rating scale was used to assess effectiveness . RESULTS OROS-MPH showed statistically significant superiority to IR-MPH in remission rate based on the 18 ADHD symptoms ( p=0.0002 , X2=13.8 , df=1 ) and severity of ADHD and ODD symptoms ( p=0.004 , F=8.4 , df=1,127 ) , as well as on the following secondary assessment s : IOWA Conners , Conners Parent Rating Scale ( short version ) , Parent Stress Index , ( short version ) ; Visual Analogue Scale for social play ; Clinical Global Impression-Severity , Clinical Global Impression-Improvement and Parent Satisfaction with treatment . OROS-MPH and IR-MPH were both well tolerated with a similar side effect profile . CONCLUSIONS Once-daily OROS-MPH is significantly more effective than usual care with IR-MPH based on multiple outcome measures including remission rate",
"BACKGROUND Attention deficit hyperactivity disorder is increased in children with intellectual disability . Previous research has suggested stimulants are less effective than in typically developing children but no studies have titrated medication for individual optimal dosing or tested the effects for longer than 4 weeks . METHOD One hundred and twenty two drug-free children aged 7 - 15 with hyperkinetic disorder and IQ 30 - 69 were recruited to a double-blind , placebo-controlled trial that r and omized participants using minimization by probability , stratified by referral source and IQ level in a one to one ratio . Methylpheni date was compared with placebo . Dose titration comprised at least 1 week each of low ( 0.5 mg/kg/day ) , medium ( 1.0 mg/kg/day ) and high dose ( 1.5 mg/kg/day ) . Parent and teacher Attention deficit hyperactivity disorder ( ADHD ) index of the Conners Rating Scale-Short Version at 16 weeks provided the primary outcome measures . Clinical response was determined with the Clinical Global Impressions scale ( CGI-I ) . Adverse effects were evaluated by a parent-rated question naire , weight , pulse and blood pressure . Analyses were by intention to treat . TRIAL REGISTRATION IS RCT N 68384912 . RESULTS Methylpheni date was superior to placebo with effect sizes of 0.39 [ 95 % confidence intervals ( CIs ) 0.09 , 0.70 ] and 0.52 ( 95 % CIs 0.23 , 0.82 ) for the parent and teacher Conners ADHD index . Four ( 7 % ) children on placebo versus 24 ( 40 % ) of those on methylpheni date were judged improved or much improved on the CGI . IQ and autistic symptoms did not affect treatment efficacy . Active medication was associated with sleep difficulty , loss of appetite and weight loss but there were no significant differences in pulse or blood pressure . CONCLUSIONS Optimal dosing of methylpheni date is practical and effective in some children with hyperkinetic disorder and intellectual disability . Adverse effects typical of methylpheni date were seen and medication use may require close monitoring in this vulnerable group",
"Thirteen children ( ages 5.6 to 11.2 years ) with autism and symptoms of attention-deficit hyperactivity disorder ( ADHD ) participated in a double-blind , placebo-controlled crossover study of methylpheni date ( 0.3 and 0.6 mg/kg per dose ) . Eight subjects responded positively , based upon a minimum 50 % decrease on the Conners Hyperactivity Index . Ratings of stereotypy and inappropriate speech , which are often associated with autistic core features , also decreased . However , no changes were found on the Child Autism Rating Scale , a global assessment of autistic symptomotology . Significant adverse side effects occurred in some children including social withdrawal and irritability , especially at the 0.6 mg/kg dose . Results suggest that methylpheni date can be efficacious for children with autism and ADHD symptoms . However , this group of children seems to be particularly susceptible to adverse side effects",
"Measurement of health-related quality of life ( HRQOL ) in attention-deficit-hyperactivity disorder ( ADHD ) gives a more complete picture of day-to-day functioning and treatment effects than behavioural rating alone . The aim of this pilot study was to investigate the impact of the combined diagnoses of developmental coordination disorder ( DCD ) and ADHD on HRQOL , and the effectiveness of methylpheni date ( MPH ) on HRQOL . HRQOL was established using the Dutch-Child-AZL-TNO- Quality -of-Life ( DUX-25 ) and the TNO-AZL-Child- Quality -of-Life ( TACQOL ) question naires , completed by children and parents . HRQOL of these children was compared with that of 23 age- and sex-matched healthy controls . Twenty-three children ( 21 males , two females ; mean age 8 y 6 mo , [ SD 3 mo ] range 7 y-10 y 8 mo ) with ADHD/DCD entered a 4-week , open-label MPH study , after MPH-sensitivity was established , in a double-blind , placebo-controlled trial . In these children 's self- and proxy reports , impact of both DCD and ADHD was reflected in lower general well-being ( self and proxy report p=0.001 ) due to lower functioning in motor ( selfp=0.026 ; proxy 0.001 ) , autonomic ( self p cognitive ( self p=0.001 ; proxy p=0.01 ) , and social ( self and proxy p domains . HRQOL scores improved in 18 children receiving MPH ( p=0.001 ) versus controls . The ADHD /DCD group also demonstrated a significant improvement in ADHD symptoms ( p motor functioning ( p Additional motor therapy will still be needed in about half of the children with ADHD/DCD receiving MPH , within multimodal treatment including educational and psychosocial assistance",
"BACKGROUND In addition to cognitive impairment , there are disruptions to mood and emotion processing in attention-deficit/hyperactivity disorder ( ADHD ) but little is known about their neural basis . We examined ADHD disturbances in mood and emotion recognition and underlying neural systems before and after treatment with stimulant medication . METHODS Participants were 51 unmedicated ADHD adolescents and 51 matched healthy control subjects rated for depressed and anxious mood and accuracy for identifying facial expressions of basic emotion . Brain function was recorded using event-related potentials ( ERPs ) while subjects viewed these expressions . ADHD subjects were retested after 4 weeks , following treatment with methylpheni date ( MPH ) . RESULTS ADHD subjects showed a profile of emotion-related impairment : higher depression and anxiety , deficits in identifying threat-related emotional expressions in particular , and alterations in ERPs . There was a pronounced reduction in occipital activity during the early perceptual analysis of emotional expression ( within 120 msec ) , followed by an exaggeration of activity associated with structural encoding ( 120 - 220 msec ) and subsequent reduction and slowing of temporal brain activity subserving context processing ( 300 - 400 msec ) . Methylpheni date normalized neural activity and produced some improvement of emotion recognition but had no impact on negative mood . Improvements in neural activity with MPH were consistent predictors of improvement in clinical features of emotional lability and hyperactivity . CONCLUSIONS Objective behavioral and brain function measures of emotion processing may provide a valuable addition to the clinical armamentarium for assessing emotional disturbances in ADHD and the efficacy of stimulants for treating these disturbances",
"BACKGROUND In the recent past , psychiatrists and paediatricians have avoided prescribing stimulant medication , such as methylpheni date and dexamphetamine to patients with autism spectrum disorders ( ASD ) because of both doubts about efficacy and concern that these medications make stereotypies worse . Recently , a number of small trials have suggested that methypheni date does have a role in the management of hyperactivity in children with autistic spectrum disorders . METHODS Children with ASD and attention deficit hyperactivity disorder ( ADHD ) , and children with ADHD without ASD received st and ard treatment with methypheni date from one specialist centre . A combination of st and ardized and novel outcome tools was used to allow both an exploratory retrospective study of 174 children and then a prospect i ve study of a further 52 children to be carried out . RESULTS After treatment with stimulants , the subjects in both groups showed statistically significant improvements in target symptoms of ' hyperactivity ' , ' impulsivity ' , ' inattention ' , ' oppositionality ' , ' aggression ' and ' intermittent explosive rage ' . The Clinical Global Impression-Improvement and efficacy index measures also improved in each group . In both the retrospective and the prospect i ve studies , there was no statistically significant difference in the degree of improvements between each group . Importantly , neither tics nor repetitive behaviours worsened in either group . Children in the ' ADHD-only ' group who were prescribed stimulants experienced significant ' nausea ' , ' giddiness ' , ' headaches ' and ' sleep difficulties ' , whereas sleep difficulties were the only side effect that emerged in children in the ASD with ADHD group . CONCLUSIONS Both studies presented here support previous findings from smaller studies that show children with autism and ADHD can respond as well to stimulants as children with ADHD alone . Although r and omized controlled trials remain the gold st and ard for efficacy studies , systems like this that allow clinicians to continue rigorous and consistent monitoring for many years have a valuable role to play . Furthermore , such monitoring systems which now exist electronically can easily accumulate large data sets and reveal details about long-term effectiveness and long-term side effects of medication that are unlikely to be discovered in short-term trials",
"An up-to- date review of drug treatment in psychoses of early childhood is presented . At the present time , of all biological interventions in these developmental disorders , drug treatment alone remains a valuable addition or an essential treatment modality of the total treatment . Experience has shown that a therapeutically effective potent drug can make the autistic child more amenable to other therapies , including special education . However , knowledge is lacking about the effect of various psychoactive agents on cognition in this patient population as well as their influence on growth , weight , endocrine systems , and organs . Drugs currently in use treat symptoms , not diseases . A great need for classification in this area persists . The same symptoms may be caused by a variety of etiologic factors , and autism may or may not be the earliest expression of childhood schizophrenia . It is suggested that clinical distinctions be correlated or even improved by certain biochemical , neuroendocrine , and physiological criteria ; this also may be of considerable value in predicting whether a child can benefit from a specific drug",
"INTRODUCTION AND HYPOTHESIS Some authors draw a connection between the dopaminergic pathways and emotional perception . The present study is based on that association and addresses the question whether methylpheni date and the result ing amelioration of the disturbed dopamine metabolism lead to an improvement of the facial affect recognition abilities in children with attention-deficit/hyperactivity disorder ( ADHD ) . METHODS A computer test was conducted on 21 participants , aged 7 - 14 years and with a diagnosis of ADHD - some with comorbid oppositional defiant disorder - conducted the FEFA ( Frankfurt Test and Training of Facial Affect ) , a computer test to examine their facial affect recognition abilities . It consists of two subtests , one with faces and one with eye pairs . All participants were tested in a double-blind cross-over study , once under placebo and once under methylpheni date . RESULTS AND DISCUSSION The collected data showed that methylpheni date leads to amelioration of facial affect recognition abilities , but not on a significant level . Reasons for missing significance may be the small sample size or the fact that there exists some overlapping in cerebral connections and metabolic pathways of the site of action of methylpheni date and the affected dopaminergic areas in ADHD . However , consistent with the endophenotype concept , certain gene locations of the dopaminergic metabolism as both an aetiological factor for ADHD and the deficient facial affect recognition abilities with these individuals were considered . Consulting current literature they were found to be not concordant . Therefore , we conclude that the lacking significance of the methylpheni date affect on facial affect recognition is based on this fact",
"The use of psychostimulants in autistic disorder has not received extensive evaluation . Furthermore , their use for the symptomatic control of autistic disorder has been felt to be contraindicated . This study investigates the use of methylpheni date ( MPH ) for the treatment of selected symptoms of autistic disorder . Ten children , ages 7–11 , with a DSM-III-R diagnosis of autistic disorder participated in a double-blind crossover study using placebo and two MPH doses ( 10 mg or 20 mg bid ) . Subjects showed modest but statistically significant improvement on MPH over placebo . No significant side effects including worsening stereotypic movements occurred on either dose . Improvement in hyperactivity and lack of adverse effects suggest that MPH may be useful in the treatment of hyperactive autistic children",
"BACKGROUND It has been suggested that the severity of autism spectrum disorder ( ASD ) symptoms is positively correlated with the level of circulating or stored toxic metals , and that excretion of these heavy metals , brought about by the use of pharmaceutical chelating agents , results in improved symptoms . OBJECTIVES To assess the potential benefits and adverse effects of pharmaceutical chelating agents ( referred to as chelation therapy throughout this review ) for autism spectrum disorder ( ASD ) symptoms . SEARCH METHODS We search ed the following data bases on 6 November 2014 : CENTRAL , Ovid MEDLINE , Ovid MEDLINE In-Process , Embase , PsycINFO , Cumulative Index to Nursing and Allied Health Literature ( CINAHL ) and 15 other data bases , including three trials registers . In addition we checked references lists and contacted experts . SELECTION CRITERIA All r and omised controlled trials of pharmaceutical chelating agents compared with placebo in individuals with ASD . DATA COLLECTION AND ANALYSIS Two review authors independently selected studies , assessed them for risk of bias and extracted relevant data . We did not conduct a meta- analysis , as only one study was included . MAIN RESULTS We excluded nine studies because they were non-r and omised trials or were withdrawn before enrolment . We included one study , which was conducted in two phases . During the first phase of the study , 77 children with ASD were r and omly assigned to receive seven days of glutathione lotion or placebo lotion , followed by three days of oral dimercaptosuccinic acid ( DMSA ) . Forty-nine children who were found to be high excreters of heavy metals during phase one continued on to phase two to receive three days of oral DMSA or placebo followed by 11 days off , with the cycle repeated up to six times . The second phase thus assessed the effectiveness of multiple doses of oral DMSA compared with placebo in children who were high excreters of heavy metals and who received a three-day course of oral DMSA . Overall , no evidence suggests that multiple rounds of oral DMSA had an effect on ASD symptoms . AUTHORS ' CONCLUSIONS This review included data from only one study , which had method ological limitations . As such , no clinical trial evidence was found to suggest that pharmaceutical chelation is an effective intervention for ASD . Given prior reports of serious adverse events , such as hypocalcaemia , renal impairment and reported death , the risks of using chelation for ASD currently outweigh proven benefits . Before further trials are conducted , evidence that supports a causal link between heavy metals and autism and methods that ensure the safety of participants are needed"
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4117542e-06ff-11f0-808a-c43d1ab1c353
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We undertook a systematic review and meta- analysis of published papers assessing dietary protein and bone health . We found little benefit of increasing protein intake for bone health in healthy adults but no indication of any detrimental effect , at least within the protein intakes of the population s studied . This systematic review and meta- analysis analysed the relationship between dietary protein and bone health across the life-course . The PubMed data base was search ed for all relevant human studies from the 1st January 1976 to 22nd January 2016 , including all bone outcomes except calcium metabolism . The search es identified 127 papers for inclusion , including 74 correlational studies , 23 fracture or osteoporosis risk studies and 30 supplementation trials . Protein intake accounted for 0–4 % of areal BMC and areal BMD variance in adults and 0–14 % of areal BMC variance in children and adolescents . However , when confounder adjusted ( 5 studies ) adult lumbar spine and femoral neck BMD associations were not statistically significant . There was no association between protein intake and relative risk ( RR ) of osteoporotic fractures for total ( RR(r and om ) = 0.94 ; 0.72 to 1.23 , I2 = 32 % ) , animal ( RR ( r and om ) = 0.98 ; 0.76 to 1.27 , I2 = 46 % ) or vegetable protein ( RR ( fixed ) = 0.97 ( 0.89 to 1.09 , I2 = 15 % ) . In total protein supplementation studies , pooled effect sizes were not statistically significant for LSBMD ( total n = 255 , MD(fixed ) = 0.04 g/cm2 ( 0.00 to 0.08 , P = 0.07 ) , I2 = 0 % ) or FNBMD ( total n = 435 , MD(r and om ) = 0.01 g/cm2 ( −0.03 to 0.05 , P = 0.59 ) , I2 = 68 % ) . There appears to be little benefit of increasing protein intake for bone health in healthy adults but there is also clearly no indication of any detrimental effect , at least within the protein intakes of the population s studied ( around 0.8–1.3 g/Kg/day ) . More studies are urgently required on the association between protein intake and bone health in children and adolescents
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[
"Dietary data from a prospect i ve study were used to relate factors influencing calcium balance ( estimates of dietary calcium intake , protein intake from nondairy animal sources ( meat , fish , and eggs ) , and coffee consumption ) to the incidence of hip fracture . During the years 1977 - 1983 , women and men born between 1925 and 1940 and living in one of three Norwegian counties were invited to a cardiovascular screening that included a dietary survey . The attendance rate at screening was 91.1 % , and 90.7 % of these persons ( 19,752 women and 20,035 men ) filled in and returned a semiquantitative dietary question naire . This cohort was followed for an average of 11.4 years ( range , 0.01 - 13.8 years ) with respect to hip fracture , defined as cervical or trochanteric fracture . During follow-up , 213 hip fractures were identified , excluding fractures associated with high-energy trauma and metastatic bone disease . There was no clear association between calcium intake or nondairy animal protein intake and hip fracture in this cohort . However , an elevated risk of fracture was found in women with a high intake of protein from nondairy animal sources in the presence of low calcium intake ( relative risk = 1.96 ( 95 % confidence interval 1.09 - 3.56 ) for the highest quarter of nondairy protein intake and the lowest quarter of calcium intake vs. the three lower quarters of protein intake and the three higher quarters of calcium intake ) . Women who drank nine or more cups of coffee per day also had an increased risk of fracture , while there was no association between coffee consumption and hip fracture in men . Although these findings do not necessarily imply causal relations , they suggest the presence of risk factors for hip fracture that act through a negative calcium balance in this population",
"BACKGROUND The effect of meat protein on calcium retention at different calcium intakes is unresolved . OBJECTIVE The objective was to test the effect of dietary protein on calcium retention at low and high intakes of calcium . DESIGN In a r and omized controlled feeding study with a 2 x 2 factorial crossover design , healthy postmenopausal women ( n = 27 ) consumed either approximately 675 or approximately 1510 mg Ca/d , with both low and high protein ( providing 10 % and 20 % energy ) for 7 wk each , separated by a 3-wk washout period . After 3 wk , the entire diet was extrinsically labeled with (47)Ca , and isotope retention was monitored by whole-body scintillation counting . Clinical markers of calcium and bone metabolism were measured . RESULTS High compared with low dietary protein significantly increased calcium retention from the low-calcium ( 29.5 % compared with 26.0 % absorbed ) but not the high-calcium diet ( 18 % absorbed ) . For the low-calcium diet , this effect nearly balanced a protein-related 0.5-mmol/d greater urinary calcium excretion . Protein-related calciuretic effects were independent of dietary calcium . Testing at 1 , 2 , 3 , 5 , and 7 wk showed no long-term adaptation in urinary acidity or urinary calcium excretion . High compared with low dietary protein decreased urinary deoxypyridinoline and increased serum insulin-like growth factor I without affecting parathyroid hormone , osteocalcin , bone-specific alkaline phosphatase , or tartrate-resistant acid phosphatase . CONCLUSIONS In healthy postmenopausal women , a moderate increase in dietary protein , from 10 % to 20 % of energy , slightly improved calcium absorption from a low-calcium diet , nearly compensating for a slight increase in urinary calcium excretion . Under practical dietary conditions , increased dietary protein from animal sources was not detrimental to calcium balance or short-term indicators of bone health",
"High dietary acid load ( DAL ) may be detrimental to bone mineral density ( BMD ) . The objectives of the study were to : ( 1 ) evaluate the cross-sectional relation between DAL and BMD ; and ( 2 ) determine whether calcium intake modifies this association . Men ( n = 1218 ) and women ( n = 907 ) aged ≥60 years were included from the National Health and Nutrition Examination Survey 2005 - 2008 . Nutrient intake from 2 , 24-hour recalls was used to calculate net endogenous acid production ( NEAP ) and potential renal acid load ( PRAL ) ( mEq/d ) . PRAL was calculated from dietary calcium ( PRALdiet ) and diet + supplemental calcium ( PRALtotal ) . Tests for linear trend in adjusted mean BMD of the hip and lumbar spine were performed across energy-adjusted NEAP and PRAL quartiles . Modification by calcium intake ( dietary or total ) above or below 800 mg/d was assessed by interaction terms . Overall , mean age was 69 ± 0.3 years . Among women , there was no association between NEAP and BMD . PRALdiet was positively associated with proximal femur BMD ( p trend = 0.04 ) . No associations were observed with PRALtotal at any BMD site ( p range , 0.38 - 0.82 ) . Among men , no significant associations were observed between BMD and NEAP or PRAL . However , an interaction between PRALdiet and calcium intake was observed with proximal femur BMD ( p = 0.08 ) . An inverse association between PRALdiet and proximal femur BMD was detected among men with dietary calcium ( p = 0.02 ) ; no associations were found among men with ≥800 mg/d ( p = 0.98 ) . A significant interaction with PRALtotal was not observed . In conclusion , when supplemental calcium is considered , there is no association between DAL and BMD among adults . Men with low dietary calcium showed an inverse relation with PRAL at the proximal femur ; in women no interaction was observed . This study highlights the importance of calcium intake in counteracting the adverse effect of DAL on bone health . Further research should determine the relation between DAL and change in BMD with very low calcium intake",
"Objective : Postmenopausal decreases in body composition , physical performance , and bone mass have been shown to be reversed by estrogen , but given the concerns regarding its use , women are looking for alternatives such as soy isoflavones . Most studies on the effects of soy on bone mineral density ( BMD ) in postmenopausal women have been short-term , that is , 3 to 6 months , and failed to provide conclusive evidence . There is no evidence of its effects on physical performance . The aim of the present study was to investigate the effects of soy plus isoflavones on BMD and physical performance in postmenopausal women . Methods : This was a 2-year r and omized controlled trial . A total of 203 healthy postmenopausal women were given either 25 g of soy protein without isoflavones , 25 g of soy protein with 90 mg of isoflavones , or 25 g of milk protein ( casein and whey ) as a control agent for 24 months . Women were followed every 6 months with BMD and physical performance measurements for 2 years . Primary analysis was intent-to-treat analysis . Analysis of variance , & khgr;2 and Fisher 's exact tests , and analysis of covariance were used . Results : There was a significant decrease in the BMD of the lumbar spine and femoral neck in those who completed the study in all groups . Soy isoflavones prevented major bone loss from baseline at the femoral trochanter with no between-group significance . Physical performance measurements decreased in all the groups . Conclusions : Twenty-five grams of soy protein with 90 mg of isoflavones has no added benefit in preventing bone loss or improving physical performance",
"Dietary protein increases urinary calcium losses and has been associated with higher rates of hip fracture in cross-cultural studies . However , the relation between protein and risk of osteoporotic bone fractures among individuals has not been examined in detail . In this prospect i ve study , usual dietary intake was measured in 1980 in a cohort of 85,900 women , aged 35 - 59 years , who were participants in the Nurses ' Health Study . A mailed food frequency question naire was used and incident hip ( n = 234 ) and distal forearm ( n = 1,628 ) fractures were identified by self-report during the following 12 years . Information on other factors related to osteoporosis , including obesity , use of postmenopausal estrogen , smoking , and physical activity , was collected on biennial question naires . Dietary measures were up date d in 1984 and 1986 . Protein was associated with an increased risk of forearm fracture ( relative risk ( RR ) = 1.22 , 95 % confidence interval ( Cl ) 1.04 - 1.43 , p for trend = 0.01 ) for women who consumed more than 95 g per day compared with those who consumed less than 68 g per day . A similar increase in risk was observed for animal protein , but no association was found for consumption of vegetable protein . Women who consumed five or more servings of red meat per week also had a significantly increased risk of forearm fracture ( RR = 1.23 , 95 % Cl 1.01 - 1.50 ) compared with women who ate red meat less than once per week . Recall of teenage diet did not reveal any increased risk of forearm fracture for women with higher consumption of animal protein or red meat during this earlier period of life . No association was observed between adult protein intake and the incidence of hip fractures , though power to assess this association was low",
"Background : Above-average dietary protein , as a single nutrient , improves musculoskeletal health . Evaluating the link between dietary protein and musculoskeletal health from a whole-diet perspective is important , as dietary guidelines focus on dietary patterns . Objective : We examined the prospect i ve association of novel dietary protein food clusters ( derived from established dietary pattern techniques ) with appendicular lean mass ( ALM ) , quadriceps strength ( QS ) , and bone mineral density ( BMD ) in 2986 men and women , aged 19 - 72 y , from the Framingham Third Generation Study . Design : Total protein intake was estimated by food-frequency question naire in 2002 - 2005 . A cluster analysis was used to classify participants into mutually exclusive groups , which were determined by using the percentage of contribution of food intake to overall protein intake . General linear modeling was used to 1 ) estimate the association between protein intake ( grams per day ) and BMD , ALM , appendicular lean mass normalized for height ( ALM/ht2 ) , and QS ( 2008 - 2011 ) and to 2 ) calculate adjusted least-squares mean outcomes across quartiles of protein ( grams per day ) and protein food clusters . Results : The mean ± SD age of subjects was 40 ± 9 y ; 82 % of participants met the Recommended Daily Allowance ( 0.8 g · kg body weight-1 · d-1 ) . The following 6 dietary protein food clusters were identified : fast food and full-fat dairy , fish , red meat , chicken , low-fat milk , and legumes . BMD was not different across quartiles of protein intake ( P-trend range = 0.32 - 0.82 ) ; but significant positive trends were observed for ALM , ALM/ht2 ( P significantly lower ALM , ALM/ht2 , and QS than did those in the higher quartiles of intake ( quartiles 2 - 4 ; ( P ranges = 0.0001 - 0.003 , 0.0007 - 0.003 , and 0.009 - 0.05 , respectively ) . However , there were no associations between protein clusters and any musculoskeletal outcome in adjusted models . Conclusions : In a protein-replete cohort of adults , dietary protein is associated with ALM and QS but not with BMD . In this study , dietary protein food patterns do not provide further insight into beneficial protein effects on muscle outcomes",
"This study was conducted to determine whether the markers of bone resorption , pyridinium cross-links of collagen , are sensitive to changes in dietary protein and calcium intake . Fifteen young healthy subjects ( 7 males and 8 females ) participated in three 5-d diet periods . Dietary intake during each dietary period consisted of : 1 ) low nitrogen and low calcium [ 0.49 + /- 0.11 g protein/ ( kg.d ) , 429 + /- 190 mg calcium/d ] ; 2 ) low nitrogen and high calcium [ 0.44 + /- 0.08 g protein/(kg.d ) , 1643 + /- 171 mg calcium/d ] ; and 3 ) a high nitrogen and high calcium [ 2.71 + /- 0.75 g protein/(kg.d ) , 1589 + /- 633 mg calcium/d ] diet , and this was compared with subjects ' baseline dietary intake [ 0.99 + /- 0.51 g protein/(kg.d ) , 589 + /- 152 mg calcium/d ] . The order of these diets was r and omly assigned . Twenty-four-hour and 3-h urine sample s were collected before and during each dietary period and were analyzed for pyridinium cross-links ( pyridinoline , deoxypyridinoline ) , nitrogen and creatinine . The rate of pyrdinium cross-link excretion did not vary with protein intake but was approximately 33 % lower ( P calcium intake is accompanied by a reduced rate of bone resorption and that this effect is independent of dietary protein intake",
"Dietary protein has been shown to increase urinary Ca excretion in r and omised controlled trials , and diets high in protein may have detrimental effects on bone health ; however , studies examining the relationship between dietary protein and bone health have conflicting results . In the present study , we examined the relationship between dietary protein ( total , animal and vegetable protein ) and lumbar spine trabecular volumetric bone mineral density ( vBMD ) among participants enrolled in the Multi-Ethnic Study of Atherosclerosis ( n 1658 ) . Protein intake was assessed using a FFQ obtained at baseline examination ( 2000 - 2 ) . Lumbar spine vBMD was measured using quantitative computed tomography ( 2002 - 5 ) , on average 3 years later . Multivariable linear and robust regression techniques were used to examine the associations between dietary protein and vBMD . Sex and race/ethnicity jointly modified the association of dietary protein with vBMD ( P for interaction = 0·03 ) . Among white women , higher vegetable protein intake was associated with higher vBMD ( P for trend = 0·03 ) , after adjustment for age , BMI , physical activity , alcohol consumption , current smoking , educational level , hormone therapy use , menopause and additional dietary factors . There were no consistently significant associations for total and animal protein intakes among white women or other sex and racial/ethnic groups . In conclusion , data from the present large , multi-ethnic , population -based study suggest that a higher level of protein intake , when substituted for fat , is not associated with poor bone health . Differences in the relationship between protein source and race/ethnicity of study population s may in part explain the inconsistent findings reported previously",
"BACKGROUND There is currently no consensus on the effect of dietary protein intake on the skeleton , but there is some indication that low calcium intakes adversely influence the effect of dietary protein on fracture risk . OBJECTIVE The objective of the present study was to determine whether supplemental calcium citrate malate and vitamin D influence any associations between protein intake and change in bone mineral density ( BMD ) . DESIGN Associations between protein intake and change in BMD were examined in 342 healthy men and women ( aged > or = 65 y ) who had completed a 3-y , r and omized , placebo-controlled trial of calcium and vitamin D supplementation . Protein intake was assessed at the midpoint of the study with the use of a food-frequency question naire and BMD was assessed every 6 mo by dual-energy X-ray absorptiometry . RESULTS The mean ( + /-SD ) protein intake of all subjects was 79.1 + /- 25.6 g/d and the mean total calcium intakes of the supplemented and placebo groups were 1346 + /- 358 and 871 + /- 413 mg/d , respectively . Higher protein intake was significantly associated with a favorable 3-y change in total-body BMD in the supplemented group ( in a model containing terms for age , sex , weight , total energy intake , and dietary calcium intake ) but not in the placebo group . The pattern of change in femoral neck BMD with increasing protein intake in the supplemented group was similar to that for the total body . CONCLUSION Increasing protein intake may have a favorable effect on change in BMD in elderly subjects supplemented with calcium citrate malate and vitamin",
"BACKGROUND No published studies have directly examined the effect of soy protein with isoflavones on bone or bone turnover in perimenopausal women . OBJECTIVE Our objective was to determine the effects of 24 wk of consumption of soy protein isolate with isoflavones ( 80.4 mg/d ) in attenuating bone loss during the menopausal transition . DESIGN Perimenopausal subjects were r and omly assigned , double blind , to treatment : isoflavone-rich soy ( SPI+ ; n = 24 ) , isoflavone-poor soy ( SPI- ; n = 24 ) , or whey ( control ; n = 21 ) protein . At baseline and posttreatment , lumbar spine bone mineral density ( BMD ) and bone mineral content ( BMC ) were measured by using dual-energy X-ray absorptiometry . At baseline , midtreatment , and posttreatment , urinary N:-telopeptides and serum bone-specific alkaline phosphatase ( BAP ) were measured . RESULTS The percentage change in lumbar spine BMD and BMC , respectively , did not differ from zero in the SPI+ or SPI- groups , but loss occurred in the control group ( -1.28 % , P : = 0.0041 ; -1.73 % , P : = 0.0037 ) . By regression analysis , SPI+ treatment had a positive effect on change in BMD ( 5.6 % ; P : = 0.023 ) and BMC ( 10.1 % ; P : = 0.0032 ) . Baseline BMD and BMC ( P : baseline body weight ( P : = 0.0036 ) and bone-free lean weight ( P : = 0.016 ) contributed positively to percentage change in BMD and BMC , respectively . Serum BAP posttreatment was negatively related to percentage change in BMD ( P : = 0.0016 ) and BMC ( P : = 0.019 ) . Contrast coding using analyses of covariance with BMD or BMC as the outcome showed that isoflavones , not soy protein , exerted the effect . CONCLUSION Soy isoflavones attenuated bone loss from the lumbar spine in perimenopausal women",
"BACKGROUND Different sources of dietary protein may have different effects on bone metabolism . Animal foods provide predominantly acid precursors , whereas protein in vegetable foods is accompanied by base precursors not found in animal foods . Imbalance between dietary acid and base precursors leads to a chronic net dietary acid load that may have adverse consequences on bone . OBJECTIVE We wanted to test the hypothesis that a high dietary ratio of animal to vegetable foods , quantified by protein content , increases bone loss and the risk of fracture . DESIGN This was a prospect i ve cohort study with a mean ( + /-SD ) of 7.0+/-1.5 y of follow-up of 1035 community-dwelling white women aged > 65 y. Protein intake was measured by using a food-frequency question naire and bone mineral density was measured by dual-energy X-ray absorptiometry . RESULTS Bone mineral density was not significantly associated with the ratio of animal to vegetable protein intake . Women with a high ratio had a higher rate of bone loss at the femoral neck than did those with a low ratio ( P = 0.02 ) and a greater risk of hip fracture ( relative risk = 3.7 , P = 0.04 ) . These associations were unaffected by adjustment for age , weight , estrogen use , tobacco use , exercise , total calcium intake , and total protein intake . CONCLUSIONS Elderly women with a high dietary ratio of animal to vegetable protein intake have more rapid femoral neck bone loss and a greater risk of hip fracture than do those with a low ratio . This suggests that an increase in vegetable protein intake and a decrease in animal protein intake may decrease bone loss and the risk of hip fracture . This possibility should be confirmed in other prospect i ve studies and tested in a r and omized trial",
"BACKGROUND Protein and alkalizing minerals are increasingly described as playing a major role in influencing bone status , not only in the elderly but also in children and adolescents . OBJECTIVE We examined whether the long-term dietary protein intake and diet net acid load are associated with bone status in children . DESIGN In a prospect i ve study design in 229 healthy children and adolescents aged 6 - 18 y , long-term dietary intakes were calculated from 3-d weighed dietary records that were collected yearly over the 4-y period before a one-time bone analysis . Dietary acid load was characterized as potential renal acid load ( PRAL ) by using an algorithm including dietary protein , phosphorus , magnesium , and potassium . Proximal forearm bone variables were measured by peripheral quantitative computed tomography . RESULTS After adjustment for age , sex , and energy intake and control for forearm muscularity , BMI , growth velocity , and pubertal development , we observed that long-term dietary protein intake was significantly positively associated with periosteal circumference ( P cortical area ( P bone mineral content ( P polar strength strain index ( P Children with a higher dietary PRAL had significantly less cortical area ( P bone mineral content ( P Long-term calcium intake had no significant effect on any bone variable . CONCLUSIONS Long-term dietary protein intake appears to act anabolically on diaphyseal bone strength during growth , and this may be negated , at least partly , if dietary PRAL is high , ie , if the intake of alkalizing minerals is low",
"In a 4-yr clinical trial , effect on single-photon absorptiometric measurements of arm bones of usual intakes of energy and 14 nutrients plus vitamin-mineral supplements was studied in 99 women , aged 35 - 65 , r and omly assigned to placebo ( NS ) or calcium-supplemented ( 1.5 g)(S ) groups . Cross-sectional analysis of initial bone measurements showed vitamin C ( r = 0.313 , p less than 0.05 ) and niacin ( r = 0.353 , p less than 0.01 ) correlated with ulna in postmenopausal subjects ( n = 67 ) . Longitudinal analysis of bone-change rates of postmenopausal subjects ( NS + S ) showed higher calcium intakes associated with lower loss rates of humerus bone-mineral content ( BMC ) ( r = 0.360 , p less than 0.01 ) . In postmenopausal NS but not S subjects , energy , protein , calcium , phosphorus , zinc , and folate correlate significantly with change in radius BMC ; high levels of intake correlated with slower loss ( p less than 0.05 ) . Several nutrients besides calcium are related to bone loss in women",
"BACKGROUND The role of dietary protein in bone metabolism is controversial . OBJECTIVE We investigated the associations of dietary protein intake with baseline bone mineral density ( BMD ) and the rate of bone loss over 3 y in postmenopausal elderly women . DESIGN Women aged 65 - 77 y ( n = 489 ) were enrolled in an osteoporosis intervention trial . We studied the associations of protein intake as a percentage of energy with baseline BMD and the rate of bone loss in 96 women in the placebo group ( n = 96 ) . We also examined the effect of the interaction of dietary calcium intake with protein intake on BMD . RESULTS In the cross-sectional study , a higher intake of protein was associated with higher BMD . BMD was significantly higher ( P 408 mg/d . There was no significant effect of protein intake on hip BMD . In the longitudinal study of the placebo group , there was no association between protein intake and the rate of bone loss . CONCLUSIONS The highest quartile of protein intake (: 72 g/d ) was associated with higher BMD in elderly women at baseline only when the calcium intake exceeded 408 mg/d . In the longitudinal study , no association was seen between protein intake and the rate of bone loss , perhaps because the sample size was too small or the follow-up period of 3 y was not long enough to detect changes",
"Calcium balance is decreased by an increased intake of purified proteins , although the effects of common dietary sources of protein ( like meat ) on calcium economy remain controversial . We compared the effects of several weeks of controlled high and low meat diets on body calcium retention , using sensitive radiotracer and whole body scintillation counting methodology . Healthy postmenopausal women ( n = 15 ) consumed diets with similar calcium content ( approximately 600 mg ) , but either low or high in meat ( 12 vs. 20 % of energy as protein ) for 8 wk each , in a r and omized crossover design . After 4 wk of equilibration of each diet , calcium retention was measured by extrinsically labeling the 2-d menu with (47)Ca , followed by whole body scintillation counting for 28 d. Urinary and blood indicators of bone metabolism were also determined for each diet . Calcium retention was not different during the high and low meat dietary periods ( d 28 , mean + /- pooled SD : 17.1 and 15.6 % , + /-0.6 % , respectively ; P = 0.09 ) . An initially higher renal acid excretion in subjects consuming the high meat compared with the low meat diet decreased significantly with time . The diets did not affect urinary calcium loss or indicators of bone metabolism . In conclusion , under controlled conditions , a high meat compared with a low meat diet for 8 wk did not affect calcium retention or biomarkers of bone metabolism in healthy postmenopausal women . Calcium retention is not reduced when subjects consume a high protein diet from common dietary sources such as meat",
"BACKGROUND Soy foods contain several components ( isoflavones and amino acids ) that potentially affect bone . Few long-term , large clinical trials of soy as a means of improving bone mineral density ( BMD ) in late postmenopausal women have been conducted . OBJECTIVE Our goal was to evaluate the long-term effect of dietary soy protein and /or soy isoflavone consumption on skeletal health in late postmenopausal women . DESIGN We conducted a r and omized , double-blind , placebo-controlled clinical trial in 131 healthy ambulatory women aged > 60 y. Ninety-seven women completed the trial . After a 1-mo baseline period , subjects were r and omly assigned into 1 of 4 intervention groups : soy protein ( 18 g ) + isoflavone tablets ( 105 mg isoflavone aglycone equivalents ) , soy protein + placebo tablets , control protein + isoflavone tablets , and control protein + placebo tablets . RESULTS Consumption of protein powder and isoflavone pills did not differ between groups , and compliance with the study powder and pills was 80 - 90 % . No significant differences in BMD were observed between groups from baseline to 1 y after the intervention or in BMD change between equol and non-equol producers . However , there were significant negative correlations between total dietary protein ( per kg ) and markers of bone turnover ( P soy protein and isoflavones ( either alone or together ) did not affect BMD , they should not be considered as effective interventions for preserving skeletal health in older women . The negative correlation between dietary protein and bone turnover suggests that increasing protein intakes may suppress skeletal turnover . This trial was registered at Clinical Trials.gov as NCT00668447",
"Abstract : Quantitative ultrasound ( QUS ) assessment of bone is a strong predictor of hip fractures and is currently an FDA -approved tool to identify women at risk of osteoporosis . However , few studies have investigated the lifestyle and genetic correlates of QUS in women . This study investigated the cross-sectional associates of several lifestyle , demographic and genetic factors with calcaneal QUS parameters ( broadb and ultrasound attenuation ( BUA ) and speed of sound ( SOS ) ) in 393 women aged 45–53 years . Leisure-time and historical physical activity , dietary calcium and protein , body composition , vitamin D receptor genotypes , menopause status , other health behaviors , calcaneal QUS parameters and bone mineral density ( BMD ) were assessed at a single clinic visit . Lean mass , recent physical activity and African-American race were the strongest correlates of SOS whereas dietary protein , calcium and recent physical activity were the strongest correlates of BUA . These predictors explained 13 % and 6 % of the variance in SOS and BUA , respectively . Smoking , alcohol intake , education , hormone replacement therapy , calcium and vitamin D supplements , historical physical activity and vitamin D receptor genotypes were not significantly associated with BUA or SOS . Lean body mass and premenopausal status were the strongest correlates of lumbar BMD whereas lean body mass , physical activity , African-American race and body mass index were significantly related to femoral neck BMD . Physical activity remained predictive of SOS after controlling for lumbar BMD . The spectrum and magnitude of risk factors for SOS and BUA , including lean body mass , physical activity , race , protein and calcium intake , parallel previously observed predictors of BMD",
"Recent reports suggest that soy protein may reduce the risk of osteoporosis in peri- and postmenopausal women . The objective of this study was to examine whether soy supplementation exerts beneficial effects on serum and urinary biomarkers of bone metabolism in postmenopausal women , regardless of whether or not they are on hormone replacement therapy ( HRT ) . A total of 71 women were r and omly assigned to either soy protein ( SP ) or milk-based protein ( MBP ) , 40 g daily for 3 months , in a double-blind parallel design . Forty-two women completed the study ( 20 on SP and 22 on MBP ) . Overall , both protein supplements positively influenced serum IGF-I , known to correlate with bone formation . However , SP had a more pronounced effect on IGF-I than MBP . Urinary deoxypyridinoline ( Dpd ) excretion , a specific biomarker of bone resorption , was significantly reduced by SP , but not by MBP when all women were included . Furthermore , women on MBP experienced a 33 % increase in urinary calcium excretion , whereas SP did not have such an effect . To evaluate whether SP affects women differently on the basis of their HRT status , data from women on HRT ( n = 22 ) and those not on HRT ( n = 20 ) were analyzed separately . The sub analysis of the data indicated that SP had the greatest impact on serum IGF-I ( an increase of 97 % ) in the women not on HRT . The changes in urinary Dpd due to SP were only observed in women not on HRT , indicating that the overall decrease in Dpd occurred with SP in the absence of HRT . These results indicate that soy protein may positively influence bone and calcium homeostasis in postmenopausal women , particularly those not on HRT",
"Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load ( PRAL ) diet on calcium ( Ca ) absorption and retention and markers of bone metabolism . In a r and omized crossover design , 16 postmenopausal women consumed 2 diets : 1 with low protein and low PRAL ( LPLP ; total protein : 61 g/d ; PRAL : -48 mEq/d ) and 1 with high protein and high PRAL ( HPHP ; total protein : 118 g/d ; PRAL : 33 mEq/d ) for 7 wk each separated by a 1-wk break . Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca . Compared with the LPLP diet , the HPHP diet increased participants ' serum IGF-I concentrations ( P decreased serum intact PTH concentrations ( P increased fractional (47)Ca absorption ( mean ± pooled SD : 22.3 vs. 26.5 ± 5.4 % ; P and urinary Ca excretion ( 156 vs. 203 ± 63 mg/d ; P = 0.005 ) . The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods ( 55 vs. 28 ± 51 mg/d ) . The dietary treatments did not affect other markers of bone metabolism . In summary , a diet high in protein and PRAL increases the fractional absorption of dietary Ca , which partially compensates for increased urinary Ca , in postmenopausal women . The increased IGF-I and decreased PTH concentrations in serum , with no change in biomarkers of bone resorption or formation , indicate a high-protein diet has no adverse effects on bone health",
"Abstract Aim : The aim of the study was to investigate the influence of dietary intake of commercial hydrolyzed collagen ( Gelatine Royal ® ) on bone remodeling in pre-pubertal children . Methods : A r and omized double-blind study was carried out in 60 children ( 9.42±1.31 years ) divided into three groups according to the amount of partially hydrolyzed collagen taken daily for 4 months : placebo ( G-I , n=18 ) , collagen ( G-II , n=20 ) and collagen+calcium ( G-III , n=22 ) groups . Analyses of the following biochemical markers were carried out : total and bone alkaline phosphatase ( tALP and bALP ) , osteocalcin , tartrate-resistant acid phosphatase ( TRAP ) , type I collagen carboxy-terminal telopeptide , lipids , calcium , 25-hydroxyvitamin D , insulin-like growth factor-1 ( IGF-1 ) , thyroid-stimulating hormone , free thyroxin and intact parathormone . Results : There was a significantly greater increase in serum IGF-1 in G-III than in G-II ( p in plasma tALP in G-III than in G-I ( p ) . Serum bALP behavior significantly ( p decrease ) . Plasma TRAP behavior significantly differed between G-II and G-I ( p<0.01 ) and between G-III and G-II ( p<0.05 ) . Conclusion : Daily dietary intake of hydrolyzed collagen seems to have a potential role in enhancing bone remodeling at key stages of growth and development",
"Objective : To determine the effect of high-protein diets , which have recently been promoted for their health benefits , on urinary calcium losses and bone turnover in older subjects . Design : R and omized controlled cross-over study . Setting : Teaching hospital and university . Subjects : Twenty hyperlipidemic men and postmenopausal women ( age 56±2 y ) completed the study . Interventions : One-month test and control phases during which subjects consumed equi-energy metabolic diets high in calcium ( 1578 and 1593 mg/day , respectively ) . On the test diet 11 % of total dietary energy from starch in the control bread was replaced by protein ( wheat gluten ) , result ing in 27 % of energy from protein on the test diet vs 16 % on the control diet . Main outcome measure : Urinary calcium excretion . Results : Compared with the control diet , at week 4 , the test diet increased mean ( ±s.e.m . ) 24 h urinary output of calcium ( 139±15 vs 227±21 mg , P=0.004 ) . The treatment difference in urinary calcium loss correlated with the serum anion gap as a marker of metabolic acid production ( r=0.57 , P=0.011 ) . Serum calcium levels were marginally lower 2.41±0.02 vs 2.38±0.02 mmol/l ( P=0.075 ) , but there was no significant treatment difference in calcium balance , possibly related to the high background calcium intake on both diets . Conclusions : In the presence of high dietary calcium intakes the vegetable protein gluten does not appear to have a negative effect on calcium balance despite increased urinary calcium loss . Sponsorship : The University-Industry Research Partnership Program of the Natural Sciences and Engineering Research Council of Canada , Loblaw Br and s Limited , Toronto , ON , and Kraft Canada Inc. Don Mills , ON . DJAJ is funded as a Canada Research Chair in Metabolism and Nutrition at the University of Toronto by the Federal Government of Canada , Ottawa",
"Background / Objectives : The effect of vegan diet on bone loss has not been studied . The aim of this study was to examine the association between veganism and bone loss in postmenopausal women . Subjects/ Methods : The study was design ed as a prospect i ve longitudinal investigation with 210 women , including 105 vegans and 105 omnivores . Femoral neck ( FN ) bone mineral density ( BMD ) was measured in 2008 and 2010 by dual-energy X-ray absorptiometry ( Hologic QDR4500 ) . The incidence of vertebral fracture was ascertained by X-ray report . Serum levels of C-terminal telopeptide of type I collagen ( βCTX ) and N-terminal propeptide of type I procollagen ( PINP ) were measured by Roche Elecsys assays . Serum concentration of 25-hydroxyvitamin D and parathyroid hormone were measured by electrochemiluminescence . Results : Among the 210 women who initially participated in the study in 2008 , 181 women had completed the study and 29 women were lost to follow-up . The rate of loss in FN BMD was −1.91±3.45%/year in omnivores and −0.86±3.81%/year ( P=0.08 ) in vegans . Lower body weight , higher intakes of animal protein and lipid , and corticosteroid use were associated with greater rate of bone loss . The 2-year incidence of fracture was 5.7 % ( n=5/88 ) in vegans , which was not significantly different from omnivores ( 5.4 % , n=6/93 ) . There were no significant differences in βCTX and PINP between vegans and omnivores . The prevalence of vitamin D insufficiency in vegans was higher than in omnivores ( 73 % versus 46 % ; P=0.0003 ) . Conclusions : Vegan diet did not have adverse effect on bone loss and fracture . Corticosteroid use and high intakes of animal protein and animal lipid were negatively associated with bone loss ",
"Excess dietary proteins and \" acid ash \" diets have been suspected to increase the risk of osteoporosis , but experimental and epidemiological evidence is mixed . We aim ed to determine whether the association between protein intake and the overall acid-base equilibrium of the diet ( as renal net acid excretion [ RNAE ] estimate ) and fracture risk vary according to calcium intake . During an average of 8.37 + /- 1.73 yr of follow-up , 2408 women reported a fracture ( excluding high-impact trauma ) among 36,217 postmenopausal women from the E3N prospect i ve study . We used Cox regression models to study the interaction between calcium and , respectively , proteins and RNAE , from the 1993 dietary question naire for fracture risk determination , adjusting for potential confounders . There was no overall association between fracture risk and total protein or RNAE . However , in the lowest quartile of calcium ( fracture risk ( RR = 1.51 for highest versus lowest quartile ; 95 % CI , 1.17 - 1.94 ) . An increasing fracture risk with increasing animal protein intake was also observed ( trend , p interaction for fracture risk was observed between RNAE and calcium . In this Western population of postmenopausal women with normal to high protein intake and fairly high calcium intake , there was no overall association between total protein or RNAE and fracture risk . However , there was some evidence that high protein-high acid ash diets were associated with an increased risk of fracture when calcium intake was low ( < 400 mg/1000 kcal )",
"Summary This cross-sectional study showed that , although vegans had lower dietary calcium and protein intakes than omnivores , veganism did not have adverse effect on bone mineral density and did not alter body composition . Introduction Whether a lifelong vegetarian diet has any negative effect on bone health is a contentious issue . We undertook this study to examine the association between lifelong vegetarian diet and bone mineral density and body composition in a group of postmenopausal women . Methods One hundred and five Mahayana Buddhist nuns and 105 omnivorous women ( average age = 62 , range = 50–85 ) were r and omly sample d from monasteries in Ho Chi Minh City and invited to participate in the study . By religious rule , the nuns do not eat meat or seafood ( i.e. , vegans ) . Bone mineral density ( BMD ) at the lumbar spine ( LS ) , femoral neck ( FN ) , and whole body ( WB ) was measured by DXA ( Hologic QDR 4500 ) . Lean mass , fat mass , and percent fat mass were also obtained from the DXA whole body scan . Dietary calcium and protein intakes were estimated from a vali date d food frequency question naire . Results There was no significant difference between vegans and omnivores in LSBMD ( 0.74 ± 0.14 vs. 0.77 ± 0.14 g/cm2 ; mean ± SD ; P = 0.18 ) , FNBMD ( 0.62 ± 0.11 vs. 0.63 ± 0.11 g/cm2 ; P = 0.35 ) , WBBMD ( 0.88 ± 0.11 vs. 0.90 ± 0.12 g/cm2 ; P = 0.31 ) , lean mass ( 32 ± 5 vs. 33 ± 4 kg ; P = 0.47 ) , and fat mass ( 19 ± 5 vs. 19 ± 5 kg ; P = 0.77 ) either before or after adjusting for age . The prevalence of osteoporosis ( T scores ≤ −2.5 ) at the femoral neck in vegans and omnivores was 17.1 % and 14.3 % ( P = 0.57 ) , respectively . The median intake of dietary calcium was lower in vegans compared to omnivores ( 330 ± 205 vs. 682 ± 417 mg/day , P and BMD . Further analysis suggested that whole body BMD , but not lumbar spine or femoral neck BMD , was positively correlated with the ratio of animal protein to vegetable protein . Conclusion These results suggest that , although vegans have much lower intakes of dietary calcium and protein than omnivores , veganism does not have adverse effect on bone mineral density and does not alter body composition",
"CONTEXT It has been assumed that the increase in urine calcium ( Ca ) that accompanies an increase in dietary protein was due to increased bone resorption . However , studies using stable Ca isotopes have found that dietary protein increases Ca absorption without increasing bone resorption . OBJECTIVE The objective of the study was to investigate the impact of a moderately high protein diet on bone mineral density ( BMD ) . DESIGN This was a r and omized , double-blind , placebo-controlled trial of protein supplementation daily for 18 months . SETTING The study was conducted at two institutional research centers . PARTICIPANTS Two hundred eight older women and men with a body mass index between 19 and 32 kg/m(2 ) and a self-reported protein intake between 0.6 and 1.0 g/kg participated in the study . INTERVENTION Subjects were asked to incorporate either a 45-g whey protein or isocaloric maltodextrin supplement into their usual diet for 18 months . MAIN OUTCOME MEASURE BMD by dual-energy x-ray absorptiometry , body composition , and markers of skeletal and mineral metabolism were measured at baseline and at 9 and 18 months . RESULTS There were no significant differences between groups for changes in L-spine BMD ( primary outcome ) or the other skeletal sites of interest . Truncal lean mass was significantly higher in the protein group at 18 months ( P = .048 ) . C-terminal telopeptide ( P = .0414 ) , IGF-1 ( P = .0054 ) , and urinary urea ( P estimated glomerular filtration rate at 18 months . CONCLUSION Our data suggest that protein supplementation above the recommended dietary allowance ( 0.8 g/kg ) may preserve fat-free mass without adversely affecting skeletal health or renal function in healthy older adults",
"Abstract : Lifestyle factors , such as diet , are believed to be involved in modifying bone health , although the results remain controversial , particularly in children and adolescents . The objective of the study was to identify associations between dietary factors and whole body bone measurements in 10-year-old children . The study was a cross-sectional analysis of a r and om sample of 105 healthy Danish children , aged 10 years ( 9.97 ± 0.09 ) . Whole body bone mineral content ( BMC ) and bone area ( BA ) were determined by dual-energy X-ray absorptiometry . The influence of diet ( 7 day food records ) on BMC and BA were examined in bi- and multivariate analyses . The mean intakes of calcium , protein , phosphorus and sodium were 1226 mg , 78 g , 1523 mg and 3.3 g , respectively . In bivariate analyses , BMC and BA were strongly positively correlated with height ( p . BMC was adjusted for size by including BA , height and weight in the multiple linear regression , and BA was adjusted for size by including height and weight in the multiple linear regression . In multivariate analyses , size-adjusted BMC was positively associated with calcium intake ( p = 0.02 ) . Size-adjusted BA was positively associated with dietary protein ( p = 0.003 ) , and negatively associated with intakes of sodium ( p = 0.048 ) and phosphorus ( p = 0.01 ) . In conclusion , calcium intake was positively associated with bone mineralization . There was a positive association between protein and BA , while for phosphorus and sodium the association was negative . The findings suggest that in addition to calcium , the intake of other nutrients influences bone development in prepubertal children",
"OBJECTIVE The risk factors for fractures are incompletely understood . An outst and ing question concerns the optimal amount of dietary calcium needed to minimise the risk of fracture . DESIGN We examined the associations of dietary calcium and other nutrients with self-reported fracture risk in a prospect i ve cohort study . Nutrient intakes were estimated using a semi-quantitative food-frequency question naire administered at recruitment . SETTING The UK . PARTICIPANTS A total of 26 749 women and 7947 men aged 20 - 89 years . RESULTS Over an average of 5.2 years of follow-up , 1555 women and 343 men reported one or more fractures , 72 % of these result ing from a fall . Among women , fracture risk was higher at lower calcium intakes , with a relative risk of 1.75 ( 95 % confidence interval ( CI ) 1.33 - 2.29 ) among women with a calcium intake of dietary calcium with fracture risk was stronger among women aged under 50 years at recruitment than among women aged 50 and above . Dietary calcium intake was not associated with fracture risk in men . Fracture risk was not related to the dietary intake of any other nutrient examined . CONCLUSION In this population , women with a low dietary calcium intake had an increased risk of bone fracture , and this association was more marked among younger women than among older women",
"Introduction : Investigations in rodents as well as in vitro experiments have suggested an anabolic influence of specific collagen peptides ( SCP ) on bone formation and bone mineral density ( BMD ) . The goal of the study was to investigate the effect of 12-month daily oral administration of 5 g SCP vs. placebo ( CG : control group ) on BMD in postmenopausal women with primary , age-related reduction in BMD . Methods : 131 women were enrolled in this r and omized , placebo-controlled double-blinded investigation . The primary endpoint was the change in BMD of the femoral neck and the spine after 12 months . In addition , plasma levels of bone markers — amino-terminal propeptide of type I collagen ( P1NP ) and C-telopeptide of type I collagen ( CTX 1)—were analysed . Results : A total of 102 women completed the study , but all subjects were included in the intention-to-treat ( ITT ) analysis ( age 64.3 ± 7.2 years ; Body Mass Index , BMI 23.6 ± 3.6 kg/m2 ; T-score spine −2.4 ± 0.6 ; T-score femoral neck −1.4 ± 0.5 ) . In the SCP group ( n = 66 ) , BMD of the spine and of the femoral neck increased significantly compared to the control group ( n = 65 ) ( T-score spine : SCP + 0.1 ± 0.26 ; CG −0.03 ± 0.18 ; ANCOVA p = 0.030 ; T-score femoral neck : SCP + 0.09 ± 0.24 ; CG −0.01 ± 0.19 ; ANCOVA p = 0.003 ) . P1NP increased significantly in the SCP group ( p = 0.007 ) , whereas CTX 1 increased significantly in the control group ( p = 0.011 ) . Conclusions : These data demonstrate that the intake of SCP increased BMD in postmenopausal women with primary , age-related reduction of BMD . In addition , SCP supplementation was associated with a favorable shift in bone markers , indicating increased bone formation and reduced bone degradation",
"Malnutrition has been often suggested as contributing to both the high incidence of hip fracture in elderly people and its complications . In a recent prospect i ve controlled r and omized study , the clinical outcome of elderly patients with osteoporotic fracture of the proximal femur ( hip fracture ) improved by giving a simple oral dietary supplement . This study , however , did not prove that protein was responsible for the clinical improvement since the supplement also contained vitamins and minerals . We addressed this question by comparing the clinical outcome and bone mineral density ( BMD ) changes in elderly patients with hip fracture , receiving two different dietary supplements with different protein contents . Sixty-two patients ( mean age 82 ) admitted into the orthopedic ward for fracture of the proximal femur were r and omized into two groups . One group ( n = 33 ) received 250 ml/day of an oral nutritional supplement containing protein ( 20.4 g ) , mineral salts ( Ca : 0.525 g ) and vitamins A = 750 IU ; D3 = 25 IU ) for a mean of 38 days . A control group ( n = 29 ) received the same supplement dose , but with no protein , for the same period of time . The clinical course was significantly better in the group receiving protein , with 79 % having a favorable course as compared to 36 % ( p less than 0.02 ) in the control group during the stay in the recovery hospital . The rate of complications and deaths was also significantly lower in the protein-supplemented vs the control group ( 52 vs 80 % , p less than 0.05 ) 7 months after hip fracture . The median hospital stay was significantly lower in the protein-supplemented group ( 69 vs 102 days , p less than 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS",
"This prospect i ve population -based study assessed predictors of hip fracture risk in white men . Participants were members of the Epidemiologic Follow-up Study cohort of the First National Health and Nutrition Examination Survey , a nationally representative sample of noninstitutionalized civilians who were followed for a maximum of 22 years . A cohort of 2879 white men ( 2249 in the nutrition and weight-loss sub sample , 1437 in the bone density sub sample ) aged 45 - 74 years at baseline ( 1971 - 1975 ) were observed through 1992 . Ninety-four percent of the original cohort were successfully traced . Hospital records and death certificates were used to identify a total of 71 hip fracture cases ( 61 in the nutrition and weight-loss sub sample , 26 in the bone-density sub sample ) . Among the factors evaluated were age at baseline , previous fractures other than hip , body mass index , smoking status , alcohol consumption , nonrecreational physical activity , weight loss from maximum , calcium intake , number of calories , protein consumption , chronic disease prevalence , and phalangeal bone density . The risk adjusted relative risk ( RR ) of hip fracture was significantly associated with presence of one or more chronic conditions ( RR = 1.91 , 95 % confidence interval [ CI ] = 1.19 - 3.06 ) , weight loss from maximum > or = 10 % ( RR = 2.27 , 95 % CI 1.13 - 4.59 ) , and 1 SD change in phalangeal bone density ( RR = 1.73 , 95 % CI 1.11 - 2.68 ) . No other variables were significantly related to hip fracture risk . Although based on a small number of cases , this is one of the first prospect i ve studies to relate weight loss and bone density to hip fracture risk in men",
"Summary Association between dietary protein and fracture risk is unclear . We examined association between energy-adjusted protein intake and hip fracture risk in elders . The risk of hip fracture was reduced in upper quartiles of protein intake when compared with lowest quartile . Introduction Studies of the association between dietary protein intake and hip fracture risk are conflicting . Therefore , we examined protein intake and hip fracture risk in a population -based group of elderly men and women . Methods Five hundred seventy-six women and 370 men from the Framingham Osteoporosis Study with no previous history of hip fracture completed Food Frequency Question naires . Energy-adjusted protein intake was evaluated as a continuous variable and as quartiles . Incidence rates and hazard ratios were calculated , adjusting for age , BMI , sex , and energy intake . Results Among 946 participants ( mean age 75 years ) , mean protein intake was found to be 68 gm/d . Increased protein intake was associated with a decreased risk of hip fracture compared to those in the lowest quartile of protein intake ( Q2 HR = 0.70 , Q3 HR = 0.56 , and Q4 HR = 0.63 ; all p values ≥ 0.044 ) , p for trend was 0.07 . When a threshold effect was considered ( Q2–4 vs Q1 ) , intakes in the higher quartiles combined were associated with a significantly lower risk for hip fracture ( HR = 0.63 ; p = 0.04 ) . Conclusion Our results are consistent with reduced risk of hip fracture with higher dietary protein intake . Larger prospect i ve studies are needed to confirm and extend this finding in elderly men and women",
"ABSTRACT A soy protein – based supplement may optimize bone health , support physical growth , and stimulate bone formation . This study aim ed to assess the effect of a daily soy protein supplement ( SPS ) on nutritional status , bone formation markers , lipid profile , and daily energy and macronutrient intake in children . One hundred seven participants ( 62 girls ) , ages 2 to 9 , started the study and were r and omly assigned to lunch fruit juice with ( n = 57 , intervention group ) or without ( n = 50 , control group ) addition of 45 g ( 230 Kcal ) of a commercial SPS during 12 months ; 84 children ( 51 girls , 33 boys ) completed the study ( 45 and 39 intervention and control , respectively ) . Nutritional assessment included anthropometry and nutrient intakes ; initial and final blood sample s were taken ; insulin-like growth factor-I ( IGF-I ) , osteocalcin , bone specific alkaline phosphatase ( BAP ) , insulin-like growth factor binding protein-3 ( IGFBP-3 ) , cholesterol , triglycerides , low-density lipoprotein ( LDL ) , and high-density lipoprotein ( HDL ) were analyzed . Statistically significant changes ( p body mass index and weight for age Z scores were observed between groups while changes in body composition were not . Changes in energy , total protein , and carbohydrate intakes were significantly higher in the intervention group ( p Calorie intake changes were statistically significant between groups ( p BAP decreased in both groups , with values within normal ranges . Osteocalcin , IGFBP-3 , and lipid profile were not different between groups . IGF-I levels and IGF/IGFBP-3 ratio increased significantly in both groups . In conclusion , changes in macronutrient and energy intake and nutritional status in the intervention group compared to control group may ensure harmonious and adequate bone health and development",
"Background / Aims : The role of dietary protein in bone health is controversial . The objective of the present study was to examine the association between protein intake , dietary calcium , and bone structure measured by broadb and ultrasound attenuation ( BUA ) . Methods : Our analysis includes 8,178 female study participants of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) Potsdam Study . Ultrasound bone measurements were performed on the right os calcis , and BUA was determined . Dietary intake was assessed by a st and ardized food frequency question naire . We applied linear regression models to estimate the association between dietary protein and BUA . Results : After multivariate adjustment , high intake of animal protein was associated with decreased BUA values ( β = –0.03 ; p = 0.010 ) whereas high vegetable protein intake was related to an increased BUA ( β = 0.11 ; p = 0.007 ) . The effect of dietary animal protein on BUA was modified by calcium intake . Conclusion : High consumption of protein from animal origin may be unfavourable , whereas a higher vegetable protein intake may be beneficial for bone health . Our results strengthen the hypothesis that high calcium intake combined with adequate protein intake based on a high ratio of vegetable to animal protein may be protective against osteoporosis",
"Summary This 30-month study investigating bone change and its determinants in 438 perimenopausal Chinese women revealed that the fastest bone loss occurred in women undergoing menopausal transition but maintenance of body weight and physical fitness were beneficial for bone health . Soy protein intake also seemed to exert a protective effect . Introduction This 30-month follow-up study aims to investigate change in bone mineral density and its determinants in Hong Kong Chinese perimenopausal women . Methods Four hundred and thirty-eight women aged 45 to 55 years were recruited through r and om telephone dialing and primary care clinic . Bone mass , body composition , lifestyle measurements were obtained at baseline and at 9- , 18- and 30-month follow-ups . Univariate and stepwise multiple regression analyses were performed with the regression coefficients of BMD/C ( derived from baseline and follow-up measurements ) as the outcome variables . Menopausal status was classified as pre- or postmenopausal or transitional . Results Menopausal status was the strongest determinant of bone changes . An annual bone loss of about 0.5 % was observed among premenopausal , 2 % to 2.5 % among transitional , and about 1.5 % in postmenopausal women . Multiple regression analyses , revealed that a positive regression slope of body weight was protective for follow-up bone loss at all sites . Number of pregnancy , soy protein intake and walking were protective for total body BMC . Higher baseline LM was also protective for neck of femur BMD . Conclusion Maintenance of body weight and physical fitness were observed to have a protective effect on for bone loss in Chinese perimenopausal women",
"CONTEXT Protein is an essential component of muscle and bone . However , the acidic byproducts of protein metabolism may have a negative impact on the musculoskeletal system , particularly in older individuals with declining renal function . OBJECTIVE We sought to determine whether adding an alkaline salt , potassium bicarbonate ( KHCO3 ) , allows protein to have a more favorable net impact on intermediary indices of muscle and bone conservation than it does in the usual acidic environment . DESIGN We conducted a 41-d r and omized , placebo-controlled , double-blind study of KHCO3 or placebo with a 16-d phase-in and two successive 10-d metabolic diets containing low ( 0.5 g/kg ) or high ( 1.5 g/kg ) protein in r and om order with a 5-d washout between diets . SETTING The study was conducted in a metabolic research unit . PARTICIPANTS Nineteen healthy subjects ages 54 - 82 yr participated . INTERVENTION KHCO3 ( up to 90 mmol/d ) or placebo was administered for 41 d. MAIN OUTCOME MEASURES We measured 24-h urinary nitrogen excretion , IGF-I , 24-h urinary calcium excretion , and fractional calcium absorption . RESULTS KHCO3 reduced the rise in urinary nitrogen excretion that accompanied an increase in protein intake ( P = 0.015 ) and was associated with higher IGF-I levels on the low-protein diet ( P = 0.027 ) with a similar trend on the high-protein diet ( P = 0.050 ) . KHCO3 was also associated with higher fractional calcium absorption on the low-protein diet ( P = 0.041 ) with a similar trend on the high-protein diet ( P = 0.064 ) . CONCLUSIONS In older adults , KHCO3 attenuates the protein-induced rise in urinary nitrogen excretion , and this may be mediated by IGF-I. KHCO3 may also promote calcium absorption independent of the dietary protein content",
"UNLABELLED The role of protein intake in osteoporosis is unclear . In a case-control study in Utah ( n = 2501 ) , increasing level of protein intake was associated with a decreased risk of hip fracture in men and women 50 - 69 years of age but not in those 70 - 89 years of age . Protein intake may be important for optimal bone health . INTRODUCTION Protein is an important component of bone , but the role of dietary protein intake in osteoporosis and fracture risk remains controversial . MATERIAL AND METHODS The role of dietary protein intake in osteoporotic hip fracture was evaluated in a statewide case-control study in Utah . Patients , 50 - 89 years of age , with hip fracture ( cases ) were ascertained through surveillance of 18 Utah hospitals during 1997 - 2001 . Age- and gender-matched controls were r and omly selected . Participants were interviewed in their place of residence , and diet was assessed using a picture-sort food frequency question naire previously reported to give a useful measure of usual dietary intake in the elderly Utah population . The association between protein intake and risk of hip fracture was examined across quartiles of protein intake and stratified by age group for 1167 cases ( 831 women , 336 men ) and 1334 controls ( 885 women , 449 men ) . RESULTS In logistic regression analyses that controlled for gender , body mass index , smoking status , alcohol use , calcium , vitamin D , potassium , physical activity , and estrogen use in women , the odds ratios ( OR ) of hip fracture decreased across increasing quartiles of total protein intake for participants 50 - 69 years of age ( OR : 1.0 [ reference ] ; 0.51 [ 95 % CI : 0.30 - 0.87 ] ; 0.53 [ 0.31 - 0.89 ] ; 0.35 [ 0.21 - 0.59 ] ; p calcium and potassium intake did not differ appreciably from the results presented above . CONCLUSION Higher total protein intake was associated with a reduced risk of hip fracture in men and women 50 - 69 years of age but not in men and women 70 - 89 years of age . The association between dietary protein intake and risk of hip fracture may be modified by age . Our study supports the hypothesis that adequate dietary protein is important for optimal bone health in the elderly 50 - 69 years of age",
"objective To assess the effect of a dietary soy protein supplement containing isoflavones on lipids and indices of bone resorption in postmenopausal women",
"Objective : The aim of this study was to assess the independent and additive effects of soy protein isolate ( SPI ) and moderate-intensity exercise ( EX ) on bone turnover and bone mineral density ( BMD ) . Design : This study used a placebo-controlled , double-blind ( soy ) , r and omized 2 ( SPI vs milk protein isolate [ MPI ] ) × 2 ( EX vs no EX ) design . Sixty-one postmenopausal women were r and omized , and 43 ( 62 ± 5 y ) completed the 9-month intervention ( SPI , n = 10 ; MPI , n = 12 ; SPI + EX , n = 11 ; MPI + EX , n = 10 ) . Serum C-terminal cross-linked telopeptides of type I collagen and serum bone-specific alkaline phosphatase were measured as markers of bone resorption and formation , respectively . BMD was measured by dual-energy x-ray absorptiometry . Results : At 9 months , SPI reduced serum C-terminal cross-linked telopeptides ( −13.3 % ± 15.3 % vs −1.5 % ± 21.0 % ; P = 0.02 ) and serum bone-specific alkaline phosphatase ( −4.7 % ± 14.7 % vs 6.5 % ± 17.7 % ; P = 0.02 ) compared to milk protein isolate . EX attenuated the reduction in serum C-terminal cross-linked telopeptides ( −1.9 % ± 21.6 % vs −12.4 % ± 15.3 % ; P = 0.04 ) ; however , no EX effects were apparent in serum bone-specific alkaline phosphatase at 9 months ( 2.8 % ± 16.1 % vs −1.0 % ± 18.3 % ; P = 0.28 ) . Neither SPI nor EX affected BMD at any site ; however , change in BMD was related to change in fat mass ( r = 0.40 , P In postmenopausal women ( 1 ) SPI reduces bone turnover with no impact on BMD over 9 months ; ( 2 ) moderate-intensity endurance exercise training did not favorably alter bone turnover and had no impact on BMD ; and ( 3 ) there were no additive effects of soy and exercise on bone turnover or BMD",
"Objective To examine the effects of food groups and dietary nutrients on bone loss in elderly Chinese population . Design Prospect i ve cohort study . Setting : A longitudinal study started at 2001 in Hong Kong . Participants 1225 Chinese men and 992 women aged 65 years and over in the community . Methods Daily intake of food groups and dietary nutrients at baseline was assessed by a food frequency question naire . Nutrient intake was adjusted for energy intake by residual method . Linear regression was used to examine the association of BMD change and food group or energy-adjusted nutrient intake with adjustment for demographic , anthropometric , lifestyle factors , and daily energy intake ( for food group only ) . Results Higher fish intake was associated with smaller bone loss in hip ( B=−0.611 , p=0.004 ) and femoral neck ( B=−0.724 , p=0.040 ) in men . None of the food groups were associated with bone loss in both measured sites in women . For men , lower intake of protein ( B=−0.012 , p=0.003 ) , phosphorus ( B=−0.0008 , p=0.001 ) , sodium ( B=−0.0002 , p=0.023 ) and isoflavone ( B=−1.084 , p=0.030 ) was associated with greater BMD loss in hip , whereas lower intake of protein ( B=−0.018 , p=0.006 ) and sodium ( B=−0.0004 , p=0.018 ) was associated with greater BMD loss in femoral neck . However , these significant associations disappeared after further adjustment for energy-adjusted calcium and vitamin D intakes . None of the nutrients were associated with BMD loss in both measured sites in women . Conclusions Greater fish intake may help to reduce bone loss in this sample of elderly Chinese men . The significant association between various nutrients and bone loss in elderly Chinese men was likely due to the influence of dietary calcium and vitamin D intakes . The role of food groups and dietary nutrients on bone health in this sample of elderly Chinese women seems to be minimal",
"Currently there is no consensus on the impact of dietary protein on calcium and bone metabolism . This study was conducted to examine the effect of increasing protein intake on urinary calcium excretion and to compare circulating levels of IGF-I and biochemical markers of bone turnover in healthy older men and women who consumed either a high or a low protein food supplement for 9 wk . Thirty-two subjects with usual protein intakes of less than 0.85 g/kg.d were r and omly assigned to daily high ( 0.75 g/kg ) or low ( 0.04 g/kg ) protein supplement groups . Isocaloric diets were maintained by advising subjects to reduce their intake of carbohydrates . Selected biochemical measurements were made at baseline and on d 35 and either d 49 or 63 . Changes in urinary calcium excretion in the two groups did not differ significantly over the course of the study . The high protein group had significantly higher levels of serum IGF-I ( P = 0.008 ) and lower levels of urinary N-telopeptide ( P = 0.038 ) over the period of d 35 - 49 or 63 . We conclude that increasing protein intake from 0.78 to 1.55 g/kg.d with meat supplements in combination with reducing carbohydrate intake did not alter urine calcium excretion , but was associated with higher circulating levels of IGF-I , a bone growth factor , and lowered levels of urinary N-telopeptide , a marker of bone resorption . In contrast to the widely held belief that increased protein intake results in calcium wasting , meat supplements , when exchanged isocalorically for carbohydrates , may have a favorable impact on the skeleton in healthy older men and women",
"The effects of dietary protein on bone structure and metabolism have been controversial , with evidence for and against beneficial effects . Because no long-term r and omized , controlled studies have been performed , a two-year study of protein supplementation in 219 healthy ambulant women aged 70 to 80 years was undertaken . Participants were r and omized to either a high-protein drink containing 30 g of whey protein ( n = 109 ) or a placebo drink identical in energy content , appearance , and taste containing 2.1 g of protein ( n = 110 ) . Both drinks provided 600 mg of calcium . Dual-energy X-ray absorptiometric ( DXA ) hip areal bone mineral density ( aBMD ) , 24-hour urinary calcium excretion , and serum insulin-like growth factor 1 ( IGF-1 ) were measured at baseline and at 1 and 2 years . Quantitative computed tomographic ( QCT ) hip volumetric bone mineral density ( vBMD ) and a femoral neck engineering strength analysis were undertaken at baseline and at 2 years . Baseline average protein intake was 1.1 g/kg of body weight per day . There was a significant decrease in hip DXA aBMD and QCT vBMD over 2 years with no between-group differences . Femoral neck strength was unchanged in either group over time . The 24-hour urinary calcium excretion increased significantly from baseline in both groups at 1 year but returned to baseline in the placebo group at 2 years , at which time the protein group had a marginally higher value . Compared with the placebo group , the protein group had significantly higher serum IGF-1 level at 1 and 2 years ( 7.3 % to 8.0 % , p protein-replete healthy ambulant women , 30 g of extra protein increased IGF-1 but did not have beneficial or deleterious effects on bone mass or strength . The effect of protein supplementation in population s with low dietary protein intake requires urgent attention",
"Milk contains several components effective for bone health . In the previous in vitro and in vivo studies , we have shown that milk whey protein , especially its basic protein fraction ( milk basic protein [ MBP ] ) , promoted bone formation and suppressed bone resorption . This present study examines the effect of MBP on the biochemical markers of bone metabolism in healthy adult men . Experimental beverages containing MBP ( 300 mg of MBP a day ) were given to 30 normal healthy adult men for 16 days . The serum osteocalcin concentration had increased significantly after 16 days of ingesting the experimental beverage containing MBP . Urinary cross-linked N-teleopeptides of type-I collagen ( NTx ) excretion had decreased significantly after 16 days of ingesting MBP . The urinary NTx excretion was related to the serum osteocalcin concentration after 16 days of ingestion . These results suggest that MBP promoted bone formation and suppressed bone resorption , while maintaining the balance of bone remodeling",
"Fracture of the proximal femur is the most dramatic clinical sequela of osteoporosis [ 1 , 2 ] . It is associated with a high mortality rate , need for long-term medical care , and prolonged disability [ 3 - 5 ] . Protein malnutrition is often seen in elderly persons and is more severe in patients with hip fracture [ 6 - 11 ] . Protein deficiency may contribute to the occurrence of hip fracture by reducing muscle strength , impairing movement coordination , and diminishing the protective layer of soft tissue padding [ 9 , 10 , 12 - 14 ] It may also be associated with lower bone mineral density at the proximal femur [ 15 ] . Furthermore , malnutrition in general and protein deficiency in particular at admission and during recovery may adversely influence clinical outcome after hip fracture [ 7 , 9 , 10 , 16 - 18 ] . Protein restriction has been shown to reduce plasma levels of insulin-like growth factor-I ( IGF-I ) by inducing resistance to the action of growth hormone in the liver and increasing the metabolic clearance rate of the growth factor [ 19 - 23 ] . Furthermore , evidence shows that protein depletion may blunt the effect of IGF-I on target organs [ 20 ] . Thus , low protein intake in elderly persons may be detrimental to skeletal integrity , muscle strength , and immune response [ 11 , 24 - 27 ] because of decreased production and action of IGF-I , which favorably influences these systems [ 28 - 33 ] . Previous studies [ 16 , 17 ] have shown that a 5-week course of protein supplements can reduce the medical complication rate and duration of hospital stay in patients with recent hip fracture . These findings were independent of energy , calcium , and vitamin D intake [ 17 ] . Whether these observations were related to the restoration of decreased IGF-I levels and whether bone may benefit from long-term protein supplementation are not known . We investigated whether protein supplements in vitamin D-replete patients with a recent hip fracture who were receiving calcium supplements could increase circulating IGF-I levels and favorably influence bone mineral density . Methods Patients Patients were recruited in the orthopedic ward of Geneva University Hospital , the referral center that receives 94.6 % of all patients with hip fracture from an area with a population of approximately 400 000 persons [ 5 ] . The protocol was approved by the ethical committee of the Geneva University Hospital Department of Surgery . Inclusion criteria were age greater than 60 years ; recent hip fracture ( within 2 weeks ) attributable to osteoporosis ( that is , a fracture after a minor trauma , such as a fall from st and ing height ) ; and the ability to give written , informed consent . Exclusion criteria were pathologic fracture ; fracture caused by severe trauma ; history of contralateral hip fracture ; severe mental impairment ; active metabolic bone disease ; renal failure ( plasma creatinine concentration 200 mol/L ) ; acute illness that could interfere with the study protocol ; severe malnutrition ( serum albumin level Using a r and om number table , we assigned patients to receive an oral protein supplement composed of 90 % milk proteins or a placebo made isocaloric by the addition of maltodextrins . Patients took the assigned intervention 5 days a week for 6 months in addition to their regular diet . All patients received one oral dose of vitamin D3 , 200 000 IU ( vitamine D3B.O.N. , Doms-Adrian , Courbevoie , France ) , to correct any possible vitamin D deficiency [ 34 ] . The daily protein supplement ( Meritene , S and oz Nutrition Ltd. , Berne , Switzerl and ) provided 1050 kJ ( 250 kcal ) of energy in the form of 20 g of proteins , 3.1 g of lipids , and 35.7 g of carbohydrates ( 54.4 g in placebo ) . The other constituents of the 65 g powder supplement were vitamin A ( 1000 IU ) , vitamin K1 ( 30 g ) , vitamin C ( 20 mg ) , calcium ( 550 mg ) , magnesium ( 91 mg ) , phosphorus ( 429 mg ) , and sodium ( 228 mg ) . The supplement is design ed to normalize but not overcompensate for the insufficient dietary intake of protein of elderly persons with a recent fracture of the proximal femur [ 16 ] . Compliance was verified by weekly phone calls and by counting the remaining nutritional supplement bags , which were forwarded monthly by mail . Clinical Data Medical history , clinical characteristics , anthropometric data , and performance status according to an Activities of Daily Living score [ 35 ] were evaluated . Dietary intakes were recorded by using a food-frequency question naire [ 36 ] about the week before the fracture . Food intakes were analyzed by using a nutrient software system ( Fruitdor , Astra-Calve , Paris , France ) . Dietary intake of calcium , phosphorus , and protein was calculated from intake of dairy products , meat , fish , and vegetables . Because many patients were unable to st and a few days after hip fracture , their height was determined with a fathom measure while they were recumbent . Body weight was determined with a scale that correlated highly with that provided by measurement of whole body bone , fat , and lean mass as assessed by dual x-ray absorptiometry [ 37 ] . Mid-arm circumference was measured with a tape measure ( coefficient of variation , 2 % ) . Isometric muscle strength of the biceps of the dominant arm was evaluated with a dynamometer ( Lido , Lidoactive Isokinetic System , Loredan Biomedical Inc. , West Sacramento , California ) , which measures the peak torque ( coefficient of variation dynamometer ( Vigorimeter , Martin Medizin-Technik , Tuttlingen , Germany ) [ 38 ] . The mean of three measurements was used for calculation . Biochemical Data Within 120 hours after surgery , we used st and ard methods to analyze venous blood sample s for protein-corrected plasma levels of calcium , phosphate , creatinine , total proteins , albumin , and prealbumin . We also measured levels of IGF-I ( Nichols Institute , San Juan Capistrano , California ) after acid-ethanol extraction and cryoprecipitation [ 39 ] , intact parathyroid hormone ( Immulite , Diagnostic Products , Los Angeles , California ) , calcitriol , calcidiol ( Incstar , Stillwater , Minnesota ) , and osteocalcin ( CIS-BIO International , Gif-sur-Yvette , France ) . Biochemical measurements were repeated 6 and 12 months after the fracture . Serum IGF-I binding proteins were measured by Western lig and blot analysis [ 40 ] . Briefly , 3 L of serum was boiled and separated onto 15 % sodium dodecylsulfate polyacrilamide gel electrophoresis under nonreducing conditions . Proteins were electrically blotted onto a nitrocellulose membrane , and IGF-I binding proteins were detected after incubating the membranes with radioiodinated IGF-I at 4C for 24 hours . Insulin-like growth factor binding proteins were quantified by phosphorimaging ( Molecular Dynamics , Sunnyvale , California ) . The intensity of the b and s corresponding to the appropriate molecular weights [ 40 ] was expressed as the percentage of total bound radioactive IGF-I. Measurements of calcium , phosphate , and creatinine were obtained from the second fasting morning urine . The ratio of hydroxyproline to creatinine in the same sample was taken as a reflection of bone resorption . Markers of bone resorption ( pyridinoline and deoxypyridinoline ) in the first morning spot urine were measured by detecting fluorescence emission after acid hydrolysis and separation with isocratic reverse-phase high-performance liquid chromatography ( BioRad System , Munich , Germany ) , and the values were adjusted to the creatinine concentration . Immunologic Data Concentrations of IgA , IgG , IgM , and isohemagglutinins were measured by using st and ard methods . Cell-mediated immunity was assessed by using a skin-test antigens for cellular hypersensitivity system ( STACH , Institut Merieux , Lyon , France ) , which evaluates the size of the skin reaction to various antigens injected intradermally [ 41 ] . Bone Mass Assessment We measured areal bone mineral density at the lumbar spine ( anteroposterior and lateral views ) , the contralateral proximal femur ( femoral neck and trochanter ) , and the contralateral mid-femoral shaft . We also measured whole-body bone mineral content , fat , and lean mass by using dual x-ray absorptiometry ( Hologic QDR-2000 , Waltham , Massachusetts ) . The coefficients of variation of these measurements are reported elsewhere [ 37 , 42 ] . Vertebral Deformity Two series of lateral radiography of the thoracic and lumbar spine were taken at the start of the study and at 12 months . The films were examined by a single investigator ( who was unaware of treatment group assignment ) according to a 6-point analysis procedure for each vertebral body from T4 to L4 [ 43 , 44 ] ( intra-observer coefficient of variation , 1.8 % to 3.1 % ) . At baseline , fracture was defined by a decrease of 20 % in the ratio of anterior or middle height to posterior height . Patients were considered to have a new vertebral deformity if the anterior , middle , or posterior height decreased by more than 20 % between the two examinations . Statistical Analysis All values are given as the mean SD for baseline measurement and the mean SE for comparisons of outcome results . All analyses were performed by using the SAS procedure ( Cary , North Carolina ) . One-way analysis of variance was used . A two-tailed P value less than 0.05 was considered significant . Role of the Funding Sources This study was supported by grants from S and oz Nutrition Ltd. , Berne , Switzerl and , and the Swiss National Research Science Foundation . The skin-test antigens for cellular hypersensitivity system was supplied by Rhone-Poulenc , Thalwil , Switzerl and . No organization influenced the design , conduct , or reporting of the study . Results Of 842 patients evaluated from April 1992 to February 1994 , 82 were recruited into the r and omized , double-blind , placebo-controlled trial . This low enrollment rate was due to patients ' poor medical or cognitive conditions and reluctance to give informed consent .",
"It has been suggested that bone health in adulthood is programmed by development in utero . Most previous investigations addressing this topic have focussed on bone mineral density or content , rather than other indicators of bone health , such as biochemical markers of bone turnover . This study investigated whether potential predictors , from different stages of life , influence bone resorption in men aged 49 - 51years in the Newcastle Thous and Families birth cohort . The cohort originally consisted of all 1142 births in the city of Newcastle upon Tyne , UK in May and June 1947 . Detailed information was collected prospect ively during childhood , including birth weight and socio-economic circumstances . At 49 - 51years of age , 574 study members completed a detailed ' Health and Lifestyle ' question naire , including the European Prospect i ve Investigation of Cancer ( EPIC ) food frequency question naire and 412 study members attended for clinical examination , including 172 men in whom bone resorption was assessed by measurement of serum beta C-telopeptide of type 1 collagen ( CTX ) . A significant trend was seen between increasingly disadvantaged socio-economic status at birth and increased bone resorption ( p=0.04 , r-squared 2.6 % ) . However , birth weight , st and ardised for sex and gestational age , was not associated with serum CTX ( p=0.77 , r-squared 0.05 % ) . Significant trends were also seen between increasing total energy intake ( p=0.03 , r-squared 2.9 % ) , dietary intake of saturated fat ( p=0.02 , r-squared 2.6 % ) , protein ( p=0.04 , r-squared 2.5 % ) and carbohydrates ( p=0.04 , r-squared 2.6 % ) and higher serum CTX . However , on adjustment for total energy intake , none of the other dietary variables was significant at the univariate level maintained significance . Our findings suggest that early socio-economic disadvantage and later dietary factors may be associated with increased bone resorption in middle aged men . However , as little of the variance in serum CTX was explained by the variables included within this investigation , further longitudinal studies , with sufficient statistical power , are required to assess predictors of bone resorption in adulthood and their relative importance",
"AIM To compare the nutritional status and dietary intake of elderly women admitted with hip fracture ( HF ) versus a control group without fracture and without known abnormalities of bone mineral density . DESIGN Descriptive and observational study . LOCATION Hospital Neurotraumatológico in Jaen ( Spain ) and three urban Primary Health Care centers in Jaen city ( San Felipe , Virgen de la Capilla and El Valle ) . PARTICIPANTS A total of 44 women with HF , which was considered osteoporotic , and a control group composed of 42 women with a similar age range , selected r and omly from the medical out patients who visit their Primary Health Care centers . MEASUREMENTS We record sociodemographic data . Dietary intake before the fracture and anthropometric variables in the first 72hours after admission were assessed . RESULTS Patients with HF had lower weight ( 67.2±10.1 kg versus 72.0±10.1 kg , P ) , BMI ( 27.6±3.7kg/m(2 ) versus 31.3±4.6kg/m(2 ) , P higher intake , in terms of macronutrients and energy consumption , was detected in the control group , as well as lower than recommended intake of calcium and vitamin D in both groups , which was more marked in patients with HF . Logistic regression found that the HF was associated with a lower BMI as well as lower intakes of protein , carbohydrates and calcium . CONCLUSIONS Adequate nutritional status and adequate intake of essential macro- and micronutrients seem to prevent osteoporotic HF",
"Almost 30 % of hip fractures occur in men ; the mortality , morbidity , and loss of independence after hip fractures are greater in men than in women . To comprehensively evaluate risk factors for hip fracture in older men , we performed a prospect i ve study of 5994 men , primarily white , age 65 + years recruited at six US clinical centers . During a mean of 8.6 years of 97 % complete follow-up , 178 men experienced incident hip fractures . Information on risk factors including femoral neck bone mineral density ( FNBMD ) was obtained at the baseline visit . Cox proportional hazards models were used to calculate the hazard ratio ( HR ) with 95 % confidence intervals ; Fine and Gray models adjusted for competing mortality risk . Older age ( ≥75 years ) , low FNBMD , currently smoking , greater height and height loss since age 25 years , history of fracture , use of tricyclic antidepressants , history of myocardial infa rct ion or angina , hyperthyroidism or Parkinson 's disease , lower protein intake , and lower executive function were all associated with an increased hip fracture risk . Further adjustment for competing mortality attenuated HR for smoking , hyperthyroidism , and Parkinson 's disease . The incidence rate of hip fracture per 1000 person-years ( PY ) was greatest in men with FNBMD T-scores experienced hip fracture at rates of 14.52 versus 0.88 per 1000 PY in men age Older men with low FNBMD , multiple risk factors , and multimorbidity have a high risk of hip fracture . Many of these assessment s can easily be incorporated into routine clinical practice and may lead to improved risk stratification . © 2016 American Society for Bone and Mineral Research",
"We studied the effects of daily intake of milk basic protein ( MBP ) on radial bone mineral density ( BMD ) in healthy adult women . Thirty-three healthy women were r and omly assigned to a 6-month trial with either placebo or MBP ( 40 mg per day ) . The radial BMD of each volunteer was measured at the beginning of and at six months after the trial . The mean BMD value at the 6th month in the MBP group increased significantly at both 1/6 and 1/10 portion from the distal end of the radius , whereas that in the control group did not . The BMD gain of each volunteer in the MBP group was significantly higher than that in the placebo group . Thus a daily MBP supplementation of 40 mg in healthy adult women can significantly increase radial BMD",
"Abstract It has been hypothesized that high protein intakes are associated with lower bone mineral content ( BMC ) . Previous studies yield conflicting results and thus far no studies have undertaken the interaction of body mass index ( BMI ) and physical activity with protein intakes in relation to BMC and bone mineral density ( BMD ) . Objective To evaluate the associations of dietary total protein ( TP ) , animal protein ( AP ) and plant protein ( PP ) intakes with BMC and BMD and their changes . We tested also the interactions of protein intake with , obesity ( BMI ≤30 vs. > 30 kg/m2 ) and physical activity level ( passive vs. active ) . Design / Setting Prospect i ve cohort study ( Osteoporosis Risk-Factor and Fracture-Prevention Study ) . Participants / measures At the baseline , 554 women aged 65 - 72 years filled out a 3-day food record and a question naire covering data on lifestyle , physical activity , diseases , and medications . Intervention group received calcium 1000 mg/d and cholecalciferol 800 IU for 3 years . Control group received neither supplementation nor placebo . Bone density was measured at baseline and year 3 , using dual energy x-ray absorptiometry . Multivariable regression analyses were conducted to examine the associations between protein intake and BMD and BMC . Results In cross-sectional analyses energy-adjusted TP ( P≤0·029 ) and AP ( P≤0·045 ) but not PP ( g/d ) were negatively associated with femoral neck ( FN ) BMD and BMC . Women with TP≥1·2 g/kg/body weight ( BW ) ( Ptrend≤0·009 ) had lower FN , lumbar spine ( LS ) and total BMD and BMC . In follow-up analysis , TP ( g/kg/BW ) was inversely associated with LS BMD and LS BMC . The detrimental associations were stronger in women with BMI associated with LS BMD and FN BMC changes . Conclusions This study suggests detrimental associations between protein intake and bone health . However , these negative associations maybe counteracted by BMI > 30 kg/m2 and physical activity"
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BACKGROUND Despite the increasing number of studies evaluating patient reported outcome measures ( PROs ) , there is no clearness regarding which restorative treatment offers major benefits based on the pediatric patient perspective . AIM To compare different restorative techniques in pediatric dentistry regarding patient-reported outcomes . DESIGN Literature search ing was carried out on prospect i ve studies indexed in PubMed , Scopus and OpenGrey . A Mixed Treatment Comparisons ( MTC ) meta- analysis was undertaken considering the results from review ed studies . Anxiety , pain and quality of life were extracted as mean with st and ard deviation , percentage of pain , and mean difference of scores with st and ard deviation , respectively . For direct comparisons , data were combined using a r and om-effect model . Heterogeneity was assessed with the I2 statistic . For indirect comparisons , fixed and r and om effects were chosen through comparison of competing models based on the Deviance Information Criteria ( DIC ) . The expected efficacy ranking based on the posterior probabilities of all treatment rankings was also calculated . RESULTS An initial search result ed in 4,322 articles , of which 17 were finally selected . Due to unavailability of data , only pain , anxiety and oral health related quality of life ( OHRQoL ) were statistically analyzed . The difference in means ( 95 % CI ) of anxiety between treatments using only h and instruments with or without chemomechanical agents were -5.35 ( -6.42 to -4.20 ) and -5.79 ( -7.77 to -3.79 ) respectively when compared to conventional treatment using rotary instruments and /or local anesthesia . Regarding pain , there was a trend for treatments without rotary instruments and local anesthesia to be less frequently reported as painful . No statistical difference was found intragroup nor among treatments for OHRQoL. CONCLUSIONS Anxiety and pain are directly related with more invasive restorative treatments . On the other h and , quality of life is not improved regardless of the restorative technique used . Further well- design ed prospect i ve studies regarding PROs in children are still necessary
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"The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement aims to improve the reporting of r and omized controlled trials ( RCTs ) ; however , it lacks guidance on the reporting of patient-reported outcomes ( PROs ) , which are often inadequately reported in trials , thus limiting the value of these data . In this article , we describe the development of the CONSORT PRO extension based on the method ological framework for guideline development proposed by the Enhancing the Quality and Transparency of Health Research ( EQUATOR ) Network . Five CONSORT PRO checklist items are recommended for RCTs in which PROs are primary or important secondary end points . These recommendations urge that the PROs be identified as a primary or secondary outcome in the abstract , that a description of the hypothesis of the PROs and relevant domains be provided ( ie , if a multidimensional PRO tool has been used ) , that evidence of the PRO instrument 's validity and reliability be provided or cited , that the statistical approaches for dealing with missing data be explicitly stated , and that PRO-specific limitations of study findings and generalizability of results to other population s and clinical practice be discussed . Examples and an up date d CONSORT flow diagram with PRO items are provided . It is recommended that the CONSORT PRO guidance supplement the st and ard CONSORT guidelines for reporting RCTs with PROs as primary or secondary outcomes . Improved reporting of PRO data should facilitate robust interpretation of the results from RCTs and inform patient care",
"Introduction Despite the widespread acceptance of conventional treatment using composite resin in primary teeth , there is limited evidence that this approach is the best option in paediatric clinics . Atraumatic restorative treatment ( ART ) using high-viscosity glass ionomer cement has gradually become more popular because it performs well in clinical studies , is easy to h and le and is patient friendly . Therefore , the aim of this r and omised clinical trial study is to compare the restoration longevity of conventional treatment using composite resin with that of ART in posterior primary teeth . As secondary outcomes , cost-efficacy and patient self-reported discomfort will also be tested . Methods and analysis Children aged 3–6 years presenting with at least one occlusal and /or occlusal-proximal cavity will be r and omly assigned to one of two groups according to the dental treatment : ART ( experimental group ) or composite resin restoration ( control group ) . The dental treatment will be performed at a dental care trailer located in an educational complex in Barueri/SP , Brazil . The unit of r and omisation will be the child . A sample size of 240 teeth with occlusal cavities and 188 teeth with occlusal-proximal cavities has been calculated . The primary outcome will be restoration longevity , which will be clinical ly assessed after 6 , 12 , 18 and 24 months by two examiners . The duration of the dental treatment and the cost of all material s used will be considered when estimating the cost-efficacy of each treatment . Individual discomfort will be measured after each dental procedure using the Facial Scale of Wong-Baker . Ethics and dissemination This clinical trial was approved by the local ethics committee from the Faculty of Dentistry of the University of São Paulo ( registration no. 1.556.018 ) . Participants will be included after their legal guardians have signed an informed consent form containing detailed information about the research . Trial registration number www . clinical trials.gov , NCT02562456 ; Pre- results",
"Background Scotl and has high levels of untreated dental caries in primary teeth . The Hall Technique is a simplified method of managing carious primary molars using preformed metal crowns ( PMCs ) cemented with no local anaesthesia , caries removal or tooth preparation . This study compared the acceptability of the Hall Technique for children , their carers , and dentists , and clinical outcomes for the technique , with conventional restorations . Methods General dental practice based , split mouth , r and omized controlled trial ( 132 children , aged 3–10 ) . General dental practitioners ( GDPs , n = 17 ) in Tayside , Scotl and ( dmft 2.7 ) placed conventional ( Control ) restorations in carious primary molars , and Hall Technique PMCs on the contralateral molar ( matched clinical ly and radiographically ) . Dentists ranked the degree of discomfort they felt the child experienced for each procedure ; then children , their carers and dentists stated which technique they preferred . The teeth were followed up clinical ly and radiographically . Results 128 conventional restorations were placed on 132 control teeth , and 128 PMCs on 132 intervention teeth . Using a 5 point scale , 118 Hall PMCs ( 89 % ) were rated as no apparent discomfort up to mild , not significant ; for Control restorations the figure was 103 ( 78 % ) . Significant , unacceptable discomfort was recorded for two Hall PMCs ( 1.5 % ) and six Control restorations ( 4.5 % ) . 77 % of children , 83 % of carers and 81 % of dentists who expressed a preference , preferred the Hall technique , and this was significant ( Chi square , p 124 children ( 94 % of the initial sample ) with a minimum follow-up of 23 months . The Hall PMCs outperformed the Control restorations : a ) ' Major ' failures ( signs and symptoms of irreversible pulpal disease ) : 19 Control restorations ( 15 % ) ; three Hall PMCs ( 2 % ) ( P ) ' Minor ' failures ( loss of restoration , caries progression ) : 57 Control restorations ( 46 % ) ; six Hall PMCs ( 5 % ) ( P ) Pain : 13 Control restorations ( 11 % ) ; two Hall PMCs ( 2 % ) ( P = 0.003 ) . Conclusion The Hall Technique was preferred to conventional restorations by the majority of children , carers and GDPs . After two years , Hall PMCs showed more favourable outcomes for pulpal health and restoration longevity than conventional restorations . The Hall Technique appears to offer an effective treatment option for carious primary molar teeth . Trial registration numberCurrent Controlled Trials IS RCT N47267892 – A r and omized controlled trial in primary care of a novel method of using preformed metal crowns to manage decay in primary molar teeth : the Hall technique",
"Background In many parts of the world , school-age children have high dental treatment needs ; however , there is often low , or no , dental care provision . Although Atraumatic Restorative Treatment ( ART ) was developed to address this , its survival rate in occluso-proximal lesions is low . An alternative , the Hall Technique ( HT ) has shown better relative outcomes for occluso-proximal lesions , but has not been directly compared to ART or tested in field setting s. This trial will compare ART and the HT for the most clinical ly- and cost-effective strategy for managing occluso-proximal lesions in primary molars , in a school setting , using low-technology and child-friendly dental techniques . Methods / Design This two-arm , parallel group , patient-r and omized controlled , superiority trial will have treatment provided in schools . Schoolchildren ( n = 124 , age 6–8 ) with at least one occluso-proximal carious primary molar lesion will have r and om allocation to treatment with ART or HT . Baseline measures and outcome data will be assessed through participant report , clinical examination and parent report/ question naires . The primary outcome is survival rate , a composite measure of absence of Minor Failures ( a defect in the restoration/crown , but not interfering with tooth health ) and Major Failures ( signs or symptoms of irreversible pulp damage , such as dental fistula/abscess , tooth fracture or failures that can not be repaired ) . Secondary outcomes are : ( 1 ) child-reported discomfort , ( 2 ) childrens ’ and ( 3 ) parents ’ concerns around dental appearance and ( 4 ) acceptability of treatments , ( 5 ) occlusal-vertical dimensions ( OVD ) changes , ( 6 ) plaque index , ( 7 ) gingival health , ( 8) decayed , missing , filled teeth in permanent teeth (DMFT)/decayed , missing , filled teeth in primary teeth ( dmft ) , ( 9 ) oral health-related- quality of life , reported by children and parents/caregivers , ( 10 ) the incremental cost-effectiveness , and ( 11 ) operator effect . A trained and calibrated examiner will evaluate the treated teeth after 1 week , then 1 , 6 , 12 , 24 and 36 months post treatment . Kaplan-Meier and Cox regression tests will be used to investigate the primary outcome . The Mann-Whitney or t test , Friedman test , paired t test or Wilcoxon test and Ordinal Logistic Regression Analysis will be used to analyze the secondary outcomes . Discussion The results of this trial will support decision-making by clinicians and policy-makers for managing occluso-proximal lesions in setting s with constrained re sources and limited dental access . Trial registration www . clinical trials.gov , NCT02569047 , registered 5 October 2015",
"Atraumatic restorative treatment ( ART ) and minimal intervention treatment ( MIT ) techniques were evaluated under field conditions in 5 regions of the Western Cape Province of South Africa , where caries prevalence exceeds 60 % and remains mostly untreated . The purpose of the study was to compare and evaluate results of ART and MIT techniques in the primary dentition of 6 - 9 year-old schoolchildren using glass-ionomer ( GI ) ( Fuji IX ) and compomer ( Dyract AP ) material s. At baseline 401 children were treated , and 1,119 restorations placed by 5 calibrated dentists , 53 % with ART ( using h and instruments only ) and 47 % with MIT ( minimal use of slow h and -piece ) techniques . Evaluations were done with a CPI periodontal probe to measure marginal defects and to detect decay . A pain assessment for the restoration procedures indicated that 80 % of subjects experienced no pain , 18 % discomfort and slight pain , and 2 % required local anaesthetic . After one year 90.5 % of subjects and 80 % of restorations were followed up ( 11.1 % lost as a result of exfoliation ) ; of these restorations 86 % were clinical ly acceptable ( 84.1 % of the ART and 88 % of the MIT ) . With the art technique 82.7 % of GI restorations and 85.6 % , of compomer restorations were acceptable . With the MIT technique 86.5 % of GI restorations and 89.9 % of compomer restorations were acceptable . Success of restorations per region varied significantly : regions 1 and 2 - 90 % , region 3 - 80 % , region 4 - 70 % and region 5 - 95 % . There were no significant statistical differences in respect of material s or methods employed . ART and MIT techniques were well accepted as complementary caries approaches by operators . One-year results show that ART and MIT techniques were successful , substantiating its use for the primary dentition in areas with high caries prevalence . Longer-term assessment s are required",
"OBJECTIVE To compare the level of pain among children treated according to the Atraumatic Restorative Treatment ( ART ) and the Conventional Restorative Treatment ( CRT ) . STUDY DESIGN Forty children of both genders , 4- to 7-years old , presenting Class I cavitated dentin lesions in primary molars were r and omly allocated to 2 groups . One group ( CRT ) received conventional restorative treatment using rotary instruments , while in the other one ( ART ) h and instruments were used to perform the restorations . All children were treated by the same operator A high-viscosity glass-ionomer cement ( Fuji IX ) was used to restore the teeth in both groups . Children 's pain was measured at the end of the first restorative treatment session using the Wong-Baker FACES Pain Rating Scale ( dependent variable ) . Age , gender , treatment time and treatment group were independent variables . ANOVA and ANCOVA tests were used to analyze the data . RESULTS The CRT procedure took longer than the ART procedure ( p ART group reported less pain than those from the CRT group ( p = 0.0037 ) . Four year olds reported more pain than 5- to 7-year olds ( p ART were less time consuming , children felt less pain when the ART approach was used , and younger children ( 4-years ) reported more pain than the older ones for both restorative treatments",
"BACKGROUND More conservative techniques for managing dental caries including ' partial ' and ' no caries removal ' have been increasingly of interest . AIM To compare children 's behaviour and pain perception , also technique acceptability ( parents and dentists ) , when approximal dentinal lesions ( ICDAS 3 - 5 ) in primary molars ( 3 - 8-year-olds ) were managed with three treatment strategies ; conventional restorations ( CR ) , hall technique ( HT ) , and non-restorative caries treatment ( N RCT ) . DESIGN Secondary care-based , three-arm parallel-group , r and omised controlled trial , with 169 participants treated by 12 dentists . OUTCOME MEASURES child 's pain perception ( Visual Analogue Scale of Faces ) ; behaviour ( Frankl scale ) ; and parents ' and dentists ' treatment opinions ( 5-point Likert scales ) . RESULTS Children showed more negative behaviour in the CR group ( 37 % ) compared to N RCT ( 21 % ) and HT ( 13 % ) ( P = 0.047 , CI = 0.41 to 0.52 ) . Pain intensity was rated ' very low ' or ' low ' in 88 % N RCT , 81 % HT , and 72 % CR ( P = 0.11 , CI = 0.10 to 0.12 ) . N RCT and HT were ' very easy ' or ' easy ' to perform for > 77 % of dentists , compared to 50 % in CR group ( P parents ' rating of their child 's level of comfort ( P = 0.46 , CI = 0.45 to 0.48 ) . CONCLUSIONS Dentists reported more negative behaviour in CR group . For all techniques , children 's pain perception and dentist/parent acceptability were similar",
"BACKGROUND To compare changes in child dental anxiety after treatment for early childhood caries ( ECC ) using two treatment approaches . METHODS Children with ECC were r and omized to test ( atraumatic restorative treatment (ART)-based approach ) or control ( st and ard care approach ) groups . Children aged 3 years or older completed a dental anxiety scale at baseline and follow up . Changes in child dental anxiety from baseline to follow up were tested using the chi-squared statistic , Wilcoxon rank sum test , McNemar 's test and multinomial logistic regression . RESULTS Two hundred and fifty-four children were r and omized ( N = 127 test , N = 127 control ) . At baseline , 193 children completed the dental anxiety scale , 211 at follow up and 170 completed the scale on both occasions . Children who were anxious at baseline ( 11 % ) were no longer anxious at follow up , and 11 % non-anxious children became anxious . Multinomial logistic regression found each increment in the number of visits increased the odds of worsening dental anxiety ( odds ratio ( OR ) , 2.2 ; P worsening anxiety ( OR , 0.50 ; P = 0.05 ) . CONCLUSIONS The ART-based approach to managing ECC result ed in similar levels of dental anxiety to the st and ard treatment approach and provides a valuable alternative approach to the management of ECC in a primary dental care setting",
"AIM The aim is to investigate possible differences in discomfort during treatment with the atraumatic restorative treatment ( ART ) or the Conventional restorative method with and without local analgesia ( LA ) . METHODS The study group consisted of 6 and 7 year old children with no dental experience ( mean age 6.98 , SD + /- 0.52 ) r and omly divided into four treatment groups : Conventional method with and without LA and ART with and without LA . One or two proximal lesions in primary molars were treated . The heart rate and the behaviour ( Venham ) were measured . STATISTICS Statistical analysis was performed in SPSS version 10.0 . RESULTS In a first session 300 children were treated and 109 children for a second time in the same way as at the first visit . During the first session ART without LA gave the least discomfort while the Conventional method without LA gave the most discomfort . During the second treatment the least discomfort was observed with ART without LA and the most discomfort in the Conventional way with LA . CONCLUSION There is a constant preference for h and instruments ; the bur is increasingly accepted . The experience with LA is the reverse",
"OBJECTIVE To examine predictors of dental anxiety trajectories in a longitudinal study of New Zeal and ers . METHODS Prospect i ve study of a complete birth cohort born in 1972/73 in Dunedin , New Zeal and , with dental anxiety scale ( DAS ) scores and dental utilization determined at ages 15 , 18 , 26 and 32 years . Personality traits were assessed at a superfactor and ( more fine-grained ) subscale level via the Multidimensional Personality Question naire at age 18 years . Group-based trajectory analysis was used to identify dental anxiety trajectories . RESULTS DAS scores from at least three assessment s were available for 828 participants . Six dental anxiety trajectories were observed : stable nonanxious low ( 39.6 % ) ; stable nonanxious medium ( 37.9 % ) ; recovery ( 1.6 % ) ; adult-onset anxious ( 7.7 % ) ; stable anxious ( 7.2 % ) and adolescent-onset anxious ( 5.9 % ) . Multivariate analysis showed that males and those with higher DMFS at age 15 years were more likely to be in the stable nonanxious low trajectory group . Membership of the stable nonanxious medium group was predicted by the dental caries experience at age 15 years . Participants who had lost one or more teeth between ages 26 and 32 years had almost twice the relative risk for membership of the adult-onset anxious group . Personality traits predicted group membership . Specifically , high scorers ( via median split ) on the ' stress reaction ' subscale had over twice the risk of being in the stable anxious group ; low scorers on the traditionalism subscale were more likely to be members of the recovery trajectory group ; and high scorers on the ' social closeness ' subscale had half the risk of being in the stable anxious group . Dental caries experience at age 5 years was also a predictor for the stable anxious group . Membership of the late-adolescent-onset anxious group was predicted by higher dental caries experience by age 15 years , but none of the other predictors was significant . CONCLUSION Six discrete trajectories of dental anxiety have been observed . Some trajectories ( totalling more than 90 % of the cohort ) had clear associations with external influences , but others were more strongly associated with characteristics such as personality traits . A mix of both influences was observed with only the stable anxious dental anxiety trajectory",
"Aim : To assess the influence of different variables on the survival of class II glass ionomer cements ( GIC ) in a clinical study among 6–7 year old schoolchildren in and around Dar es Salaam , Tanzania . Methods : 217 children were r and omly divided into three groups . In the conventional group , Class-II cavities were excavated with burs , in the ART group they were excavated with h and instruments and in the Carisolv ™ group excavation took place with a chemical solution and special blunt h and instruments . The preparations in all groups were restored with h and mixed GIC ( Fuji IX ) by 4 operators . After restoration , residual caries and cervical gaps were assessed on bite-wing radiographs . The quality of the restorations was established and the survival rate determined in two subsequent evaluations . Results : 195 children ( 90 % ) were present at the first evaluation which took place after 7 months and 194 ( 89 % ) were present at the second evaluation , after one year . At the first evaluation the survival rate of the ART-restorations was 38 % , of the conventional restorations 50 % , and of the Carisolv ™ restorations 35 % . Survival rates at the time of the second evaluation were 30 % , 42 % and 28 % respectively . The differences between the three treatment groups were , however , not significant ( p=0.200 at t=1 and p=0.247 at t=2 ) . In the first evaluation 161 bitewings were available of the 195 restorations , while for the second evaluation 130 . There was no significant relation between residual caries and the success/failure rate ( p=0.140 at t=1 and p=0.201 at t=2 ) . Also , cervical gaps appeared to have no relation with the failure rate ( p=0.057 at t=1 and p=0.833 at t=2 ) However , together those variables have a significant influence on the survival rate ( p = 0.025 ) . Conclusion : The combination of two variables ( residual caries and cervical gaps ) has considerable influence on the survival rate of class II GIC restorations compared to each variable alone",
"BACKGROUND The aim of this study was to compare changes in child oral health-related quality of life ( COHRQoL ) after treatment for early childhood caries ( ECC ) using two alternative treatment approaches . METHODS A r and omized control trial with r and om allocation of parent/child dyads with ECC to test ( minimum intervention ) or control ( st and ard care ) . Participating parents completed the Early Childhood Oral Health Impact Scale ( ECOHIS ) at baseline and follow-up . Changes in ECOHIS scores and extent of COHRQoL impacts between and within groups were tested using the chi-squared statistic for groups , Wilcoxon 's rank-sum test , and matched-pairs signed-rank test . RESULTS Two hundred and fifty-four children were r and omized ( test = 127 ; control = 127 ) . At baseline , mean ECOHIS score 11.1 , sd 8.2 ; mean age = 3.8 years , sd 0.90 ; mean dmft = 4.9 , sd 4.0 ; and 59 % male . After a mean interval of 11.4 months , 210 children were followed-up and returned a completed question naire ( test = 111 ; control = 99 ) . There was no significant difference in COHRQoL changes between test and control . For all the children combined , there were significantly fewer impacts at follow-up in the child and family domains and the total ECOHIS , Wilcoxon signed-rank test , p COHRQoL improved with primary dental care for ECC , and there was no statistically significant difference between test and control in the extent of the improvement"
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Background The choice of measure for use as a primary outcome in geriatric research is contingent upon the construct of interest and evidence for its psychometric properties . The Late-Life Function and Disability Instrument ( LLFDI ) has been widely used to assess functional limitations and disability in studies with older adults . The primary aim of this systematic review was to evaluate the current available evidence for the psychometric properties of the LLFDI . Methods Published studies of any design reporting results based on administration of the original version of the LLFDI in community-dwelling older adults were identified after search es of 9 electronic data bases . Data related to construct validity ( convergent/divergent and known-groups validity ) , test-retest reliability and sensitivity to change were extracted . Effect sizes were calculated for within-group changes and summarized graphically . Results Seventy-one studies including 17,301 older adults met inclusion criteria . Data supporting the convergent/divergent and known-groups validity for both the Function and Disability components were extracted from 30 and 18 studies , respectively . High test-retest reliability was found for the Function component , while results for the Disability component were more variable . Sensitivity to change of the LLFDI was confirmed based on findings from 25 studies . The basic lower extremity subscale and overall summary score of the Function component and limitation dimension of the Disability component were associated with the strongest relative effect sizes . Conclusions There is extensive evidence to support the construct validity and sensitivity to change of the LLFDI among various clinical population s of community-dwelling older adults . Further work is needed on predictive validity and values for clinical ly important change . Findings from this review can be used to guide the selection of the most appropriate LLFDI subscale for use an outcome measure in geriatric research and practice
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"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",
"OBJECTIVES To determine the effects of primary care-based , multicomponent physical activity counseling ( PAC ) promoting physical activity ( PA ) guidelines on gait speed and related measures of PA and function in older veterans . DESIGN R and omized controlled trial . SETTING Veterans Affairs Medical Center of Durham , North Carolina . PARTICIPANTS Three hundred ninety-eight male veterans aged 70 and older . INTERVENTION Twelve months of usual care ( UC ) or multicomponent PAC consisting of baseline in-person and every other week and then monthly telephone counseling by a lifestyle counselor , one-time clinical endorsement of PA , monthly automated telephone messaging from the primary care provider , and quarterly tailored mailings of progress in PA . MEASUREMENTS Gait speed ( usual and rapid ) , self-reported PA , function , and disability at baseline and 3 , 6 , and 12 months . RESULTS Although no between-group differences were noted for usual gait speed , rapid gait speed improved significantly more for the PAC group ( 1.56 + /- 0.41 m/s to 1.68 + /- 0.44 m/s ) than with UC ( 1.57 + /- 0.40 m/sec to 1.59 + /- 0.42 m/sec , P=.04 ) . Minutes of moderate/vigorous PA increased significantly in the PAC group ( from 57.1 + /- 99.3 to 126.6 + /- 142.9 min/wk ) but not in the UC group ( from 60.2 + /- 116.1 to 69.6 + /- 116.1 min/wk , P functional/disability outcomes were small . CONCLUSION In this group of older male veterans , multicomponent PA significantly improved rapid gait and PA . Translation from increased PA to overall functioning was not observed . Integration with primary care was successful",
"Background and Purpose — To determine the effect of a multifaceted stroke telerehabilitation ( STeleR ) intervention on physical function , and secondarily on disability , in veterans poststroke . Methods — We conducted a prospect i ve , r and omized , multisite , single-blinded trial in 52 veterans with stroke from 3 Veterans Affairs medical centers . Veterans with a stroke in the preceding 24 months were r and omized to the STeleR intervention or usual care . The STeleR intervention consisted of 3 home visits , 5 telephone calls , and an in-home messaging device provided over 3 months to instruct patients in functionally based exercises and adaptive strategies . Usual care participants received routine rehabilitation care as prescribed by their physicians . The primary outcome measures were improvement in function at 6 months , measured by both the motor subscale of the Telephone Version of Functional Independence Measure and by the function scales of the Late-Life Function and Disability Instrument . Results — The 2 complementary primary outcomes ( Late-Life Function and Disability Instrument Function and Telephone Version of Functional Independence Measure ) improved at 6 months for the STeleR group and declined for the usual care group , but the differences were not statistically significant ( P=0.25 , Late-Life Function and Disability Instrument ; P=0.316 ) . Several of secondary outcomes were statistically significant . At 6 months , compared with the usual care group , the STeleR group showed statistically significant improvements in 4 of the 5 Late-Life Function and Disability Instrument disability component subscales ( P STeleR intervention significantly improved physical function , with improvements persisting up to 3 months after completing the intervention . STeleR could be a useful supplement to traditional poststroke rehabilitation given the limited re sources available for in-home rehabilitation for stroke survivors . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00384748",
"Background Self-rated health ( SRH ) is a widely used indicator of general health and multiple studies have supported the predictive validity of SRH in older population s concerning future health , functional decline , disability , and mortality . The aim of this study was to use the theoretical framework of the International Classification of Functioning , Disability and Health ( ICF ) to create a better underst and ing of factors associated with SRH among community-dwelling older people in urban and rural areas . Methods The study design was population -based and cross-sectional . Participants were 185 Icel and ers , r and omly selected from a national registry , community-dwelling , 65 - 88 years old , 63 % urban residents , and 52 % men . Participants were asked : \" In general , would you say your health is excellent , very good , good , fair , or poor ? \" Associations with SRH were analyzed with ordinal logistic regression . Explanatory variables represented aspects of body functions , activities , participation , environmental factors and personal factors components of the ICF . Results Univariate analysis revealed that SRH was significantly associated with all analyzed ICF components through 16 out of 18 explanatory variables . Multivariate analysis , however , demonstrated that SRH had an independent association with five variables representing ICF body functions , activities , and personal factors components : The likelihood of a better SRH increased with advanced lower extremity capacity ( adjusted odds ratio [ adjOR ] = 1.05 , p upper extremity capacity ( adjOR = 1.13 , p = 0.040 ) , household physical activity ( adjOR = 1.01 , p = 0.016 ) , and older age ( adjOR = 1.09 , p = 0.006 ) ; but decreased with more depressive symptoms ( adjOR = 0.79 , p community-dwelling older people . Some of these , such as physical capacity , depressive symptoms , and habitual physical activity are of particular interest due to their potential for change through public health interventions . The use of ICF conceptual framework and widely accepted st and ardized assessment s should make these results comparable and relevant in an international context",
"Introduction Older breast cancer survivors ( BCS ) report more falls and functional limitations than women with no cancer history . Exercise training could reduce risk factors for future falls and disability . Methods We conducted a r and omized , controlled trial in 106 early-stage , postmenopausal BCS who were ≥50 years old at diagnosis and post-treatment . Women were r and omly assigned to a 1-year resistance + impact exercise program or a stretching placebo program . Endpoints were one repetition maximum bench press and leg press strength , timed five chair st and s , 4 m usual walk speed , timed stance tests , h and grip strength , self-report physical function , and fatigue . We also examined the influence of age , adjuvant hormone therapy use , and exercise adherence on study outcomes . Results Women in the resistance + impact training program significantly improved maximal leg ( p .02 ) and bench ( p .02 ) press strength compared to the stretching group . Women who attended 50 % or more of prescribed resistance training sessions had significantly better changes in maximal strength measures compared to less adherent women . Conclusions Resistance + impact exercise is superior to stretching at improving maximal muscle strength and exercise adherence contributes to the degree of improvement . Implication s for cancer survivorsOlder BCS can safely engage in resistance exercise that improves lower and upper body strength , thereby reducing a risk factor for falls and future disability . However , the ability of resistance training to shift other indices of fall and disability risk , i.e. , balance and function , is unclear . Strategies to promote adherence to resistance training could lead to greater improvements in strength ",
"PURPOSE Diet and exercise interventions have been tested in cancer survivors as a means to reduce late effects and comorbidity , but few have assessed adherence and health outcomes long term . METHODS Between July 2005 and May 2007 , the Reach Out to Enhance Wellness ( RENEW ) trial accrued 641 locoregionally staged , long-term ( ≥ 5 years from diagnosis ) colorectal , breast , and prostate cancer survivors in the United States ( 21 states ) , Canada , and the United Kingdom . All participants were sedentary ( The trial tested a diet-exercise intervention delivered via mailed print material s and telephone counseling . RENEW used a wait-list control , cross-over design ( ie , participants received the year-long intervention immediately or after a 1-year delay ) , which allowed the opportunity to assess program efficacy ( previously reported primary outcome ) , durability , and reproducibility ( reported herein ) . Measures included diet quality ( DQ ) , PA , BMI , and physical function ( PF ) . RESULTS No significant relapse was observed in the immediate-intervention arm for DQ , PA , and BMI ; however , rates of functional decline increased when the intervention ceased . From year 1 to year 2 , significant improvements were observed in the delayed-intervention arm ; mean change scores in behaviors and BMI and PF slopes were as follows : DQ score , 5.2 ( 95 % CI , 3.4 to 7.0 ) ; PA , 45.8 min/wk ( 95 % CI , 26.9 to 64.6 min/wk ) ; BMI , -0.56 ( 95 % CI , -0.75 to -0.36 ) ; and Short Form-36 PF , -1.02 versus -5.52 ( P experienced significant improvements in DQ , PA , and BMI from baseline to 2-year follow-up ( P Older cancer survivors respond favorably to lifestyle interventions and make durable changes in DQ and PA that contribute to sustained weight loss . These changes positively reorient functional decline trajectories during intervention delivery",
"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",
"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 There is limited evidence supporting the hypothesized environment-disability link . The objectives of this study were to ( a ) identify the prevalence of community mobility barriers and transportation facilitators and ( b ) examine whether barriers and facilitators were associated with disability among older adults with functional limitations . METHODS Four hundred and thirty-five participants aged 65 + years old with functional limitations were recruited from the Multicenter Osteoarthritis Study , a prospect i ve study of community-dwelling adults with or at risk of developing symptomatic knee osteoarthritis . Presence of community barriers and facilitators was ascertained by the Home and Community Environment survey . Two domains of disability , ( a ) daily activity limitation ( DAL ) and ( b ) daily activity frequency ( DAF ) , were assessed with the Late-Life Disability Instrument . Covariates included age , gender , education , race , comorbidity , body mass index , knee pain , and functional limitation . Multivariable logistic regression was used to examine adjusted associations of community factors with presence of DAL and DAF . RESULTS Approximately one third of the participants lived in a community with high mobility barriers and low transportation facilitators . High mobility barriers was associated with greater odds of DAL ( odds ratio [ OR ] = 2.0 , 95 % confidence interval [ CI ] 1.2 - 3.1 ) after adjusting for covariates , and high transportation facilitators was associated with lower odds of DAL ( OR = 0.5 , 95 % CI 0.3 - 0.8 ) but not with DAF in adjusted models . CONCLUSION People with functional limitations who live in communities that were more restrictive felt more limited in doing daily activities but did not perform these daily activities any less frequently",
"BACKGROUND The recent development of the Late-Life Function and Disability Instrument ( LL-FDI ) was an important contribution to the measurement of function and disability in older adults . The present study examined the psychometric properties and construct validity of the LL-FDI measure in a sample of older women . METHODS Older black ( n = 81 ) and white ( n = 168 ) women completed the LL-FDI , several measures of physical function , and physical activity measures , and had their body mass index assessed at baseline of an ongoing prospect i ve study . Confirmatory factor analyses ( CFA ) and correlational analyses were used to examine factorial and construct validity of the measure . RESULTS The CFA , using an iterative model modification technique , result ed in an acceptable 15-item solution for the function component and an 8-item solution for the disability component . This abbreviated instrument demonstrated high correlations with the original scales . Construct validity for the LL-FDI was supported . Participants who demonstrated better physical function , reported being more active , and had lower body mass index reported less disability and less difficulty with function on the LL-FDI . CONCLUSIONS The LL-FDI appears to be an effective instrument for assessing function and disability in older women , and the abbreviated version reported here may prove useful in certain circumstances due to its brevity . However , continued determination of the construct validity of the complete and abbreviated scales is recommended",
"Objective . To determine the tolerance and feasibility of aquatic-based power training for improving lower limb muscle power , impairments , and mobility in adults with symptomatic knee OA . Participants . Twenty-nine adults , age 50 years and over , with symptomatic knee OA ( ACR clinical criteria ) and mobility limitation ( 400-meter walk time slower than median for sex and decade ) completed 45-minute aquatic power training sessions twice weekly for 6 weeks . Main Outcome Measurements . Prospect i ve outcomes included tolerance of the program , as well as change in stair climb power , 400-meter walk time , overall and knee-specific pain , activities of daily living ( ADL ) , quality of life ( QOL ) , and lower limb function at 6- and 12-week follow-up . Results . The training intensity required modification for 9 of the 29 participants . Lower limb muscle power , ADL , QOL , and overall pain were improved immediately and 6 weeks following completion ( all P 400-meter walk times , and lower limb function did not differ from baseline . Conclusions . A 6-week aquatic rehabilitation program appears to be well tolerated by adults with symptomatic knee OA with mobility limitations and may result in improved lower limb muscle power , symptoms , ADL , and QOL . However , this intervention may have insufficient specificity or intensity for improving physical function",
"OBJECTIVE To evaluate whether a customized exercise tolerance testing ( ETT ) protocol based on an individual 's habitual gait speed ( HGS ) on level ground would be a valid mode of exercise testing older adults . Although ETT provides a useful means to risk-stratify adults , age-related declines in gait speed paradoxically limit the utility of st and ard ETT protocol s for evaluating older adults . A customized ETT protocol may be a useful alternative to these st and ard methods , and this study hypothesized that this alternative approach would be valid . DESIGN We performed a cross-sectional analysis of baseline data from a r and omized controlled trial of older adults with observed mobility problems . Screening was performed using a treadmill-based ETT protocol customized for each individual 's HGS . We determined the content validity by assessing the results of the ETTs , and we evaluated the construct validity of treadmill time in relation to the Physical Activity Scale for the Elderly ( PASE ) and the Late Life Function and Disability Instrument ( LLFDI ) . SETTING Outpatient rehabilitation center . PARTICIPANTS Community-dwelling , mobility-limited older adults ( N=141 ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Cardiac instability , ETT duration , peak heart rate , peak systolic blood pressure , PASE , and LLFDI . RESULTS Acute cardiac instability was identified in 4 of the participants who underwent ETT . The remaining participants ( n=137 , 68 % female ; mean age , 75.3 y ) were included in the subsequent analyses . Mean exercise duration was 9.39 minutes , with no significant differences in duration s being observed after evaluating among tertiles by HGS status . Mean peak heart rate and mean peak systolic blood pressure were 126.6 beats/min and 175.0 mmHg , respectively . Within separate multivariate models , ETT duration in each of the 3 gait speed groups was significantly associated ( P Mobility-limited older adults can complete this customized ETT protocol , allowing for the identification of acute cardiac instability and the achievement of optimal exercise parameters",
"BACKGROUND This study was design ed to evaluate the benefits of InVEST ( Increased Velocity Specific to Task ) training on limb power and mobility among mobility-limited older adults . METHODS We conducted a single blinded , r and omized controlled trial among 138 mobility-limited community-dwelling older adults , evaluating two 16-week supervised exercise programs . The intervention group participated in InVEST training , and the control group participated in the National Institute on Aging 's ( NIA ) strength training program . Primary outcomes were changes in limb power per kilogram and mobility performance as measured by the Short Physical Performance Battery ( SPPB ) . RESULTS After 16 weeks , InVEST produced significantly greater improvements in limb power than NIA ( p=.02 ) . There was no significant difference in strength improvements . Both groups had significant changes in SPPB of greater than 1 unit . Self-reported function was also significantly improved in both groups . Differences between groups were not statistically different . In a post hoc analysis when participants were categorized by the manifestation of baseline leg velocity impairments ( N=68 ) , InVEST training produced effect size differences in SPPB that were clinical ly meaningful ( SPPB Group x Time difference 0.73 units , p=.05 ) . CONCLUSIONS Among mobility-limited older adults , both NIA and InVEST produce robust changes in observed physical performance and self-reported function . These improvements were not meaningfully different by statistical or clinical criteria . Compared with NIA , InVEST training produced greater improvements in limb power and equivalent improvements in strength . Observed differences between NIA and InVEST based upon baseline leg impairment status are informative for futures studies",
"PURPOSE To compare two self-administered , one interviewer-administered , and one performance-based measure of physical function in community-based older persons . METHODS Eighty-three subjects were recruited from meal sites , senior recreation centers , and senior housing units for a comprehensive geriatric assessment program . At the time of screening , study participants self-administered the Functional Status Question naire ( FSQ ) and were administered the Katz Activities of Daily Living ( ADL ) and the Older Americans Re sources and Services Instrumental Activities of Daily Living ( OARS-IADL ) instruments by interview . Participants also completed the Physical Performance Test ( PPT ) and were given the Medical Outcomes Study SF-36 to self-administer on site or at home and return by mail . RESULTS All 83 subjects completed FSQ , Katz ADL , OARS-IADL , and PPT ; 72 returned SF-36 forms . Correlations between the two self-administered physical function measures ( FSQ and SF-36 ) were higher than between self-administered and interviewer-assessed ( ADL and OARS-IADL ) or performance-based ( PPT ) measures . When assessed for construct validity , the self-administered , OARS , and PPT measures had comparable correlations with role limitations as a result of physical health problems , but relationships between physical functional status measures and other SF-36 measures of health were inconsistent . CONCLUSION The relationships between commonly used self-administered , interviewer-administered , and performance-based measures of physical function were inconsistent and weak , suggesting that these instruments are not measuring the same construct",
"Background / Aim : In elderly persons , fall-related injury is a serious public health problem . We investigated the impact of essential nutritional elements on falls in the elderly . Methods : Clinical function , balance , gait and disability tests and health and nutritional status assessment s were performed . All subjects were interviewed regarding the occurrence of falls in the last year . Blood tests for serum vitamin D , folate and B12 were conducted among a r and omly selected sub sample of 54 participants in the same month . Results : One hundred 65- to 91-year-old volunteers participated in the study , and 29 of them fell at least once during the past year . The depression score was higher ( indicating more depressive symptoms ) among fallers compared with non-fallers ( 4.0 ± 3.2 vs. 2.5 ± 2.3 , respectively ) . The overall function score ( indicating better function ) was marginally higher in non-fallers . Subsequent comparisons between fallers and non-fallers were adjusted for overall function and depression scores . Serum folate was significantly lower in fallers ( 9.5 ± 7.1 vs. 16.2 ± 6.7 ng/ml , p = 0.02 ) . Dietary intake was equal in both groups . Correlation analyses indicate a significant association between vitamin D and the functional measurements : timed get up and go ( negative ) , Berg balance test , overall functional score , lower extremity score and limitation score ( positive correlation coefficients ) . Serum folate was highly and negatively associated with the number of falls and with prescribed medications and was the only protective factor against falls in a multivariate analysis . Conclusions : Vitamin D was related to most functional and balance measurements . Serum folate was protective against falls . For every 1 ng/ml increase in serum folate the occurrence of falls decreased by 19 %",
"Purpose : To examine the effectiveness of a novel intervention aim ed at decreasing indices related to frailty through systematic , Progressive Functional Rehabilitation ( PFR ) . Methods : Pre‐frail volunteers were recruited to participate in a 15 week exercise intervention or control group . Those who met study criteria and consented were r and omized into one of three groups : control , seated exercise , or Wii ® ‐fit . Test measures were completed before and after the 15 week intervention period on all participants . Measures included : Senior Fitness Test , Body Weight , Balance Efficacy Scale , CHAMPS , Late‐Life Function and Disability Index , MOS SF‐36 . Attendance was also recorded . Results : There were improvements on several of the measures included in the Senior Fitness Test including chair st and s , arm curls , step 2 , six minute walk , sit and reach , and the timed up and go . A few participants did lose weight . All of the differences reflected improved physical functional status in the seated exercise or Wii‐fit groups compared with the control group . Discussion : Increased physical activity was beneficial for all who participated . There were improvements in physical performance scores on several of the measures on the senior fitness test in both the seated exercise and Wii‐fit groups . Participants in the Wii‐fit group also showed improvement in their reported caloric expenditure and balance confidence . Conclusion : This pilot study suggests a rehabilitation effect that was similar to the effect of community based senior fitness classes . A home video game console system with weight vest could be an effective alternative for pre‐frail senior adults to group exercise classes",
"BACKGROUND To compare the frequencies of risk factors , we describe risks for depression as a function of race among consecutively admitted participants in a r and omized clinical trial of indicated depression prevention in later life . METHODS Seventy-two black and 143 white participants were screened for risk factors for depression . RESULTS Black participants were more likely to have fewer years of education and lower household income . They were more likely to be obese , live alone , experience functional disability , have a history of alcohol and drug abuse , and have lower scores on the Mini-mental State Examination and the Executive Interview ( EXIT ) . White participants were not found to have greater prevalence or higher mean score on any risk factor . On average , black participants experienced approximately one more risk factor than white participants ( t(213 ) = 3.32 , p = 0.0011 ) . CONCLUSIONS In our sample , black participants had higher frequencies of eight risk factors for depression and a greater mean number of risk factors compared to white participants",
"BACKGROUND This study applied item response theory ( IRT ) and computer adaptive testing ( CAT ) method ologies to develop a prototype function and disability assessment instrument for use in aging research . Herein , we report on the development of the CAT version of the Late-Life Function and Disability Instrument ( Late-Life FDI ) and evaluate its psychometric properties . METHODS We used confirmatory factor analysis , IRT methods , validation , and computer simulation analyses of data collected from 671 older adults residing in residential care facilities . We compared accuracy , precision , and sensitivity to change of scores from CAT versions of two Late-Life FDI scales with scores from the fixed-form instrument . Score estimates from the prototype CAT versus the original instrument were compared in a sample of 40 older adults . RESULTS Distinct function and disability domains were identified within the Late-Life FDI item bank and used to construct two prototype CAT scales . Using retrospective data , scores from computer simulations of the prototype CAT scales were highly correlated with scores from the original instrument . The results of computer simulation , accuracy , precision , and sensitivity to change of the CATs closely approximated those of the fixed-form scales , especially for the 10- or 15-item CAT versions . In the prospect i ve study , each CAT was administered in CAT scores were highly correlated with scores generated from the original instrument . CONCLUSIONS CAT scores of the Late-Life FDI were highly comparable to those obtained from the full-length instrument with a small loss in accuracy , precision , and sensitivity to change",
"CONTEXT Five-year survival rates for early stage colorectal , breast , and prostate cancer currently exceed 90 % and are increasing . Cancer survivors are at greater risk for second malignancies , other comorbidities , and accelerated functional decline . Lifestyle interventions may provide benefit , but it is unknown whether long-term cancer survivors can modify their lifestyle behaviors sufficiently to improve functional status . OBJECTIVE To determine whether a telephone counseling and mailed print material -based diet and exercise intervention is effective in reorienting functional decline in older , overweight cancer survivors . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial of 641 overweight ( body mass index > or = 25 and or = 5 years ) survivors ( aged 65 - 91 years ) of colorectal , breast , and prostate cancer , who were r and omly assigned to an intervention group ( n = 319 ) or delayed intervention ( control ) group ( n = 322 ) in Canada , the United Kingdom , and 21 US states . Individuals were recruited for the Reach out to Enhance Wellness ( RENEW ) trial from July 1 , 2005 , through May 17 , 2007 . INTERVENTION A 12-month , home-based tailored program of telephone counseling and mailed material s promoting exercise , improved diet quality , and modest weight loss . The control group was wait-listed for 12 months . MAIN OUTCOME MEASURES Change in self-reported physical function on the Short-Form 36 physical function subscale ( score range , 0 - 100 ; a high score indicates better functioning ) from baseline to 12 months was the primary end point . Secondary outcomes included changes in function on the basic and advanced lower extremity function subscales of the Late Life Function and Disability Index ( score range , 0 - 100 ) , physical activity , body mass index , and overall health-related quality of life . RESULTS The mean baseline Short-Form 36 physical function score was 75.7 . At the 12-month follow-up , the mean function scores declined less rapidly in the intervention group ( -2.15 ; 95 % confidence interval [ CI ] , -0.36 to -3.93 ) compared with the control group ( -4.84 ; 95 % CI , -3.04 to -6.63 ) ( P = .03 ) . The mean baseline basic lower extremity function score was 78.2 . The mean changes in basic lower extremity function were 0.34 ( 95 % CI , -0.84 to 1.52 ) in the intervention group compared with -1.89 ( 95 % CI , -0.70 to -3.09 ) in the control group ( P = .005 ) . Physical activity , dietary behaviors , and overall quality of life increased significantly in the intervention group compared with the control group , and weight loss also was greater ( 2.06 kg [ 95 % CI , 1.69 to 2.43 kg ] vs 0.92 kg [ 95 % CI , 0.51 to 1.33 kg ] , respectively ; P Among older , long-term survivors of colorectal , breast , and prostate cancer , a diet and exercise intervention reduced the rate of self-reported functional decline compared with no intervention . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00303875",
"OBJECTIVES To test the effect of tai chi on the progression of pre clinical disability to manifest disability compared with seated flexibility exercise , and to examine whether tai chi mediates delayed disability by reducing impairments in musculoskeletal , cardiovascular , and neurologic systems , and related functional limitations . DESIGN Multisite parallel group individually r and omized controlled trial . SETTING General community . PARTICIPANTS Pre clinical ly disabled community-dwelling people older than 70 years ( n=503 ) , without major medical conditions or moderate to severe cognitive impairment . INTERVENTION Modified Sun style tai chi exercise compared with seated flexibility exercise , both programs delivered in groups for 60 minutes twice weekly for 24 weeks . MAIN OUTCOME MEASURES Disability measured with the Late-Life Function and Disability Instrument . Secondary outcomes were impairments and functional limitations of the musculoskeletal , neurologic , and cardiovascular systems . RESULTS There was little change within or between the 2 groups . The mean change in the Disability Frequency Score was 0.3 and 0.1 points ( 100-point scale ) for the intervention and control groups , respectively ( adjusted difference -.21 ; 95 % confidence interval [ CI ] -.99 to .56 ) . The mean change in the Disability Limitation Score was -0.1 and -.04 points for the intervention and control groups , respectively ( adjusted difference -0.6 ; 95 % CI -2.31 to 1.11 ) . There was little effect on impairments or functional limitations . A higher proportion of intervention participants ceased attending the exercise program ( difference=17.9 % , 95 % CI 9.6 - 25.8 ) . Multiple imputation of missing data did not change the results . CONCLUSIONS Modified Sun style tai chi did not have an impact on impairment , functional limitations , or disability in pre clinical ly disabled older people when delivered for 24 weeks . Withdrawal from the exercise classes was high but did not explain the None result . Improved compliance , or a longer or more intensive program , may be required",
"PURPOSE To compare the effects of functional home exercise of repeated sit-to-st and s with low-intensity progressive resistance training , on performance measures in mobility-limited adults over 80 years of age . SETTING Participants ' homes . DESIGN Community-dwelling older adults > or = 80 years of age were invited to participate in a r and omised controlled clinical trial . Baseline and outcome measures were : comfortable gait velocity , 30-s chair-st and test , 15-s step test , Berg Balance Scale , Modified Falls Efficacy Scale and the Late-Life Function and Disability Instrument-function component . Participants r and omised to the intervention group performed repeated sit-to-st and s using a Gr and St and System ; a biofeedback device that recorded and displayed the number of repetitions performed . Participants r and omised to the control group performed knee extensions using ankle cuff weights . Both groups performed the exercises daily for 6 weeks . RESULTS Sixty-six older adults took part . The intervention group had a statistically significant improvement in Berg Balance Scale mean score , 1.67 + /- 2.64 points , P = 0.001 ( control group 0.73 + /- 3.63 points , P = 0.258 ) , indicating an improvement in balance over the 6-week exercise period . There was no statistically significant effect of either intervention on the other outcome measures . CONCLUSIONS In a highly variable population of older adults with mobility limitations , low-intensity functional home exercise of repeated sit-to-st and s using the Gr and St and System improved Berg Balance Scale score while low-intensity progressive resistance training did not . While statistically significant , the improvement in Berg Balance Scale score was modest raising the issue of what extent of change in score is clinical ly significant in this population",
"Background Functional limitations have been operationally defined for studies of rehabilitation science through measures of physical performance and patient-reported function . Although conceived as representing similar concepts , differences between these 2 modes of measuring physical functioning have not been adequately characterized scientifically . Objective The purpose of this study was to compare the Short Physical Performance Battery ( SPPB ) with the function component of the Late-Life Function and Disability Instrument ( LLFDI ) with respect to their association with physiologic factors and other psychosocial and health factors potentially influencing rehabilitative care . Design This study was a cross-sectional analysis of baseline data from a sample of community-dwelling older adults ( N=137 ) with mobility limitations enrolled in a r and omized controlled trial of exercise . Methods A performance-based measure of function ( the SPPB ) and a self-report measure of function ( the LLFDI ) served as functional outcomes . Physiologic factors included measures of leg strength , leg velocity , and exercise tolerance test ( ETT ) duration , which served as a surrogate measure of aerobic capacity . Psychosocial and health factors included age , sex , height , body mass index , number of chronic conditions , depression , and falls efficacy . Results Separate multivariable regression models predicting SPPB and LLFDI scores described 33 % and 42 % of the variance in each outcome ( R2 ) , respectively . Leg velocity and ETT duration were positively associated with both performance-based and patient-reported functional measures . Leg strength and age were positively associated with SPPB scores , whereas number of chronic conditions , sex , and falls efficacy were associated with the LLFDI scores . Limitations This study included older adults with mobility limitations and may not generalize to other population s. Conclusions Performance-based and patient-reported measures of physical function appear to assess different aspects of an older person 's functioning . The SPPB was associated with age and physiologic factors , whereas patient-reported function measured by the LLFDI was associated with these factors as well as with psychosocial and health factors",
"Objectives : To evaluate the effect of a group-based functional and specific balance training programme that included dual-task exercises on balance function in healthy older adults . Design : A single-blind r and omized controlled trial . Setting : General community . Participants : Sixty-six community-dwelling older adults ( age 77.0 ± 6.5 years ) , without functional balance impairment were recruited and allocated at r and om to an intervention group ( n = 33 ) or a reference group ( n = 33 ) . Intervention : The intervention group received 24 training sessions over three months that included perturbation as well as dual-task exercises . The reference group received no intervention . Outcome measures : The voluntary step execution times during single- and dual-task conditions , stabilogram-diffusion analysis in upright st and ing , and self-reported physical function ; all were measured assessed at baseline and at the end of intervention . The intervention group was retested after six months . Results : Compared with the reference group , participation in group-based functional and specific balance training led to faster voluntary step execution times under single-task ( P = 0.02 ; effect size ( ES ) = 0.34 ) and dual-task ( P = 0.036 ; ES = 0.55 ) conditions ; lower transition displacement and shorter transition time of the stabilogram-diffusion analysis under eyes-closed conditions ( P = 0.007 , ES = 0.30 and P = 0.08 , ES = 0.44 , respectively ) ; and improved self-reported lower extremity function ( P = 0.006 , ES = 0.37 ) . Effects were lost at six-month follow-up . Conclusions : Functional and specific balance training can improve voluntary stepping and balance control in healthy older non-fallers , parameters previously found to be related to increased risk of falls and injury in older adults",
"CONTEXT Generalized anxiety disorder ( GAD ) is one of the most common psychiatric disorders in older adults ; however , few data exist to guide clinicians in efficacious and safe treatment . Selective serotonin reuptake inhibitors ( SSRIs ) are efficacious for younger adults with GAD , but benefits and risks may be different in older adults . OBJECTIVE To examine the efficacy , safety , and tolerability of the SSRI escitalopram in older adults with GAD . DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled trial in primary care practice s and related specialty clinics in Pittsburgh , Pennsylvania , of 177 participants aged 60 years or older with a principal diagnosis of GAD r and omized to receive either escitalopram or placebo and conducted between January 2005 and January 2008 . INTERVENTIONS Twelve weeks of 10 to 20 mg/d of escitalopram ( n = 85 ) or matching placebo ( n = 92 ) . MAIN OUTCOME MEASURES Cumulative response defined by Clinical Global Impressions-Improvement score of much or very much improved ; time to response ; and anxiety and role functioning changes measured by the Clinical Global Impressions-Improvement scale , Hamilton Anxiety Rating Scale , Penn State Worry Question naire , Late-Life Function and Disability Instrument activity limitations subscale , and the role-emotional impairment and social function subscales of the Medical Outcome Survey 36-item Short Form . RESULTS In the primary analytic strategy in which participants ( n = 33 ) were censored at the time of dropout , mean cumulative response rate for escitalopram was 69 % ( 95 % confidence interval [ CI ] , 58%-80 % ) vs 51 % ( 95 % CI , 40%-62 % ) for placebo ( P = .03 ) . A conservative intention-to-treat analysis showed no difference in mean cumulative response rate between escitalopram and placebo ( 57 % ; 95 % CI , 46%-67 % ; vs 45 % ; 95 % CI , 35%-55 % ; P = .11 ) . Participants treated with escitalopram showed greater improvement than with placebo in anxiety symptoms and role functioning ( Clinical Global Impressions-Improvement scale : effect size , 0.93 ; 95 % CI , 0.50 - 1.36 ; P Penn State Worry Question naire : 0.30 ; 95 % CI , 0.23 - 0.48 ; P = .01 ; activity limitations : 0.32 ; 95 % CI , 0.01 - 0.63 ; P = .04 ; and the role-emotional impairment and social function : 0.96 ; 95 % CI , 0.03 - 1.90 ; P = .04 ) . Adverse effects of escitalopram ( P were fatigue or somnolence ( 35 patients [ 41.1 % ] ) , sleep disturbance ( 12 [ 14.1 % ] ) , and urinary symptoms ( 8 [ 9.4 % ] ) . CONCLUSIONS Older adults with GAD r and omized to escitalopram had a higher cumulative response rate for improvement vs placebo over 12 weeks ; however , response rates were not significantly different using an intention-to-treat analysis . Further study is required to assess efficacy and safety over longer treatment duration s. TRIAL REGISTRATION clinical trials.gov Identifier : NCT00105586",
"Background Definitive evidence that exercise interventions that improve gait also reduce disability is lacking . A task-oriented , motor sequence learning exercise intervention has been shown to reduce the energy cost of walking and improve gait speed , but whether the intervention also improves activity and participation has not been demonstrated . Objective The objective of this study was to compare the impact of a task-oriented , motor sequence learning exercise ( TO ) intervention and the impact of an impairment-oriented , multicomponent exercise ( IO ) intervention on activity and participation outcomes in older adults with mobility limitations . The mediating effects of a change in the energy cost of walking on changes in activity and participation also were determined . Design This study was a single-blind , r and omized controlled trial . Setting The study was conducted in an ambulatory clinical research training center . Participants The study participants were 47 older adults ( mean age=77.2 years , SD=5.5 ) with slow and variable gait . Intervention The intervention was a 12-week , physical therapist – guided program of TO or IO . Measurements Measures of activity ( gait speed over an instrumented walkway ; daily physical activity measured with an accelerometer ; confidence in walking determined with the Gait Efficacy Scale ; and physical function determined with the total , basic lower-extremity , and advanced lower-extremity components of the Late-Life Function and Disability Instrument [ Late-Life FDI ] ) and participation ( disability limitation dimension and instrumental role [ home and community task performance ] domain components of the Late-Life FDI ) were recorded before and after the intervention . The energy cost of walking was determined from the rate of oxygen consumption during self-paced treadmill walking at the physiological steady state st and ardized by walking speed . An adjusted comparison of activity and participation outcomes in the treatment arms was made by use of an analysis of covariance model , with baseline and change in energy cost of walking added to the model to test for mediation . Tests were used to determine the significance of the mediating effects . Results Activity improved in TO but not in IO for confidence in walking ( Gait Efficacy Scale ; mean adjusted difference=9.8 [ SD=3.5 ] ) and physical function ( Late-Life FDI basic lower-extremity component ; mean adjusted difference=3.5 [ SD=1.7 ] ) . Improvements in TO were marginally greater than those in IO for gait speed , physical activity , and total physical function . Participation improved marginally more in TO than in IO for disability limitations and instrumental role . Limitations The older adults were r and omized to the intervention group , but differences in baseline measures had to be accounted for in the analyses . Conclusions A TO intervention that improved gait also led to improvements in some activity and participation outcomes in older adults with mobility limitations"
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411754ec-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND The World Health Organization estimates that 1.9 million deaths worldwide are attributable to physical inactivity . Chronic diseases associated with physical inactivity include cancer , diabetes and coronary heart disease . OBJECTIVES The purpose of this systematic review is to summarize the evidence of the effectiveness of school-based interventions in promoting physical activity and fitness in children and adolescents . SEARCH STRATEGY The search strategy included search ing several data bases . In addition , reference lists of included articles and background papers were review ed for potentially relevant studies , as well as references from relevant Cochrane review s. Primary authors of included studies were contacted as needed for additional information . SELECTION CRITERIA To be included , the intervention had to be relevant to public health practice , implemented , facilitated , or promoted by staff in local public health units , implemented in a school setting and aim ed at increasing physical activity , report on outcomes for children and adolescents ( aged 6 to 18 years ) , and use a prospect i ve design with a control group . DATA COLLECTION AND ANALYSIS St and ardized tools were used by two independent review ers to rate each study 's method ological quality and for data extraction . Where discrepancies existed discussion occurred until consensus was reached . The results were summarized narratively due to wide variations in the population s , interventions evaluated and outcomes measured . MAIN RESULTS 13,841 titles were identified and screened and 482 articles were retrieved . Multiple publications on the same project were combined and counted as one project , result ing in 395 distinct project accounts ( studies ) . Of the 395 studies 104 were deemed relevant and of those , four were assessed as having strong method ological quality , 22 were of moderate quality and 78 were considered weak . In total 26 studies were included in the review . There is good evidence that school-based physical activity interventions have a positive impact on four of the nine outcome measures . Specifically positive effects were observed for duration of physical activity , television viewing , VO2 max , and blood cholesterol . Generally school-based interventions had no effect on leisure time physical activity rates , systolic and diastolic blood pressure , body mass index , and pulse rate . At a minimum , a combination of printed educational material s and changes to the school curriculum that promote physical activity result in positive effects . AUTHORS ' CONCLUSIONS Given that there are no harmful effects and that there is some evidence of positive effects on lifestyle behaviours and physical health status measures , ongoing physical activity promotion in schools is recommended at this time
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"The effects of cardiovascular risk reduction are typically assessed by self-reported behavior change and physiological outcomes . There is a need to enhance evaluation protocol s by including direct observation measures of targeted health behaviors . To improve the evaluation of a family-based diet and physical activity change program , families were observed during a planned visit to the San Diego Zoo . This st and ardized environment afforded many options for dietary intake and physical activity . Thirty families who had participated in a 1-year intervention program and 30 control families were observed . Caucasian and Mexican-American families were equally represented . Observations in this st and ard environment discriminated between intervention and control families , and the findings indicated that intervention effects generalized to this novel setting . Intervention families consumed fewer calories , ate less sodium , and walked further than did control families . Ethnic differences were noted",
"Self-monitoring is often used in health behaviour change programs ; but it is not known to what extent self-monitoring data are valid and useful in predicting changes in cardiovascular disease ( CVD ) risk . Subjects included 72 Anglo adults , 68 Anglo children , 80 Mexican-American adults and 94 Mexican-American children . Subjects were families with fifth and sixth grade children who participated in an 18-session family-based diet and exercise change program design ed to reduce CVD risk . During the intervention , each participant self-monitored diet and aerobic physical activity . Families were measured at baseline , 3 , 12 , and 24 months . For adults , self-monitored changes in diet correlated with changes in body mass index , systolic blood pressure , total cholesterol and LDL 1 and 2 years later . Correlations between self-monitored diet and diet-related risk factor changes were not observed among children . Correlations between self-monitored exercise and subsequent risk factor changes were not observed among adults . For children , self monitored changes in aerobic physical activity correlated significantly with changes in VO2Max and HDL/LDL ratio 1 and 2 years later . Thus , this study provides some support for the predictive validity of diet self-monitoring in adults and exercise self-monitoring in children",
"This project tests the effectiveness of a family-based health behavior change intervention in two ethnic groups . The aim is to help family members initiate and maintain dietary and physical activity behaviors believed to be linked to risk factors for cardiovascular disease . This paper describes the project and the baseline results . Twelve San Diego elementary schools were r and omly assigned to intervention or control conditions . Hispanic and Anglo families with a fifth or sixth grade child were recruited to participate in a two-year study . The intervention emphasizes enjoyable experiences design ed to transmit knowledge and skills required for long-term changes in diet and physical activity habits . Groups of families met at schools for 12 weekly sessions and six maintenance sessions distributed throughout the following nine months . Outcome behavioral and physiologic measures will be collected at baseline , three months , 12 months , and 24 months . Differences between Anglo and Mexican-American subjects justify targeted activities specific to these groups"
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This paper review s the literature regarding the effects of cannabinoid administration on sleep in humans . A literature search using a set of cannabinoid and sleep-related terms was conducted across eight electronic data bases . Human studies that involved the administration of cannabinoids and at least one quantitative sleep-related measure were included . Review papers , opinion pieces , letters or editorials , case studies ( final N Thirty-nine publications were included in the review . Findings were mixed and showed various effects of cannabinoid administration on several aspects of sleep . Method ological issues in the majority of studies to date , however , preclude any definitive conclusion
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"UNLABELLED We assessed the efficacy of dronabinol ( Marinol capsules ; Solvay Pharmaceuticals , Brussels , Belgium ) , a synthetic Delta(9)-THC ( tetrahydrocannabinol ) , in 30 patients taking opioids for chronic pain to determine its potential analgesic effects as an adjuvant treatment . Phase I of this 2-phase study was a r and omized , single-dose , double-blinded , placebo-controlled , crossover trial in which subjects were r and omly administered either 10 mg or 20 mg of dronabinol or identical placebo capsules over the course of three , 8-hour visits . Baseline self-report measures , hourly ratings of pain intensity , pain relief , pain bothersomeness , treatment satisfaction , mood , side effects , and blood serum levels were obtained . Phase II was an extended open-label titrated trial of dronabinol as add-on medication to patients on stable doses of opioids . Results of the Phase I study showed that patients who received dronabinol experienced decreased pain intensity and increased satisfaction compared with placebo . No differences in benefit were found between the 20 mg and 10 mg doses . In the Phase II trial , titrated dronabinol contributed to significant relief of pain , reduced pain bothersomeness , and increased satisfaction compared with baseline . The incidence of side effects was dose-related . Overall , the use of dronabinol was found to result in additional analgesia among patients taking opioids for chronic noncancer pain . PERSPECTIVE This study examines the effect of adding a cannabinoid to the regimen of patients with chronic pain who report significant pain despite taking stable doses of opioids . The results of our preliminary study suggest that dronabinol , a synthetic THC , may have an additive effect on pain relief",
"OBJECTIVES Young people are sleeping less . Short sleep duration has a range of negative consequences including a hypothesized link with psychological distress , which has yet to be studied DESIGN Prospect i ve cohort study SETTING Community-based sample from Australia PARTICIPANTS Twenty thous and ( 20,822 ) young adults ( aged 17 - 24 ) identified through the state vehicle licensing authority . A r and om sample ( n = 5000 ) was approached for follow-up 12 - 18 months later , with 2837 providing full data . MAIN OUTCOME MEASURE Psychological distress , determined by a Kessler 10 score > 21 , at baseline ; and as both onset and persistence of distress at follow-up . RESULTS Shorter sleep duration was linearly associated with prevalent psychological distress : relative risk ( RR ) 1.14 ( 95 % CI 1.12 to 1.15 ) . Only the very short ( for onset of psychological distress ( RR 3.25 [ 95 % CI 1.84 , 5.75 ] ) . Of 945 cohort participants reporting psychological distress at baseline , 419 ( 44 % ) were distressed at follow-up . Each hour less of sleep increased the risk of psychological distress persisting after adjustment for potential confounding variables : RR 1.05 ( 95 % CI 1.01 to 1.10 ) . Long sleep duration showed no association with distress at any time point . CONCLUSIONS Self-reported shorter sleep duration is linearly associated with prevalent and persistent psychological distress in young adults . In contrast , only the very short sleepers had a raised risk of new onset of distress . Different approaches to sleep duration measurement yield different results and should guide any interventions to improve subjective sleep duration in young adults",
"This study compared the efficacy of a tetrahydrocannabinol : cannabidiol ( THC : CBD ) extract , a nonopioid analgesic endocannabinoid system modulator , and a THC extract , with placebo , in relieving pain in patients with advanced cancer . In total , 177 patients with cancer pain , who experienced inadequate analgesia despite chronic opioid dosing , entered a two-week , multicenter , double-blind , r and omized , placebo-controlled , parallel-group trial . Patients were r and omized to THC : CBD extract ( n = 60 ) , THC extract ( n = 58 ) , or placebo ( n = 59 ) . The primary analysis of change from baseline in mean pain Numerical Rating Scale ( NRS ) score was statistically significantly in favor of THC : CBD compared with placebo ( improvement of -1.37 vs. -0.69 ) , whereas the THC group showed a nonsignificant change ( -1.01 vs. -0.69 ) . Twice as many patients taking THC : CBD showed a reduction of more than 30 % from baseline pain NRS score when compared with placebo ( 23 [ 43 % ] vs. 12 [ 21 % ] ) . The associated odds ratio was statistically significant , whereas the number of THC group responders was similar to placebo ( 12 [ 23 % ] vs. 12 [ 21 % ] ) and did not reach statistical significance . There was no change from baseline in median dose of opioid background medication or mean number of doses of breakthrough medication across treatment groups . No significant group differences were found in the NRS sleep quality or nausea scores or the pain control assessment . However , the results from the European Organisation for Research and Treatment of Cancer Quality of Life Cancer Question naire showed a worsening in nausea and vomiting with THC : CBD compared with placebo ( P = 0.02 ) , whereas THC had no difference ( P = 1.0 ) . Most drug-related adverse events were mild/moderate in severity . This study shows that THC : CBD extract is efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids",
"Troubled sleep is a commonly cited consequence of adolescent drug use , but it has rarely been studied as a cause . Nor have there been any studies of the extent to which sleep behavior can spread in social networks from person to person to person . Here we map the social networks of 8,349 adolescents in order to study how sleep behavior spreads , how drug use behavior spreads , and how a friend 's sleep behavior influences one 's own drug use . We find clusters of poor sleep behavior and drug use that extend up to four degrees of separation ( to one 's friends ' friends ' friends ' friends ) in the social network . Prospect i ve regression models show that being central in the network negatively influences future sleep outcomes , but not vice versa . Moreover , if a friend sleeps ≤7 hours , it increases the likelihood a person sleeps ≤7 hours by 11 % . If a friend uses marijuana , it increases the likelihood of marijuana use by 110 % . Finally , the likelihood that an individual uses drugs increases by 19 % when a friend sleeps ≤7 hours , and a mediation analysis shows that 20 % of this effect results from the spread of sleep behavior from one person to another . This is the first study to suggest that the spread of one behavior in social networks influences the spread of another . The results indicate that interventions should focus on healthy sleep to prevent drug use and targeting specific individuals may improve outcomes across the entire social network",
"The objective was to determine whether a cannabis-based medicinal extract ( CBME ) benefits a range of symptoms due to multiple sclerosis ( MS ) . A parallel group , double-blind , r and omized , placebo-controlled study was undertaken in three centres , recruiting 160 out patients with MS experiencing significant problems from at least one of the following : spasticity , spasms , bladder problems , tremor or pain . The interventions were oromucosal sprays of matched placebo , or whole plant CBME containing equal amounts of delta-9- tetrahydrocannabinol ( THC ) and cannabidiol ( CBD ) at a dose of 2.5- 120 mg of each daily , in divided doses . The primary outcome measure was a Visual Analogue Scale ( VAS ) score for each patient ’s most troublesome symptom . Additional measures included VAS scores of other symptoms , and measures of disability , cognition , mood , sleep and fatigue . Following CBME the primary symptom score reduced from mean ( SE ) 74.36 ( 11.1 ) to 48.89 ( 22.0 ) following CBME and from 74.31 ( 12.5 ) to 54.79 ( 26.3 ) following placebo [ ns ] . Spasticity VAS scores were significantly reduced by CBME ( Sativex ) in comparison with placebo ( P- 0.001 ) . There were no significant adverse effects on cognition or mood and intoxication was generally mild",
"Objective : To test the effectiveness and long term safety of cannabinoids in multiple sclerosis ( MS ) , in a follow up to the main Cannabinoids in Multiple Sclerosis ( CAMS ) study . Methods : In total , 630 patients with stable MS with muscle spasticity from 33 UK centres were r and omised to receive oral Δ9-tetrahydrocannabinol ( Δ9-THC ) , cannabis extract , or placebo in the main 15 week CAMS study . The primary outcome was change in the Ashworth spasticity scale . Secondary outcomes were the Rivermead Mobility Index , timed 10 metre walk , UK Neurological Disability Score , postal Barthel Index , General Health Question naire-30 , and a series of nine category rating scales . Following the main study , patients were invited to continue medication , double blinded , for up to12 months in the follow up study reported here . Results : Intention to treat analysis of data from the 80 % of patients followed up for 12 months showed evidence of a small treatment effect on muscle spasticity as measured by change in Ashworth score from baseline to 12 months ( Δ9-THC mean reduction 1·82 ( n = 154 , 95 % confidence interval ( CI ) 0.53 to 3.12 ) , cannabis extract 0.10 ( n = 172 , 95 % CI −0.99 to 1.19 ) , placebo −0.23 ( n = 176 , 95 % CI −1.41 to 0.94 ) ; p = 0.04 unadjusted for ambulatory status and centre , p = 0.01 adjusted ) . There was suggestive evidence for treatment effects of Δ9-THC on some aspects of disability . There were no major safety concerns . Overall , patients felt that these drugs were helpful in treating their disease . Conclusions : These data provide limited evidence for a longer term treatment effect of cannabinoids . A long term placebo controlled study is now needed to establish whether cannabinoids may have a role beyond symptom amelioration in MS",
"Background : Central pain in multiple sclerosis ( MS ) is common and often refractory to treatment . Methods : We conducted a single-center , 5-week ( 1-week run-in , 4-week treatment ) , r and omized , double-blind , placebo-controlled , parallel-group trial in 66 patients with MS and central pain states ( 59 dysesthetic , seven painful spasms ) of a whole-plant cannabis-based medicine ( CBM ) , containing delta-9-tetrahydrocannabinol : cannabidiol ( THC : CBD ) delivered via an oromucosal spray , as adjunctive analgesic treatment . Each spray delivered 2.7 mg of THC and 2.5 of CBD , and patients could gradually self-titrate to a maximum of 48 sprays in 24 hours . Results : Sixty-four patients ( 97 % ) completed the trial , 34 received CBM . In week 4 , the mean number of daily sprays taken of CBM ( n = 32 ) was 9.6 ( range 2 to 25 , SD = 6.0 ) and of placebo ( n = 31 ) was 19.1 ( range 1 to 47 , SD = 12.9 ) . Pain and sleep disturbance were recorded daily on an 11-point numerical rating scale . CBM was superior to placebo in reducing the mean intensity of pain ( CBM mean change −2.7 , 95 % CI : −3.4 to −2.0 , placebo –1.4 95 % CI : −2.0 to −0.8 , comparison between groups , p = 0.005 ) and sleep disturbance ( CBM mean change –2.5 , 95 % CI : −3.4 to −1.7 , placebo –0.8 , 95 % CI : −1.5 to −0.1 , comparison between groups , p = 0.003 ) . CBM was generally well tolerated , although more patients on CBM than placebo reported dizziness , dry mouth , and somnolence . Cognitive side effects were limited to long-term memory storage . Conclusions : Cannabis-based medicine is effective in reducing pain and sleep disturbance in patients with multiple sclerosis related central neuropathic pain and is mostly well tolerated",
"BACKGROUND Spasticity is a disabling complication of multiple sclerosis , affecting many patients with the condition . We report the first Phase 3 placebo-controlled study of an oral antispasticity agent to use an enriched study design . METHODS A 19-week follow-up , multicentre , double-blind , r and omized , placebo-controlled , parallel-group study in subjects with multiple sclerosis spasticity not fully relieved with current antispasticity therapy . Subjects were treated with nabiximols , as add-on therapy , in a single-blind manner for 4weeks , after which those achieving an improvement in spasticity of ≥20 % progressed to a 12-week r and omized , placebo-controlled phase . RESULTS Of the 572 subjects enrolled , 272 achieved a ≥20 % improvement after 4weeks of single-blind treatment , and 241 were r and omized . The primary end-point was the difference between treatments in the mean spasticity Numeric Rating Scale ( NRS ) in the r and omized , controlled phase of the study . Intention-to-treat ( ITT ) analysis showed a highly significant difference in favour of nabiximols ( P=0.0002 ) . Secondary end-points of responder analysis , Spasm Frequency Score , Sleep Disturbance NRS Patient , Carer and Clinician Global Impression of Change were all significant in favour of nabiximols . CONCLUSIONS The enriched study design provides a method of determining the efficacy and safety of nabiximols in a way that more closely reflects proposed clinical practice , by limiting exposure to those patients who are likely to benefit from it . Hence , the difference between active and placebo should be a reflection of efficacy and safety in the population intended for treatment",
"Abstract : The effects of cannabis extracts on nocturnal sleep , early-morning performance , memory , and sleepiness were studied in 8 healthy volunteers ( 4 males , 4 females ; 21 to 34 years ) . The study was double-blind and placebo-controlled with a 4-way crossover design . The 4 treatments were placebo , 15 mg Δ-9-tetrahydrocannabinol ( THC ) , 5 mg THC combined with 5 mg cannabidiol ( CBD ) , and 15 mg THC combined with 15 mg CBD . These were formulated in 50:50 ethanol to propylene glycol and administered using an oromucosal spray during a 30-minute period from 10 pm . The electroencephalogram was recorded during the sleep period ( 11 pm to 7 am ) . Performance , sleep latency , and subjective assessment s of sleepiness and mood were measured from 8:30 am ( 10 hours after drug administration ) . There were no effects of 15 mg THC on nocturnal sleep . With the concomitant administration of the drugs ( 5 mg THC and 5 mg CBD to 15 mg THC and 15 mg CBD ) , there was a decrease in stage 3 sleep , and with the higher dose combination , wakefulness was increased . The next day , with 15 mg THC , memory was impaired , sleep latency was reduced , and the subjects reported increased sleepiness and changes in mood . With the lower dose combination , reaction time was faster on the digit recall task , and with the higher dose combination , subjects reported increased sleepiness and changes in mood . Fifteen milligrams THC would appear to be sedative , while 15 mg CBD appears to have alerting properties as it increased awake activity during sleep and counteracted the residual sedative activity of 15 mg THC",
"Background : Chronic neuropathic pain affects 1%–2 % of the adult population and is often refractory to st and ard pharmacologic treatment . Patients with chronic pain have reported using smoked cannabis to relieve pain , improve sleep and improve mood . Methods : Adults with post-traumatic or postsurgical neuropathic pain were r and omly assigned to receive cannabis at four potencies ( 0 % , 2.5 % , 6 % and 9.4 % tetrahydrocannabinol ) over four 14-day periods in a crossover trial . Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle , followed by a nine-day washout period . Daily average pain intensity was measured using an 11-point numeric rating scale . We recorded effects on mood , sleep and quality of life , as well as adverse events . Results : We recruited 23 participants ( mean age 45.4 [ st and ard deviation 12.3 ] years , 12 women [ 52 % ] ) , of whom 21 completed the trial . The average daily pain intensity , measured on the 11-point numeric rating scale , was lower on the prespecified primary contrast of 9.4 % v. 0 % tetrahydrocannabinol ( 5.4 v. 6.1 , respectively ; difference = 0.7 , 95 % confidence interval [ CI ] 0.02–1.4 ) . Preparations with intermediate potency yielded intermediate but nonsignificant degrees of relief . Participants receiving 9.4 % tetrahydrocannabinol reported improved ability to fall asleep ( easier , p = 0.001 ; faster , p drowsy , p = 0.003 ) and improved quality of sleep ( less wakefulness , p = 0.01 ) relative to 0 % tetrahydrocannabinol . We found no differences in mood or quality of life . The most common drug-related adverse events during the period when participants received 9.4 % tetrahydrocannabinol were headache , dry eyes , burning sensation in areas of neuropathic pain , dizziness , numbness and cough . Conclusion : A single inhalation of 25 mg of 9.4 % tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain , improved sleep and was well tolerated . Further long-term safety and efficacy studies are indicated . ( International St and ard R and omised Controlled Trial Register no. IS RCT N68314063",
"Objective Multiple sclerosis ( MS ) is associated with chronic symptoms , including muscle stiffness , spasms , pain and insomnia . Here we report the results of the Multiple Sclerosis and Extract of Cannabis ( MUSEC ) study that aim ed to substantiate the patient based findings of previous studies . Patients and methods Patients with stable MS at 22 UK centres were r and omised to oral cannabis extract ( CE ) ( N=144 ) or placebo ( N=135 ) , stratified by centre , walking ability and use of antispastic medication . This double blind , placebo controlled , phase III study had a screening period , a 2 week dose titration phase from 5 mg to a maximum of 25 mg of tetrahydrocannabinol daily and a 10 week maintenance phase . The primary outcome measure was a category rating scale ( CRS ) measuring patient reported change in muscle stiffness from baseline . Further CRSs assessed body pain , spasms and sleep quality . Three vali date d MS specific patient reported outcome measures assessed aspects of spasticity , physical and psychological impact , and walking ability . Results The rate of relief from muscle stiffness after 12 weeks was almost twice as high with CE than with placebo ( 29.4 % vs 15.7 % ; OR 2.26 ; 95 % CI 1.24 to 4.13 ; p=0.004 , one sided ) . Similar results were found after 4 weeks and 8 weeks , and also for all further CRSs . Results from the MS scales supported these findings . Conclusion The study met its primary objective to demonstrate the superiority of CE over placebo in the treatment of muscle stiffness in MS . This was supported by results for secondary efficacy variables . Adverse events in participants treated with CE were consistent with the known side effects of cannabinoids . No new safety concerns were observed . Trial registration number NCT00552604",
"BACKGROUND : Sleep disorders affect many patients with chronic pain conditions . Cannabis has been reported by several patient population s to help sleep . We evaluated the safety and efficacy of nabilone , a synthetic cannabinoid , on sleep disturbance in fibromyalgia ( FM ) , a disease characterized by widespread chronic pain and insomnia . METHODS : We conducted a r and omized , double-blind , active-control , equivalency crossover trial to compare nabilone ( 0.5–1.0 mg before bedtime ) to amitriptyline ( 10–20 mg before bedtime ) in patients with FM with chronic insomnia . Subjects received each drug for 2 wk with a 2-wk washout period . The primary outcome was sleep quality , measured by the Insomnia Severity Index and the Leeds Sleep Evaluation Question naire . Secondary outcomes included pain , mood , quality of life , and adverse events ( AEs ) . RESULTS : Thirty-one subjects were enrolled and 29 completed the trial ( 26 women , mean age 49.5 yr ) . Although sleep was improved by both amitriptyline and nabilone , nabilone was superior to amitriptyline ( Insomnia Severity Index difference = 3.2 ; 95 % confidence interval = 1.2–5.3 ) . Nabilone was marginally better on the restfulness ( Leeds Sleep Evaluation Question naire difference = 0.5 [ 0.0–1.0 ] ) but not on wakefulness ( difference = 0.3 [ −0.2 to 0.8 ] ) . No effects on pain , mood , or quality of life were observed . AEs were mostly mild to moderate and were more frequent with nabilone . The most common AEs for nabilone were dizziness , nausea , and dry mouth . CONCLUSIONS : Nabilone is effective in improving sleep in patients with FM and is well tolerated . Low-dose nabilone given once daily at bedtime may be considered as an alternative to amitriptyline . Longer trials are needed to determine the duration of effect and to characterize long-term safety",
"BACKGROUND Multiple sclerosis is associated with muscle stiffness , spasms , pain , and tremor . Much anecdotal evidence suggests that cannabinoids could help these symptoms . Our aim was to test the notion that cannabinoids have a beneficial effect on spasticity and other symptoms related to multiple sclerosis . METHODS We did a r and omised , placebo-controlled trial , to which we enrolled 667 patients with stable multiple sclerosis and muscle spasticity . 630 participants were treated at 33 UK centres with oral cannabis extract ( n=211 ) , Delta9-tetrahydrocannabinol ( Delta9-THC ; n=206 ) , or placebo ( n=213 ) . Trial duration was 15 weeks . Our primary outcome measure was change in overall spasticity scores , using the Ashworth scale . Analysis was by intention to treat . FINDINGS 611 of 630 patients were followed up for the primary endpoint . We noted no treatment effect of cannabinoids on the primary outcome ( p=0.40 ) . The estimated difference in mean reduction in total Ashworth score for participants taking cannabis extract compared with placebo was 0.32 ( 95 % CI -1.04 to 1.67 ) , and for those taking Delta9-THC versus placebo it was 0.94 ( -0.44 to 2.31 ) . There was evidence of a treatment effect on patient-reported spasticity and pain ( p=0.003 ) , with improvement in spasticity reported in 61 % ( n=121 , 95 % CI 54.6 - 68.2 ) , 60 % ( n=108 , 52.5 - 66.8 ) , and 46 % ( n=91 , 39.0 - 52.9 ) of participants on cannabis extract , Delta9-THC , and placebo , respectively . INTERPRETATION Treatment with cannabinoids did not have a beneficial effect on spasticity when assessed with the Ashworth scale . However , though there was a degree of unmasking among the patients in the active treatment groups , objective improvement in mobility and patients ' opinion of an improvement in pain suggest cannabinoids might be clinical ly useful",
"& NA ; The objective was to investigate the effectiveness of cannabis‐based medicines for treatment of chronic pain associated with brachial plexus root avulsion . This condition is an excellent human model of central neuropathic pain as it represents an unusually homogenous group in terms of anatomical location of injury , pain descriptions and patient demographics . Forty‐eight patients with at least one avulsed root and baseline pain score of four or more on an 11‐point ordinate scale participated in a r and omised , double‐blind , placebo‐controlled , three period crossover study . All patients had intractable symptoms regardless of current analgesic therapy . Patients entered a baseline period of 2 weeks , followed by three , 2‐week treatment periods during each of which they received one of three oromucosal spray preparations . These were placebo and two whole plant extracts of Cannabis sativa L. : GW‐1000‐02 ( Sativex ® ) , containing Δ9tetrahydrocannabinol (THC):cannabidiol ( CBD ) in an approximate 1:1 ratio and GW‐2000‐02 , containing primarily THC . The primary outcome measure was the mean pain severity score during the last 7 days of treatment . Secondary outcome measures included pain related quality of life assessment s. The primary outcome measure failed to fall by the two points defined in our hypothesis . However , both this measure and measures of sleep showed statistically significant improvements . The study medications were generally well tolerated with the majority of adverse events , including intoxication type reactions , being mild to moderate in severity and resolving spontaneously . Studies of longer duration in neuropathic pain are required to confirm a clinical ly relevant , improvement in the treatment of this condition",
"Rationale Dronabinol ( Δ9tetrahydrocannabinol ) is approved for HIV-related anorexia , yet , little is known about its effects in HIV-positive marijuana smokers . HIV-negative marijuana smokers require higher than recommended dronabinol doses to experience expected effects . Objectives Employing a within-subjects , double-blind , placebo-controlled design , we assessed the effects of repeated high-dose dronabinol in HIV-positive marijuana smokers taking antiretroviral medication . Methods Participants ( N = 7 ) , who smoked marijuana 4.2 ± 2.3 days/week , resided in a residential laboratory for two 16-day stays , receiving dronabinol ( 10 mg QID ) in one stay and placebo in the other . Efficacy was assessed with objective ly verified food intake and body weight . Tolerability was measured with sleep , subjective , and cognitive assessment s. For analyses , each inpatient stay was divided into two phases , days 1–8 and 9–16 ; we compared dronabinol ’s effects with placebo in each 8-day phase to investigate tolerance . Results Despite sustained increases in self-reported food cravings , dronabinol only increased caloric intake in the initial 8 days of dosing . Similarly , sleep quality was improved only in the first 8 days of dosing . Dronabinol ’s mood-enhancing effects were sustained across the 16-day inpatient stay . Dronabinol was well tolerated , causing few negative subjective or cognitive effects . Conclusions In HIV-positive marijuana smokers , high dronabinol doses safely and effectively increased caloric intake . However , repeated high-dose dronabinol appeared to result in selective tolerance to these effects . These findings indicate that HIV-positive individuals who smoke marijuana may require higher dronabinol doses than are recommended by the FDA . Future research to establish optimal dosing regimens , and reduce the development of tolerance , is required",
"OBJECTIVES To assess the efficacy of a cannabis-based medicine ( CBM ) in the treatment of pain due to rheumatoid arthritis ( RA ) . METHODS We compared a CBM ( Sativex ) with placebo in a r and omized , double-blind , parallel group study in 58 patients over 5 weeks of treatment . The CBM was administered by oromucosal spray in the evening and assessment s were made the following morning . Efficacy outcomes assessed were pain on movement , pain at rest , morning stiffness and sleep quality measured by a numerical rating scale , the Short-Form McGill Pain Question naire ( SF-MPQ ) and the DAS28 measure of disease activity . RESULTS Seventy-five patients were screened and 58 met the eligibility criteria . Thirty-one were r and omized to the CBM and 27 to placebo . Mean ( S.D. ) daily dose achieved in the final treatment week was 5.4 ( 0.84 ) actuations for the CBM and 5.3 ( 1.18 ) for placebo . In comparison with placebo , the CBM produced statistically significant improvements in pain on movement , pain at rest , quality of sleep , DAS28 and the SF-MPQ pain at present component . There was no effect on morning stiffness but baseline scores were low . The large majority of adverse effects were mild or moderate , and there were no adverse effect-related withdrawals or serious adverse effects in the active treatment group . CONCLUSIONS In the first ever controlled trial of a CBM in RA , a significant analgesic effect was observed and disease activity was significantly suppressed following Sativex treatment . Whilst the differences are small and variable across the population , they represent benefits of clinical relevance and show the need for more detailed investigation in this indication",
"Three Cannabis Based Medicinal Extracts ( CBMEs ) for sublingual use became available in 2000 . A total of 34 ‘ N of 1 ’ studies were undertaken using this novel therapy for patients with chronic , mainly neuropathic , pain and associated symptoms to explore efficacy , tolerability , safety and dosages . Three CBMEs ( Δ9 Tetrahydrocannabinol ( THC ) , Cannabidiol ( CBD ) and a 1 : 1 mixture of them both ) were given over a 12‐week period . After an initial open‐label period , the CBMEs were used in a r and omised , double‐blind , placebo controlled , crossover trial . Extracts which contained THC proved most effective in symptom control . Regimens for the use of the sublingual spray emerged and a wide range of dosing requirements was observed . Side‐effects were common , reflecting a learning curve for both patient and study team . These were generally acceptable and little different to those seen when other psycho‐active agents are used for chronic pain . These initial experiences with CBME open the way to more detailed and extensive studies",
"Background Many patients with amyotrophic lateral sclerosis ( ALS ) experience cramps during the course of the disease but so far , none of the medications used has been of proven benefit . The objective was to determine the effect of orally administered tetrahydrocannabinol ( THC ) on cramps in ALS patients . Methods The authors conducted a r and omised , double-blind , placebo-controlled crossover trial in 27 ALS patients suffering from moderate to severe ( visual analogue scale ( VAS ) ; VAS≥4 ) daily cramps . There were 7 women and 20 men with a mean age of 57 years and a mean functional ALS score ( ALSFRS-R ) of 38.4 . Patients were r and omly assigned to receive 5 mg THC twice daily followed by placebo or vice versa . Each treatment period lasted for 2 weeks and was preceded by a 2-week drug-free observation period ( run-in , wash-out period respectively ) . The primary outcome measure was change in cramp intensity as assessed by a VAS . Secondary outcome measures included the number of cramps per day , number of cramps during daytime and bedtime , intensity of fasciculations ( VAS ) as well as vali date d measures of quality of life ( ALSAQ-40 ) , quality of sleep ( SDQ ) , appetite ( FAACT ) and depression ( HADS ) . Results Complete data were available from 22 patients . THC was well tolerated . There was no evidence for a treatment effect on cramp intensity , number of cramps , fasciculation intensity or any of the other secondary outcome measures . Conclusions This interventional study with orally administered THC 5 mg twice daily did not demonstrate subjective improvement of cramp intensity in ALS patients",
"The duration of behavioral impairment after marijuana smoking remains a matter of some debate . Alcohol and marijuana are frequently used together , but there has been little study of the effects of this drug combination on mood and behavior the day after use . The present study was design ed to address these issues . Fourteen male and female subjects were each studied under four conditions : alcohol alone , marijuana alone , alcohol and marijuana in combination , and no active treatment . Mood and performance assessment s were made during acute intoxication and twice the following day ( morning and mid-afternoon ) . Acutely , each drug alone produced moderate levels of subjective intoxication and some degree of behavioral impairment . The drug combination produced the greatest level of impairment on most tasks and “ strong ” overall subjective ratings . There were few significant interactions between the two drugs , indicating that their effects tended to be additive . Only weak evidence was obtained for subjective or behavioral effects the day after active drug treatments , although consistent time-of-day effects ( morning versus afternoon ) were observed on several subjective and behavioral measures . In sum , this study provided little evidence that moderate doses of alcohol and marijuana , consumed either alone or in combination , produce behavioral or subjective impairment the following day",
"Objective To compare the analgesic efficacy and side effects of the synthetic cannabinoid nabilone with those of the weak opioid dihydrocodeine for chronic neuropathic pain . Design R and omised , double blind , crossover trial of 14 weeks ’ duration comparing dihydrocodeine and nabilone . Setting Outpatient units of three hospitals in the United Kingdom . Participants 96 patients with chronic neuropathic pain , aged 23 - 84 years . Main outcome measures The primary outcome was difference between nabilone and dihydrocodeine in pain , as measured by the mean visual analogue score computed over the last 2 weeks of each treatment period . Secondary outcomes were changes in mood , quality of life , sleep , and psychometric function . Side effects were measured by a question naire . Intervention Patients received a maximum daily dose of 240 mg dihydrocodeine or 2 mg nabilone at the end of each escalating treatment period of 6 weeks . Treatment periods were separated by a 2 week washout period . Results Mean baseline visual analogue score was 69.6 mm ( range 29.4 - 95.2 ) on a 0 - 100 mm scale . 73 patients were included in the available case analysis and 64 patients in the per protocol analysis . The mean score was 6.0 mm longer for nabilone than for dihydrocodeine ( 95 % confidence interval 1.4 to 10.5 ) in the available case analysis and 5.6 mm ( 10.3 to 0.8 ) in the per protocol analysis . Side effects were more frequent with nabilone . Conclusion Dihydrocodeine provided better pain relief than the synthetic cannabinoid nabilone and had slightly fewer side effects , although no major adverse events occurred for either drug . Trial registration Current Controlled Trials IS RCT N15330757",
"UNLABELLED Patients with advanced cancer who have pain that responds poorly to opioid therapy pose a clinical challenge . Nabiximols ( Nabiximols is the U.S. Adopted Name [ USAN ] for Sativex [ GW Pharma Ltd , Wiltshire , U.K. ] , which does not yet have an INN ) , a novel cannabinoid formulation , is undergoing investigation as add-on therapy for this population . In a r and omized , double-blind , placebo-controlled , grade d-dose study , patients with advanced cancer and opioid-refractory pain received placebo or nabiximols at a low dose ( 1 - 4 sprays/day ) , medium dose ( 6 - 10 sprays/day ) , or high dose ( 11 - 16 sprays/day ) . Average pain , worst pain and sleep disruption were measured daily during 5 weeks of treatment ; other question naires measured quality of life and mood . A total of 360 patients were r and omized ; 263 completed . There were no baseline differences across groups . The 30 % responder rate primary analysis was not significant for nabiximols versus placebo ( overall P = .59 ) . A secondary continuous responder analysis of average daily pain from baseline to end of study demonstrated that the proportion of patients reporting analgesia was greater for nabiximols than placebo overall ( P = .035 ) , and specifically in the low-dose ( P = .008 ) and medium-dose ( P = .039 ) groups . In the low-dose group , results were similar for mean average pain ( P = .006 ) , mean worst pain ( P = .011 ) , and mean sleep disruption ( P = .003 ) . Other question naires showed no significant group differences . Adverse events were dose-related and only the high-dose group compared unfavorably with placebo . This study supports the efficacy and safety of nabiximols at the 2 lower-dose levels and provides important dose information for future trials . PERSPECTIVE Nabiximols , a novel cannabinoid formulation , may be a useful add-on analgesic for patients with opioid-refractory cancer pain . A r and omized , double-blind , placebo-controlled , grade d-dose study demonstrated efficacy and safety at low and medium doses",
"Abstract Cannabinoids are known to have analgesic properties . We evaluated the effect of oro‐mucosal sativex , ( THC : CBD ) , an endocannabinoid system modulator , on pain and allodynia , in 125 patients with neuropathic pain of peripheral origin in a five‐week , r and omised , double‐blind , placebo‐controlled , parallel design trial . Patients remained on their existing stable analgesia . A self‐titrating regimen was used to optimise drug administration . Sixty‐three patients were r and omised to receive sativex and 62 placebo . The mean reduction in pain intensity scores ( primary outcome measure ) was greater in patients receiving sativex than placebo ( mean adjusted scores −1.48 points vs. −0.52 points on a 0–10 Numerical Rating Scale ( p = 0.004 ; 95 % CI : −1.59 , −0.32 ) . Improvements in Neuropathic Pain Scale composite score ( p = 0.007 ) , sleep NRS ( p = 0.001 ) , dynamic allodynia ( p = 0.042 ) , punctate allodynia ( p = 0.021 ) , Pain Disability Index ( p = 0.003 ) and Patient ’s Global Impression of Change ( p vs. placebo . Sedative and gastrointestinal side effects were reported more commonly by patients on active medication . Of all participants , 18 % on sativex and 3 % on placebo withdrew during the study . An open‐label extension study showed that the initial pain relief was maintained without dose escalation or toxicity for 52 weeks",
"Objectives : Individuals with HIV constitute the largest group using cannabinoids for medicinal reasons ; yet , no studies have directly compared the tolerability and efficacy of smoked marijuana and oral dronabinol maintenance in HIV-positive marijuana smokers . This placebo-controlled within-subjects study evaluated marijuana and dronabinol across a range of behaviors : eating topography , mood , cognitive performance , physiologic measures , and sleep . Methods : HIV-positive marijuana smokers ( n = 10 ) completed 2 16-day inpatient phases . Each dronabinol ( 5 and 10 mg ) and marijuana ( 2.0 % and 3.9 % Δ9-tetrahydrocannabinol [ THC ] ) dose was administered 4 times daily for 4 days , but only 1 drug was active per day , thereby maintaining double-blind dosing . Four days of placebo washout separated each active cannabinoid condition . Results : As compared with placebo , marijuana and dronabinol dose dependently increased daily caloric intake and body weight in HIV-positive marijuana smokers . All cannabinoid conditions produced significant intoxication , except for low-dose dronabinol ( 5 mg ) ; the intoxication was rated positively ( eg , “ good drug effect ” ) with little evidence of discomfort and no impairment of cognitive performance . Effects of marijuana and dronabinol were comparable , except that only marijuana ( 3.9 % THC ) improved ratings of sleep . Conclusions : These data suggest that for HIV-positive marijuana smokers , both dronabinol ( at doses 8 times current recommendations ) and marijuana were well tolerated and produced substantial and comparable increases in food intake ",
"Neuropathic pain ( NeP ) is prevalent in patients with peripheral neuropathy ( PN ) , regardless of etiology . We sought to compare the efficacy of the cannabinoid nabilone as either monotherapy or adjuvant therapy with a first-line medication for NeP , gabapentin , in a patient population with PN-NeP. Patients diagnosed with PN-NeP were permitted to initiate monotherapy ( nabilone or gabapentin ) or add one of these two medications ( adjuvant therapy ) to their existing NeP treatment regimen in a non-r and omized open-label nature . Baseline data collected included a primary outcome ( visual analog scores [ VAS ] of pain ) and secondary outcomes ( quality of life [ EuroQol 5 Domains and Short-Form 36 ] assessment s and assessment s of sleep [ Medical Outcomes Sleep Study Scale { MOSSS } ] , anxiety and depression [ Hospital Anxiety and Depression Scale ] , and pain [ Brief Pain Inventory ] ) . Re assessment and modulation of dosing and /or medications occurred at 3- and 6-month intervals . Medication adverse effects and drug efficacy , as well as question naires , were assessed at 6 months . Matched analysis of variance testing was performed to compare 3- and 6-month scores with baseline , as well as to compare therapies at equal time points . Significant improvements in pain VAS were seen in all treatment groups at 6 months . Numerous sleep parameters within MOSSS , Brief Pain Inventory , and Short-Form 36 improved in patients receiving nabilone or gabapentin either as monotherapy or adjuvant treatment . Hospital Anxiety and Depression Scale-A scores were significantly improved in all treatment groups . Sleep adequacy and the sleep problems index within the MOSSS improved in nabilone monotherapy patients in particular . The benefits of monotherapy or adjuvant therapy with nabilone appear comparable to gabapentin for management of NeP. We advocate for head-to-head r and omized , double-blind studies for current therapies for NeP in order to determine potential advantages beneficial in this patient population",
"TOC summary This enriched‐enrollment , r and omized , double‐blind , placebo‐controlled , flexible‐dose adjuvant study demonstrated that nabilone provided improvements in pain , anxiety , quality of life and patient satisfaction for patients with diabetic neuropathic pain . ABSTRACT Cannabinoids are emerging as potential options for neuropathic pain treatment . This study evaluated an oral cannabinoid , nabilone , in the treatment of refractory human diabetic peripheral neuropathic pain ( DPN ) . We performed a single‐center , r and omized , double‐blind , placebo‐controlled , flexible‐dose study with an enriched enrolment r and omized withdrawal design . DPN subjects with a pain score ⩾4 ( 0‐10 scale ) continued regular pain medications and were administered single‐blinded adjuvant nabilone for 4 weeks . Subjects achieving ⩾30 % pain relief ( 26/37 ) were then r and omized and treated with either flexible‐dose nabilone 1‐4 mg/day ( n = 13 ) or placebo ( n = 13 ) in a further 5‐week double‐blind treatment period , with 30 % ( 11/37 ) of subjects deemed run‐in‐phase nabilone nonresponders . For nabilone run‐in‐phase responders , there was an improvement in the change in mean end‐point neuropathic pain vs placebo ( mean treatment reduction of 1.27 ; 95 % confidence interval 2.29‐0.25 , P = 0.02 ) , with an average nabilone dose at end point of 2.9 ± 1.1 mg/day , and improvements from baseline for the anxiety subscale of the Hospital Anxiety and Depression Scale , the Medical Outcomes Study sleep scale problems index , and the European Quality of Life‐5‐Domains index score ( each P greater global end‐point improvement with nabilone than with placebo ( 100 % vs 31 % ; P 0.05 ) . Medication‐related confusion led to discontinuation in 2/37 subjects during single‐blind nabilone treatment . Potential unmasking occurred in 62 % of both groups . Flexible‐dose nabilone 1‐4 mg/day was effective in relieving DPN symptoms , improving disturbed sleep , quality of life , and overall patient status . Nabilone was well tolerated and successful as adjuvant in patients with DPN",
"Cannabinoids have been used for pain relief for centuries and recent studies have investigated their analgesic and anti-inflammatory mechanisms , as well as clinical efficacy , in treating chronic pain . We report an open-label study addressed to evaluate the effect and adverse events of orally administered Δ -9-tetrahydrocannabinol ( Δ -9-THC ) in 13 patients with chronic nonmalignant pain ( CNMP ) unresponsive to conventional pharmacotherapy . The effect of the treatment was assessed on an eight-item HRQoL question naire . Five out of 13 patients reported adequate response to the treatment while eight patients reported inadequate or no response . Seven patients did not experience any adverse events ( AEs ) , six patients reported AEs , two of which discontinued the treatment . We conclude that oral THC may be a valuable therapeutic option for selected patients with CNMP that are unresponsive to previous treatments , though further research is warranted to characterize those patients",
"The reinforcing and subjective effects of oral delta-9-tetrahydrocannabinol ( THC ) and smoked marijuana were studied in two groups of regular marijuana users . One group ( N = 10 ) was tested with smoked marijuana and the other ( N = 11 ) with oral THC . Reinforcing effects were measured with a discrete-trial choice procedure which allowed subjects to choose between the self-administration of active drug or placebo on two independent occasions . Subjective effects and heart rate were measured before and after drug administration . Smoked active marijuana was chosen over placebo on both choice occasions by all subjects . Similarly , oral THC was chosen over placebo on both occasions by all but one subject . Both active drug treatments produced qualitatively and quantitatively similar subjective effects , and both significantly increased heart rate , although the time course of effects differed substantially between the two treatments . The results demonstrate that both smoked marijuana and oral THC can serve as positive reinforcers in human subjects under laboratory conditions . The experimental paradigm used here should prove useful for identifying factors that influence the self-administration of marijuana and other cannabinoids by humans",
"Purpose Cannabinoids have been shown to have analgesic properties in animal studies , but a potential role for these drugs in acute pain management has not been established . It was hypothesized that nabilone , an oral cannabinoid synthetic tetrahydrocannabinol analogue , decreases morphine consumption , pain scores , nausea and vomiting following major surgery . Methods A double-blind , r and omized , placebo-controlled , parallel-group pilot trial compared the effects of two different doses , 1 mg ( n = 11 ) and 2 mg ( n = 9 ) of nabilone , ketoprofen 50 mg ( n = 11 ) or placebo ( n = 10 ) , given at eight-hour intervals for 24 hr . Outcomes included morphine consumption , pain scores and emesis after major surgery . Secondary outcomes included patient tolerability of the study medication . Results Forty-one patients ( mean age 52 ± 2 yr ) undergoing gynecologic ( 46 % ) , orthopedic ( 44 % ) , or other ( 10 % ) surgery were recruited . Cumulative 24-hr morphine consumption was not different between the four groups , but pain scores at rest and on movement were significantly higher in the 2 mg nabilone group compared to the other groups . There were no significant differences between groups with respect to episodes of nausea and vomiting , quality of sleep , sedation , euphoria , pruritus , or the number and severity of adverse events . No serious adverse event was recorded . Conclusions Contrary to the main hypothesis , high dose nabilone in the presence of morphine patient controlled analgesia is associated with an increase in pain scores in patients undergoing major surgery . RésuméObjectifLes propriétés analgésiques des cannabinoïdes ont été démontrées chez des animaux , mais leur rôle possible sur le contrôle de la douleur aiguë n’a pas été établi . Notre hypothèse voulait que la nabilone , analogue synthétique oral du cannabinoïde tétrahydrocannabinol , diminue la consommation de morphine , les scores de douleur , les nausées et les vomissements à la suite d’une opération chirurgicale majeure . MéthodeDans une étude pilote de groupes parallèles , r and omisée , à double insu et contrôlée contre placebo , les effets de deux doses de nabilone , 1 mg ( n = 11 ) et 2 mg ( n = 9 ) , de 50 mg de kétoprofène ( n = 11 ) ou d’un placebo ( n = 10 ) , administrés à 8 h d’intervalle pendant 24 h , ont été comparés . La consommation de morphine , les scores de douleur et les vomissements ont été notés après une chirurgie majeure . Les effets de la médication sur le patient étaient également étudiés . RésultatsQuarante et un patients ( moyenne d’âge de 52 ± 2 ans ) subissant une intervention gynécologique ( 46 % ) , orthopédique ( 44 % ) ou autre ( 10 % ) ont été recrutés . La consommation cumulative de morphine sur 24 h était similaire dans les quatre groupes , mais les scores de douleur au repos et au mouvement ont été significativement plus élevés dans le groupe nabilone 2 mg . Aucune différence intergroupe significative n’est apparue quant aux épisodes de nausées et de vomissements , la qualité du sommeil , la sédation , l’euphorie , le prurit ou le nombre et la sévérité des événements indésirables . Aucun incident sérieux n’a été enregistré . Conclusion Contrairement à notre hypothèse , une forte dose de nabilone , en présence de morphine administrée comme analgésie auto-contrôlée , est associée à une hausse des scores de douleur chez les patients qui subissent une chirurgie majeure",
"Δ9-Tetrahydrocannabinol ( Δ9-THC ) , the most prominent psychoactive cannabinoid in Cannabis sativa L. ( marijuana ) , has been reported to have properties of appetite stimulation , promotion of weight gain , and antiemetic efficacy in selected patient population s. In this 4-week , double-blind , crossover study , 11 female patients with primary anorexia nervosa ( PAN ) were evaluated on Δ9-THC and on an active placebo , diazepam . All patients participated in a st and ardized behavior modification treatment program . The following data were obtained : ( 1 ) daily weight , ( 2 ) daily caloric intake , and ( 3 ) weekly psychiatric assessment s. The two groups were comparable on all measures at baseline except for two items on the behavioral rating scales . The only significant differences found between the changes over time on Δ9-THC versus diazepam were more pathology on Δ9-THC for somatization , interpersonal sensitivity , and sleep disturbance . Three patients experienced severe dysphoric reactions consisting of paranoid ideation and feelings of loss of control during Δ9-THC administration . One week after the study ended , each subject was given the highest dose level of Δ8-THC achieved in the study , and periodic blood sample s were obtained coincident with self-rated “ subjective high ” assessment s and pulse measurements . Quantitative analyses of these sample s indicated peak times of 1 to 5 hours postdose for Δ9- THC and for its primary active metabolite , 11-hydroxy-THC , which generally coincided with peak times for “ subjective high ” and pulse rate . The results of this clinical investigation suggest that Δ9-THC is not efficacious , in short-term administration , in the treatment of primary anorexia nervosa and is associated with significant psychic disturbance in some PAN patients",
"Abstract Background : Muscle spasticity is common in multiple sclerosis ( MS ) , occurring in more than 60 % of patients . Objective : To compare Sativex with placebo in relieving symptoms of spasticity due to MS . Methods : A 15-week , multicenter , double-blind , r and omized , placebo-controlled , parallel-group study in 337 subjects with MS spasticity not fully relieved with current anti-spasticity therapy . Results : The primary endpoint was a spasticity 0–10 numeric rating scale ( NRS ) . Intention-to-treat ( ITT ) analysis showed a non-significant improvement in NRS score , in favor of Sativex . The per protocol ( PP ) population ( 79 % of subjects ) change in NRS score and responder analyses ( ≥30 % improvement from baseline ) were both significantly superior for Sativex , compared with placebo : −1·3 versus −0·8 points ( change from baseline , p=0·035 ) ; and 36 % versus 24 % ( responders , p=0·040 ) . These were supported by the time to response ( ITT : p=0·068 ; PP : p=0·025 ) analyses , carer global impression of change assessment ( p=0·013 ) and timed 10-meter walk ( p=0·042 ) . Among the subjects who achieved a ≥30 % response in spasticity with Sativex , 98 , 94 and 73 % reported improvements of 10 , 20 and 30 % , respectively , at least once during the first 4 weeks of treatment . Sativex was generally well tolerated , with most adverse events reported being mild-to-moderate in severity . Discussion and conclusions : The 0–10 NRS and responder PP analyses demonstrated that Sativex treatment result ed in a significant reduction in treatment-resistant spasticity , in subjects with advanced MS and severe spasticity . The response observed within the first 4 weeks of treatment appears to be a useful aid to prediction of responder/non-responder status",
"BACKGROUND Very few prospect i ve studies examine the relationship between childhood sleep problems and subsequent substance use . In this study , we examined how sleep problems at ages 3 - 8 predicted onset of alcohol , cigarette , and marijuana use in adolescence . We also investigated the relationships between childhood sleep problems and adolescent internalizing and externalizing problems . METHODS Study participants were 292 boys and 94 girls from a community sample of high risk families and controls in an ongoing longitudinal study . RESULTS Controlling for parental alcoholism , sleep problems at ages 3 - 8 predicted onset of alcohol , cigarette , and marijuana use among boys and onset of alcohol use among girls . Childhood sleep problems were related to maternal ratings of internalizing and externalizing problems during adolescence for both boys and girls . Adjusting for these problems did not weaken the effects of sleep problems on onset of substance use . CONCLUSIONS This is to our knowledge the first study that prospect ively examines gender differences in the relationship between sleep problems and early onset of substance use . Childhood sleep problems predicted early onset of substance use for boys but not girls . If childhood sleep problems indeed increase the probability of substance use onset , greater attention by parents to sleep problems in children and adolescents would potentially have ameliorative long-term effects . Parents are encouraged to explore different ways to help their children sleep better , including obtaining information and suggestions from their primary care physicians"
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The relevance of dairy produce for the diminishment of osteoporotic risk is still a matter of scientific debate due to the outcome of a few single observational studies . This review will address the most robust point estimate on the role of dairy products , as reported in systematic review s and meta-analyses on r and omised controlled trials in the case of bone mineralisation or prospect i ve studies in the case of fracture risk . Plain dairy products or those fortified with Ca and /or vitamin D improve total body bone mineral content ( BMC ) by 45 - 50 g over 1 year when the daily baseline Ca intake is lower than 750 mg in Caucasians and Chinese girls . In Caucasian and Chinese women , Ca from ( fortified ) dairy products increases bone mineral density ( BMD ) by 0·7 - 1·8 % over 2 years dependent on the site of measurement . Despite the results on BMC , there are currently no studies that have investigated the potential of dairy products to reduce fracture risk in children . In adult Caucasian women , daily intake of 200 - 250 ml of milk is associated with a reduction in fracture risk of 5 % or higher . In conclusion , the role of dairy products for BMC or BMD has been sufficiently established in Chinese and Caucasian girls and women . In Caucasian women , drinking milk also reduces fracture risk . More research on the role of dairy products within the context of bone health-promoting diets is needed in specific ethnicities , other than Chinese and Caucasians , and in men
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"Dietary data from a prospect i ve study were used to relate factors influencing calcium balance ( estimates of dietary calcium intake , protein intake from nondairy animal sources ( meat , fish , and eggs ) , and coffee consumption ) to the incidence of hip fracture . During the years 1977 - 1983 , women and men born between 1925 and 1940 and living in one of three Norwegian counties were invited to a cardiovascular screening that included a dietary survey . The attendance rate at screening was 91.1 % , and 90.7 % of these persons ( 19,752 women and 20,035 men ) filled in and returned a semiquantitative dietary question naire . This cohort was followed for an average of 11.4 years ( range , 0.01 - 13.8 years ) with respect to hip fracture , defined as cervical or trochanteric fracture . During follow-up , 213 hip fractures were identified , excluding fractures associated with high-energy trauma and metastatic bone disease . There was no clear association between calcium intake or nondairy animal protein intake and hip fracture in this cohort . However , an elevated risk of fracture was found in women with a high intake of protein from nondairy animal sources in the presence of low calcium intake ( relative risk = 1.96 ( 95 % confidence interval 1.09 - 3.56 ) for the highest quarter of nondairy protein intake and the lowest quarter of calcium intake vs. the three lower quarters of protein intake and the three higher quarters of calcium intake ) . Women who drank nine or more cups of coffee per day also had an increased risk of fracture , while there was no association between coffee consumption and hip fracture in men . Although these findings do not necessarily imply causal relations , they suggest the presence of risk factors for hip fracture that act through a negative calcium balance in this population",
"Background It has been suggested that a higher calcium intake might favourably modify cardiovascular risk factors . However , findings of an ultimately decreased risk of cardiovascular disease ( CVD ) are limited . Instead , recent evidence warns that taking calcium supplements might increase myocardial infa rct ion ( MI ) risk . Objective To prospect ively evaluate the associations of dietary calcium intake and calcium supplementation with MI and stroke risk and overall CVD mortality . Methods Data from 23 980 Heidelberg cohort participants of the European Prospect i ve Investigation into Cancer and Nutrition study , aged 35–64 years and free of major CVD events at recruitment , were analysed . Multivariate Cox regression models were used to estimate HRs and 95 % CIs . Results After an average follow-up time of 11 years , 354 MI and 260 stroke cases and 267 CVD deaths were documented . Compared with the lowest quartile , the third quartile of total dietary and dairy calcium intake had a significantly reduced MI risk , with a HR of 0.69 ( 95 % CI 0.50 to 0.94 ) and 0.68 ( 95 % CI 0.50 to 0.93 ) , respectively . Associations for stroke risk and CVD mortality were overall None . In comparison with non-users of any supplements , users of calcium supplements had a statistically significantly increased MI risk ( HR=1.86 ; 95 % CI 1.17 to 2.96 ) , which was more pronounced for calcium supplement only users ( HR=2.39 ; 95 % CI 1.12 to 5.12 ) . Conclusions Increasing calcium intake from diet might not confer significant cardiovascular benefits , while calcium supplements , which might raise MI risk , should be taken with caution",
"Objective The primary aim of the present study was to examine the effectiveness of daily consumption of vitamin D3-enriched , reduced-fat Gouda-type cheese on 25-hydroxyvitamin D ( 25(OH)D ) concentration in postmenopausal women . Health-related quality of life ( HRQL ) indices were examined as secondary outcomes . Design This is a single-blinded ( i.e. , to study participants ) , r and omized , controlled food-based dietary intervention study . Methods A sample of 79 postmenopausal women ( 55–75 years old ) was r and omized either to a control group ( CG : n = 39 ) or an intervention group ( IG : n = 40 ) that consumed , as part of their usual diet , 60 g of either non-enriched or vitamin D3 enriched Gouda-type cheese , respectively , for eight consecutive weeks ( i.e. , from January to March 2015 ) . Sixty grams of enriched cheese provided a daily dose of 5.7 μg of vitamin D3 . Results There was a differential response of mean ( 95 % CI ) serum 25(OH)D levels in the IG and CG , with the former increasing and the latter decreasing significantly over the eight weeks of the trial [ i.e. , by 5.1 ( 3.4 , 6.9 ) nmol/L vs. −4.6 ( −6.4 , −2.8 ) nmol/L , P with 25(OH)D levels respectively ) . The emotional well-being scale of the HRQL score increased in the IG compared to a decrease in the CG ( 3.2 vs. −3.8 , P = 0.028 ) . However , none of the other seven scales of the HRQL score significantly differentiated between study groups ( P > 0.1 ) . Conclusions Consumption of 60 g of vitamin D3-enriched , reduced-fat Gouda-type cheese provided a daily dose of 5.7 μg of additional vitamin D3 and was effective in increasing mean serum 25(OH)D concentration and in counteracting vitamin D deficiency during winter months in postmenopausal women in Greece",
"No diet score exists that summarizes the features of a diet that is optimal for bone mineral density ( BMD ) in the elderly . Our aims were ( a ) to develop a BMD-Diet Score reflecting a diet that may be beneficial for BMD based on the existing literature , and ( b ) to examine the association of the BMD-Diet Score and the Healthy Diet Indicator , a score based on guidelines of the World Health Organization , with BMD in Dutch elderly participating in a prospect i ve cohort study , the Rotterdam Study ( n = 5144 ) . Baseline dietary intake , assessed using a food frequency question naire , was categorized into food groups . Food groups that were consistently associated with BMD in the literature were included in the BMD-Diet Score . BMD was measured repeatedly and was assessed using dual energy X-ray absorptiometry . The BMD-Diet Score considered intake of vegetables , fruits , fish , whole grains , legumes/beans and dairy products as “ high-BMD ” components and meat and confectionary as “ low-BMD ” components . After adjustment , the BMD-Diet Score was positively associated with BMD ( β ( 95 % confidence interval ) = 0.009 ( 0.005 , 0.012 ) g/cm2 per st and ard deviation ) . This effect size was approximately three times as large as has been observed for the Healthy Diet Indicator . The food groups included in our BMD-Diet Score could be considered in the development of future dietary guidelines for healthy ageing",
"BACKGROUND Little is known about the relative effectiveness of calcium supplementation from food or pills with or without vitamin D supplementation for bone mass accrual during the rapid growth period . OBJECTIVE The purpose was to examine the effects of both food-based and pill supplements of calcium and vitamin D on bone mass and body composition in girls aged 10 - 12 y. DESIGN This placebo-controlled intervention trial r and omly assigned 195 healthy girls at Tanner stage I-II , aged 10 - 12 y , with dietary calcium intakes 1 of 4 groups : calcium ( 1000 mg ) + vitamin D3 ( 200 IU ) , calcium ( 1000 mg ) , cheese ( 1000 mg calcium ) , and placebo . Primary outcomes were bone indexes of the hip , spine , and whole body by dual-energy X-ray absorptiometry and of the radius and tibia by peripheral quantitative computed tomography . RESULTS With the use of intention-to-treat or efficacy analysis , calcium supplementation with cheese result ed in a higher percentage change in cortical thickness of the tibia than did placebo , calcium , or calcium + vitamin D treatment ( P = 0.01 , 0.038 , and 0.004 , respectively ) and in higher whole-body bone mineral density than did placebo treatment ( P = 0.044 ) when compliance was > 50 % . With the use of a hierarchical linear model with r and om effects to control for growth velocity , these differences disappeared . CONCLUSIONS Increasing calcium intake by consuming cheese appears to be more beneficial for cortical bone mass accrual than the consumption of tablets containing a similar amount of calcium . Diverse patterns of growth velocity may mask the efficacy of supplementation in a short-term trial of children transiting through puberty",
"BACKGROUND Short-term studies established that calcium influences bone accretion during growth . Whether long-term supplementation influences bone accretion in young adults is not known . OBJECTIVE This study evaluated the long-term effects of calcium supplementation on bone accretion among females from childhood to young adulthood . DESIGN A 4-y r and omized clinical trial recruited 354 females in pubertal stage 2 and optionally was extended for an additional 3 y. The mean dietary calcium intake of the participants over 7 y was approximately 830 mg/d ; calcium-supplemented persons received an additional approximately 670 mg/d . Primary outcome variables were distal and proximal radius bone mineral density ( BMD ) , total-body BMD ( TBBMD ) , and metacarpal cortical indexes . RESULTS Multivariate analyses of the primary outcomes indicated that calcium-supplementation effects vary over time . Follow-up univariate analyses indicated that all primary outcomes were significantly larger in the supplemented group than in the placebo group at the year 4 endpoint . However , at the year 7 endpoint , this effect vanished for TBBMD and distal radius BMD . Longitudinal models for TBBMD and proximal radius BMD , according to the time since menarche , showed a highly significant effect of supplementation during the pubertal growth spurt and a diminishing effect thereafter . Post hoc stratifications by compliance-adjusted total calcium intake and by final stature or metacarpal total cross-sectional area showed that calcium effects depend on compliance and body frame . CONCLUSIONS Calcium supplementation significantly influenced bone accretion in young females during the pubertal growth spurt . By young adulthood , significant effects remained at metacarpals and at the forearm of tall persons , which indicated that the calcium requirement for growth is associated with skeletal size . These results may be important for both primary prevention of osteoporosis and prevention of bone fragility fractures during growth",
"BACKGROUND Despite numerous animal studies that have illustrated the impact of additional vitamin D in the diet of hens on the result ing egg vitamin D content , the effect of the consumption of such eggs on vitamin D status of healthy individuals has not , to our knowledge , been tested . OBJECTIVE We performed a r and omized controlled trial ( RCT ) to investigate the effect of the consumption of vitamin D-enhanced eggs ( produced by feeding hens at the maximum concentration of vitamin D3 or serum 25-hydroxyvitamin D [ 25(OH)D3 ] lawfully allowed in feed ) on winter serum 25(OH)D in healthy adults . DESIGN We conducted an 8-wk winter RCT in adults aged 45 - 70 y ( n = 55 ) who were stratified into 3 groups and were requested to consume ≤2 eggs/wk ( control group , in which status was expected to decline ) , 7 vitamin D3-enhanced eggs/wk , or seven 25(OH)D3-enhanced eggs/wk . Serum 25(OH)D was the primary outcome . RESULTS Although there was no significant difference ( P > 0.1 ; ANOVA ) in the mean preintervention serum 25(OH)D in the 3 groups , it was ∼7 - 8 nmol/L lower in the control group than in the 2 groups who consumed vitamin D-enhanced eggs . With the use of an ANCOVA , in which baseline 25(OH)D was accounted for , vitamin D3-egg and 25(OH)D3-egg groups were shown to have had significantly higher ( P ≤ 0.005 ) postintervention serum 25(OH)D than in the control group . With the use of a within-group analysis , it was shown that , although serum 25(OH)D in the control group significantly decreased over winter ( mean ± SD : -6.4 ± 6.7 nmol/L ; P = 0.001 ) , there was no change in the 2 groups who consumed vitamin D-enhanced eggs ( P > 0.1 for both ) . CONCLUSION Weekly consumption of 7 vitamin D-enhanced eggs has an important impact on winter vitamin D status in adults . This trial was registered at clinical trials.gov as NCT02678364",
"The aim of this population -based , prospect i ve cohort study was to investigate long-term associations between dietary calcium intake and fractures , non-fatal cardiovascular disease ( CVD ) , and death from all causes . Participants were from the Melbourne Collaborative Cohort Study , which was established in 1990 to 1994 . A total of 41,514 men and women ( ∼99 % aged 40 to 69 years at baseline ) were followed up for a mean ( SD ) of 12 ( 1.5 ) years . Primary outcome measures were time to death from all causes ( n = 2855 ) , CVD-related deaths ( n = 557 ) , cerebrovascular disease-related deaths ( n = 139 ) , incident non-fatal CVD ( n = 1827 ) , incident stroke events ( n = 537 ) , and incident fractures ( n = 788 ) . A total of 12,097 participants ( aged ≥50 years ) were eligible for fracture analysis and 34,468 for non-fatal CVD and mortality analyses . Mortality was ascertained by record linkage to registries . Fractures and CVD were ascertained from interview ∼13 years after baseline . Quartiles of baseline energy-adjusted calcium intake from food were estimated using a food-frequency question naire . Hazard ratios ( HR ) and odds ratios ( OR ) were calculated for quartiles of dietary calcium intake . Highest and lowest quartiles of energy-adjusted dietary calcium intakes represented unadjusted means ( SD ) of 1348 ( 316 ) mg/d and 473 ( 91 ) mg/d , respectively . Overall , there were 788 ( 10.3 % ) incident fractures , 1827 ( 9.0 % ) incident CVD , and 2855 people ( 8.6 % ) died . Comparing the highest with the lowest quartile of calcium intake , for all-cause mortality , the HR was 0.86 ( 95 % confidence interval [ CI ] 0.76 - 0.98 , p(trend ) = 0.01 ) ; for non-fatal CVD and stroke , the OR was 0.84 ( 95 % CI 0.70 - 0.99 , p(trend ) = 0.04 ) and 0.69 ( 95 % CI 0.51 - 0.93 , p(trend ) = 0.02 ) , respectively ; and the OR for fracture was 0.70 ( 95 % CI 0.54 - 0.92 , p(trend ) = 0.004 ) . In summary , for older men and women , calcium intakes of up to 1348 ( 316 ) mg/d from food were associated with decreased risks for fracture , non-fatal CVD , stroke , and all-cause mortality",
"BACKGROUND Relatively little is known about the relations between dietary patterns and bone health in adolescence , which is a period of substantial bone mass accrual . OBJECTIVES We derived dietary patterns that were hypothesized to be related to bone health on the basis of their protein , calcium , and potassium contents and investigated their prospect i ve associations with bone mineral density ( BMD ) , bone area , and bone mineral content ( BMC ) in a cohort of young adults . DESIGN The study included 1024 young adults born to mothers who were participating in the Western Australian Pregnancy Cohort ( Raine ) Study . Dietary information was obtained from food-frequency question naires at 14 and 17 y of age . Dietary patterns were characterized according to protein , calcium , and potassium intakes with the use of reduced-rank regression . BMD , bone area , and BMC were estimated with the use of a total body dual-energy X-ray absorptiometry scan at 20 y of age . RESULTS We identified 2 major dietary patterns . The first pattern was positively correlated with intakes of protein , calcium , and potassium and had high factor loadings for low-fat dairy products , whole grains , and vegetables . The second pattern was positively correlated with protein intake but negatively correlated with intakes of calcium and potassium and had high factor loadings for meat , poultry , fish , and eggs . After adjustment for anthropometric , sociodemographic , and lifestyle factors , a higher z score for the first pattern at 14 y of age was positively associated with BMD and BMC at 20 y of age [ differences : 8.6 mg/cm(2 ) ( 95 % CI : 3.0 , 14.1 mg/cm(2 ) ) and 21.9 g ( 95 % CI : 6.5 , 37.3 g ) , respectively , per SD increase in z score ] . The z score for this same pattern at 17 y of age was not associated with bone outcomes at 20 y of age . The second pattern at 14 or 17 y of age was not associated with BMD , BMC , or bone area . CONCLUSIONS A dietary pattern characterized by high intakes of protein , calcium , and potassium in midadolescence was associated with higher BMD and BMC at 20 y of age . Our results indicate that high consumption of low-fat dairy products , whole grains , and vegetables in adolescence are associated with beneficial effects on bone development",
"The early days of nutritional science were a heady time . Working out the metabolic roles and many benefits of specific nutrients was both exciting and clearly important . In more recent times , emphasis has shifted somewhat from metabolism to policy . In a sense , this represents a major victory for nutrition . Less than a century ago , E. V. McCollum had to struggle with the prevailing notion that food was primarily fuel . The idea that not eating something could make one sick was considered laughable . Now , it is taken for granted that the quality of what we eat is at least as important as the quantity , an underst and ing that leads naturally to the determining of nutrient intake requirements . It is not surprising , therefore , that 7 of the last 14 Atwater lectures dealt more or less explicitly with the issue of requirements . This one will be no exception to that pattern . In my McCollum lecture of 5 y ago ( 1 ) , I called attention to what I perceived as a broadening of the way deficiency disease might be conceptualized . The original nutrient deficiency diseases were all of short latency and involved discrete body systems and dysfunctions . Rickets , pellagra , and beriberi are good cases in point . And , while the working science has progressed far beyond these beginnings , these short latency diseases have remained the implicit model for much of our thinking about nutritional deficiency and , to a substantial extent , our determination of nutrient intake requirements . For example , in the first of the dietary reference intake books , that for bone-related nutrients ( 2 ) , the intake requirement for vitamin D was explicitly pegged solely to the prevention of rickets/osteomalacia . As is evident on a moment ’s reflection , short latency was a prerequisite for the discovery of a connection between nutrient intake and disease . Had the outcome of an inadequate intake not been discrete and not been manifested promptly , it is doubtful that we ever would have recognized the connection between cause and effect ( i.e. nutrient intake and health or disease ) . But the science has gone far beyond that point , and it seems that there is no inherent reason why inadequate intake of the same nutrients involved in short-latency diseases could not be producing long latency deficiency disease as well . Moreover , as is now generally recognized , nutrients act through multiple mechanisms , and low intakes might be expected to lead to disorders quite distinct from the disease originally connected with the nutrient . Vitamin D is a good case in point . Total body inputs closer to those that must have prevailed during hominid evolution are associated with reduced risk of disorders as varied as Type I diabetes , hypertension , osteoporosis , various cancers , multiple sclerosis , and periodontal disease , to name only some ( 3–24 ) . ( For several of these disorders there is now what is referred to as ‘ ‘ level I evidence , ’’ i.e. r and omized controlled trials , confirming what had been found both in observational studies and in extensive bench and small animal studies . ) This broadened scheme is illustrated graphically in Figure 1",
"Objective To assess factors associated with bone mineral density ( BMD ) in postmenopausal women in a longitudinal study , and to examine the relative contribution of lean mass , fat mass , dietary patterns , and years since menopause to BMD . Methods Two hundred and eighty-two postmenopausal women were r and omly selected from Hongqi Community Health Center , in Harbin City , China . All participants were followed up from 2009 to 2011 . Dietary data were collected using a Food Frequency Question naire . BMD of the left hip , the lumbar spine , and the total body , and the body composition were measured by dual-energy X-ray absorptiometry at baseline and follow-up . Results Lean mass and fat mass were positively associated with BMD of the spine , hip , and the total body at both baseline and follow-up . The association between fat mass and BMD at the spine at baseline ( P = 0.210 ) and at the spine ( P = 0.116 ) and hip ( P = 0.073 ) in the second year was not statistically significant when height was adjusted . Six dietary patterns were identified but only cereal grains-fruits pattern ( P = 0.001 in the spine , P = 0.037 in hip ) and milk-root vegetables pattern ( P = 0.010 in hip ) were associated with BMD of the spine and hip . The linear mixed model of follow-up data showed that lean mass , years since menopause , and age of menophania were the significant determinants of BMD of all sites . Moreover , lean mass was the best determinant of BMD ( VIP = 1.936 ) . Conclusion Lean mass , years since menopause , age of menophania and dietary patterns are the important determinants of BMD of the spine , hip , and the total body . Lean mass is the best determinant of BMD",
"OBJECTIVE To investigate whether dietary phylloquinone and menaquinones intakes are related to risk of type 2 diabetes . RESEARCH DESIGN AND METHODS We used data from a prospect i ve cohort study in 38,094 Dutch men and women , aged 20–70 years . Dietary phylloquinone and menaquinones intakes were assessed using a vali date d food frequency question naire . Diabetes case patients were ascertained mainly via self-report and verified against medical records . RESULTS During 10.3 years of follow-up , 918 incident cases of diabetes were documented . In a multivariate model adjusting for diabetes risk factors and dietary factors , phylloquinone intake tended to be associated ( P = 0.08 ) with a reduced risk of type 2 diabetes with a hazard ratio ( HR ) of 0.81 ( 95 % CI 0.66–0.99 ) for the highest versus the lowest quartile . For menaquinones intake , a linear , inverse association ( P = 0.038 ) with risk of type 2 diabetes was observed with an HR of 0.93 ( 0.87–1.00 ) for each 10-μg increment in the multivariate model . CONCLUSIONS This study shows that both phylloquinone and menaquinones intakes may be associated with a reduced risk of type 2 diabetes",
"Dairy foods are rich in bone-beneficial nutrients , yet the role of dairy foods in hip fracture prevention remains controversial . Our objective was to evaluate the association of milk , yogurt , cheese , cream , and milk + yogurt intakes with incident hip fracture in the Framingham Original Cohort . A total of 830 men and women from the Framingham Original Cohort , a prospect i ve cohort study , completed a food-frequency question naire ( 1988 to 1989 ) and were followed for hip fracture until 2008 . In this population -based study , Cox-proportional hazards regression was used to estimate hazard ratios ( HR ) by categories of energy-adjusted dairy intake ( servings/wk ) , adjusting for st and ard confounders and covariates . The exposure was energy-adjusted intakes of milk , yogurt , cheese , cream , and milk + yogurt ( servings/wk ) . Risk of hip fracture over the follow-up was the primary outcome ; the hypothesis being tested was formulated after data collection . The mean age at baseline was 77 years ( SD 4.9 , range 68 to 96 ) . Ninety-seven hip fractures occurred over the mean follow-up time of 11.6 years ( range 0.04 to 21.9 years ) . The mean ± SD ( servings/wk ) of dairy intakes at baseline were : milk = 6.0 ± 6.4 ; yogurt = 0.4 ± 1.3 ; cheese = 2.6 ± 3.1 ; and cream = 3.4 ± 5.5 . Participants with medium ( > 1 and lower hip fracture risk than those with low ( ≤1 serving/wk ) intake ( high versus low intake HR 0.58 , 95 % confidence interval [ CI ] 0.31 - 1.06 , p = 0.078 ; medium versus low intake HR 0.61 , 95 % CI 0.36 - 1.08 , p = 0.071 ; p trend = 0.178 ] . There appeared to be a threshold for milk , with 40 % lower risk of hip fracture among those with medium/high milk intake compared with those with low intake ( p = 0.061 ) . A similar threshold was observed for milk + yogurt intake ( p = 0.104 ) . These associations were further attenuated after adjustment for femoral neck bone mineral density . No significant associations were seen for other dairy foods ( p range = 0.117 to 0.746 ) . These results suggest that greater intakes of milk and milk + yogurt may lower risk for hip fracture in older adults through mechanisms that are partially , but not entirely , attributable to effects on bone mineral density",
"Summary Eighteen months of daily consumption of milk containing 250 mg calcium prevented bone mineral density ( BMD ) loss at the hip and the femoral neck in postmenopausal Chinese women aged 45 to 65 . Introduction Estrogen-related bone loss in postmenopausal women can be prevented by the consumption of milk with high doses of calcium and soymilk with high doses of isoflavones . However , high doses of calcium and isoflavones may not be necessary to attain a beneficial effect of milk and soymilk on BMD . We hypothesized that BMD will increase in postmenopausal Chinese women who consume daily 250 mg calcium in milk or soymilk . Milk prevented bone loss at the hip and the femoral neck in postmenopausal Chinese women . Methods A total of 141 eligible Chinese women without osteoporosis , aged 45–65 , and postmenopausal for more than 2 years were r and omized into groups receiving for 18 months ( A ) milk with 250 mg calcium daily , ( B ) soymilk with 250 mg calcium daily , or ( C ) neither milk nor soymilk . Dual-energy X-ray absorptiometry measured the BMD of the spine and hip at 0 , 6 , 12 , and 18 months . Results The BMD in the hip ( 2.52 % ) and the femoral neck ( 2.82 % ) of the women consuming milk was significantly higher ( hip , P = 0.01 ; femoral neck , P reduction in BMD at all sites ; the reduction in BMD was only significant at the hip during 12 months ( P = 0.008 ) and at the femoral neck during 18 months ( P = 0.005 ) . Conclusions Daily consumption of milk containing 250 mg calcium over 18 months prevents BMD loss at the hip and the femoral neck in postmenopausal Chinese women",
"Low dietary calcium intake has been demonstrated to be a risk factor for hip and vertebral fractures in studies conducted among Hong Kong Chinese . Few studies have demonstrated the effect of milk supplementation in bone accretion in Chinese children . The aim was to examine the effects of milk powder supplementation in enhancing bone accretion in Chinese children . Three hundred and forty-four children , aged 9–10 years old , were r and omized to receive milk powder equivalent to 1300 mg and 650 mg calcium , and to a control group , respectively . Bone mineral density ( BMD ) at the proximal femur , lumbar spine and total body were measured at 6 months , 12 months and 18 months . The treatment effects were modeled using linear mixed effect models and compared using linear contrast F-tests , by intention-to-treat . Subjects r and omized to milk powder equivalent to 1300 mg calcium had significantly higher increase in BMD at both the total hip ( 7.4±0.4 % in treatment group versus 6.3±0.4 % in the control ) and the spine ( 8.4±0.5 % in the treatment group versus 7.0±0.5 % in the control group ) . Subjects r and omized to milk powder equivalent to 650 mg calcium had smaller increases in BMD at the total hip and spine , although the increase in BMD at the total body was significantly higher ( 3.1±0.3 % in treatment group versus 2.4±0.2 % in controls ) . It is concluded that supplementing the diet of Chinese children with milk powder was effective in enhancing bone accretion ",
"BACKGROUND Hypovitaminosis D , especially during cold seasons , is quite prevalent among primary school children in Tehran . The present study aim ed to compare the efficacy of calcium-vitamin D-fortified-milk , -orange juice and supplement in primary school children . METHODS Children aged 9 - 12 years from both sexes were r and omly assigned to one of six groups to receive plain milk , fortified milk , plain orange juice , fortified orange juice , supplement or placebo . Both fortified-milk and -juice contained 100 IU of vitamin D and 500 mg of calcium per 200 mL package , whereas supplement contained 200 IU of vitamin D and 500 mg of calcium . The duration of intervention was 12 weeks , from November 2008 to March 2009 . RESULTS A total of 410 children completed the study . Regression analysis with adjustment for both sex and initial values of 25(OH)D revealed that consumption of either supplement , fortified orange juice or fortified milk result ed in a 20.8 nm [ confidence interval ( CI ) = 17.4 - 23.9 ] , 9.9 nm ( CI = 7.4 - 12.3 ) or 6.9 nm ( CI = 3.3 - 10.5 ) increase in circulating 25(OH)D compared to the related control groups . However , changes in serum osteocalcin and intact parathyroid hormone in the supplement group did not differ from those of fortified milk or plain milk . The increment of osteocalcin in both plain milk and fortified milk was more than in fortified orange juice , although the difference was statistically insignificant . CONCLUSIONS Despite having double amount of vitamin D and being more effective in raising serum 25(OH)D , supplementation did not confer additional benefit in terms of osteocalcin and intact parathyroid hormone compared to either fortified or plain milk",
"Introduction and HypothesisCalcium supplementation enhances bone mass accrual during administration , with a sustained benefit observed using milk-based calcium but not calcium salts . We tested the hypothesis that calcium from milk minerals but not calcium carbonate will be sustained after supplementation was discontinued . Methods Ninety-nine pre-pubertal boys and girls aged 5–11 years were followed for 12 months after being r and omized to receive 800 mg/day of calcium from milk minerals ( MM ) or calcium carbonate ( CC ) , or a placebo ( Pla ) in a 10-month double blind study . Total body and regional BMC , and femoral shaft bone dimensions were measured using dual energy x-ray absorptiometry . Group differences were determined using ANCOVA . Results In the intention to treat analysis of the entire sample , no group differences were observed in increments in BMC or bone dimensions during or after supplementation . In those children who remained pre-pubertal , greater gains in pelvis BMC in the milk mineral group than controls were sustained ( 37.9 versus 29.3 % respectively , p children consuming about 800 mg calcium daily , calcium supplementation with milk minerals or calcium carbonate does not appear to be produce biologically meaningful benefits to skeletal health . A benefit of calcium supplementation in pre-pubertal was evident , but inconclusive , with the biological significance of the effect of calcium supplementation at the pelvis , and the longevity of this effect to be determined",
"Objective : To compare the short-term effect of a high milk and a high meat intake , identical in protein amount , on bone turnover during prepuberty . Setting : A University Department . Design and Subjects : From 28 , r and omly recruited , 8-year-old boys , first 14 were assigned to the milk group and next 14 to the meat group . In each group , 12 boys finished the dietary intervention . Intervention : Milk ( 1.5 l/day ) and meat ( 250 g/d ) , both containing ∼53 g of protein , were given together with the habitual diet for 7 days . At baseline and day−7 , serum osteocalcin ( s-OC ) , bone-specific alkaline phosphatase ( s-BAP ) and C-terminal telopeptides of type I collagen ( s-CTX ) were measured ( immunoassay ) and dietary intake was estimated ( a 3-day weighted food record ) . Results : Baseline s-OC , s-BAP and s-CTX were not significantly different between the groups . After 7 days , the average protein intake increased in both groups by 47.5 g ; the milk group had higher ( P decreased ( P⩽0.04 ) in the milk group ( −30.9 % ; −18.7 % , respectively ) compared with the meat group ( + 6.4 % ; −1.0 % , respectively ) and s-BAP decreased ( P=0.06 ) both in the milk ( −3.9 % ) and the meat group ( −7.5 % ) . Conclusions : At the equal protein intake , milk , but not meat , decreased bone turnover in prepubertal boys after 7 days . This effect was probably due to some milk-derived compounds , rather than to the total protein intake . Future studies should eluci date the mechanism(s ) of milk-related decline of bone turnover and its relevance for peak bone mass during growth . Sponsorship : University PhD scholarships",
"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",
"This study examined the effects of increasing milk on bone and body composition responses to resistance training in adolescents . Twenty-eight boys ( 13 to 17 years of age ) were r and omly assigned to consume , in addition to their habitual diet , 3 servings/day of 1 % fluid milk ( n=14 ) or juice not fortified with calcium ( n=14 ) while engaged in a 12-week resistance-training program . For all subjects combined , there were significant ( P changes in height ( + 0.5 % ) , sigmaseven skin folds ( -7.7 % ) , body mass ( + 2.6 % ) , lean body mass ( + 5.1 % ) , fat mass ( -9.3 % ) , whole-body bone mineral content ( + 3.6 % ) , bone mineral density ( + 1.8 % ) , and maximal strength in the squat ( + 43 % ) and bench press ( + 23 % ) . Compared with juice , the milk group had a significantly greater increase in bone mineral density ( 0.014 vs 0.028 g/cm(2 ) ) . Increasing intake of milk in physically active adolescent boys may enhance bone health",
"The Chinese diet is low in calcium ( less than 500 mg/day on average ) , and previous observational studies have suggested an association between a low calcium intake and risk of hip and vertebral fracture . In this study , we r and omly assigned 200 postmenopausal Chinese women ( age range , 55 - 59 years ) to receive 50 g of milk powder containing 800 mg of calcium per day or to a control group . The following are the mean percentage changes ( and SEs ) in height and bone mineral density ( BMD ) over 24 months : for height , -0.1 + /- 0.2 cm in the milk supplementation group and -0.2 + /- 0.1 cm in the control group ; for BMD at the total hip , -0.06 + /- 0.22 % in the milk supplementation group and -0.88 + /- 0.26 % in the control group ; for BMD at the spine ( L1-L4 ) , -0.56 + /- 0.29 % in the milk supplementation group and -1.5 + /- 0.29 % in the control group ; for total body BMD , -0.32 + /- 0.16 % in the milk supplementation group and -1.2 + /- 0.19 % in the control group ( p loss in terms of both height and BMD than the control group ( p Serum parathyroid hormone ( PTH ) concentration was lower and serum 25-hyroxyvitamin D [ 25(OH)D ] level was higher in the milk supplementation group than the control group at 12 months ( p diet of postmenopausal Chinese women with high calcium milk powder retards bone loss",
"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",
"The etiologic role of dietary calcium and vitamin D intake in primary prevention of osteoporotic fractures is uncertain , despite considerable research efforts . With the aim to examine these associations with an improved precision , we used data from a large population -based prospect i ve cohort study in central Sweden . We estimated nutrient intake from a self-administered food-frequency question naire filled in by 60,689 women , aged 40 - 74 years at baseline during 1987 - 1990 . During follow-up , we observed 3986 women with a fracture at any site and 1535 with a hip fracture . Rate ratio of fractures ( RR ) and 95 % CI were estimated using Cox proportional hazards models . We found no dose-response association between dietary calcium intake and fracture risk . The age-adjusted RR of hip fracture was 1.01 ( 95 % CI 0.96 - 1.06 ) per 300 mg calcium/day and the corresponding risk of any osteoporotic fracture was 0.99 ( 95 % CI 0.96 - 1.03 ) . Furthermore , women with an estimated calcium intake below 400 mg/day and those with a calcium intake higher than 1200 mg/day both had a similar age-adjusted hip fracture risk as those with intermediate calcium intakes : RR 1.07 ( 95 % CI 0.92 - 1.24 ) and RR 1.00 ( 95 % CI 0.79 - 1.27 ) , respectively . Vitamin D intake was not associated with fracture risk . Furthermore , women in the highest quintiles compared to the lowest quintiles of both calcium and vitamin D intake had an age-adjusted RR of 1.02 for all fractures ( 95 % CI 0.88 - 1.17 ) . Dietary calcium or vitamin D intakes estimated at middle and older age do not seem to be of major importance for the primary prevention of osteoporotic fractures in women",
"IMPORTANCE Milk consumption during adolescence is recommended to promote peak bone mass and thereby reduce fracture risk in later life . However , its role in hip fracture prevention is not established and high consumption may adversely influence risk by increasing height . OBJECTIVES To determine whether milk consumption during teenage years influences risk of hip fracture in older adults and to investigate the role of attained height in this association . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study over 22 years of follow-up in more than 96,000 white postmenopausal women from the Nurses ' Health Study and men aged 50 years and older from the Health Professionals Follow-up Study in the United States . EXPOSURES Frequency of consumption of milk and other foods during ages 13 to 18 years and attained height were reported at baseline . Current diet , weight , smoking , physical activity , medication use , and other risk factors for hip fractures were reported on biennial question naires . MAIN OUTCOMES AND MEASURES Cox proportional hazards models were used to calculate relative risks ( RRs ) of first incidence of hip fracture from low-trauma events per glass ( 8 fl oz or 240 mL ) of milk consumed per day during teenage years . RESULTS During follow-up , 1226 hip fractures were identified in women and 490 in men . After controlling for known risk factors and current milk consumption , each additional glass of milk per day during teenage years was associated with a significant 9 % higher risk of hip fracture in men ( RR = 1.09 ; 95 % CI , 1.01 - 1.17 ) . The association was attenuated when height was added to the model ( RR = 1.06 ; 95 % CI , 0.98 - 1.14 ) . Teenage milk consumption was not associated with hip fractures in women ( RR = 1.00 per glass per day ; 95 % CI , 0.95 - 1.05 ) . CONCLUSIONS AND RELEVANCE Greater milk consumption during teenage years was not associated with a lower risk of hip fracture in older adults . The positive association observed in men was partially mediated through attained height"
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"The aim of this study was to determine the reliability of the conditioned pain modulation ( CPM ) paradigm assessed by an objective electrophysiological method , the nociceptive withdrawal reflex ( NWR ) , and psychophysical measures , using hypothetical sample sizes for future studies as analytical goals . Thirty-four healthy volunteers participated in two identical experimental sessions , separated by 1 to 3 weeks . In each session , the cold pressor test ( CPT ) was used to induce CPM , and the NWR thresholds , electrical pain detection thresholds and pain intensity ratings after suprathreshold electrical stimulation were assessed before and during CPT . CPM was consistently detected by all methods , and the electrophysiological measures did not introduce additional variation to the assessment . In particular , 99 % of the trials result ed in higher NWR thresholds during CPT , with an average increase of 3.4 mA ( p higher electrical pain detection thresholds during CPT , with an average increase of 2.2 mA ( p Pain intensity ratings after suprathreshold electrical stimulation were reduced during CPT in 84 % of the trials , displaying an average decrease of 1.5 points in a numeric rating scale ( p CPM reliability was acceptable for all assessment methods in terms of sample sizes for potential experiments . The presented results are encouraging with regards to the use of the CPM as an assessment tool in experimental and clinical pain . Trial Registration : Clinical Trials.gov",
"The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the method ological reporting of animal studies in grant applications and publications . The main workshop recommendation is that at a minimum studies should report on sample -size estimation , whether and how animals were r and omized , whether investigators were blind to the treatment , and the h and ling of data . We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators , review ers , funding agencies and journal editors . Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress",
"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",
"Objectives : This study examined whether the administration of intranasal oxytocin was associated with pain sensitivity , endogenous pain inhibitory capacity , and negative mood states . Material s and Methods : A total of 30 pain-free , young adults each completed 3 laboratory sessions on consecutive days . The first session ( baseline ) assessed ischemic pain sensitivity , endogenous pain inhibition via conditioned pain modulation ( CPM ) , and negative mood using the Profile of Mood States . CPM was tested on the dominant forearm and ipsilateral masseter muscle using algometry ( test stimulus ) and the cold pressor task ( conditioning stimulus ; nondominant h and ) . For the second and third sessions , participants initially completed the State-Trait Anxiety Inventory and then self-administered a single ( 40 IU/1 mL ) dose of intranasal oxytocin or placebo in a r and omized counterbalanced order . Thirty minutes postadministration , participants again completed the State-Trait Anxiety Inventory and repeated assessment s of ischemic pain sensitivity and CPM followed by the Profile of Mood States . Results : Findings demonstrated that ischemic pain sensitivity did not significantly differ across the 3 study sessions . CPM at the masseter , but not the forearm , was significantly greater following administration of oxytocin compared to placebo . Negative mood was also significantly lower following administration of oxytocin compared to placebo . Similarly , anxiety significantly decreased following administration of oxytocin but not placebo . Discussion : This study incorporated a placebo-controlled , double-blind , within-subjects crossover design with r and omized administration of intranasal oxytocin and placebo . The data suggest that the administration of intranasal oxytocin may augment endogenous pain inhibitory capacity and reduce negative mood states including anxiety",
" BACKGROUND Tapentadol is an analgesic agent for treatment of acute and chronic pain that activates the µ-opioid receptor combined with inhibition of neuronal norepinephrine reuptake . Both mechanisms are implicated in activation of descending inhibitory pain pathways . In this study , we investigated the influence of tapentadol on conditioned pain modulation ( CPM , an experimental measure of endogenous pain inhibition that gates incoming pain signals as a consequence of a preceding tonic painful stimulus ) and offset analgesia ( OA , a test in which a disproportionally large amount of analgesia becomes apparent upon a slight decrease in noxious heat stimulation ) . METHODS Twenty-four patients with diabetic polyneuropathy ( DPN ) were r and omized to receive daily treatment with tapentadol sustained-release ( SR ) [ average daily dose 433 ( 31 ) mg ] or placebo for 4 weeks . CPM and OA were measured before and on the last day of treatment . RESULTS Before treatment , none of the patients had significant CPM or OA responses . At week 4 of treatment , CPM was significantly activated by tapentadol SR and coincided with significant analgesic responses . CPM increased from 9.1 (5.4)% ( baseline ) to 14.3 (7.2)% ( placebo ) and 24.2 (7.7)% ( tapentadol SR , P vs placebo ) ; relief of DPN pain was also greater in patients treated with tapentadol than placebo ( P=0.028 ) . Neither placebo nor tapentadol SR treatment had an effect on the magnitude of the OA responses ( P=0.78 ) . CONCLUSIONS Tapentadol 's analgesic effect in chronic pain patients with DPN is dependent on activation of descending inhibitory pain pathways as observed by CPM responses . CLINICAL TRIAL REGISTRATION The study was registered at trialregister.nl under number NTR2716",
"Summary This study demonstrates low to moderate temporal stability of conditioned pain modulation over a 7–10 month period using an established paradigm . Abstract Conditioned pain modulation ( CPM ) is a phenomenon that may be tested with a dynamic quantitative sensory test that assesses the inhibitory aspect of this pain modulatory network . Although CPM has been adopted as a clinical assessment tool in recent years , the stability of the measure has not been determined over long time intervals . The question of stability over time is crucial to our underst and ing of pain processing , and critical for the use of this tool as a clinical test . The primary objective of this study was to evaluate the stability of a CPM paradigm over time in healthy women . The secondary objective was to determine the potential influence of menstrual cycle phase on CPM . CPM was assessed 8 times in 22 healthy women during the follicular and luteal phases of 4 different cycles . The CPM effect was evidence d by a reduction in the pain rating of a test stimulus ( 6.3 ± 0.2 ) with the introduction of a conditioning stimulus ( 5.0 ± 0.3 ; P The intraclass correlation coefficient for the CPM effect was modest ( 0.39 ; CI = 0.23–0.59 ) , suggesting that there is significant variation in CPM over long time intervals . CPM did not vary across phases in the menstrual cycle . Prior to the adoption of CPM as a clinical tool to predict individual risk and aid diagnosis , additional research is needed to establish the measurement properties of CPM paradigms and evaluate factors that influence CPM effects",
"Summary Cognitively decreasing the perceived conditioning stimulus ( CS ) pain attenuates conditioned pain modulation ( CPM ) magnitude , although a ceiling effect may limit CPM enhancement after a cognitively increased CS pain . ABSTRACT Although painfulness of the conditioning stimulus ( CS ) is required for the activation of conditioned pain modulation ( CPM ) , it is still unclear whether CPM expression depends on the objective physical intensity of the CS or the subjective perception of its pain . Accordingly , we cognitively manipulated the perceived CS pain , rendering the physical aspects of the CPM paradigm untouched . Baseline CPM was measured among 48 young healthy male subjects using the parallel paradigm with contact heat as test pain and h and immersion in hot water as CS . Subjects were then r and omized into 4 groups , all of which were cognitively manipulated as to the CS‐induced pain : group 1 , placebo ( CS less painful ) ; group 2 , nocebo ( CS more painful ) ; and groups 3 and 4 , the informed control groups for groups 1 and 2 , respectively . CPM was reassessed after the manipulation . Comparing the groups by MANCOVA ( multivariate analysis of covariance ) revealed that placebo exerted decreased CS pain and consequent attenuation of CPM magnitudes , while nocebo elicited increased CS pain , but without CPM elevation ( P reduction in CS pain was associated with diminished CPM responses ( r = 0.767 ; P = .001 ) ; however , no such relationship characterized the nocebo group . Pain inhibition under CPM seems to depend on the perceived level of the CS pain rather than solely its physical intensity . Cognitively decreasing the perceived CS pain attenuates CPM magnitude , although a ceiling effect may limit CPM enhancement after cognitively increased CS pain . These findings emphasize the relevance of cognitive mechanisms in determining endogenous analgesia processes in humans",
"Summary Conditioned pain modulation ( CPM ) predicts efficacy of duloxetine in painful diabetic neuropathy ; patients with less efficient CPM are more likely to benefit from the drug . ABSTRACT This study aims to individualize the selection of drugs for neuropathic pain by examining the potential coupling of a given drug ’s mechanism of action with the patient ’s pain modulation pattern . The latter is assessed by the conditioned pain modulation ( CPM ) and temporal summation ( TS ) protocol s. We hypothesized that patients with a malfunctioning pain modulation pattern , such as less efficient CPM , would benefit more from drugs augmenting descending inhibitory pain control than would patients with a normal modulation pattern of efficient CPM . Thirty patients with painful diabetic neuropathy received 1 week of placebo , 1 week of 30 mg/d duloxetine , and 4 weeks of 60 mg/d duloxetine . Pain modulation was assessed psychophysically , both before and at the end of treatment . Patient assessment of drug efficacy , assessed weekly , was the study ’s primary outcome . Baseline CPM was found to be correlated with duloxetine efficacy ( r = 0.628 , P drug efficacy was predicted only by CPM ( P = .001 ) and not by pretreatment pain levels , neuropathy severity , depression level , or patient assessment of improvement by placebo . Furthermore , beyond its predictive value , the treatment‐induced improvement in CPM was correlated with drug efficacy ( r = −0.411 , P = .033 ) . However , this improvement occurred only in patients with less efficient CPM ( 16.8 ± 16.0 to −1.1 ± 15.5 , P CPM and duloxetine efficacy highlights the importance of pain pathophysiology in the clinical decision‐making process . This evaluative approach promotes personalized pain therapy",
"BACKGROUND Conditioned pain modulation paradigms are often used to assess the diffuse noxious inhibitory control ( DNIC ) system . DNICs provide one of the main supraspinal pain inhibitory pathways and are impaired in several chronic pain population s. Only one previous study has examined the psychometric properties of the conditioned pain modulation technique and this study did not evaluate intersession reliability . OBJECTIVES To evaluate and compare the intra- and intersession reliability of two conditioned pain modulation paradigms using different conditioning stimuli , and to determine the time course of conditioned pain inhibition following stimulus removal . METHODS An electronic pressure transducer was used to determine the pressure-pain threshold at the knee during painful conditioning of the opposite h and using the ischemic arm test and the cold pressor test . Assessment s were completed twice on one day and repeated once approximately three days later . RESULTS The two conditioning stimuli result ed in a similar increase in the pressure-pain threshold at the knee , reflecting presumed activation of the DNIC system . Intrasession intraclass correlation coefficients for the cold pressor ( 0.85 ) and ischemic arm tests ( 0.75 ) were excellent . The intersession intraclass correlation coefficient for the cold pressor test was good ( 0.66 ) but was poor for the ischemic arm test ( -0.4 ) . Inhibition of the pressure-pain threshold remained significant at 10 min following conditioning , but returned to baseline by 15 min . CONCLUSIONS Within-session reliability of DNIC assessment using conditioned pain modulation paradigms was excellent , but the applicability of assessing pain modulation over multiple sessions was influenced by the conditioning stimulus . The cold pressor test was the superior technique",
"& NA ; Little is known about sex differences in the temporal pattern of descending inhibitory mechanisms , such as descending noxious inhibitory control ( DNIC ) . Sex differences in temporal characteristics of DNIC were investigated by measuring pressure pain thresholds ( PPTs ) over time in the trapezius muscles ( local pain areas ) and the posterolateral neck muscles ( referred pain areas ) following repeated bilateral injection of hypertonic versus isotonic saline into both trapezius muscles . Ten females and 11 males received two consecutive bilateral injections , with 15 min interval , of either 5.8 % hypertonic saline ( 0.5 ml in each side for each bilateral injection ) or isotonic saline as a control in a r and omized manner . Following hypertonic saline injection , the maximal pain intensities of the first and second bilateral injections were significantly higher in females than in males . The PPTs in the trapezius muscles were significantly lower in females than in males . Significantly higher PPTs ( hypoalgesia ) in men than in women were shown 15 min after the first bilateral injection , and 7.5 and 15 min after the second bilateral injection in the referred pain areas . Importantly , the second bilateral injection failed to further increase the PPTs for both sexes . These results showed that there were sex differences in temporal characteristics of descending inhibition with long‐lasting hypoalgesia in men than in women . Repeated noxious muscular stimuli may inhibit further build‐up of DNIC , which may reflect a mechanism of plasticity of the descending inhibitory systems following recurrent nociceptive barrage for both sexes",
"Abstract Background and purpose Conditioned pain modulation ( CPM ) is a phenomenon in which pain is inhibited by heterotopic noxious stimulation . It is not known how the experimental condition affects the magnitude of the CPM response and the inter- and intra-individual variations . It is important to get the information of the test – retest reliability and inter – individual variations of CPM to apply CPM as a diagnostic tool or for screening analgesic compounds . This study evaluated ( 1 ) the magnitude of CPM , ( 2 ) the inter-individual coefficient of variation ( inter-CV ) and ( 3 ) the intra-individual coefficient of variation ( intra-CV ) to ( A ) different stimulus modalities to evoke CPM and ( B ) different assessment sites . Methods Twelve healthy men ( age 19–38 years ) participated in this study . Cold pressor pain ( CPP ) ( immersing the h and into cold water ) , tourniquet pain ( cuff around the upper arm ) and mechanical pressure pain ( craniofacial region ) were used in r and omized order as conditioning stimuli ( CS ) . The test stimulus ( TS ) was pressure pain applied to the right masseter muscle , left forearm and leg ( bilateral tibialis anterior : TA ) . The responses were pressure pain thresholds ( PPT ) , pressure pain tolerance ( PPTol ) thresholds and the pain intensity which was assessed on a visual analogue scale ( VAS , 0–10 cm ) following 1.4 and 1.6 × PPT applied to TA . The TS was applied before , during and 10 min after the CS . The intra-individual CV was estimated between different days . Results CPP induced the most powerful CPM on PPT ( 66.3 ± 10.0 % increase ) , VAS ratings ( 41.5 ± 5.3 % reduction ) and PPTol ( 32.6±4.6 % increase ) , especially at TA , and result ed in the smallest inter-CV ( 41.4–60.1 % ) . Independently of the CS , the inter-CV in general showed that the recordings from the orofacial region and the forearm had smaller values than from the leg . The smallest intra-CV value was obtained in pain ratings with CPP ( 27.0 % ) . Conclusions This study suggests that ( 1 ) the CPP evokes the largest CPM , ( 2 ) the leg as the assessment site results in the largest CPM responses and ( 3 ) the CPP causes the smallest inter- and intra-CV . Implication The present investigation implicates that the CPP is the most efficient conditioning stimulus to induce CPM when assessed by pressure pain thresholds "
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Background Frailty is widely recognised as a distinct multifactorial clinical syndrome that implies vulnerability . The links between frailty and adverse outcomes such as death and institutionalisation have been widely evidence d. There is currently no gold st and ard frailty assessment tool ; optimizing the assessment of frailty in older people therefore remains a research priority . The objective of this systematic review is to identify existing multi-component frailty assessment tools that were specifically developed to assess frailty in adults aged ≥60 years old and to systematic ally and critically evaluate the reliability and validity of these tools . Methods A systematic literature review was conducted using the st and ardised COnsensus‐based St and ards for the selection of health Measurement INstruments ( COSMIN ) checklist to assess the method ological quality of included studies . Results Five thous and sixty-three studies were identified in total : 73 of which were included for review . 38 multi-component frailty assessment tools were identified : Reliability and validity data were available for 21 % ( 8/38 ) of tools . Only 5 % ( 2/38 ) of the frailty assessment tools had evidence of reliability and validity that was within statistically significant parameters and of fair-excellent method ological quality ( the Frailty Index-Comprehensive Geriatric Assessment [ FI-CGA ] and the Tilburg Frailty Indicator [ TFI ] ) . Conclusions The TFI has the most robust evidence of reliability and validity and has been the most extensively examined in terms of psychometric properties . However , there is insufficient evidence at present to determine the best tool for use in research and clinical practice . Further in-depth evaluation of the psychometric properties of these tools is required before they can fulfil the criteria for a gold st and ard assessment tool
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"Background A frailty paradigm would be useful in primary care to identify older people at risk , but appropriate metrics at that level are lacking . We created and vali date d a simple instrument for frailty screening in Europeans aged ≥50 . Our study is based on the first wave of the Survey of Health , Ageing and Retirement in Europe ( SHARE , http://www.share-project.org ) , a large population -based survey conducted in 2004 - 2005 in twelve European countries . Methods Subjects : SHARE Wave 1 respondents ( 17,304 females and 13,811 males ) . Measures : five SHARE variables approximating Fried 's frailty definition . Analyses ( for each gender ) : 1 ) estimation of a discreet factor ( DFactor ) model based on the frailty variables using LatentGOLD ® . A single DFactor with three ordered levels or latent classes ( i.e. non-frail , pre-frail and frail ) was modelled ; 2 ) the latent classes were characterised against a biopsychosocial range of Wave 1 variables ; 3 ) the prospect i ve mortality risk ( unadjusted and age-adjusted ) for each frailty class was established on those subjects with known mortality status at Wave 2 ( 2007 - 2008 ) ( 11,384 females and 9,163 males ) ; 4 ) two web-based calculators were created for easy retrieval of a subject 's frailty class given any five measurements . Results Females : the DFactor model included 15,578 cases ( st and ard R2 = 0.61 ) . All five frailty indicators discriminated well ( p the age-adjusted Odds Ratio ( with 95 % Confidence Interval ) for mortality at Wave 2 was 2.1 ( 1.4 - 3.0 ) in the pre-frail and 4.8 ( 3.1 - 7.4 ) in the frail . Males : 12,783 cases ( st and ard R2 = 0.61 , all frailty indicators had p 3.1 % ) ; age-adjusted OR ( 95 % CI ) for mortality : 3.0 ( 2.3 - 4.0 ) in the pre-frail , 6.9 ( 4.7 - 10.2 ) in the frail . Conclusions The SHARE Frailty Instrument has sufficient construct and predictive validity , and is readily and freely accessible via web calculators . To our knowledge , SHARE-FI represents the first European research effort towards a common frailty language at the community level",
"Background Frail older people are at high risk of developing adverse outcomes , such as disability , mortality , hospitalization , and institutionalization . Previous research suggests that the Tilburg Frailty Indicator ( TFI ) is a valid and reliable instrument for measuring frailty . The aim of this study was to adapt and to test the reliability of the Polish version of the TFI . Method A st and ard guideline was used for translation and cultural adaptation of the English version of the TFI into Polish . The study included 100 Polish patients ( mean age 68.2±6.5 years ) , among them 42 men and 58 women . Cronbach ’s alpha was used for analysis of the internal consistency of the TFI . Results The mean total TFI score was 6.7±3.1 . Forty patients scored ≥5 , which corresponded to being frail . Cronbach ’s alpha reliability coefficients of the instrument ranged from 0.68 to 0.72 and item-total correlation ranged from 0.12 to 0.52 . Conclusion The TFI is valid and reproducible for assessment of frailty syndrome among a Polish population . The Polish adaptation of the TFI proved a useful and fast tool for assessing frailty",
"The easy-to-apply SOF criteria for frailty were recently vali date d in studies conducted in the U.S. only . In order to determine the ability of the SOF criteria to predict adverse health outcomes at a one-year follow-up in a sample of older out patients in Italy we carried out a prospect i ve cohort study on 265 community-dwelling out patients aged 65 + ( mean age 81.5 years ) consecutively referred to a geriatric clinic . At baseline participants underwent a comprehensive geriatric assessment ( CGA ) including evaluation of their frailty status according to the SOF criteria . At a one-year follow-up , between June and December 2010 , we investigated nursing home placement and death in all participants as well as any fall , any admission to the emergency department ( ED ) , any hospitalization and a greater disability among the subset of subjects still living at home . One year after the visit 231 subjects were still living at home ( 87.2 % ) , 9 had been placed in a nursing home ( 3.4 % ) and 25 had died ( 9.4 % ) . Frailty was associated with a greater risk of falls ( odds ratio [ OR ] 2.01 , 95 % confidence interval [ CI ] 1.05 - 3.83 , p=0.035 ) , hospitalization ( OR 2.08 , 95 % CI 1.02 - 4.24 , p=0.045 ) and death ( OR 3.07 , 95 % 1.02 - 4.24 , p=0.045 ) after correction for demographic characteristics , comorbidity including dementia and depression , socioeconomic position and severe disability . Thus , in an older outpatient population in Italy the frailty syndrome diagnosed according to the SOF criteria was an independent predictor of several adverse health outcomes ",
"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",
"BACKGROUND Frailty , as defined by the index derived from the Cardiovascular Health Study ( CHS index ) , predicts risk of adverse outcomes in older adults . Use of this index , however , is impractical in clinical practice . METHODS We conducted a prospect i ve cohort study in 6701 women 69 years or older to compare the predictive validity of a simple frailty index with the components of weight loss , inability to rise from a chair 5 times without using arms , and reduced energy level ( Study of Osteoporotic Fractures [ SOF index ] ) with that of the CHS index with the components of unintentional weight loss , poor grip strength , reduced energy level , slow walking speed , and low level of physical activity . Women were classified as robust , of intermediate status , or frail using each index . Falls were reported every 4 months for 1 year . Disability ( > or = 1 new impairment in performing instrumental activities of daily living ) was ascertained at 4(1/2 ) years , and fractures and deaths were ascertained during 9 years of follow-up . Area under the curve ( AUC ) statistics from receiver operating characteristic curve analysis and -2 log likelihood statistics were compared for models containing the CHS index vs the SOF index . RESULTS Increasing evidence of frailty as defined by either the CHS index or the SOF index was similarly associated with an increased risk of adverse outcomes . Frail women had a higher age-adjusted risk of recurrent falls ( odds ratio , 2.4 ) , disability ( odds ratio , 2.2 - 2.8 ) , nonspine fracture ( hazard ratio , 1.4 - 1.5 ) , hip fracture ( hazard ratio , 1.7 - 1.8 ) , and death ( hazard ratio , 2.4 - 2.7 ) ( P discriminating falls ( AUC = 0.61 for both models ; P = .66 ) , disability ( AUC = 0.64 ; P = .23 ) , nonspine fracture ( AUC = 0.55 ; P = .80 ) , hip fracture ( AUC = 0.63 ; P = .64 ) , or death ( AUC = 0.72 ; P = .10 ) . Results were similar when -2 log likelihood statistics were compared . CONCLUSION The simple SOF index predicts risk of falls , disability , fracture , and death as well as the more complex CHS index and may provide a useful definition of frailty to identify older women at risk of adverse health outcomes in clinical practice",
"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",
"OBJECTIVES To compare 3 methods of describing the frailty of older adults in nursing homes . DESIGN Secondary analysis of a prospect i ve cohort study . SETTING Canadian long-term care institutions . PARTICIPANTS Institutionalized older adults in the second clinical examination cohort of the Canadian Study of Health and Aging ( CSHA-2 ; n = 728 ) . MEASURES Frailty was measured using the Cardiovascular Health Survey definition ( Frail-CHS ) ; the CSHA- Clinical Frailty Scale ( CSHA-CFS ) and a frailty index ( FI ) . RESULTS The sample was very elderly ( 87.7 + /- 6.7 years ) , disabled ( 83 % ) , and showed a high level of mobility impairment ( 83 % ) . Each frailty measure correlated moderately well with each other ( 0.61 - 0.71 ) and with a disability measure ( -0.45 to -0.53 ) but only weakly with age ( 0.13 - 0.19 ) . By each measure , frailty was significantly associated ( P risk of mortality , disability and cognitive decline . In a model that included both the frailty-CHS definition and the Frailty Index only the latter was associated with a higher risk of mortality ( P new onset disability ( P CSHA-CFS and Frailty Index were included in the models . R and om combinations of 15 variables used to make up alternate 5-item Frail-CHS definitions showed that any stratification based on 5 variables allowed tertiles of risk to be discriminated . CONCLUSIONS Frailty is a robust concept and however defined , elderly people who are frail have worse outcomes than those who are not frail . The 3 measures showed varying ability to express grade s of frailty",
"BACKGROUND Selecting elderly persons who need geriatric interventions and making accurate treatment decisions are recurring challenges in geriatrics . Chronological age , although often used , does not seem to be the best selection criterion . Instead , the concept of frailty , which indicates several concurrent losses in re sources , can be used . METHODS The predictive values of chronological age and frailty were investigated in a large community sample of persons aged 65 years and older , r and omly drawn from the register of six municipalities in the northern regions of the Netherl and s ( 45 % of the original addressees ) . The participants ' generative capacity to sustain well-being ( i.e. , self-management abilities ) was used as the main outcome measure . RESULTS When using chronological age instead of frailty , both too many and too few persons were selected . Furthermore , frailty related more strongly ( with beta values ranging from -.25 to -.39 ) to a decline in the participants ' self-management abilities than did chronological age ( with beta values ranging from -.06 to -.14 ) . Chronological age added very little to the explained variances of all outcomes once frailty was included . CONCLUSIONS Using frailty as the criterion to select older persons at risk for interventions may be better than selecting persons based only on their chronological age",
"Background Frailty is a dynamic age-related condition of increased vulnerability characterized by declines across multiple physiologic systems and associated with an increased risk of death . We compared the predictive accuracy for one-month and one-year all-cause mortality of four frailty instruments in a large population of hospitalized older patients in a prospect i ve multicentre cohort study . Methods and Findings On 2033 hospitalized patients aged ≥65 years from twenty Italian geriatric units , we calculated the frailty indexes derived from the Study of Osteoporotic Fractures ( FI-SOF ) , based on the cumulative deficits model ( FI-CD ) , based on a comprehensive geriatric assessment ( FI-CGA ) , and the Multidimensional Prognostic Index ( MPI ) . The overall mortality rates were 8.6 % after one-month and 24.9 % after one-year follow-up . All frailty instruments were significantly associated with one-month and one-year all-cause mortality . The areas under the receiver operating characteristic ( ROC ) curves estimated from age- and sex-adjusted logistic regression models , accounting for clustering due to centre effect , showed that the MPI had a significant higher discriminatory accuracy than FI-SOF , FI-CD , and FI-CGA after one month ( areas under the ROC curves : FI-SOF = 0.685 vs. FI-CD = 0.738 vs. FI-CGA = 0.724 vs. MPI = 0.765 , p higher discriminatory power for predicting one-year mortality also in hospitalized older patients without functional limitations , without cognitive impairment , malnourished , with increased comorbidity , and with a high number of drugs . Conclusions All frailty instruments were significantly associated with short- and long-term all-cause mortality , but MPI demonstrated a significant higher predictive power than other frailty instruments in hospitalized older patients",
"BACKGROUND Observations that older people who enjoy life more tend to live longer suggest that psychological well-being may be a potential re source for healthier ageing . We investigated whether psychological well-being was associated with incidence of physical frailty . METHOD We used multinomial logistic regression to examine the prospect i ve relationship between psychological well-being , assessed using the CASP-19 , a question naire that assesses perceptions of control , autonomy , self-realization and pleasure , and incidence of physical frailty or pre-frailty , defined according to the Fried criteria ( unintentional weight loss , weakness , self-reported exhaustion , slow walking speed and low physical activity ) , in 2557 men and women aged 60 to ≥ 90 years from the English Longitudinal Study of Ageing ( ELSA ) . RESULTS Men and women with higher levels of psychological well-being were less likely to become frail over the 4-year follow-up period . For a st and ard deviation higher score in psychological well-being at baseline , the relative risk ratio ( RR ) for incident frailty , adjusted for age , sex and baseline frailty status , was 0.46 [ 95 % confidence interval ( CI ) 0.40 - 0.54 ] . There was a significant association between psychological well-being and risk of pre-frailty ( RR 0.69 , 95 % CI 0.63 - 0.77 ) . Examination of scores for hedonic ( pleasure ) and eud aim onic ( control , autonomy and self-realization ) well-being showed that higher scores on both were associated with decreased risk . Associations were partially attenuated by further adjustment for other potential confounding factors but persisted . Incidence of pre-frailty or frailty was associated with a decline in well-being , suggesting that the relationship is bidirectional . CONCLUSIONS Maintaining a stronger sense of psychological well-being in later life may protect against the development of physical frailty . Future research needs to establish the mechanisms underlying these findings",
"Background : There is no single generally accepted clinical definition of frailty . Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians . We aim ed to develop a tool that would be both predictive and easy to use . Methods : We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging ( CSHA ) . We followed this cohort prospect ively ; after 5 years , we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care , and correlated the results with those obtained from other established tools . Results : The CSHA Clinical Frailty Scale was highly correlated ( r = 0.80 ) with the Frailty Index . Each 1-category increment of our scale significantly increased the medium-term risks of death ( 21.2 % within about 70 mo , 95 % confidence interval [ CI ] 12.5%–30.6 % ) and entry into an institution ( 23.9 % , 95 % CI 8.8%–41.2 % ) in multivariable models that adjusted for age , sex and education . Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition , function or comorbidity in assessing risk for death ( area under the curve 0.77 for 18-month and 0.70 for 70-month mortality ) . Interpretation : Frailty is a valid and clinical ly important construct that is recognizable by physicians . Clinical judgments about frailty can yield useful predictive information",
"OBJECTIVES To determine the effect of static and dynamic frailty on mortality in older men and women . DESIGN A prospect i ve cohort study with three 3-year measurement cycles . SETTING Population based . PARTICIPANTS The sample was derived from the Longitudinal Aging Study Amsterdam and consisted of respondents who participated in two cycles ( T1 : 1992/1993 and T2 : 1995/1996 ) and for whom there was complete data on disability and chronic diseases ( N=2,257 ) . MEASUREMENTS Nine frailty markers were assessed at T1 and T2 . The frailty markers were defined in two ways : low functioning at T2 ( static frailty ) and change in functioning between T1 and T2 ( dynamic frailty ) . Survival time , calculated in days from T2 to January 1 , 2000 , was used as the outcome variable . Predictive ability was examined using Cox proportional hazards analyses separately for men and women . RESULTS Women were frailer than men . Static frailty was significantly associated with mortality in men ( relative risk (RR)=2.4 ) and in women ( RR=2.6 ) . Dynamic frailty was also associated with mortality in women ( RR=2.6 ) , but it was not significantly associated with mortality in men ( RR=1.3 ) . When disability and chronic diseases were included in the model as possible mediators , these RRs dropped to 1.6 , 2.0 , 2.1 , and 1.2 , respectively , of which the first three were still significant . CONCLUSION Frailty was associated with mortality to a greater extent in women than in men , and this effect was independent of disability and chronic disease . In men , the static definition of frailty was more predictive of mortality than the dynamic definition",
"OBJECTIVES To construct and vali date a frailty index ( FI ) that is clinical ly sensible and practical for geriatricians by basing it on a routinely used comprehensive geriatric assessment ( CGA ) instrument . DESIGN Secondary analysis of a 3-month r and omized , controlled trial of a specialized mobile geriatric assessment team . SETTING Rural Nova Scotia . Participants were seen in their homes . PARTICIPANTS Frail older adults , of whom 92 were in the intervention group and 77 in the control group . MEASUREMENTS A st and ard CGA form that accounts for impairment , disability , and comorbidity burden was scored and summed as a frailty index ( FI-CGA ) . The FI-GCA was stratified to describe three levels of frailty . Patients were followed for up to 12 months to determine how well the index predicted adverse outcomes ( institutionalization or mortality , whichever came first ) . RESULTS The three levels of frailty were mild ( FI-CGA 0 - 7 ) , moderate ( FI-CGA 7 - 13 ) , and severe ( FI-CGA>13 ) . Demographic and social traits were similar across groups , but greater frailty was associated with worse function ( r=0.55 ) and mental status ( r=0.33 ) . Those with moderate and severe frailty had a greater risk of adverse outcomes than those with mild frailty ( unadjusted hazard ratio=1.9 and 5.5 , respectively ) . There was no difference between frailty groups in mean 3-month goal -attainment scaling scores . Intrarater reliability was 0.95 . CONCLUSION The FI-CGA is a valid , reliable , and sensible clinical measure of frailty that permits risk stratification of future adverse outcomes",
"OBJECTIVE To examine the association between frailty status and incidence of disability among non-disabled older Mexican Americans . DESIGN A 10-year prospect i ve cohort study . SUBJECTS A total of 1645 non-institutionalized Mexican Americans aged 67 years and older from the Hispanic Established Population for the Epidemiological Study of the Elderly ( H-EPESE ) , who reported no limitation in activities of daily living at baseline . METHODS Frailty was defined as meeting 3 or more of the following components : ( i ) unintentional weight loss of > 2.26 kg ; ( ii ) weakness ( lowest 20 % in h and grip strength ) ; ( iii ) self-reported exhaustion ; ( iv ) slow walking speed ; and ( v ) low physical activity level . Socio-demographic factors , Mini Mental State Examination , medical conditions , body mass index , and self-reported activities of daily living were obtained . RESULTS Of the 1645 non-disabled subjects at baseline , 820 ( 50 % ) were not frail , 749 ( 45.7 % ) were pre-frail , and 71 ( 4.3 % ) were frail . The hazard ratio of activities of daily living disability at 10-year follow-up for pre-frail subjects was 1.32 ( 95 % confidence interval 1.10 - 1.58 ) and 2.42 ( 95 % confidence interval 70 - 3.46 ) for frail subjects compared with not frail subjects . This association remained statistically significant after controlling for potential confounding factors at baseline . CONCLUSION Pre-frail and frail status in older Mexican Americans was associated with an increased risk of activities of daily living disability over a 10-year period among non-disabled subjects",
"OBJECTIVES To provide a new instrument to diagnose frailty , the Frailty Trait Scale ( FTS ) , that allows a more precise assessment and monitoring of individuals . DESIGN Prospect i ve population -based cohort study . SETTING The Toledo Study for Healthy Aging , Spain . PARTICIPANTS A total of 1972 men and women aged 65 years or older . MEASUREMENTS We identified 7 frailty dimensions ( energy balance-nutrition , physical activity , nervous system , vascular system , strength , endurance , and gait speed ) represented by 12 items . Each item was pondered based on the quintiles of its distribution in the study population . Validity was evaluated by testing its association with factors related to frailty and its predictive value for adverse events . This predictive capacity was further compared with the capacity of 2 well-established frailty models ( the frailty phenotype and the Frailty Index ) . RESULTS FTS score was associated with several comorbidities and biomarkers classically associated with frailty . The FTS was associated with the incidence of hospitalization and mortality ( hazard ratio associated with a score in the highest quartile [ versus the first quartile ] = 2.3 , 95 % confidence interval [ CI ] 1.6 - 3.4 , and 2.5 , 95 % CI 1.8 - 3.6 , respectively ) . Compared with Fried et al 's definition , the FTS showed a better predictor for hospitalization in persons younger than 80 ( area under the curve [ AUC ] = 0.65 vs 0.62 , P = .01 ) , and for mortality in the oldest group ( AUC = 0.77 vs 0.72 , P = .02 ) . FTS showed similar predictive value to the Frailty Index . CONCLUSION FTS associates with many of the factors linked to frailty and has a similar predictive capacity to that provided by the classical instruments . Its characteristics offer some advantages over them , with potential utility in research and clinical practice",
"OBJECTIVE To identify the most important predictors of early disability incidence and devise a simple score of physical frailty . METHODS A cohort of 545 high-functioning women aged 75 years and older was followed for 7 years . Every year , the self-reported loss of at least one instrumental activity of daily living was chosen as definition of disability . An extension of the logistic regression for repeated responses , the r and om-effect model , was used to assess the effects of baseline predictors . The regression coefficients of the final multivariate model were scaled and rounded to create a practical score . RESULTS The proportion of women reporting disability increased from 22.1 % to 52.1 % throughout the follow-up . In the multivariate model , increasing age , lower performances in mobility and balance tests , bad perceived health , lower muscle strength , higher body mass index , lower educational level , and lower reported physical activity were strong predictors of disability . Evaluating the predictive value of the simplified predictive score on an independent cohort gave a c-statistic equal to .71 . CONCLUSION The use of a powerful fitting method allows to establish a hierarchy between the components of physical frailty and to provide a predictive score with substantial practical value for clinicians and public health professionals",
"Studies of disability in old age have focused on gross measures of physical functioning . More useful results for prevention might be gleaned from examining risk factors associated with frailty , a concept implying a broader range of more subtle problems in multiple domains . This study conceptualized frailty as involving problems or difficulties in two or more functional domains ( physical , nutritive , cognitive , and sensory ) and analyzed prospect i ve predictors . Subjects were 574 Alameda County Study respondents age 65 - 102 . One-fourth scored as frail ; there was no gender difference . Frail persons reported reduced activities , poorer mental health , and lower life satisfaction . Cumulative predictors over the previous three decades included heavy drinking , cigarette smoking , physical inactivity , depression , social isolation , fair or poor perceived health , prevalence of chronic symptoms , and prevalence of chronic conditions . By modifying these risk factors , it may be possible to postpone the onset of frailty or ameliorate its further development",
"Background If brief and easy to use self report screening tools are available to identify frail elderly , this may avoid costs and unnecessary assessment of healthy people . This study investigates the predictive validity of three self-report instruments for identifying community-dwelling frail elderly . Methods This is a prospect i ve study with 1-year follow-up among community-dwelling elderly aged 70 or older ( n = 430 ) to test sensitivity , specificity , and positive and negative predicted values of the Groningen Frailty Indicator , Tilburg Frailty Indicator and Sherbrooke Postal Question naire on development of disabilities , hospital admission and mortality . Odds ratios were calculated to compare frail versus non-frail groups for their risk for the adverse outcomes . Results Adjusted odds ratios show that those identified as frail have more than twice the risk ( GFI , 2.62 ; TFI , 2.00 ; SPQ , 2,49 ) for developing disabilities compared to the non-frail group ; those identified as frail by the TFI and SPQ have more than twice the risk of being admitted to a hospital . Sensitivity and specificity for development of disabilities are 71 % and 63 % ( GFI ) , 62 % and 71 % ( TFI ) and 83 % and 48 % ( SPQ ) . Regarding mortality , sensitivity for all tools are about 70 % and specificity between 41 % and 61 % . For hospital admission , SPQ scores the highest for sensitivity ( 76 % ) . Conclusion All three instruments do have potential to identify older persons at risk , but their predictive power is not sufficient yet . Further research on these and other instruments is needed to improve targeting frail elderly",
"BACKGROUND The adoption of a frailty paradigm in primary care would be helpful to identify adults who need priority access to specialised re sources . The frailty phenotype by Fried et al is a popular operationalisation of frailty , but it is not easily applicable in routine primary care practice . We recently created and vali date d a frailty instrument based on the Survey of Health , Ageing and Retirement in Europe ( SHARE-FI ) , in order to provide primary care practitioners with an easy , reliable and freely accessible tool for the assessment and monitoring of frailty in community dwelling adults over the age of 50 years ( www.biomed central .com/1471 - 2318/10/57 ) . AIM To provide further prospect i ve validation of SHARE-FI , with a focus on disability . METHODS DESIGN longitudinal study ( wave 1 : 2004 - 2006 ; mean follow-up : 2.4 years ) . SETTING European population -based survey ( 12 countries ) . SUBJECTS 17 567 community dwelling participants ( mean age 63.3 years ) , of whom 13 378 ( 76.2 % ) were non-frail , 3438 ( 19.6 % ) pre-frail and 751 ( 4.3 % ) frail . MAIN OUTCOME MEASURES number of difficulties with basic ( ADL ) and instrumental ( IADL ) activities of daily living . STATISTICAL ANALYSES repeated measures ANOVA with adjustment for baseline age . RESULTS By wave 2 , 3.6 % of the non-frail , 12.2 % of the pre-frail and 30.4 % of the frail had increased their number of ADL difficulties by at least one . Likewise , 6.6 % of the non-frail , 20.4 % of the prefrail and 36.6 % of the frail had , by wave 2 , increased their number of IADL difficulties by at least one . Table 1 shows the repeated measures ANOVA suggested . CONCLUSION SHARE-FI may contribute to quality in primary care by offering a quick and reliable way to assess and monitor frailty in community dwelling individuals over the age of 50 and prioritize their access to re sources , and it serves as a novel tool for audit and research",
"OBJECTIVES To construct a brief frailty index for older patients with coronary artery disease ( CAD ) undergoing coronary angiography that includes physical , cognitive , and psychosocial criteria and accurately predicts future disability and decline in health-related quality of life ( HRQL ) . DESIGN Prospect i ve cohort . SETTING An urban tertiary care hospital in Alberta , Canada . PARTICIPANTS Three hundred seventy-four patients aged 60 and older ( 73 % male ) undergoing cardiac catheterization for CAD between October 2003 and May 2007 . MEASUREMENTS Potential frailty criteria examined at baseline ( before the procedure ) included measures of balance , gait speed , cognition , self-reported health , body mass index ( BMI ) , depressive symptoms , and living alone . The outcomes assessed over 1 year were dependency in activities of daily living ( ADLs ) and HRQL . RESULTS The five best-fitting criteria from regression analyses for ADL decline were poor balance ( risk ratio (RR)=2.4 , 95 % confidence interval (CI)=1.4–4.0 ) , abnormal BMI ( RR=1.8 , 95 % CI=1.1–3.0 ) , impaired Trail-Making Test Part B performance ( RR=2.3 , 95 % CI=1.3–4.2 ) , depressive symptoms ( RR=1.8 , 95 % CI=1.1–3.1 ) , and living alone ( RR=2.2 , 95 % CI=1.3–3.8 ) . Using the five criteria as separate variables or as a summary frailty index yielded identical areas under the receiver operating characteristic curve ( 0.76 , 95 % CI=0.66–0.84 ) . Patients with three or more criteria ( vs none ) were at statistically significant greater risk for increased disability ( RR=10.4 , 95 % CI=4.4–24.2 ) and decreased HRQL ( RR=4.2 , 95 % CI=2.3–7.4 ) after 1 year . CONCLUSION This brief frailty index including physical , cognitive , and psychosocial criteria was predictive of increased disability and decreased HRQL at 1 year in older patients with CAD undergoing angiography . This index may have applications for clinicians and research ers but requires further validation",
"BACKGROUND identification of frailty is recommended in geriatric practice . However , there is a lack of frailty scores combining easy-to-collect predictors from multiple domains . OBJECTIVE to develop a frailty score including only self-reported information and easy-to-perform st and ardised measurements recommended in routine geriatric practice . DESIGN prospect i ve population -based study . SETTING / PARTICIPANTS included 1,007 Italian subjects aged 65 and over . MEASUREMENTS seventeen baseline possible mortality predictors from several domains , 4-year risk of mortality and other adverse health outcomes associated with frailty [ fractures , hospitalisation , and new and worsening activities of daily living ( ADL ) disability ] . METHODS a multivariate Cox model was used to identify the best sub-group of independent predictors and to develop a mortality prognostic score , defined as the number of adverse predictors present . Logistic regression was used to verify whether the score also predicted risk of other frailty outcomes in the cohort survivors . RESULTS nine independent mortality predictors were identified . Among subjects with score > or =3 , each one point increase in the score was associated with a doubling in mortality risk and , among survivors , with an increased risk of all the other adverse health outcomes . CONCLUSIONS nine easy-to-collect predictors may identify aged people at increased risk of adverse health outcomes associated with frailty",
"Background and aims : Objectives were to develop a frailty index ( FI ) based on a st and ard comprehensive geriatric assessment ( CGA ) derived from a clinical examination ; to assess the validity of the FI-CGA and to compare its precision with other frailty measures . Methods : Design : Secondary analysis of a prospect i ve cohort study , with five-year follow-up data . Setting : Second phase of the Canadian Study of Health and Aging ( CSHA-2 ) ; clinical examinations were performed in clinics , nursing homes , and patients ’ homes . Participants : People selected ( as either cognitively impaired cases or unimpaired controls ) to receive the CSHA-2 clinical examination ( n=2305 ; women=1431 ) . Measurements : Clinical and performance-based measures and diagnostic data were extracted to correspond to the 10 impairment domains and the single comorbidity domain of a CGA . The proportion of deficits accumulated in each domain was calculated to yield the FI-CGA . The FI-CGA was vali date d and its predictive ability compared with other frailty measures . Results : Within the seven grade s of fitness/frailty identified , subjects with greater frailty were older , less educated , and more likely to be women . The FI-CGA correlated highly with a previously vali date d , empirically-derived frailty index ( r=0.76 ) . Frailty was associated with higher risk of death ( for each increment in frailty , the hazard ratio , adjusted for age , sex and education , was 1.23 ( 95 % CI 1.18–1.29 ) and institutionalization ( HR 1.20 ; 1.10–1.32 ) . Conclusions : In a population survey , the FI-CGA is a valid means of quantifying frailty from routinely collected data",
"OBJECTIVE The Geriatric Assessment ( GA ) is an established method for evaluating and optimizing diagnostic and treatment plans . However , it requires experience and is time-consuming . Therefore , a variety of screening methods have been developed . The aim of this study was to compare their accuracy for predicting frailty among older patients with cancer qualified for abdominal surgery based on comparison to the GA . MATERIAL AND METHODS One hundred and thirty five consecutive patients ≥65years of age were prospect ively enrolled . The diagnostic performance of eight screening tests was evaluated : The Vulnerable Elderly Survey ( VES-13 ) , Triage Risk Screening Tool ( TRST ) , Geriatric 8 ( G8 ) , Groningen Frailty Index ( GFI ) , abbreviated Comprehensive Geriatric Assessment ( aCGA ) , Rockwood , Balducci and Fried score . RESULTS The prevalence of frailty as diagnosed by the GA was 73 % . Screening methods identified frail patients in 40 - 75.5 % of cases . The sensitivity and specificity of these tests in predicting frailty were 52%-97 % ( Fried score-G8 ) and 44 - 100 % ( G8-Rockwood score ) , respectively . The positive and negative predictive values were 82 - 100 % ( Balducci-Rockwood ) and 43 - 84 % ( TRST-G8 ) , respectively . Age significantly influenced the predictive value of the screening tests whereas gender and type of cancer did not . CONCLUSION At present , there is no universal screening test that adequately identifies frailty in at risk older patients . The results of this study showed that the aCGA and G8 were the best screens for older patients with cancer that qualified for elective abdominal surgery ; the G8 had the highest sensitivity and negative predictive value and the aCGA was a good overall assessment tool",
"Objectives Cognitive decline is related to frailty . Frailty can be operationalized in different ways , which have an unknown impact on the estimation of risk . Here , we compared 3 frailty measures in relation to cognitive changes and mortality in the Canadian Study of Health and Aging ( CSHA ) . Design Prospect i ve population -based study , with 5 year follow up . Participants / Setting 2,305 subjects aged 70 + years . Methods For each participant , cognitive status was measured by the errors in the Modified Mini-Mental State Examination ( 3MS ) score . Three frailty measures were used : a Frailty Index based on the Comprehensive Geriatric Assessment ( FI-CGA ) evaluated from 47 potential deficits , a Clinical Frailty Score and the Fried frailty phenotype . Multivariate Poisson regression and multivariate logistic regression were used to examine the association between baseline cognitive errors and frailty and death , respectively , while controlling for possible confounders ( age , sex , education , and baseline cognitive status ) . Results Changes in cognitive status were strongly associated with baseline cognition and frailty , however defined . In multivariate models adjusted for age , sex and education , each frailty measure was associated with cognitive decline and with mortality . The frailest people ( from the highest FI-CGA tertile ) rarely showed cognitive improvement or stabilization ( 1.5 % , 95 % CI=0.002%–2.8 % ) compared with non-frail people ( from the lowest tertile of the FI-CGA ) , of whom 27.8 % ( 95 % CI=24.5%–31.1 % ) did not deteriorate . Conclusions Frail elderly people have an increased risk of cognitive decline . All frailty measures allowed quantification of individual vulnerability and predict both cognitive changes and mortality",
"Background and aims : Frailty and mortality in psychogeriatric patients are hard to predict but important in counselling and therapeutic decision making . We have therefore developed a simple frailty risk score to predict mortality this population . Study design : Prospect i ve observational study including 401 community dwelling psychogeriatric patients ( 249 women ; mean ( SD ) age 78.0 ( 6.5 ) years ) , who had been referred to a multidisciplinary diagnostic observation centre . We used Cox proportional hazards regression models to identify and select baseline characteristics for the development and validation of a risk score for the prediction of 3 year mortality . Results : A total of 116 subjects died during follow-up ( median follow-up duration of 26 months ) . Baseline characteristics associated with mortality were : age ( hazard ratio ( HR ) 1.44 , 95 % confidence interval (CI)1.02 to 2.04 ) , male sex ( HR 2.93 , 95 % CI 1.89 to 4.59 ) , living alone ( HR 1.53 , 95 % CI 0.99 to 2.38 ) , body mass index ( BMI ) elderly mobility score number of medicines ⩾2 ( HR 2.28 , 95 % CI 1.21 to 4.31 ) , and impaired motor ( HR 1.47 , 95 % CI 0.93 to 2.32 ) and process skills ( HR 1.92 , 95 % CI 1.12 to 2.98 ) in activities of daily living . These predictors were translated into an easy-to-use frailty risk score and patients were stratified into very good ( 61 ) prognosis groups . Three year mortality rates across these groups were 8.0 % , 15.9 % , 25.9 % , 41.5 % , and 68.8 % , respectively ( p The area under the receiver operating characteristic curve ( AUC ) of the risk score was 0.78 ( 95 % CI 0.73 to 0.82 ) , indicating good discriminative performance . Conclusions : We developed and vali date d a risk score for the prediction of 3 year mortality . This risk score can be used to stratify patients into different risk categories , thereby informing patient counselling and tailored diagnostic and therapeutic decisions in clinical practice",
"Most definitions of frailty utilize US population s in their development . The concept of frailty has not been well studied in Japan , which has the largest percentage of older patients ( per capita ) in the world . We created a 5-year prospect i ve cohort study of community-dwelling older Japanese adults . Participants were not frail at baseline , based on our definition adapted from the Canadian Study for Health and Aging Clinical Frailty Scale . Participants underwent a comprehensive geriatric assessment ( CGA ) at baseline , and final assessment s were either in person or via mailed survey . We enrolled 407 individuals ( 184 men , mean age 78 ± 4 years ; 223 women , mean age 77 ± 4 years ) . Sixty-five participants met criteria for frailty by the end of the study . In univariate analyses , eighteen separate parameters were associated with frailty , some of which included : age , gender , h and grip , timed walk , systolic blood pressure , pulse pressure , cognitive status , living alone , and hearing deficits . In multivariate analyses , the following elements remained associated with frailty : timed walk , pulse pressure , cognition deficits and hearing deficits . We established cut-off points for timed walk ( 5m/3s ) and pulse pressure ( 60 mmHg ) . We then created a simple additive score for these four factors ( present = 1 ; absent = 0 ) . A score of 0 had a 93 % negative predictive value for frailty while a score of 4 had a 70 % positive predictive value . While further study is needed , this work creates an easy-to-administer tool that may be generalizable to other population"
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41175622-06ff-11f0-808a-c43d1ab1c353
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Purpose In the foot and ankle literature , a wide range of patient-reported outcome measures ( PROMs ) is used , however , consensus as to which PROMs are preferred is lacking . Selection of a PROM is among other reasons , often based on measurement properties without considering the method ological quality of the studies that evaluate these measurement properties . The aim of current study was first to identify the most frequently used foot and ankle-specific PROMs in recent orthopaedic foot and ankle literature , and second to conduct a systematic review to synthesize and critically appraise the measurement properties of these PROMS . Methods Six PubMed indexed journals focussing on foot and ankle research were screened to identify most commonly used foot and ankle-specific PROMs over a 2 year period ( 2015–2016 ) . Subsequently , a systematic literature search was performed in PubMed , EMBASE , SPORTD iscus and Scopus to identify relevant studies on their measurement properties . Method ological quality assessment was performed using the COnsensus-based St and ards for the selection of health Measurement INstruments ( COSMIN ) checklist , criteria for good measurement properties were applied , and a level of evidence was determined for the measurement properties of each domain of the question naires . Results The three most frequently reported PROMs were the Foot Function Index ( FFI ) , the Foot and Ankle Outcome Score ( FAOS ) and the Foot and Ankle Activity Measure ( FAAM ) . Among 2046 unique citations , 50 studies were included evaluating these PROMs . Evidence to support the measurement properties of the FFI was mainly lacking due to poor method ological quality . More evidence was available for the measurement properties of the FAOS and the FAAM , but overall evidence supporting all measurement properties is not yet sufficient . Conclusion The best available evidence retrieved in this review showed that the FAOS and the FAAM are promising outcome measures for evaluation of patients with foot and ankle conditions , but their shortcomings should be taken into account when interpreting results in clinical setting or trials . Level of evidence
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[
"The aims of this study were to culturally adapt and vali date the Persian version of Foot and Ankle Outcome Score ( FAOS ) and present data on its psychometric properties for patients with different foot and ankle problems . The Persian version of FAOS was developed after a st and ard forward – backward translation and cultural adaptation process . The sample included 93 patients with foot and ankle disorders who were asked to complete two question naires : FAOS and Short-Form 36 Health Survey ( SF-36 ) . To determine test – retest reliability , 60 r and omly chosen patients completed the FAOS again 2 to 6 days after the first administration . Test – retest reliability and internal consistency were assessed using intraclass correlation coefficient ( ICC ) and Cronbach ’s alpha , respectively . To evaluate convergent and divergent validity of FAOS compared to similar and dissimilar concepts of SF-36 , the Spearman ’s rank correlation was used . Dimensionality was determined by assessing item – subscale correlation corrected for overlap . The results of test – retest reliability show that all the FAOS subscales have a very high ICC , ranging from 0.92 to 0.96 . The minimum Cronbach ’s alpha level of 0.70 was exceeded by most subscales . The Spearman ’s correlation coefficient for convergent construct validity fell within 0.32 to 0.58 for the main hypotheses presented a priori between FAOS and SF-36 subscales . For dimensionality , the minimum Spearman ’s correlation coefficient of 0.40 was exceeded by most items . In conclusion , the results of our study show that the Persian version of FAOS seems to be suitable for Iranian patients with various foot and ankle problems especially lateral ankle sprain . Future studies are needed to establish stronger psychometric properties for patients with different foot and ankle problems",
"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",
"Background : Selecting optimal patient-reported outcome ( PRO ) instruments is critical to improving the quality of health care . The purpose of this study was to compare the reliability , responsiveness , and efficiency of three PRO measures : the Foot and Ankle Ability Measure – Activity of Daily Living subscale ( FAAM_ADL ) , the Foot Function Index 5-point verbal rating scale ( FFI-5pt ) , and the PROMIS Physical Function computerized adaptive test ( PF CAT ) . Methods : Data were aggregated from 10 clinical sites in the AOFAS ’s National Orthopaedic Foot and Ankle Research ( OFAR ) Network from 311 patients who underwent elective surgery for a disorder of the foot or ankle . Patients were administered the FAAM_ADL , FFI-5pt , and PF CAT at their preoperative visit and at 6 months after surgery . Reliabilities were evaluated using a Rasch model . Responsiveness was calculated using paired sample s t test and efficiency was recorded as number of seconds to complete the instrument . Results : Similar reliabilities were found for the three instruments . Item reliabilities for FAAM_ADL , FFI-5pt , and PF CAT were all .99 . Pearson reliabilities for FAAM_ADL , FFI-5pt , and PF CAT were .95 , .93 , and .96 , respectively . On average , patients completed the FAAM_ADL in 179 seconds , the FFI-5pt in 194 seconds , and the PF CAT in 44 seconds , ( P in patients ’ physical function after treatment ; the FFI-5pt did not show improvement . Conclusions : Overall , the PF CAT performed best in terms of reliability , responsiveness , and efficiency in this broad sample of foot and ankle patients . It can be a potential replacement for the conventional PRO measures , but further validation is needed in conjunction with the PROMIS Pain instruments . Level of Evidence : Level I , prospect i ve comparative outcome study",
"Purpose The aim of this study was to evaluate the responsiveness of the Foot and Ankle Outcome Score ( FAOS ) and provide data on the Minimally Important Change ( MIC ) in patients 1 year after hindfoot and ankle surgery . Methods Prospect i ve pre-operative and 1 year post-operative FAOS scores were collected from 145 patients . A patient ’s global assessment and a longitudinal derived Function Change Score were used as external anchors . To assess responsiveness , effect sizes ( ES ) and St and ardized Response Means ( SRM ) were calculated and hypotheses on their magnitudes were formulated . Additional ROC curve analysis was performed , and the Area Under the Curve ( AUC ) was calculated as a measure of responsiveness . MIC values were estimated using two different methods : ( 1 ) the mean change method and ( 2 ) the optimal cut-off point of the ROC curve . Results Responsiveness was supported by confirmation of 84 % of the hypothesized ES and SRM and almost all AUCs exceeding 0.70 . MIC values ranged from 7 ( symptoms ) to 38 ( sport ) points . They varied between calculation methods and were negatively associated with baseline values . A considerable amount of MIC values did not exceed the smallest detectable change limit , indicating that the FAOS is more suitable at group level than for longitudinally following individual patients . Conclusions The FAOS demonstrated good responsiveness in patients 1 year after hindfoot and ankle surgery . Due to their wide variation , MIC estimates derived in this study should be interpreted with caution . However , these estimates can be of value to facilitate sample size calculation in future studies .Level of evidence Diagnostic study , Level",
"The objective is to develop a Turkish version of the foot and ankle outcome score ( FAOS ) and to investigate its validity and reliability . The Turkish version of FAOS was developed after the translation and back-translation . The translated version was pretested on 20 patients with rheumatoid arthritis . Then , the Turkish FAOS was administered to 55 patients having foot and ankle problems . They were also evaluated by using the four subscales of the Turkish version of AIMS 2 , and the Turkish version of SF-36 question naire to test validity . Fifty patients filled out the FAOS for second time to determine test – retest reliability . Construct validity was investigated with use of Spearman ’s rank correlation coefficient . Test – retest reliability was assessed with use of the intraclass correlation coefficient ( ICC ) and Cronbach ’s alpha score . The psychometric properties of the Turkish FAOS were generally similar to the original FAOS . The r and om ICC for the five subscales ranged from 0.70 to 0.96 . The Cronbach ’s alpha coefficient ranged from 0.79 to 0.97 . Construct validity of the FAOS was good . The Turkish FAOS correlated with the SF-36 and AIMS 2 scales . The Turkish version of FAOS was valid and reliable instrument to assess the foot and ankle related problems . However , to assess its responsiveness further studies are needed",
"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",
"OBJECTIVE To assess the clinimetric value of the Dutch version of the Foot Function Index ( FFI ) in comparison with the original FFI using verbal rating scales ( FFI-5pt ) rather than visual analog scales ( VAS ) . METHODS A prospect i ve study was performed on 206 patients with nontraumatic forefoot complaints . Scoring , internal consistency , and construct validity of the FFI-5pt were compared with those of the original FFI , which rates all items on VAS . We also studied agreement between the scores at baseline and after one and 8 weeks and the scale scores with regard to sex , age , presence of osteoarthritis , limitation of mobility , bodily pain , and poor physical functioning ( using SF-36 ) . RESULTS Some items were not applicable ; removal of these items left 2 scales ( Pain and Disability ) with high internal consistency ( alpha = 0.88 to 0.94 ) and good agreement between both versions ( intraclass correlation coefficient 0.64 to 0.79 ) . Principal component analysis with varimax rotation using a forced 2 factor model fitted well ( 65 % explained variance ) . Test-retest reliability was high ( ICC 0.70 to 0.83 ) , while the stability over 8 weeks was lower , but still good ( ICC 0.63 to 0.71 ) . Responsiveness to change was low to moderate . However , a small number of patients reported an overall change ( 19 % ) . Scores of patients with limited mobility and poor physical health ( SF-36 ) were higher than those of patients with fewer physical problems , indicating good concurrent validity . CONCLUSION The FFI-5pt is a suitable generic measure . Its clinimetric properties are comparable with those of the original FFI . Its administration and data entry are less time consuming . However , responsiveness has to be more exactly assessed in an intervention study",
"Background There is a clear call for improved patient-centered outcomes . The Foot and Ankle Outcome Score ( FAOS ) is a region-specific patient-reported measure that has been vali date d for a number of foot and ankle diagnoses , but not hallux rigidus . Questions / Purpose sThe aim of this study was to vali date the FAOS in patients with hallux rigidus . Methods From 2007 to 2013 , 211 patients with hallux rigidus ( HR ) were included in the study . For the construct validity portion of the study , 125 patients completed a Short-Form 12 ( SF-12 ) and FAOS survey . Forty additional HR patients were prospect ively given question naires to assess the relevance of each FAOS question as it pertained to their HR . Reliability was assessed in 36 HR patients via administration of a second FAOS an average 1 month following the first . In 55 patients , preoperative and postoperative FAOS scores were compared to determine responsiveness . Results All FAOS subscales demonstrated moderate correlation coefficients with the physical functioning , role physical , bodily pain , and physical health component scores of the SF-12 , with all subscales demonstrating poor correlation with the SF-12 mental health-related domains . Content validity was high for all FAOS scores , with the exception of the daily activities subscale . All subscales achieved acceptable test – retest reliability with correlation coefficients of ≥0.72 . Furthermore , all subscales were rated as responsive to change in postoperative patients ( p < 0.001 ) . Conclusion This study demonstrates the acceptable construct and content validity , reliability , and responsiveness of the FAOS for hallux rigidus . Due to its broad applicability and proven validation across multiple foot and ankle pathologies , the FAOS represents a patient-centered outcome measure that can be reliably used for the assessment of patients with hallux rigidus",
"Background : We examined four commonly used scores , the SF-36 , the Ankle Osteoarthritis Scale ( AOS ) , the American Orthopaedic Foot and Ankle Society ( AOFAS ) Ankle Hindfoot Score , and the Foot Function Index ( FFI ) to determine their responsiveness and validity . Methods : Patients with end stage ankle arthritis were recruited into a prospect i ve multicenter cohort study and baseline and one year outcome scores were compared . The St and ardized Response Mean and Effect Size for the AOS , AOFAS , and FFI were calculated and the three region- or disease-specific scores were compared with the SF-36 to determine their criterion validity . Results : All four scores showed acceptable responsiveness , and when using the vali date d SF-36 as the st and ard the three region or disease specific scores all showed similar criterion validity . Conclusion : All four scores are responsive and can be considered for use in this population . The objective component of the AOFAS Ankle Hindfoot Score may make it harder to perform than the other three scores which have subjective components only , and as yet its objective component has not been shown to demonstrate reliability . We recommend use of a purely subjective score such as the Ankle Osteoarthritis Scale or Foot Function Index as the region- or disease-specific score of choice in this population . As the SF-36 shows acceptable responsiveness , using it alone could also be considered . Level of Evidence : II , Prospect i ve Comparative",
"In the past decade , health-related quality -of-life ( HRQoL ) assessment has become an important tool to measure change as a result of treatment in clinical trials . The aim of this project was to compare and contrast two foot-specific HRQoL question naires : the Foot Function Index ( FFI ) and the Foot Health Status Question naire ( FHSQ ) . To assist in this process , a quasi-experimental trial was performed to evaluate the effectiveness of foot orthoses in improving HRQoL in people suffering from plantar fasciitis . The results from this study found that the FFI is generally less responsive to change , particularly in the domain of Activity Limitation . Nevertheless , significant improvements were found for two out of the three domains ( Pain and Disability , but not Activity Limitation ) for the FFI , as well as the overall score of FFI . In contrast , all four domains ( Pain , Function , Footwear and General Foot Health ) of the FHSQ showed significant improvement . Our experience with the question naires also revealed that certain questions in the Activity Limitation domain of the FFI can lead to inconsistent scoring , thus casting doubts over the suitability of this domain for use with patients with plantar fasciitis . Therefore , the FHSQ has several advantages when evaluating HRQoL in patients being treated with foot orthoses for plantar fasciitis , and should be viewed as the preferred question naire",
"The foot and ankle outcome score ( FAOS ) has been evaluated for many conditions of the foot and ankle . We evaluated its construct validity in 136 patients with osteoarthritis of the ankle , its content validity in 37 patients and its responsiveness in 39 . Data were collected prospect ively from the registry of patients at our institution . All FAOS subscales were rated relevant by patients . The Pain , Activities of Daily Living , and Quality of Life subscales showed good correlation with the Physical Component score of the Short-Form-12v2 . All subscales except Symptoms were responsive to change after surgery . We concluded that the FAOS is a weak instrument for evaluating osteoarthritis of the ankle . However , some of the FAOS subscales have relative strengths that allow for its limited use while we continue to seek other satisfactory outcome instruments",
"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",
"A Foot Function Index ( FFI ) was developed to measure the impact of foot pathology on function in terms of pain , disability and activity restriction . The FFI is a self-administered index consisting of 23 items divided into 3 sub-scales . Both total and sub-scale scores are produced . The FFI was examined for test-retest reliability , internal consistency , and construct and criterion validity . A total of 87 patients with rheumatoid arthritis were used in the study . Test-retest reliability of the FFI total and sub-scale scores ranged from 0.87 to 0.69 . Internal consistency ranged from 0.96 to 0.73 . With the exception of two items , factor analysis supported the construct validity of the total index and the sub-scales . Strong correlation between the FFI total and sub-scale scores and clinical measures of foot pathology supported the criterion validity of the index . The FFI should prove useful for both clinical and research purpose",
"OBJECTIVE French validation of the Foot Function Index ( FFI ) , self- question naire design ed to evaluate rheumatoid foot according to 3 domains : pain , disability and activity restriction . METHODS The first step consisted of translation/back translation and cultural adaptation according to the vali date d methodology . The second stage was a prospect i ve validation on 53 patients with rheumatoid arthritis who filled out the FFI . The following data were collected : pain ( Visual Analog Scale ) , disability ( Health Assessment Question naire ) and activity restrictions ( McMaster Toronto Arthritis question naire ) . A test/retest procedure was performed 15 days later . The statistical analyses focused on acceptability , internal consistency ( Cronbach 's alpha and Principal Component Analysis ) , test-retest reproducibility ( concordance coefficients ) , external validity ( correlation coefficients ) and responsiveness to change . RESULTS The FFI-F is a culturally acceptable version for French patients with rheumatoid arthritis . The Cronbach 's alpha ranged from 0.85 to 0.97 . Reproducibility was correct ( correlation coefficients>0.56 ) . External validity and responsiveness to change were good . CONCLUSION The use of a rigorous methodology allowed the validation of the FFI in the French language ( FFI-F ) . This tool can be used in routine practice and clinical research for evaluating the rheumatoid foot . The FFI-F could be used in other pathologies with foot-related functional impairments",
"Introduction : The American Orthopaedic Foot and Ankle Society ( AOFAS ) Ankle-Hindfoot Score has been under recent scrutiny . The Foot and Ankle Outcome Score ( FAOS ) is an alternative subjective survey , assessing outcomes in 5 subscales . It is vali date d for lateral ankle instability and hallux valgus patients . The aim of our study was to vali date the FAOS for assessing outcomes in flexible adult acquired flatfoot deformity ( AAFD ) . Methods : Patients from the authors ’ institution diagnosed with flexible AAFD from 2006 to 2011 were eligible for the study . In all , 126 patients who completed the FAOS and the Short-Form 12 ( SF-12 ) on the same visit were included in the construct validity component . Correlation was deemed moderate if the Spearman ’s correlation coefficient was .4 to .7 . Content validity was assessed in 63 patients by a question naire that asked patients to rate the relevance of each FAOS question , with a score of 2 or greater considered acceptable . Reliability was measured using intraclass correlation coefficients ( ICCs ) in 41 patients who completed a second FAOS survey . In 49 patients , preoperative and postoperative FAOS scores were compared to determine responsiveness . Results : All of the FAOS subscales demonstrated moderate correlation with 2 physical health related SF-12 domains . Mental health related domains showed poor correlation . Content validity was high for the Quality of Life ( QoL ; mean 2.26 ) and Sports/Recreation subscales ( mean 2.12 ) . All subscales exhibited very good test – retest reliability , with ICCs of .7 and above . Symptoms , QoL , pain , and daily activities ( ADLs ) were responsive to change in postoperative patients ( P patients with ankle instability and hallux valgus , the additional findings in this study support its use as an alternative to less reliable outcome surveys . Level of Evidence : Level II , prospect i ve comparative study",
"Background : Patient-reported outcome measures are increasingly used evaluating clinical care . Many measures used to assess operative hindfoot interventions vary in content , and some have not been psychometrically vali date d in this population . The purpose of this study was to compare measurement properties of 6 lower-extremity patient-reported outcome measures , and to evaluate their reliability and validity in light of patients ’ preferences . Methods : Cross-sectional survey of 42 preoperative and 100 postoperative patients completed 6 lower-extremity outcome measures on 2 occasions : Foot Function Index ( FFI ) , Ankle Osteoarthritis Scale ( AOS ) , patient-reported items of the American Orthopaedic Foot & Ankle Society Question naire ( AOFAS ) , Lower Extremity Functional Scale ( LEFS ) , Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , and the Short Musculoskeletal Function Assessment ( SMFA ) , as well as measures of preference , and symptoms . Results : Internal consistency was good to excellent for all scales and subscales ( α = .84-.97 ; ICC [ 2,1 ] = .81-.96 ) . Correlations between scales ranged from .50 ( WOMACStiffness and FFIActivity Limitations ) to .92 ( LEFS and SMFAOverall , WOMACPain and AOSOverall , FFIOverall and AOFASOverall ) . Higher correlations occurred within instruments ( r = .97 AOSPain and AOSOverall ) and between similar subscales from different instruments ( r = .91 WOMACPain and AOSPain ) . Construct validity showed moderate to high correlations to global ratings of Pain , Stiffness , and difficulty performing Daily Activities . The highest correlations ( r > .75 ) occurred between Pain and AOSOverall ( r = .84 ) , stiffness and WOMACStiffness ( r = .81 ) , and Daily Activities and AOSDisability ( r = .87 ) . Patients rated instruments by preference . FFI , WOMAC , LEFS , and SMFA rated favorably for length . FFI , WOMAC , LEFS , and AOFAS rated high for underst and ability . FFI was rated by postoperative patients as most likely to capture change due to surgery . SMFA rated the best overall . Conclusions : Direct comparison of instruments revealed similarity between scales in construct validity and reliability . Patient preferences supported the use of these scales . Foot-specific instruments offered no clear advantage over lower-extremity instruments . Level of Evidence : Level II , prospect i ve comparative study"
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4117565e-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND The role of vitamin C ( ascorbic acid ) in the prevention and treatment of the common cold has been a subject of controversy for 60 years , but is widely sold and used as both a preventive and therapeutic agent . OBJECTIVES To discover whether oral doses of 0.2 g or more daily of vitamin C reduces the incidence , duration or severity of the common cold when used either as continuous prophylaxis or after the onset of symptoms . SEARCH STRATEGY We search ed the Cochrane Central Register of Controlled Trials ( CENTRAL ) ( The Cochrane Library Issue 4 , 2006 ) ; MEDLINE ( 1966 to December 2006 ) ; and EMBASE ( 1990 to December 2006 ) . SELECTION CRITERIA Papers were excluded if a dose less than 0.2 g per day of vitamin C was used , or if there was no placebo comparison . DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed trial quality . ' Incidence ' of colds during prophylaxis was assessed as the proportion of participants experiencing one or more colds during the study period . ' Duration ' was the mean days of illness of cold episodes . MAIN RESULTS Thirty trial comparisons involving 11,350 study participants contributed to the meta- analysis on the relative risk ( RR ) of developing a cold whilst taking prophylactic vitamin C. The pooled RR was 0.96 ( 95 % confidence intervals ( CI ) 0.92 to 1.00 ) . A subgroup of six trials involving a total of 642 marathon runners , skiers , and soldiers on sub-a rct ic exercises reported a pooled RR of 0.50 ( 95 % CI 0.38 to 0.66 ) . Thirty comparisons involving 9676 respiratory episodes contributed to a meta- analysis on common cold duration during prophylaxis . A consistent benefit was observed , representing a reduction in cold duration of 8 % ( 95 % CI 3 % to 13 % ) for adults and 13.6 % ( 95 % CI 5 % to 22 % ) for children . Seven trial comparisons involving 3294 respiratory episodes contributed to the meta- analysis of cold duration during therapy with vitamin C initiated after the onset of symptoms . No significant differences from placebo were seen . Four trial comparisons involving 2753 respiratory episodes contributed to the meta- analysis of cold severity during therapy and no significant differences from placebo were seen . AUTHORS ' CONCLUSIONS The failure of vitamin C supplementation to reduce the incidence of colds in the normal population indicates that routine mega-dose prophylaxis is not rationally justified for community use . But evidence suggests that it could be justified in people exposed to brief periods of severe physical exercise or cold environments
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[
"OBJECTIVE To determine the effect of large doses of vitamin C in the treatment of the common cold . STUDY DESIGN Double-blind , r and omised clinical trial with four intervention arms : vitamin C at daily doses of 0.03 g ( \" placebo \" ) , 1 g , 3 g , or 3 g with additives ( \" Bio-C \" ) taken at onset of a cold and for the following two days . PARTICIPANTS AND SETTING 400 healthy volunteers were recruited from staff and students of the Australian National University , Canberra , ACT , between May 1998 and November 1999 . The trial continued for 18 months . INTERVENTIONS Participants were instructed to commence medication when they had experienced early symptoms of a cold for four hours , and to record daily their symptoms , severity , doctor visits and use of other medications . MAIN OUTCOME MEASURES Duration of symptoms and cold episodes ; cumulative symptom severity scores after 7 , 14 and 28 days ; doctor visits ; and whether participants guessed which medication they were taking . RESULTS 149 participants returned records for 184 cold episodes . No significant differences were observed in any measure of cold duration or severity between the four medication groups . Although differences were not significant , the placebo group had the shortest duration of nasal , systemic and overall symptoms , and the lowest mean severity score at 14 days , and the second lowest at 7 and 28 days . CONCLUSIONS Doses of vitamin C in excess of 1 g daily taken shortly after onset of a cold did not reduce the duration or severity of cold symptoms in healthy adult volunteers when compared with a vitamin C dose less than the minimum recommended daily intake",
"A controlled study was made of the effects of natural orange juice , synthetic orange juice , and placebo in the prevention of the common cold ; both natural and synthetic orange juices contained 80 mg of ascorbic acid daily . Three-hundred sixty-two healthy normal young adult volunteers , ages 17 to 25 years , were studied for 72 days with 97 % of participants completing the trial . There was a 14 to 21 % reduction in total symptoms due to the common cold in the supplemented groups that was statistically significant ( P less than 0.05 ) . Ascorbic acid supplementation also increased the number of \" episode-free \" subjects . However , the clinical usefulness of the results does not support prophylactic ascorbic acid supplements in the well-nourished adult . The results in this study with both natural and synthetic orange juice of physiological content of ascorbic acid , are similar to those obtained using a \" megadose \" of ascorbic acid",
"Context Clinical studies of vitamin C as a potential anticancer agent have produced inconsistent results despite in vitro evidence that high concentrations kill cancer cells . Contribution Pharmacokinetic studies in healthy persons , using a depletion-repletion design , show that intravenous administration can achieve 70-fold higher blood levels of vitamin C than the highest tolerated oral dose . Caution s Although this study provides better underst and ing of the pharmacokinetic issues involved in research on vitamin C , it provides no evidence that vitamin C has any effect on cancer cells and can not be used to support its clinical use for therapeutic purpose s. The Editors Vitamin C in gram doses is taken orally by many people and administered intravenously by complementary and alternative medicine practitioners to treat patients with advanced cancer ( 1 , 2 ) . After oral intake , vitamin C plasma concentrations are tightly controlled at 70 to 85 mol/L for amounts ( as much as 300 mg daily ) that can be obtained from food ( 3 , 4 ) . However , concentrations achieved by higher pharmacologic doses are uncertain . Despite poor rationale , vitamin C in gram doses was proposed as an anticancer agent decades ago ( 5 ) . Unblinded studies with retrospective or nonr and om controls reported clinical benefit from oral and intravenous vitamin C administered to patients with terminal cancer at a dosage of 10 g daily ( 1 , 6 , 7 ) . Placebo-controlled trials in patients with cancer reported no benefit from oral vitamin C at a dosage of 10 g daily ( 8 , 9 ) , and vitamin C treatment was judged ineffective ( 10 ) . However , in vitro evidence showed that vitamin C killed cancer cells at extracellular concentrations higher than 1000 mol/L ( 11 , 12 ) , and its clinical use by some practitioners continues . We recognized that oral or intravenous routes could produce substantially different vitamin C concentrations ( 13 ) . We report here that intravenous doses can produce plasma concentrations 30- to 70-fold higher than the maximum tolerated oral doses . These data suggest that the role of vitamin C in cancer treatment should be reexamined , and insights from vitamin C pharmacokinetics can guide its clinical use . Methods Pharmacokinetic Studies in Healthy Persons The study was approved by the Institutional Review Board of the National Institute of Diabetes and Digestive and Kidney Diseases , National Institutes of Health . After we obtained written informed consent , 17 healthy volunteers ( 7 men , 10 women ; age , 19 to 27 years ) were studied as in patients by using a depletion-repletion study design ( 3 , 4 ) . Participants were hospitalized for 3 to 6 months and consumed a vitamin C-deficient diet containing less than 0.005 g of vitamin C per day . At plasma vitamin C concentrations less than 8 mol/L , persons were depleted without signs of scurvy . Vitamin C , 0.015 g twice daily , was then administered orally until participants achieved a steady state for this dose ( 0.03 g daily ) . Participants received successive oral daily vitamin C doses of 0.03 g , 0.06 g , 0.1 g , 0.2 g , 0.4 g , 1.0 g , and 2.5 g until a steady state was achieved for each dose . Bioavailability sampling was conducted at a steady state for vitamin C doses of 0.015 g , 0.03 g , 0.05 g , 0.1 g , 0.2 g , 0.5 g , and 1.25 g. For each bioavailability sampling , vitamin C was administered in the fasting state . After oral administration , blood sample s were collected at 0 , 15 , and 30 minutes and at 1 , 1.5 , 2 , 2.5 , 3 , 3.5 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 19 , 22 , and 24 hours ( 3 , 4 ) . After intravenous administration at 250 mg/min , blood sample s were collected at 0 , 2.5 , 5 , 10 , 15 , and 30 minutes and at 1 , 1.5 , 2 , 2.5 , 3 , 3.5 , 4 , 5 , 6 , 7 , 8 , 9 , and 10 hours . Data obtained from bioavailability samplings were used to determine peak plasma and urine vitamin C concentrations . Pharmacokinetic Modeling We used data from 7 men to construct a unique 3-compartment vitamin C pharmacokinetic model with parameters describing saturable absorption , tissue distribution , and renal excretion and reabsorption ( 14 ) . This model was used to predict peak plasma and urine vitamin C concentrations attained when pharmacologic doses of the vitamin are administered . For intravenous administration , it was assumed that vitamin C was infused at a rate of 1 g/min , and urine output was 100 mL/h . Vitamin C Assay Vitamin C was measured by using high-performance liquid chromatography with coulometric electrochemical detection ( 3 , 4 , 15 ) . Statistical Analysis We compared plasma vitamin C concentration curves ( against either dose or time ) by repeated- measures analyses of variance ( ANOVA ) . In addition to the repeating factor ( dose or time ) , other factors considered were sex and route of administration . In the comparison of routes of administration at multiple doses , in which sex not only was an important factor itself but also had an important interaction with route , separate ANOVA were determined for men and women to assess the importance of route of administration . Analyses were performed by using Data Desk , version 5 ( 1995 ) ( Data Description , Inc. , Ithaca , New York ) . Role of the Funding Source The funding source had no role in the design , conduct , and reporting of the study or in the decision to su bmi t the manuscript for publication . Results When 1.25 g of vitamin C was given intravenously , plasma concentrations were significantly higher than when the vitamin was given orally ( P plasma concentrations were significantly higher over all doses ( P peak values from intravenous administration were 6.6-fold higher than mean peak values from oral administration . When all doses were considered , peak plasma vitamin C concentrations increased with increasing intravenous doses , whereas peak plasma vitamin C concentrations seemed to plateau with increasing oral doses . Urine vitamin C concentrations were higher for the same dose given intravenously compared with that administered by the oral route . At the highest dose of 1.25 g , peak urine concentrations from intravenous administration were approximately 3.5 times higher than from oral administration ( data not shown ) . Figure 1 . Plasma vitamin C concentrations in healthy volunteers after intravenous or oral administration of vitamin C. Inset : The 3-compartment vitamin C pharmacokinetic model that we developed predicted that a single oral dose of 3 g , the maximum tolerated single dose , produced a peak plasma concentration of 206 mol/L ( Figure 2 , top ) . Peak predicted concentration after a single 1.25-g oral dose was slightly lower at 187 mol/L. For 200 mg , an amount obtained from vitamin C-rich foods , peak predicted concentration was approximately 90 mol/L. Plasma concentrations for all of these amounts returned to steady-state values , approximately 70 to 85 mol/L , after 24 hours . With 3 g given orally every 4 hours , the maximum tolerable ( 6 ) , peak predicted plasma concentration was approximately 220 mol/L ( Figure 2 , top ) . By contrast , after intravenous administration , predicted peak plasma vitamin C concentrations were approximately 1760 mol/L for 3 g , 2870 mol/L for 5 g , 5580 mol/L for 10 g , 13 350 mol/L for 50 g , and 15 380 mol/L for 100 g ( Figure 2 , bottom ) . Doses of 60 g given intravenously are used for cancer treatment by complementary and alternative medicine practitioners ( 2 ) . Predicted peak urine vitamin C concentrations were as much as 140-fold higher after intravenous administration compared with oral administration ( data not shown ) . Figure 2 . Predicted plasma vitamin C concentrations in healthy persons after oral ( top ) or intravenous ( IV ) ( bottom ) administration of vitamin C. Discussion Our data show that vitamin C plasma concentrations are tightly controlled when the vitamin is taken orally , even at the highest tolerated amounts . By contrast , intravenous administration bypasses tight control and results in concentrations as much as 70-fold higher than those achieved by maximum oral consumption . Both findings have clinical relevance . Vitamin C oral supplements are among the most popular sold , and gram doses are promoted for preventing and treating the common cold , managing stress , and enhancing well-being ( 1 ) . Our data show that single supplement gram doses produce transient peak plasma concentrations that at most are 2- to 3-fold higher than those from vitamin C-rich foods ( 200 to 300 mg daily ) . In either case , plasma values return to similar steady-state concentrations in 24 hours . Because differences in plasma concentrations from supplements and from food intake are not large , supplements would be expected to confer little additional benefit , a finding supported by available evidence ( 16 , 17 ) . However , consumption of fruits and vegetables , which contain vitamin C , is beneficial for unknown reasons ( 16 , 17 ) . On the basis of current knowledge and the pharmacokinetics presented here , physicians should advise their patients to consume fruits and vegetables , not vitamin C supplements , to obtain potential benefits . Just as important , our data show that intravenous administration of vitamin C produces substantially higher plasma concentrations than can be achieved with oral administration of vitamin C. This difference was previously unrecognized and may have treatment implication s. Case series published by Cameron , Campbell , and Pauling ( l , 6 , 7 ) have been controversial . In these series , several hundred patients with terminal cancer treated with 10 g of vitamin C intravenously for 10 days and then 10 g orally indefinitely were compared with more than 1000 retrospective and prospect i ve controls . Patients treated with vitamin C survived 150 to 300 days longer than controls ( 1 , 6 , 7 ) . Other research ers reported benefit consisting of increased survival , improved well-being , and reduced pain ( 1 ) . All of these"
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BACKGROUND AND PURPOSE Acute stress in surgery is ubiquitous and has an immediate impact on surgical performance and patient safety . Surgeons react with several coping strategies ; however , they recognise the necessity of formal stress management training . Thus , stress assessment is a direct need . Surgical simulation is a vali date d st and ardised training milieu design ed to replicate real-life situations . It replicates stress , prevents biases , and provides objective metrics . The complexity of stress mechanisms makes stress measurement difficult to quantify and interpret . This systematic review aims to identify studies that have used acute stress estimation measurements in surgeons or surgical trainees during real operations or surgical simulation , and to collectively present the rationale of these tools , with special emphasis in salivary markers . METHODS A search strategy was implemented to retrieve relevant articles from MEDLINE and SCOPUS data bases . The 738 articles retrieved were review ed for further evaluation according to the predetermined inclusion /exclusion criteria . RESULTS Thirty-three studies were included in this systematic review . The methods for acute stress assessment varied greatly among studies with the non-invasive techniques being the most commonly used . Subjective and objective tests for surgeons ' acute stress assessment are being presented . CONCLUSION There is a broad spectrum of acute mental stress assessment tools in the surgical field and simulation and salivary biomarkers have recently gained popularity . There is a need to maintain a consistent methodology in future research , towards a deeper underst and ing of acute stress in the surgical field
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"Background Stress can impair surgical performance and may compromise patient safety . This prospect i ve , cross-sectional study describes the feasibility , reliability , and validity of the Imperial Stress Assessment Tool ( ISAT ) as an approach to measuring stress during surgery . Methods A total of 54 procedures were observed with 11 surgeons ( 4 attendings , 4 senior residents and 3 junior residents ) in a large university teaching hospital in London , UK . Data collection involved physiological measures of operating surgeons [ heart rate ( HR ) and salivary cortisol ] and self-report question naires ( State Trait Anxiety Inventory , or STAI ) . Results In all , 23 of 54 procedures were stressful , as identified by self-reporting . For stressful procedures compared to nonstressful ones , STAI was higher ( mean ± SD ) 9.81 ± 2.20 vs. 12.87 ± 4.27 , t ( 30.64 ) = 3.15 as was the HR ( mean ± SD ) 79.94 ± 8.55 vs. 93.17 ± 14.94 , t(32.57 ) = 3.81 ) ( p HR and cortisol had specificities of 78 % and 91 % and sensitivities of 91 % and 70 % respectively for detecting stress during surgery . Conclusion ISAT is a nonintrusive , feasible approach that combines subjective and objective methods for measuring stress in the operating room . The ISAT may increase underst and ing of the effects of stress on clinical performance and outcomes , leading to improved patient care",
"Background Intermittent work breaks are common in fields with high workload but not yet for surgeons during operations . We evaluated the effects of intraoperative breaks during complex laparoscopic surgery ( 5 min every half hour ) on the surgeon . Methods Fifty-one operations were r and omized to a scheme with intraoperative breaks and release of the pneumoperitoneum ( intermittent pneumoperitoneum ( IPP ) ) or conventional conduct ( CPP ) . Stress hormones and α-amylase were determined in the surgeon ’s saliva pre- , intra- , and postoperatively . Mental performance and error scores , musculoskeletal strain , and continuous ECG were secondary endpoints . Results Regular intraoperative breaks did not prolong the operation ( IPP vs. CPP group : 176 vs. 180 min , p > 0.05 ) . The surgeon ’s cortisol levels during the operation were reduced by 22 ± 10.3 % in the IPP vs. the CPP group ( p intraoperative events in the IPP vs. the CPP group , which yielded higher α-amylase peaks . The pre- to postoperative increase in the error rates of the bp-concentration test was fourfold reduced in the IPP group ( p = 0.052 ) . The relevant locomotive strain-scores were grossly reduced by IPP ( p reduce psychological stress and preserve performance without prolongation of the operation time compared with the traditional work scheme",
"CONTEXT Heightened cardiovascular responses to mental stressors are associated with future risk of hypertension . The role of cortisol , a key stress hormone produced by the hypothalamic-pituitary-adrenal axis , remains unclear . OBJECTIVE Our objective was to examine the association between cortisol responses to laboratory-induced mental stress and incident hypertension . DESIGN AND SETTING This was a prospect i ve sub study of the Whitehall II cohort with 3 years follow-up of an occupational cohort . PARTICIPANTS Participants included 479 initially healthy men and women ( mean age , 62.7 ± 5.6 yr ) , without history or objective signs of cardiovascular disease or hypertension at study entry . INTERVENTION At the baseline assessment , salivary cortisol was measured in response to mental stressors , consisting of a 5-min Stroop task and a 5-min mirror tracing task . MAIN OUTCOME MEASURES Blood pressure was measured at study entry and at 3 yr follow-up for the determination of hypertension . RESULTS There was considerable variation in the cortisol stress response , with approximately 40 % of the sample responding to the stress tasks with an increase in cortisol of at least 1 mmol/liter . Over the 3 yr follow-up , 15.9 % of the sample developed hypertension . There was an association between cortisol stress reactivity ( per sd ) and incident hypertension ( odds ratio = 1.59 ; 95 % confidence interval = 1.17 - 2.17 ) after adjustments for age , sex , resting cortisol , blood pressure at study entry , employment grade , smoking , body mass index , glycated hemoglobin , use of statins , and blood lipids . CONCLUSION These data support the notion that cortisol reactivity , an index of hypothalamic-pituitary-adrenal function , is one of the possible mechanisms through which psychosocial stress may influence the risk of hypertension",
"Objective Most infections begin at mucosal surfaces . These surfaces are covered by the secretory proteins of the exocrine gl and s ( eg , the salivary , respiratory , and gastrointestinal gl and s ) , which provide a first line of innate defense . The release of these secretory proteins is under neuroendocrine control and thus , in theory , sensitive to modulation by psychosocial stress . This was empirically tested by measuring the salivary secretion of cystatin S , lactoferrin , & agr;-amylase , the mucins MUC5B and MUC7 , and total salivary protein in response to stressors known to evoke distinct patterns of cardiac autonomic activity . Methods Thirty-two undergraduate volunteers were each subjected to two laboratory stressors and a control condition . Stressors were an active coping memory test and a passive coping video presentation showing surgical procedures . In the control condition participants viewed a didactic video presentation . Results The stressors evoked the expected distinct patterns of cardiac autonomic activity . The memory test produced a strong increase in sympathetic activity ( evidence d by a shortened preejection period ) , and a decrease in cardiac parasympathetic activity ( evidence d by a decrease in heart rate variability ) . This active coping response was associated with an enhanced secretion ( & mgr;g/min , controlling for salivary flow rate ) of MUC7 , lactoferrin , & agr;-amylase , and total salivary protein . Conversely , the surgical video produced an increase in cardiac vagal tone and a modest increase in sympathetic activity . This passive coping response was associated with an enhanced secretion of all proteins studied . These secretory responses were generally larger than the secretory responses during the active coping memory test . Correlation analyses indicated that for both stressors autonomic and cardiovascular reactivity was positively associated with an enhanced and prolonged secretory activity . Conclusions Stress-induced modulation of innate secretory immunity may be a contributing factor in the observed relationship between stress and susceptibility to infectious diseases . We further propose a more differentiated approach to acute stress by distinguishing among stressors with distinct autonomic nervous system effects",
"STUDY OBJECTIVE Although some sedatives or analgesics are commonly used for premedication to reduce psychological tension before surgery or anesthesia , it remains unclear which drug is more suitable . Because salivary chromogranin A is a reliable index for estimating psychological tension , this variable was measured during the perioperative period after premedication . DESIGN Prospect i ve , r and omized control study . SETTING Operating room at a general hospital . PATIENTS Thirty adult female patients undergoing abdominal total hysterectomy were r and omly assigned to 3 groups of 10 patients each . INTERVENTIONS On the day before surgery , saliva was collected , and 0.1 mg/kg of midazolam ( midazolam group ) or 0.02 mg/kg of butorphanol ( butorphanol group ) was injected intramuscularly 30 minutes before entering the operating rooms . For the control group , no premedication was performed . Saliva was collected as the patient entered the operating room and then the patient received an epidural catheter insertion followed 5 minutes later by collection of the saliva . MEASUREMENTS AND MAIN RESULTS Salivary chromogranin A was assayed using a radioimmunoassay , and revised values calculated from the protein concentration of the saliva were regarded as data . Revised salivary chromogranin A levels increased in the control and butorphanol groups at the time of entrance to the operating room and after epidural treatment compared with the value of the day before surgery , whereas it did not change statistically in the midazolam group . CONCLUSIONS From the st and point of reducing psychological tension before surgery or anesthesia , midazolam as a sedative may be more suitable for premedication",
"Background Green tea has become renowned for its health benefits . In this study , we investigated the anti-stress effect of two kinds of green tea against a mental stress task load . Methods Warm water , ordinary green tea ( Sagara ) , and shaded white tea , which contains more amino acid components than Sagara , were used as test sample s in a r and omized cross-over design study . Eighteen students ( nine male and nine female ) participated in three experimental trials on different days at intervals of seven days . Saliva was collected before beverage intake and after performing the mental stress load tasks . Concentration of chromogranin A ( CgA ) in the saliva was used as an index of autonomic nervous system activity . Results CgA level increased after the mental tasks , but intake of green tea inhibited this increase ; the anti-stress effect was even greater after consumption of shaded white tea . Intake of shaded white tea also lowered Total Mood Disturbance ( TMD ) score on the Profile of Mood States ( POMS ) ; subjects in this condition tended to perform more calculations in the arithmetic task than those in the warm water treatment condition . Conclusions Salivary CgA concentration levels increased after mental stress load tasks , but ingestion of green tea inhibited this increase . This anti-stress effect was larger after the consumption of shaded white tea than after Sagara . Shaded white tea intake also lowered TMD score ( POMS ) and tended to improve performance on an arithmetic task compared to warm water , suggesting that shaded white tea might also improve mood during and after mental stress load",
"Background : Laparoscopic surgery might be beneficial for the patient , but it imposes increased physical and mental strain on the surgeon . Robot-assisted laparoscopic surgery addresses some of the laparoscopic drawbacks and may potentially reduce mental strain . This could reduce the risk of surgeon 's fatigue , mishaps and strain-induced illnesses , which may eventually improve the safety of laparoscopic surgical procedures . Methods : To test this hypothesis , a r and omized study was performed , comparing both heart rate and heart rate variability ( HRV ) of the surgeon as a measure of total and mental strain , respectively , during conventional and robot-assisted laparoscopic cholecystectomy . Results : Both heart rate and HRV ( the low-frequency b and /high-frequency b and ratio ) were significantly decreased when using robotic assistance . Conclusions : These data suggest the use of the daVinci ® Surgical System leads to less physical and mental strain of the surgeon during surgery . However , assessing mental strain by means of HRV is cumbersome since there is no clear cutoff point or scale for maximum tolerated strain levels and its related effects on surgeon 's health",
"Introduction In the present work we analyzed the hormonal ( salivary Cortisol ; sC ) , immune ( salivary Immunoglobulin A ; sIgA ) and cardiovascular ( Heart rate , HR , and systolic blood pressure , SBP ) responses induced by stress conditions in oral surgeons , r and omly recruited according to their expertise level . Material s and methods Each surgeon performed three different surgical procedures with increasing degrees of technical difficulty and under time-limited conditions , to assess whether these variants may influence the risks of stress-induced secondary hypertension among the involved health professionals . sC and sIgA sample s and cardiovascular function measurements were taken up before , during , and two hours after every surgery . Salivary sample s and cardiovascular measurements were taken also during non-surgical days , as baseline controls . Results We observed that more experienced surgeons showed a higher stress management ability compared to those with less experience or , generally , younger , which are more exposed to the risks of developing secondary hypertension . Nevertheless , indipendently of sex and experience , oral surgeons are constantly exposed to high risks of developing stress-related diseases . Conclusions On the basis of the issues addressed and the results obtained , we have highlighted the importance of the investigated stress biomarkers to monitor and to prevent stress-related pathologies among oral surgeons . This approach is aim ed to emphasize the significance of these specific stress-biomarkers , which represent a powerful instrument to evaluate stress levels in oral surgeons , and that may help to reduce the most severe life-threatening risks to which they are daily exposed . In conclusion , final goal of this study is to suggest an useful guideline to monitor the stress levels of oral and maxillofacial surgeons in order to improve their quality of life , which is inevitably reflected on the quality of the performances provided and , finally , to prevent possible mistakes in their daily activities",
"BACKGROUND The aim of this study was to determine whether instructing surgical trainees in technically dem and ing procedures causes alterations in heart rate variability ( HRV ) and mental strain in supervising surgeons . METHODS A prospect i ve study of HRV in two consultant surgeons and three endocrine surgical fellows undertaking 50 total thyroidectomy procedures was performed . Fellows and consultant surgeons performed 50 lobectomies as primary operator and 50 as assistants in a cross-over design . HRV was measured during dissection around the recurrent laryngeal nerve . The overall heart rate , time , and frequency domain parameters of HRV , specifically the low frequency/high frequency ( LF/HF ) ratio , which was used as a measure of cardiac and mental stress , were correlated with the surgical role , particularly teaching surgical fellows at critical points . RESULTS HRV data were collected between October 2009 and March 2010 . There was no statistically significant difference in the mean heart rate for either group of participants regardless of role . Energy expenditure was greater for fellows when operating ( p = 0.03 ) . Fellows demonstrated a higher LF/HF ratio when acting as the primary operator ( p = 0.02 ) . All time domain parameters of HRV increased when attending surgeons were operating , denoting more cardiac relaxation . Similarly , the LF/HF ratio was significantly greater for attending surgeons when teaching ( p = 0.05 ) , suggesting an increase in mental strain . CONCLUSIONS The teaching of complex but common endocrine surgical procedures is associated with a measurable increase in mental strain of consultant surgeons , as determined by HRV . Fellows demonstrated increased levels of stress when acting as primary operators",
"Aims : To describe heart rate ( HR ) variations in surgical residents during laparoscopy and to assess their intraoperative stress . Methods : We performed a prospect i ve , multicentric , observational , blinded , and comparative analysis of the HR in 75 obstetrics and gynecology residents during planned laparoscopy for infertility in five teaching hospitals with assisted reproductive technology centers . The surgical residents had neither heart disease nor were under medical treatment or using tobacco or drugs . We describe HR variations at 9 preselected operative steps using real-time noninvasive measures of the HR during laparoscopy . Results : Residents performed 124 laparoscopies for unexplained infertility . Their HR increased significantly during the introduction of the Palmer needle , umbilical port and second port , and during abdominopelvic exploration and dye test compared to the baseline HR , the HR after h and washing , at the end of surgery and during skin suture ( 91.6 ± 1.9 , 104.8 ± 2.3 , 95.3 ± 2.2 , 93.7 ± 2.5 , 90.7 ± 1.7 vs. 83.2 ± 1.6 , 88.6 ± 1.9 , 87.4 ± 2.1 , 88.2 ± 1.9 bpm , respectively , p HR variations during planned laparoscopy compared to the baseline HR before surgery . This ‘ static ' stress can be repeated on the same day",
"OBJECTIVE To compare psychophysiological responses among novice surgeons during performance of endoscopic sinus surgery ( ESS ) . DESIGN R and omized study . SETTING Academic institution . PARTICIPANTS Fifteen novice surgeons . MAIN OUTCOME MEASURES The psychophysiological effects of performing ESS were assessed among 15 novice surgeons at 30 minutes before ( T - 30 ) , at the beginning of ( T0 ) , at 15 minutes ( T15 ) , and 45 minutes ( T45 ) during , and at 30 minutes after ( T + 30 ) surgery . Participants were r and omized to perform ESS with a computer-assisted surgery system , to perform ESS without a computer-assisted surgery system , or to be evaluated on a nonsurgical day ( control day ) . Measured were the State-Trait Anxiety Inventory score , Visual Analog Anxiety Scale score , heart rate , blood pressure , and plasma cortisol and prolactin levels . RESULTS Anxiety as measured by the State-Trait Anxiety Inventory score was not modified by the experimental conditions . The mean ( SEM ) Visual Analog Anxiety Scale score increased ( P mean ( SEM ) systolic blood pressure ( in millimeters of mercury ) increased ( P mean ( SEM ) heart rate ( in beats per minute ) increased during ESS but was significant only at T15 ( 73 [ 4 ] ) compared with the control day ( 64 [ 3 ] ) . The mean ( SEM ) plasma cortisol level ( in micrograms per deciliter ) increased 29 % above baseline during performance of ESS and reached a maximum peak at T45 ( 12.6 [ 1.2 ] ) compared with the control day ( 9.7 [ 1.1 ] ) , while prolactin levels did not change . The Visual Analog Anxiety Scale score , heart rate , blood pressure , and endocrine biomarkers of stress were not significantly modified during performance of ESS with a computer-assisted surgery system . CONCLUSION This study demonstrates for the first time that cardiovascular and anxiety changes during performance of ESS are not associated with increased levels of prototypical endocrine stress hormones",
"BACKGROUND The adverse effects of stress on the wellness of trauma team members are well established ; however , the level of stress has never been quantitatively assessed . The aim of our study was to assess the level of stress using subjective data and objective heart rate variability ( HRV ) among attending surgeons ( ASs ) , junior residents ( JRs ) ( PGY2/PGY3 ) , and senior residents ( SRs ) ( PGY5/PGY6 ) during trauma activation and emergency surgery . METHODS We preformed a prospect i ve study enrolling participants over eight 24-hour calls in our Level I trauma center . Stress was assessed based on decrease in HRV , which was recorded using body worn sensors . Stress was defined as HRV of less than 85 % of baseline HRV . We collected subjective data on stress for each participant during calls . Three groups ( ASs , JRs , SRs ) were compared for duration of different stress levels through trauma activation and emergency surgery . RESULTS A total of 22 participants ( ASs : n = 8 , JRs : n = 7 , SRs : n = 7 ) were evaluated over 192 hours , which included 33 trauma activations and 50 emergency surgeries . Stress level increased during trauma activations and operations regardless of level of training . The ASs had significantly lower stress when compared with SRs and JRs during trauma activation ( 21.9 ± 10.7 vs. 51.9 ± 17.2 vs. 64.5 ± 11.6 ; p The level of stress was similar between JRs and SRs during trauma activation ( p = 0.37 ) and emergency surgery ( p = 0.19 ) . There was no correlation between objective ly measured stress level and subjectively measured stress using State-Trait Anxiety Inventory ( R2 = 0.16 ; p = 0.01 ) among surgeons or residents . CONCLUSIONS Surgeon wellness is a significant concern , and this study provides empirical evidence that trauma and acute care surgeons encounter mental strain and fail to recognize it . Stress management and burnout are very important in this high-intensity field , and this research may provide some insight in finding those practitioners who are at risk . LEVEL OF EVIDENCE Epidemiologic study , level II",
"Background : Stress and coping influence performance . In this study , we evaluate a novel stress management intervention for surgeons . Methods : A r and omized control group design was used . Sixteen surgeons were allocated to either the intervention or control group . The intervention group received training on coping strategies , mental rehearsal , and relaxation . Performance measures were obtained during simulated operations and included objective -structured assessment of technical skill , observational teamwork assessment for surgery , and end product assessment rated by experts . Stress was assessed using the state-trait-anxiety-inventory , observer rating , coefficient of heart rate variability ( C_HRV ) , and salivary cortisol . The number of applied surgical coping strategies ( number of coping strategies [ NC ] ) was assessed using a question naire . A t test for paired sample s investigated any within-subject changes , and multiple linear regression analysis explored between-subject effects . Interviews explored surgeons ' perceptions of the intervention . Results : The intervention group showed enhanced observational teamwork assessment for surgery performance ( t = –2.767 , P increased coping skills ( t = –4.690 , P reduced stress reflected inheart rate variability ( t = –4.008 , P No significant changes were identified in the control group . Linear regression analysis confirmed a significant effect on NC ( & bgr ; = –0.739 , P improved technical skills , decision making , and confidence . Conclusions : The intervention had beneficial effects on coping , stress , and nontechnical skills during simulated surgery",
"BACKGROUND Emotional stability is important for individual and team performance during operating room ( OR ) emergencies . We compared physiologic and psychological anxiety assessment s in OR teams during simulated events . METHODS Twenty-two teams participated in a \" can not intubate/cannot ventilate \" simulation . Participants completed the State-Trait Anxiety Inventory and wore a galvanic skin response ( GSR ) sensor . Differences in State-Trait Anxiety Inventory scores and GSR levels were analyzed . Anxiety scores were correlated with GSR levels . RESULTS Resident physicians had significantly higher trait anxiety than the nurses , certified registered nurse anesthetists , and surgical technicians ( 43.9 ± 9.9 vs 38.3 ± 9.3 , P higher trait anxiety than junior practitioners ( 43.7 ± 9.6 vs 40.0 ± 9.9 , P = .03 ) . All groups showed significant increases in GSR . Psychological and physiologic data did not correlate . CONCLUSIONS Senior practitioners and residents have higher levels of baseline trait anxiety for unclear reasons . Also , OR team training results in physiological signs of anxiety that do not correlate to self-reported psychological measurements",
"BACKGROUND Much effort in surgical education is placed on the development of clinical judgment and technical proficiency . However , little focus is placed on the management of stress associated with surgical performance . The inability to manage stress may lead to poor patient care , attrition from residency , and surgeon burnout . METHODS A blinded , matched , comparison group study to evaluate the efficacy of an educational program design ed to improve surgical resident performance during stressful scenarios was conducted . The experimental group ( n = 11 ) participated in stress training sessions , whereas the control group ( n = 15 ) did not . Both groups then completed a simulation during which stress was evaluated using objective and subjective measures , and resident performance was grade d using a st and ardized checklist . RESULTS Performance checklist scores were 5 % higher in the experimental group than the control group ( P = .54 ) . No change existed in anxiety state according to the State Trait Anxiety Inventory ( P = .34 ) or in heart rate under stress ( P = .17 ) between groups . CONCLUSIONS There was a trend toward improved performance scoring but no difference in anxiety levels after stress training . However , 91 % of residents rated the stress training as valuable",
"Objective To demonstrate that virtual reality ( VR ) training transfers technical skills to the operating room ( OR ) environment . Summary Background Data The use of VR surgical simulation to train skills and reduce error risk in the OR has never been demonstrated in a prospect i ve , r and omized , blinded study . Methods Sixteen surgical residents ( PGY 1–4 ) had baseline psychomotor abilities assessed , then were r and omized to either VR training ( MIST VR simulator diathermy task ) until expert criterion levels established by experienced laparoscopists were achieved ( n = 8) , or control non-VR-trained ( n = 8) . All subjects performed laparoscopic cholecystectomy with an attending surgeon blinded to training status . Videotapes of gallbladder dissection were review ed independently by two investigators blinded to subject identity and training , and scored for eight predefined errors for each procedure minute ( interrater reliability of error assessment r > 0.80 ) . Results No differences in baseline assessment s were found between groups . Gallbladder dissection was 29 % faster for VR-trained residents . Non-VR-trained residents were nine times more likely to transiently fail to make progress ( P injure the gallbladder or burn nontarget tissue ( chi-square = 4.27 , P .04 ) . Mean errors were six times less likely to occur in the VR-trained group ( 1.19 vs. 7.38 errors per case;P VR surgical simulation to reach specific target criteria significantly improved the OR performance of residents during laparoscopic cholecystectomy . This validation of transfer of training skills from VR to OR sets the stage for more sophisticated uses of VR in assessment , training , error reduction , and certification of surgeons",
"BACKGROUND Simulator training is well established to improve technical and non-technical skills in critical situations . Few data exist about stress experienced during simulator training . This study aims to evaluate performance and stress in intensivists before and after two different simulator-based training approaches . METHODS Thirty-two intensivists took part in one of six 1-day simulator courses . The courses were r and omised to either crew re source management ( CRM ) training , which contains psychological teaching and simulator scenarios , or classic simulator training ( MED ) . Before and after the course each participant took part in a 10-min test scenario . Before ( T1 ) and after ( T2 ) the scenario , and then again 15 min later ( T3 ) , saliva sample s were taken , and amylase and cortisol were measured . Non-technical skills were evaluated using the Anaesthetist 's Non-Technical Skills ( ANTS ) assessment tool . Clinical performance of the participants in the test scenarios was rated using a checklist . RESULTS Twenty-nine participants completed the course ( 17-CRM , 12-MED ) . ANTS scores as well as clinical performances were significantly better in the post-intervention scenario , with no differences between the groups . Both cortisol concentration and amylase activity showed a significant increase during the test scenarios . In the post-intervention scenario , the increase in amylase but not cortisol was significantly smaller . There were no differences between the CRM and MED group . CONCLUSIONS High fidelity patient simulation produces significant stress . After a 1-day simulator training , stress response measured by salivary alpha-amylase was reduced . Clinical performance and non-technical skills improved after 1 day of simulator training . Neither stress nor performance differed between the groups",
"HYPOTHESIS Mental strain measured by heart rate variability differs during laparoscopic and conventional sigmoid resections . DESIGN Prospect i ve r and omized study . SETTING University hospital . PARTICIPANTS Two surgeons performed 10 conventional and 10 laparoscopic sigmoid resections , alternating roles as primary surgeon and assistant . The kind of technique was r and omly chosen each time . INTERVENTION Electrocardiograms of the surgeon and assistant were continuously recorded during the procedures and heart rate variability was analyzed off-line . The first 10 procedures ( 5 laparoscopic and 5 conventional ) were performed by the more experienced and the next 10 by the less experienced surgeon . MAIN OUTCOME MEASURES Heart rate variability was determined by power spectral analysis as heart rate in beats per minute , high frequency ( HF ) and low frequency ( LF ) components in normalized units , and LF/HF ratio . RESULTS Results are given for heart rate , HF , LF , and LF/HF ratio for the following variables : laparoscopic surgery : 87.9 , 14.7 , 90.1 , 7.5 ; conventional surgery : 90.2 , 17.1 , 87.6 , 6.4 ; surgeon : 94.0 , 13.5 , 91.4 , 8.4 ; first assistant : 84.1 , 17.8 , 86.3 , 5.6 ; more experienced surgeon : 93.1 , 16.5 , 87.8 , 6.4 ; and less experienced surgeon : 85.0 , 14.8 , 90.0 , 7.5 . The LF/HF ratio was significantly higher ( P laparoscopic compared with conventional surgery and for the surgeon compared with the assistant ( P laparoscopic colorectal surgery causes higher mental strain in surgeons than performing conventional surgery",
"Purpose There have been no studies examining the effect of optimized ergonomic and technical environment on the psychological and physiological stress of the surgeon . The aim of this study was to examine whether optimized ergonomics and technical aids within a modern operating room ( OR ) affect psychological and physiological stress in experienced laparoscopic surgeons . Methods This was a prospect i ve case-controlled study including 10 experienced surgeons . Surgery was performed in 2 different ORs : a st and ard room and a modern room ( OR1-suite , Karl Storz ) . The surgeons filled out question naires concerning physical and psychological wellbeing before and after surgery and had their heart rate variability registered during surgery . Results Preoperative to postoperative physical strain and pain measurements revealed a systematic al difference with 14 of 15 parameters favoring the modern OR . Two of these parameters reached statistical significance . We did not find any significant differences in the subjective parameters of surgeon satisfaction or the measured heart rate variability parameters . Conclusions Physical strain on the surgeon was reduced when performing laparoscopic cholecystectomy in a modern OR compared with a st and ard room",
"BACKGROUND Prior work using simulation for assessing intubation skills has largely focused on the use of observer-generated performance measures in the form of checklists and global ratings scales . PURPOSE The purpose of our work was to investigate whether patient-centered simulation data could be used to quantify learner 's performance during direct laryngoscopy . METHODS We design ed a pretest/posttest prospect i ve intervention study of residents ' ( n = 25 ) intubation skills . RESULTS When assessing validity , all of the patient-centered simulation variables showed significant correlations with the previously vali date d observer-generated performance measures ( r = 0.331 - 0.463 , P ≤ 0.001 ) . When assessing reliability , there were significant correlations between all of the sensor variables , confirming moderate to high inter-item reliability ( r = 0.259 - 0.794 , P ≤ 0.05 ) . The observer-generated performance measures showed significant improvement in use of the Macintosh blade ( T1 = 2.10/5.00 , T2 = 3.64/5.00 , P = 0.001 ) . However , this was not the case for the Miller blade ( T1 = 1.30/5.00 , T2 = 1.75/5.00 , P = 0.119 ) . Overall , the patient-centered simulation variables provided a high level of detail regarding performance improvement areas . CONCLUSION This study presents a multilevel analysis of sensor-generated simulation data . As the sensors provide sound , formative data regarding patient contact , the outputs may be used for specific criterion measures and detailed performance feedback",
"BACKGROUND Surgeons are often subject to excessive levels of acute stress that can impair their performance . Mental practice ( MP ) is a strategy used in other high-performance industries to alleviate anxiety . This study investigated if MP reduces stress in novice surgeons . STUDY DESIGN A prospect i ve , r and omized controlled design was used with 20 novice surgeons recruited by r and om sampling . After baseline testing , participants underwent training on an evidence -based virtual reality ( VR ) curriculum . They then performed 5 VR laparoscopic cholecystectomies ( LC ) after being r and omized to MP or control groups . The MP group performed 30 minutes of MP using a vali date d MP training protocol before each LC ; control participants conducted an unrelated activity . Stress was assessed subjectively using the vali date d State-Trait Anxiety-Inventory ( STAI ) question naire and objective ly with a continuous heart rate ( HR ) monitor and salivary cortisol . Mental imagery was assessed using the vali date d mental imagery question naire . RESULTS Eighteen participants completed the study . There were no intergroup differences in baseline stress , imagery , or technical ability . Comparing the MP group with controls , subjective stress ( STAI ) was lower for the MP group ( median 8.40 vs 11.31 , p Objective stress was also significantly reduced for the MP group in terms of the average HR ( median 72 vs 88 beats/minute , p maximum HR ( median 102 vs 119 beats/minute , p stress and imagery , indicating that improved imagery was associated with lower stress ( p subjective , cardiovascular , and neuroendocrine response to stress on a VR simulator . Additional research should determine whether this effect extends beyond novice surgeons and transfers to the operating room",
"The purpose of this study was to investigate the effect of three different skin thermistor attachment methods on weighted mean skin temperature ( WMT(sk ) ) at three different ambient temperatures ( approximately 24 ° C ( TEMP ) ; approximately 30 ° C ( WARM ) ; approximately 35 ° C ( HOT ) ) compared to uncovered thermistors . Eleven , non-acclimated , volunteers completed three 5 min bouts of submaximal cycling ( approximately 70 W mechanical work)-one at each environmental condition in sequential order ( TEMP , WARM , HOT ) . One thermistor was fixed to the sternal notch whilst four skin thermistors were spaced at 3 cm intervals on each of the sites on the limbs as per the formula of Ramanathan ( 1964 J. Appl . Physiol . 19 531 - 3 ) . Each thermistor was either held against the skin uncovered ( UC ) or attached with surgical acrylic film dressing ( T ) ; surgical acrylic film dressing and hypoallergenic surgical tape ( TT ) or surgical acrylic film dressing , hypoallergenic surgical tape and surgical b and age ( TTC ) . The WMT(sk ) calculated was significantly lower in UC compared to T , TT and TTC ( p of skin thermistor attachment can result in the significant over-estimation of weighted mean skin temperature"
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411756d6-06ff-11f0-808a-c43d1ab1c353
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OBJECTIVES The objective of the study was to assess the usability of minimal important difference ( MID ) and minimal clinical ly important difference ( MCID ) for measuring meaningful changes in disease-specific and generic health-related quality -of-life ( HRQoL ) outcomes in patient-centered care . STUDY DESIGN AND SETTING We adopted a two-step literature review process . First , we used PubMed and Google scholar to identify a broad range of search terms . Next , we search ed OVID Medline , JSTOR , and PubMed for terms " MID , " and " MCID . " We excluded non-English language studies , articles older than 1995 , those not related to generic- and disease-specific HRQoL measures , and protocol s of future studies . Studies were grouped according to generic- and disease-specific measures . We assessed MID or MCID calculation methods , effect sizes , estimated values , and significance . RESULTS Eighty articles satisfied the inclusion criteria . Our synthesis provides a comprehensive assessment of MID or MCID for 10 generic-specific and 80 disease-specific instruments . We observed a lack of consistency in the application of methods for computing MID or MCID for generic and disease-specific HRQoL measures . Only 43 ( 54 % ) studies used both anchor and distribution methods to elicit MID or MCID . Thirty-four articles estimated MID values only , whereas 47 articles estimated MCID . CONCLUSION The anchor-based method yields conservative estimates of MID or MCID , compared to the distribution-based method . The distribution method does not take into account patient perspectives and should be accompanied by anchor method while computing MID . The MID should be interpreted with caution , and available estimates for a particular instrument must be used . This will help in integrating the MID estimates into the overall research or clinical plan for a specific context
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"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",
"To provide additional evidence regarding the plausible range of the differences in health-related quality of life ( HRQL ) question naire scores within which the minimal important difference ( MID ) falls , we review ed the results of 32 r and omized controlled trials in individual subjects ( N of 1 RCTs ) with chronic diseases . These trials had been conducted to establish whether a patient was obtaining more good than harm from a medication . Each N of 1 RCT included a series of pairs of treatment periods , one period on active drug , and one on placebo or alternative drug . We examined the relationship between small ( MID ) , medium , and large differences between periods within pairs , as indicated by Global Ratings and differences between these same periods according to HRQL question naires . The results showed a mean difference of 0.29 points per question in HRQL question naire scores corresponded to the MID . Differences of approximately 0.66 points per question corresponded to a moderate difference as ranked by the Global Rating ; difference of about 1.09 points per question represented marked difference",
"The minimal important difference ( MID ) is the smallest benefit of treatment that would result in clinicians recommending it to their patients . The MID is necessary to calculate sample size for r and omized clinical trials , but its chosen value is often arbitrary . This study set out to determine the practicability of surveying physicians to elicit the MID for clinical trial sample -size calculation . Using a mail survey , we elicited the MID of different physician specialties ( family medicine , internal medicine , vascular surgery ) for using propranolol to slow abdominal aortic aneurysm ( AAA ) growth assuming that propranolol was efficacious in this condition . We used different outcome measures ( growth rate or proportion of patients requiring surgery ) and different methods of data presentation for the proportion of patients requiring surgery ( absolute risk reduction or number needed to treat ) . The MID varied significantly by physician specialty , experience with AAA and propranolol , and the method used to elicit the MID . Consequently , sample -size calculations using these various MIDs varied from 116 to 3015 . Future attempts to elicit the MID need to consider carefully who is surveyed , how data are presented , and how opinions are elicited",
"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",
"OBJECTIVE To determine the impact on a responder type analysis of using three published methods to obtain the minimally important difference ( MID ) on the conclusion of a r and omized controlled trial ( RCT ) . STUDY DESIGN AND SETTING Using data from an RCT of supportive-expressive group therapy ( SEGT-intervention ) vs. st and ard care ( control ) in women with metastatic breast cancer , we measured individual responsiveness to change according to three levels of predefined MID ( 0.2 SD , 0.5 SD , and 1 st and ard error of measurement ) of the following six vali date d question naires : Profile of Mood States , Impact of Event Scale , Psychosocial Adjustment to Illness Scale , EORTC Quality -of-Life Question naire Core-30 , Mental Adjustment to Cancer , and a pain visual analog scale . The proportion of women improved by SEGT and the number needed to treat according to three levels of MID were calculated . RESULTS There was no consistent difference in the net proportion of women improving with the SEGT vs. control arm according to the three different levels of MID . CONCLUSION The choice between different levels of distribution-based MID did not make an important difference in the net proportion of women improving with the SEGT . Future research should compare MID derived from clinical anchors , in particular patient opinions",
"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",
"PURPOSE Although it is the most powerful predictor of early prostate cancer treatment-related complications and quality -of-life ( QOL ) outcomes , most studies do not stratify results by baseline function . Further , reporting functional outcomes as averaged numerical results may obscure informatively disparate courses . Using levels of treatment-related dysfunction , we address these problems and present the final QOL outcomes of our prospect i ve cohort study of patients with early prostate cancer . METHODS We created categories for sexual , bowel , and urinary function , measured using numerical scores of the vali date d Prostate Cancer Symptom Indices and stratified into \" normal , \" \" intermediate \" and \" poor \" levels of function by incorporating patient-reported symptom and distress information . We present QOL outcomes for 409 patients 36 months after radical prostatectomy , external-beam radiation therapy , and brachytherapy . RESULTS Different levels of baseline sexual , bowel , and urinary function produced distinctive treatment-related changes from baseline to 36 months . In general , the average scale increases in dysfunction were greatest among patients with normal baseline function , although patients with normal and intermediate baseline function had similar increases in sexual dysfunction . For patients whose baseline urinary obstruction/irritation was poor , both average scale scores and most patients ' level of function improved after treatment , particularly after surgery . CONCLUSION The use of functional levels to stratify treatment-related outcomes by pretreatment functional status and to display the proportions of patients with improved , stable , or worsened function after treatment provides information that more specifically conveys the expected impact of treatment to patients choosing among localized prostate cancer treatments",
"To assess the impact of disease and treatment on patients with advanced non-small cell lung cancer ( NSCLC ) , we set out to determine a clinical ly meaningful change ( CMC ) on the Lung Cancer Subscale ( LCS ) and the Trial Outcome Index ( TOI ) of the Functional Assessment of Cancer Therapy-Lung ( FACT-L ) question naire . We used data from Eastern Cooperative Oncology Group study 5592 ( E5592 ) , a r and omized trial comparing three chemotherapeutic regimens in 599 advanced NSCLC patients . Patients completed the FACT-L at baseline ( pretreatment ) , 6 weeks , 12 weeks , and 6 months . Comparing across baseline performance status ( 0 vs. 1 ) , prior weight loss ( or = 5 % ) , and primary disease symptoms ( 1 ) , LCS and TOI score differences ranged from 2.4 to 3.6 and 6.5 to 9.2 , respectively ( all Ps improvement in LCS score from baseline to 12 weeks was 2.4 points in patients who had responded to treatment versus 0.0 points in patients who had progressive disease . Twelve-week LCS change scores for patients progressing early were 3.1 points worse than those of patients progressing later ( mean = -1.2 vs.1.9 , respectively ) . Similarly , the average TOI change score from baseline to 12 weeks was -6.1 for patients who had progressive disease versus -0.8 points for patients who had responded to treatment . Twelve-week TOI change scores for patients progressing early ( mean = -8.1 ) were 5.7 points worse than those of patients progressing later ( mean = -8.1 vs. -2.4 , respectively ) . Analyses assuming nonr and om missing data result ed in slightly larger differences . Clinical ly relevant change scores were estimated as two to three points for the LCS and five to seven points for the TOI , setting upper limits for minimal CMCs . These values were comparable to suggested distribution-based criteria of a minimally important difference . These results support use of a two to three point change in the LCS and five to six point change on the TOI of the FACT-L as a CMC , and offer practical direction for inclusion of important patient-based endpoints in lung cancer clinical trials",
"Background . It is generally agreed that r and omized controlled trials should be powered to detect small but clinical ly significant treatment effects . Toward these ends , minimal important difference ( MID ) was proposed as a benchmark for design ing trials and for interpreting health-related quality -of-life instrument scores . MID was defined in 1989 as “ the smallest difference in score in the domain of interest which patients perceive as beneficial and which would m and ate , in the absence of troubling side effects and excessive cost , a change in the patient ’s management . ” Objective . 1 ) To exp and the idea of minimal clinical ly important difference so as to take into account harms as well as benefits . 2 ) To propose concepts and methods with which to do so . Summary . The authors define sufficiently important difference ( SID ) as the smallest amount of patient-valued benefit that an intervention would require to justify associated costs , risks , and other harms . As a means toward estimation of SID , the authors propose benefit-harm tradeoff methods , in which domains of benefit and harm are systematic ally traded off against each other and assessed in relation to the global decision of whether a treatment choice is worthwhile . Specific SID estimates can be used to power and interpret clinical trials or to inform health services research and /or public health policy . This article briefly describes the evolution of the important difference concept and outlines similarities and differences between MID and SID"
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This study examined the effect of lifestyle interventions on cardiovascular disease risk factors among workers . The study comprised a systematic review and meta- analysis of controlled trials . Relevant controlled trials were search ed , with selection s based on the Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines . Risk of bias was assessed using the Scottish Intercollegiate Guidelines Network ( SIGN ) . Of 1174 identified publications , one low- quality study was excluded . Finally , 10 were analyzed . The effect sizes were analyzed for heterogeneity , and r and om effect models ( Hedge 's g ) were used . A subgroup analysis was performed on the follow-up point of intervention ( ≤ 12 months vs. > 12 months ) . Publication bias was also analyzed . Interventions were effective for systolic ( g = 0.66 , 95 % CI : 0.27 - 1.60 ) and diastolic blood pressure ( g = 0.63 , 95 % CI : 0.21 - 1.06 ) , and BMI ( g = 0.71 , 95 % CI : 0.15 - 1.11 ) . Interventions were ineffective for weight ( g = 0.18 , 95 % CI : -0.04 , 0.40 ) and LDL-cholesterol ( g = 0.46 , 95 % CI : -0.02 , 0.93 ) . There was high heterogeneity between studies ( I2 = 78.45 to I2 = 94.61 ) . There was no statistically significant publication bias , except for systolic blood pressure . Interventions to reduce risk of cardiovascular disease risk might be effective in improving physical outcomes , but additional high- quality trials are needed in the future
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"OBJECTIVE To evaluate the effectiveness of a worksite health promotion program on improving cardiovascular disease risk factors . METHODS In St Louis , Missouri from 2005 to 2006 , 151 employees ( 134 F , 17 M , 81 % overweight/obese ) participated in a cohort-r and omized trial comparing assessment s + intervention ( worksite A ) with assessment s only ( worksite B ) for 1 year . All participants received personal health reports containing their assessment results . The intervention was design ed to promote physical activity and favorable dietary patterns using pedometers , healthy snack cart , WeightWatchers(R ) meetings , group exercise classes , seminars , team competitions , and participation rewards . Outcomes included BMI , body composition , blood pressure , fitness , lipids , and Framingham 10-year coronary heart disease risk . RESULTS 123 participants , aged 45+/-9 yr , with BMI 32.9+/-8.8 kg/m(2 ) completed 1 year . Improvements ( P fitness , blood pressure , and total- , HDL- , and LDL-cholesterol . Additional improvements occurred at worksite A in BMI , fat mass , Framingham risk score , and prevalence of the metabolic syndrome ; only the changes in BMI and fat mass were different between worksites . CONCLUSION A multi-faceted worksite intervention promoted favorable changes in cardiovascular disease risk factors , but many of the improvements were achieved with worksite health assessment s and personalized health reports in the absence of an intervention",
"BACKGROUND Cardiovascular disease ( CVD ) and diabetes account for one-third of the mortality difference between African American and white patients . We evaluated the effect of a CVD risk reduction intervention in African Americans with diabetes . METHODS We r and omized 359 African Americans with type 2 diabetes to receive usual care or a nurse telephone intervention . The 12-month intervention provided monthly self-management support and quarterly medication management facilitation . Co primary outcomes were changes in systolic blood pressure ( SBP ) , hemoglobin A1c ( HbA1c ) , and low-density lipoprotein cholesterol ( LDL-C ) over 12 months . We estimated between-intervention group differences over time using linear mixed-effects models . The secondary outcome was self-reported medication adherence . RESULTS The sample was 72 % female ; 49 % had low health literacy , and 37 % had annual income Model-based estimates for mean baseline SBP , HbA1c , and LDL-C were 136.8 mm Hg ( 95 % CI 135.0 - 138.6 ) , 8.0 % ( 95 % CI 7.8 - 8.2 ) , and 99.1 mg/dL ( 95 % CI 94.7 - 103.5 ) , respectively . Intervention patients received 9.9 ( SD 3.0 ) intervention calls on average . Primary providers replied to 76 % of nurse medication management facilitation contacts , 18 % of these result ed in medication changes . There were no between-group differences over time for SBP ( P = .11 ) , HbA1c ( P = .66 ) , or LDL-C ( P = .79 ) . Intervention patients were more likely than those receiving usual care to report improved medication adherence ( odds ratio 4.4 , 95 % CI 1.8 - 10.6 , P = .0008 ) , but adherent patients did not exhibit relative improvement in primary outcomes . CONCLUSIONS This intervention improved self-reported medication adherence but not CVD risk factor control among African Americans with diabetes . Further research is needed to determine how to maximally impact CVD risk factors in African American patients",
"Background Overweight ( Body Mass Index [ BMI ] ≥ 25 kg/m2 ) and obesity ( BMI ≥ 30 kg/m2 ) are associated with increased cardiovascular risk , posing a considerable burden to public health . The main aim of this study was to investigate lifestyle intervention effects on cardiovascular risk factors in healthy overweight employees . Methods Participants were 276 healthy overweight employees ( 69.2 % male ; mean age 44.0 years [ SD 9.2 ] ; mean BMI 29.7 kg/m2 [ SD 3.1 ] ) . They were r and omized to one of two intervention groups receiving a six month lifestyle intervention with behavior counseling by phone ( phone group ) or e-mail ( Internet group ) , or to a control group receiving usual care . Body weight , height , waist circumference , sum of skinfolds , blood pressure , total cholesterol level and predicted aerobic fitness were measured at baseline , at 6 and at 24 months . Regression analyses included the 141 participants with complete data . Results At 6 months a significant favorable effect on total cholesterol level ( -0.2 mmol/l , 95%CI -0.5 to -0.0 ) was observed in the phone group and a trend for improved aerobic fitness ( 1.9 ml/kg/min , 95%CI -0.2 to 3.9 ) in the Internet group . At two years , favorable trends for body weight ( -2.1 kg , 95%CI -4.4 to 0.2 ) and aerobic fitness ( 2.3 ml/kg/min , 95%CI -0.2 to 4.8 ) were observed in the Internet group . Conclusions The intervention effects were independent of the used communication mode . However short-term results were in favor of the phone group and long-term results in favor of the internet group . Thus , we found limited evidence for our lifestyle intervention to be effective in reducing cardiovascular risk in a group of apparently healthy overweight workers . Trial registration IS RCT",
"BACKGROUND Physical inactivity and obesity are major public health problems . Our objective was to investigate the effectiveness of an individual counseling intervention at the workplace on physical activity fitness and health . Counseling content derived from the Patient-centered Assessment and Counseling for Exercise and Nutrition ( PACE ) program . METHODS A total of 299 employees of three municipal services in the Dutch town of Enschede were r and omly allocated into intervention ( n = 131 ) and control group ( n = 168 ) . Over a 9-month period , intervention group subjects were offered seven counseling sessions . Counseling was based on the individual 's stage of behavioral change using PACE physical activity and nutrition protocol s. Subjects in both the intervention and control group received written information about several lifestyle factors . Primary outcome measures were physical activity ( total energy expenditure , during sports activities , during physical activity leisure time other than sports , and meeting the moderate-intensity public health recommendations ) ; cardiorespiratory fitness ; and prevalence of musculoskeletal symptoms . Secondary outcome measures were body composition ( body mass index [ BMI ] , and percentage of body fat measured via skinfold thicknesses ) ; blood pressure ; and blood cholesterol . RESULTS There were significant positive effects on total energy expenditure , physical activity during sports , cardiorespiratory fitness , percentage of body fat , and blood cholesterol . No effects were found for the proportion of subjects meeting the public health recommendation of moderate-intensity physical activity , physical activity during leisure time other than sports , prevalence of musculoskeletal symptoms , body mass index , and blood pressure . CONCLUSIONS Individual face-to-face counseling at the workplace based on PACE protocol s positively influenced physical activity levels and some components of physical fitness . The implementation of workplace counseling programs for individuals should therefore be promoted",
"Background Intensive diet and physical activity interventions have been found to reduce cardiovascular disease ( CVD ) risk , but are re source intensive . The American Heart Association recently recommended motivational interviewing ( MI ) as an effective approach for low-intensity interventions to promote health-related outcomes such as weight loss . However , there is limited research evaluating the long-term effectiveness of MI-based interventions on health-related outcomes associated with CVD risk . The current research evaluated the effectiveness of a six-month low-intensity MI intervention in a UK primary -care setting in maintaining reductions in CVD risk factors at12 months post-intervention . Methods Primary -care patients were r and omised to an intervention group that received st and ard exercise and nutrition information plus up to five face-to-face MI sessions , delivered by a physical activity specialist and registered dietician over a 6-month period , or to a minimal intervention comparison group that received the st and ard information only . Follow-up measures of behavioural ( vigorous and moderate physical activity , walking , physical activity stage-of-change , fruit and vegetable intake , and dietary fat intake ) and biomedical ( weight , body mass index [ BMI ] , blood pressure , cholesterol ) outcomes were taken immediately post-intervention and at a 12-month follow-up occasion . Results Intent-to-treat analyses revealed significant differences between groups for walking and cholesterol . Obese and hypercholesterolemic patients at baseline exhibited significant improvements in BMI and cholesterol respectively among those allocated to the intervention group compared to the comparison group . Post-intervention improvements in other health-related outcomes including blood pressure , weight , and BMI were not maintained . Conclusions The present study suggests that a low-intensity MI counselling intervention is effective in bringing about long-term changes in some , but not all , health-related outcomes ( walking , cholesterol levels ) associated with CVD risk . The intervention was particularly effective for patients with elevated levels of CVD risk factors at baseline . Based on these findings future interventions should be conducted in a primary care setting and target patients with high risk of CVD . Future research should investigate how the long-term gains in health-related outcomes brought about by the MI-counselling intervention in the current study could be extended to a wider range of health outcomes",
"The Paris Cardiovascular Risk Factor Prevention Trial was design ed to determine whether individualised intervention could induce a reduction in the coronary risk factor levels in young men . Three thous and three hundred and thirty-six men aged 25 to 35 , working in the 160 sections of a large Parisian administration , were examined . The section were r and omly allocated to a control and an intervention group . Advice concerning diet , cigarette smoking , and physical activity was provided repeatedly to the subjects in the intervention group . Two years after the first intervention , the first 1292 subjects who entered the study , whether from the intervention or the control group , were recalled ; 86 % of the intervention group and 84 % of the control group responded . The changes in weight , blood pressure , and cigarette smoking in the intervention group , corrected for changes in the control group , were respectively -0.4 kg ( p = 0.06 ) , -1.4 mm Hg ( p less than 0.05 ) , and -1.2 cigarettes ( p less than 0.01 ) . There was no difference between the two groups in serum cholesterol change . Most of these results concerning young men are in agreement with recently reported results of community intervention programmes in middle-aged men",
"BACKGROUND The long-term effectiveness of multicomponent worksite health promotion programs targeting cardiovascular disease risk factors remains unclear in Japan . This study was conducted to evaluate the effectiveness of such a health promotion program consisting of a main program provided over 4 days and a follow-up program provided over 1 year . METHODS The subjects of this r and omized controlled trial were male employees working for a building maintenance company in Japan . The intervention group ( n = 152 ) and the control group ( n = 150 ) consisted of employees having abnormal findings in at least one of the following items at baseline health examination : body mass index ( BMI ) , systolic ( SBP ) or diastolic blood pressure , total cholesterol , HDL cholesterol , triglycerides , and fasting blood glucose . Evaluation was conducted at 18 months after the main program . RESULTS BMI , SBP , total cholesterol , and triglycerides improved significantly in the intervention group compared with the control group ( P BMI , total cholesterol , and triglycerides improved significantly in the intervention group ( P multicomponent health promotion program provided to employees was shown to be effective in improving obesity , high blood pressure , and hyperlipidemia when evaluated 18 months after the main intervention program",
"AIMS This study was conducted to compare the effects of two years of lifestyle intervention to no intervention or one year of intervention on diabetes risk factors in male workers with impaired fasting glucose ( IFG ) or diabetes . METHODS We conducted a r and omized lifestyle intervention trial design ed to alter personal lifestyles among 123 industrial male workers ( CG ; control group , n=75 ; OIG ; one-year intervention group , n=23 ; TIG ; two-year intervention group , n=25 ) . The intervention consisted of two parts , the main program ( face-to-face counseling five times/12 weeks ) and a follow-up program ( e-mail counseling ten times/30 weeks ) . Assessment s included biochemical characteristics , anthropometry and nutrient intake at baseline and after two years . RESULTS After two years , systolic blood pressure , HOMA-IR , HDL cholesterol and total energy intake ( p weight , body mass index , waist circumference , blood pressure , fasting plasma glucose ( FPG ) , HbA1c and nutrient intake ( total energy , carbohydrate , protein and sodium ) were significantly decreased ( p level of FPG and HbA1c ( p diabetes risk factors than OIG"
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Financial incentives to improve health have received increasing attention , but are subject to ethical concerns . Monetary Contingency Contracts ( MCCs ) , which require individuals to deposit money that is refunded contingent on reaching a goal , are a potential alternative strategy . This review evaluates systematic ally the evidence for weight loss – related MCCs . R and omised controlled trials testing the effect of weight loss – related MCCs were identified in online data bases . R and om-effects meta-analyses were used to calculate overall effect sizes for weight loss and participant retention . The association between MCC characteristics and weight loss/participant retention effects was calculated using meta-regression . There was a significant small-to-medium effect of MCCs on weight loss during treatment when one outlier study was removed . Group refunds , deposit not paid as lump sum , participants setting their own deposit size and additional behaviour change techniques were associated with greater weight loss during treatment . Post-treatment , there was no significant effect of MCCs on weight loss . There was a significant small-to-medium effect of MCCs on participant retention during treatment . Research er-set deposits paid as one lump sum , refunds delivered on an all-or-nothing basis and refunds contingent on attendance at classes were associated with greater retention during treatment . Post-treatment , there was no significant effect of MCCs on participant retention . The results support the use of MCCs to promote weight loss and participant retention up to the point that the incentive is removed and identifies the conditions under which MCCs work best
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"In an experimental study of weight reduction , 62 obese men and women were administered a pretreatment question naire and r and omly assigned to three experimental treatment groups : ( a ) an external control group with a nonrefundable contingency ; ( 6 ) a self-control group with a refundable contingency ; and ( c ) a self-control group with a nonrefundable contingency . The results indicated that the self-control and external-control treatments were equally effective in producing reduction in weight . However , both self-control interventions were more effective than the external-control intervention in promoting maintenance of weight loss",
"Weight losses and psychological well-being were examined at 30 months in 69 men and 61 women initially treated with behavior therapy as a function of ( a ) initial weight loss and ( b ) weight-loss goals . Initial weight losses were positively , not negatively , related to weight loss at 30 months . Weight loss goals did not predict short-term or long-term weight loss . People who reached weight goals had better long-term weight losses than those who did not , but this finding was largely due to differences in initial weight loss . Psychological well-being at 30 months was not related to initial weight losses or goals . Although correlational rather than experimental , these results do not support the hypothesis that obese patients should be encouraged to set lower weight-loss goals",
"Forty smokers and 47 overweight individuals were recruited for a home correspondence program for either smoking cessation or weight loss . Participants were assigned to one of four programs for changing their respective health behaviors : ( 1 ) a home correspondence program conducted entirely by mail , ( 2 ) the mail program with supplemental financial contigency contracts tied to completion of written homework , ( 3 ) the correspondence programs supplemented both by homework contracts and by regular calls to a telephone answering system , and ( 4 ) a st and ard behavioral group program which acted as a comparison condition . Results showed that all three correspondence approaches produced significant changes in health behaviors equal to the changes experienced by participants in the st and ard group program . The implication of these findings for development of low cost programs for disease prevention are discussed",
"ABSTRACT BACKGROUND Previous efforts to use incentives for weight loss have result ed in substantial weight regain after 16 weeks . OBJECTIVE To evaluate a longer term weight loss intervention using financial incentives . DESIGN A 32-week , three-arm r and omized controlled trial of financial incentives for weight loss consisting of a 24-week weight loss phase during which all participants were given a weight loss goal of 1 pound per week , followed by an 8-week maintenance phase . PARTICIPANTS Veterans who were patients at the Philadelphia Veterans Affairs Medical Center with BMI s of 30–40.INTERVENTION Participants were r and omly assigned to participate in either a weight-monitoring program involving a consultation with a dietician and monthly weigh-ins ( control condition ) , or the same program with one of two financial incentive plans . Both incentive arms used deposit contracts ( DC ) in which participants put their own money at risk ( matched 1:1 ) , which they lost if they failed to lose weight . In one incentive arm participants were told that the period after 24 weeks was for weight-loss maintenance ; in the other , no such distinction was made . MAIN MEASUREWeight loss after 32 weeks . KEY RESULTS Results were analyzed using intention-to-treat . There was no difference in weight loss between the incentive arms ( P = 0.80 ) . Incentive participants lost more weight than control participants [ mean DC = 8.70 pounds , mean control = 1.17 , P = 0.04 , 95 % CI of the difference in means ( 0.56 , 14.50 ) ] . Follow-up data 36 weeks after the 32-week intervention had ended indicated weight regain ; the net weight loss between the incentive and control groups was no longer significant ( mean DC = 1.2 pounds , 95 % CI , -2.58–5.00 ; mean control = 0.27 , 95 % CI , -3.77–4.30 , P = 0.76 ) . CONCLUSIONS Financial incentives produced significant weight loss over an 8-month intervention ; however , participants regained weight post-intervention",
"The goal of this study was to evaluate a correspondence weight control program , and to assess the impact of three program elements ( weekly homework , interim weigh-ins , and participation deposits ) individually and in combination . All treated participants received 15 weekly st and ard lessons by mail . Three program features were varied factorially : a ) homework assignments , b ) interim weigh-ins and c ) a deposit refunded contingent on returning homework and /or attending interim weigh-ins . Participants were assigned r and omly to active treatment conditions or a delayed treatment control group . Among treated males ( N = 14 ) , initial average weight loss and BMI reduction were 9.6 kg and 3.1 respectively ; average net weight loss and BMI reduction at one year follow-up were 5.8 kg and 1.9 respectively . Among treated females ( N = 128 ) , initial average weight loss and BMI reduction were 3.1 kg and 1.2 respectively ; average net weight loss and BMI reduction at one year were 2.3 kg and .88 respectively . Women in all treated groups , except lessons only , showed a greater BMI reduction than untreated controls at the end of treatment . Women in conditions including both homework and interim weigh-ins had greater initial BMI reductions ( M = 1.6 ) than those who received lessons only ( M = .76 ) . At one year , net BMI reductions were comparable across all treated groups . Of the 42 women initially registered in conditions that included both homework and weigh-ins , 12 who denied joining other programs lost at least 4.5 kg ( M = 7.1 ) during treatment , and 7 had a net loss of at least 4.5 kg ( M = 8.0 ) at one year without apparent involvement in any other program",
"Abstract The relative efficacy of the major techniques typically used in behavioral treatment programs for weight reduction was investigated using obese adult volunteers . Study 1 compared the effects of self-monitoring , self-control procedures , monetary rewards , aversive imagery and relaxation training . These procedures result ed in significantly greater weight reduction than either a no treatment group or subjects who graphed and recorded daily weight . Self-monitoring of daily caloric intake was as effective as the other methods , both singly and combined , over a 4 week treatment period . Study 2 compared the long-term effects of self-monitoring vs the full complement of behavioral techniques used in Study 1 . The full behavior management program was significantly more effective , both during the treatment period and at 3 and 12 week follow-ups , although self-monitoring again produced substantial weight loss",
"In a study of the management of obesity 43 patients were r and omly assigned to behavior therapy , will power , and no-treatment control groups . The behavioral treatment involved contingency contracting , stimulus control , self-monitoring , energy expenditure , and group reinforcement procedures over an 18-week period . The will power patients were told to do the same thing as the behavior therapy patients ; however , instead of having formal contingencies and meeting regularly , they were told to apply \" will power \" on their own , as this was the most important aspect of losing weight . The third group was a st and ard no-treatment control group . Analyses of covariance indicated that ( a ) the behavior therapy group lost significantly more weight than the will power ( p less than .05 ) and no-treatment control ( p less than .01 ) groups , and ( b ) the will power and no-treatment control groups did not differ significantly from each other . An 18-week maintenance follow-up of the behavior therapy group indicated that there was no significant weight gain from the end of treatment to follow-up . Also , an analysis of time spent per patient suggested that the behavioral treatment employed in this study was more efficient than previous treatments",
"OBJECTIVE To investigate the influence of weight loss expectations ( expected 1-year BMI loss , dream and maximum acceptable BMI ) on attrition in obese patients seeking treatment . RESEARCH METHODS AND PROCEDURES Obese subjects ( 1,785 ; 1,393 women ; median age , 46 years ; median BMI , 36.7 kg/m(2 ) ) seeking treatment in 23 medical Italian centers were evaluated . Baseline diet and weight history , weight loss expectations , and primary motivation for seeking treatment ( health or improving appearance ) were systematic ally recorded . Psychiatric distress , binge eating , and body image dissatisfaction were tested at baseline by self-administered question naires ( Symptom Check List-90 , Binge Eating Scale , and Body Uneasiness Test ) . Attrition and BMI change at 12 months were prospect ively recorded . RESULTS At 12 months , 923 of 1,785 patients ( 51.7 % ) had discontinued treatment . Compared with continuers , drop-outs had a significantly lower age , a lower age at first dieting , lower dream BMI , a higher expected 1-year BMI loss , and a higher weight phobia . At logistic regression analysis , the strongest predictors of attrition at 12 months were lower age and higher expected 1-year BMI loss . The risk of drop-out increased systematic ally for unit increase in expected BMI loss at 12 months ( hazard ratio , 1.12 ; 95 % confidence interval , 1.04 to 1.20 ; p = 0.0018 ) . The risk was particularly elevated in the first 6 months . DISCUSSION Baseline weight loss expectations are independent cognitive predictors of attrition in obese patients entering a weight-losing program ; the higher the expectations , the higher attrition at 12 months . Unrealistic weight goals should be tackled at the very beginning of treatment",
" Thirty-six individuals participated in a worksite weight-loss program in which the central component was a self-motivation program of biweekly payroll deductions refunded contingent on meeting self-selected weight-loss goals . Half were assigned to early treatment and the remainder to a delayed treatment control group . Nine additional individuals also enrolled at the time of delayed treatment and were included in descriptive analyses of factors associated with weight loss . Results showed low program attrition over 6 months ( 6 % ) and mean weight losses ( 12.3 lb ) that are competitive with those obtained in clinical setting s. Although not different at baseline , participants in the delayed treatment group lost more than twice as much weight as those in the early treatment condition . This difference was interpreted as either a strong seasonal effect or a critical mass effect related to the proportion of employees at the worksite participating in the program . We conclude that self-motivation programs for health behavior change using the payroll system as an organization framework offer a promising new methodology for promoting healthful behaviors in work setting",
"CONTEXT Identifying effective obesity treatment is both a clinical challenge and a public health priority due to the health consequences of obesity . OBJECTIVE To determine whether common decision errors identified by behavioral economists such as prospect theory , loss aversion , and regret could be used to design an effective weight loss intervention . DESIGN , SETTING , AND PARTICIPANTS Fifty-seven healthy participants aged 30 - 70 years with a body mass index of 30 - 40 were r and omized to 3 weight loss plans : monthly weigh-ins , a lottery incentive program , or a deposit contract that allowed for participant matching , with a weight loss goal of 1 lb ( 0.45 kg ) a week for 16 weeks . Participants were recruited May-August 2007 at the Philadelphia VA Medical Center in Pennsylvania and were followed up through June 2008 . MAIN OUTCOME MEASURES Weight loss after 16 weeks . RESULTS The incentive groups lost significantly more weight than the control group ( mean , 3.9 lb ) . Compared with the control group , the lottery group lost a mean of 13.1 lb ( 95 % confidence interval [ CI ] of the difference in means , 1.95 - 16.40 ; P = .02 ) and the deposit contract group lost a mean of 14.0 lb ( 95 % CI of the difference in means , 3.69 - 16.43 ; P = .006 ) . About half of those in both incentive groups met the 16-lb target weight loss : 47.4 % ( 95 % CI , 24.5%-71.1 % ) in the deposit contract group and 52.6 % ( 95 % CI , 28.9%-75.6 % ) in the lottery group , whereas 10.5 % ( 95 % CI , 1.3%-33.1 % ; P = .01 ) in the control group met the 16-lb target . Although the net weight loss between enrollment in the study and at the end of 7 months was larger in the incentive groups ( 9.2 lb ; t = 1.21 ; 95 % CI , -3.20 to 12.66 ; P = .23 , in the lottery group and 6.2 lb ; t = 0.52 ; 95 % CI , -5.17 to 8.75 ; P = .61 in the deposit contract group ) than in the control group ( 4.4 lb ) , these differences were not statistically significant . However , incentive participants weighed significantly less at 7 months than at the study start ( P = .01 for the lottery group ; P = .03 for the deposit contract group ) whereas controls did not . CONCLUSIONS The use of economic incentives produced significant weight loss during the 16 weeks of intervention that was not fully sustained . The longer-term use of incentives should be evaluated . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00520611"
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OBJECTIVE The high dem and for obesity treatment and conventional therapies ' lack of effectiveness increases the use of alternative products . This study was aim ed at assessing evidence from r and omised clinical trials regarding the effectiveness of alternative weight-loss products ' ingredients . METHODS A survey was conducted in Ensenada , Baja California , to assess the frequency of consuming alternative products used for weight reduction . The ingredients in the products most in dem and were included in this review . The Pubmed data base was search ed for all r and omised clinical trial papers including these ingredients and assessing weight loss . RESULTS Thirty-six percent of the subjects question ed had used alternative methods for weight-loss , 83 % of them being women . The most frequently used products were shakes , tea , pills and flaxseed/linseed . Sixteen r and omised clinical trials using four ingredients were used : Garcinia cambogia , green tea , L-carnitina and flaxseed . Only two studies ( green tea and Garcinia cambogia ) showed significant weight-loss ( 25 % ) amongst control and experimental groups . There was no significant difference between the groups in the studies regarding L-carnitina and flaxseed . CONCLUSIONS There is a lack of evidence regarding quality studies justifying the use of alternative products for weight loss
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"The effect of a 3-tier intervention including dietary modifications ( ie , moderate energy restriction , decreased carbohydrate , increased protein ) , increased physical activity , and the use of carnitine as a dietary supplement was evaluated on plasma lipids and the atherogenicity of low-density lipoprotein ( LDL ) particles in a population of overweight and obese premenopausal ( aged 20 - 45 years ) women . Carnitine or a placebo ( cellulose ) was r and omly assigned to the participants using a double-blind design . Carnitine supplementation was postulated to enhance fat oxidation result ing in lower concentrations of plasma triglycerides . Seventy women completed the 10-week protocol , which followed a reduction in their energy intake by 15 % and a macronutrient energy distribution of 30 % protein , 30 % fat , and 40 % carbohydrate . In addition , subjects increased the number of steps taken per day by 4500 . As no differences were observed between the carnitine and placebo groups in all the measured parameters , all subjects were pooled together for statistical analysis . Participants decreased ( P caloric intake ( between 4132.8 and 7770 kJ ) and followed prescribed dietary modifications as assessed by dietary records . The average number of steps increased from 8950+/-3432 to 12764+/-4642 ( P Body weight , plasma total cholesterol , LDL cholesterol , and triglyceride were decreased by 4.5 % , 8.0 % , 12.3 % , and 19.2 % ( P apolipoproteins B and E decreased by 4.5 % and 15 % ( P LDL mean particle size was increased from 26.74 to 26.86 nm ( P smaller LDL subfraction ( P LDL lag time increased by 9.3 % ( P LDL conjugated diene formation decreased by 23 % ( P susceptibility of LDL to oxidation was decreased after the intervention . This study suggests that moderate weight loss ( < 5 % of body weight ) associated with reduced caloric intake , lower dietary carbohydrate , and increased physical activity impacts the atherogenicity of LDL",
"BACKGROUND Current interest in the role of functional foods in weight control has focused on plant ingredients capable of interfering with the sympathoadrenal system . OBJECTIVE We investigated whether a green tea extract , by virtue of its high content of caffeine and catechin polyphenols , could increase 24-h energy expenditure ( EE ) and fat oxidation in humans . DESIGN Twenty-four-hour EE , the respiratory quotient ( RQ ) , and the urinary excretion of nitrogen and catecholamines were measured in a respiratory chamber in 10 healthy men . On 3 separate occasions , subjects were r and omly assigned among 3 treatments : green tea extract ( 50 mg caffeine and 90 mg epigallocatechin gallate ) , caffeine ( 50 mg ) , and placebo , which they ingested at breakfast , lunch , and dinner . RESULTS Relative to placebo , treatment with the green tea extract result ed in a significant increase in 24-h EE ( 4 % ; P decrease in 24-h RQ ( from 0.88 to 0.85 ; P . Twenty-four-hour urinary norepinephrine excretion was higher during treatment with the green tea extract than with the placebo ( 40 % , P EE and RQ nor on urinary nitrogen or catecholamines . CONCLUSIONS Green tea has thermogenic properties and promotes fat oxidation beyond that explained by its caffeine content per se . The green tea extract may play a role in the control of body composition via sympathetic activation of thermogenesis , fat oxidation , or both",
"Alpha-linolenic acid ( ALA ) is a major dietary ( n-3 ) fatty acid . ALA is converted to longer-chain ( n-3 ) PUFA , such as eicosapentaenoic acid ( EPA ) and possibly docosahexaenoic acid ( DHA ) . EPA and DHA are fish-based ( n-3 ) fatty acids that have proven cardioprotective properties . We studied the effect of daily supplementation with 3 g of ALA on the plasma concentration of long-chain ( n-3 ) fatty acids in a predominantly African-American population with chronic illness . In a r and omized , double-blind trial , 56 participants were given 3 g ALA/d from flaxseed oil capsules ( n = 31 ) or olive oil placebo capsules ( n = 25 ) . Plasma EPA levels at 12 wk in the flaxseed oil group increased by 60 % , from 24.09 + /- 16.71 to 38.56 + /- 28.92 micromol/L ( P = 0.004 ) , whereas no change occurred in the olive oil group . Plasma docosapentaenoic acid ( DPA ) levels in the flaxseed oil group increased by 25 % from 19.94 + /- 9.22 to 27.03 + /- 17.17 micromol/L ( P = 0.03 ) with no change in the olive oil group . Plasma DHA levels did not change in either group . This study demonstrates the efficacy of the conversion of ALA to EPA and DPA in a minority population with chronic disease . ALA may be an alternative to fish oil ; however , additional clinical trials with ALA are warranted",
"We assessed the effect of ingestion of green tea ( GT ) extract along with a low-energy diet ( LED ) on resting energy expenditure ( REE ) , substrate oxidation and body weight as GT has been shown to increase energy expenditure and fat oxidation in the short term in both animals and people . Forty-six overweight women ( BMI 27.6 ( sd 1.8 ) kg/m2 ) were fed in energy balance from day 1 to day 3 , followed by a LED with GT ( 1125 mg tea catechins + 225 mg caffeine/d ) or placebo ( PLAC ) from day 4 to day 87 . Caffeine intake was st and ardised to 300 mg/d . Energy expenditure was measured on days 4 and 32 . Reductions in weight ( 4.19 ( sd 2.0 ) kg PLAC , 4.21 ( sd 2.7 ) kg GT ) , BMI , waist : hip ratio , fat mass and fat-free mass were not statistically different between treatments . REE as a function of fat-free mass and fat mass was significantly reduced over 32 d in the PLAC group ( P Dietary restraint increased over time ( P disinhibition and general hunger decreased ( P hungry over time and less thirsty , and showed increased prospect i ve food consumption compared with PLAC ( P GT along with a LED had no additional benefit for any measures of body weight or body composition . Although the decrease in REE as a function of fat-free mass and fat mass was not significant with GT treatment , whereas it was with PLAC treatment , no significant effect of treatment over time was seen , suggesting that a robust limitation of REE reduction during a LED was not achieved by GT",
"OBJECTIVES Carnitine deficiency impairs fatty acid beta-oxidation and may partly explain weight gain in valproate-treated patients . The aim of this study was to determine whether l-carnitine supplementation improves weight loss outcomes in bipolar patients taking sodium valproate . METHODS Sixty bipolar patients with clinical ly significant weight gain thought to be related to sodium valproate , who had been taking sodium valproate for > or=6 months , were r and omized to l-carnitine ( 15 mg/kg/day ) or placebo for 26 weeks , in conjunction with a moderately energy-restricted , low-fat diet . The primary outcome measure was weight change . RESULTS l-carnitine had no effect on mean weight loss compared with placebo ( -1.9 kg versus - 0.9 kg ) ( F = 0.778 , df = 1,58 , p = 0.381 ) . The number of people in each group able to lose any weight was identical ( = 0 , p = 1.0 ) ; more patients in the carnitine group ( nine versus five ) achieved a clinical ly significant weight loss ( > or=5 % ) but this was not statistically significant ( p = 1.0 , Fisher 's exact test ) . CONCLUSIONS At the dose prescribed in this study carnitine supplementation did not improve weight loss outcomes in valproate-treated bipolar patients consuming an energy-restricted , low-fat diet",
"OBJECTIVE : Assessment of the effect of 2-week supplementation with (−)-hydroxycitrate ( HCA ) and HCA combined with medium-chain triglycerides ( MCT ) on satiety , fat oxidation , energy expenditure ( EE ) and body weight ( BW ) loss . DESIGN : Three intervention periods of 2 weeks separated by washout periods of 4 weeks . Double-blind , placebo-controlled , r and omised and cross-over design .SUBJECTS : Eleven overweight male subjects ( mean±s.d . ; age , 47±16 y ; body mass index , 27.4 ± 8.2 kg/m2).INTERVENTION : Subjects consumed three self-selected meals and four iso-energetic ( 420 kJ ) snacks daily with either no supplementation ( PLA ) , 500 mg HCA ( HCA ) or 500 mg HCA and 3 g MCT ( HCA+MCT ) . Each intervention ended with a 36 h stay in the respiration chamber . RESULTS : There was a significant BW loss during the 2 weeks of intervention ( PLA , −1.0 ± 0.4 kg , P treatments . 24 h EE ( PLA , 11.8 ± 0.2 MJ ; HCA , 11.7 ± 0.1 MJ ; HCA+MCT , 11.5 ± 0.1 MJ ) , 24 h RQ ( 0.85 ± 0.00 in all treatments ) and the area under the curve of the appetite-related parameters were not different between treatments . CONCLUSION : Two-week supplementation with HCA and HCA combined with MCT did not result in increased satiety , fat oxidation , 24 h EE or BW loss compared to PLA , in subjects losing BW",
"Objectives : To study the effects of green tea on body weight , and biochemical and hormonal profiles in obese Chinese women with polycystic ovary syndrome ( PCOS ) . Methods : Thirty-four obese Chinese women with PCOS were r and omized into either treatment with green tea capsules or placebo for 3 months . The anthropomentric measurements , and biochemical and hormonal profiles before and after treatment in each group were compared . Results : The body weight of the green tea group decreased by a nonsignificant 2.4 % after treatment ; whereas the body weight , body mass index ( BMI ) , and body fat content of the control group were significantly higher after 3 months . There were no differences in any of the hormone levels measured in either group . The biochemical profiles of the two groups were also similar except that there was a small but significant rise in the triglyceride level in the green tea group . Fewer patients in the green tea group remained amenorrhoeic , but this was not significantly different from the control group . Conclusions : Green tea supplementation did not significantly reduce body weight in obese women with PCOS , nor did it alter the glucose or lipid metabolism",
"BACKGROUND A previous study has demonstrated that L-carnitine reduces plasma lipoprotein(a ) ( Lp[a ] ) levels in patients with hypercholesterolemia . OBJECTIVE To test a tolerable Lp(a)-reducing agent in diabetic patients , we assessed the effect of a dietary supplementation of L-carnitine on plasma lipid levels , particularly Lp(a ) , of patients with type 2 diabetes mellitus ( DM ) and hypercholesterolemia . METHODS In this 6-month , r and omized , double-masked , placebo-controlled clinical trial , patients were enrolled , assessed , and followed up at the Diabetic and Metabolic Diseases Center of the Department of Internal Medicine and Therapeutics at the University of Pavia , Pavia , Italy . All study patients had newly diagnosed type 2 DM that was managed through dietary restriction alone throughout the study , as well as hypercholesterolemia . Patients were r and omized to 1 of 2 groups . One group received L-carnitine , one 1-g tablet BID . The other group received a corresponding placebo . We assessed body mass index , fasting plasma glucose , postpr and ial plasma glucose , glycosylated hemoglobin , fasting plasma insulin , total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , triglycerides , apolipoprotein ( apo ) A-I , apo B , and Lp(a ) at baseline and at 1 , 3 , and 6 months of treatment . RESULTS This study included 94 patients . The treatment group included 24 men and 22 women ( mean [ SD ] age , 52 [ 6 ] years ) . The placebo group included 23 men and 25 women ( mean [ SD ] age , 50 [ 7 ] years ) . The baseline characteristics of the groups did not differ significantly . The mean ( SD ) body weight , height , and body mass index were 78.2 ( 5.8 ) kg , 1.70 ( 0.04 ) m , and 27.3 ( 2.5 ) kg/m(2 ) , respectively , in the L-carnitine group and 77.6 ( 6.4 ) kg , 1.71 ( 0.05 ) m , and 26.8 ( 2.2 ) kg/m(2 ) , respectively , in the placebo group . In the treatment group , Lp(a ) was significantly reduced at 3 and 6 months compared with baseline ( P Lp(a ) value in patients taking L-carnitine compared with those taking placebo . Between-group differences in other variables did not reach a level of significance at months 3 and 6 . No drug-related adverse events were reported or observed . CONCLUSION In this preliminary study , after 3 and 6 months , L-carnitine significantly lowered the plasma Lp(a ) level compared with placebo in selected hypercholesterolemic patients with newly diagnosed type 2 DM",
"OBJECTIVE The body fat reducing effect and reduction of risks for cardiovascular disease by a green tea extract ( GTE ) high in catechins was investigated in humans with typical lifestyles . RESEARCH METHODS AND PROCEDURES Japanese women and men with visceral fat-type obesity were recruited for the trial . After a 2-week diet run-in period , a 12-week double-blind parallel multicenter trial was performed , in which the subjects ingested green tea containing 583 mg of catechins ( catechin group ) or 96 mg of catechins ( control group ) per day . R and omization was stratified by gender and body mass index at each medical institution . The subjects were instructed to maintain their usual dietary intake and normal physical activity . RESULTS Data were analyzed using per- protocol sample s of 240 subjects ( catechin group ; n = 123 , control group ; n = 117 ) . Decreases in body weight , body mass index , body fat ratio , body fat mass , waist circumference , hip circumference , visceral fat area , and subcutaneous fat area were found to be greater in the catechin group than in the control group . A greater decrease in systolic blood pressure ( SBP ) was found in the catechin group compared with the control group for subjects whose initial SBP was 130 mm Hg or higher . Low-density lipoprotein ( LDL ) cholesterol was also decreased to a greater extent in the catechin group . No adverse effect was found . DISCUSSION The continuous ingestion of a GTE high in catechins led to a reduction in body fat , SBP , and LDL cholesterol , suggesting that the ingestion of such an extract contributes to a decrease in obesity and cardiovascular disease risks",
"(-)-Hydroxycitric acid ( HCA ) reportedly promotes weight loss , in part , through suppression of hunger . However , this mechanism has never been evaluated in humans in a controlled study . Eighty-nine mildly overweight females were prescribed 5020-kJ diets for 12 weeks as part of a double-blind , placebo-controlled parallel group study . Forty-two participants ingested 400-mg caplets of Garcinia cambogia 30 - 60 min prior to meals for a total dose of 2.4 g/day ( 1.2 g/day HCA ) . Forty-seven participants ingested matched placebos . Weight and body composition were assessed at baseline and every other week for 12 weeks . Food intake and appetitive variables were assessed at baseline and monthly for 12 weeks . Both groups lost body weight with the active group achieving a significantly greater reduction ( 3 . 7+/-3.1 kg versus 2.4+/-2.9 kg ) . No effects of the HCA were observed on appetitive variables . The active treatment group did not exhibit better dietary compliance or significant correlations between appetitive variables and energy intake or weight change . This study does not support a satiety effect of HCA",
"The association of television viewing and obesity in data collected during cycles II and III of the National Health Examination Survey was examined . Cycle II examined 6,965 children aged 6 to 11 years and cycle III examined 6,671 children aged 12 to 17 years . Included in the cycle III sample were 2,153 subjects previously studied during cycle II . These surveys , therefore , provided two cross-sectional sample s and one prospect i ve sample . In all three sample s , significant associations of the time spent watching television and the prevalence of obesity were observed . In 12- to 17-year-old adolescents , the prevalence of obesity increased by 2 % for each additional hour of television viewed . The associations persisted when controlled for prior obesity , region , season , population density , race , socioeconomic class , and a variety of other family variables . The consistency , temporal sequence , strength , and specificity of the associations suggest that television viewing may cause obesity in at least some children and adolescents . The potential effects of obesity on activity and the consumption of calorically dense foods are consistent with this hypothesis",
"The aim of this study was to assess the effects of 2 weeks of supplementation with (-)-hydroxycitrate ( HCA ) and HCA combined with medium-chain triglycerides ( MCT ) on satiety and energy intake . The experimental design consisted of three intervention periods of 2 weeks separated by washout periods of 2 or 6 weeks in a double-blind , placebo-controlled , r and omized , and crossover design . Seven male and 14 female normal to moderately obese subjects ( mean+/-S.D. ; age , 43+/-10 years ; body mass index , 27.6+/-2.0 kg/m(2 ) ) participated in this study . Subjects consumed three self-selected meals and four isoenergetic snacks daily with either no supplementation ( PLA ) , with 500 mg HCA ( HCA ) , or 500 mg HCA and 3 g MCT ( HCA+MCT ) . Each intervention period ended with a test day , consisting of a st and ardized breakfast and ad libitum a lunch and a dinner . There was a significant body weight ( BW ) loss during the 2 weeks of intervention ( PLA , -0.5+/-0.3 kg , P energy intake ( PLA , 8.1+/-0.3 MJ ; HCA , 8.3+/-0.3 MJ ; HCA+MCT , 8.4+/-0.3 MJ ) and the area under the curve of the appetite-related parameters during the test day were similar for all treatments . Two weeks of supplementation with HCA and HCA combined with MCT did not result in increased satiety or decreased energy intake compared to placebo in subjects losing BW",
"Summary Background Both hempseed oil ( HO ) and flaxseed oil ( FO ) contain high amounts of essential fatty acids ( FAs ) ; i.e. linoleic acid ( LA , 18:2n-6 ) and alpha-linolenic acid ( ALA , 18:3n-3 ) , but almost in opposite ratios . An excessive intake of one essential FA over the other may interfere with the metabolism of the other while the metabolisms of LA and ALA compete for the same enzymes . It is not known whether there is a difference between n-3 and n-6 FA of plant origin in the effects on serum lipid profile . Aim of the study To compare the effects of HO and FO on the profile of serum lipids and fasting concentrations of serum total and lipoprotein lipids , plasma glucose and insulin , and haemostatic factors in healthy humans . Methods Fourteen healthy volunteers participated in the study . A r and omised , double-blind crossover design was used . The volunteers consumed HO and FO ( 30 ml/day ) for 4 weeks each . The periods were separated by a 4-week washout period . Results The HO period result ed in higher proportions of both LA and gamma-linolenic acid in serum cholesteryl esters ( CE ) and triglycerides ( TG ) as compared with the FO period ( P ALA in both serum CE and TG as compared with the HO period ( P proportion of arachidonic acid in CE was lower after the FO period than after the HO period ( P total-to-HDL cholesterol ratio compared with the FO period ( P = 0.065 ) . No significant differences were found between the periods in measured values of fasting serum total or lipoprotein lipids , plasma glucose , insulin or hemostatic factors . Conclusions The effects of HO and FO on the profile of serum lipids differed significantly , with only minor effects on concentrations of fasting serum total or lipoprotein lipids , and no significant changes in concentrations of plasma glucose or insulin or in haemostatic factors",
"(-)-Hydroxycitrate ( HCA ) might promote weight maintenance by limiting the capacity for de novo lipogenesis ( DNL ) . It was investigated whether HCA may reduce DNL in humans during a persistent excess of energy intake as carbohydrate . In a double-blind , placebo-controlled , r and omized and cross-over design , 10 sedentary lean male subjects ( mean+/-S.D. , age : 24+/-5 years , BMI : 21.8+/-2.1 kg/m2 ) performed a glycogen depletion exercise test followed by a 3-day high-fat diet ( F/CHO/P , 60/25/15 % energy ; 100 % of energy expenditure ( EE ) ) and a 7-day high-CHO diet ( F/CHO/P , 85/10 % energy ; 130 - 175 % of EE ; overfeeding ) . During overfeeding , they ingested 3 x 500 mg/day HCA or placebo ( PLA ) . Each intervention ended with a 60-h stay in the respiration chamber ( days 9 and 10 ) . Body weight increased during overfeeding ( mean+/-S.E. , HCA : 2.9+/-0.2 kg , PLA : 2.8+/-0.2 kg ) . Respiratory quotient ( RQ ) was > 1.00 in all subjects indicating that DNL was present . On day 9 , 24-h EE was lower with HCA compared to PLA ( P resting metabolic rate and RQ during night were lower ( P Non-protein RQ , fat balance and net fat synthesis as DNL tended to be lower ( P HCA compared to PLA indicating lower DNL ; activity-induced EE was higher with HCA ( P HCA during overfeeding with carbohydrates may reduce DNL",
"Background : A combination of tyrosine , capsaicin , catechines and caffeine may stimulate the sympathetic nervous system and promote satiety , lipolysis and thermogenesis . In addition , dietary calcium may increase fecal fat excretion . Objective : To investigate the acute and subchronic effect of a supplement containing the above mentioned agents or placebo taken t.i.d on thermogenesis , body fat loss and fecal fat excretion . Design : In total , 80 overweight – obese subjects ( ( body mass index ) 31.2±2.5 kg/m2 , mean±s.d . ) underwent an initial 4-week hypocaloric diet ( 3.4 MJ/day ) . Those who lost>4 % body weight were instructed to consume a hypocaloric diet ( −1.3 MJ/day ) and were r and omized to receive either placebo ( n=23 ) or bioactive supplement ( n=57 ) in a double-blind , 8-week intervention . The thermogenic effect of the compound was tested at the first and last day of intervention , and blood pressure , heart rate , body weight and composition were assessed . Results : Weight loss during the induction phase was 6.8±1.9 kg . At the first exposure the thermogenic effect of the bioactive supplement exceeded that of placebo by 87.3 kJ/4 h ( 95%CI : 50.9;123.7 , P=0.005 ) and after 8 weeks this effect was sustained ( 85.5 kJ/4 h ( 47.6;123.4 ) , P=0.03 ) . Body fat mass decreased more in the supplement group by 0.9 kg ( 0.5 ; 1.3 ) compared with placebo ( P effect on fecal fat excretion , blood pressure or heart rate . Conclusion : The bioactive supplement increased 4-h thermogenesis by 90 kJ more than placebo , and the effect was maintained after 8 weeks and accompanied by a slight reduction in fat mass . These bioactive components may support weight maintenance after a hypocaloric diet",
"CONTEXT Lifestyle changes to lose weight can be difficult ; hence , both prescription and nonprescription diet products are appealing . Usage patterns of the nonprescription products phenylpropanolamine ( PPA ) and ephedra are of particular interest because of recent safety concerns . OBJECTIVE To estimate the prevalence of overall and specific nonprescription weight loss product use by demographic characteristics , prescription diet pill use , diabetic status , and lifestyle choices . DESIGN AND SETTING The Behavioral Risk Factor Surveillance System , a r and om-digit telephone survey conducted in 1998 in 5 states : Florida , Iowa , Michigan , West Virginia , and Wisconsin . PARTICIPANTS Population -based sample of 14 679 noninstitutionalized adults 18 years or older . MAIN OUTCOME MEASURES Prevalence of nonprescription weight loss product use in 1996 - 1998 . RESULTS Seven percent reported overall nonprescription weight loss product use , 2 % reported PPA use , and 1 % reported ephedra product use . Overall use was especially common among young obese women ( 28.4 % ) . Moreover , 7.9 % of normal-weight women reported use . There was no difference in nonprescription weight loss product use by daily consumption of fruits and vegetables ; however , more users than nonusers reported being physically active ( for those who exercised > /=30 minutes 5 times per week , odds ratio , 1.5 ; 95 % confidence interval , 1.2 - 2.0 ) . Among prescription weight loss product users , 33.8 % also took nonprescription product . CONCLUSIONS With increasing rates of obesity , nonprescription product use is likely to increase . Clinicians should know about their patients ' use of both prescription and nonprescription weight loss products "
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BACKGROUND Stroke affects 15 million people per year worldwide . Despite recent developments in acute stroke treatment , prevention remains very important . Stroke has a high rate of recurrence ; therefore secondary prevention is also important . Many clinical approaches to control risk factors have been proposed . One of these approaches is the prescription of beta-blockers that have effects beyond the reduction of blood pressure , which can reduce the recurrence of stroke . OBJECTIVES To evaluate the efficacy of beta-blockers for preventing stroke recurrence and for reducing death and major vascular events in people with a previous stroke or transient ischaemic attack ( TIA ) , and to determine their safety , particularly with regard to the development of diabetes mellitus . SEARCH METHODS We search ed the Cochrane Stroke Group Trials Register ( May 2014 ) , the Cochrane Central Register of Controlled Trials ( CENTRAL ) and the Cochrane Data base of Systematic Review s ( CDSR ) ( The Cochrane Library 2014 , Issue 5 ) , the Data base of Abstract s of Review s of Effects ( DARE ) ( May 2014 ) , MEDLINE ( 1966 to May 2014 ) , EMBASE ( 1980 to May 2014 ) , and Latin American and Caribbean Health Sciences Literature ( LILACS ) ( 1982 to May 2014 ) . We also search ed ongoing trials registers and reference lists . SELECTION CRITERIA R and omised controlled trials ( RCTs ) that included participants with previous stroke or TIA due to arterial thrombosis or embolism . The intervention was any beta-blocker versus control , or beta-blocker plus other treatment versus other treatment . DATA COLLECTION AND ANALYSIS Two review authors independently screened the trials identified , appraised quality , and extracted data . MAIN RESULTS We included two RCTs involving 2193 participants in the review . Both studies r and omised participants to either beta-blocker ( atenolol 5 mg ) or placebo and were of a high method ological quality . We noted no statistical differences among the groups in risks of fatal and non-fatal stroke ( risk ratio ( RR ) 0.94 , 95 % confidence interval ( CI ) 0.76 to 1.18 ) . For other outcomes analysed ( major vascular events , death from all causes , death from cardiovascular causes ) , we observed no significant differences between the groups . There were minor blood pressure reductions in the intervention group . Neither of the included studies reported the occurrence of diabetes among their outcomes or assessed quality of life . Adverse events were significantly more frequent in participants taking atenolol than in those given placebo , and were the most common reason given for discontinuing treatment ( RR 1.85 , 95 % CI 1.45 to 2.35 ) . AUTHORS ' CONCLUSIONS To date , no available evidence supports the routine use of beta-blockers for secondary prevention after stroke or TIA . More studies with larger sample s are needed
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"Although the benefits of antihypertensive treatment in \" young \" elderly ( under 70 years ) hypertensive patients are well established , the value of treatment in older patients ( 70 - 84 years ) is less clear . The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was a prospect i ve , r and omised , double-blind , intervention study set up to compare the effects of active antihypertensive therapy ( three beta-blockers and one diuretic ) and placebo on the frequency of fatal and non-fatal stroke and myocardial infa rct ion and other cardiovascular death in hypertensive Swedish men and women aged 70 - 84 years . We recruited 1627 patients at 116 health centres throughout Sweden , who were willing to participate , and who met the entry criteria of three separate recordings during a 1-month placebo run-in period of systolic blood pressure between 180 and 230 mm Hg with a diastolic pressure of at least 90 mm Hg , or a diastolic pressure between 105 and 120 mm Hg irrespective of the systolic pressure . The total duration of the study was 65 months and the average time in the study was 25 months . 812 patients were r and omly allocated active treatment and 815 placebo . The mean difference in supine blood pressure between the active treatment and placebo groups at the last follow-up before an endpoint , death , or study termination was 19.5/8.1 mm Hg . Compared with placebo , active treatment significantly reduced the number of primary endpoints ( 94 vs 58 ; p = 0.0031 ) and stroke morbidity and mortality ( 53 vs 29 ; p = 0.0081 ) . Although we did not set out to study an effect on total mortality , we also noted a significantly reduced number of deaths in the active treatment group ( 63 vs 36 ; p = 0.0079 ) . The benefits of treatment were discernible up to age 84 years . We conclude that antihypertensive treatment in hypertensive men and women aged 70 - 84 confers highly significant and clinical ly relevant reductions in cardiovascular morbidity and mortality as well as in total mortality",
"BACKGROUND AND PURPOSE Few community-based studies have examined the long-term risk of recurrent stroke after an acute first-ever stroke . This study aim ed to determine the absolute and relative risks of a first recurrent stroke over the first 5 years after a first-ever stroke and the predictors of such recurrence in a population -based series of people with first-ever stroke in Perth , Western Australia . METHODS Between February 1989 and August 1990 , all people with a suspected acute stroke or transient ischemic attack of the brain who were resident in a geographically defined region of Perth , Western Australia , with a population of 138 708 people , were registered prospect ively and assessed according to st and ardized diagnostic criteria . Patients were followed up prospect ively at 4 months , 12 months , and 5 years after the index event . RESULTS Three hundred seventy patients with a first-ever stroke were registered , of whom 351 survived > 2 days . Data were available for 98 % of the cohort at 5 years , by which time 199 patients ( 58 % ) had died and 52 ( 15 % ) had experienced a recurrent stroke , 12 ( 23 % ) of which were fatal within 28 days . The 5-year cumulative risk of first recurrent stroke was 22.5 % ( 95 % confidence limits [ CL ] , 16.8 % , 28.1 % ) . The risk of recurrent stroke was greatest in the first 6 months after stroke , at 8.8 % ( 95 % CL , 5.4 % , 12.1 % ) . After adjustment for age and sex , the prognostic factors for recurrent stroke were advanced , but not extreme , age ( 75 to 84 years ) ( hazard ratio [ HR ] , 2.6 ; 95 % CL , 1.1 , 6.2 ) , hemorrhagic index stroke ( HR , 2.1 ; 95 % CL , 0.98 , 4.4 ) , and diabetes mellitus ( HR , 2.1 ; 95 % CL , 0.95 , 4.4 ) . CONCLUSIONS Approximately 1 in 6 survivors ( 15 % ) of a first-ever stroke experience a recurrent stroke over the next 5 years , of which 25 % are fatal within 28 days . The pathological subtype of the recurrent stroke is the same as that of the index stroke in 88 % of cases . The predictors of first recurrent stroke in this study were advanced age , hemorrhagic index stroke , and diabetes mellitus , but numbers of recurrent events were modest . Because the risk of recurrent stroke is highest ( 8.8 % ) in the first 6 months after stroke , strategies for secondary prevention should be initiated as soon as possible after the index event",
"BACKGROUND Calcium antagonists are a first-line treatment for hypertension . The effectiveness of diltiazem , a non-dihydropyridine calcium antagonist , in reducing cardiovascular morbidity or mortality is unclear . We compared the effects of diltiazem with that of diuretics , beta-blockers , or both on cardiovascular morbidity and mortality in hypertensive patients . METHODS In a prospect i ve , r and omised , open , blinded endpoint study , we enrolled 10,881 patients , aged 50 - 74 years , at health centres in Norway and Sweden , who had diastolic blood pressure of 100 mm Hg or more . We r and omly assigned patients diltiazem , or diuretics , beta-blockers , or both . The combined primary endpoint was fatal and non-fatal stroke , myocardial infa rct ion , and other cardiovascular death . Analysis was done by intention to treat . FINDINGS Systolic and diastolic blood pressure were lowered effectively in the diltiazem and diuretic and beta-blocker groups ( reduction 20.3/18.7 vs 23.3/18.7 mm Hg ; difference in systolic reduction p Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 in the diuretic and beta-blocker group ( 6.4 vs 7.9 events per 1000 patient-years ; 0.80 [ 0.65 - 0.99 ] , p=0.04 ) and fatal and non-fatal myocardial infa rct ion in 183 and 157 patients ( 7.4 vs 6.3 events per 1000 patient-years ; 1.16 [ 0.94 - 1.44 ] , p=0.17 ) . INTERPRETATION Diltiazem was as effective as treatment based on diuretics , beta-blockers , or both in preventing the combined primary endpoint of all stroke , myocardial infa rct ion , and other cardiovascular death",
"To collect background data for a prospect i ve clinical trial of beta-blocking agents in the prevention of deaths after stroke , the long-term prognosis in 60 patients discharged from a stroke unit on beta-blocker therapy was compared with the outcome in 60 matched patients with stroke but without beta-blockers . Matching included sex , age , type of stroke , and presence or absence of hypertension and cardiac failure . Thirteen patients ( 22 % ) in the beta-blocker group died during a median followup of 41 months . Of the 60 patients not on beta-blockade at discharge , 21 ( 35 % ) died during a median followup of 36 months . By life-table technique and log-rank test , the relative risk for death was 0.60:1.00 ( p = 0.14 ) . During followup , 12 recurrent strokes were observed in patients on beta-blockers and 19 in patients without beta-blockers ( relative risk 0.57:1.00 ; p = 0.12 ) . It appeared that the reduction in mortality could only marginally be ascribed to fewer deaths from myocardial infa rct ion ; other causes of death were also less frequent in beta-blocker-treated patients . The results emphasize that supplementary information on the effect of beta-blocking agents on mortality after stroke is needed before a larger trial of beta-blocker therapy in patients with manifest cerebrovascular disease can be initiated",
"BACKGROUND Angiotensin-converting-enzyme ( ACE ) inhibitors have been used for more than a decade to treat high blood pressure , despite the lack of data from r and omised intervention trials to show that such treatment affects cardiovascular morbidity and mortality . The Captopril Prevention Project ( CAPPP ) is a r and omised intervention trial to compare the effects of ACE inhibition and conventional therapy on cardiovascular morbidity and mortality in patients with hypertension . METHODS CAPPP was a prospect i ve , r and omised , open trial with blinded endpoint evaluation . 10,985 patients were enrolled at 536 health centres in Sweden and Finl and . Patients aged 25 - 66 years with a measured diastolic blood pressure of 100 mm Hg or more on two occasions were r and omly assigned captopril or conventional antihypertensive treatment ( diuretics , beta-blockers ) . Analysis was by intention-to-treat . The primary endpoint was a composite of fatal and non-fatal myocardial infa rct ion , stroke , and other cardiovascular deaths . FINDINGS Of 5492 patients assigned captopril and 5493 assigned conventional therapy , 14 and 13 , respectively , were lost to follow-up . Primary endpoint events occurred in 363 patients in the captopril group ( 11.1 per 1000 patient-years ) and 335 in the conventional-treatment group ( 10.2 per 1000 patient-years ; relative risk 1.05 [ 95 % CI 0.90 - 1.22 ] , p=0 - 52 ) . Cardiovascular mortality was lower with captopril than with conventional treatment ( 76 vs 95 events ; relative risk 0.77 [ 0.57 - 1 - 04 ] , p=0.092 ) , the rate of fatal and non-fatal myocardial infa rct ion was similar ( 162 vs 161 ) , but fatal and non-fatal stroke was more common with captopril ( 189 vs 148 ; 1.25 [ 1 - 01 - 1 - 55 ] . p=0.044 ) . INTERPRETATION Captopril and conventional treatment did not differ in efficacy in preventing cardiovascular morbidity and mortality . The difference in stroke risk is probably due to the lower levels of blood pressure obtained initially in previously treated patients r and omised to conventional therapy",
"BACKGROUND Blood pressure reduction achieved with beta-blockers and diuretics is the best recorded intervention to date for prevention of cardiovascular morbidity and death in patients with hypertension . Left ventricular hypertrophy ( LVH ) is a strong independent indicator of risk of cardiovascular morbidity and death . We aim ed to establish whether selective blocking of angiotensin II improves LVH beyond reducing blood pressure and , consequently , reduces cardiovascular morbidity and death . METHODS We did a double-masked , r and omised , parallel-group trial in 9193 participants aged 55 - 80 years with essential hypertension ( sitting blood pressure 160 - 200/95 - 115 mm Hg ) and LVH ascertained by electrocardiography ( ECG ) . We assigned participants once daily losartan-based or atenolol-based antihypertensive treatment for at least 4 years and until 1040 patients had a primary cardiovascular event ( death , myocardial infa rct ion , or stroke ) . We used Cox regression analysis to compare regimens . FINDINGS Blood pressure fell by 30.2/16.6 ( SD 18.5/10.1 ) and 29.1/16.8 mm Hg ( 19.2/10.1 ) in the losartan and atenolol groups , respectively . The primary composite endpoint occurred in 508 losartan ( 23.8 per 1000 patient-years ) and 588 atenolol patients ( 27.9 per 1000 patient-years ; relative risk 0.87 , 95 % CI 0.77 - 0.98 , p=0.021 ) . 204 losartan and 234 atenolol patients died from cardiovascular disease ( 0.89 , 0.73 - 1.07 , p=0.206 ) ; 232 and 309 , respectively , had fatal or non-fatal stroke ( 0.75 , 0.63 - 0.89 , p=0.001 ) ; and myocardial infa rct ion ( non-fatal and fatal ) occurred in 198 and 188 , respectively ( 1.07 , 0.88 - 1.31 , p=0.491 ) . New-onset diabetes was less frequent with losartan . Interpretation Losartan prevents more cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated . Losartan seems to confer benefits beyond reduction in blood pressure",
"BACKGROUND The efficacy of new antihypertensive drugs has been question ed . We compared the effects of conventional and newer antihypertensive drugs on cardiovascular mortality and morbidity in elderly patients . METHODS We did a prospect i ve , r and omised trial in 6614 patients aged 70 - 84 years with hypertension ( blood pressure > or = 180 mm Hg systolic , > or = 105 mm Hg diastolic , or both ) . Patients were r and omly assigned conventional antihypertensive drugs ( atenolol 50 mg , metoprolol 100 mg , pindolol 5 mg , or hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily ) or newer drugs ( enalapril 10 mg or lisinopril 10 mg , or felodipine 2.5 mg or isradipine 2 - 5 mg daily ) . We assessed fatal stroke , fatal myocardial infa rct ion , and other fatal cardiovascular disease . Analysis was by intention to treat . FINDINGS Blood pressure was decreased similarly in all treatment groups . The primary combined endpoint of fatal stroke , fatal myocardial infa rct ion , and other fatal cardiovascular disease occurred in 221 of 2213 patients in the conventional drugs group ( 19.8 events per 1000 patient-years ) and in 438 of 4401 in the newer drugs group ( 19.8 per 1000 ; relative risk 0.99 [ 95 % CI 0.84 - 1.16 ] , p=0.89 ) . The combined endpoint of fatal and non-fatal stroke , fatal and non-fatal myocardial infa rct ion , and other cardiovascular mortality occurred in 460 patients taking conventional drugs and in 887 taking newer drugs ( 0.96 [ 0.86 - 1.08 ] , p=0.49 ) . INTERPRETATION Old and new antihypertensive drugs were similar in prevention of cardiovascular mortality or major events . Decrease in blood pressure was of major importance for the prevention of cardiovascular events",
"BACKGROUND The Valsartan Antihypertensive Long-term Use Evaluation ( VALUE ) trial was design ed to test the hypothesis that for the same blood-pressure control , valsartan would reduce cardiac morbidity and mortality more than amlodipine in hypertensive patients at high cardiovascular risk . METHODS 15?245 patients , aged 50 years or older with treated or untreated hypertension and high risk of cardiac events participated in a r and omised , double-blind , parallel-group comparison of therapy based on valsartan or amlodipine . Duration of treatment was event-driven and the trial lasted until at least 1450 patients had reached a primary endpoint , defined as a composite of cardiac mortality and morbidity . Patients from 31 countries were followed up for a mean of 4.2 years . FINDINGS Blood pressure was reduced by both treatments , but the effects of the amlodipine-based regimen were more pronounced , especially in the early period ( blood pressure 4.0/2.1 mm Hg lower in amlodipine than valsartan group after 1 month ; 1.5/1.3 mm Hg after 1 year ; p valsartan group ( 10.6 % , 25.5 per 1000 patient-years ) and 789 in the amlodipine group ( 10.4 % , 24.7 per 1000 patient-years ; hazard ratio 1.04 , 95 % CI 0.94 - 1.15 , p=0.49 ) . INTERPRETATION The main outcome of cardiac disease did not differ between the treatment groups . Unequal reductions in blood pressure might account for differences between the groups in cause-specific outcomes . The findings emphasise the importance of prompt blood-pressure control in hypertensive patients at high cardiovascular risk",
"BACKGROUND Recent data suggest that atenolol may be inferior to other antihypertensive drugs in reducing cardiovascular risk in older individuals with hypertension , despite lowering peripheral blood pressure ( BP ) . We hypothesized that that atenolol fails to reduce central BP as much as other agents . The aim of the present study was to compare the hemodynamic effects of atenolol and eprosartan in a double-blind , r and omized , cross-over study . METHODS After a 2-week placebo run-in , 21 subjects with never-treated hypertension underwent 6 weeks of therapy with atenolol ( 50 mg ) and eprosartan ( 600 mg ) . Central BP and augmentation index were assessed using pulse wave analysis , and aortic pulse wave velocity was measured , at baseline and at the end of each treatment . RESULTS Both drugs reduced peripheral BP to the same degree . However , there was a significantly greater reduction in central systolic BP with eprosartan ( means + /- SEM : 16 + /- 3 v 11 + /- 2 mm Hg ; P = .03 ) . Despite identical reductions in mean pressure , atenolol reduced aortic pulse wave velocity more than eprosartan ( 0.8 + /- 0.1 v 0.5 + /- 0.1 m/sec ; P = .005 ) . Conversely , augmentation index and N-terminal pro-brain natiuretic peptide levels were reduced significantly after eprosartan ( 6 % + /- 2 % and 11 + /- 5 pg/mL , respectively ) but were increased after atenolol ( 7 % + /- 2 % and 67 + /- 24 pg/mL , respectively ) . CONCLUSIONS These data indicate that despite similar effects on peripheral BP and a greater effect on aortic stiffness , atenolol had less impact on central systolic BP than eprosartan because it failed to reduce wave reflection . This provides one potential explanation for the failure of atenolol to improve outcome in older patients with essential hypertension",
"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",
"BACKGROUND The apparent shortfall in prevention of coronary heart disease ( CHD ) noted in early hypertension trials has been attributed to disadvantages of the diuretics and beta blockers used . For a given reduction in blood pressure , some suggested that newer agents would confer advantages over diuretics and beta blockers . Our aim , therefore , was to compare the effect on non-fatal myocardial infa rct ion and fatal CHD of combinations of atenolol with a thiazide versus amlodipine with perindopril . METHODS We did a multicentre , prospect i ve , r and omised controlled trial in 19 257 patients with hypertension who were aged 40 - 79 years and had at least three other cardiovascular risk factors . Patients were assigned either amlodipine 5 - 10 mg adding perindopril 4 - 8 mg as required ( amlodipine-based regimen ; n=9639 ) or atenolol 50 - 100 mg adding bendroflumethiazide 1.25 - 2.5 mg and potassium as required ( atenolol-based regimen ; n=9618 ) . Our primary endpoint was non-fatal myocardial infa rct ion ( including silent myocardial infa rct ion ) and fatal CHD . Analysis was by intention to treat . FINDINGS The study was stopped prematurely after 5.5 years ' median follow-up and accumulated in total 106 153 patient-years of observation . Though not significant , compared with the atenolol-based regimen , fewer individuals on the amlodipine-based regimen had a primary endpoint ( 429 vs 474 ; unadjusted HR 0.90 , 95 % CI 0.79 - 1.02 , p=0.1052 ) , fatal and non-fatal stroke ( 327 vs 422 ; 0.77 , 0.66 - 0.89 , p=0.0003 ) , total cardiovascular events and procedures ( 1362 vs 1602 ; 0.84 , 0.78 - 0.90 , p all-cause mortality ( 738 vs 820 ; 0.89 , 0.81 - 0.99 , p=0.025 ) . The incidence of developing diabetes was less on the amlodipine-based regimen ( 567 vs 799 ; 0.70 , 0.63 - 0.78 , p amlodipine-based regimen prevented more major cardiovascular events and induced less diabetes than the atenolol-based regimen . On the basis of previous trial evidence , these effects might not be entirely explained by better control of blood pressure , and this issue is addressed in the accompanying article . Nevertheless , the results have implication s with respect to optimum combinations of antihypertensive agents ",
"A r and omised trial of the treatment of hypertension in 884 patients aged 60 to 79 years at the onset showed a reduction of 18/11 mm Hg in blood pressure over a mean follow up period of 4.4 years . The principal antihypertensive agents were atenolol and bendrofluazide . There was a reduction in the rate of fatal stroke in the treatment group to 30 % of that in the control group ( 95 % confidence interval 11 - 84 % , p less than 0.025 ) . The rate of all strokes ( fatal and non-fatal ) in the treatment group was 58 % of that in the control group ( 95 % confidence interval 35 - 96 % , p less than 0.03 ) . The incidence of myocardial infa rct ion and total mortality was unaffected by treatment . Question naires completed by the patients and their relatives failed to identify any differences in symptoms that were likely to be due to treatment",
"Background and Purpose : & bgr;‐Blockers prevent vascular events in patients after myocardial infa rct ion and lower blood pressure , the main risk factor for stroke . Hence , we assessed the effects of atenolol on the occurrence of death from vascular causes , stroke , or myocardial infa rct ion and on blood pressure in patients after a transient ischemic attack or nondisabling ischemic stroke . Methods : In a double‐blind , placebo‐controlled r and omized clinical trial we studied the occurrence of the outcome event death from vascular causes , nonfatal stroke , or nonfatal myocardial infa rct ion and the outcome event fatal or nonfatal stroke as well as blood pressure on follow‐up . A total of 1,473 aspirin‐treated patients with transient ischemic attack or nondisabling ischemic stroke were r and omized to 50 mg atenolol daily or placebo . The mean follow‐up was 2.6 years . Results : Patients on atenolol had a risk of 97/732 ( 13.3 % ) for the combined outcome event versus a risk of 95/741 ( 12.8 % ) for those on placebo ( adjusted hazard ratio , 1.00 ; 95 % confidence interval , 0.76‐1.33 ) . The adjusted hazard ratio for fatal or nonfatal stroke was 0.82 ( 95 % confidence interval , 0.57‐1.19 ) . More patients on & bgr;‐blocker ( 153 ) reported adverse effects than on placebo ( 103 ) . At the first follow‐up visit after r and omization ( median at 4 months ) systolic blood pressure in the atenolol group had dropped by 8.0 mm Hg compared with 2.2 mm Hg in the placebo group ( difference , 5.8 mm Hg ; 95 % confidence interval , 2.9‐8.6 mm Hg ) . For diastolic blood pressure this difference was 2.9 mm Hg ( 95 % confidence interval , 1.5‐4.4 mm Hg ) . Conclusions : Our data neither confirm nor rule out that atenolol prevents important vascular events in patients after transient ischemic attack or nondisabling ischemic stroke , given the modest effect on blood pressure , the restrictions in patient selection , and the limited number of patient‐years . ( Stroke 1993;24:543‐548",
"To evaluate the effects of antihypertensive agents on the circadian blood pressure ( BP ) of patients with previous brain infa rct ion , the ambulatory BP was measured non-invasively for 24 h before and after administration of antihypertensive agents . One hundred milligrams of acebutolol twice daily ( n = 15 ) is effective in lowering the BP during the daytime , but has little effect during the night and the morning . Twenty milligrams of slow-release nifedipine twice daily ( n = 14 ) produced a consistent reduction in the BP over the entire 24-h period and effectively blunted the rise in BP in the morning . Captopril ( 12.5 mg ) twice daily ( n = 15 ) produced a mild reduction in BP with little change in the circadian pattern . The slow-release nifedipine group had the greatest decrease in mean systolic and diastolic BP . The heart rate significantly increased after administration of slow-release nifedipine and decreased after administration of acebutolol . To reduce stroke recurrence , we should consider the effects of antihypertensive agents on circadian BP in hypertensive patients with previous brain infa rct ion",
"Men aged 40 - 64 years with mild to moderate hypertension [ diastolic blood pressure ( DBP ) 100 - 130 mmHg ] were r and omized to treatment with a diuretic ( n = 3272 ) or a beta-blocker ( n = 3297 ) , with additional drugs if necessary , to determine whether a beta-blocker based treatment differs from thiazide diuretic based treatment with regard to the prevention of coronary heart disease ( CHD ) events and death . Patients with previous CHD , stroke or other serious diseases , or with contraindications to diuretics or beta-blockers were excluded . If normotension ( DBP less than 95 mmHg ) was not achieved by monotherapy , other antihypertensive drugs were added , but the two basic drugs were not crossed over . Patients were assessed at 6-monthly intervals . The mean follow-up for end-points was 45.1 months . Blood pressure ( BP ) side effects and end-points were recorded in a st and ardized manner . Entry characteristics and the BP reduction achieved were very similar in both treatment groups . All analyses were made on an intention-to-treat basis . The incidence of CHD did not differ between the two treatment groups . The incidence of fatal stroke tended to be lower in the beta-blocker treated group than in the diuretic treated group . Total mortality and the total number of end-points were similar in both groups . The percentage of patients withdrawn due to side effects was similar , whereas the number of reported symptoms , according to a question naire , was higher for patients on beta-blockers . The incidence of diabetes did not differ between the two groups . Subgroup analyses did not detect a difference in the effect of beta-blockers compared with diuretics in smokers as opposed to non-smokers , and beta-blockers also had the same effects as diuretics in the quartile with the highest predicted risk for CHD . Beta-blockers and thiazide diuretics were approximately equally well tolerated . The two drugs had a similar BP reducing effect although additional drugs had to be given more often in the diuretic group . Antihypertensive treatment based on a beta-blocker or on a thiazide diuretic could not be shown to affect the prevention of hypertensive complications , including CHD , to a different extent"
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41179114-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND When treating elevated blood pressure , doctors need to know what blood pressure ( BP ) target they should try to achieve . The st and ard of clinical practice for some time has been st and ard BP targets ( controlled trials comparing patients r and omized to lower or to st and ard BP targets and providing data on any of the primary outcomes below . DATA COLLECTION AND ANALYSIS Two review ers ( JAA , MIP ) independently assessed the included trials and data entry . Primary outcomes were total mortality ; total serious adverse events ; total cardiovascular events ; myocardial infa rct ion , stroke , congestive heart failure and end stage renal disease . Secondary outcomes were achieved mean systolic and diastolic BP and withdrawals due to adverse effects . MAIN RESULTS No trials comparing different systolic BP targets were found . Seven trials ( 22,089 subjects ) comparing different diastolic BP targets were included . Despite a -4/-3 mmHg greater achieved reduction in systolic/diastolic BP , p total mortality ( RR 0.92 , 95 % CI 0.86 - 1.15 ) , myocardial infa rct ion ( RR 0.90 , 95 % CI 0.74 - 1.09 ) , stroke ( RR 0.99 , 95 % CI 0.79 - 1.25 ) , congestive heart failure ( RR 0.88 , 95 % CI 0.59 - 1.32 ) , major cardiovascular events ( RR 0.94 , 95 % CI 0.83 - 1.07 ) , or end-stage renal disease ( RR 1.01 , 95 % CI 0.81 - 1.27 ) . The net health effect of lower targets can not be fully assessed due to lack of information regarding all total serious adverse events and withdrawals due to adverse effects in 6 of 7 trials . A sensitivity analysis in diabetic patients and in patients with chronic renal disease also did not show a reduction in any of the mortality and morbidity outcomes with lower targets as compared to st and ard targets . AUTHORS ' CONCLUSIONS Treating patients to lower than st and ard BP targets , , does not reduce mortality or morbidity . Because guidelines are recommending even lower targets for diabetes mellitus and chronic renal disease , we are currently conducting systematic review s in those groups of patients
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"CONTEXT Individuals with diabetes are at increased risk for cardiovascular disease ( CVD ) , but more aggressive targets for risk factor control have not been tested . OBJECTIVE To compare progression of sub clinical atherosclerosis in adults with type 2 diabetes treated to reach aggressive targets of low-density lipoprotein cholesterol ( LDL-C ) of 70 mg/dL or lower and systolic blood pressure ( SBP ) of 115 mm Hg or lower vs st and ard targets of LDL-C of 100 mg/dL or lower and SBP of 130 mm Hg or lower . DESIGN , SETTING , AND PARTICIPANTS A r and omized , open-label , blinded-to-end point , 3-year trial from April 2003-July 2007 at 4 clinical centers in Oklahoma , Arizona , and South Dakota . Participants were 499 American Indian men and women aged 40 years or older with type 2 diabetes and no prior CVD events . INTERVENTIONS Participants were r and omized to aggressive ( n=252 ) vs st and ard ( n=247 ) treatment groups with stepped treatment algorithms defined for both . MAIN OUTCOME MEASURES Primary end point was progression of atherosclerosis measured by common carotid artery intimal medial thickness ( IMT ) . Secondary end points were other carotid and cardiac ultrasonographic measures and clinical events . RESULTS Mean target LDL-C and SBP levels for both groups were reached and maintained . Mean ( 95 % confidence interval ) levels for LDL-C in the last 12 months were 72 ( 69 - 75 ) and 104 ( 101 - 106 ) mg/dL and SBP levels were 117 ( 115 - 118 ) and 129 ( 128 - 130 ) mm Hg in the aggressive vs st and ard groups , respectively . Compared with baseline , IMT regressed in the aggressive group and progressed in the st and ard group ( -0.012 mm vs 0.038 mm ; P carotid arterial cross-sectional area also regressed ( -0.02 mm(2 ) vs 1.05 mm(2 ) ; P left ventricular mass index ( -2.4 g/m(2.7 ) vs -1.2 g/m(2.7 ) ; P = .03 ) in the aggressive group . Rates of adverse events ( 38.5 % and 26.7 % ; P = .005 ) and serious adverse events ( n = 4 vs 1 ; P = .18 ) related to blood pressure medications were higher in the aggressive group . Clinical CVD events ( 1.6/100 and 1.5/100 person-years ; P = .87 ) did not differ significantly between groups . CONCLUSIONS Reducing LDL-C and SBP to lower targets result ed in regression of carotid IMT and greater decrease in left ventricular mass in individuals with type 2 diabetes . Clinical events were lower than expected and did not differ significantly between groups . Further follow-up is needed to determine whether these improvements will result in lower long-term CVD event rates and costs and favorable risk-benefit outcomes . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00047424",
"BACKGROUND In patients who have vascular disease or high-risk diabetes without heart failure , angiotensin-converting-enzyme ( ACE ) inhibitors reduce mortality and morbidity from cardiovascular causes , but the role of angiotensin-receptor blockers ( ARBs ) in such patients is unknown . We compared the ACE inhibitor ramipril , the ARB telmisartan , and the combination of the two drugs in patients with vascular disease or high-risk diabetes . METHODS After a 3-week , single-blind run-in period , patients underwent double-blind r and omization , with 8576 assigned to receive 10 mg of ramipril per day , 8542 assigned to receive 80 mg of telmisartan per day , and 8502 assigned to receive both drugs ( combination therapy ) . The primary composite outcome was death from cardiovascular causes , myocardial infa rct ion , stroke , or hospitalization for heart failure . RESULTS Mean blood pressure was lower in both the telmisartan group ( a 0.9/0.6 mm Hg greater reduction ) and the combination-therapy group ( a 2.4/1.4 mm Hg greater reduction ) than in the ramipril group . At a median follow-up of 56 months , the primary outcome had occurred in 1412 patients in the ramipril group ( 16.5 % ) , as compared with 1423 patients in the telmisartan group ( 16.7 % ; relative risk , 1.01 ; 95 % confidence interval [ CI ] , 0.94 to 1.09 ) . As compared with the ramipril group , the telmisartan group had lower rates of cough ( 1.1 % vs. 4.2 % , P angioedema ( 0.1 % vs. 0.3 % , P=0.01 ) and a higher rate of hypotensive symptoms ( 2.6 % vs. 1.7 % , P rate of syncope was the same in the two groups ( 0.2 % ) . In the combination-therapy group , the primary outcome occurred in 1386 patients ( 16.3 % ; relative risk , 0.99 ; 95 % CI , 0.92 to 1.07 ) ; as compared with the ramipril group , there was an increased risk of hypotensive symptoms ( 4.8 % vs. 1.7 % , P syncope ( 0.3 % vs. 0.2 % , P=0.03 ) , and renal dysfunction ( 13.5 % vs. 10.2 % , P CONCLUSIONS Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema . The combination of the two drugs was associated with more adverse events without an increase in benefit . ( Clinical Trials.gov number , NCT00153101 [ Clinical Trials.gov ] . )",
"The Hypertension Optimal Treatment ( HOT ) Study is a prospect i ve , r and omized , multicenter study which will be conducted in some 20 countries world-wide . Two major issues will be investigated : i ) What is the optimal target diastolic blood pressure during antihypertensive treatment with regard to the reduction in cardiovascular morbidity and mortality ? In order to address this question patients will be r and omized to three different therapeutic goals : a diastolic blood pressure acetylsalicylic acid ( ASA , aspirin ) 75 mg o.d . in comparison with placebo on cardiovascular morbidity and mortality . The first aim will be investigated in accordance with the PROBE design ( Prospect i ve R and omized Open Blinded Endpoint evaluation ) , whereas the evaluation of aspirin versus placebo will be conducted under double blind conditions . It is estimated that 1,100 clinical events will be needed in order to answer the question regarding the relationship between target diastolic blood pressure and major cardiovascular events . The collection of these events will require the enrollment of at least 18,000 hypertensive men and women aged 50 - 80 years to be followed for 2.5 years ( about 40,000 patient years ) . All patients will be given felodipine 5 mg o.d . as basic antihypertensive treatment with the addition of a beta-blocker or an ACE-inhibitor in a second step , with further predetermined increments in dosage as required in order to obtain the r and omized therapeutic goal",
"The objective of this study was to investigate the relationship between hypertension and risk of stroke in the elderly . The study was performed within the framework of the Rotterdam Study , a prospect i ve population -based cohort study . The risk of first-ever stroke was associated with hypertension ( relative risk , 1.6 ; 95 % CI , 1.2 to 2.0 ) and with isolated systolic hypertension ( relative risk , 1.7 ; 95 % CI , 1.1 to 2.6 ) . We found a continuous increase in stroke incidence with increasing blood pressure in nontreated subjects . In treated subjects , we found a J-shaped relation between blood pressure and the risk of stroke . In the lowest category of diastolic blood pressure , the increase of stroke risk was statistically significant compared with the reference category . Hypertension and isolated systolic hypertension are strong risk factors for stroke in the elderly . The increased stroke risk in the lowest stratum of blood pressure in treated hypertensive patients may indicate that the therapeutic goal of \" the lower the better \" is not the optimal strategy in the elderly",
"OBJECTIVES The study evaluated the risk of cardiovascular mortality according to combined spontaneous ( non-treatment-related ) changes in both systolic and diastolic blood pressure ( BP ) . BACKGROUND Long-term longitudinal changes in blood pressure may be a more accurate determinant of cardiovascular risk since changes in systolic or diastolic blood pressure over a period of time reflect the evolution of arterial and arteriolar alterations . METHODS Two independent French male cohorts were studied : the IPC cohort ( Investigations Préventives et Cliniques ) composed of 15,561 men aged 20 to 82 years who had had two visits spaced four to 10 years apart , and the Paris Prospect i ve Study composed of 6,246 men aged 42 to 53 years , examined annually for a period of four years . None of the subjects were taking antihypertensive medication . Annual changes in BP were estimated , and subjects were divided into groups according to the increase , lack of change , or decrease of systolic or diastolic BP . Nine groups were formed by combining the changes of systolic and diastolic BP . Cardiovascular mortality was assessed for a mean period of 13.5 years for the IPC Study and 17 years for the Paris Prospect i ve Study . RESULTS In both cohorts , after adjustment for age and major risk factors , the group with an increase in systolic and a decrease in diastolic BP presented the highest relative risk of cardiovascular mortality compared to the group with no changes in either systolic or diastolic BP ( relative risk : 2.07 [ 1.05 to 4.06 ] in the IPC Study and 2.16 [ 1.16 to 4.01 ] in the Paris Prospect i ve Study ) . CONCLUSIONS Assessment of spontaneous changes of BP over a long period of time can contribute to the evaluation of cardiovascular risk . Subjects whose systolic BP increased while their diastolic BP decreased had the highest cardiovascular risk independently of absolute values of BP or other risk factors",
"OBJECTIVE The Appropriate Blood Pressure Control in Diabetes ( ABCD ) Trial is a prospect i ve r and omized blinded clinical trial that compares the effects of intensive versus moderate blood pressure control on the incidence and progression of type 2 diabetic complications . The current article discusses the results of 5.3 years of follow-up of 470 patients with hypertension and evaluates the effects of intensive and moderate blood pressure therapy using nisoldipine versus enalapril as the initial antihypertensive medication for nephropathy , retinopathy , and neuropathy . RESEARCH DESIGN AND METHODS The 470 hypertensive subjects , defined as having a baseline diastolic blood pressure of > or = 90 mmHg , were r and omized to intensive blood pressure control ( diastolic blood pressure goal of 75 mmHg ) versus moderate blood pressure control ( diastolic blood pressure goal of 80 - 89 mmHg ) . RESULTS The mean blood pressure achieved was 132/78 mmHg in the intensive group and 138/86 mmHg in the moderate control group . During the 5-year follow-up period , no difference was observed between intensive versus moderate blood pressure control and those r and omized to nisoldipine versus enalapril with regard to the change in creatinine clearance . After the first year of antihypertensive treatment , creatinine clearance stabilized in both the intensive and moderate blood pressure control groups in those patients with baseline normo- or microalbuminuria . In contrast , patients starting with overt albuminuria demonstrated a steady decline in creatinine clearance of 5 - 6 ml.min-1.1.73 m-2 per year throughout the follow-up period whether they were on intensive or moderate therapy . There was also no difference between the interventions with regard to individuals progressing from normoalbuminuria to microalbuminuria ( 25 % intensive therapy vs. 18 % moderate therapy , P = 0.20 ) or microalbuminuria to overt albuminuria ( 16 % intensive therapy vs. 23 % moderate therapy , P = 0.28 ) . Intensive therapy demonstrated a lower overall incidence of deaths , 5.5 vs. 10.7 % , P = 0.037 . Over a 5-year follow-up period , there was no difference between the intensive and moderate groups with regard to the progression of diabetic retinopathy and neuropathy . In addition , the use of nisoldipine versus enalapril had no differential effect on diabetic retinopathy and neuropathy . CONCLUSIONS Blood pressure control of 138/86 or 132/78 mmHg with either nisoldipine or enalapril as the initial antihypertensive medication appeared to stabilize renal function in hypertensive type 2 diabetic patients without overt albuminuria over a 5-year period . The more intensive blood pressure control decreased all-cause mortality",
"CONTEXT Hypertension is a leading cause of end-stage renal disease ( ESRD ) in the United States , with no known treatment to prevent progressive declines leading to ESRD . OBJECTIVE To compare the effects of 2 levels of blood pressure ( BP ) control and 3 antihypertensive drug classes on glomerular filtration rate ( GFR ) decline in hypertension . DESIGN R and omized 3 x 2 factorial trial with enrollment from February 1995 to September 1998 . SETTING AND PARTICIPANTS A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease ( GFR , 20 - 65 mL/min per 1.73 m(2 ) ) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years . INTERVENTIONS Participants were r and omly assigned to 1 of 2 mean arterial pressure goals , 102 to 107 mm Hg ( usual ; n = 554 ) or 92 mm Hg or less ( lower ; n = 540 ) , and to initial treatment with either a beta-blocker ( metoprolol 50 - 200 mg/d ; n = 441 ) , an angiotensin-converting enzyme inhibitor ( ramipril 2.5 - 10 mg/d ; n = 436 ) or a dihydropyridine calcium channel blocker , ( amlodipine 5 - 10 mg/d ; n = 217 ) . Open-label agents were added to achieve the assigned BP goals . MAIN OUTCOME MEASURES Rate of change in GFR ( GFR slope ) ; clinical composite outcome of reduction in GFR by 50 % or more ( or > or = 25 mL/min per 1.73 m2 ) from baseline , ESRD , or death . Three primary treatment comparisons were specified : lower vs usual BP goal ; ramipril vs metoprolol ; and amlodipine vs metoprolol . RESULTS Achieved BP averaged ( SD ) 128/78 ( 12/8 ) mm Hg in the lower BP group and 141/85 ( 12/7 ) mm Hg in the usual BP group . The mean ( SE ) GFR slope from baseline through 4 years did not differ significantly between the lower BP group ( -2.21 [ 0.17 ] mL/min per 1.73 m2 per year ) and the usual BP group ( -1.95 [ 0.17 ] mL/min per 1.73 m2 per year ; P = .24 ) , and the lower BP goal did not significantly reduce the rate of the clinical composite outcome ( risk reduction for lower BP group = 2 % ; 95 % confidence interval [ CI ] , -22 % to 21 % ; P = .85 ) . None of the drug group comparisons showed consistent significant differences in the GFR slope . However , compared with the metoprolol and amlodipine groups , the ramipril group manifested risk reductions in the clinical composite outcome of 22 % ( 95 % CI , 1%-38 % ; P = .04 ) and 38 % ( 95 % CI , 14%-56 % ; P = .004 ) , respectively . There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups . CONCLUSIONS No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal . Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline",
"Background — Bias in studies of preventive medications can occur when healthier patients are more likely to initiate and adhere to therapy than less healthy patients . We sought evidence of this bias by examining associations between statin exposure and various outcomes that should not be causally affected by statin exposure , such as workplace and motor vehicle accidents . Methods and Results — We conducted a prospect i ve cohort study of statin patients using data from British Columbia , Canada , a multiethnic society with a population of 4.3 million people . Study subjects were 141 086 patients who initiated statins for primary prevention . We examined the association between adherence and multiple outcomes such as accidents and screening procedures using multivariable-adjusted Cox proportional hazards models . The study population was 49 % female and had an average age of 61 years . The results from our multivariable-adjusted models showed that more adherent patients were less likely to have accidents than less adherent patients . This effect was greatest for motor vehicle accidents ( hazard ratio , 0.75 ; 95 % confidence interval , 0.72 to 0.79 ) and workplace accidents ( hazard ratio , 0.77 ; 95 % confidence interval , 0.74 to 0.81 ) . More adherent patients had a greater likelihood of using screening services ( hazard ratio , 1.17 ; 95 % confidence interval , 1.15 to 1.20 ) and a lower likelihood of developing other diseases likely to be unrelated to a biological affect of a statin ( hazard ratio , 0.87 ; 95 % confidence interval , 0.86 to 0.89 ) . Conclusions — Our study contributes compelling evidence that patients who adhere to statins are systematic ally more health seeking than comparable patients who do not remain adherent . Caution is warranted when interpreting analyses that attribute surprising protective effects to preventive medications",
"Summary We report the efficacy of therapy over 5 years follow-up in 758 non-insulin-dependent diabetic patients in a prospect i ve , r and omised controlled study of therapy of mild hypertension . Patients were recruited who on antihypertensive therapy had systolic blood pressure over 150 mmHg or diastolic over 85 mmHg , or if not on therapy had systolic blood pressure over 160 mmHg or diastolic over 90 mmHg . Their mean blood pressure at entry to the study was 160/94 mmHg at a mean age of 57 years . They were allocated to tight control ( aim ing for systolic less tight control ( aim ing for systolic primary therapy either with a beta blocker ( atenolol ) or with an antiotensin converting enzyme inhibitor ( captopril ) , with addition of other agents as required . Over 5 years , the mean blood pressure in the tight control group was significantly lower ( 143/82 vs 154/88 mmHg , p atenolol or captopril . The proportion of patients requiring three or more antihypertensive therapies to maintain tight control in those allocated to atenolol or captopril increased from 16 and 15 % , respectively at 2 years to 25 and 26 % , respectively at 5 years , whereas in the less tight control group at 2 and 5 years only 5 and 7 % , respectively required three or more therapies . There was no difference in the incidence of side effects or hypoglycaemic episodes between those allocated to atenolol or captopril , but those allocated to atenolol increased their body weight by a mean of 2.3 kg compared with 0.5 kg in those allocated to captopril ( p atenolol was also associated with small increases in triglyceride , and decreases in LDL and HDL cholesterol , which are of uncertain clinical relevance . The study is continuing to determine whether the improved blood pressure control , which was obtained , will be beneficial in maintaining the health of patients by decreasing the incidence of major clinical complications , principally myocardial infa rct ion and strokes , and microvascular complications , such as severe retinopathy requiring photocoagulation and deterioration of renal function . [ Diabetologia ( 1996 ) 39 : 1554–1561",
"The Action to Control Cardiovascular Disease in Diabetes ( ACCORD ) blood pressure trial is an unmasked , open-label , r and omized trial with a sample size of 4,733 participants . This report describes the rationale , design , and methods of the blood pressure interventions in ACCORD . Participants eligible for the blood pressure trial are r and omized to 1 of 2 groups with different treatment goals : systolic blood pressure The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease ( CVD ) event , specifically nonfatal myocardial infa rct ion or stroke , or cardiovascular death during a follow-up period ranging from 4 - 8 years . The ACCORD blood pressure trial should provide the first definitive clinical trial data on the possible benefit of treating to a more aggressive systolic blood pressure goal in reducing CVD events in patients with diabetes mellitus",
"The Modification of Diet in Renal Disease Study showed a beneficial effect of a lower-than-usual blood pressure ( BP ) goal on the progression of renal disease in patients with proteinuria . The purpose of the present analyses was to examine the achieved BP , baseline characteristics that helped or hindered achievement of the BP goals , and safety of the BP interventions . Five hundred eighty-five patients with baseline glomerular filtration rate between 13 and 55 mL/min per 1.73 m2 ( 0.22 to 0.92 mL/s per 1.73 m2 ) were r and omly assigned to either a usual or low BP goal ( mean arterial pressure Few patients had a history of cardiovascular disease . All antihypertensive agents were permitted , but angiotensin-converting enzyme inhibitors ( with or without diuretics ) followed by calcium channel blockers were preferred . The mean ( + /- SD ) of the mean arterial pressures during follow-up in the low and usual BP groups was 93.0 + /- 7.3 and 97.7 + /- 7.7 mm Hg , respectively . Follow-up BP was significantly higher in subgroups of patients with preexisting hypertension , baseline mean arterial pressure > 92 mm Hg , a diagnosis of polycystic kidney disease or glomerular diseases , baseline urinary protein excretion > 1 g/d , age > or = 61 years , and black race . The frequency of medication changes and incidence of symptoms of low BP were greater in the low BP group , but there were no significant differences between BP groups in stop points , hospitalizations , or death . When data from both groups were combined , each 1-mm Hg increase in follow-up systolic BP was associated with a 1.35-times greater risk of hospitalization for cardiovascular or cerebrovascular disease . Lower BP than usually recommended for the prevention of cardiovascular disease is achievable by several medication regimens without serious adverse effects in patients with chronic renal disease without cardiovascular disease . For patients with urinary protein excretion > 1 g/d , target BP should be a mean arterial pressure of < or = 92 mm Hg , equivalent to 125/75 mm Hg",
"Abstract Objective : To determine whether tight control of blood pressure prevents macrovascular and microvascular complications in patients with type 2 diabetes . Design : R and omised controlled trial comparing tight control of blood pressure aim ing at a blood pressure of angiotensin converting enzyme inhibitor captopril or a β blocker atenolol as main treatment ) with less tight control aim ing at a blood pressure of 20 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Subjects : 1148 hypertensive patients with type 2 diabetes ( mean age 56 , mean blood pressure at entry 160/94 mm Hg ) ; 758 patients were allocated to tight control of blood pressure and 390 patients to less tight control with a median follow up of 8.4 years . Main outcome measures : Predefined clinical end points , fatal and non-fatal , related to diabetes , deaths related to diabetes , and all cause mortality . Surrogate measures of microvascular disease included urinary albumin excretion and retinal photography . Results : Mean blood pressure during follow up was significantly reduced in the group assigned tight blood pressure control ( 144/82 mm Hg ) compared with the group assigned to less tight control ( 154/87 mm Hg ) ( P Reductions in risk in the group assigned to tight control compared with that assigned to less tight control were 24 % in diabetes related end points ( 95 % confidence interval 8 % to 38 % ) ( P=0.0046 ) , 32 % in deaths related to diabetes ( 6 % to 51 % ) ( P=0.019 ) , 44 % in strokes ( 11 % to 65 % ) ( P=0.013 ) , and 37 % in microvascular end points ( 11 % to 56 % ) ( P=0.0092 ) , predominantly owing to a reduced risk of retinal photocoagulation . There was a non-significant reduction in all cause mortality . After nine years of follow up the group assigned to tight blood pressure control also had a 34 % reduction in risk in the proportion of patients with deterioration of retinopathy by two steps ( 99 % confidence interval 11 % to 50 % ) ( P=0.0004 ) and a 47 % reduced risk ( 7 % to 70 % ) ( P=0.004 ) of deterioration in visual acuity by three lines of the early treatment of diabetic retinopathy study ( ETDRS ) chart . After nine years of follow up 29 % of patients in the group assigned to tight control required three or more treatments to lower blood pressure to achieve target blood pressures . Conclusion : Tight blood pressure control in patients with hypertension and type 2 diabetes achieves a clinical ly important reduction in the risk of deaths related to diabetes , complications related to diabetes , progression of diabetic retinopathy , and deterioration in visual acuity",
"Background The Hypertension Optimal Treatment ( HOT ) Study investigated 18 790 hypertensives r and omized to three diastolic blood pressure ( DBP ) targets ( ⩽ 90 , ⩽ 85 , ⩽ 80 mmHg ) for 3.8 years and found marked , significant reductions in cardiovascular events and mortality the lower the target DBP in the subset of diabetics . We investigated whether the benefits of intensive DBP lowering could be extended to other subgroups , and whether there are hypertensives in whom the risk of aggressive DBP lowering may outnumber the benefits . Methods and results The 18 790 patients were stratified as : medium/high – very high global cardiovascular risk ; men/women ; older/younger ; current smokers/non-smokers ; higher/lower serum cholesterol ; higher/lower serum creatinine ; with/without diabetes ; with/without ischaemic heart disease ( IHD ) . Comparisons were made between the less aggressive target group ( DBP risks ( RR ) with 95 % confidence intervals . Benefits were greatest in diabetics ( RR 0.53 for cardiovascular events , and 0.67 for cardiovascular death ) , whereas in smokers more intensive DBP lowering was associated with increased risk of all types of cardiovascular event ( RR 1.71–2.67 ; P = 0.01–0.001 ) , except myocardial infa rct ion . After excluding smokers , intensive DBP lowering was associated with significant reductions in cardiovascular events in diabetics ( −49 % ) , high – very high risk patients ( −23 % ) , IHD patients ( −32 % ) , patients with lower creatinine ( −18 % ) , women ( −33 % ) and older patients ( −23 % ) . Conclusions Although subanalyses have only a descriptive value , it appears reasonable to recommend intensive antihypertensive treatment to hypertensives with diabetes , IHD and high global cardiovascular risk . In smokers , treatment intensification should be associated with the greatest efforts to induce smoking cessation ",
"The Hypertension Optimal Treatment ( HOT ) Study is a prospect i ve , r and omized , multicenter trial being conducted in 26 countries . Its main aim is to evaluate the relationship between three levels of target diastolic blood pressure ( cardiovascular morbidity and mortality in hypertensive patients . In addition , the study will examine the effects on morbidity and mortality of a low dose , 75 mg daily , of acetylsalicylic acid ( ASA , aspirin ) or placebo . In the HOT Study , basic antihypertensive treatment is initiated with the calcium antagonist felodipine at a dose of 5 mg daily . If target blood pressure is not reached , additional antihypertensive therapy with either an angiotensin converting enzyme ( ACE ) inhibitor or a beta-adrenoceptor blocking agent is given . Further dosage adjustments are made in accordance with a set protocol . As a fifth and final step , a diuretic may be added . Inclusion of patients was stopped on April 30 , 1994 . At that time 19,196 patients had been r and omized . There were 9,055 ( 47 % ) women and 10,141 ( 53 % ) men with an average age of 61.5 + /- 7.5 ( SD ) years . At enrollment , 52 % of patients were receiving antihypertensive treatment . These patients entered a wash-out period of at least 2 weeks before r and omization . The average r and omization blood pressure in untreated patients was 169 + /- 14/106 + /- 3 mmHg and in the treated patients 170 + /- 14/105 + /- 3 mmHg . On August 15 , 1994 , blood pressure data were available for 14,710 and 10,275 patients , who had completed 3 and 6 months treatment , respectively . The average reduction in diastolic blood pressure was 22 mmHg after 6 months . ( ABSTRACT TRUNCATED AT 250 WORDS",
"BACKGROUND Despite treatment , there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals . Inadequate reduction of their blood pressure is a likely cause , but the optimum target blood pressure is not known . The impact of acetylsalicylic acid ( aspirin ) has never been investigated in patients with hypertension . We aim ed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension . METHODS 18790 patients , from 26 countries , aged 50 - 80 years ( mean 61.5 years ) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg ( mean 105 mm Hg ) were r and omly assigned a target diastolic blood pressure . 6264 patients were allocated to the target pressure Felodipine was given as baseline therapy with the addition of other agents , according to a five-step regimen . In addition , 9399 patients were r and omly assigned 75 mg/day acetylsalicylic acid ( Bamycor , Astra ) and 9391 patients were assigned placebo . FINDINGS Diastolic blood pressure was reduced by 20.3 mm Hg , 22.3 mm Hg , and 24.3 mm Hg , in the major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg ; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg . Further reduction below these blood pressures was safe . In patients with diabetes mellitus there was a 51 % reduction in major cardiovascular events in target group Acetylsalicylic acid reduced major cardiovascular events by 15 % ( p=0.03 ) and all myocardial infa rct ion by 36 % ( p=0.002 ) , with no effect on stroke . There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group , and 129 versus 70 non-fatal major bleeds in the two groups , respectively ( p patients with hypertension was associated with a low rate of cardiovascular events . The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg . Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infa rct ion . There was no effect on the incidence of stroke or fatal bleeds , but non-fatal major bleeds were twice as common",
"Diabetic nephropathy is the most common cause of end-stage renal disease in the United States . We undertook a study to assess the impact of assignment to different levels of blood pressure control on the course of type 1 diabetic nephropathy in patients receiving angiotensin-converting enzyme ( ACE ) inhibitor therapy . We also examined the long-term course of this well-characterized cohort of patients receiving ACE inhibitor therapy . One hundred twenty-nine patients with type 1 diabetes and diabetic nephropathy who had previously participated in the Angiotensin-Converting Enzyme Inhibition in Diabetic Nephropathy Study who had a serum creatinine level less than 4.0 mg/dL were r and omly assigned to a mean arterial blood pressure ( MAP ) goal of 92 mm Hg or less ( group I ) or 100 to 107 mm Hg ( group II ) . Patients received varying doses of ramipril as the primary therapeutic antihypertensive agent . All patients were followed for a minimum of 2 years . Outcome measures included iothalamate clearance , 24-hour creatinine clearance , creatinine clearance estimated by the Cockcroft and Gault formula , and urinary protein excretion . The average difference in MAP between groups was 6 mm Hg over the 24-month follow-up . The median iothalamate clearance in group I was 62 mL/min/1.73 m(2 ) at baseline and 54 mL/min/1.73 m(2 ) at the end of the study compared with a baseline of 64 mL/min/1.73 m(2 ) and final 58 mL/min/1.73 m(2 ) in group II . There were no statistically significant differences in the rate of decline in renal function between groups . There was a significant difference in follow-up total urinary protein excretion between group I ( 535 mg/24 h ) and group II ( 1,723 mg/24 h ; P = 0.02 ) . Thirty-two percent of 126 patients achieved a final total protein excretion less than 500 mg/24 h. Patients from groups I and II had equivalent rates of adverse events . In patients with type 1 diabetes mellitus and diabetic nephropathy , the MAP goal should be 92 mm Hg or less for optimal renoprotection , if defined as including decreased proteinuria . With the combination of ACE inhibition and intensive blood pressure control , many patients can achieve regression or apparent remission of clinical evidence of diabetic nephropathy",
"A novel design for intervention studies is presented , the so called PROBE study ( Prospect i ve R and omized Open , Blinded End-point ) . This design is compared to the classical double-blind design . Among the advantages of the PROBE design are lower cost and greater similarity to st and ard clinical practice , which should make the results more easily applicable in routine medical care . Since end-points are evaluated by a blinded end-point committee it is obvious that there should be no difference between the two types of trials in this regard",
"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 quantitative systematic review , or meta- analysis , uses statistical methods to combine the results of multiple studies . Meta-analyses have been done for systematic review s of therapeutic trials , diagnostic test evaluations , and epidemiologic studies . Although the statistical methods involved may at first appear to be mathematically complex , their purpose is simple : They are trying to answer four basic questions . Are the results of the different studies similar ? To the extent that they are similar , what is the best overall estimate ? How precise and robust is this estimate ? Finally , can dissimilarities be explained ? This article provides some guidance in underst and ing the key technical aspects of the quantitative approach to these questions . We have avoided using equations and statistical notations ; interested readers will find implementations of the described methods in the listed references . We focus here on the quantitative synthesis of reports of r and omized , controlled , therapeutic trials because far more meta-analyses on therapeutic studies than on other types of studies have been published . For practical reasons , we present a stepwise description of the tasks that are performed when statistical methods are used to combine data . These tasks are 1 ) deciding whether to combine data and defining what to combine , 2 ) evaluating the statistical heterogeneity of the data , 3 ) estimating a common effect , 4 ) exploring and explaining heterogeneity , 5 ) assessing the potential for bias , and 6 ) presenting the results . Deciding Whether To Combine Data and Defining What To Combine By the time one performs a quantitative synthesis , certain decisions should already have been made about the formulation of the question and the selection of included studies . These topics were discussed in two previous articles in this series [ 1 , 2 ] . Statistical tests can not compensate for lack of common sense , clinical acumen , and biological plausibility in the design of the protocol of a meta- analysis . Thus , a reader of a systematic review should always address these issues before evaluating the statistical methods that have been used and the results that have been generated . Combining poor- quality data , overly biased data , or data that do not make sense can easily produce unreliable results . The data to be combined in a meta- analysis are usually either binary or continuous . Binary data involve a yes/no categorization ( for example , death or survival ) . Continuous data take a range of values ( for example , change in diastolic blood pressure after antihypertensive treatment , measured in mm Hg ) . When one is comparing groups of patients , binary data can be summarized by using several measures of treatment effect that were discussed earlier in this series [ 3 ] . These measures include the risk ratio ; the odds ratio ; the risk difference ; and , when study duration is important , the incidence rate . Another useful clinical measure , the number needed to treat ( NNT ) , is derived from the inverse of the risk difference [ 3 ] . Treatment effect measures , such as the risk ratio and the odds ratio , provide an estimate of the relative efficacy of an intervention , whereas the risk difference describes the intervention 's absolute benefit . The various measures of treatment effect offer complementary information , and all should be examined [ 4 ] . Continuous data can be summarized by the raw mean difference between the treatment and control groups when the treatment effect is measured on the same scale ( for example , diastolic blood pressure in mm Hg ) , by the st and ardized mean difference when different scales are used to measure the same treatment effect ( for example , different pain scales being combined ) , or by the correlation coefficients between two continuous variables [ 5 ] . The st and ardized mean difference , also called the effect size , is obtained by dividing the difference between the mean in the treatment group and the mean in the control group by the SD in the control group . Evaluating the Statistical Heterogeneity of the Data This step is intended to answer the question , Are the results of the different studies similar ( homogeneous ) ? It is important to answer this question before combining any data . To do this , one must calculate the magnitude of the statistical diversity ( heterogeneity ) of the treatment effect that exists among the different sets of data . Statistical diversity can be thought of as attributable to one or both of two causes . First , study results can differ because of r and om sampling error . Even if the true effect is the same in each study , the results of different studies would be expected to vary r and omly around the true common fixed effect . This diversity is called the within- study variance . Second , each study may have been drawn from a different population , depending on the particular patients chosen and the interventions and conditions unique to the study . Therefore , even if each study enrolled a large patient sample , the treatment effect would be expected to differ . These differences , called r and om effects , describe the between- study variation with regard to an overall mean of the effects of all of the studies that could be undertaken . The test most commonly used to assess the statistical significance of between- study heterogeneity is based on the chi-square distribution [ 6 ] . It provides a measure of the sum of the squared differences between the results observed and the results expected in each study , under the assumption that each study estimates the same common treatment effect . A large total deviation indicates that a single common treatment effect is unlikely . Any pooled estimate calculated must account for the between- study heterogeneity . In practice , this test has low sensitivity for detecting heterogeneity , and it has been suggested that a liberal significance level , such as 0.1 , should be used [ 6 ] . Estimating a Common Effect The questions that this step tries to answers are , 1 ) To the extent that data are similar , what is their best common point estimate of a therapeutic effect , and 2 ) how precise is this estimate ? The mathematical process involved in this step generally involves combining ( pooling ) the results of different studies into an overall estimate . Compared with the results of individual studies , pooled results can increase statistical power and lead to more precise estimates of treatment effect . Each study is given a weight according to the precision of its results . The rationale is that studies with narrow CIs should be weighted more heavily than studies with greater uncertainty . The precision is generally expressed by the inverse of the variance of the estimate of each study . The variance has two components : the variance of the individual study and the variance between different studies . When the between- study variance is found to be or assumed to be zero , each study is simply weighted by the inverse of its own variance , which is a function of the study size and the number of events in the study . This approach characterizes a fixed-effects model , as exemplified by the Mantel-Haenszel method [ 7 , 8 ] or the Peto method [ 9 ] for dichotomous data . The Peto method has been particularly popular in the past . It has the advantage of simple calculation ; however , although it is appropriate in most cases , it may introduce large biases if the data are unbalanced [ 10 , 11 ] . On the other h and , r and om-effects models also add the between- study variance to the within- study variance of each individual study when the pooled mean of the r and om effects is calculated . The r and om-effects model most commonly used for dichotomous data is the DerSimonian and Laird estimate of the between- study variance [ 12 ] . Fixed- and r and om-effects models for continuous data have also been described [ 13 ] . Pooled results are generally reported as a point estimate and CI , typically a 95 % CI . Other quantitative techniques for combining data , such as the Confidence Profile Method [ 14 ] , use Bayesian methods to calculate posterior probability distributions for effects of interest . Bayesian statistics are based on the principle that each observation or set of observations should be viewed in conjunction with a prior probability describing the prior knowledge about the phenomenon of interest [ 15 ] . The new observations alter this prior probability to generate a posterior probability . Traditional meta- analysis assumes that nothing is known about the magnitude of the treatment effect before r and omized trials are performed . In Bayesian terms , the prior probability distribution is noninformative . Bayesian approaches may also allow the incorporation of indirect evidence in generating prior distributions [ 14 ] and may be particularly helpful in situations in which few data from r and omized studies exist [ 16 ] . Bayesian analyses may also be used to account for the uncertainty introduced by estimating the between- study variance in the r and om-effects model , leading to more appropriate estimates and predictions of treatment efficacy [ 17 ] . Exploring and Explaining Heterogeneity The next important issue is whether the common estimate obtained in the previous step is robust . Sensitivity analyses determine whether the common estimate is influenced by changes in the assumptions and in the protocol for combining the data . A comparison of the results of fixed- and r and om-effects models is one such sensitivity analysis [ 18 ] . Generally , the r and om-effects model produces wider CIs than does the fixed-effects model , and the level of statistical significance may therefore be different depending on the model used . The pooled point estimate per se is less likely to be affected , although exceptions are possible [ 19 ] . Other sensitivity analyses may include the examination of the residuals and the chi-square components [ 13 ] and assessment of the effect of deleting each study in turn . Statistically significant results that depend on a single study may require further exploration . Cumulative Meta- Analysis",
"OBJECTIVE To provide up date d , evidence -based recommendations for the therapy of hypertension in adults . OPTIONS For patients with hypertension , a number of antihypertensive agents may control blood pressure . R and omized trials evaluating first-line therapy with thiazides , beta-adrenergic antagonists , angiotensin-converting enzyme inhibitors , calcium channel blockers , alpha-blockers , central ly acting agents or angiotensin II receptor antagonists were review ed . OUTCOMES The health outcomes that were considered were changes in blood pressure , cardiovascular morbidity , and cardiovascular and /or all-cause mortality rates . Economic outcomes were not considered due to insufficient evidence . EVIDENCE MEDLINE was search ed for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension . Reference lists were scanned , experts were polled , and the personal files of the subgroup members and authors were used to identify other published studies . All relevant articles were review ed and appraised , using prespecified levels of evidence , by content experts and method ological experts . VALUES A high value was placed on the avoidance of cardiovascular morbidity and mortality . BENEFITS , HARMS AND COSTS Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension . In certain setting s , and for specific classes of drugs , blood-pressure lowering has been associated with reduced cardiovascular morbidity and /or mortality . RECOMMENDATIONS The present document contains detailed recommendations pertaining to treatment thresholds , target blood pressures , and choice of agents in various setting s in patients with hypertension . The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus , the amalgamation of the previous sections on treatment of hypertension in the young and old into one section , increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke . Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk , the presence and /or absence of target organ damage , and comorbidities . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group . Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation . Only those recommendations achieving high levels of consensus are reported here . These guidelines will continue to be up date d annually",
"BACKGROUND In chronic nephropathies , inhibition of angiotensin-converting enzyme ( ACE ) is renoprotective , but can further renoprotection be achieved by reduction of blood pressure to lower than usual targets ? We aim ed to assess the effect of intensified versus conventional blood-pressure control on progression to end-stage renal disease . METHODS We undertook a multicentre , r and omised controlled trial of patients with non-diabetic proteinuric nephropathies receiving background treatment with the ACE inhibitor ramipril ( 2.5 - 5 mg/day ) . We r and omly assigned participants either conventional ( diastolic intensified ( systolic/diastolic blood-pressure control . To achieve the intensified blood-pressure level , patients received add-on therapy with the dihydropyridine calcium-channel blocker felodipine ( 5 - 10 mg/day ) . The primary outcome measure was time to end-stage renal disease over 36 months ' follow-up , and analysis was by intention to treat . FINDINGS Of 338 patients who were r and omised , three ( two assigned intensified and one allocated conventional blood-pressure control ) never took study drugs and they were excluded . Over a median follow-up of 19 months ( IQR 12 - 35 ) , 38/167 ( 23 % ) patients assigned to intensified blood-pressure control and 34/168 ( 20 % ) allocated conventional control progressed to end-stage renal disease ( hazard ratio 1.00 [ 95 % CI 0.61 - 1.64 ] ; p=0.99 ) . INTERPRETATION In patients with non-diabetic proteinuric nephropathies receiving background ACE-inhibitor therapy , no additional benefit from further blood-pressure reduction by felodipine could be shown",
"OBJECTIVES The aim of this study was to determine whether pulse pressure is a risk factor for coronary artery disease using data from the MRC trial of treatment of mild hypertension , and whether the effect of anti-hypertensive drug therapy on pulse pressure may be a determinant of outcome in treated patients . METHODS Logistic regression and Cox regression analyses were used to compare systolic and diastolic blood pressure , pulse pressure and mean blood pressure as predictors of coronary events and stroke in the MRC Mild Hypertension Trial . The effects of anti-hypertensive drug treatment with bendrofluazide and propranolol on pulse pressure were assessed using 1-year follow-up data . Event rates in the placebo-treated group and responses to anti-hypertensive treatment were measured in quartiles of age-adjusted entry pulse pressure . A ' four-corners ' analysis was performed , with subjects divided into the upper and lower halves of the distributions of systolic and diastolic blood pressure at entry . RESULTS Pulse pressure was a stronger predictor of coronary events than systolic , diastolic or mean blood pressure in males by logistic regression . Pulse pressure was similar to systolic pressure as a coronary event predictor on Cox regression . Stroke was predicted most strongly by mean blood pressure . Fatal and non-fatal coronary event rates increased progressively in ascending quartiles of age-adjusted pulse pressure , but there was also a strong correlation with systolic blood pressure . The values of partial logistic regression coefficients in models containing both systolic and diastolic blood pressure also supported a role for pulse pressure in predicting coronary events and for mean blood pressure in predicting stroke . Coronary risk , but not stroke , was inversely related to diastolic blood pressure in the four-corners analysis . In a Cox model , regressions of coronary event probability on systolic blood pressure at entry were significantly and inversely related to diastolic blood pressure categorized in quartiles . Bendrofluazide but not propranolol decreased pulse pressure significantly and was associated with a reduction in cardiovascular events overall , but no definite relationship between the effect of drugs on pulse pressure and specific responses to treatment was seen . CONCLUSION Pulse pressure is a strong risk factor for coronary events in untreated hypertensive male subjects in the MRC Mild Hypertension Trial , whereas stroke is best predicted by mean blood pressure . Bendrofluazide and propranolol have different effects on pulse pressure which may be related to their relative efficacy in the treatment of hypertension , but this possibility requires further study in more suitable population",
"BACKGROUND The Hypertension Optimal Treatment ( HOT ) Study has provided information about cardiovascular events in 18790 hypertensives , subjected to pronounced blood pressure ( BP ) lowering for a mean of 3.8 years . The HOT study data have subsequently been analysed after stratification of the patients according to global cardiovascular risk , and it has been found that , despite intensive blood pressure lowering in all risk strata , morbid event rates increased with increasing risk stratum . OBJECTIVES Previously analysed global risk strata were based on combinations of risk factors . The analyses presented here were intended to provide information on the relative role that the presence of each individual factor may have in increasing cardiovascular risk , despite good BP control . METHODS Risk ratios ( RR ) for patients with and those without a risk factor were calculated with 95 % confidence intervals ( CI ) using a Cox proportional hazard model , and adjusted for all variables except the one under examination . RESULTS For all risk factors considered and for all types of event , RR were always greater than 1 , indicating a greater risk in the presence , compared with that in the absence of each factor . The male gender was a statistically significant risk for cardiovascular ( CV ) events , CV and total mortality and particularly for myocardial infa rct ion ( MI ) ; age > or = 65 years for CV events , stroke , CV and particularly total mortality ; smoking for all events analysed , but particularly for total mortality ( twice higher in smokers than in non-smokers ) ; high serum cholesterol ( > 6.8 mmol/l ) for CV events , MI and CV mortality ; high serum creatinine ( > 155 micromol/l ) for CV events , stroke , CV and total mortality ; diabetes for CV events , stroke , total mortality and particularly CV mortality ; and ischaemic heart disease for all events analysed . Adjusted RR were often close to or greater than 2 . CONCLUSIONS Each of the risk factors considered was found to be an important cause of residual risk , despite good BP control . These findings emphasize the importance of addressing other correctable risk factors , e.g. smoking , hypercholesterolaemia and diabetes , as well as rigorous control of blood pressure , and of initiating antihypertensive therapy before cardiovascular and renal damage becomes manifest",
"BACKGROUND Although several important studies have been performed in hypertensive type 2 diabetic patients , it is not known whether lowering blood pressure in normotensive ( BP offers any beneficial results on vascular complications . The current study evaluated the effect of intensive versus moderate diastolic blood pressure ( DBP ) control on diabetic vascular complications in 480 normotensive type 2 diabetic patients . METHODS The current study was a prospect i ve , r and omized controlled trial in normotensive type 2 diabetic subjects . The subjects were r and omized to intensive ( 10 mm Hg below the baseline DBP ) versus moderate ( 80 to 89 mm Hg ) DBP control . Patients in the moderate therapy group were given placebo , while the patients r and omized to intensive therapy received either nisoldipine or enalapril in a blinded manner as the initial antihypertensive medication . The primary end point evaluated was the change in creatinine clearance with the secondary endpoints consisting of change in urinary albumin excretion , progression of retinopathy and neuropathy and the incidence of cardiovascular disease . RESULTS The mean follow-up was 5.3 years . Mean BP in the intensive group was 128 + /- 0.8/75 + /- 0.3 mm Hg versus 137 + /- 0.7/81 + /- 0.3 mm Hg in the moderate group , P creatinine clearance ( P = 0.43 ) , a lower percentage of patients in the intensive group progressed from normoalbuminuria to microalbuminuria ( P = 0.012 ) and microalbuminuria to overt albuminuria ( P = 0.028 ) . The intensive BP control group also demonstrated less progression of diabetic retinopathy ( P = 0.019 ) and a lower incidence of strokes ( P = 0.03 ) . The results were the same whether enalapril or nisoldipine was used as the initial antihypertensive agent . CONCLUSION Over a five-year follow-up period , intensive ( approximately 128/75 mm Hg ) BP control in normotensive type 2 diabetic patients : ( 1 ) slowed the progression to incipient and overt diabetic nephropathy ; ( 2 ) decreased the progression of diabetic retinopathy ; and ( 3 ) diminished the incidence of stroke",
"The Hypertension Optimal Treatment ( HOT ) Study is an ongoing prospect i ve , r and omized , multicenter trial conducted in 26 countries . Its two main aims are to evaluate the relationship between three levels of target diastolic blood pressure ( incidence of cardiovascular morbidity and mortality in hypertensive patients and the effects on morbidity and mortality of a low dose , 75 mg daily , of acetylsalicylic acid ( ASA , aspirin ) compared with placebo . Altogether 19,193 patients have been recruited and r and omized and one-year data are now available for all patients . This is a report on the blood pressures achieved , the tolerability and other available data after 12 months of follow-up of all patients . Special reference will be given to the subgroup of elderly patients ( > or = 65 years , n = 6,113 ) as compared to younger patients ( On average , the target group diastolic blood pressure has reached 86 mmHg , the target group target blood pressures is 84 % in the target group elderly subgroup ( > or = 65 years of age ) the percentage of patients at target is higher for all target groups , being 86 , 76 and 61 % , respectively , at 12 months . Antihypertensive treatment is initiated with a calcium antagonist , felodipine , at a dose of 5 mg once daily . If target blood pressure is not reached , additional antihypertensive therapy , with either an angiotensin converting enzyme ( ACE ) inhibitor or a beta-adrenoceptor blocking agent , is given . Further dose adjustments are made in accordance with a set protocol . As a fifth and final step a diuretic may be added . Side effects have been relatively few in this large multinational series of intensively treated hypertensive patients . Only ankle edema , 2.6 % and 3.0 % , and coughing , 1.3 % and 0.8 % , in young and elderly patients , respectively , exceed a frequency of 1 % , and 88 % of all patients are still taking their baseline therapy felodipine after one year . The one-year data presented here indicate that it should be possible to fulfill the primary aims of the HOT Study",
"The Hypertension Optimal Treatment ( HOT ) Study is an ongoing prospect i ve r and omized , multicentre trial conducted in 26 countries . There are two main aims of the study . The first is to evaluate the relationship between three levels of target diastolic blood pressure ( of cardiovascular morbidity and mortality in hypertensive patients . The second is to determine the effect on morbidity and mortality of a low dose , 75 mg daily , of acetylsalicylic acid ( ASA , aspirin ) compared with placebo . Altogether 18,790 patients have been recruited and r and omized , and two-year data are now available for all patients . This is a report on the blood pressures achieved , the tolerability , and other available data after 24 months of follow-up of all patients . Special emphasis is given to the subgroup of elderly patients ( > or = 65 years , n = 5988 ) compared with young patients ( On average , patients in the diastolic blood pressure target group have reached 85 mmHg , in the target blood pressure in each target group at 24 months of follow-up is 85 % in the elderly subgroup ( > or = 65 years of age ) , the percentage of patients achieving target at 24 months is higher for all target groups , namely 89 % in the treatment was initiated with a calcium antagonist , felodipine , at a dose of 5 mg once daily . If target blood pressure was not reached , additional antihypertensive therapy , with either an angiotensin converting enzyme ( ACE ) inhibitor or a beta-adrenoceptor blocking agent , was given . Further dose adjustments were made in accordance with a set protocol . As a fifth , and final , step , a diuretic could be added . There have been relatively few side effects in this large , multinational study of hypertensive patients . Only ankle oedema and coughing exceed a frequency of 0.5 % ( ankle oedema 1.3 % in young and 1.7 % in elderly ; coughing 0.5 % in young and elderly ) . After two years , 84 % of all patients are still taking their baseline therapy , felodipine . The 24-month data presented here indicate that it should be possible to fulfil the primary aims of the HOT Study",
"BACKGROUND Cardiovascular morbidity is a major burden in patients with type 2 diabetes . In the Steno-2 Study , we compared the effect of a targeted , intensified , multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria . METHODS The primary end point of this open , parallel trial was a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , nonfatal stroke , revascularization , and amputation . Eighty patients were r and omly assigned to receive conventional treatment in accordance with national guidelines and 80 to receive intensive treatment , with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia , hypertension , dyslipidemia , and microalbuminuria , along with secondary prevention of cardiovascular disease with aspirin . RESULTS The mean age of the patients was 55.1 years , and the mean follow-up was 7.8 years . The decline in glycosylated hemoglobin values , systolic and diastolic blood pressure , serum cholesterol and triglyceride levels measured after an overnight fast , and urinary albumin excretion rate were all significantly greater in the intensive-therapy group than in the conventional-therapy group . Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease ( hazard ratio , 0.47 ; 95 percent confidence interval , 0.24 to 0.73 ) , nephropathy ( hazard ratio , 0.39 ; 95 percent confidence interval , 0.17 to 0.87 ) , retinopathy ( hazard ratio , 0.42 ; 95 percent confidence interval , 0.21 to 0.86 ) , and autonomic neuropathy ( hazard ratio , 0.37 ; 95 percent confidence interval , 0.18 to 0.79 ) . CONCLUSIONS A target-driven , long-term , intensified intervention aim ed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent",
"Hypertensive nephrosclerosis is a progressive renal disease and the leading cause of end-stage renal disease ( ESRD ) in blacks in the United States . It is generally believed that hypertensive renal injury is responsible for progressive renal failure ; however , it is not known whether pharmacologic lowering of blood pressure to any level prevents progression of renal disease . Accordingly , we performed a long-term prospect i ve r and omized trial to determine whether \" strict \" [ diastolic blood pressure ( DBP ) 65 to 80 mm Hg ] versus \" conventional \" ( DBP 85 to 95 mm Hg ) blood pressure control is associated with a slower rate of decline in glomerular filtration rate . Eighty-seven non-diabetic patients ( age 25 to 73 ; 68 black , 58 male ) with long-st and ing hypertension ( DBP > or = 95 mm Hg ) , chronic renal insufficiency ( GFR . DBP was pharmacologically lowered to DBP and GFR ( renal clearance of 125I-iothalamate ) were measured at baseline , at three months and every six months post-r and omization . The rate of decline in GFR ( GFR slope , in ml/min/1.73 m2/year ) , estimated by the method of maximum likelihood in a mixed effects model , was the primary outcome variable . In a secondary analysis , 50 % reduction in GFR ( or a doubling of serum creatinine ) from baseline , ESRD and death were combined . ( ABSTRACT TRUNCATED AT 250 WORDS",
"OBJECTIVE - To examine the prevalence , incidence , predisposing factors for hypertension , its hazards as an ingredient of the cardiovascular risk profile , and the implication s of this information for prevention and treatment . METHODS - Prospect i ve longitudinal analysis of 36-year follow-up data from the Framingham Study of the relation of antecedent blood pressure to occurrence of subsequent cardiovascular morbidity and mortality depending on the metabolically linked burden of associated risk factors . RESULTS - Hypertension is one of the most prevalent and powerful contributors to cardiovascular diseases , the leading cause of death in the United States . There is , on average , a 20 mm Hg systolic and 10 mm Hg diastolic increment increase in blood pressure from age 30 to 65 years . Isolated systolic hypertension is the dominant variety . There is no evidence of a decline in the prevalence of hypertension over 4 decades despite improvements in its detection and treatment . Hypertension contributes to all of the major atherosclerotic cardiovascular disease outcomes increasing risk , on average , 2- to 3-fold . Coronary disease , the most lethal and common sequela , deserves highest priority . Hypertension clusters with dyslipidemia , insulin resistance , glucose intolerance , and obesity , occurring in isolation in less than 20 % . The hazard depends on the number of these associated metabolically linked risk factors present . Coexistent overt cardiovascular disease also influences the hazard and choice of therapy . CONCLUSION - The absence of a decline in the prevalence of hypertension indicates an urgent need for primary prevention by weight control , exercise , and reduced salt and alcohol intake . The urgency and choice of therapy of existing hypertension should be based on the multivariate cardiovascular risk profile that more appropriately targets hypertensive persons for treatment and prevention of cardiovascular sequelae",
"Context We do not know the optimal blood pressure needed to slow progression of chronic kidney disease . Contribution In this multicenter trial , 840 adults with mostly nondiabetic kidney disease and moderately to severely decreased glomerular filtration rate were r and omly assigned to usual blood pressure control ( target : mean arterial pressure or a low blood pressure goal ( target : mean arterial pressure kidney failure in the low compared with the usual blood pressure group was 0.68 ( 95 % CI , 0.57 to 0.82 ) . Implication s A low blood pressure target slows progression of nondiabetic kidney disease . The Editors The Seventh Report of the Joint National Commission on Prevention , Detection , Assessment and Treatment of Hypertension and the National Kidney Foundation Kidney Disease Outcome Quality Initiative Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease recommend a target blood pressure of less than 130/80 mm Hg in patients with chronic kidney disease ( 1 , 2 ) . These guidelines are based on data from observational studies demonstrating that persons with chronic kidney disease are at high risk for cardiovascular disease and from subgroup analyses of the Modification of Diet in Renal Disease ( MDRD ) Study suggesting that a low target blood pressure may slow the decline in kidney function in persons with moderate to high levels of proteinuria ( 3 ) . However , no published trials in diabetic or nondiabetic kidney disease have demonstrated that a lower target blood pressure reduces the incidence of kidney failure . Many types of chronic kidney disease progress slowly , requiring years for the onset of kidney failure . In clinical trials , progression of kidney disease is usually assessed by change in kidney function , which is measured as the glomerular filtration rate ( GFR ) or serum creatinine concentration . Two r and omized , controlled trials in nondiabetic kidney disease have compared the effects of a low target blood pressure with those of a usual target blood pressure on the decline in GFR ( 3 , 4 ) . The MDRD Study enrolled participants with predominantly nondiabetic kidney diseases , a baseline GFR of 13 to 55 mL/min per 1.73 m2 , and median proteinuria of 0.35 g/d ( 3 ) . In that study , a low target blood pressure did not produce a slower projected mean decline in GFR at 3 years compared with the usual target blood pressure . However , participants with greater proteinuria significantly benefited from the low target blood pressure ( 3 ) . On the basis of these findings , it was recommended that participants with proteinuria greater than 1 g/d have a lower target blood pressure . The African American Study of Kidney Disease and Hypertension ( AASK ) enrolled participants with hypertensive nephrosclerosis , a baseline GFR of 20 to 70 mL/min per 1.73 m2 , and median baseline proteinuria of 0.081 g/d ( 4 ) . In that study , a lower target blood pressure did not reduce the mean decline in GFR or the risk for the composite outcome of reduction in GFR of at least 50 % , kidney failure , or all-cause mortality during a median follow-up of 4 years . The average rates of decline in GFR in the MDRD Study and AASK were 4 mL/min per 1.73 m2 per year and 2 mL/min per 1.73 m2 per year , respectively , and relatively few participants developed kidney failure during the observation period . The long-term effect of a low target blood pressure on the onset of kidney failure may differ from the effect on decline in GFR observed during the trial . Therefore , we evaluated the effects of a low target blood pressure on the onset of kidney failure and all-cause mortality through extended follow-up after completion of the MDRD Study . Methods The MDRD R and omized , Controlled Trial The MDRD Study was a r and omized , controlled trial of the effect of dietary protein restriction and strict control of blood pressure on the progression of kidney disease . Details of the design and r and omization criteria are provided elsewhere ( 5 , 6 ) . The trial was conducted from 1989 to 1993 . Eligibility criteria for enrollment were age 18 to 70 years and presence of chronic kidney disease , with a serum creatinine concentration of 123.8 mol/L ( 1.4 mg/dL ) to 618.8 mol/L ( 7.0 mg/dL ) in men and 106.1 mol/L ( 1.2 mg/dL ) to 618.8 mol/L ( 7.0 mg/dL ) in women . Persons with diabetes requiring therapy with insulin , class III or IV congestive heart failure , renal artery stenosis , history of kidney transplantation , or frequent hospitalizations were excluded . Eight hundred forty participants were enrolled : Study A included 585 participants with a baseline GFR of 25 to 55 mL/min per 1.73 m2 , and study B included 255 participants with a baseline GFR of 13 to 24 mL/min per 1.73 m2 . Participants in both studies were r and omly assigned to a low or a usual target blood pressure . The low target blood pressure was a mean arterial pressure less than 92 mm Hg ( equivalent to a blood pressure less than 125/75 mm Hg ) for participants 60 years of age or younger and less than 98 mm Hg for participants 61 years of age or older . The usual target blood pressure was a mean arterial pressure less than 107 mm Hg ( equivalent to a blood pressure of 140/90 mm Hg ) for participants 60 years of age or younger and less than 113 mm Hg for participants 61 years of age or older . Participants in study A were r and omly assigned to receive a usual-protein diet ( 1.0 g/kg of body weight daily ) or a low-protein diet ( 0.6 g/kg daily ) , whereas participants in study B were r and omly assigned to receive a low-protein diet ( 0.6 g/kg daily ) or a very-low-protein diet ( 0.28 g/kg daily , with keto acid and amino acid supplementation ) . No interactions were noted between the dietary intervention and the blood pressure intervention ( 3 ) . Participants were followed up to 4 years . The rate of decline in GFR , measured as kidney clearance of 125I-iothalamate , was the primary outcome . Long-Term Follow-up ( 19932000 ) of the MDRD Study The investigational review boards of the Clevel and Clinic ( Data Coordinating Center for the MDRD Study ) and Tufts-New Engl and Medical Center approved the long-term follow-up study . Kidney failure , defined by the requirement for dialysis or kidney transplantation , and a composite of kidney failure or all-cause mortality were the outcomes of interest for our analysis . All-cause mortality before kidney failure was included in the composite outcome because it is a competing risk factor for kidney failure . Participants were censored on 31 December 2000 if neither of these outcomes had occurred . Blood Pressure Measurement During the Trial ( 19891993 ) Trained personnel measured blood pressure monthly by using a r and om-zero mercury sphygmomanometer . Therapeutic regimens were modified monthly or more often as needed to achieve target blood pressure . For our analysis , mean follow-up blood pressure during the study was defined as the average of all blood pressure measurements obtained after the 4th month of follow-up . This definition differs from that of previous studies , in which the average of all blood pressure measurements during follow-up was calculated ( 3 , 7 ) . The change in definition was introduced to allow comparison with the AASK Study . During Long-Term Follow-up ( 19932000 ) No specific target blood pressure was recommended after completion of the trial . Blood pressure was measured by using the same methods in a large subgroup of participants 9 months after the end of the study ( phase V ) . Thereafter , blood pressure measurements are not available . Antihypertensive Regimens During the Trial ( 19891993 ) After r and om allocation , therapeutic regimens were modified to achieve the target blood pressure . Nonpharmacologic therapy consisted of recommendations for exercise and weight loss and reductions in intake of dietary sodium and alcohol . For pharmacologic therapy , use of all agents was allowed , in the interest of achieving blood pressure goals . However , angiotensin-converting enzyme ( ACE ) inhibitors , with or without a diuretic , were encouraged as agents of first choice . Calcium-channel blockers , with or without a diuretic , were encouraged as agents of second choice . During Long-Term Follow-up ( 19932000 ) Because the MDRD Study did not evaluate the effects of individual antihypertensive agents on decline in kidney function , no specific pharmacologic therapy was recommended after completion of the trial . Outcomes The onset of kidney failure was ascertained from the U.S. Renal Data System by using participants ' Social Security number , name , sex , and date of birth . Data on all-cause mortality were obtained from the National Death Index by using the same identifying information . One hundred eighty-five participants were recorded as starting dialysis or receiving a kidney transplant during or shortly after the r and omized trial in both the MDRD Study data base and the U.S. Renal Data System data base . The recorded date of kidney failure agreed between the 2 data bases to within 1 day for 50 % of these participants , to within 30 days for 90 % , and to within 120 days for 97 % . Nine participants recorded as reaching kidney failure in the MDRD Study data base were not found in the U.S. Renal Data System data base . Except in the case of these 9 participants ( 4 of whom were in the usual target blood pressure group and 5 of whom were in the low target blood pressure group ) , data obtained from U.S. Renal Data System data base were used in all analyses to define the date of kidney failure . All deaths that were coded in the U.S. Renal Data System data base were confirmed in the National Death Index . For all analyses , the date in the National Death Index was used as the date of death so as to maintain consistency with participants who died but had not reached kidney failure and therefore were not included in the U.S. Renal Data System data base . Statistical Analyses We combined participants from studies A and B to improve statistical power . This approach was",
"BACKGROUND Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes . We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors . METHODS In this r and omized study , 10,251 patients ( mean age , 62.2 years ) with a median glycated hemoglobin level of 8.1 % were assigned to receive intensive therapy ( targeting a glycated hemoglobin level below 6.0 % ) or st and ard therapy ( targeting a level from 7.0 to 7.9 % ) . Of these patients , 38 % were women , and 35 % had had a previous cardiovascular event . The primary outcome was a composite of nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes . The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up . RESULTS At 1 year , stable median glycated hemoglobin levels of 6.4 % and 7.5 % were achieved in the intensive-therapy group and the st and ard-therapy group , respectively . During follow-up , the primary outcome occurred in 352 patients in the intensive-therapy group , as compared with 371 in the st and ard-therapy group ( hazard ratio , 0.90 ; 95 % confidence interval [ CI ] , 0.78 to 1.04 ; P=0.16 ) . At the same time , 257 patients in the intensive-therapy group died , as compared with 203 patients in the st and ard-therapy group ( hazard ratio , 1.22 ; 95 % CI , 1.01 to 1.46 ; P=0.04 ) . Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group ( P st and ard therapy , the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events . These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes . ( Clinical Trials.gov number , NCT00000620 ."
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OBJECTIVE Impaired awareness of hypoglycemia ( IAH ) increases the risk of severe hypoglycemia ( SH ) sixfold and affects 30 % of adults with type 1 diabetes ( T1D ) . This systematic review and meta- analysis looks at the educational , technological , and pharmacological interventions aim ed at restoring hypoglycemia awareness ( HA ) in adults with T1D . RESEARCH DESIGN AND METHODS We search ed The Cochrane Library , MEDLINE , Embase , Science Citation Index Exp and ed , Social Sciences Citation Index , PsycINFO , and CINAHL from inception until 1 October 2014 . Included studies described HA status at baseline . Outcome measures were SH rates , change in HA , counterregulatory hormone responses , and glycemic control . RESULTS Forty-three studies ( 18 r and omized controlled trials , 25 before- and -after studies ) met the inclusion criteria , comprising 27 educational , 11 technological , and 5 pharmacological interventions . Educational interventions included structured diabetes education on flexible insulin therapy , including psychotherapeutic and behavioral techniques . These were able to reduce SH and improve glycemic control , with greater benefit from the latter two techniques in improving IAH . Technological interventions ( insulin pump therapy , continuous glucose monitoring , and sensor-augmented pump ) reduced SH , improved glycemic control , and restored awareness when used in combination with structured education and frequent contact . Pharmacological studies included four insulin studies and one noninsulin study , but with low background SH prevalence rates . CONCLUSIONS This review provides evidence for the effectiveness of a stepped-care approach in the management of patients with IAH , initially with structured diabetes education in flexible insulin therapy , which may incorporate psychotherapeutic and behavioral therapies , progressing to diabetes technology , incorporating sensors and insulin pumps , in those with persisting need
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"Summary In patients with insulin-dependent diabetes mellitus ( IDDM ) good glycaemic control confers an enhanced risk of hypoglycaemia . Nocturnal hypoglycaemia occurs frequently and contributes to the syndrome of hypoglycaemia unawareness . In order to avoid nocturnal hypoglycaemia we substituted night-time continuous subcutaneous insulin infusion ( CSII ) therapy in 14 patients with well-controlled IDDM using a multiple injection regimen for the more variable bedtime NPH insulin . During a stepwise hypoglycaemic clamp we studied the effect of this regimen on counterregulatory hormonal responses , warning symptoms and cognitive function . In addition , we investigated the incidence of daytime hypoglycaemia and the acceptability of night-time CSII treatment . CSII was associated with a lower frequency of hypoglycaemia ( mean ± SEM ) : 16.1 ± 3.1 vs 23.6 ± 3.3 ) episodes during the last 6 weeks of treatment , p = 0.03 ( CSII vs NPH ) ) with maintenance of good glycaemic control ( HbA1c 7.2 ± 0.2 vs 7.1 ± 0.2 % , p = 0.2 ) . Hypoglycaemic thresholds for the growth hormone response and for autonomic symptoms were lower for CSII treatment than for NPH treatment . Of 14 patients 6 decided to continue with the nocturnal CSII treatment . In conclusion , nocturnal CSII improves warning symptoms and counterregulatory hormonal responses to hypoglycaemia and is an acceptable treatment strategy for patients suffering from hypoglycaemia unawareness , as demonstrated in this acute feasibility study . [ Diabetologia ( 1998 ) 41 : 322–329",
"Currently , the major indications for solitary islet transplantation are recurrent severe hypoglycemia and labile glucose control . Quantifying these problems remains subjective . We have developed a scoring system for both hypoglycemia and glycemic lability , established normative data , and used them in patients who have undergone islet transplantation . A composite hypoglycemic score ( HYPO score ) was devised based on the frequency , severity , and degree of unawareness of the hypoglycemia . In addition , using 4 weeks of glucose records , a lability index ( LI ) was calculated based on the change in glucose levels over time and compared with a clinical assessment of glycemic lability . A mean amplitude of glycemic excursions ( MAGE ) was also calculated based on 2 consecutive days of seven readings each day . These scores were determined in 100 r and omly selected subjects with type 1 diabetes from our general clinic to serve as a control group and in patients before and after islet transplantation . The mean age of the control diabetic subjects was 38.4 + /- 1.3 years ( + /-SE ) , with a duration of diabetes of 21.5 + /- 1.1 years . The median HYPO score in the control subjects was 143 ( 25th to 75th interquartile range : 46 - 423 ) . The LI in the diabetic control subjects was 223 ( 25th to 75th interquartile range : 130 - 329 mmol/l(2)/h.week(-1 ) ) . The LI correlated much more closely than the MAGE with the clinical assessment of lability . A HYPO score of > or = 1,047 ( 90th percentile ) or an LI > or = 433 mmol/l(2)/h.week(-1 ) ( 90th percentile ) indicated serious problems with hypoglycemia or glycemic lability , respectively . The islet transplant patients ( n = 51 ) were 42.1 + /- 1.4 years old , with a duration of diabetes of 25.7 + /- 1.4 years . Islet transplant patients had a mean HYPO score of 1,234 + /- 184 pretransplant , which was significantly higher than that of the control subjects ( P median LI pretransplant was 497 mmol/l(2)/h.week(-1 ) ( 25th to 75th interquartile range : 330 - 692 ) , significantly higher than that of control subjects ( P HYPO score and LI provide measures of the extent of problems with hypoglycemia and glycemic lability , respectively , complement the clinical assessment of the problems with glucose control before islet transplantation , and will allow comparison of selection of subjects for transplants between centers",
"OBJECTIVE To prospect ively evaluate the frequency and severity of hypoglycemic episodes in IDDM subjects who declare themselves to have reduced awareness of hypoglycemia , to vali date their self- design ations in their natural environment , and to determine objective ly the presence or absence of autonomic and neuroglycopenic symptoms associated with their low blood glucose ( BG ) levels . RESEARCH DESIGN AND METHODS A total of 78 insulin-dependent diabetes mellitus ( IDDM ) subjects ( mean age 38.3 ± 9.2 years ; duration of diabetes 19.3 ± 10.4 years ) completed two sets of assessment s separated by 6 months . The assessment s included reports of frequency and severity of low BG , symptoms associated with low BG , and a BG symptom/estimation trial using a h and -held computer ( HHC ) . Diaries of hypoglycemic episodes were kept for the intervening 6 months . HbA1 levels were determined at each assessment . RESULTS Of the subjects , 39 declared themselves as having reduced awareness of hypoglycemia ( reduced-awareness subjects ) . There were no differences between these reduced-awareness subjects and aware subjects with regard to age , sex , disease duration , insulin dose , or HbA1 . During the HHC trials , reduced-awareness subjects were significantly less accurate in detecting BG ( 33.2 ± 47 vs. 47.6 ± 50 % detection , P = 0.001 ) and had significantly fewer autonomic ( 0.41 ± 0.82 vs. 1.08 ± 1.22 , P = 0.006 , reduced-awareness vs. aware ) and neuroglycopenic ( 0.44 ± 0.85 vs. 1.18 ± 1.32 , P = 0.004 , reduced-awareness vs. aware ) symptoms per subject . Prospect i ve diary records revealed that reduced-awareness subjects experienced more moderate ( 351 vs. 238 , P = 0.026 ) and severe ( 50 vs. 17 , P = 0.0062 ) hypoglycemic events . The second assessment results were similar to the first and verified the reliability of the data . CONCLUSIONS IDDM subjects who believe they have reduced awareness of hypoglycemia are generally correct . They have a history of more moderate and severe hypoglycemia , are less accurate at detecting BG , and prospect ively experience more moderate and severe hypoglycemia than do aware subjects . Neither disease duration nor level of glucose control explains their reduced awareness of hypoglycemia . Reduced-awareness individuals may benefit from interventions design ed to teach them to recognize all of their potential early warning symptoms",
"OBJECTIVE To determine the effect of blood glucose awareness training ( BGAT ) on epinephrine and symptom responses to hypoglycemia in patients with type 1 diabetes enrolled in an intensive diabetes treatment ( IDT ) program . RESEARCH DESIGN AND METHODS A total of 47 subjects with uncomplicated diabetes ( duration 9 + /- 3 years : HbA1c 9.0 + /- 1.2 % ; reference range 4 - 6 % ) enrolled in a 4-month outpatient IDT program were r and omized to classes in BGAT ( n = 25 ) ( BGAT group ) or cholesterol awareness ( n = 22 ) ( control group ) . Subjects underwent stepped hypoglycemic clamp studies before and at completion of IDT . Plasma glucose was lowered from 6.7 mmol/l ( baseline ) to 4.4 , 3.9 , 3.3 , 2.8 , and 2.2 mmol/l over 190 min . Symptoms , counterregulatory hormones , and ability of the subject to estimate their glucose level were assessed at each plateau . At home , subjects used a h and held computer to first estimate and then measure and record blood glucose levels for 70 trials over a 4-week period immediately before IDT and again immediately following the educational intervention . RESULTS HbA1c decreased in both BGAT group ( 9.1 + /- 1.4 to 7.9 + /- 1.1 % ; P Frequency of hypoglycemia ( Epinephrine responses after IDT were greater in the BGAT group ( repeated measure analysis of variance [ ANOVA ] , F = 3.5 , P hypoglycemia ( HbA1c after IDT 2 percentage points ) showed that frequency of hypoglycemia increased in both the groups : from 0.50 + /- 0.09 to 0.80 + /- 0.11 episodes per day ( P epinephrine response in control subjects decreased with IDT while the response in the BGAT subjects was preserved ( repeated measure ANOVA , F = 4.4 , P BGAT is a useful intervention to decrease blunting of counterregulatory responses associated with improved glycemic control and may modify the severity of hypoglycemia associated with improved glycemic control in type 1 diabetes",
"Aims /hypothesisThe aim of this study was to evaluate the implementation of a course teaching flexible , intensive insulin therapy on glycaemic control and severe hypoglycaemia in routine care . Methods This is a continuous quality -assurance project involving hospital diabetes centres . Every third year each centre re-examines 50 consecutive patients ( evaluation sample ) 1 year after participation in the course . Ninety-six diabetes centres in Germany participated and 9,583 patients with type 1 diabetes ( 190 evaluation sample s ) were re-examined between 1992 and 2004 . The intervention was a 5-day inpatient course for groups of up to ten patients with a fixed curriculum of education and training for dietary flexibility and insulin adjustment . The main outcome measures were HbA1c and severe hypoglycaemia . Results Mean baseline HbA1c was 8.1 % , and had decreased to 7.3 % at follow-up ; incidence of severe hypoglycaemia was 0.37 events per patient per year prior to intervention and 0.14 after intervention . In mixed-effects models adjusted for effects of centres , age and diabetes duration , the mean difference was −0.7 % ( 95 % CI −0.9 to −0.6 % , p the incidence of severe hypoglycaemia was three-fold higher in the lowest quartile than in the highest quartile of HbA1c , whereas the risk was comparable across the range of HbA1c values after intervention . Conclusions /interpretationImplemented as part of a continuous quality -assurance programme the self-management programme is effective and safe in routine care . Improvement of glycaemic control can be achieved without increasing the risk of severe hypoglycaemia",
"OBJECTIVE To determine the frequency of hypoglycemia in patients with type I diabetes and impaired awareness of hypoglycemia by prospect i ve assessment . RESEARCH DESIGN AND METHODS A prospect i ve study was undertaken for 12 months in 60 patients with type I diabetes : 29 had impaired awareness of hypoglycemia and 31 retained normal awareness of hypoglycemia . The two groups of patients were matched for age , age at onset of diabetes , duration of diabetes , and glycemic control . Episodes of severe hypoglycemia were recorded within 24 h of the event and verified where possible by witnesses . RESULTS During the 12 months , 19 ( 66 % ) of the patients with impaired awareness had one or more episodes of severe hypoglycemia with an overall incidence of 2.8 episodes · patient–1 · year–1 . By comparison , 8 ( 26 % ) of the patients with normal awareness experienced severe hypoglycemia ( P ) . Severe hypoglycemia occurred at different times of the day in the two groups : patients with impaired awareness experienced a greater proportion of episodes during the evening ( P = 0.03 ) , and patients with normal awareness experienced a greater proportion in the early morning ( P = 0.05 ) . An assessment of fear of hypoglycemia revealed that patients with impaired awareness of hypoglycemia worried more about hypoglycemia than did patients with normal awareness ( P = 0.008 ) , but did not modify their behavior accordingly . CONCLUSIONS This prospect i ve evaluation demonstrated that impaired awareness of hypoglycemia predisposes to a sixfold increase in the frequency of severe hypoglycemia , much of which occurred at home during waking hours",
"BACKGROUND Severe hypoglycemia can have a dramatic impact on daily life for people with diabetes . Hypoglycemia is quantifiable by the HYPO-Score derived from the frequency of severe hypoglycemia over a year and a component based on 4 weeks of glucose records . The latter gives a modified HYPO-Score as a short-term measure of hypoglycemia . We used a continuous glucose monitoring system ( CGMS ) in patients with severe hypoglycemia to assess if we could decrease hypoglycemia as measured by the modified HYPO-Score . METHODS Sixteen type 1 diabetes subjects , 52.0 + /- 2.3 years old with a diabetes duration of 29.4 + /- 2.8 years having problematic hypoglycemia were enrolled . All used multiple daily insulin injections , and the glycosylated hemoglobin level was 8.4 + /- 0.3 % . After a month of gathering hypoglycemia information for baseline modified HYPO-Score , subjects wore the CGMS for 2 months , and a modified HYPO-Score was repeated . To assess long-term benefit , CGMS was then discontinued for 3 months , and a final modified HYPO-Score was determined . RESULTS The modified HYPO-Score decreased from 857 + /- 184 to 444 + /- 92 ( P = 0.055 ) ( intention-to-treat basis ) . Further analysis of the modified HYPO-Score when the CGMS was actually functioning showed it decreased from 857 + /- 184 to 366 + /- 86 ( P = 0.023 ) . Severe hypoglycemia episodes dropped from 16 at baseline to three when wearing the CGMS . The number of hypoglycemia episodes fear of hypoglycemia with CGMS . In 11 who completed modified Final Month HYPO-Scores , the number of severe hypoglycemic events rose to six . At study end , 13 of 16 subjects elected to continue using the CGMS . CONCLUSIONS When the CGMS was worn and functioning there was a significant decrease in the modified HYPO-Score and number of hypoglycemic values < 3.0",
"BACKGROUND Impaired awareness of hypoglycaemia ( IAH ) is common in adults with Type 1 diabetes mellitus ( T1DM ) and is a major risk factor for severe hypoglycaemia . Little is known about its effect on employment status . AIMS To examine the effect that IAH has on the employment status or employability of people with T1DM . METHODS A r and omly selected cohort of adults of employment age with T1DM completed a question naire detailing the history of their diabetes , their occupational history ( including job and industry type ) and assessing both their hypoglycaemia awareness status and whether in their view their ability to obtain or retain employment had been adversely affected by having diabetes . RESULTS A total of 252 patients participated , with the following characteristics : 135 males , mean HbA1c 8.5 % [ st and ard deviation ( SD ) 1.4 ] , mean age 43.3 years ( SD 13.2 ) , mean duration of diabetes 21.3 years ( SD 12.8 ) and prevalence of IAH 23.4 % . The employment rate was comparable between those with preserved awareness ( 73 % ) and the IAH group ( 66 % ) ( not significant ) . People with IAH were older ( P having diabetes affected their ability to work ( P as economically active as those with normal awareness of hypoglycaemia , although subjects with IAH were significantly more likely to feel that having diabetes had adversely affected their capacity for employment",
"Hypoglycemia unawareness is a major limiting factor in the management of type 1 diabetes ( 1 ) . This common problem , reported to occur in about 25 % of patients with type 1 diabetes ( 2 ) , is characterized by loss of autonomic warning symptoms before development of neuroglycopenia ( 2 ) . Hypoglycemia unawareness is associated with a sevenfold increase in the frequency of severe hypoglycemia ( 3 ) , which may be accompanied by seizure and coma . In the past decade , several risk factors for hypoglycemia unawareness have been identified , including long duration of diabetes , tight glycemic control ( low hemoglobin A1c values ) , and repeated episodes of hypoglycemia ( 1 , 2 , 4 - 7 ) . It has been thought that reduced counterregulatory hormone responses to hypoglycemia ( 4 , 5 ) are primarily responsible for hypoglycemia unawareness . However , recent studies suggest that impaired -adrenergic sensitivity ( 8 - 10 ) may also be involved . Patients with type 1 diabetes experience progressive reduction in the plasma catecholamine response to hypoglycemia ( 11 ) . This phenomenon may be an intrinsic element of type 1 diabetes or a consequence of cortisol release during hypoglycemia , which has been shown to blunt catecholamine response during subsequent hypoglycemic episodes ( 12 ) . Hypoglycemia-aware patients with type 1 diabetes who have reduced catecholamine responses during hypoglycemia have increased -adrenergic sensitivity ( 10 ) , perhaps because increases in plasma cortisol during hypoglycemia upregulate -receptors ( 13 , 14 ) . With continued episodes of hypoglycemia , the maximally enhanced -adrenergic sensitivity decreases and hypoglycemia unawareness ensues , probably because of exhausted -receptor upregulation ( 9 ) . Indeed , a single episode of hypoglycemia reduces -adrenergic sensitivity in patients with type 1 diabetes who are already compensating for reduced catecholamine response to hypoglycemia with maximally enhanced -adrenergic sensitivity ( 10 ) . Studies of patients with insulinoma ( 15 ) , those who have had pancreas transplantation ( 16 ) , and those with type 1 diabetes ( 17 - 21 ) indicate that hypoglycemia unawareness can be reversed by avoidance of hypoglycemia . In patients with type 1 diabetes ( 17 - 21 ) , hypoglycemia unawareness has been shown to occur in the absence of improved plasma catecholamine responses ( 20 , 22 ) , suggesting that increased sensitivity to catecholamines may be the primary mechanism . We sought to examine the effect of strict avoidance of hypoglycemia for 4 months in 10 patients with diabetes of long duration , hypoglycemia unawareness , and a history of severe hypoglycemia . Methods Participants The protocol was approved by the Ethical Committee of the University of Tbingen School of Medicine . Ten men with type 1 diabetes who had self-reported reduced awareness of hypoglycemia and a history of severe hypoglycemia as defined by the Diabetes Control and Complications Trial ( 7 , 23 ) ( hypoglycemia result ing in coma or seizure , requiring assistance of another person and treatment with glucagon or intravenous glucose ) were studied . All participants gave written informed consent . Clinical characteristics are shown in the Table . Table . Patient Characteristics and Responses during Hypoglycemic Clamp In all participants , autonomic neuropathy was excluded by st and ard cardiovascular testing ( variation in resting heart rate according to spectral analysis , the Valsalva maneuver , lying-to-st and ing , and deep breathing [ 24 ] ) . All patients were receiving an intensive insulin regimen with injections of long-acting insulin in the morning and at bedtime and short-acting insulin before meals ( usually three times daily ) . We compared the study patients with 10 patients who had type 1 diabetes and hypoglycemia awareness and 10 nondiabetic controls ; data on these 20 persons were published elsewhere ( 10 ) . These 20 persons had been studied by using methods identical to those in the present study . Prevention of Hypoglycemia To avoid hypoglycemia , we followed modifications of the guidelines proposed by Amiel ( 25 ) . Target prepr and ial blood glucose levels were increased from 5.6 mmol/L to 8.3 mmol/L ( 100 mg/dL to 150 mg/dL ) , and target bedtime blood glucose levels were increased from 5.6 mmol/L to 10 mmol/L ( 100 mg/dL to 180 mg/dL ) to avoid nighttime hypoglycemia . To achieve these targets , the dose of long-acting insulin ( preferably that given at bedtime ) was reduced . The daily short-acting insulin dose was reduced and adjusted individually to the carbohydrate content of the meal to be consumed and the actual blood glucose level . Patients were instructed to measure blood glucose at least five times daily . During the study , participants were contacted at least biweekly for adjustments of insulin dosage intended to prevent blood glucose levels from decreasing to less than 3.9 mmol/L ( 70 mg/dL ) . Patient adherence to the new blood glucose targets was reinforced by discussion with patients of the importance of the problem . Protocol Participants underwent hyperinsulinemic hypoglycemic clamp before and after 4 months of prevention of hypoglycemia . Isoproterenol testing was performed to measure -adrenergic sensitivity before and after 2 and 4 months of prevention of hypoglycemia . Isoproterenol testing was performed approximately 1 week before the corresponding hypoglycemic clamp . For both the hypoglycemic clamp and the isoproterenol test , participants were admitted to the university 's clinical research unit at 8:00 pm . They had been instructed to reduce their insulin dose by 10 % for 3 days before testing to avoid blood glucose lower than 5 mmol/L ( 90 mg/dL ) . They had injected their last regular dose of insulin before dinner on the day before testing . At 11:00 pm , they injected a 10 % reduced dose of neutral protamine Hagedorn insulin to avoid blood glucose levels less than 6.7 mmol/L ( 120 mg/dL ) . During the night , blood glucose was checked every 2 hours . Oral administration of 10 g of glucose was planned if blood glucose levels decreased below 6.7 mmol/L ( 120 mg/dL ) ; this did not occur in any patient . Isoproterenol Testing At 7:00 a.m. , an indwelling catheter was inserted into an antecubital vein for infusion of insulin and injection of isoproterenol . A variable insulin infusion ( 0 to 1 mU/kg/min ) was begun to keep blood glucose levels between 6.7 and 10 mmol/L ( 120180 mg/dL ) during isoproterenol testing . Participants were connected to a computer-assisted electrocardiograph ( NeuroDiag , Munich , Germany ) for determination of cardiovascular responses . Blood pressure was recorded by using an automatic device ( DINAMAP , Critikon , Tampa , Florida ) . Appropriately diluted isoproterenol ( Isuprel , Sanofi , Brussels , Belgium ) was injected as a 5-mL bolus in a forearm vein through a three-way valve in doses of 0 ( 5 mL NaCl , 0.9 % ) , 0.25 , 0.5 , 0.75 , 1.0 , 1.5 , 2.0 , 2.5 , 3.0 , and 4.0 g. The interval between each injection was 20 minutes . An electrocardiogram was recorded online for 1 minute before and 5 minutes after each injection . The basal heart rate was defined as the mean of the rate obtained in the 20 seconds before the first injection . The maximal heart rate was usually reached approximately 30 to 60 seconds after each injection and returned to baseline before the end of the 5-minute recording interval . The maximal heart rate was determined by search ing for the shortest RR interval after injection ; extrasystoles were excluded by graphical analysis of heart rate recordings . Blood pressure was recorded at baseline and at 2 minutes and 5 minutes after injection , by which time heart rate had returned to baseline . Blood glucose was measured every 15 minutes . The test was stopped prematurely if the increase in heart rate exceeded 50 beats/min or maximal blood pressure exceeded 170/90 mm Hg . -Adrenergic sensitivity was expressed as the dose of isoproterenol that increased heart rate by 25 beats/min ( IC25 ) . This value was determined by fitting a curve through the change in heart rates plotted over the isoproterenol doses and calculating the intercept , with the change in heart rate equal to 25 beats/min . Hypoglycemic Clamp At 7:00 a.m. , indwelling catheters were inserted into an antecubital vein for infusion of glucose and insulin and into a dorsal h and vein for arterial blood sampling . The h and was kept in a heated chamber during this procedure . An insulin infusion with a constant rate of 1 mU/kg per minute was begun , and blood glucose was clamped at 3 mmol/L ( 54 mg/dL ) for 180 minutes . Afterward , participants received a st and ardized meal containing 48 g of carbohydrates and were discharged as soon as blood glucose levels exceeded 6.7 mmol/L ( 120 mg/dL ) . Symptom Question naire A semiquantitative symptom question naire was administered twice before hypoglycemic clamp and at 30 , 90 , 150 , and 180 minutes during the clamp . Participants scored their symptoms from 0 ( none ) to 7 ( severe ) in response to 9 autonomic symptoms ( tremor , sweating , shivering , hunger , pounding heart , anxiety , nausea , feeling tearful ) , 10 neuroglycopenic symptoms ( difficulty speaking , double vision , headache , drowsiness , blurred vision , tingling around the mouth , inability to concentrate , confusion , tiredness , weakness ) and 10 dummy symptoms . All of these symptoms were presented to patients in r and om order ( 26 ) . Total symptom score and the neuroglycopenic and autonomic symptom scores were calculated for each time point . Blood Sampling and Analysis Plasma epinephrine and norepinephrine levels were measured at 30 and 15 minutes before and 30 , 90 , 150 , and 180 minutes during hypoglycemic clamp . Blood glucose was measured at the bedside by using a Hemocue blood glucose photometer ( Hemocue AB , Angelham , Sweden ) . Catecholamines were measured in ethylenediamine tetraacetic acidtreated plasma by using high-performance liquid chromatography with electrochemical detection ( ClinRep Analysis Kit , Recipe Pharma , Munich , Germany ) . Statistical Analysis Unless otherwise stated , data are given as the mean ( SE ) . For increments of catecholamine",
"OBJECTIVE To investigate the effects of a multiple injection regimen with a mixture of 75 % lispro and 25 % intermediate-acting insulin ( lispro high mixture [ HM ] ) before meals on glycemic control , physiological responses to hypoglycemia , well-being , and treatment satisfaction . RESEARCH DESIGN AND METHODS We studied 35 type 1 diabetes patients . After an 8- to 10-week lead-in period , patients were r and omized to HM or human regular insulin therapy for 12 - 14 weeks . During the lead-in and treatment periods , HbA1c levels and hypoglycemic frequencies were measured , and patients completed the Well-Being Question naire and the Diabetes Treatment Satisfaction Question naire . In 19 patients , responses to hypoglycemia were tested during stepped euglycemic-hypoglycemic clamps . RESULTS HM treatment improved postpr and ial glycemia but had no effect on HbA1c , frequency of hypoglycemia , well-being , or treatment satisfaction . During experimental hypoglycemia , HM therapy was associated with a slightly lower total adrenaline response and a higher autonomic symptom threshold ( i.e. , the autonomic symptom response occurred at a lower blood glucose level ) than human regular insulin therapy . We speculate that this effect result ed from an accumulation of insulin during the night . CONCLUSIONS Multiple injection therapy with HM rather than human regular insulin before meals does not offer advantages regarding glycemic control , frequency of hypoglycemia , well-being , or treatment satisfaction . In addition , this regimen causes an attenuation of the adrenaline and autonomic symptom responses to hypoglycemia",
"OBJECTIVE Blood glucose awareness training ( BGAT ) has been shown to improve awareness of blood glucose ( BG ) fluctuations among adults with type 1 diabetes . This study investigates the long-term ( 12-month ) benefits of BGAT-2 . RESEARCH DESIGN AND METHODS A total of 73 adults with type 1 diabetes participated in a 6-month repeated baseline design with a 12-month follow-up . At 6 months and 1 month before BGAT-2 and at 1,6 , and 12 months after BGAT-2 , subjects used a h and held computer for 50 trials and completed psychological tests . Throughout assessment , subjects completed diaries , recording occurrences of diabetic ketoacidosis , severe hypoglycemia , and motor vehicle violations During follow-up , 50 % of the subjects received booster training . RESULTS During the first and last halves of both the baseline period and the follow-up period , dependent variables were generally stable . However , from baseline to follow-up , BGAT-2 led to 1 ) improved detection of hypoglycemia and hyperglycemia ; 2 ) improved judgment regarding when to lower high BG , raise low BG , and not drive while hypoglycemic ; 3 ) reduction in occurrence of diabetic ketoacidosis , severe hypoglycemia , and motor vehicle violations ; and 4 ) improvement in terms of worry about hypoglycemia , quality of life , and diabetes knowledge . Reduction in severe hypoglycemia was not associated with a worsening of metabolic control ( HbA1 ) . The presence or absence of booster training did not differentially affect these benefits . CONCLUSION BGAT has sustained broad-ranging benefits , independent of booster intervention",
"Although both diabetes and the efficacy of medical management are international issues , psycho-educational interventions might be culturally bound . Blood Glucose Awareness Training ( BGAT ) is a psycho-educational program for patients with type 1 diabetes mellitus . It is focused on improving recognition and management of extreme blood glucose levels , and is the best documented American psycho-educational program for this purpose . A r and omized controlled clinical trial of BGAT 's long-term benefits in a non-American setting has been lacking . One hundred and eleven adults with type 1 diabetes mellitus from Switzerl and and Germany participated . After a 6 months baseline assessment , subjects were r and omly assigned to receive either 2 months of BGAT ( n = 56 ) or a physician-guided self-help control intervention ( n = 55 ) . BGAT improved recognition of low ( p = 0.008 ) , high ( p = .03 ) , and overall blood glucose ( p = 0.001 ) , and reduced frequency of severe hypoglycemia ( p = 0.04 ) , without compromising metabolic control . BGAT reduced both the external locus of control ( p fear of hypoglycemia ( p BGAT was efficacious in reducing adverse clinical events and achieving clinical ly desirable goals in a European , as well as American setting",
"& NA ; Insulin‐dependent diabetes mellitus ( IDDM ) patients make critical daily self‐care decisions on the basis of what they estimate their blood glucose ( BG ) levels to be . This study : a ) replicated efficacy of St and ard Blood Glucose Awareness Training ( BGAT ) , b ) evaluated the relative efficacy of an Intensive Blood Glucose Awareness Training ( BGAT ) to enhance patient accuracy of BG estimation , and c ) evaluated the mechanisms and ancillary effects of BGAT . Thirty‐nine subjects were r and omly assigned to one of three groups . Compared with Control , both St and ard and Intensive BGAT improved accuracy ( p less than 0.001 ) . Intensive BGAT post‐treatment accuracy relative to St and ard BGAT did not reach statistical significance ( p = 0.177 ) . Greater improvement in accuracy was associated with poorer pretreatment accuracy . Only Intensive BGAT improved metabolic control ( glycosylated hemoglobin ) , and this improvement was associated with poorer pretreatment control . The effects of BGAT were highly specific , affecting only accuracy and metabolic control , and not affecting fear of hypoglycemia , diabetes knowledge , of frequency of blood glucose monitoring",
"OBJECTIVE To test the effect of an automated system providing real-time estimates of HbA1c , glucose variability , and risk for hypoglycemia . RESEARCH DESIGN AND METHODS For 1 year , 120 adults with type 1 diabetes ( 69 female/51 male , age = 39.1 [ 14.3 ] years , duration of diabetes 20.3 [ 12.9 ] years , HbA1c = 8.0 [ 1.5 ] ) , performed self-monitoring of blood glucose ( SMBG ) and received feedback at three increasingly complex levels , each continuing for 3 months : level 1—routine SMBG ; level 2—adding estimated HbA1c , hypoglycemia risk , and glucose variability ; and level 3—adding estimates of symptoms potentially related to hypoglycemia . The subjects were r and omized to feedback sequences of either levels 1 - 2 - 3 or levels 2 - 3 - 1 . HbA1c , symptomatic hypoglycemia , and blood glucose awareness were evaluated at baseline and at the end of each level . RESULTS For all subjects , HbA1c was reduced from 8.0 to 7.6 from baseline to the end of study ( P = 0.001 ) . This effect was confined to subjects with baseline HbA1c > 8.0 ( from 9.3 to 8.5 , P Incidence of symptomatic moderate/severe hypoglycemia was reduced from 5.72 to 3.74 episodes/person/month ( P = 0.019 ) , more prominently for subjects with a history of severe hypoglycemia ( from 7.20 to 4.00 episodes , P = 0.008 ) and for those who were hypoglycemia unaware ( from 6.44 to 3.71 episodes , P = 0.045 ) . The subjects ’ ratings of the feedback were positive , with up to 89 % approval of the provided features . CONCLUSIONS Feedback of SMBG data and summary SMBG-based measures result ed in improvement in average glycemic control and reduction in moderate/severe hypoglycemia . These effects were most prominent in subjects who were at highest risk at the baseline",
"OBJECTIVE DAFNE ( Dose Adjustment For Normal Eating ) , a structured education program in flexible insulin therapy , has been widely adopted in the U.K. after validation in a r and omized trial . To determine benefits in routine practice , we collected biomedical and psychological data from all participants attending during a 12-month period . RESEARCH DESIGN AND METHODS HbA1c , weight , self-reported hypoglycemia awareness , severe hypoglycemia frequency , PAID ( Problem Areas In Diabetes ) , HADS ( Hospital Anxiety and Depression Scale ) , and EuroQol Group 5-Dimension Self-Report Question naire scores were recorded prior to DAFNE and after 1 year . RESULTS Complete baseline and follow-up HbA1c data were available for 639 ( 54.9 % ) of 1,163 attendees . HbA1c fell from 8.51 ± 1.41 ( mean ± SD ) to 8.24 ± 1.29 % ( difference 0.27 [ 95 % CI 0.16–0.38 ] ; P 8.5 % . Severe hypoglycemia rate fell from 1.7 ± 8.5 to 0.6 ± 3.7 episodes per person per year ( 1.1 [ 0.7–1.4 ] ) and hypoglycemia recognition improved in 43 % of those reporting unawareness . Baseline psychological distress was evident , with a PAID score of 25.2 and HADS scores of 5.3 ( anxiety ) and 4.8 ( depression ) , falling to 16.7 ( 8.5 [ 6.6–10.4 ] ) , 4.6 ( 0.7 [ 0.4–1.0 ] ) , and 4.2 ( 0.6 [ 0.3–0.8 ] ) , respectively ( all P year ) . Clinical ly relevant anxiety and depression ( HADS ≥8 ) fell from 24.4 to 18.0 % and 20.9 to 15.5 % , respectively . CONCLUSIONS A structured education program delivered in routine clinical practice not only improves HbA1c while reducing severe hypoglycemia rate and restoring hypoglycemia awareness but also reduces psychological distress and improves perceived well-being ",
"OBJECTIVE Impaired awareness of hypoglycemia ( IAH ) and defective counterregulation significantly increase severe hypoglycemia risk in type 1 diabetes ( T1D ) . We evaluated restoration of IAH/defective counterregulation by a treatment strategy targeted at hypoglycemia avoidance in adults with T1D with IAH ( Gold score ≥4 ) participating in the U.K.-based multicenter HypoCOMPaSS r and omized controlled trial . RESEARCH DESIGN AND METHODS Eighteen subjects with T1D and IAH ( mean ± SD age 50 ± 9 years , T1D duration 35 ± 10 years , HbA1c 8.1 ± 1.0 % [ 65 ± 10.9 mmol/mol ] ) underwent stepped hyperinsulinemic-hypoglycemic clamp studies before and after a 6-month intervention . The intervention comprised the HypoCOMPaSS education tool in all and r and omized allocation , in a 2 × 2 factorial study design , to multiple daily insulin analog injections or continuous subcutaneous insulin infusion therapy and conventional glucose monitoring or real-time continuous glucose monitoring . Symptoms , cognitive function , and counterregulatory hormones were measured at each glucose plateau ( 5.0 , 3.8 , 3.4 , 2.8 , and 2.4 mmol/L ) , with each step lasting 40 min with subjects kept blinded to their actual glucose value throughout clamp studies . RESULTS After intervention , glucose concentrations at which subjects first felt hypoglycemic increased ( mean ± SE from 2.6 ± 0.1 to 3.1 ± 0.2 mmol/L , P = 0.02 ) , and symptom and plasma metanephrine responses to hypoglycemia were higher ( median area under curve for symptoms , 580 [ interquartile range { IQR } 420–780 ] vs. 710 [ 460–1,260 ] , P = 0.02 ; metanephrine , 2,412 [ −3,026 to 7,279 ] vs. 5,180 [ −771 to 11,513 ] , P = 0.01 ) . Glycemic threshold for deterioration of cognitive function measured by four-choice reaction time was unchanged , while the color-word Stroop test showed a degree of adaptation . CONCLUSIONS Even in long-st and ing T1D , IAH and defective counterregulation may be improved by a clinical strategy aim ed at hypoglycemia avoidance",
"PURPOSE To investigate hypoglycemic and hyperglycemic symptoms , accuracy of estimating blood glucose , and their relation to glycemic control and counterregulatory hormone levels in insulin-dependent diabetes mellitus . PATIENTS AND METHODS During r and omly ordered stepped hypoglycemic and hyperglycemic insulin clamps on two separate days , 42 patients with insulin-dependent diabetes mellitus rated the intensity of 40 moods and symptoms when glucose was 8.9 , 5.6 and 2.2 mmol/L , and 8.9 , 14.4 and 21.1 mmol/L. The subjects were blinded to their actual glucose levels and asked to estimate them at each step . Epinephrine , norepinephrine , cortisol , growth hormone , and glucagon were measured at each glucose plateau . RESULTS Cluster analysis yielded five symptom groups during hypoglycemia : autonomic symptoms , negative moods , positive moods , feeling weak/dizzy , and feeling relaxed . At 2.2 mmol/L , mean scores for all five symptom groups and 11 of 17 unclustered symptoms differed from those reported at the baseline glucose of 8.9 mmol/L ( P intensity of autonomic symptoms correlated positively with HbA1 ( r = .43 , P cortisol ( r = .62 , P symptoms different from those they reported as their usual manifestations of changing glucose levels . CONCLUSIONS Since the majority of patients made clinical ly serious errors in glucose estimation , and many used symptoms that did not discriminate hyperglycemia and hypoglycemia , individualized training to increase awareness of glucose-related symptoms and glucose levels may help patients reduce the frequency or severity of hyperglycemic and hypoglycemic events",
"OBJECTIVE To assess the potential of insulin lispro to limit the frequency of severe hypoglycaemia without compromising glycaemic control in a cohort of patients with type 1 diabetes who are at a high risk of severe hypoglycemia . Research design and methods An open-label , r and omised , 12-month comparative crossover study of insulin lispro and regular human insulin was performed in 33 patients with type 1 diabetes with impaired hypoglycaemia awareness . The efficacy of each treatment was evaluated by glycaemic control ( HbA(1c ) ) , eight-point home blood glucose profiles , and the frequency and severity of hypoglycaemic episodes and quality of life . RESULTS Eighteen ( 55 % ) patients experienced one or more episodes of severe hypoglycaemia in the 48 weeks of study . There was a trend to a lower incidence of severe hypoglycaemia during treatment with insulin lispro in comparison with regular human insulin ( 55 vs 84 episodes , p=0.087 ) . This result ed principally from a 47 % lower incidence of nocturnal severe hypoglycaemia with insulin lispro ( 25 vs 47 episodes , p=0.11 ) . The lower frequency of severe hypoglycaemia associated with insulin lispro was not explained by differences in glycated haemoglobin between insulin treatments ( HbA(1c ) 9.1 % insulin lispro vs 9.3 % regular human insulin ) . CONCLUSIONS In individuals with type 1 diabetes , who have impaired awareness of hypoglycaemia , treatment with insulin lispro may be associated with a lower incidence of severe hypoglycaemia manifested predominantly through less frequent nocturnal episodes . Insulin lispro may have a beneficial role in the management of patients with diabetes at risk of severe hypoglycaemia , although a larger study is required to confirm these findings",
"OBJECTIVE Blood glucose awareness training ( BGAT ) teaches individuals with insulin-dependent diabetes to more accurately estimate/detect their blood glucose ( BG ) fluctuations . It has not , however , consistently result ed in improved ability to detect low BG . To assess an enhanced version of BGAT ( BGAT-II ) , with more focus on increasing sensitivity to low BG events , a multicenter study was undertaken . Following up on previous findings that BGAT is most effective with individuals who are least accurate in estimating BG , this study explicitly recruited subjects who did and did not report reduced awareness of hypoglycemia . RESEARCH DESIGN AND METHODS Seventy-eight subjects from three research sites participated in a repeated baseline design . Subjects ' BG estimation accuracy and BG profiles were assessed 6 months before , immediately before , and immediately after BGAT-II . RESULTS Post-treatment , BGAT-II led to better overall accuracy in detecting BG fluctuations and better detection of both low and high BG levels . This was achieved while the number of low readings of self-monitoring of blood glucose ( SMBG ) was reduced . Reduction in the number of low SMBG events was significant only for subjects reporting awareness of hypoglycemia . Detection of low BG was significant only for subjects reporting reduced awareness of hypoglycemia . Both groups demonstrated equivalent improvements in detection of high BG levels . CONCLUSIONS BGAT may be an effective behavioral strategy for reversing hypoglycemic unawareness and an adjunct to intensive insulin therapy to reduce the occurrence of severe hypoglycemia",
"OBJECTIVE Evaluation of an ambulatory diabetes teaching and treatment refresher programme ( DTTP ) for the optimization of intensified insulin therapy in patients with type 1 diabetes ( refresher course ) . METHODS 85 out patients took part in this prospect i ve multicentre trial . Metabolic and psychosocial data were analyzed at baseline ( V1 ) , 6 weeks ( V2 ) and 12 months after DTTP ( V3 ) . RESULTS In patients with baseline HbA1c>7 % ( 88 % ) , HbA1c decreased by 0.36 % ( p=0.004 ) . The percentage of patients with HbA1c≤7 % increased from 21.3 to 34.9 % and with HbA1c above 10 % decreased from 6.6 to 1.6 % at V3 . The incidence of hypoglycaemia decreased significantly : non severe hypoglycaemia from 3.31 to 1.39 episodes/pat/week ( p=0.001 ) and severe hypoglycaemia from 0.16 to 0.03 episodes/pat/year ( p=0.02 ) . The treatment satisfaction increased by + 10 of maximal ±18 points . The negative influence of diabetes on quality of life decreased from -1.93 to -1.69 points ( p=0.031 ) . CONCLUSION In a group of patients with moderately controlled diabetes type 1 who were already treated with intensified insulin therapy , metabolic control , treatment satisfaction and quality of life were improved after participation in an ambulatory DTTP without increasing insulin dosage , number of injections or insulin species . PRACTICE IMPLICATION S This DTTP is effective for the optimization of intensified insulin therapy",
"Aim : Insulin lispro used in an intensive basal/bolus regimen produces equivalent glycaemic control to human‐soluble insulin but reduces rates of hypoglycaemia . We tested the hypothesis that the use of rapid‐acting analogues might prevent the development of defective hypoglycaemic counterregulation during intensive insulin therapy",
"Context Clinicians often split evening insulin dosing ( short-acting insulin at dinner and long-acting insulin at bedtime rather than both types with dinner ) to avoid nocturnal hypoglycemia in patients with type 1 diabetes mellitus . Although split dosing makes sense theoretically , no rigorous studies have examined its effects on glycemic control . Contribution In this r and omized , controlled crossover trial , episodes of nocturnal hypoglycemia were less frequent and fasting blood glucose and hemoglobin A1c levels were lower with split evening insulin than with mixed dosing at dinner . Clinical Implication s This study supports splitting evening insulin dosing to improve glycemic control in patients with intensively treated type 1 diabetes . The Editors Nocturnal hypoglycemia is common in patients with type 1 diabetes mellitus ( 1 - 7 ) . When insulin treatment is intensified to achieve near-normoglycemia , the frequency of hypoglycemia increases ; approximately half of these episodes occur at night ( 2 , 3 ) . Unrecognized nocturnal hypoglycemia is common ( 1 , 3 - 8 ) . Overtreatment of symptomatic nocturnal hypoglycemia with snacks often results in hyperglycemia the next day ( 9 - 11 ) . Asymptomatic nocturnal hypoglycemia can cause morning headache and malaise and may result in diminished awareness , reduced responses of adrenaline , and adaptation of cognitive function during the episode ( 12 - 15 ) . Recurrent nocturnal hypoglycemia may contribute to the vicious cycle of hypoglycemia unawareness and impaired hormonal counterregulation in patients with type 1 diabetes , leading to increased risk for severe hypoglycemia ( 16 ) . The nonphysiologic pharmacokinetics and pharmacodynamics of insoluble , intermediate-acting insulin preparations , such as neutral protamine Hagedorn ( NPH ) insulin , play a central role in inducing nocturnal hypoglycemia in type 1 diabetes ( 4 ) . When injected at dinner , NPH insulin results in excess plasma insulin bioavailability at approximately midnight , a time at which patients with type 1 diabetes are more insulin sensitive ( 17 , 18 ) ; thus , the risk for hypoglycemia increases between midnight and 3:00 a.m. Later , insulin deficiency develops at dawn ( 4 , 18 ) and contributes to fasting hyperglycemia . When the nocturnal peak plasma level of insulin produced by an evening injection of intermediate-acting ( NPH ) insulin is postponed by 3 to 4 hours as a result of injecting NPH insulin at bedtime instead of at dinner , fasting and postbreakfast blood glucose levels decrease ( 19 ) . Although the pharmacokinetics and pharmacodynamics of NPH insulin would suggest that splitting of the evening insulin regimen ( administering short-acting insulin at dinner and NPH insulin at bedtime ) should decrease the risk for nocturnal hypoglycemia , to the best of our knowledge no data indicate this in patients with type 1 diabetes mellitus . W e tested the hypothesis that in intensive treatment of type 1 diabetes , splitting the evening insulin administration rather than mixing short-acting and NPH insulin at dinner reduces the risk for nocturnal hypoglycemia and improves glycemic control , awareness of hypoglycemia , and counterregulation to hypoglycemia . Although split dosing makes sense theoretically , no rigorous studies have examined its effects on glycemic control . Methods Patients We recruited 22 patients ( 10 women , 12 men ; mean age [ SD ] , 29 3 years ) with type 1 diabetes mellitus ( mean duration of diagnosed diabetes [ SD ] , 14 2 years ) receiving long-term intensive insulin treatment ( multiple insulin injections with regular human insulin before meals and NPH insulin at bedtime ) from the outpatient Diabetes Clinic of the Department of Internal Medicine at the University of Perugia . At baseline , the mean ( SD ) body mass index of the cohort was 23 1 kg/m2 , and the mean ( SD ) hemoglobin A1c value was 6.7 % 0.4 % . Patients had no detectable microangiopathic complications ; autonomic neuropathy , as assessed by using a st and ard battery of cardiovascular tests [ 20 ] ; peripheral neuropathy ; or microalbuminuria . The patients had no history or clinical evidence of hypertension and were taking no medications other than insulin . We excluded 1 ) patients with hypoglycemia unawareness , defined as an absence of symptoms while the blood glucose level is approximately 2.5 to 2.8 mmol/L [ 45 to 50 mg/dL ] and 2 ) patients with a history of severe hypoglycemia , defined as episodes of hypoglycemia requiring assistance from another person in the previous year . All patients in the study gave informed consent . The Institutional Review Board of University of Perugia in Perugia , Italy , approved this study . Study Design After a 1-month run-in period , during which patients continued their usual regimen of multiple daily insulin injections , we r and omly assigned patients to receive one of the two following treatment regimens for the first 4-month treatment period : 1 ) a continued regimen of four daily insulin injections ( evening split treatment)that is , administration of regular insulin before dinner and NPH insulin at bedtime [ usually between 10:30 p.m. and 11:00 p.m. ] or 2 ) a regimen of regular insulin at breakfast and lunch and a mixture of regular and NPH insulins at dinner ( evening mixed treatment ) . Thereafter , the patients were switched to the other treatment for an additional 4 months . Insulin ( short-acting and NPH ) was administered with syringes to achieve the target values for fasting blood glucose of 5.0 to 6.7 mmol/L ( 90 to 120 mg/dL ) before meals and at bedtime [ 2 ] . The dose of mealtime regular insulin was titrated on the basis of the blood glucose measurement obtained 1 ) before the meal and 2 ) on the previous day , 4 to 5 hours after that meal , or , in the case of the evening meal , at bedtime . The dose of NPH insulin given at dinner or at bedtime was titrated on the basis of the predinner or bedtime blood glucose level , respectively . The patients were instructed to measure capillary blood glucose levels by using Reflolux S ( Boehringer Mannheim , Mannheim , Germany ) before each insulin injection , at bedtime , and every other day at 3:00 a.m. The patients were also asked to skip no more than one of their daily capillary glucose measurements and to keep diaries of blood glucose values , insulin dosage , and hypoglycemic episodes ( blood glucose level 4.0 mmol/L [ 72 mg/dL ] ) occurring any time during the day . To prevent nocturnal hypoglycemia , the patient instructions included a suggestion to consume a snack containing approximately 20 g of carbohydrates ( approximately 20 g of bread and approximately 60 mL of 2 % milk ) when the capillary blood glucose level at bedtime was less than 7.0 mmol/L ( blood glucose level at 3:00 a.m. was 4.0 mmol/L or less ( 72 mg/dL ) at any time during the night . If such a snack did not relieve hypoglycemic symptoms in approximately 10 minutes , patients were told to have another snack ( for a total of 40 g of carbohydrates ) . Throughout the study , patients visited the outpatient clinic monthly to su bmi t their diaries and had frequent telephone contacts ( every 3 to 6 days ) with the investigators . At the end of each treatment period , patients were admitted to the clinical research unit of the hospital , where blood glucose was monitored overnight ; the next morning , counterregulatory and symptomatic responses to hypoglycemia and cognitive performance were evaluated during a hyperinsulinemic , stepped hypoglycemic clamp study . Hemoglobin A1c values were measured before r and omization and at the end of both treatment periods . In-Hospital Evaluation Overnight Testing Patients were admitted for overnight evaluations after dinner ( and , thus , after premeal insulin administration ) , at approximately 9:00 p.m. A h and vein of the nondominant arm was cannulated retro grade ly , and the h and was maintained in a hot pad ( approximately 60 C ) for sampling of arterialized-venous blood ( 21 ) . A second venous line of the ipsilateral arm was cannulated for intravenous infusion of glucose whenever an infusion was needed to prevent hypoglycemia ( that is , to prevent a decrease in plasma glucose level to 4.0 mmol/L [ 72 mg/dL ] ) . Glucose was infused whenever the plasma glucose level decreased to less than 4.4 mmol/L ( television until 11:00 p.m. , at which time patients receiving the evening split regimen had their bedtime injection of NPH insulin . Overnight , patients gave blood sample s for measurement of plasma glucose and insulin levels every 30 minutes . Stepped Hypoglycemic Clamp Studies At 8:30 a.m. on the following morning , a variable intravenous infusion of human regular insulin ( diluted to 1 U/mL in 2 mL of the patient 's blood and sodium chloride [ NaCl 0.9 % ] to a final volume of 100 mL ) was begun to maintain a plasma glucose level of 5.0 mmol/L ( 90 mg/dL ) . Infusion continued until 10:00 a.m. For this procedure , which was done according to a previously described algorithm ( 22 ) , we used an intravenous syringe pump ( Harvard Apparatus , Ealing , South Natick , Massachusetts ) . At 10:00 a.m. , the rate of intravenous insulin infusion was increased to 1 mU/kg 1 min 1 until 2:30 p.m. ( 270 minutes ) , followed by 2 mU/kg 1 min 1 for an additional 90 minutes , until 4:00 p.m. ( time , 360 minutes ) . Plasma glucose was clamped by variable glucose infusion at sequential target glucose values of 4.3 , 3.7 , 3.0 , and 2.3 mmol/L ( 78 , 66 , 54 , and 42 mg/dL ) ; at each target level , blood was drawn to measure hormone and metabolite levels , and patients were assessed for symptoms of hypoglycemia and for cognitive function ( 23 - 25 ) . Symptoms were quantified by asking the patients to score ( on a scale in which 0 = none and 5 = severe ) each of the following symptoms : dizziness , tingling , blurred vision , difficulty in thinking , faintness , anxiety , palpitations , hunger , sweating , irritability ,",
"AIM To determine potential for amelioration of recurrent severe hypoglycaemia without worsening in overall control in individuals with long-st and ing Type 1 diabetes ( T1DM ) . METHODS Twenty-one people with T1DM characterized by altered hypoglycaemia awareness and debilitating severe hypoglycaemia were r and omized in a pilot 24-week prospect i ve study to optimized analogue therapy ( ANALOGUE ; lispro/glargine ) ; continuous subcutaneous insulin infusion therapy ( CSII ; lispro ) ; or re-education with relaxation of blood glucose targets on existing conventional insulin regimen ( EDUCATION ) . Glycaemic profiles and duration of biochemical hypoglycaemia were measured by continuous subcutaneous glucose monitoring and self-monitored blood glucose . RESULTS Further severe hypoglycaemia was prevented in five participants ( 71 % ) in each group ( P = 0.06 ) . Incidence of severe hypoglycaemia was : 0.6 ( ANALOGUE ) , 0.9 ( CSII ) , and 3.7 ( EDUCATION ) episodes per patient year . Restoration of hypoglycaemia awareness was confirmed by vali date d question naire in three ( 43 % ) ANALOGUE , four ( 57 % ) CSII and five ( 71 % ) EDUCATION patients . Glycated haemoglobin ( HbA1c ) was significantly improved in the ANALOGUE group between weeks 0 and 24 ( 8.6 + /- 1.1 vs. 7.6 + /- 0.8 % ; P = 0.04 for change ) . Non-significant improvement was seen in the CSII group ( 8.5 + /- 1.9 vs. 7.4 + /- 1.0 % ; P = 0.06 ) . No change in HbA1c was seen in the EDUCATION group ( 8.5 + /- 1.1 vs. 8.3 + /- 1.0 % ; P = 0.54 ) . There were no episodes of diabetic ketoacidosis or any other adverse events in any group . CONCLUSIONS In this pilot r and omized trial comparing optimized ANALOGUE , CSII or EDUCATION alone in unselected individuals with recurrent severe hypoglycaemia , we show potential for restoring hypoglycaemia awareness and preventing further severe hypoglycaemia with concomitant improvement in glycaemic control in ANALOGUE and CSII groups",
"OBJECTIVE Aim of this study was to investigate the effectiveness of a patient education program for the treatment of hypoglycemia-associated problems in type 1 diabetic in patients . METHODS In this observational controlled pre-post study , the intervention group ( IG ; N = 105 ) participated in the new program , controls ( control group CG ; N = 102 ) received conventional patient education on hypoglycemia . RESULTS Follow-up data ( mean follow-up : 6.63 months ) were obtained from 177 patients ( 85.6 % ) . Though severe hypoglycemia also decreased in CG to some degree , the decrease in IG was higher than in CG , but fails to reach significance between groups . Hypoglycemia awareness remained constant in IG , whereas some deterioration was observed in CG ( p = 0.06 ) . Prevalence of hypoglycemia-related problems decreased in IG , whereas in CG it remained constant . No differential effects with regard to psychological well being , fear of hypoglycemia and late complications , and control beliefs were observed . CONCLUSION The results suggest that the new intervention program is an effective treatment . The effectiveness should be confirmed , however , in a r and omized controlled trial , also incorporating outpatient setting s. PRACTICE IMPLICATION S A self-management intervention targeting the patients ' health beliefs and attitudes towards hypoglycemia and their diabetes self-management , rather than knowledge-centered patient education , can help to ameliorate or even prevent hypoglycemia-associated problems",
"Severe hypoglycemia ( SH ) can be a significant problem for patients around the world with Type 1 Diabetes Mellitus ( T1DM ) . To avoid SH , patients need to better manage , and reduce the occurrence of , preceding mild hypoglycemia . Hypoglycemia Anticipation , Awareness and Treatment Training ( HAATT ) , developed in the United States specifically to address such issues , was evaluated at short- and long-term follow-up in a medically , economically and culturally different setting ; Bulgaria . Sixty adults with T1DM and a history of recurrent SH ( 20 each from Sofia , Russe , and Varna , Bulgaria ) were r and omized to Self-Monitoring of Blood Glucose ( SMBG ) or SMBG+ HAATT . For 6 months before and 1 to 6 and 13 to 18 months after intervention , participants recorded occurrence of moderate , severe , and nocturnal hypoglycemia . For 1-month pre- and post-intervention , participants completed daily diaries concerning their diabetes management . Relative to SMBG , HAATT produced significant improvement in occurrence of low BG , moderate , severe , and nocturnal hypoglycemia , and detection and treatment of low BG ( p values compromise in metabolic control . At long-term follow-up , HAATT participants continued to have significantly fewer episodes of moderate and severe hypoglycemia . These findings suggest that a structured , specialized psycho-educational treatment program ( HAATT ) can be highly effective in managing hypoglycemia",
"IMPORTANCE Hypoglycemia is a critical obstacle to the care of patients with type 1 diabetes . Sensor-augmented insulin pump with automated low-glucose insulin suspension has the potential to reduce the incidence of major hypoglycemic events . OBJECTIVE To determine the incidence of severe and moderate hypoglycemia with sensor-augmented pump with low-glucose suspension compared with st and ard insulin pump therapy . DESIGN , SETTING , AND PARTICIPANTS A r and omized clinical trial involving 95 patients with type 1 diabetes , recruited from December 2009 to January 2012 in Australia . INTERVENTIONS Patients were r and omized to insulin pump only or automated insulin suspension for 6 months . MAIN OUTCOMES AND MEASURES The primary outcome was the combined incidence of severe ( hypoglycemic seizure or coma ) and moderate hypoglycemia ( an event requiring assistance for treatment ) . In a subgroup , counterregulatory hormone responses to hypoglycemia were assessed using the hypoglycemic clamp technique . RESULTS Of the 95 patients r and omized , 49 were assigned to the st and ard-pump ( pump-only ) therapy and 46 to the low-glucose suspension group . The mean ( SD ) age was 18.6 ( 11.8 ) years ; duration of diabetes , 11.0 ( 8.9 ) years ; and duration of pump therapy , 4.1 ( 3.4 ) years . The baseline rate of severe and moderate hypoglycemic events in the pump-only group was 20.7 vs 129.6 events per 100 patient months in the low-glucose suspension group . After 6 months of treatment , the event rates decreased from 28 to 16 in the pump-only group vs 175 to 35 in the low-glucose suspension group . The adjusted incidence rate per 100 patient-months was 34.2 ( 95 % CI , 22.0 - 53.3 ) for the pump-only group vs 9.5 ( 95 % CI , 5.2 - 17.4 ) for the low-glucose suspension group . The incidence rate ratio was 3.6 ( 95 % CI , 1.7 - 7.5 ; P glycated hemoglobin in either group : mean , 7.4 ( 95 % CI , 7.2 - 7.6 ) to 7.4 ( 95 % CI , 7.2 - 7.7 ) in the pump-only group vs mean , 7.6 ( 95 % , CI , 7.4 - 7.9 ) to 7.5 ( 95 % CI , 7.3 - 7.7 ) in the low-glucose suspension group . Counterregulatory hormone responses to hypoglycemia were not changed . There were no episodes of diabetic ketoacidosis or hyperglycemia with ketosis . CONCLUSIONS AND RELEVANCE Sensor-augmented pump therapy with automated insulin suspension reduced the combined rate of severe and moderate hypoglycemia in patients with type 1 diabetes . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12610000024044",
"The purpose of this prospect i ve before- and -after study was to determine whether there are psychosocial and physical benefits of a self-awareness intervention for adults with type 1 diabetes and hypoglycemia unawareness ( HU ) . A total of 29 adults participated in the self-awareness intervention of 8 sessions , each lasting 3 hours . Psychosocial ( integration , diabetes quality of life ) and physical ( number of body cues , HU-related events , HbA1c ) measures were taken at baseline and at 6 , 12 , and 18 months post-intervention . Post-intervention the participants detected more cues of euglycemia and hypoglycemia and experienced significant increases in integration and metabolic control ( HbA1c ) . The number of HU-related events was not decreased and diabetes quality -of-life results were unstable . A self-awareness intervention can have physical and psychosocial benefits and has implication s for diabetes education . This intervention needs to be tested in a multi-centre r and omized control trial",
"Summary Hypoglycaemia unawareness , is a major risk factor for severe hypoglycaemia and a contraindication to the therapeutic goal of near-normoglycaemia in IDDM . We tested two hypotheses , first , that hypoglycaemia unawareness is reversible as long as hypoglycaemia is meticulously prevented by careful intensive insulin therapy in patients with short and long IDDM duration , and that such a result can be maintained long-term . Second , that intensive insulin therapy which strictly prevents hypoglycaemia , can maintain long-term near-normoglycaemia . We studied 21 IDDM patients with hypoglycaemia unawareness and frequent mild/severe hypoglycaemia episodes while on “ conventional ” insulin therapy , and 20 nondiabetic control subjects . Neuroendocrine and symptom responses , and deterioration in cognitive function were assessed in a stepped hypoglycaemia clamp before , and again after 2 weeks , 3 months and 1 year of either intensive insulin therapy which meticulously prevented hypoglycaemia ( based on physiologic insulin replacement and continuous education , experimental group , EXP , n=16 ) , or maintenance of the original “ conventional ” therapy ( control group , CON , n=5 ) . At entry to the study , all 21 IDDM- patients had subnormal neuroendocrine and symptom responses , and less deterioration of cognitive function during hypoglycaemia . After intensive insulin therapy in EXP , the frequency of hypoglycaemia decreased from 0.5±0.05 to 0.045±0.02 episodes/patient-day ; HbA1C increased from 5.83±0.18 to 6.94±0.13 % ( range in non-diabetic subjects 3.8–5.5 % ) over a 1-year period ; all counterregulatory hormone and symptom responses to hypoglycaemia improved between 2 weeks and 3 months , with the exception of glucagon which improved at 1 year ; and cognitive function deteriorated further as early as 2 weeks ( p The improvement in plasma adrenaline and symptom responses inversely correlated with IDDM duration . In contrast , in CON , neither frequency of hypoglycaemia , nor neuroendocrine responses to hypoglycaemia improved . Thus , meticulous prevention of hypoglycaemia by intensive insulin therapy reverses hypoglycaemia unawareness even in patients with long-term IDDM , and is compatible with long-term near-normoglycaemia . Because carefully conducted intensive insulin therapy reduces , not increases the frequency of moderate/severe hypoglycaemia , intensive insulin therapy should be extended to the majority of IDDM patients in whom it is desirable to prevent/delay the onset/progression of microvascular complications ",
"The effect of propranolol on the occurrence of hypoglycaemic symptoms was assessed in insulin-dependent diabetic patients with hypoglycaemia unawareness . A double-blind , r and omised parallel group study ( 2:1 fashion ) was conducted over 4-week period . The propranolol group ( n = 9 ) received 20 mg ( week 1 and 2 ) and 30 mg ( week 3 and 4 ) twice daily , and the other group ( n = 5 ) a matched placebo for 4 weeks . Patients included had experienced at least two severe hypoglycaemic episodes ( coma or seizures ) during the previous year , which were characterised by a lack of adrenergic symptoms and required the assistance of another person . The mean number of hypoglycaemias during the study period was similar in both groups ( placebo : 13 + /- 2 propranolol : 11 + /- 1 ) , whereas the number of totally asymptomatic hypoglycaemias ( propranolol than on placebo ( 3 + /- 1 vs 8 + /- 3 , NS ) and the number of symptomatic hypoglycaemias was higher ( 7.2 + /- 2 vs 4.6 + /- 1 , NS ) . Subjective evaluation of treatment by the investigators showed 0/5 successes in the placebo group and 5/9 in the propranolol group ( chi2 = 4.32 , p = 0.038 ) . The main advantage of propranolol over placebo was an increased incidence of sweating . The ratio [ number of hypoglycaemias with sweating/total number of hypoglycaemias ] being higher with propranolol ( 0.28 + /- 0.08 vs 0.06 + /- 0.02 , p = 0.06 ) . This pilot study suggests that beta-blockers may be useful in restoring adrenergic symptoms during hypoglycaemia in insulin-dependent diabetic patients without warning symptoms of hypoglycaemia . This beneficial effect seems to be predominantly related to an increase in hypoglycaemia-induced sweating . A larger study is needed to confirm or invali date these preliminary results",
"OBJECTIVE In a r and omized , multi-centre trial , the efficacy of a self-management-oriented education programme ( PRIMAS ) for people with type 1 diabetes was compared with an established education programme as control group ( CG ) . Primary outcome was the effect on glycaemic control in a 6-month follow-up . Secondary outcomes were the impact on emotional aspects , self-management related aspects and hypoglycaemia problems . METHODS The study was conducted in an outpatient setting . 160 participants were r and omized . Baseline characteristics in PRIMAS and CG were similar ( age 45.1±13.5 vs. 45.9±13.1 years , p=.716 ; diabetes duration 18.8±12.3 vs. 19.8±13.4 years , p=.615 ; BMI 26.5±4.6 vs. 27.5±5.0kg/m(2 ) , p=.236 ; HbA1c 8.3±1.1 vs. 8.1±1.0 % , p=.236 ) . RESULTS At follow-up there was a significant 0.4 percentage points greater reduction of HbA1c in PRIMAS compared to CG ( Δ -0.4±1.0 % vs. Δ 0.0±0.6 % ; p=.012 ) . Also , diabetes-related distress ( Δ -0.3±0.7 vs. -0.1±0.4 , p=.032 ) and dissatisfaction with diabetes treatment ( Δ -3.3±6.9 vs. -1.9±5.6 , p=.024 ) decreased more in PRIMAS . Diabetes empowerment ( Δ 2.6±5.9 vs. 0.8±5.1 , p=.037 ) and diabetes self-efficacy ( Δ 1.4±3.6 vs. 0.2±4.0 , p=.013 ) increased in PRIMAS . Incidence of severe hypoglycemia , hypoglycemia awareness , diabetes knowledge , and self-care behaviour improved in both groups with no significant differences between groups . CONCLUSION PRIMAS is more effective in lowering HbA1c than a previously established education programmes and also showed superiority in reducing diabetes-related distress and increasing diabetes empowerment , diabetes self-efficacy and satisfaction with insulin therapy",
"BACKGROUND In a r and omized , prospect i ve multi-centre trial , the effect of a specific training programme ( HyPOS ) for patients with hypoglycaemia problems was compared with a control group ( CG ) , receiving a st and ardized education programme aim ing at avoidance of hypoglycaemia by optimization of insulin therapy . METHODS A total of 164 type 1 diabetes patients ( age 46.0 + /- 12.5 yrs , HbA(1c ) 7.3 + /- 1.0 % , 50 % male ) were r and omized . Hypoglycaemia awareness was measured by the hypoglycaemia awareness question naire ( HAQ ) and by a visual analogue scale ( VAS ) . There were no baseline differences . RESULTS After a 6-month follow-up , hypoglycaemia awareness significantly improved in HyPOS compared to that in the CG ( Delta HAQ 0.7 [ 95 % CL 0.1 - 1.2 ] , p = 0.024 , Delta VAS 0.8 [ 95 % CL 0.2 - 1.2 ] , p = 0.015 ) . In HyPOS , the threshold for detection of low blood glucose ( Delta 0.2 mmol/L [ 95 % CL 0.03 - 0.04 ] , p = 0.02 ) and the treatment of low blood glucose ( Delta 4.6 g [ 95 % CL 1.6 - 7.6 ] , p = 0.03 ) increased significantly . The number of undetected hypogylcaemic episodes ( Delta - 1.4 episodes per week [ 95 % CL 0.4 - 2.5 ] , p = 0.01 ) and the rate of mild hypoglycaemia dropped significantly in HyPOS ( Delta 2.1 % [ 95 % CL 0.5 - 5.3 ] , p = 0.015 ) . The numbers of severe ( Delta 0.3 events per patient per year [ 95 % CL - 0.04 - 1.0 ] , p = 0.037 ) and very severe hypoglycaemic episodes ( Delta 0.3 events per patient per year [ 95 % CL - 0.1 - 0.7 ] , p = 0.09 ) were lower in HyPOS , but these differences were not significant . CONCLUSION Compared to the CG , HyPOS demonstrates additional benefits in terms of improving impaired hypoglycaemia awareness , reducing mild hypoglycaemia , detecting low blood glucose , and treating low blood glucose",
"OBJECTIVE Blood glucose awareness training ( BGAT ) has been found effective in teaching individuals with insulin-requiring diabetes to improve their ability to better recognize blood glucose ( BG ) fluctuations . This study investigated whether subjects who underwent BGAT a mean of 4.9 years previously were superior to past control subjects in terms of their ability to recognize BG fluctuations , and whether past BGAT subjects had fewer automobile crashes and lost work days and better glycosylated hemoglobin than control subjects . Additionally , the beneficial effects of providing booster training to past BGAT subjects also was evaluated . RESEARCH DESIGN AND METHODS This study followed up 28 past BGAT subjects . Half of these subjects ( n = 14 ) received a simple booster-training program . Twelve previous control subjects also were evaluated . Booster subjects were given a BGAT diary to complete for 2 weeks before evaluation . Evaluation for all subjects included completion of a retrospective question naire on work and driving history , blood drawing for a glycosylated hemoglobin analysis , and having subjects estimate and measure their BG levels 50–80 times during a 3- to 4-week period during their daily routine . RESULTS At long-term follow-up , BGAT subjects had significantly fewer automobile crashes than control subjects . BGAT subjects receiving booster training were significantly more accurate at estimating their BG levels and were more aware of hypoglycemia . Post hoc analyses indicated that the ability to accurately estimate BG fluctuations correlated positively with follow-up glycosylated hemoglobin and the number of hypoglycemic and hyperglycemic symptoms participants demonstrated . Both BGAT and control subjects demonstrated significantly improved glycosylated hemoglobin relative to baseline measures . CONCLUSIONS These data suggest that BGAT has long-term benefits , which can be enhanced with booster training . Specifically , BGAT and simple booster training may result in reduction of severe hypoglycemic episodes and automobile crashes in the long term",
"PURPOSE Patients with intensively treated insulin-dependent diabetes mellitus ( IDDM ) exhibit more severe defects in counterregulatory hormone secretion and symptom recognition during hypoglycemia than do conventionally treated patients . In this prospect i ve study in patients with preexisting defects in counterregulation , we examined the induction and reversibility of impaired symptomatic and adrenomedullary responses to hypoglycemia in 5 patients with IDDM ( diabetes duration of 2 to 16 years ; aged 19 to 36 years ; 3 women , 2 men ) who were receiving intensive therapy . METHODS Counterregulatory responses were assessed by using a single-step ( approximately 2.8 mmol/L plasma glucose ) and multiple-step ( from approximately 5 mmol/L to 2.2 mmol/L plasma glucose ) clamped hypoglycemia procedure . Patients were first studied after a stable period of conventional insulin therapy ( glycosylated hemoglobin [ HbA1c ] 9.5 + /- 1.2 % ) , then after 3 to 5 months of intensive therapy ( HbA1c 6.6 + /- 0.2 % ) , and a third time after resuming conventional therapy ( HbA1c 8.7 + /- 0.9 % ) . RESULTS Intensive therapy was associated with a 44 % decline ( P average plasma epinephrine increase during hypoglycemia , and the plasma glucose level required to stimulate epinephrine secretion fell from 3.7 + /- 0.2 to 3.0 + /- 0.1 mmol/L ( P threshold , but not the magnitude , of the plasma norepinephrine response was similarly altered . Hypoglycemic symptoms also decreased in intensity ( by 67 % , P glucose level required for symptom activation fell from 3.4 + /- 0.3 to 2.7 + /- 0.2 mmol/L , P conventional therapy was resumed , the abnormalities in the epinephrine response due to intensive therapy were almost completely reversed . However , the reduction in symptoms and the altered thresholds for plasma norepinephrine were not reversed . CONCLUSIONS There is dissociation between the treatment-associated defects in hypoglycemia counterregulation in IDDM , and an increase in average glycemia produced by a return to conventional insulin therapy is not sufficient to reverse hypoglycemia unawareness worsened by intensive therapy",
"OBJECTIVE To determine whether impaired awareness of hypoglycemia ( IAH ) can be improved and severe hypoglycemia ( SH ) prevented in type 1 diabetes , we compared an insulin pump ( continuous subcutaneous insulin infusion [ CSII ] ) with multiple daily injections ( MDIs ) and adjuvant real-time continuous glucose monitoring ( RT ) with conventional self-monitoring of blood glucose ( SMBG ) . RESEARCH DESIGN AND METHODS A 24-week 2 × 2 factorial r and omized controlled trial in adults with type 1 diabetes and IAH was conducted . All received comparable education , support , and congruent therapeutic targets aim ed at rigorous avoidance of biochemical hypoglycemia without relaxing overall control . Primary end point was between-intervention difference in 24-week hypoglycemia awareness ( Gold score ) . RESULTS A total of 96 participants ( mean diabetes duration 29 years ) were r and omized . Overall , biochemical hypoglycemia ( ≤3.0 mmol/L ) decreased ( 53 ± 63 to 24 ± 56 min/24 h ; P = 0.004 [ t test ] ) without deterioration in HbA1c . Hypoglycemia awareness improved ( 5.1 ± 1.1 to 4.1 ± 1.6 ; P = 0.0001 [ t test ] ) with decreased SH ( 8.9 ± 13.4 to 0.8 ± 1.8 episodes/patient-year ; P = 0.0001 [ t test ] ) . At 24 weeks , there was no significant difference in awareness comparing CSII with MDI ( 4.1 ± 1.6 vs. 4.2 ± 1.7 ; difference 0.1 ; 95 % CI −0.6 to 0.8 ) and RT with SMBG ( 4.3 ± 1.6 vs. 4.0 ± 1.7 ; difference −0.3 ; 95 % CI −1.0 to 0.4 ) . Between-group analyses demonstrated comparable reductions in SH , fear of hypoglycemia , and insulin doses with equivalent HbA1c . Treatment satisfaction was higher with CSII than MDI ( 32 ± 3 vs. 29 ± 6 ; P = 0.0003 [ t test ] ) , but comparable with SMBG and RT ( 30 ± 5 vs. 30 ± 5 ; P = 0.79 [ t test ] ) . CONCLUSIONS Hypoglycemia awareness can be improved and recurrent SH prevented in long-st and ing type 1 diabetes without relaxing HbA1c . Similar biomedical outcomes can be attained with conventional MDI and SMBG regimens compared with CSII/RT , although satisfaction was higher with CSII",
"OBJECTIVE To develop and pilot a novel intervention addressing motivational and cognitive barriers to avoiding hypoglycemia in people with type 1 diabetes and persistent impaired awareness of hypoglycemia ( IAH ) despite training in flexible insulin therapy . RESEARCH DESIGN AND METHODS A 6-week intervention using motivational interviewing and cognitive behavioral techniques was design ed . Diabetes educators were trained and supported in its delivery to 23 people with IAH ( Gold score ≥4 ) . RESULTS Twelve months postcourse , hypoglycemia awareness had improved ( P 0.001 ) . Median ( range ) rates of severe hypoglycemia ( SH ) fell from 3 ( 0–104 ) to 0 ( 0–3 ) per person per year ( P weeks ( P HbA1c was unchanged . CONCLUSIONS A pilot intervention targeting motivation and cognitions around hypoglycemia engaged patients with resistant IAH and recurrent SH and was associated with significant improvement , supporting the hypothesis that these factors underpin problematic hypoglycemia"
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OBJECTIVE Few r and omized clinical studies have evaluated the impact of diet and physical activity on testosterone levels in obese men with conflicting results . Conversely , studies on bariatric surgery in men generally have shown an increase in testosterone levels . The aim of this study is to perform a systematic review and meta- analysis of available trials on the effect of body weight loss on sex hormones levels . DESIGN Meta- analysis . METHODS An extensive Medline search was performed including the following words : ' testosterone ' , ' diet ' , ' weight loss ' , ' bariatric surgery ' , and ' males ' . The search was restricted to data from January 1 , 1969 up to August 31 , 2012 . RESULTS Out of 266 retrieved articles , 24 were included in the study . Of the latter , 22 evaluated the effect of diet or bariatric surgery , whereas two compared diet and bariatric surgery . Overall , both a low-calorie diet and bariatric surgery are associated with a significant ( P in plasma sex hormone-binding globulin-bound and -unbound testosterone levels ( total testosterone ( TT ) ) , with bariatric surgery being more effective in comparison with the low-calorie diet ( TT increase : 8.73 ( 6.51 - 10.95 ) vs 2.87 ( 1.68 - 4.07 ) for bariatric surgery and the low-calorie diet , respectively ; both P baseline ) . And rogen rise is greater in those patients who lose more weight as well as in younger , non-diabetic subjects with a greater degree of obesity . Body weight loss is also associated with a decrease in estradiol and an increase in gonadotropins levels . Multiple regression analysis shows that the degree of body weight loss is the best determinant of TT rise ( B=2.50±0.98 , P=0.029 ) . CONCLUSIONS These data show that weight loss is associated with an increase in both bound and unbound testosterone levels . The normalization of sex hormones induced by body weight loss is a possible mechanism contributing to the beneficial effects of surgery in morbid obesity
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"INTRODUCTION Limited information is available concerning the general and sexual health status of European men . AIM To investigate the age-related changes in general and sexual health in middle-aged and older men from different countries of the European Union . METHODS This is a cross-sectional multicenter survey performed on a sample of 3,369 community-dwelling men aged 40 - 79 years old ( mean 60 + or - 11 years ) . Subjects were r and omly selected from eight European centers including centers from nontransitional ( Florence [ Italy ] , Leuven [ Belgium ] , Malmö[Sweden ] , Manchester [ United Kingdom ] , Santiago de Compostela [ Spain ] ) and transitional countries ( Lodz [ Pol and ] , Szeged [ Hungary ] , Tartu [ Estonia ] ) . MAIN OUTCOME MEASURES Different parameters were evaluated including the Beck 's Depression Inventory for the quantification of depressive symptoms , the Short Form-36 Health Survey for the assessment of the quality of life ( QoL ) , the International Prostate Symptom Score for the evaluation of lower urinary tract symptoms , and the European Male Ageing Study sexual function question naire for the study of sexual function . RESULTS More than 50 % of subjects reported the presence of one or more common morbidities . Overall , hypertension ( 29 % ) , obesity ( 24 % ) , and heart diseases ( 16 % ) were the most prevalent conditions . Around 30 % of men reported erectile dysfunction ( ED ) and 6 % reported severe orgasmic impairment , both of which were closely associated with age and concomitant morbidities . Only 38 % of men reporting ED were concerned about it . Furthermore , concern about ED increased with age , peaking in the 50 - 59 years age b and , but decreased thereafter . Men in transitional countries reported a higher prevalence of morbidities and impairment of sexual function as well as a lower QoL. CONCLUSION Sexual health declined while concomitant morbidities increased in European men as a function of age . The burden of general and sexual health is higher in transitional countries , emphasizing the need to develop more effective strategies to promote healthy aging for men in these countries",
"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 and aim : Male hypogonadism has been linked to obesity and diabetes . We aim ed to study the association of changes in insulin sensitivity and testosterone levels in severe obese patients su bmi tted to bariatric surgery . Subjects and methods : Prospect i ve intervention study with twenty consecutive patients who underwent bariatric surgery studied before and after significant weight loss . Serum testosterone , SHBG , fasting glucose , and insulin were measured among others . Free testosterone was calculated with the Vermeulen formula and insulin sensitivity with the homeostatic model assessment ( HOMA ) . Results : At baseline , thirteen patients had low total testosterone levels , whereas eight of these patients also had free testosterone levels below the reference range obtained from the control group . After bariatric surgery total testosterone , SHBG , and free testosterone significantly increased and achieved normal values in all evaluated patients . Insulin sensitivity improved in all of them . Multivariate linear regression showed that changes in fasting glucose ( β=−1.868 , p= 0.001 ) , insulin ( β=−3.782 , p= 0.001 ) , weight ( β=−0.622 , p= 0.002 ) , and SHBG ( β=−0.635 , p= 0.022 ) were associated with changes in free testosterone ( adjusted R2 = 0.936 , F=26.613 , p= 0.001 ) . When insulin resistance calculated by HOMA was in the model instead of insulin and glucose , it also was associated ( β=−3.488 , p= 0.008 ) with free testosterone ( adjusted R2 = 0.821 , F=11.111 , p= 0.005 ) . Conclusion : Circulating testosterone in obese men increases after bariatric surgery in parallel with an improvement in insulin sensitivity ",
"Summary Background The main associations of body-mass index ( BMI ) with overall and cause-specific mortality can best be assessed by long-term prospect i ve follow-up of large numbers of people . The Prospect i ve Studies Collaboration aim ed to investigate these associations by sharing data from many studies . Methods Collaborative analyses were undertaken of baseline BMI versus mortality in 57 prospect i ve studies with 894 576 participants , mostly in western Europe and North America ( 61 % [ n=541 452 ] male , mean recruitment age 46 [ SD 11 ] years , median recruitment year 1979 [ IQR 1975–85 ] , mean BMI 25 [ SD 4 ] kg/m2 ) . The analyses were adjusted for age , sex , smoking status , and study . To limit reverse causality , the first 5 years of follow-up were excluded , leaving 66 552 deaths of known cause during a mean of 8 ( SD 6 ) further years of follow-up ( mean age at death 67 [ SD 10 ] years ) : 30 416 vascular ; 2070 diabetic , renal or hepatic ; 22 592 neoplastic ; 3770 respiratory ; 7704 other . Findings In both sexes , mortality was lowest at about 22·5–25 kg/m2 . Above this range , positive associations were recorded for several specific causes and inverse associations for none , the absolute excess risks for higher BMI and smoking were roughly additive , and each 5 kg/m2 higher BMI was on average associated with about 30 % higher overall mortality ( hazard ratio per 5 kg/m2 [ HR ] 1·29 [ 95 % CI 1·27–1·32 ] ) : 40 % for vascular mortality ( HR 1·41 [ 1·37–1·45 ] ) ; 60–120 % for diabetic , renal , and hepatic mortality ( HRs 2·16 [ 1·89–2·46 ] , 1·59 [ 1·27–1·99 ] , and 1·82 [ 1·59–2·09 ] , respectively ) ; 10 % for neoplastic mortality ( HR 1·10 [ 1·06–1·15 ] ) ; and 20 % for respiratory and for all other mortality ( HRs 1·20 [ 1·07–1·34 ] and 1·20 [ 1·16–1·25 ] , respectively ) . Below the range 22·5–25 kg/m2 , BMI was associated inversely with overall mortality , mainly because of strong inverse associations with respiratory disease and lung cancer . These inverse associations were much stronger for smokers than for non-smokers , despite cigarette consumption per smoker varying little with BMI . Interpretation Although other anthropometric measures ( eg , waist circumference , waist-to-hip ratio ) could well add extra information to BMI , and BMI to them , BMI is in itself a strong predictor of overall mortality both above and below the apparent optimum of about 22·5–25 kg/m2 . The progressive excess mortality above this range is due mainly to vascular disease and is probably largely causal . At 30–35 kg/m2 , median survival is reduced by 2–4 years ; at 40–45 kg/m2 , it is reduced by 8–10 years ( which is comparable with the effects of smoking ) . The definite excess mortality below 22·5 kg/m2 is due mainly to smoking-related diseases , and is not fully explained . Funding UK Medical Research Council , British Heart Foundation , Cancer Research UK , EU BIOMED programme , US National Institute on Aging , and Clinical Trial Service Unit ( Oxford , UK )",
"OBJECTIVE To study the impact of a weight-loss program on sex hormones and sexual function among 38 middle-aged obese men ( BMI > or=35 kg/m(2 ) ) . RESEARCH METHODS AND PROCEDURES A r and omized controlled clinical trial was conducted . The treatment group ( n = 19 ) participated in a 4-month weight-loss program including 10 weeks on a very-low-energy diet ( VLED ) and 17 behavior modification visits . There was no intervention in the control group ( n = 19 ) . Both groups were followed for 8 months , i.e. , 22 weeks after the active weight loss in the treatment group . The outcome measures ( weight , sex hormones , sexual function , leptin , and metabolic variables ) were obtained at baseline and at three time-points during follow-up . RESULTS The mean weight loss in the treatment group was 21 kg at the end of the 10-week VLED . At the end of follow-up , the maintained weight loss was 17 kg of baseline weight . The control group was weight stable throughout the study . In the treatment group , increases in sex hormone-binding globulin , testosterone , and high-density lipoprotein-cholesterol , as well as decreases in insulin and leptin , were maintained until the end of follow-up , although with VLED , the level of several hormones and metabolic variables improved transiently during the rapid weight loss . There were no significant changes in the question naire scores on sexual function in either group . DISCUSSION We conclude that obese men lose weight and increase their serum testosterone level on a weight-loss program with VLED and behavior modification . However , they do not change their sexual function scores ",
"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",
"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",
"INTRODUCTION Endocrine disorders may adversely affect men 's sexual function . AIM To provide recommendations based on best evidence for diagnosis and treatment of endocrine-related male sexual dysfunctions . METHODS The Endocrine Aspects of Male Sexual Dysfunctions Committee , including 11 members from eight countries and four continents , collaborated with the Endocrine subcommittee of the St and ards Committee of the International Society for Sexual Medicine . Medical literature was review ed in detail , followed by extensive internal committee discussion over 2 years , then public presentation and discussion with the other experts before finalizing the report . MAIN OUTCOME MEASURE Recommendations based on grading of evidence -base medical literature and interactive discussion . RESULTS From animal studies , it is derived that testosterone modulates mechanisms involved in erectile machinery , including expression of enzymes that both initiate and terminate erection . In addition , testosterone is essential for sexual motivation . Whether these findings could be extrapolated to human erections is unclear . Testosterone plays a broad role in men 's overall health . Recent studies have established strong associations between low testosterone and metabolic and cardiovascular imbalances . In some studies , low testosterone decreased longevity ; however , longitudinal studies do not support the predictive value of low testosterone for further cardiovascular events . The article proposes a st and ardized process for diagnosis and treatment of endocrine-related male sexual dysfunctions , updating the knowledge on testosterone and prostate safety . There is no compelling evidence that testosterone treatment causes prostate cancer or its progression in men without severe testosterone deficiency ( TD ) . The possible roles of prolactin and thyroid hormones are also examined . CONCLUSIONS Men with erectile dysfunction , hypoactive sexual desire and retarded ejaculation , as well as those with visceral obesity and metabolic diseases , should be screened for TD and treated . Prospect i ve interventional studies are required before screening for TD in more conditions , including cardiovascular diseases , and considering correction as preventive medicine as much data suggests",
"The effects of weight loss on erectile function and hormones have not been well studied . The aim of this study was to measure the degree to which sexual function and in particular erectile function and hormonal environment change after substantial weight loss , surgically and non-surgically induced in the morbidly obese male in a prospect i ve r and omized long-term controlled trial . Furthermore , how surgery makes a difference when treating morbidly obese men was envisaged in this context . We prospect ively studied 20 morbidly obese men for 24 months , divided into two groups : group A included 10 patients who underwent life style modifications ( exercise and diet ) for 4 months and subsequently gastric bypass , and another 10 patients in group B were kept on weekly follow-up . None of the men were taking phosphodiesterase type-5 inhibitors . All patients underwent International Index of Erectile Function (IIEF)-5 question naire , serum oestradiol , prolactin ( PRL ) , luteinizing ( LH ) and follicle-stimulating ( FSH ) hormones , free and total testosterone ( FT and TT ) at baseline ( time 0 ) , surgery - 4 months latter baseline ( time 1 ) and final evaluation - 24 months ( time 2 ) . From times 0 to 1 , group A presented a mean body mass index ( BMI ) reduction of 12.6 ( p 0.05 ) . The BMI reductions between times 0 and 2 were 24.7 ( p 0.05 ) for groups A and B respectively . BMI average between the two groups was similar at time 0 ( p = 0.2142 ) , and different at times 1 ( p = 0.0033 ) and 2 ( p Increase in IIEF-5 score ( p = 0.0469 ) , TT ( p = 0.0349 ) and FSH levels ( p = 0.0025 ) , and reduction in PRL level ( p IIEF-5 , TT and FT increased significantly in group A ( p = 0.0224 , 0.0043 and 0.0149 respectively ) . Surgery-induced weight loss increased erectile function quality measured by IIEF-5 question naire , increased TT , FT and FSH and reduced PRL levels . The hormonal impact verified could justify the improvement in erectile function . Lifestyle modifications impacted BMI without hormonal or sexual impact in morbidly obese . New studies are warranted in the field to support our data",
"One of the main goals of weight reduction in morbidly obese subjects is its benefit on coronary heart disease ( CHD ) risk . A cross-sectional study was design ed to r and omly assign 79 morbidly obese subjects ( 27 men and 52 women ; age : 30 - 45 years ) either to a diet protocol ( 20 kcal per kg fat-free mass ( FFM ) ; 55 % carbohydrates , 30 % fat , and 15 % proteins ) or to malabsorptive surgery ( biliopancreatic diversion ) . Fatness parameters , measured by dual-energy X-ray absorptiometry , lipid profile , insulin , leptin , sex steroid hormones and sex hormone-binding globulin ( SHBG ) levels were compared at baseline and 1 year after the beginning of the study . The data showed that plasma SHBG levels , but not testosterone levels , correlated negatively to fasting insulin levels and positively to HDL-cholesterol in both men and women . Total leptin levels were significantly lower ( P plasma leptin correlated significantly and positively with insulin but negatively with SHBG.A step-down regression analysis showed that FFM and SHBG , but not insulin levels , were the most powerful independent variables for predicting HDL-cholesterol levels in morbidly obese patients . The negative relationship between SHBG levels and CHD risk appears to be mediated by a concomitant variation in body fatness . Finally , in obese patients , SHBG levels seem to be an indicator of total adiposity rather than an index of an altered insulin/glucose homeostasis",
"The few studies that have examined body composition after a carbohydrate-restricted diet have reported enhanced fat loss and preservation of lean body mass in obese individuals . The role of hormones in mediating this response is unclear . We examined the effects of a 6-week carbohydrate-restricted diet on total and regional body composition and the relationships with fasting hormone concentrations . Twelve healthy normal-weight men switched from their habitual diet ( 48 % carbohydrate ) to a carbohydrate-restricted diet ( 8 % carbohydrate ) for 6 weeks and 8 men served as controls , consuming their normal diet . Subjects were encouraged to consume adequate dietary energy to maintain body mass during the intervention . Total and regional body composition and fasting blood sample s were assessed at weeks 0 , 3 , and 6 of the experimental period . Fat mass was significantly ( P lean body mass significantly increased ( + 1.1 kg ) at week 6 . There was a significant decrease in serum insulin ( -34 % ) , and an increase in total thyroxine ( T(4 ) ) ( + 11 % ) and the free T(4 ) index ( + 13 % ) . Approximately 70 % of the variability in fat loss on the carbohydrate-restricted diet was accounted for by the decrease in serum insulin concentrations . There were no significant changes in glucagon , total or free testosterone , sex hormone binding globulin ( SHBG ) , insulin-like growth factor-I ( IGF-I ) , cortisol , or triiodothyronine ( T(3 ) ) uptake , nor were there significant changes in body composition or hormones in the control group . Thus , we conclude that a carbohydrate-restricted diet result ed in a significant reduction in fat mass and a concomitant increase in lean body mass in normal-weight men , which may be partially mediated by the reduction in circulating insulin concentrations",
"CONTEXT The cause of declining testosterone ( T ) in aging men and their relationships with risk factors are unclear . OBJECTIVE The objective of the study was to investigate the relationships between lifestyle and health with reproductive hormones in aging men . DESIGN This was a baseline cross-sectional survey on 3200 community-dwelling men aged 40 - 79 yr from a prospect i ve cohort study in eight European countries . RESULTS Four predictors were associated with distinct modes of altered function : 1 ) age : lower free T ( FT ; -3.12 pmol/liter.yr , P total T ( TT ; -2.32 nmol/liter ) and FT ( -17.60 pmol/liter ) for body mass index ( BMI ; > or = 25 to LH , indicating hypothalamus/pituitary dysfunction ; 3 ) comorbidity : lower TT ( -0.80 nmol/liter , P LH in younger men but higher LH in older men ; and 4 ) smoking : higher SHBG ( 5.96 nmol/liter , P TT ( 1.31 nmol/liter , P T-LH-negative feedback due to elevated SHBG . CONCLUSIONS Complex multiple alterations in the hypothalamic-pituitary-testicular axis function exist in aging men against a background of progressive age-related testicular impairment . These changes are differentially linked to specific risk factors . Some risk factors operate independently of but others interact with age , in contributing to the T decline . These potentially modifiable risk factors suggest possible preventative measures to maintain T during aging in men",
"OBJECTIVE Isolated hypogonadotropic hypogonadism ( IHH ) is frequently observed in severely obese men , probably as a result of increased estradiol ( E(2 ) ) production and E(2)-mediated negative feedback on pituitary LH secretion . Aromatase inhibitors can reverse this process . This study evaluates whether letrozole once a week can normalize serum testosterone in severely obese men and maintain its long term effect . DESIGN Open , uncontrolled 6-month pilot study in 12 severely obese men ( body mass index>35.0 kg/m(2 ) ) with obesity-related IHH and free testosterone levels , treated with 2.5 mg letrozole once a week for 6 months . RESULTS Six weeks of treatment reduced total E(2 ) from 123+/-11 to 58+/-7 pmol/l ( P serum LH from 4.4+/-0.6 to 11.1+/-1.5 U/l ( P Total testosterone rose from 5.9+/-0.5 to 19.6+/-1.4 nmol/l ( P free testosterone from 163+/-13 to 604+/-50 pmol/l ( P Total testosterone rose to within the normal range in all subjects , whereas free testosterone rose to supraphysiological levels in 7 out of 12 men . The testosterone and E(2 ) levels were stable throughout the week and during the 6-month treatment period . CONCLUSION Letrozole 2.5 mg once a week produced a sustained normalization of serum total testosterone in obese men with IHH . However , free testosterone frequently rose to supraphysiological levels . Therefore , a starting dose < 2.5 mg once a week is recommended",
"INTRODUCTION Although penile blood flow ( PBF ) has been recommended as an additional diagnostic test in identifying erectile dysfunction ( ED ) patients at risk for latent cardiovascular disease , no study has ever assessed the possible association of PBF and the relational component of sexual function with incident major cardiovascular events ( MACE ) . AIM The aim of this study is to investigate whether severity of ED , PBF , and other factors related to a couple 's relationship predict incident MACE . METHODS A consecutive series of 1,687 patients was studied . Different clinical , biochemical , and instrumental ( penile flow at color Doppler ultrasound ) parameters were evaluated . MAIN OUTCOME MEASURES Information on MACE was obtained through the City of Florence Registry Office . RESULTS During a mean follow-up of 4.3 + /- 2.6 years , 139 MACE , 15 of which were fatal , were observed . Cox regression analysis , after adjustment for age and Chronic Disease Score , showed that severe ED predicted MACE ( hazard ratio [ HR ] 1.75 ; 95 % confidence interval 1.10 - 2.78 ; P risk of MACE ( HR = 2.67 [ 1.42 - 5.04 ] and 1.57 [ 1.01 - 2.47 ] , respectively , for flaccid [ sexual interest in the partner and low sexual interest in the patient proved to have a protective effect against MACE . CONCLUSIONS The investigation of male sexuality , and in particular PBF , and sexual desire , could provide insights not only into present cardiovascular status but also into prospect i ve risk",
"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",
"PURPOSE The purpose of this study was to examine the physiological effects of a weight-loss dietary regimen with or without exercise . METHODS Thirty-five overweight men were matched and r and omly placed into either a control group ( C ; N = 6 ) or one of three dietary groups ; a diet-only group ( D ; N = 8) , a diet group that performed aerobic exercise three times per week ( DE ; N = 11 ) ; and a diet group that performed both aerobic and strength training three times per week ( DES ; N = 10 ) . RESULTS After 12 wk , D , DE , and DES demonstrated a similar and significant ( P body mass ( -9.64 , -8.99 , and -9.90 kg , respectively ) with fat mass comprising 69 , 78 , and 97 % of the total loss in body mass , respectively . The diet-only group also demonstrated a significant reduction in fat-free mass . Maximum strength , as determined by 1-RM testing in the bench press and squat exercise was significantly increased for DES in both the bench press ( + 19.6 % ) and squat exercise ( + 32.6 % ) . Absolute peak O2 consumption was significantly elevated in DE ( + 24.8 % ) and DES ( + 15.4 % ) . There were no differences in performance during a 30-s Wingate test for the DE and DES , whereas D demonstrated a significant decline in peak and mean power output . Resting metabolic rate ( RMR ) ( kcal x d(-1 ) ) was not significantly different for any of the groups except for the DE group . There were no significant changes in basal concentrations of serum glucose , BUN , cortisol , testosterone , and high density lipoprotein ( HDL ) cholesterol for any of the groups . Serum total cholesterol and low density lipoprotein ( LDL ) cholesterol were significantly decreased for all dietary groups . Serum triglycerides were significantly reduced for D and DES at week 6 and remained lower at week 12 for D , while triglycerides returned to baseline values for DES . CONCLUSIONS These data indicate that a weight-loss dietary regimen in conjunction with aerobic and resistance exercise prevents the normal decline in fat-free mass and muscular power and augments body composition , maximal strength , and maximum oxygen consumption compared with weight-loss induced by diet alone"
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BACKGROUND Although the importance of smoking as a risk factor for coronary heart disease is beyond doubt , the speed and magnitude of risk reduction when a smoker with coronary heart disease quits are still subjects of debate . OBJECTIVES To estimate the magnitude of risk reduction when a patient with CHD stops smoking . SEARCH STRATEGY We search ed the Cochrane Register of Controlled Trials ( CENTRAL ) , MEDLINE , EMBASE , Science Citation Index , CINAHL , PsychLit , Dissertation Abstract s , BIDS ISI Index to Scientific and Technical Proceedings , UK National Research Register from the start of each data base . Sixty-one large international cohort studies of cardiovascular disease were identified , and contact made with authors to search for any unpublished results . The search was supplemented by cross-checking references and contact with various experts . Date of last search was April 2003 . SELECTION CRITERIA Any prospect i ve cohort studies of patients with a diagnosis of CHD , which include all-cause mortality as an outcome measure . Smoking status must be measured on at least two occasions to ascertain which smokers have quit , and followed-up for at least two years . DATA COLLECTION AND ANALYSIS Eligibility and trial quality were assessed independently by two review ers . MAIN RESULTS Twenty studies were included . There was a 36 % reduction in crude relative risk ( RR ) of mortality for those who quit smoking compared with those who continued to smoke ( RR 0.64 , 95 % confidence interval 0.58 to 0.71 ) . There was also a reduction in non-fatal myocardial infa rct ions ( crude RR 0.68 , 95 % confidence interval 0.57 to 0.82 ) . Many studies did not adequately address quality issues , such as control of confounding , and misclassification of smoking status . However , there was little difference in the results for the six ' higher quality ' studies , and little heterogeneity between these studies . This review was not able to assess how quickly the risk of mortality was reduced . REVIEW ER 'S CONCLUSIONS Quitting smoking is associated with a substantial reduction in risk of all-cause mortality among patients with CHD . The pooled crude RR was 0.64 ( 95 % CI 0.58 to 0.71 ) . This 36 % risk reduction appears substantial compared with other secondary preventive therapies such as cholesterol lowering which have received greater attention in recent years . The risk reduction associated with quitting smoking seems consistent regardless of differences between the studies in terms of index cardiac events , age , sex , country , and time period . However , relatively few studies have included large numbers of older people , women , or people of non-European descent , and most were carried out in Western countries
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"Background PTCA is performed primarily to improve health-related quality of life ( HRQOL ) in patients with symptomatic coronary artery disease . In patients undergoing PTCA , smoking has been shown to increase risks of late myocardial infa rct ion and death . Whether smoking also affects HRQOL after PTCA is currently unknown . Methods and Results We examined the relation between smoking status and HRQOL among 1432 patients who underwent PTCA as part of 2 multicenter clinical trials . HRQOL was assessed with the use of the Medical Outcomes Study SF-36 question naire . Patients were classified as smokers ( n=301 ) , quitters ( n=141 ) , or nonsmokers ( n=990 ) on the basis of their smoking status at the time of their index procedure and during the first year of follow-up . For the overall population , HRQOL improved significantly after PTCA for all scales except general health perception , with improvements ranging from 5.5 points for mental health to 23.2 points for role-physical functioning . After adjustment for baseline characteristics and initial HRQOL , nonsmokers had gains at 6 months that were larger than those of smokers for all health domains : physical function ( 15.4 versus 10.4 points ) , role-physical ( 24.5 versus 13.9 ) , pain ( 18.4 versus 13.3 ) , general health perception ( 1.7 versus −4.5 ) , vitality ( 11.0 versus 4.7 ) , social function ( 12.8 versus 3.5 ) , role-emotional ( 13.5 versus 6.7 ) , and mental health ( 6.8 versus 0.8;P 6-month HRQOL improvements that were greater than those in smokers for all domains as well . Findings were similar at 1 year . Conclusions Quality -of-life benefits of PTCA are diminished by continued smoking . Efforts to promote smoking cessation at the time of PTCA may substantially improve the health outcomes of these procedures",
"STUDY OBJECTIVE --To examine the effect on mortality of stopping smoking after myocardial infa rct ion and the psychosocial factors that influence the decision to stop . DESIGN -- Analysis of smokers in a large prospect i ve study . Self completed question naires provided information on psychosocial factors . SETTING --Coronary care units at six English hospitals participating in a multicentre clinical trial . SUBJECTS -- These comprised consenting myocardial infa rct ion survivors who had been identified as smokers and who completed question naires within seven days of infa rct at six hospitals participating in the Anglo-Sc and inavian study of early thrombolysis . The 532 patients identified have been followed for over five and a half years . The main outcome measure was five year all cause mortality . MAIN RESULTS --Smokers who stopped within one month showed significantly reduced mortality compared with those who persisted , adjusting for other prognostic indicators ( odds ratio 0.56 , 95 % confidence interval 0.33 , 0.98 ) . Overall , 74 % stopped smoking . Being married , low life stress levels before infa rct , and higher social class were associated with stopping smoking but the differentials were small . Of the clinical variables , a final diagnosis of definite myocardial infa rct ion was associated with stopping smoking . All associations remained after multiple logistic regression . CONCLUSION --Smoking cessation can halve the smokers ' odds of dying after myocardial infa rct ion and psychosocial factors play a small but important role in the important decision to stop smoking . Health professionals should continue to stress the importance of stopping smoking to all patients as there is little evidence to support specific directing of advice to relatively \" stress or \" socially isolated \" groups",
"AIMS To analyse ( 1 ) the prognostic importance of clinical findings and lipids in patients with a previous myocardial infa rct ion and ( 2 ) the relative and absolute benefit of simvastatin in patients at low , medium and high predicted risk . METHODS The 4S was a double-blind , r and omized , clinical trial of long-term treatment with simvastatin or matching placebo in patients with myocardial infa rct ion or angina pectoris , serum total cholesterol 5.5 - 8.0 mmol x l(-1 ) , and serum triglycerides The present study only deals with those 3525 patients who had a previous myocardial infa rct ion . End-points comprised coronary death , definite and probable hospital verified myocardial infa rct ion , and resuscitated cardiac arrest . Because there were few women the primary analyses were performed among men . RESULTS A Cox model analysis in the placebo group identified the following independent predictors of coronary events : a history of hypertension ( P=0.023 ) , diabetes ( P=0.0001 ) , smoking after the myocardial infa rct ion ( P=0.010 ) , total cholesterol ( P=0.020 ) , and HDL cholesterol ( P=0.062 ) . The relative reduction of risk by simvastatin treatment in patients at low , medium and high predicted risk was 38 % , 39 % and 42 % , respectively , but the corresponding absolute benefit per 100 patients treated for 6 years increased from 7.9 to 16.2 . CONCLUSION In addition to serum lipids , clinical variables contributed significantly to prediction . The relative benefit from simvastatin treatment was independent of predicted risk , but the absolute benefit increased from low to high risk",
"BACKGROUND The long-term clinical effects of smoking and smoking cessation after venous coronary bypass surgery have not been well established . METHODS AND RESULTS Four hundred fifteen patients who underwent venous coronary bypass surgery between April 1976 and April 1977 were followed up prospect ively for 15 years . Multivariate Cox survival analysis revealed that patients who smoked at the time of surgery had no elevated risks for clinical events compared with nonsmokers . However , smoking behavior at 1 and 5 years after surgery appeared to be an important predictor of clinical events during the subsequent follow-up period . Compared with patients who stopped smoking since surgery , smokers at 1 year after surgery had more than twice the risk for myocardial infa rct ion and reoperation . Patients who were still smoking at 5 years after surgery had even more elevated risks for myocardial infa rct ion and reoperation and a significantly increased risk for angina pectoris compared with patients who stopped smoking since surgery and patients who never smoked . Patients who started to smoke again within 5 years after surgery had increased risks for reoperation and angina pectoris . No differences in outcome were found between patients who stopped smoking since surgery and nonsmokers . CONCLUSIONS Our results show that smoking cessation after coronary bypass surgery may have important beneficial effects on clinical events during long-term follow-up",
"The importance of three risk factors -- serum total cholesterol , systolic blood pressure , and cigarette smoking -- on the risk of new major ischaemic heart disease events in men who already have evidence of ischaemic heart disease was assessed . Data from the initial examination in a large prospect i ve study of cardiovascular disease in middle aged men ( the British Regional Heart Study ) were used to separate 7710 men into three groups on the basis of a resting electrocardiogram , a st and ardised chest pain question naire , and recall of a doctor 's diagnosis of angina or of a previous heart attack : ( group 1 ) no evidence of ischaemic heart disease ( 75 % ) , ( group 2 ) evidence of ischaemic heart disease short of a definite myocardial infa rct ion ( 20 % ) , ( group 3 ) definite myocardial infa rct ion ( 6 % ) . In the average follow up period of 7.5 years , 443 men suffered a new major event caused by ischaemic heart disease ( fatal or non-fatal myocardial infa rct ion or sudden cardiac death ) . Age st and ardised event rates were determined for each of the three groups for varying levels of the established risk factors . Cigarette smoking is strongly associated with the event rate in group 1 but in men with existing heart disease , especially group 3 , differences in risk between the smoking categories were smaller . The strong relation between systolic blood pressure and event rate persisted in groups 1 and 2 but not in group 3 . The positive association between serum concentration of total cholesterol and the event rate was strongest in group 1 and weaker in groups 2 and 3 , though it remained highly significant . These observations , taken together with the results of previous prospect i ve studies and intervention trials , suggest that the important association between serum total cholesterol and the risk of heart attack persists in men with pre-existing ischaemic heart disease , including myocardial infa rct ion . Therefore , in these men the reduction of serum total cholesterol concentration may be at least as important as it is in men without evidence of ischaemic heart disease",
"Data from the Diet and Reinfa rct ion Trial were examined to check the prognostic effects of plasma fibrinogen , plasma viscosity , white blood cell count , haemoglobin and mean platelet volume in 92 deaths among 1755 men who had recently recovered from acute myocardial infa rct ion . All these variables were significantly associated with all-cause mortality over the following 18 months ( haemoglobin negatively , the others positively ) . Those who gave up smoking following their infa rct had a lower mortality than those who continued to smoke ( 4.1 % and 7.9 % respectively ) , and this effect appeared to be mediated by fibrinogen levels . Smoking habit accounted for only part of the prognostic effect of fibrinogen and white blood cell count . Haematological variables have an important prognostic significance after myocardial infa rct ion . Cessation of smoking after myocardial infa rct ion is worthwhile and has a favourable effect on plasma fibrinogen",
"Long-term follow-up was obtained on 138 patients who participated in a prospect i ve , r and omized study comparing two weeks with three weeks of hospitalization following uncomplicated acute myocardial infa rct ion . Follow-up information was available on 123 ( 89 % ) of all r and omized patients . The mean follow-up period was 35 months for those patients who died and 99 months for those who survived . No differences were found between the two groups with respect to survival , cardiac-related deaths , frequency or severity of angina pectoris , subsequent myocardial infa rct ion , incidence of congestive heart failure , number of ventricular aneurysms , or subsequent medical therapy . A significantly greater number of survivors in both groups stopped smoking and had a normal initial heart size than those who died . This long-term follow-up study further supports the conclusions of earlier short-term studies that two weeks of hospitalization is safe in patients with uncomplicated acute myocardial infa rct ion",
"We describe the 2- and 5-year prognoses following coronary artery bypass grafting ( CABG ) in relation to smoking habits among consecutive patients being operated on in western Sweden during a 3-year period . Among the 2,121 patients , 10.2 % admitted smoking at coronary angiography as compared with 7.5 % 2 years after CABG ( NS ) . Among smokers , the mortality during the subsequent 2 years was 8.9 % as compared with 6.5 % for exsmokers and 7.3 % for never smokers ( NS ) . During the 5-year follow-up , smokers had a mortality of 18.8 % as compared with 13.6 % for exsmokers and 12.5 % for never smokers ( p = 0.03 ) . When correcting for dissimilarities in previous history , smoking was a strongly significant independent ( p < 0.0001 ) predictor of 5-year mortality",
"A prospect i ve follow-up study was carried out to investigate the relation between smoking and risk of death after an acute myocardial infa rct ion . The study consisted of male patients under the age of 65 years , who had had an acute myocardial infa rct ion between 1972 and 1975 in North Karelia , Finl and . Of these patients , 888 survived the first six months after the acute infa rct ion and were followed-up for three years after the infa rct ion with regard to their deaths . The cumulative all-causes mortality rate of the patients who were still smoking six months after the acute myocardial infa rct ion was 1.7 times that of the patients who had stopped smoking within the first six months . There was a dose-response relation between the number of cigarettes smoked daily and the mortality . The impact of smoking was greatest in the subgroups of patients with an otherwise good prognosis . We estimated that 28 per cent of the deaths in the whole group of initial smokers was attributable to continuing smoking after the infa rct ion . On the basis of these findings we suggest that the anti-smoking advice should be an important part of the modern comprehensive care of patients with an acute myocardial infa rct ion",
"This prospect i ve study examines the question ' Is it too late to stop smoking cigarettes once you have had a myocardial infa rct ion ? ' One hundred and nineteen cigarette smokers ( 90 men , 29 women ) who survived their first myocardial infa rct ion for one month were followed for five years or until their death if earlier . The age corrected mortality rate of men who continued to smoke cigarettes was 2.2 times the age corrected mortality rate of those who stopped smoking after their infa rct . The women who continued to smoke had 2.4 times the age corrected mortality of those who stopped smoking . The age and sex corrected mortality rates for the combined group of men and women show that those who stopped smoking after their infa rct ion have 55 % of the mortality of those who continued to smoke ( P less than 0.05 ) . These results suggest that smoking is not merely a ' risk factor ' for myocardial infa rct ion but is also a causal factor whose effects can be avoided by both men and women after an initial myocardial infa rct ion",
"Prognosis during 5 years of follow-up after first myocardial infa rct ion ( MI ) in a group of men ( aged 40 to 55 years ) was related to risk factors determined at the time of MI . Progression of coronary artery disease ( CAD ) was measured by the occurrence of severe angina pectoris , recurrent myocardial infa rct ion , and cardiac death . Only smoking and serum cholesterol level influenced prognosis . It was possible to identify a subgroup ( patients smoking less than 20 cigarettes/day and having a cholesterol level of less than 7.0 mmoles/L ) with low risk for progression of CAD . A r and omly applied 6-week rehabilitation program shortly after MI was associated with a 50 % decrease in progressive CAD when compared to the control group . Since only a slight decrease in cholesterol levels was found in the rehabilitation group , a direct effect of the rehabilitation program could thus not be excluded because the second important risk factor , smoking , did not show differences between the two groups . The smoking habits at the time of MI determined the continuation of cigarette smoking and rehabilitation did not influence smoking habits ",
"Men incurring coronary heart disease ( CHD ) during surveillance of an employed population were studied for risk factors associated with additional myocardial infa rct ions . The coronaryprone Type A behavior pattern measured by a test score , number of cigarettes smoked daily , and serum cholesterol were significant discriminators between the 67 men with recurrent CHD and the 220 with but a single clinical CHD event . Diastolic blood pressure and fasting serum triglycerides were not significant discriminators . Statistical analyses directed to possible sources of bias occasioned by the combined retrospective- prospect i ve study design revealed that these problems are negligible and do not alter the findings observed . Type A score appears relatively unaffected by whether the measure was made before or after the initial CHD event . Multivariable discriminant function equations showed Type A score to be the strongest single predictor of recurrent CHD among the variables available . Number of cigarettes smoked and serum cholesterol accounted for additional variance . Future field trials for the secondary prevention of myocardial infa rct ion would be strengthened by consideration of the possible role of Type A behavior",
"In a prospect i ve study of 7735 middle-aged men , both current and ex-cigarette-smokers had a risk of a major IHD event , within an average 6.2 years of screening , more than twice that in men who had never smoked cigarettes ; men who had given up smoking more than 20 years ago still had an increased risk . This excess risk among ex-smokers is only to a small extent explained by their higher blood pressure , serum total cholesterol , and body-mass index . An increased prevalence of IHD in men who had recently given up smoking also made a small contribution to excess risk . In both current and former cigarette smokers , the number of years a man had smoked cigarettes ( \" smoking-years \" ) was the clearest indicator of IHD risk due to cigarettes . The major benefit of giving up smoking may lie in halting the accumulation of smoking years",
"OBJECTIVES The purpose of this study was to evaluate the clinical outcome of a large cohort of patients who suffered an acute myocardial infa rct ion with absolutely normal epicardial coronary arteries at the post-myocardial infa rct ion coronary angiogram . The aetiological and prognostic factors in this population were also analysed . BACKGROUND Few data exist concerning the outcome , and aetiological and prognostic factors , of patients with myocardial infa rct ion and angiographically absolutely normal coronary arteries . METHODS Ninety-one patients ( 34 females/57 males ; mean age 50+/-13 years , range 24 - -78 years ) admitted with an acute myocardial infa rct ion had absolutely normal coronary arteries at the angiogram performed 6.2+/-4 days ( range 1 - -15 days ) after the myocardial infa rct ion , defined by smooth contours and no focal reduction ( NC ) . Of the 91 NC patients , 71 were evaluated prospect ively , alongside a systematic search of all aetiological factors reported in the literature . The NC patients were matched for age , sex , and the same period of myocardial infa rct ion onset with a group of 91 patients with coronary artery stenosis ( > 50 % diameter stenosis ) at the angiogram performed 7.3+/-4 days ( range 1 - -15 days ) after the myocardial infa rct ion ( SC ) . RESULTS The percent of smokers was similar between the two groups ; higher prevalence rates of coronary heart disease family history , obesity , hypertension , hypercholesterolaemia and diabetes mellitus were found in SC ( P=0.043 to 0.0001 ) . In NC , coronary spasm was found in 15.5 % , congenital coagulation disorders in 12.8 % , collagen tissue disorders in 2.2 % , embolization in 2.2 % , and oral contraceptive use in 1.1 % . Left ventricular ejection fraction at hospital discharge was higher in NC ( 60%+/-13 % ) than in SC ( 55%+/-13 % , P=0.04 ) . The mean follow-up was 35 months ( range 1 - -100 months ) . Kaplan-Meier event-free survival , with the combined end-point defined as death , reinfa rct ion , heart failure and stroke was 75 % in NC vs 50 % in SC ( P Survival rate was 94.5 % in NC compared to 92 % in SC ( ns ) . Univariate predictors of events in NC were left ventricular ejection fraction ( P=0.03 ) , age ( P=0.02 ) , diabetes ( P=0.01 ) , and smoking ( P=0.03 ) . Using Cox multivariate analysis , independent predictors of long-term outcome in NC patients were left ventricular ejection fraction ( P=0.003 ) and diabetes ( P=0.004 ) . CONCLUSION Aetiological factors , predominantly coronary spasm and inherited coagulation disorder , can be detected in only one third of the patients with myocardial infa rct ion and absolutely normal coronary angiograms despite a systematic search in a prospect i ve population . Mortality rates are similar but morbidity is lower in myocardial infa rct ion patients with absolutely normal coronary angiography compared with those with coronary artery stenosis . The only two independent factors predictive of poor outcome in myocardial infa rct ion patients with normal coronary arteries are left ventricular function and diabetes",
"The purpose of this study was to examine the effects of aspirin use on mortality and morbidity rates in a subset of the control group of the Program on the Surgical Control of the Hyperlipidemias ( POSCH ) that was stratified by cigarette smoking status at the time of r and omization . The clinical impact of aspirin intake in cigarette smokers and former cigarette smokers has not been well studied . POSCH was a r and omized , controlled , clinical trial design ed to ascertain the effects of lipid modification by the partial ileal bypass operation on clinical end-points and arteriographic changes in postmyocardial infa rct ion subjects with hypercholesterolemia . Cohorts of cigarette smokers in the diet-control group were evaluated for overall and atherosclerotic coronary heart disease ( ACHD ) mortality rates and recurrent confirmed nonfatal myocardial infa rct ion rates . In current cigarette smokers at baseline ( n = 90 ) with a mean follow-up of 8.3 years , the overall mortality rate was 45.2 % in patients with no aspirin use and 10.4 % in patients who reported even infrequent aspirin use ( relative risk = 4.3 , 95 % confidence interval ( CI ) = 2.4 to 10.6 , p ACHD mortality in this cohort , the relative risk was 17.1 ( 35.7 % vs 2.1 % , 95 % CI = 1.4 to 125.0 , p ACHD mortality and nonfatal myocardial infa rct ion , the relative risk was 2.4 ( 40.5 % vs 16.7 % , 95 % CI = 1.2 to 5.1 , p = 0.018 ) . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Smoking is the most important modifiable risk factor for coronary heart disease and its reduction is a target for primary health care.1 The participants in most studies of the smoking habits of patients with coronary heart disease are enrolled after acute cardiac events.2 There are few documented studies of the changes in the smoking habits of patients with angina . This study examined variations in self reported smoking habits over a five year period in a primary care cohort of patients diagnosed as having angina . Patients clinical ly diagnosed as having angina at least six months previously were identified from the disease registers of 18 general practice s in the Greater Belfast area . These general practice s were chosen to",
" A group of 456 consecutive patients seen less than or equal to 6 h after the onset of acute myocardial infa rct ion associated with ST segment elevation received thrombolytic therapy and were followed up for 12 months . Intravenous streptokinase was given to 315 patients and recombinant tissue-type plasminogen activator ( rt-PA ) to 141 patients . Reinfa rct ion rate and risk factors for reinfa rct ion were assessed . Management after thrombolysis was conservative ; revascularization procedures were reserved for patients with symptoms refractory to medical therapy or for those with left main coronary artery stenosis . Coronary artery surgery or angioplasty was performed in only 3.7 % of patients during the first 30 days after thrombolysis and in only 8.6 % by 1 year . Most patients ( 79 % ) underwent coronary arteriography . Twenty-six patients ( 5.7 % ) exhibited signs of threatened reinfa rct ion at 1 month after thrombolytic therapy as did 43 patients ( 9.4 % ) by 1 year . Reinfa rct ion was prevented in four of these patients by early readministration of thrombolytic therapy . Multivariate analysis of possible risk factors for reinfa rct ion identified at the time of initial infa rct ion showed current cigarette smoking to be the only predictive factor ( reinfa rct ion occurred in 12.5 % of smokers versus 6.3 % of nonsmokers , p = 0.04 ) . A second analysis of risk factors identified 3 weeks after initial infa rct ion , including the severity of residual stenosis at coronary arteriography and exercise test variables , again showed continued cigarette smoking to be the only factor predictive of reinfa rct ion . Twenty percent of patients who continued to smoke developed reinfa rct ion compared with 5.1 % of those who stopped ( p less than 0.01 ) . ( ABSTRACT TRUNCATED AT 250 WORDS",
"The impact of smoking cessation on coronary heart disease ( CHD ) and lung cancer was assessed after 10.5 years of follow-up in the 12,866 men in the Multiple Risk Factor Intervention Trial ( MRFIT ) . Those men who died of lung cancer ( n = 119 ) were either cigarette smokers at entry or ex-smokers ; no lung cancer deaths occurred among the 1,859 men who reported never smoking cigarettes . The risk of lung cancer for smokers , adjusted for selected baseline variables using a Cox proportional hazards model , increased as the number of cigarettes smoked increased ( B = 0.0203 , SE = 0.0076 ) . There was not the same grade d response for CHD among smokers at entry . The risk of CHD death was greater among smokers than nonsmokers ( RR = 1.57 ) ( B = -0.0034 , S.E. = 0.0048 ) . After one year of cessation , the relative risk of dying of CHD for the quitters as compared to non-quitters ( RR = 0.63 ) was significantly lower even after adjusting for baseline differences and changes in other risk factors . The relative risk for smokers who quit for at least the first three years of the trial was even lower compared to non-quitters ( RR = 0.38 ) . However , the relative risk for lung cancer for quitters versus non-quitters was close to 1 both for quitters at 12 months and at three years . These data support the benefits of cessation in relation to CHD and are consistent with other epidemiologic studies which suggest that the lag time for a beneficial effect of smoking cessation on lung cancer may be as long as 20 years",
"Risk factors for major ischaemic heart disease ( acute myocardial infa rct ion or sudden death ) have been investigated in a prospect i ve study of 7735 men aged 40 - 59 years drawn from general practice s in 24 British towns . After a mean follow-up of 4.2 years , there have been 202 cases of major ischaemic heart disease . Univariate estimates of the risk of ischaemic heart disease show that serum total cholesterol , HDL-cholesterol and triglyceride concentrations , systolic and diastolic blood pressures , cigarette smoking , and body mass index are all associated with increased risk of ischaemic heart disease . Evidence of ischaemic heart disease at initial examination is also strongly associated with increased risk of subsequent ischaemic heart disease . All these factors were then considered simultaneously using multiple logistic models . Definite myocardial infa rct ion on electrocardiogram and recall of a doctor diagnosis of ischaemic heart disease remained predictive of subsequent major ischaemic heart disease , after allowance for all other risk factors . Serum total cholesterol , blood pressure , and cigarette smoking each remained as highly significant independent risk factors whereas overweight , above average levels of HDL-cholesterol and serum triglyceride were not predictive of risk after allowance for the above factors . Men with and without pre-existing ischaemic heart disease were examined separately in the same way ( using multiple logistic models ) . The strength of association between the principal risk factors and subsequent major ischaemic heart disease was reduced in the men with pre-existing ischaemic heart disease , only age and serum total cholesterol remaining highly significant . Overall the levels of the major risk factors commonly encountered in British men have a marked effect on the risk of ischaemic heart disease . Modification of these risk factors in the general population constitutes an important national priority",
"The Norwegian Multicenter Group Study noted the effect of smoking habits before and after myocardial infa rct ion and their relation to mortality and reinfa rct ion rate after treatment with timolol in patients surviving acute myocardial infa rct ion . The mean follow up period was 17.3 ( range 12 - 33 ) months . No relation was found between initial smoking habits and risk category after infa rct ion or between initial smoking habits and later outcome . At the time of their first infa rct smokers were seven years younger than non-smokers . One moth after infa rct ion nearly 60 % of the smokers had stopped smoking completely . A significantly lower incidence of early cardiac death and lower total mortality was found in patients treated with timolol in both those who continued smoking and in the combined non-smoking groups and a significantly lower reinfa rct ion rate among non-smokers . Cessation of smoking alone was associated with a reduced reinfa rct ion rate by 45 % but a non-significant reduction in mortality by 26 % . It is concluded that treatment with timolol and cessation of smoking have an additive effect in reducing mortality and reinfa rct ion rate after myocardial infa rct ion",
"Objective : To determine the impact of an episode of serious cardiovascular disease on smoking behavior and to identify factors associated with smoking cessation in this setting . Design : Prospect i ve observational study in which smokers admitted to a coronary care unit ( CCU ) were followed for one year after hospital discharge to determine subsequent smoking behavior . Setting : Coronary care unit of a teaching hospital . Patients : Preadmission smoking status was assessed in all 828 patients admitted to the CCU during one year . The 310 smokers surviving to hospital discharge were followed and their smoking behaviors assessed by self-report at six and 12 months . Intervention : None . Measurements and main results : Six months after discharge , 32 % of survivors were not smoking ; the rate of sustained cessation at one year was 25 % . Smokers with a new diagnosis of coronary heart disease ( CHD ) made during hospitalization had the highest cessation rate ( 53 % vs. 31 % , p=0.01 ) . On multivariate analysis , smoking cessation was more likely if patients were discharged with a diagnosis of CHD , had no prior history of CHD , were lighter smokers ( smokers admitted because of suspected myocardial infa rct ion ( MI ) , cessation was more likely if the diagnosis was CHD than if it was noncoronary ( 37 % vs. 19 % , p smoking cessation than did coronary insufficiency . Conclusion : Hospitalization in a CCU is a stimulus to long-term smoking cessation , especially for lighter smokers and those with a new diagnosis of CHD . Admission to a CCU may represent a time when smoking habits are particularly susceptible to intervention . Smoking cessation in this setting should improve patient outcomes because cessation reduces cardiovascular mortality , even when quitting occurs after the onset of CHD",
"UNLABELLED We assessed the effect of stopping smoking on future cardiac events ( cardiac death and non-fatal myocardial infa rct ion ( MI ) ) in 90 male smokers with previous MI by a prospect i ve follow-up study . At the time of enrollment , the patients were divided into 2 groups according to their current smoking status ( Group A : those who had stopped smoking ( n = 60 ) , and Group B : those who were still smoking ( n = 30 ) ) . Follow-up was performed prospect ively by annual postal question naires . During the mean follow-up period of 3.1 + /- 1.4 years , 13 cardiac events ( 11 cardiac deaths and 2 cases of non-fatal MI ) occurred in the 87 evaluable patients . The cardiac event rates in Groups A and B were 8.5 % and 28.6 % , respectively , and the relative risk was 3.4 ( Group A vs B , p less than 0.05 ) by univariate analysis . The relative risk using multivariate analysis ( Cox ) was also statistically significant ( 3.1 , p less than 0.05 ) . HDL-cholesterol was significantly lower in Group B than in Group A , but other coronary risk factors apart from smoking were not significantly different between the two groups . At the end of the follow-up period , 89.8 % of the patients in Group A remained nonsmokers and 21 % of the patients in Group B had stopped smoking . CONCLUSION Stopping smoking significantly reduced the risk of future cardiac events in male smokers with previous MI . This prospect i ve follow-up study demonstrated that a significant reduction in the risk of future cardiac events could be achieved by stopping smoking in this group of patients",
" Data from 9740 Scottish men and women aged 40 - 59 years , selected at r and om in a population survey during 1984 - 86 , were used to compare self-reported smoking habits and biochemical measures of tobacco smoke inhalation in three groups : 625 with diagnosed coronary heart disease ; 1497 undiagnosed , but with suggestive question naire symptoms or electro-cardiographic signs ; and 7618 with no diagnosis or evidence of coronary disease , nor cardiovascular medication . Men and women with a diagnosis of coronary heart disease reported that they had tried to reduce their cigarette consumption or had quit more often than did the two comparison groups , but this effect was considerably greater in men than in women . Men in all groups had a higher cigarette quitting rate , but this may be due to switching to pipes and cigars . However , the biochemical measurement of tobacco smoke inhalation by cotinine showed that those with a coronary diagnosis had the highest overall levels of tobacco smoke inhalation , and the highest level of cotinine per self-reported cigarette , cigar , or ounce ( 30 g ) of pipe tobacco consumed . Self-reporting after a coronary diagnosis is consequently distorted , and an objective measure of smoke inhalation is to be preferred . In both sexes , particularly women , intake of tobacco products remains higher than that in the general population , whether or not it was even higher before they were diagnosed . Those responsible for continuing care of coronary patients need to be aware that health education and compliance are less effective in this group than they should be , both in male patients and , even more so , in women",
"BACKGROUND Studies have shown that cigarette smokers constitute a substantial proportion of patients with acute coronary syndromes ( ACS ) and have platelet-rich coronary thrombi . We characterized the influence of smoking status on outcome of patients with ACS without persistent ST-segment elevation and tested the hypothesis that selective inhibition of the platelet glycoprotein IIb/IIIa receptor with eptifibatide would improve outcomes among cigarette smokers . METHODS The study population included patients enrolled in the PURSUIT trial ( Platelet Glycoprotein IIb/IIIa in Unstable Angina : Receptor Suppression Using Integrilin Therapy ) with known smoking status presenting with ischemic chest pain Patients were r and omly assigned to receive a bolus and infusion of either eptifibatide or placebo in addition to st and ard therapy . The primary end point was a composite of death or nonfatal myocardial infa rct ion within 30 days . RESULTS Of the 9406 patients with known smoking status , 2677 were current smokers , 3086 were former smokers , and 3643 were nonsmokers . Cigarette smokers had better 30-day outcomes ( 12.3 % , 16.8 % , and 15.4 % for smokers , former smokers , and nonsmokers , respectively ; P = .001 ) . However , after adjusting for differences in baseline clinical variables , smoking status was not a predictor of 30-day outcome ( P = .45 ) . There was a reduction in the composite end point overall with eptifibatide compared with placebo ( 14.3 % vs 15 . 7 % , P = .054 ) but no interaction between smoking status and treatment strategy ( P = .68 ) . CONCLUSIONS Among patients with ACS without persistent ST-segment elevation , cigarette smokers had better short-term outcomes because of their more favorable clinical profile . Although prior studies have suggested that smokers more commonly have platelet-rich thrombi than nonsmokers , eptifibatide did not result in more improvement in their outcome compared with former smokers or nonsmokers",
"Background Smoking cessation decreases the risk for myocardial infa rct ion among people without previous coronary disease , but its effect on risk reduction after a first myocardial infa rct ion has not been well studied . Contribution The research ers retrospectively observed relative risk for recurrent coronary events in patients discharged from the hospital after an incident myocardial infa rct ion . Compared to nonsmokers , active smokers were 1.5 times more likely to have reinfa rct ion . Among persons who had stopped smoking , relative risk decreased gradually to the nonsmokers ' level over 36 months . Implication s Physicians should emphasize the proven benefits of smoking cessation to encourage patients to quit after a first myocardial infa rct ion . The Editors Smoking is a risk factor for coronary artery disease ( 1 ) . Among persons without coronary disease who quit smoking , the risk for incident coronary disease decreases and approaches that of nonsmokers within 2 to 3 years after cessation ( 2 , 3 ) . Some studies ( 4 - 17 ) show that quitting smoking after myocardial infa rct ion also seems to reduce the risk for adverse outcomes , including death . However , these studies of persons with established disease generally focused on men 65 years of age or younger , had limited information about possible confounding factors , did not evaluate the time course of the potential benefits of smoking cessation , and did not compare results to those in nonsmokers . In contrast to these studies showing a benefit of smoking cessation after myocardial infa rct ion , some evidence suggests that after infa rct ion , smokers may not have an elevated risk for recurrent events compared with never-smokers , a finding termed the smoker 's paradox ( 18 - 24 ) . We examined the association between smoking status and risk for recurrent coronary events and explored the time course of potential benefits of cessation in a large population -based inception cohort of persons who survived to hospital discharge after an incident myocardial infa rct ion . Methods Setting and Participants The study setting was Group Health Cooperative ( GHC ) , a health maintenance organization with more than 500 000 enrollees , based in western Washington State . The organization 's model of health care delivery is structured so that most routine care for enrollees , including care after myocardial infa rct ion , is provided by personal primary care physicians . Group Health Cooperative employs more than 300 primary care physicians and contracts with more than 500 other physicians . Eligible patients included all GHC enrollees who survived to hospital discharge after a first myocardial infa rct ion during the period from July 1986 ( women ) or July 1989 ( men ) through December 1996 . Patients with incident myocardial infa rct ion were identified by International Classification of Diseases , 9th revision , codes from the computerized discharge abstract s of the two GHC hospitals , bills for out-of-plan services provided by non-GHC physicians and health care facilities , and Washington State death records . A trained records abstract or , assisted by study physicians , vali date d the incident infa rct ions by review ing available inpatient medical records . Previous work ( 25 ) has confirmed the accuracy and completeness of the methods used for ascertainment of myocardial infa rct ion . Persons were excluded if they were younger than 30 or older than 79 years of age at the time of the incident infa rct ion , had previously had a myocardial infa rct ion , had the incident infa rct ion as a result of surgery or another procedure , died before hospital discharge , or had no information available in the medical record after the incident infa rct ion . A total of 50 patients ( 1.8 % of the total otherwise eligible patients ) were discharged alive from the hospital but had no information in the chart after the incident infa rct ion . Persons were also excluded if they had made fewer than four visits to GHC or had been enrolled in GHC for less than 1 year before the incident infa rct ion . Among persons otherwise eligible for inclusion , 9.3 % were excluded because of inadequate duration of enrollment in GHC . Of the 2677 patients who were initially eligible , 58 were excluded because of indeterminate smoking status , leaving 2619 persons ( 97.8 % of the original cohort ) for analysis . The Human Subjects Review Committees of GHC approved the study . Smoking Status We identified smoking status on the basis of ambulatory care and inpatient records . The GHC ambulatory medical record is an important re source because it serves as the primary method of communication among GHC physicians . It includes not only notes from ambulatory care visits but also discharge summaries of hospitalizations , results of laboratory and diagnostic tests , consultant reports , responses to annual GHC health question naires , and up date d problem lists . Data collection included a review of the entire GHC ambulatory medical record for the period before the first infa rct ion , the period of hospitalization associated with the incident infa rct ion , and the period after the infa rct ion up to a predetermined date in 1996 , 1997 , or 1998 . Patients were classified as nonsmokers ( persons with no history of smoking in the medical record ) , former smokers ( persons who had smoked but had quit before the incident myocardial infa rct ion ) , quitters ( persons who were smoking at the time of the incident myocardial infa rct ion and quit after the infa rct ion ) , and active smokers ( persons who were smoking at the time of the incident myocardial infa rct ion and continued to smoke during follow-up ) . Only those persons who quit smoking after their incident infa rct ion and maintained cessation for the duration of follow-up were classified as quitters . Information about the quit date , number of cigarettes smoked per day , and duration of smoking over time was also recorded . Patients were closely monitored after the incident infa rct ion ; 97.6 % had a clinic visit within 3 months after hospital discharge , and the median number of visits ( physician , nurse , or emergency department visits or hospitalizations ) during the first year after the incident infa rct ion was 9 ( 25th , 75th percentiles : 6 , 14 ) . Clinical and Medication Covariates Trained research assistants review ed the ambulatory care and inpatient medical records to collect information about potential risk factors for coronary disease , such as use of health services ; marital status ; alcohol consumption ; body weight ; height ; and medical conditions such as hypertension , diabetes , and congestive heart failure . Congestive heart failure was determined to have occurred on the basis of the notes of the primary care physician and consultants and the results of diagnostic tests . Hypertension was defined as pharmacologically treated hypertension ; diabetes was defined as diabetes pharmacologically treated with oral hypoglycemic agents or insulin . In addition , laboratory values for r and om serum glucose , total cholesterol , and high-density lipoprotein cholesterol were recorded . Medication use was assessed at the time of hospital discharge after the incident infa rct ion by using information from the discharge summary supplemented with information from the first outpatient visit and the GHC computerized pharmacy data base . The status of the clinical and medication covariates was determined at the time of hospital discharge . Laboratory information was taken from the period before the incident infa rct ion . End Point The outcome of interest was recurrent coronary events , defined as nonfatal myocardial infa rct ion or coronary death . Information on these end points was obtained from the GHC ambulatory medical record , available inpatient records , and the results of matches between Washington State death records and GHC enrollment records . In patients with established coronary disease , if the underlying cause of death was heart disease , heart failure , or arrhythmia , the death was classified as a coronary death . Statistical Analysis Follow-up time began at the date of discharge from the hospital after the incident infa rct ion , and it extended to the date of the first recurrent infa rct ion , coronary death , or censoring . Persons were censored at the date of death from causes other than heart disease , the date of unenrollment from GHC , or the end of the assigned follow-up period . Cox proportional-hazards regression analysis with a time-dependent smoking status variable was used to model the association of smoking status and recurrent coronary events after adjustment for potential confounding factors ( 26 ) . A patient who quit smoking during hospitalization for the incident myocardial infa rct ion was classified as a quitter . For those who quit smoking after discharge , smoking status was modeled with person-years accrued initially as if the patient were an active smoker and then after cessation as if the patient were a quitter . To investigate the risk for recurrent coronary events in relation to the duration of smoking cessation , we divided follow-up time into four mutually exclusive categories of duration of cessation ( 0 to time since hospital discharge and time since cessation of smoking were similar for many quitters . To help discern whether the change seen among quitters in the hazard ratio over time was due to smoking cessation rather than to any other characteristic of smokers that changed over time after discharge , we also evaluated whether the coronary event hazard ratio among active smokers varied with time since infa rct ion . We calculated the unadjusted rates of recurrent",
"Through a multicenter registry of patients in the Coronary Artery Surgery Study , we prospect ively evaluated morbidity and mortality in 4,165 smokers with angiographically proved coronary artery disease , 2,675 of whom continued to smoke and 1,490 of whom quit . At five years , mortality ( adjusted by Cox analysis for baseline differences ) was 22 % for those who continued smoking and 15 % for quitters . The relative risk ( also from the Cox analysis ) for mortality in continuers vs quitters was 1.55 ( 95 % confidence interval , 1.29 to 1.85 ) . The adverse effect of smoking mainly took the form of higher frequencies of myocardial infa rct ion -- associated death and sudden death : the frequencies of these events during follow-up in continuers vs quitters were 7.9 % vs 4.4 % for myocardial infa rct ion -- associated death and 2.8 % vs 1.5 % for sudden death . This study supports the recommendation that patients with coronary artery disease should stop smoking"
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Abstract Enhanced Recovery or Fast Track Recovery after Surgery protocol s ( ERAS ) have significantly changed perioperative care following colorectal surgery and are promoted as reducing the stress response to surgery . The present systematic review aim ed to examine the impact on the magnitude of the systemic inflammatory response ( SIR ) for each ERAS component following colorectal surgery using objective markers such as C-reactive protein ( CRP ) and interleukin-6 (IL-6).A literature search was performed of the US National Library of Medicine ( MEDLINE ) , EMBASE , PubMed , and the Cochrane Data base of Systematic Review s using appropriate keywords and subject headings to February 2015.Included studies had to assess the impact of the selected ERAS component on the SIR using either CRP or IL-6.Nineteen studies , including 1898 patients , were included . Fourteen studies ( 1246 patients ) examined the impact of laparoscopic surgery on the postoperative markers of SIR . Ten of these studies ( 1040 patients ) reported that laparoscopic surgery reduced postoperative CRP . One study ( 53 patients ) reported reduced postoperative CRP using opioid-minimising analgesia . One study ( 142 patients ) reported no change in postoperative CRP following preoperative carbohydrate loading . Two studies ( 108 patients ) reported conflicting results with respect to the impact of goal -directed fluid therapy on postoperative IL-6 . No studies examined the effect of other ERAS components , including mechanical bowel preparation , antibiotic prophylaxis , thromboprophylaxis , and avoidance of nasogastric tubes and peritoneal drains on markers of the postoperative SIR following colorectal surgery . The present systematic review shows that , with the exception of laparoscopic surgery , objective evidence of the effect of individual components of ERAS protocol s in reducing the stress response following colorectal surgery is limited
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"BACKGROUND Undernutrition and weight loss are important determinants of clinical outcome in older patients after hip fracture but the effectiveness of nutritional support programs in routine clinical practice remains controversial . AIMS OF THE PROJECT : To determine if oral nutritional supplements given daily for 28 days after hip fracture surgery could prevent weight loss and /or lead to improved clinical outcomes ( mortality rates , discharge destination , activities of daily living or length of hospital stay ) in non-malnourished community-dwelling older women with hip fracture . METHODS One hundred and nine women with BMI range 20 - 30 kg/m(2 ) were allocated to either nutritional supplements ( 352 kcal/day ) or usual hospital nutrition using a quasi-r and omisation technique . Body weight changes were monitored at 4 and 8 weeks and clinical outcomes were recorded at discharge and at 6 months . RESULTS No significant differences in weight change or clinical outcomes were seen between the two groups . Compliance with consuming the nutritional supplements was quite variable and there was a significant negative correlation between the amount of supplement consumed and subsequent weight change ( r=-0.36 , P=0.019 ) . CONCLUSIONS Poor compliance with oral nutritional supplements is an important determinant of the effectiveness of oral nutritional interventions in preventing weight loss after hip fracture . Whilst this may explain the lack of clinical improvements seen , our data do not support the routine use of oral nutritional supplements in non-malnourished hip fracture patients",
"PURPOSE : Urinary bladder drainage for several days after pelvic surgery is a common surgical practice , despite insufficient evidence supporting its routine use . The aim of this study was to prospect ively evaluate the utility of urinary bladder drainage after pelvic colorectal surgery . METHODS : Patients undergoing pelvic surgery were prospect ively r and omly assigned to 3 groups . In group A , the Foley catheter was removed on postoperative day 1 , and in groups B and C it was removed on postoperative days 3 and 5 , respectively . Male patients with severe prostatic symptoms were excluded from the study . The main outcome criterion was acute urinary retention requiring reinsertion of the Foley catheter . RESULTS : A total of 118 patients ( 68 males ) at a mean age of 55 years were included in this study ( group A , 41 patients ; group B , 38 ; and group C , 39 ) . Overall , urinary retention after removal of the Foley catheter occurred in 12 ( 10 % ) of the patients : 6 ( 14.6 % ) in group A , 2 ( 5.3 % ) in group B , and 4 ( 10.5 % ) in group C ( P = .39 ) . Symptomatic urinary tract infection was diagnosed in 5 patients in group A , 3 in group B , and 9 in group C , but this difference did not reach statistical significance . Likewise , there were no significant differences in anastomotic leak and intra-abdominal abscess rates among the 3 groups . CONCLUSIONS : Routine prolonged urinary bladder catheterization after pelvic surgery may not be required , and the Foley catheter may be safely removed on postoperative day 1 . Larger studies are needed to confirm the findings of this study",
"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",
"Objective This prospect i ve r and omized study determined the influence of closed-suction drainage on the incidence of postoperative complications after elective hepatic resection . Summary Background Data Routine drainage is no longer advocated after several intra-abdominal surgical procedures . Methods A series of 81 patients who underwent elective hepatic resection were r and omly allocated to either a nondrainage group ( n = 39 ) and a drainage group with closed-suction drainage ( n = 42 ) . Indications for resection were 42 benign lesions and 39 malignant tumors , including 19 with cirrhosis . Major hepatic resection was performed in 25 patients and minor resection , in 56 . All patients underwent ultrasonography with puncture for bacteriologic cultures of all fluid collection s within the first 5 postoperative days . Results One patient died in each group . Ultrasonography found a significantly higher rate of subphrenic collection s in the drainage group compared with the nondrainage group ( respectively , 36 % vs. 15 % , p infected in the drainage group ( n = 6 ) than in the nondrainage group ( n = 2 ) . After major liver resection , the rate of intra-abdominal postoperative complications ( i.e. , subphrenic fluid collection s , hematomas , and bilomas ) was similar between the two groups . Conclusion Minor liver resection is safer without drainage . Major liver resection can be performed with or without abdominal drainage",
"Objective : To assess with a single-blinded , multicenter , r and omized trial , the postoperative results in patients undergoing sphincter-saving rectal resection for cancer without preoperative mechanical bowel preparation ( MBP ) . Background : The collective evidence from literature strongly suggests that MBP , before elective colonic surgery , is of no benefit in terms of postoperative morbidity . Very few data and no r and omized study are available for rectal surgery and preliminary results conclude toward the safety of rectal resection without MBP . Methods : From October 2007 to January 2009 , patients scheduled for elective rectal cancer sphincter-saving resection were r and omized to receive preoperative MBP ( ie , retro grade enema and oral laxatives ) or not . Primary endpoint was the overall 30-day morbidity rate . Secondary endpoints included mortality rate , anastomotic leakage rate , major morbidity rate ( Dindo III or more ) , degree of discomfort for the patient , and hospital stay . Results : A total of 178 patients ( 103 men ) , including 89 in both groups ( no-MBP and MBP groups ) , were included in the study . The overall and infectious morbidity rates were significantly higher in no-MBP versus MBP group , 44 % versus 27 % , P = 0.018 , and 34 % versus 16 % , P = 0.005 , respectively . Regarding both anastomotic leakage and major morbidity rates , there was no significant difference between no-MBP and MBP group : 19 % versus 10 % ( P = 0.09 ) and 18 % versus 11 % ( P = 0.69 ) , respectively . Moderate or severe discomfort was reported by 40 % of prepared patients . Mortality rate ( 1.1 % vs 3.4 % ) and mean hospital stay ( 16 vs 14 days ) did not differ significantly between both groups . Conclusions : This first r and omized trial demonstrated that rectal cancer surgery without MBP was associated with higher risk of overall and infectious morbidity rates without any significant increase of anastomotic leakage rate . Thus , it suggests continuing to perform MBP before elective rectal resection for cancer . This study is registered with clinical trials.gov , number NCT00554892",
"Postoperative oral nutritional supplementation has been shown to be of clinical benefit . This study examined the clinical effects and cost of administration of oral supplements both before and after surgery",
"Background Surgical interventions activate a cascade of reactions that result in an aseptic inflammatory reaction . This inflammatory response initiates the organism ’s innate immunity . Laparoscopic surgery reduces the trauma , and patients benefit from diminished surgical trauma and maintained immune function . Cytokine levels and C-reactive protein ( CRP ) are related to the magnitude of surgical trauma and surgical stress . Toll-like receptors ( TLRs ) 2 and 4 are the first sensor-recognition receptors of the invading pathogens for the innate immune response . This study aim ed to compare the inflammatory response and then the stress response during laparoscopic and open colectomy for cancer by calculating TLR-2 and TLR-4 as the first sensor-recognition receptors together with interleukin-6 ( IL-6 ) , tumor necrosis factor-α ( TNF-α ) , and high-sensitivity CRP ( hsCRP ) . Methods A total 40 patients with colorectal cancer were r and omized in two groups : group A ( open colectomy , n = 20 ) and group B ( laparoscopic colectomy , n = 20 ) . An epidural catheter was placed in all patients 1 h preoperatively . Rupivocaine was administered perioperatively and 48 h postoperatively . Blood sample s were taken for calculation of IL-6 , TNF-α , hsCRP , TLR-2 , and TLR-4 preoperatively and 5 min after deflation of pneumoperitoneum ( group B ) or 5 min after division of the colon ( group A ) , then 6 and 24 h postoperatively . Results The mean operative time was 115 for group A and 142 min for group B. The mean blood loss was respectively 240 and 105 ml ( P the mean hospital stay was respectively 8 and 5 days ( P The IL-6 level was significant higher in group A than in group B at 6 and 24 h postoperatively ( P and the hsCRP level was significant higher in group A than in group B at 24 h postoperatively ( P 0.001 ) . The TNF-α values did not differ between the two groups . The TLR-2 level was significantly higher in group A than in group B at 5 min ( P = 0.013 ) and 24 h ( P = 0.007 ) postoperatively . The TLR-4 level was significant higher in group A than in group B at 5 min postoperatively ( P = 0.03 ) . Conclusion The inflammatory response and the result ant stress response are significantly less during laparoscopic colectomy than during open colectomy for colorectal cancer . This is an obvious short-term clinical benefit for the patient , providing tinder for further study to investigate the long-term results of laparoscopic colectomy versus open colectomy for colorectal cancer ( Registered clinical trial no. NCT00942461 ; www . clinical trials.gov )",
"UNLABELLED Infusions of carbohydrates before surgery reduce postoperative insulin resistance . We in-vestigated the effects of a carbohydrate drink , given shortly before surgery , on postoperative metabolism . METHOD Insulin sensitivity , glucose turnover ( [ 6,6 , 2H2]-D-glucose ) and substrate utilization were measured using hyperinsulinemic normoglycemic clamps and indirect calorimetry in two matched groups of patients before and after elective colorectal surgery . The drink group ( n = 7 ) received 800 ml of an isoosmolar carbohydrate rich beverage the evening before the operation ( 100 g carbohydrates ) , as well as another 400 ml ( 50 g carbohydrates ) 2 h before the initiation of anesthesia . The fasted group ( n = 7 ) was operated after an overnight fast . RESULTS After surgery , energy expenditure increased in both groups . Endogenous glucose production was higher after surgery and the difference was significant during low insulin infusion rates in both groups ( P endogenous glucose production by the two step insulin infusion was similar pre- and postoperatively in both groups . At the high insulin infusion rate postoperatively , whole body glucose disposal was more reduced in the fasted group ( -49 + /- 6 % vs -26 + /- 8 % , P insulin infusion rates , glucose oxidation decreased postoperatively only in the fasted group ( P postoperative levels of fat oxidation were greater in the fasted group ( P changes in cortisol and glucagon were found and no differences were found between the treatment groups . CONCLUSIONS Patients given a carbohydrate drink shortly before elective colorectal surgery displayed less reduced insulin sensitivity after surgery as compared to patients who were operated after an overnight fast",
"BACKGROUND In-vitro studies indicate that platelet function and the coagulation cascade are impaired by hypothermia . However , the extent to which perioperative hypothermia influences bleeding during surgery remains unknown . Accordingly , we tested the hypothesis that mild hypothermia increases blood loss and allogeneic transfusion requirements during hip arthroplasty . METHODS Blood loss and transfusion requirements were evaluated in 60 patients undergoing primary , unilateral total hip arthroplasties who were r and omly assigned to normothermia ( final intraoperative core temperature 36.6 [ 0.4 ] degrees C ) or mild hypothermia ( 35.0 [ 0.5 ] degrees C ) . Crystalloid , colloid , scavenged red cells , and allogeneic blood were administered by strict protocol . FINDINGS Intra- and postoperative blood loss was significantly greater in the hypothermic patients : 2.2 ( 0.5 ) L vs 1.7 ( 0.3 ) L , p allogeneic packed red cells were required in seven of the 30 hypothermic patients , whereas only one normothermic patient required a unit of allogeneic blood ( p core temperature in patients undergoing hip arthroplasty will thus augment blood loss by approximately 500 mL. INTERPRETATION The maintenance of intraoperative normothermia reduces blood loss and allogeneic blood requirements in patients undergoing total hip arthroplasty",
"BACKGROUND Patients who undergo surgery are at risk of malnutrition due to periods of starvation , the stress of surgery , and subsequent increase in metabolic rate . There are limited data on nutritional outcome of surgical patients . AIMS To investigate changes in nutritional status and the influence of oral supplements on nutritional status , morbidity , and quality of life in postoperative surgical patients . METHODS Entry was determined by the presence of malnutrition , as defined by a body mass index ( BMI ) ⩽20 kg/m2 , anthropometric measurements ⩽15th percentile on admission , or initiation of oral diet postoperatively and /or a weight loss of 5 % or more during the operative period . We studied 101 patients : 52 were r and omised to the treatment group ( TG ) and prescribed a 1.5 kcal/ml nutritional supplement ; 49 patients were r and omised to the control group ( CG ) and continued with routine nutritional management . Nutritional status was assessed by weight , anthropometry , and grip strength , with measurements taken at two weekly intervals for 10 weeks . Complications , namely wound infection , chest infection , and antibiotic use were documented . Quality of life ( QOL ) was assessed using the UK SF-36 question naire . RESULTS Patients in the control group lost a maximum mean ( SD ) of 5.96 ( 4.21 ) kg in weight over a period of eight weeks while patients in group TG lost less weight overall ( maximum mean ( SD ) 3.40 ( 0.89 ) kg ( p 4 ) . Anthropometry , grip strength , and QOL were similarly significantly different between groups ( p required antibiotic prescriptions compared with the control group ( 15/49 ) . CONCLUSIONS Nutritional status declined for two months after discharge . Postoperative nutritional supplementation improved nutritional status , QOL , and morbidity in these patients",
"As the U.S. population ages , major surgical procedures are being performed in elderly patients with increasing frequency ( 1 ) , but few data are available to guide preoperative risk stratification . Several studies have described correlates of cardiac morbidity and mortality in patients undergoing noncardiac surgery ( 2 - 8 ) , but the number of elderly patients in most series has been small . Furthermore , few data are available on noncardiac complications , the overall complication rate , and length of stay . We describe the influence of age on perioperative complication and mortality rates in a large cohort of patients undergoing noncardiac surgery . As discussed elsewhere , age was not an independent correlate of major cardiac complications in this cohort ( 7 ) . This analysis tests the hypothesis that advanced age is a correlate of the overall rate of complications , after adjustment for functional status . Methods Patients All patients 50 years of age or older who underwent major nonemergent noncardiac procedures at Brigham and Women 's Hospital , Boston , Massachusetts , from 18 July 1989 to 28 February 1994 were eligible for the study . Major noncardiac procedures were defined as those with an expected length of stay of 2 or more days . Procedures were electively scheduled or were performed nonemergently during inpatient admissions . Eligibility criteria included the ability to speak English and adequate cognitive function to give informed consent . The enrollment and clinical data collection protocol s were approved by the institutional review board of Brigham and Women 's Hospital . The full study protocol included preoperative interviews by clinical study personnel ( physicians or research nurses ) . Of the 4315 patients who provided informed consent to participate , 621 ( 14.4 % ) did not provide consent before surgery for the serial interview portion of the study , which included interviews 1 and 6 months after surgery . Patients who were not interviewed before surgery were not excluded on the basis of age or clinical status , but solely according to the availability of study personnel . Data Collection The data collection protocol is described elsewhere ( 7 , 9 , 10 ) . In brief , patients who provided informed consent to the full study protocol underwent preoperative evaluation by clinical investigators ( physicians or research nurses ) using a structured data form . These evaluations included detailed medical histories , physical examinations , and laboratory tests . For patients who did not undergo this evaluation because they could not be approached or because they declined participation in the interview portion of the study , we obtained clinical data from the structured evaluation by the anesthesiologist found in the medical record . This data source was also used to obtain American Society of Anesthesiologists classification for all patients . Hence , prospect ively recorded clinical data were available for all patients . Consenting patients agreed to postoperative sampling of creatine kinase and , if total creatine kinase levels were elevated , measurement of creatine kinaseMB immediately after surgery , at 8 p.m. on the evening of surgery , and on the next two mornings . In all other enrolled patients , creatine kinaseMB was measured according to the physician 's orders . Among all participants , the mean ( SD ) number of cardiac enzyme sample s obtained was 4.0 2.2 . Electrocardiography was performed in the recovery room and on the first , third , and fifth postoperative days if the patient remained hospitalized . The Charlson Comorbidity Index , a weighted comorbidity score based on the number and the severity of 16 selected medical diseases , was used to quantify the burden of medical comorbid conditions ( 11 ) . The mean number of other common comorbid conditions in this population was calculated for all patients . Preoperative functional status was assessed in 3890 patients by performing structured interviews using the Specific Activity Scale , an ordinally scaled , four-class instrument based on metabolic expenditure in various personal care , housework , occupational , and recreational activities ( 12 , 13 ) . This group included 196 patients who consented to preoperative interviews but did not consent to the full study protocol , including long-term follow-up . Classification of Outcomes The occurrence of major cardiac events postoperatively was classified by a single review er who was blinded to preoperative clinical data and who evaluated only postoperative clinical information , including cardiac enzyme measurements , electrocardiograms , and clinical events . Myocardial infa rct ion was diagnosed on the basis of creatine kinaseMB levels and electrocardiographic findings ( 10 ) . Major cardiac complications were unstable angina ( postoperative typical chest pain associated with ischemic electrocardiographic changes ) , myocardial infa rct ion , cardiogenic pulmonary edema , documented ventricular tachycardia , ventricular fibrillation or primary cardiac arrest , and sustained complete heart block requiring pacemaker . Major noncardiac events were pulmonary embolism documented by autopsy , angiography , or a high-probability ventilationperfusion scan ; respiratory failure requiring intubation for more than 2 days or reintubation ; noncardiogenic pulmonary edema ; lobar pneumonia confirmed by chest radiography and requiring antibiotic therapy ; acute renal failure requiring dialysis ; or cerebrovascular accident with new neurologic deficit . In-hospital mortality was also recorded , and the combined end point of major cardiac or noncardiac complications or death was used in these analyses . Statistical Analysis To evaluate the impact of age on postoperative complications , we performed analyses in which age was considered as a continuous variable and as four categories ( 50 to 59 years , 60 to 69 years , 70 to 79 years , and 80 years ) . Because age was not linearly associated with the risk for outcomes , categorized age variables are used throughout this report . Univariate correlations between clinical characteristics and age category were analyzed by using the chi-square test and the Fisher exact test for categorical variables and a t-test or Wilcoxon test for continuous variables . Because several clinical and laboratory variables are associated with age and because it is difficult to exclude the association of age with the event of interest , we included all relevant clinical variables in the multivariate analysis . Logistic regression analysis was used to determine the independent association of age with postoperative complications while controlling for the presence of comorbid conditions , sex , ethnicity , functional status as measured by Specific Activity Scale class , type of procedure , and preoperative laboratory data . Patients for whom data on selected variables were missing were excluded from the model . Clinical ly relevant variables from the regression model were analyzed for potential interactions , and potentially significant interaction terms were considered in the regression models . A two-sided P value less than 0.05 was considered statistically significant in all analyses . Linear regression models were used to estimate the independent variation in length of stay attributable to age , controlling for sex , ethnicity , preoperative clinical characteristics , American Society of Anesthesiologists classification , type of procedure , postoperative events , and in-hospital mortality . The logarithmic transformation of length of stay was used because of the non-normal distribution of this variable . The percentage change in the geometric mean of length of stay in the final model was used to estimate the numbers of adjusted hospital days attributable to age groups . All analyses were performed by using SAS statistical software for Windows , version 6.12 ( SAS Institute , Inc. , Cary , North Carolina ) . Role of the Funding Source The funding source had no role in data collection and analysis or in subsequent decisions about publication of manuscripts . Results Patients The study sample constituted 4315 patients who had a mean age of 67 9 years ; 2096 patients ( 48 % ) were male and 3903 ( 90 % ) were white . Twenty-four percent ( 1015 patients ) were younger than 59 years , 38 % ( 1646 patients ) were 60 to 69 years of age , 31 % ( 1341 patients ) were 70 to 79 years of age , and 7 % ( 313 patients ) were older than 80 years of age . These patients undergoing elective surgery had a low prevalence of comorbid conditions , and 3187 ( 74 % ) patients had Charlson Comorbidity Index scores of 0 through 2 . The types of procedures performed were orthopedic ( 35 % ) , intrathoracic ( 12 % ) , abdominal ( 12 % ) , abdominal aortic aneurysm ( 5 % ) , other vascular ( 17 % ) , and other general surgical procedures ( 33 % ) . In the oldest age group , significantly fewer patients were male and nonwhite compared with the younger age groups ( Table 1 ) . The number of comorbid conditions and the average Charlson Comorbidity Index scores increased with increasing age . The distribution of Specific Activity Scale class and American Society of Anesthesiology class was also significantly worse in the older age groups ; a greater proportion of patients 70 to 79 years of age and 80 years of age was classified as class 3 or 4 . As expected , the type of surgical procedure performed varied among age groups . Higher percentages of older patients underwent orthopedic procedures , aortic aneurysm repair , and other vascular surgeries ( Table 1 ) . Table 1 . Patient Characteristics Perioperative Complications Major or fatal perioperative complications occurred in 44 ( 4.3 % ) patients younger than 59 years of age , 93 ( 5.7 % ) patients 60 to 69 years of age , 129 ( 9.6 % ) patients 70 to 79 years of age , and 39 ( 12.5 % ) patients 80 years of age or older ( P risk for cardiogenic pulmonary edema , myocardial infa rct ion , ventricular arrhythmias , bacterial pneumonia , respiratory failure requiring intubation , and in-hospital mortality . All other major complications",
"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 It was hypothesized that routine operative drainage is unnecessary for elective hepatic resection . METHODS A review was made of the clinical records of patients undergoing liver resection at a tertiary referral hepatobiliary surgery center since the conclusion in April of 1994 of our previous r and omized drainage trial . The main outcome measures were operative drainage versus no operative drainage assessed for possible association with diagnoses , extent of hepatectomy , hospital course , and postoperative radiologic percutaneous drainage procedures . RESULTS Of 1,165 patients , 184 were operatively drained with closed drains according to specific practice criteria and 981 were not subject to operative drainage . Patients who were not operatively drained had length of stay ( 10.1 days ) , mortality ( 2 % ) , and complication rate ( 34 % ) comparable with the nondrained patients in the previous r and omized trial . Ten percent of these patients required postoperative percutaneous drainage . Patients who were operatively drained were a group who were at higher risk for biliary leakage or infections and consequently had a significantly longer hospital stay , greater mortality , higher complication rate , and required a greater number of percutaneous abdominal drainages . CONCLUSIONS The 84 % of patients not operatively drained had no greater adverse outcome . After hepatic resection , routine drainage of the abdomen is unnecessary",
"This systematic review and meta- analysis summarizes the clinical effects of increasing perioperative blood flow using fluids with or without inotropes/vasoactive drugs to explicit defined goals in adults . We included r and omized controlled trials of adult patients ( aged 16 years or older ) undergoing surgery . We included 31 studies of 5292 participants . There was no difference in mortality at the longest follow-up : 282/2615 ( 10.8 % ) died in the control group and 238/2677 ( 8.9 % ) in the treatment group , RR of 0.89 ( 95 % CI : 0.76 - 1.05 ; P=0.18 ) . However , the results were sensitive to analytical methods and withdrawal of studies with method ological limitations . The intervention reduced the rate of three morbidities ( renal failure , respiratory failure , and wound infections ) but not the rates of arrhythmia , myocardial infa rct ion , congestive cardiac failure , venous thrombosis , and other types of infections . The number of patients with complications was also reduced by the intervention . Hospital length of stay was reduced in the treatment group by 1.16 days . There was no difference in critical care length of stay . The primary analysis of this review showed no difference between groups but this result was sensitive to the method of analysis , withdrawal of studies with method ological limitations , and was dominated by a single large study . Patients receiving this intervention stayed in hospital 1 day less with fewer complications . It is unlikely that the intervention causes harm . The balance of current evidence does not support widespread implementation of this approach to reduce mortality but does suggest that complications and duration of hospital stay are reduced",
"MASTER is a multicenter registry of consecutively recruited patients with symptomatic , objective ly confirmed , acute venous thromboembolism . One fifth of the patients enrolled had cancer . In these patients , venous thromboembolism has peculiar features , and its management is more problematic . Background Clinical characteristics and management of acute deep vein thrombosis and pulmonary embolism ( PE ) have been reported to be different in patients with and without cancer . The aim of this paper was to provide information on clinical characteristics and management of acute venous thromboembolism in patients with cancer by means of a large prospect i ve registry . Design and Methods MASTER is a multicenter registry of consecutively recruited patients with symptomatic , objective ly confirmed , acute venous thromboembolism . Information about clinical characteristics and management was collected by an electronic data network at the time of the index event . Results A total of 2119 patients were enrolled , of whom 424 ( 20 % ) had cancer . The incidence of bilateral lower limb deep vein thrombosis was significantly higher in patients with cancer than in patients without cancer ( 8.5 % versus 4.6 % ; p rates of iliocaval thombosis ( 22.6 % versus 14 % ; p upper limb deep vein thrombosis ( 9.9 % versus 4.8 % ; p Major bleeding ( 3.3 % versus 1.1 % ; p=0.001 ) , in-hospital treatment ( 73.3 % versus 66.6 % ; p=0.02 ) and inferior vena cava filter implantation ( 7.3 % versus 4.1 % ; p=0.005 ) were significantly more frequent in patients with cancer , in whom oral anticoagulants were less often used ( 64.2 % versus 82 % ; p acute venous thromboembolism is different and often more extensive in cancer patients than in patients free from malignancy . Moreover , the management of the acute phase of venous thromboembolism is more problematic in cancer patients , especially because of a higher rate of major bleeding and the need for implantation of inferior vena cava filters",
"Purpose This study evaluated differences in stress response and immunological function following laparoscopic and conventional total mesorectal excision ( TME ) for rectal cancer . Methods Patients with non-metastasized rectal cancer were prospect ively r and omized to open ( n = 18 ) or laparoscopic ( n = 22 ) TME . Blood sample s were taken preoperatively ( baseline ) , 2 , 24 , and 72 h following surgery . Systemic white blood cell and monocyte count , C-reactive protein , interleukin-6 ( IL-6 ) , interleukin-8 ( IL-8 ) , HLA-DR expression on monocytes , growth hormone , prolactin , and cortisol were measured . Results Forty patients with a median age of 66 years ( interquartile range , 60–74 years ) were included . Eighteen patients ( 45 % ) were r and omized to open surgery and 22 patients ( 55 % ) to laparoscopic surgery . Patient demographics in terms of gender , age , BMI , ASA classification , localization of the tumor , and type of neoadjuvant therapy were comparable for both groups . Laparoscopic surgery result ed in a significantly better short-term preservation of postoperative immune function . HLA-DR expression on monocytes was significantly higher ( 64 % vs 50 % , P = 0.014 ) and IL-6 level increase was significantly lower ( 4.6 vs 10.8 , P = 0.003 ) 2 h after laparoscopic surgery . No differences between the open and laparoscopic technique were observed in postoperative white blood cell count , monocyte count , C-reactive protein , IL-8 , growth hormone , prolactin , and cortisol levels . ConclusionS hort-term postoperative immune and inflammatory functions tended to be better after laparoscopic rectal surgery . However , the differences were not consistent at all time intervals , making a definitive conclusion difficult . Better preserved inflammatory function 2 h after surgery may reflect a reduction in operative trauma when the laparoscopic technique is compared with open rectal procedures",
"Background The most common side effect of epidural or spinal anesthesia is hypotension with functional hypovolemia prompting fluid infusions or administration of vasopressors . Short-term studies ( 20 min ) in patients undergoing lumbar epidural anesthesia suggest that plasma volume may increase when hypotension is present , which may have implication s for the choice of treatment of hypotension . However , no long-term information or measurements of plasma volumes with or without hypotension after epidural anesthesia are available . Methods In 12 healthy volunteers , the authors assessed plasma ( 125I-albumin ) and erythrocyte ( 51Cr-EDTA ) volumes before and 90 min after administration of 10 ml bupivacaine , 0.5 % , via a thoracic epidural catheter ( T7–T10 ) . After 90 min ( t = 90 ) , subjects were r and omized to administration of fluid ( 7 ml/kg hydroxyethyl starch ) or a vasopressor ( 0.2 mg/kg ephedrine ) , and 40 min later ( t = 130 ) , plasma and erythrocyte volumes were measured . At the same time points , mean corpuscular volume and hematocrit were measured . Systolic and diastolic blood pressure , heart rate , and hemoglobin were measured every 5 min throughout the study . Volume kinetic analysis was performed for the volunteers receiving hydroxyethyl starch . Results Plasma volume did not change per se after thoracic epidural anesthesia despite a decrease in blood pressure . Plasma volume increased with fluid administration but remained unchanged with vasopressors despite that both treatments had similar hemodynamic effects . Hemoglobin concentrations were not significantly altered by the epidural blockade or ephedrine administration but decreased significantly after hydroxyethyl starch administration . Volume kinetic analysis showed that the infused fluid exp and ed a rather small volume , approximately 1.5 l. The elimination constant was 56 ml/min . Conclusions Thoracic epidural anesthesia per se does not lead to changes in blood volumes despite a reduction in blood pressure . When fluid is infused , there is a dilution , and the fluid initially seems to be located central ly . Because administration of hydroxyethyl starch and ephedrine has similar hemodynamic effects , the latter may be preferred in patients with cardiopulmonary diseases in which perioperative fluid overload is undesirable",
"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 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",
"Major surgery induces an immuno-inflammatory response accompanied by oxidative stress that may impair cellular function and delay recovery . The objective of the study was to investigate the effect of an enteral supplement , containing glutamine and antioxidants , on circulating levels of immuno-inflammatory markers after major gastrointestinal tract surgery . Patients ( n 21 ) undergoing major gastrointestinal tract surgery were r and omised in a single-centre , open-label study . The effects on circulating levels of immuno-inflammatory markers were determined on the day before surgery and on days 1 , 3 , 5 and 7 after surgery . Major gastrointestinal surgery increased IL-6 , TNF receptor 55/60 ( TNF-R55 ) and C-reactive protein ( CRP ) . Surgery reduced human leucocyte antigen-DR ( HLA-DR ) expression on monocytes . CRP decrease was more pronounced in the first 7 d in the treatment group compared with the control group . In the treatment group , from the moment Module AOX was administered on day 1 after surgery , TNF receptor 75/80 ( TNF-R75 ) level decreased until the third post-operative day and then stabilised , whereas in the control group the TNF-R75 level continued to increase . The results of the present pilot study suggest that enteral nutrition enriched with glutamine and antioxidants possibly moderates the immuno-inflammatory response ( CRP , TNF-R75 ) after surgery",
"Postoperative insulin resistance is a well-characterized metabolic state that has been shown to correlate with the length of postoperative stay in hospital . Preoperative intravenous or oral carbohydrate treatment has been shown to attenuate the development of postoperative insulin resistance measured 1 day after surgery . To study the effects of preoperative oral carbohydrate treatment on postoperative changes in insulin resistance and substrate utilization , in the absence of postoperative confounding factors , 15 patients were double-blindly treated with either a carbohydrate-rich beverage ( 12.5 % ) ( n = 8) or placebo ( n = 7 ) before undergoing total hip replacement surgery . Insulin sensitivity , endogenous glucose release , and substrate oxidation rates were measured before and immediately after surgery . Whole body insulin sensitivity decreased by 18 % in the treatment group vs. 43 % in the placebo group ( P insulin-induced nonoxidative glucose disposal after surgery . The better preservation of insulin sensitivity in the treatment group was attributable to a less reduced glucose disposal in peripheral tissues and increased glucose oxidation rates",
"The present study examined the hypothesis that altered motility of the gastrointestinal tract affects absorption of probe markers of intestinal permeability . Seven healthy subjects , aged 32 - 44 years , received saline , 600 micrograms atropine or 10 mg metoclopramide in r and omized order at weekly intervals . After 10 min they ingested a test solution containing 5 g lactulose , 5 g mannitol and 2 g 3-O-methyl glucose in 100 ml tap water . The molarity of the solution was 542 mmol l-1 and the dose administered was 80 ml m-2 body surface area . Gastric emptying was measured by ultrasound , mouth-to-caecum transit time by breath hydrogen analysis and sugar concentrations by gas-liquid chromatography . Gastric emptying half-times ( min ) were [ mean ( 95 % confidence intervals ) ] 14.9 ( 11:4 - 18.5 ) after saline , 22 ( 18.7 - 25.2 ) after atropine and 10.3 ( 7.0 - 12.6 ) after metoclopramide ( P less than 0.002 ) . Transit times ( min ) were 68.9 ( 52 - 85.2 ) after saline , 143 ( 126 - 159 ) after atropine and 38 ( 21.2 - 54.5 ) after metoclopramide ; P less than 0.0001 . Analysis of plasma levels of mannitol and 3-O-methyl glucose showed a significant within-subject effect of drug with time ( P less than 0.03 ) . Urinary excretion of mannitol in the first 5 h after ingestion of the test solution was 1256 ( 974 - 1620 ) mg after saline , 1560 ( 1210 - 2013 ) mg after atropine and 955 ( 740 - 1232 ) mg after metoclopramide ( P less than 0.03 ) . There were no significant differences in lactulose and 3-O-methyl glucose urinary excretion between drug treatments . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Objective : To evaluate whether ischemic preconditioning ( IP ) with continuous clamping or intermittent clamping ( IC ) of the portal triad confers better protection during liver surgery . Summary Background Data : IP and IC are distinct protective approaches against ischemic injury . Since both strategies proved to be superior in r and omized controlled trials ( RCTs ) to continuous inflow occlusion alone , we design ed a RCT to compare IP and IC in patients undergoing major liver resection . Methods : Noncirrhotic patients undergoing major liver resection were r and omized to receive IP with inflow occlusion ( n = 36 ) or IC ( n = 37 ) . Primary endpoints were postoperative liver injury and intraoperative blood loss . Postoperative liver injury was assessed by peak values of AST ( alanine aminotransferase ) and ALT ( aspartate aminotransferase ) , as well as the area under the curve ( AUC ) of the postoperative transaminase course . Secondary endpoints included resection time , the need of blood transfusion , ICU , and hospital stay as well as postoperative complications and mortality . Results : Both groups were comparable regarding demographics , ASA score , type of hepatectomy , duration of inflow occlusion ( range , 30–75 minutes ) , and resection surface . The transection-related blood loss was 146 versus 250 mL ( P = 0.008 ) , and when st and ardized to the resection surface 1.2 versus 1.8 mL/cm2 ( P = 0.01 ) for IP and IC , respectively . Although peak AST , AUCAST , and AUCALT were lower for IC , the differences did not reach statistical significance . Overall ( 42 % vs. 38 % ) and major ( 33 vs. 27 % ) postoperative complications as well as median ICU ( 1 vs. 1 day ) and hospital stay ( 10 vs. 11 days ) were similar between both groups . Conclusions : Both IP and IC appear to be equally effective in protecting against postoperative liver injury in noncirrhotic patients undergoing major liver resection . However , IP is associated with lower blood loss and shorter transection time . Therefore , both strategies can be recommended for noncirrhotic patients undergoing liver resection",
"HYPOTHESIS Better knowledge of independent risk factors might decrease mortality and morbidity rates following colorectal surgery . DESIGN Prospect i ve multicenter study . INTERVENTIONS From June to September 2002 , consecutive patients undergoing open or laparoscopic surgery ( electively or on an emergent basis ) for colorectal cancers or diverticular disease were prospect ively included . Exclusion criteria were colectomy for other causes ( eg , inflammatory bowel diseases , benign polyps ) . The structured sheet of data collection included more than 200 items on all perioperative data concerning the patient , the disease , and the operating surgeons . Postoperative mortality and morbidity were defined as in-hospital death and complications . RESULTS Among 1421 patients , the in-hospital death rate was 3.4 % and the overall morbidity rate was 35 % . Four independent preoperative risk factors of mortality were found : emergency surgery , loss of more than 10 % of weight , neurological comorbidity , and age older than 70 years . Six independent risk factors of morbidity were found : age older than 70 years , neurologic comorbidity , hypoalbuminemia , cardiorespiratory comorbidity , long duration of operation , and peritoneal contamination . CONCLUSION Colorectal resection in France is associated with a 3.4 % mortality rate and a 35 % morbidity rate . Knowledge of the risk factors could help surgeons manage cases",
"Background : Post‐operative insulin resistance and hyperglycaemia are associated with an impaired outcome after surgery . Pre‐operative oral carbohydrate loading ( CHO ) reduces post‐operative insulin resistance with a reduced risk of hyperglycaemia during post‐operative nutrition . Insulin‐resistant diabetic patients have not been given CHO because the effects on pre‐operative glycaemia and gastric emptying are unknown",
"BACKGROUND Occult hypovolaemia is a key factor in the aetiology of postoperative morbidity and may not be detected by routine heart rate and arterial pressure measurements . Intraoperative gut hypoperfusion during major surgery is associated with increased morbidity and postoperative hospital stay . We assessed whether using intraoperative oesophageal Doppler guided fluid management to minimize hypovolaemia would reduce postoperative hospital stay and the time before return of gut function after colorectal surgery . METHODS This single centre , blinded , prospect i ve controlled trial r and omized 128 consecutive consenting patients undergoing colorectal resection to oesophageal Doppler guided or central venous pressure (CVP)-based ( conventional ) intraoperative fluid management . The intervention group patients followed a dynamic oesophageal Doppler guided fluid protocol whereas control patients were managed using routine cardiovascular monitoring aim ing for a CVP between 12 and 15 mm Hg . RESULTS The median postoperative stay in the Doppler guided fluid group was 10 vs 11.5 days in the control group P median time to resuming full diet in the Doppler guided fluid group was 6 vs 7 for controls P cardiac output , stroke volume , and oxygen delivery . Twenty-nine ( 45.3 % ) control patients suffered gastrointestinal morbidity compared with nine ( 14.1 % ) in the Doppler guided fluid group P overall morbidity was also significantly higher in the control group P=0.05 . CONCLUSIONS Intraoperative oesophageal Doppler guided fluid management was associated with a 1.5-day median reduction in postoperative hospital stay . Patients recovered gut function significantly faster and suffered significantly less gastrointestinal and overall morbidity",
"Abstract . Background : A transverse skin crease incision for right hemicolectomy may result in more rapid recovery than traditional vertical midline incision . This hypothesis was tested with a prospect i ve r and omised trial . Methods : Patients from 2 centres undergoing right hemicolectomy were r and omised to received a midline or transverse incision . Incision lengths were sufficient to enable unrestricted resection of the right colon . Patients and carers were blinded to the incisions using strategically placed dressings . Analgesia and oral intake were controlled by the patient . Operative details and recovery parameters were compared . Results : A total of 28 patients were r and omised . Demographic data and tumour characteristics of the two treatment groups were similar . The transverse incision group had a slightly shorter median wound ( 10 cm vs. 11 cm , p Operative time , analgesia requirements , recovery parameters ( time to discharge , 6.5 vs. 6.5 days ) and frequency of complications were otherwise comparable . Conclusions : A transverse skin crease incision for right hemicolectomy results in a slightly smaller wound but no other advantages were demonstrated compared with a traditional vertical midline incision",
"BACKGROUND Voiding dysfunction is frequently observed after rectal resection and justifies urinary drainage . However , there is no agreement about the optimal duration of this postoperative drainage . The aim of this controlled trial was to compare 1 versus 5 days of transurethral catheterization after rectal resection , with special reference to urinary tract infection and bladder retention . METHODS One hundred twenty-six patients undergoing rectal resection were included in a prospect i ve r and omized study design ed to compare the results for patients undergoing 1 day of transurethral catheterization after rectal resection ( 1-day group ) with those for patients undergoing 5 days ' catheterization ( 5-day group ) . RESULTS Patients were r and omly assigned to the 1-day and 5-day groups ( n = 64 and 62 , respectively ) . Clinical findings and surgical procedures were comparable in both groups . Acute urinary retention occurred in 16 patients ( 25 % ) in the 1-day group versus 6 ( 10 % ) in the 5-day group ( P Urinary tract infection was observed in 13 of 64 patients ( 20 % ) in the 1-day group versus 26 of 62 ( 42 % ) in the 5-day group ( P analysis revealed that after 1 day of catheterization carcinoma of the low rectum and lymph node metastasis were significant risk factors for acute urinary retention ( P patients without low rectum carcinoma , the acute urinary retention rate was comparable in both groups ( 14 % in the 1-day group versus 7 % in the 5-day group ) , but the urinary tract infection rate was significantly lower in the 1-day group versus the 5-day group ( 14 % vs 40 , P < .01 ) . CONCLUSIONS Our controlled study showed that after rectal resection 1 day of urinary drainage can be recommended for most patients . Five-day drainage should be reserved for patients with low rectal carcinoma",
"UNLABELLED It is not known whether patients with postoperative nausea and vomiting ( PONV ) have delayed gastric emptying compared with patients without PONV . We compared the perioperative rate of gastric emptying in patients experiencing PONV with the rate in those without PONV immediately after laparoscopic cholecystectomy . Gastric emptying was studied by the acetaminophen method . Acetaminophen is not absorbed from the stomach but is rapidly absorbed from the small intestine , and the rate of gastric emptying therefore determines the rate of absorption of acetaminophen administered into the stomach . Forty patients ( ASA physical status I and II ) were included in the study . After the induction of anesthesia , a gastric tube was positioned in the stomach and 1.5 g of acetaminophen dissolved in 200 mL of water was administered . Venous blood sample s for the determination of serum acetaminophen concentrations were taken before and at 15-min intervals during a period of 180 min after the administration of acetaminophen . Twenty-six patients experienced nausea during the first 4 h postoperatively . The other 14 patients had no nausea . There were no statistically significant differences in the maximal acetaminophen concentration , the time taken to reach the maximal concentration , or the area under the serum acetaminophen concentration time curves from 0 to 60 , 0 - 120 , and 0 - 180 min between the groups of patients with or without PONV . We did not find any relationship between postoperative gastric emptying and PONV , and therefore gastric emptying is not a predictor of PONV . IMPLICATION S The incidence of postoperative nausea and vomiting is frequent after laparoscopic cholecystectomy . This study has shown that perioperative gastric emptying is not a predictor of early postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy",
"Background Due to potentially superior short-term outcomes compared with open colorectal surgery , laparoscopic surgery is currently being implemented in clinical practice worldwide . In parallel , enhanced recovery after surgery ( ERAS ) programs are shown to improve postoperative recovery in open colorectal surgery . This study reports outcomes in laparoscopic versus open surgery in conjunction with compliance to the ERAS protocol . Methods The association between surgical approach ( laparoscopic or open surgery ) , compliance to the ERAS protocol , postoperative symptoms , complications , and length of stay after surgery was studied . Between January 2007 to December 2010 , 114 consecutive patients underwent elective high anterior resection with laparoscopic-assisted ( n = 55 ) or open resection ( n = 59 ) . All clinical data ( 114 variables ) were prospect ively recorded . Results The overall preoperative ERAS- protocol compliance was 77 % for both the laparoscopic and open group . Laparoscopic surgery result ed in shorter total length of stay ( median 4 vs. 6 days , p = 0.04 ) , earlier pain control ( median 2 vs. 3 days , p = 0.008 ) , shorter need for intravenous infusions , improved mobilization on the first postoperative day ( POD1 ) , and lower inflammatory response ( CRP ( POD1 ) 54 ± 24 vs. 67 ± 31 mg/l , p = 0.017 ) compared with open resection . The trends in fewer postoperative complications ( 9.1 vs. 16.9 % ; odds ratio ( OR ) 0.55 ; 95 % confidence interval ( CI ) 0.17–1.81 ) and overall postoperative symptoms delaying recovery ( 20 vs. 30.5 % ; OR 0.63 ; 95 % CI 0.22–1.34 ) in laparoscopic surgery were not statistically significant . Conclusions The use of laparoscopy in colorectal surgery within an ERAS protocol results in faster recovery compared with open resection",
"Background and Objectives Postoperative urinary retention may occur in between 10 % and 60 % of patients after major surgery . Continuous lumbar epidural analgesia , in contrast to thoracic epidural analgesia , may inhibit urinary bladder function . Postoperative urinary drainage has been common in patients with continuous epidural analgesia , despite the lack of scientific evidence for its indication after thoracic epidural analgesia . This study describes 100 patients who underwent elective colonic resection with 48 hours of continuous thoracic epidural analgesia and only 24 hours of urinary drainage . Methods This is a prospect i ve , uncontrolled study with well-defined general anesthesia , postoperative analgesia , and nursing care programs in patients with a planned 2-day hospital stay , urinary catheter removal on the first postoperative morning , and epidural catheter removal on the second postoperative morning . Follow-up in the outpatient clinic was on days 8 and 30 . Results Nine patients needed bladder recatheterization , 8 as a single procedure and 1 patient a second recatheterization with removal on day 7 . This patient had urinary infection on day 10 and was readmitted for 5 days because of urosepsis and , subsequently , for cystitis and left-sided epididymitis . Three patients had uncomplicated urinary infection . No patients had urological complaints at 30 days follow-up ( 95 % confidence limit , 0 % to 3.6 % ) . Conclusion The low incidence of urinary retention ( 9 % ) and urinary infection ( 4 % ) suggests that routine bladder catheterization beyond postoperative day 1 may not be necessary in patients with ongoing continuous low-dose thoracic epidural analgesia",
"Objective It has been demonstrated that colon operation combined with fast-track ( FT ) surgery and laparoscopic technique can shorten the length of hospital stay , accelerate recovery of intestinal function , and reduce the occurrence of post-operative complications . However , there are no reports regarding the combined effects of FT colon operation and laparoscopic technique on humoral inflammatory cellular immunity . Methods This was a prospect i ve , controlled study . One hundred sixty-three colon cancer patients underwent the traditional protocol and open operation ( traditional open group , n = 42 ) , the traditional protocol and laparoscopic operation ( traditional laparoscopic group , n = 40 ) , the FT protocol and open operation ( FT open group , n = 41 ) , or the FT protocol and laparoscopic operation ( FT laparoscopic group , n = 40 ) . Blood sample s were taken prior to operation as well as on days 1 , 3 , and 5 after operation . The number of lymphocyte sub population s was determined by flow cytometry , and serum interleukin-6 and C-reactive protein levels were measured . Post-operative hospital stay , post-operative morbidity , readmission rate , and in-hospital mortality were recorded . Results Compared with open operation , laparoscopic colon operation effectively inhibited the release of post-operative inflammatory factors and yielded good protection via post-operative cell immunity . FT surgery had a better protective role with respect to the post-operative immune system compared with traditional peri-operative care . Inflammatory reactions , based on interleukin-6 and C-reactive protein levels , were less intense following FT laparoscopic operation compared to FT open operation ; however , there were no differences in specific immunity ( CD3 + and CD4 + counts , and the CD4+/CD8 + ratio ) during these two types of surgical procedures . Post-operative hospital stay in patients r and omized to the FT laparoscopic group was significantly shorter than in the other three treatment groups ( P Post-operative complications in patients who underwent FT laparoscopic treatment were less than in the other three treatment groups ( P readmission rate and in-hospital mortality . Conclusions The laparoscopic technique and FT surgery rehabilitation program effectively inhibited release of post-operative inflammatory factors with a reduction in peri-operative trauma and stress , which together played a protective role on the post-operative immune system . Combining two treatment measures during colon operation produced better protective effects via the immune system . The beneficial clinical effects support that the better-preserved post-operative immune system may also contribute to the improvement of post-operative results in FT laparoscopic patients ",
"Background : Nasogastric ( NG ) intubation is widely used following elective abdominal operations although it is associated with morbidity and discomfort . The present study is a r and omised controlled trial on the effect of early oral feeding without NG decompression following elective colorectal resection for cancer",
"AIM Recent evidence suggests that the provision of energy-containing fluids is safe and may impact positively on markers of recovery . The aims of this study were to assess the tolerance of preoperative carbohydrate fluid administration and to determine its effect on postoperative metabolic and clinical responses . METHODS Patients admitted to the Royal Infirmary of Edinburgh for major , elective abdominal surgery were recruited to this double-blind , r and omised study and received either a placebo drink or carbohydrate ( 12.6g/100ml ) drink ( CHOD ) . Patients consumed 800 ml of their drink on the evening before surgery and 400 ml on the day of surgery 2 - 3 h before the induction of anaesthesia . Nutritional status was determined using body mass index ( BMI ) and upper arm anthropometry ; all measurements were taken preoperatively , postoperatively and at discharge . Blood glucose and insulin concentrations were also measured preoperatively and on the first post operative day . Length of hospital stay ( LOS ) and postoperative complications were recorded . RESULTS Seventy-two patients were recruited and 65 ( 34 male:31 female ) completed this study . Thirty-four patients were r and omised to receive the placebo drink ( control group ) and 31 patients to receive the carbohydrate drink ( CHOD group ) . Groups were well-matched in terms of gender and age . There were no differences between the two groups at baseline for BMI ( control : -25.1+/-1.7 kg/m2 ; CHOD -25.2+/-1.2 kg/m2 ) , upper arm anthropometry or surgical procedure . At discharge loss of muscle mass ( arm muscle circumference ) was significantly greater in the control group when compared with the CHOD group ( control : -1.1+/-0.15 cm ; CHOD : -0.5+/-0.16 cm ; P Baseline insulin ( control : 20.7+/-4.9 mU/l ; CHOD : 24.6+/-6.2 mU/l ) and glucose ( control : 6.0+/-1.4 mmol/l ; CHOD 5.7+/-1.4 mmol/l ) were comparable in the two groups and did not differ postoperatively . No complications were recorded as a result of preoperative fluid consumption . Postoperative morbidity occurred in six patients from each group . Median LOS in the control group was 10 days ( IQR=6 ) , and 8 days ( IQR=4 ) in the CHOD group . CONCLUSION Preoperative consumption of carbohydrate-containing fluids is safe . Provision of a carbohydrate energy source prior to surgery may attenuate depletion of muscle mass after surgery . Further studies are required to determine if this preservation of muscle mass is reflected in improved function and reduced rehabilitation time",
"Abstract PURPOSE : This study was design ed to evaluate differences in both the peritoneal and systemic immune response after laparoscopic and conventional surgical approaches . METHODS : Patients with a primary carcinoma were prospect ively r and omized to curative laparoscopic ( n = 12 ) or conventional ( n = 14 ) colon resection . The proinflammatory cytokines interleukin-6 , interleukin-8 , and tumor necrosis factor-alpha were measured in the peritoneal drain fluid and in the serum . C-reactive protein and leukocyte counts and the differences in leukocyte sub population s and expression of human leukocyte antigen-DR on monocytes were measured perioperatively . RESULTS : Significantly higher levels of proinflammatory cytokine were found in the peritoneal drain fluid than in the circulation after both procedures . Serum interleukin-6 and interleukin-8 levels were significantly lower 2 hours after laparoscopic surgery than with the conventional procedure . Postoperative cellular immune counts and human leukocyte antigen-DR expression normalized earlier after the laparoscopic approach . CONCLUSIONS : The systemic proinflammatory concentrations after both surgical approaches represent only a small fragment of what is generated in the peritoneal drain fluid . Even if the immediate levels of proinflammatory cytokines in the serum are significantly lower in the laparoscopic group , the same cytokines locally produced showed no differences , which suggests that the two intra-abdominal approaches are equally traumatic . No differences in cellular response were observed between the groups",
"Scintigraphy is the current gold st and ard for the quantification of gastric emptying ; however , results vary with meal composition . We modified a dual phase meal for administration to patients in the early post-operative period and aim ed to test the reproducibility of the method , to obtain normal ranges and to compare these with previous data . Twenty healthy volunteers ( 10 male , 10 female ) , studied prospect ively , were compared with 10 historical male volunteers . Each volunteer was studied twice ( Test 1 at day 0 and Test 2 at day 7 - 10 ) . After an overnight fast , subjects had Meal A consisting of a 60 g pancake labelled with 3 MBq of non-absorbable 99mTc-ion exchange resin and 100 ml of water labelled with 0.5 MBq of non-absorbable 111In-diethylenetriamine pentaacetic acid ( 111In-DTPA ) . Anterior and posterior gamma camera images of the stomach were obtained every 20 min for 3 h. The time for 50 % emptying ( T50 ) was derived from time-activity curves . Data obtained for males were compared with historical data using a similar technique with Meal B , consisting of two pancakes and a 200 ml milkshake labelled with identical amounts of radioisotopes . The mean ( 95 % CI ) T50 values for solid phase emptying for males and females using Meal A , and for historical males using Meal B , were 51.1 min ( 44.1 - 58.1 ) , 58.6 min ( 52.7 - 64.5 ) and 128.9 min ( 112.8 - 145.1 ) , respectively . Corresponding figures for the liquid phase were 33.2 min ( 26.1 - 40.3 ) , 50.2 min ( 38.4 - 62.1 ) and 30.7 min ( 21.4 - 39.9 ) . Bl and -Altman plots for each phase showed good agreement between Tests 1 and 2 for Meal A. The modified test meal gave reproducible results in healthy volunteers ; however , solid phase emptying was significantly faster than that of the bulkier test meal in historical subjects",
"OBJECTIVE To study the development of insulin resistance and changes in stress hormone concentrations in patients undergoing elective operations of different magnitude . DESIGN Prospect i ve open study . SETTING University hospital , Sweden . SUBJECTS 12 otherwise healthy patients , undergoing elective surgery for cholecystectomy ( n = 6 ) and inguinal hernia repair ( n = 6 ) . INTERVENTIONS Insulin sensitivity was measured by the normoglycaemic , hyperinsulinaemic glucose clamp technique before operation ( control ) and on the first postoperative day . MAIN OUTCOME MEASURE Relative insulin sensitivity ( compared with preoperative ) on the day after each operation . Changes in stress hormone concentrations in relation to the relative change in insulin sensitivity . RESULTS After hernia repair , mean ( SEM ) insulin sensitivity was reduced by 32 (4)% , p changes in concentrations of catecholamines , glucagon , cortisol and growth hormone after operation were only small , and did not correlate with the relative changes in insulin sensitivity . CONCLUSIONS Insulin resistance develops even after a minor elective operation , ( inguinal hernia repair ) . The degree of postoperative insulin resistance was more pronounced after open cholecystectomy . The alteration in insulin sensitivity could not be related to simultaneous changes in the hormones studied",
"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",
"Purpose A postoperative decrease in the gastric emptying ( GE ) rate may delay the early start of oral feeding and alter the bioavailability of orally administered drugs . The aim of this study was to compare the effect on early gastric emptying between two anesthetic techniques . Methods Fifty patients ( age , 19–69 years ) undergoing day-case laparascopic cholecystectomy were r and omly assigned to received either total intravenous anesthesia with propofol/remifentanil/rocuronium ( TIVA ; n = 25 ) or inhalational opioid-free anesthesia with sevoflurane/rocuronium ( mask induction ; GAS ; n = 25 ) . Postoperative gastric emptying was evaluated by the acetaminophen method . After arrival in the recovery unit , acetaminophen ( paracetamol ) 1.5 g was given through a nasogastric tube , and blood sample s were drawn during a 2-h period . The area under the serum-acetaminophen concentration curve from 0–60 min ( AUC60 ) , the maximal concentration ( Cmax ) , and the time to reach C-max ( Tmax ) were calculated . Results Twelve patients were excluded due to surgical complications ( e.g. , conversion to open surgery ) and difficulty in drawing blood sample s ( TIVA , n = 7 ; GAS , n = 5 ) . Gastric emptying parameters were ( mean ± SD ) : TIVA , AUC60 , 2458 ± 2775 min·µmol·l−1 ; Cmax , 71 ± 61 µmol·l−1 ; and Tmax , 81 ± 37 min ; and GAS , AUC60 , 2059 ± 2633 min·µmol·l−1 ; Cmax , 53 ± 53 µmol·l−1 ; and Tmax , 83 ± 41 min . There were no significant differences between groups . Conclusion There was no major difference in early postoperative gastric emptying between inhalation anesthesia with sevoflurane versus total intravenous anesthesia with propofol-remifentanil . Both groups showed a pattern of delayed gastric emptying , and the variability in gastric emptying was high . Perioperative factors other than anesthetic technique may have more influence on gastric emptying",
"This r and omized clinical trial compared the use of thoracic epidural anaesthesia – analgesia ( TEA ) with morphine patient‐controlled analgesia ( PCA ) for pain relief after laparoscopic colectomy",
"Background Overnight fasting is routine before elective surgery . This may not be the optimal way to prepare for surgical stress , however , because intravenous carbohydrate supplementation instead of fasting has recently been shown to reduce postoperative insulin resistance . In the current study , gastric emptying of a carbohydrate-rich drink was investigated before elective surgery and in a control situation . Methods Twelve patients scheduled for elective surgery were r and omly given 400 mL of either a carbohydrate-rich drink ( 285 mOsm/kg , 12.0 % carbohydrates , n = 6 ) or water 4 hours before being anesthetized . Gastric emptying was measured ( gamma camera , 99Tcm ) . Each patient repeated the protocol postoperatively as a control . All values were presented as the mean ± SEM by means of a nonparametric statistical evaluation . Results Despite the increased anxiety experienced by patients before surgery ( p , gastric emptying did not differ between the experimental and control situations . Initially , water emptied more rapidly than carbohydrate . However , after 90 minutes , the stomach was emptied regardless of the solution administered ( 3.2 ± 1.1 % [ mean ± SEM ] remaining in the stomach in the carbohydrate group versus 2.3 ± 1.2 % remaining in the stomach in the water group ) . Conclusions Preoperative anxiety does not prolong gastric emptying . The stomach had been emptied 90 minutes after Ingestion of both the carbohydrate-rich drink and water , thereby indicating the possibility of allowing an intake of iso-osmolar carbohydrate-rich fluids before surgery",
"We studied the effects of different preoperative oral fluid protocol s on preoperative discomfort , residual gastric fluid volumes , and gastric acidity . Two-hundred-fifty-two elective abdominal surgery patients ( ASA physical status I – II ) were r and omized to preparation with a 12.5 % carbohydrate drink ( CHO ) , placebo ( flavored water ) , or overnight fasting . The CHO and Placebo groups were double-blinded and were given 800 mL to drink on the evening before and 400 mL on the morning of surgery . Visual analog scales were used to score 11 different discomfort variables . CHO did not increase gastric fluid volumes or affect acidity , and there were no adverse events . The visual analog scale scores in a control situation were not different between groups . During the waiting period before surgery , the CHO-treated group was less hungry and less anxious than both the other groups ( P ≤ 0.05 ) . CHO reduced thirst as effectively as placebo ( P decreasing thirst , hunger , anxiety , malaise , and unfitness in the CHO group ( P The Placebo group experienced decreasing unfitness and malaise , whereas nausea , tiredness , and inability to concentrate increased ( P group , hunger , thirst , tiredness , weakness , and inability to concentrate increased ( P conclusion , CHO significantly reduces preoperative discomfort without adversely affecting gastric contents",
"Purpose To determine whether , in obese [ body mass index ( BMI ) > 30 kg·m2 ] patients , oral intake of 300 mL clear liquid two hours before elective surgery affects the volume and pH of gastric contents at induction of anesthesia . Methods A single-blind , r and omized study of 126 adult patients , age ≥18 yr , ASA physical status I or II , BMI > 30 kg·m2 who were scheduled for elective surgery under general anesthesia . Patients were excluded if they had diabetes mellitus , symptoms of gastroesophageal reflux , or had taken medication within 24 hr that affects gastric secretion , gastric fluid pH or gastric emptying . All patients fasted from midnight and were r and omly assigned to fasting or fluid group . Two hours before their scheduled time of surgery , all patients drank 10 mL of water containing phenol red 50 mg . Those in the fluid group followed with 300 mL clear liquid of their choice . Immediately following induction of general anesthesia and tracheal intubation , gastric contents were aspirated through a multiorifice Salem sump tube . The fluid volume , pH and phenol red concentration were recorded . Results Median ( range ) values in fasting vs fluid groups were : gastric fluid volume 26 ( 3–107 ) mL vs 30 ( 3–187 ) mL , pH 1.78 ( 1.31–7.08 ) vs 1.77 ( 1.27–7.34 ) and phenol red retrieval 0.1 (0–30)% vs 0.2 (0–15)% . Differences between groups were not statistically significant . Conclusion Obese patients without comorbid conditions should follow the same fasting guidelines as non-obese patients and be allowed to drink clear liquid until two hours before elective surgery , inasmuch as obesity per se is not considered a risk factor for pulmonary aspiration . RésuméObjectifDéterminer si , chez des patients obèses [ indice de masse corporelle ( IMC ) > 30 kg·m2 ] , la prise orale de 300 mL de liquide clair deux heures avant de subir une opération réglée a un effet sur le volume et le pH du contenu gastrique lors de l’induction anesthésique . MéthodeUne étude r and omisée , à simple insu , a été menée auprès de 126 patients adultes , ≥18 ans , d’état physique ASA I ou II , d’IMC > 30 kg·m2 , devant subir une intervention chirurgicale réglée sous anesthésie générale . La présence de diabète , ou de symptômes de reflux gastro-œsophagien ou la prise de médicaments , dans les 24 h avant l’opération , pouvant affecter la sécrétion gastrique , le pH du liquide gastrique ou l’évacuation gastrique entraînaient l’exclusion du patient . Tous les patients , à jeun depuis minuit , ont été répartis en deux groupes : jeûne ou liquide . Deux heures avant l’heure prévue de l’opération , tous les patients ont bu 10 mL d’eau contenant 50 mg de rouge de phénol . Les patients du groupe « liquide » ont pris ensuite 300 mL d’un liquide clair de leur choix . Immédiatement après l’induction de l’anesthésie et l’intubation endotrachéale , le contenu gastrique a été aspiré au moyen d’une sonde multiorifice Salem . Le volume de liquide , le pH et les concentrations de rouge de phénol ont été notés . RésultatsLes valeurs moyennes ( étendue ) du groupe de jeûne vs le groupe « liquide » ont été : volume de liquide gastrique 26 ( 3–107 ) mL vs 30 ( 3–187 ) mL , pH 1,78 ( 1,31–7,08 ) vs 1,77 ( 1,27–7,34 ) et repérage du rouge de phénol 0,1 ( 0–30 ) % vs 0,2 ( 0–15 ) % . Il n’y avait pas de différence intergroupe significative . Conclusion Les patients obèses , sans symptômes comorbides , devraient suivre les mêmes directives de jeûne que les patients non obèses . Ils peuvent boire un liquide clair jusqu’à deux heures avant une opération réglée , étant donné que l’obésité en elle-même n’est pas considérée comme un facteur de risque d’aspiration pulmonaire",
"INTRODUCTION Postoperative traditional feeding protocol s are not based on scientific studies , but rather on anecdotal evidence . We present the first prospect i ve trial of aggressive postoperative bowel stimulation following radical hysterectomy in an attempt to determine its effect on the length of hospital stay . METHODS Twenty consecutive patients undergoing radical hysterectomy were entered onto a prospect i ve trial of aggressive postoperative bowel stimulation , which consisted of 30 cc milk of magnesia p.o . b.i.d . starting on postoperative day 1 and biscolic suppositories q.d . starting on day 2 . A clear liquid diet was begun following flatus or bowel movement and patients were discharged 12 h after tolerating a clear liquid diet . Diet was slowly advanced at home . RESULTS Median time to flatus was 3 days , bowel movement 3 days , and clear liquid diet 3 days . Median time to discharge was 4 days . No patients developed ileus or bowel obstructions and there were no readmissions for bowel complications . Our median time to discharge of 4 days represents a 50 % reduction in hospital stay compared to our previous prospect i ve study using traditional postoperative bowel management ( 8 days ) , which was statistically significant at P = 0.001 . CONCLUSION Aggressive bowel stimulation with milk of magnesia and biscolic suppositories result ed in early return of bowel function and early discharge with no noticeable complications",
"BACKGROUND There is a need for an accurate measure of surgical outcomes so that hospitals and surgeons can be compared properly regardless of case mix . POSSUM ( Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity ) uses a physiological score and an operative severity score to calculate risks of mortality and morbidity . In a previous small study it was found that Portsmouth POSSUM ( P-POSSUM ; a modification of the POSSUM system ) provided a more accurate prediction of mortality . METHODS Some 10000 general surgical interventions ( excluding paediatric and day cases ) were studied prospect ively between August 1993 and November 1995 . The POSSUM mortality equation was applied to the full 10000 surgical episodes . The 10000 patients were arranged in chronological order and the first 2500 were used as a training set to produce the modified P-POSSUM predictor equation . This was then applied prospect ively to the remaining 7500 patients arranged chronologically in five groups of 1500 . RESULTS The original POSSUM logistic regression equation for mortality overpredicts the overall risk of death by more than twofold and the risk of death for patients at lowest risk ( 5 per cent or less ) by more than sevenfold . The P-POSSUM equation produced a very close fit with the observed in-hospital mortality . CONCLUSION P-POSSUM provides an accurate method for comparative surgical audit",
"To determine the impact of in-hospital postoperative complications on long-term survival , we prospect ively studied consecutive patients ≥70 yr of age undergoing noncardiac surgery . Potential clinical risk factors were measured and evaluated for their association with the occurrence of long-term postoperative mortality . Long-term survival was determined by using the Kaplan-Meier method . Multivariate correlates of survival were analyzed with the Cox proportional hazards model . The survival of the study group was also compared with the age- and gender-matched general United States population . Five hundred seventeen patients who survived the initial hospitalization were studied . The mean follow-up duration was 28.6 ± 12.8 mo . One hundred sixty-four of 517 patients ( 31.7 % ) were deceased at the time of follow-up . A history of cancer ( hazard ratio [ HR ] 2.44 , 95 % confidence interval [ CI ] 1.78–3.38 , P II ( HR 2.27 , 95 % CI 1.61–3.21 , P neurologic disease ( HR 1.59 , 95 % CI 1.13–2.24 , P = 0.008 ) , age ( HR 1.42 per decade , 95 % CI 1.11–1.81 , P = 0.005 ) , postoperative pulmonary complications ( HR 2.41 , 95 % CI 1.30–4.48 , P = 0.005 ) , and renal complications ( HR 6.07 , 95 % CI 2.23–16.52 , P decreased long-term survival . Compared with the United States population , patients with complications had a greater increase in mortality risk in the first 3 mo after surgery ( HR 7.3 versus general population ) than those without complications ( HR 2.9 , P = 0.023 ) . An effort to improve perioperative care delivery to elderly surgical patients must include measures to minimize in-hospital postoperative complications , particularly those involving the pulmonary and renal systems",
"BACKGROUND The ERAS ( enhanced recovery after surgery ) care has been shown in r and omized clinical trials to improve outcome after colorectal surgery compared to traditional care . The impact of different levels of compliance and specific elements , particularly out with a trial setting , is poorly understood . OBJECTIVE This study evaluated the individual impact of specific patient factors and perioperative enhanced recovery protocol compliance on postoperative outcome after elective primary colorectal cancer resection . METHODS The international , multicenter ERAS registry data , collected between November 2008 and March 2013 , was review ed . Patient demographics , disease characteristics , and perioperative ERAS protocol compliance were assessed . Linear regression was undertaken for primary admission duration and logistic regression for the development of any postoperative complication . FINDINGS A total of 1509 colonic and 843 rectal resections were undertaken in 13 centers from 6 countries . Median length of stay for colorectal resections was 6 days , with readmissions in 216 ( 9.2 % ) , complications in 948 ( 40 % ) , and reoperation in 167 ( 7.1 % ) of 2352 patients . Laparoscopic surgery was associated with reduced complications [ odds ratio ( OR ) = 0.68 ; P length of stay ( OR = 0.83 , P fewer complications ( OR = 0.69 , P primary hospital admission ( OR = 0.88 , P Shorter hospital stay was associated with preoperative carbohydrate and fluid loading ( OR = 0.89 , P = 0.001 ) , and totally intravenous anesthesia ( OR = 0.86 , P stay was associated with intraoperative epidural analgesia ( OR = 1.07 , P = 0.019 ) . Reduced postoperative complications were associated with restrictive perioperative intravenous fluids ( OR = 0.35 , P laparoscopic surgery independently improve outcome",
"AIMS Adjuvant therapy after surgery for colorectal cancer is often denied to the elderly for various reasons . This study was to determine morbidity and mortality risk after surgery in the elderly and whether this is affected by adjuvant therapy . METHODS Data were collected prospect ively and entered on a data base for all patients undergoing resection of colorectal cancer between January 1994 and July 2000 . A total of 304 patients were included , 65 aged 80 years and over . RESULTS There were 84 deaths , 21 ( 30 % ) in the over 80s , and 63 ( 26 % ) in the under 80s ( P=0.51 ) . The ' in-hospital ' mortality was 10.1 % in the over 80s and 3.8 % in the under 80s ( P=0.056 ) . In the over 80s the colon was more affected than the rectum ( P=0.002 ) . The over 80s were less likely to be offered adjuvant therapy , 7.2 % vs 42.1 % ( P 5 year survival ( all-cause mortality ) in the over 80s was 58.5 % and 47.6 % in the under 80s ( P=0.25 ) . Cox 's regression analysis of all patients identified the following factors to be independently related to overall survival : age>80 years , post-operative leak , increasing Dukes stage and distant recurrence of disease . CONCLUSION This study has demonstrated that surgery should not be denied to elderly patients with colorectal cancer as despite a higher post-operative morbidity and mortality rate and with the absence of adjuvant therapy , favourable long-term outcome can be achieved by resectional surgery alone",
"BACKGROUND AND AIMS Nutritional supplements are widely administered in hospitals and can benefit clinical outcome . The aim here was to determine the effect of routine post-operative nutritional supplementation on the nutritional status and clinical outcome of adult orthopaedic patients . METHODS A prospect i ve controlled study was conducted on two adult orthopaedic wards . Patients in the study group were prescribed two nutritional supplements/day post-operatively . Nutritional and biochemical indices and incidence of clinical complications were observed . RESULTS Of 181 patients studied , 14 in the supplemented group and 34 in the control ( P=0.005 ) developed major complications . There were 22 occurrences of major complications in the supplemented group and 55 in the control ( P=0.0002 ) . There was no significant difference in the number of minor complications between the two groups ( P=0.2 ) . There was no statistical difference in changes in nutritional parameters or in albumin or CRP between the two groups . There were significantly greater reductions in transferrin ( P=0.002 ) and in haemoglobin ( P=0.002 ) in the control group at week 1 . The median costs of hospital stay were 2068 UK pounds in the supplemented group and 2199 UK pounds in the control . The median cost of additional treatments was 30.16 UK pounds in the supplemented group and 46.23 UK pounds in the control . CONCLUSION A significant reduction in major complications and in number and costs of additional treatments was seen in the supplemented group",
"Abstract Background : Short-term benefits of laparoscopic relative to conventional colorectal resections have been demonstrated in r and omized controlled trials . It has been suggested that a diminished cytokine and acute-phase response may be responsible for these advantages . Methods : In a r and omized controlled trial , patients underwent laparoscopic ( n=30 ) or conventional ( n=30 ) resection of colorectal tumors . Plasma levels of interleukin-1 receptor antagonist ( IL-1RA ) , interleukin-6 ( IL-6 ) , interleukin-10 ( IL-10 ) , and C-reactive protein ( CRP ) were analyzed repeatedly . Postoperative peak levels and area under the curve values were calculated and compared between groups using the Mann-Whitney U-test . Results : Patient characteristics , preoperative cytokine , and CRP plasma levels were not different between each group . Postoperative peak concentrations of IL-6 ( P=0.05 ) and CRP ( P overall postoperative plasma concentrations of IL-6 ( P=0.03 ) and CRP ( P=0.002 ) were lower in the laparoscopic than in the conventional group . Peak and overall IL-1RA ( P=0.2 ; P=0.2 ) and IL-10 ( P=0.4 ; P=0.6 ) plasma concentrations , respectively , were not different between groups . Conclusions : IL-6 and CRP plasma levels were lower after laparoscopic than conventional colorectal resections . The less intense inflammatory response may be an indicator of the milder surgical trauma inflicted by laparoscopic than conventional colorectal 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",
"BACKGROUND & AIMS Postoperative metabolism is characterised by insulin resistance and a negative whole-body nitrogen balance . Preoperative carbohydrate treatment reduces insulin resistance in the first day after surgery . We hypothesised that preoperative oral carbohydrate treatment attenuates insulin resistance and improves whole-body nitrogen balance 3 days after surgery . METHODS Fourteen patients undergoing total hip replacement were double-blindly r and omised to preoperative oral carbohydrate treatment ( 12.5 % , 800 + 400 ml , n = 8) or placebo ( n = 6 ) . Glucose kinetics ( 6,6-D2-glucose ) , substrate utilisation ( indirect calorimetry ) and insulin sensitivity ( hyperinsulinaemic-euglycaemic clamp ) were measured preoperatively and on the third day after surgery . Nitrogen losses were monitored for 3 days after surgery . Values are mean ( SEM ) . Analysis of variance ( ANOVA ) statistics were used . RESULTS Endogenous glucose release during insulin infusion increased after surgery in the placebo group . Preoperative carbohydrate treatment , as compared to placebo , significantly attenuated postoperative endogenous glucose release ( 0.69 ( 0.07 ) vs. 1.21 (0.13)mg kg(-1 ) x min(-1 ) , P whole-body glucose disposal and nitrogen balance were similar between groups . CONCLUSIONS While insulin resistance in the first day after surgery has previously been characterised by reduced glucose disposal , enhanced endogenous glucose release was the main component of postoperative insulin resistance on the third postoperative day . Preoperative carbohydrate treatment attenuated endogenous glucose release on the third postoperative day",
"After more than two decades of nutritional awareness , we design ed a prospect i ve study to determine whether malnutrition is still a significant issue in hospitalized patients . Patients admitted to an intensive care unit ( ICU ) were divided into well-nourished and malnourished groups , according to their nutritional status as assessed by serum albumin level and weight/height ratio . Severity of illness , as assessed by the Therapeutic Intervention Scoring System ( TISS ) , was used to further stratify the study population . All patients were followed clinical ly until discharge or death and their outcome recorded . Of 129 patients studied , 43 % were malnourished . Length of hospital stay ( p = n.s . ) , incidence of complications ( p number of patients not discharged from hospital ( p postoperative patients admitted to the ICU ( n = 66 ) were also studied in a nutritional survey ; the results of this survey indicate that : ( a ) the incidence of malnutrition in the surgical population is similar to that in the whole study population , and ( b ) hospital-related malnutrition in surgical patients mainly develops during their preoperative stay in general wards . Whereas our conclusion that patients ' outcome is adversely affected by a poor nutritional status is not new or startling , malnutrition continues to be a persistent problem in hospitalized patients , which can be readily identified using simple and easily available indices and , furthermore , readily treated",
"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 )",
"Objective Recent prospect i ve studies have shown that ‘ fast track ’ postoperative care protocol s ( FT ) can reduce hospitalization after major intestinal surgery to 4.5 days , as compared to the 7–10 days with traditional management ( TR ) and 2.5 days after laparoscopic surgery ( LC ) . We used computerized actigraphy ( CA ) to evaluate physical activity using TR , FT and LC approaches",
" The influence of the type of abdominal incision on post‐operative pain and pulmonary function was investigated in patients operated upon for a right‐sided cancer of the large bowel",
"OBJECTIVE To identify factors limiting early discharge after laparoscopically assisted vaginal hysterectomy ( LAVH ) and abdominal hysterectomy , in a fast track setting with emphasis on information , treatment of pain , early mobilization , and early food intake . STUDY DESIGN A prospect i ve , descriptive study of 32 unselected women allocated to either abdominal hysterectomy ( n=16 ) or LAVH ( n=16 ) . The patients received the same information , care , and advice for the perioperative period except for an assumed 1-day hospital stay in the LAVH-group and 2 days in the abdominal group . RESULTS Patients were discharged median 1 day ( 1 - 3 ) after LAVH and 2 days ( 2 - 4 ) after abdominal hysterectomy . Work was resumed median 23 days after abdominal hysterectomy and 28 days after LAVH ( P > 0.05 ) . CONCLUSIONS The study questions the previously proposed advantages of shortened hospitalization and convalescence after LAVH compared with abdominal hysterectomy . Further studies with active rehabilitation are needed to demonstrate real differences between laparoscopic and open hysterectomy",
"Purpose Improved survival in patients with stage III colon cancer after a laparoscopic colectomy ( LC ) has been reported by Lacy et al. ( Lancet 359:2224–2229 , 6 ) , and preserved immunity was suggested as the reason for the survival advantage . The aim of our study was to clarify the existence of an immunological benefit after laparoscopic colon cancer surgery ( LC ) compared to open colon surgery ( OC ) . Methods From January 2006 to November 2007 , 74 patients with clinical stage III colon cancer were prospect ively assigned to undergo a LC ( n = 35 ) or an OC ( n = 39 ) . The immune factors were examined preoperatively , and on the first and fifth days postoperatively ( POD1 and POD5 ) . Results The cellular immune factors were significantly decreased ; however , there was no significant difference between the LC and OC groups except for the mHLA-DR . The LC group had a better preserved mHLA-DR on POD5 than did the OC group ( p = 0.015 ) , in addition to a faster recovery ( p mHLA-DR on POD5 was affected less by the LC compared to the OC . The LC demonstrated minimal immunological advantage when compared to the OC . However , further study is required to clarify the immunological benefits of the LC on colorectal cancer prognosis",
"Eight r and omized clinical trials and two meta‐analyses recently question ed the value of preoperative mechanical bowel preparation ( MBP ) in colorectal surgery . However , very few patients having rectal surgery were included in these studies . The aim of this study was to assess whether rectal cancer surgery can be performed safely without MBP",
"BACKGROUND & AIMS This study review ed the case mix , clinical management , and clinical outcomes of patients undergoing colorectal resection in five European centres performing different forms of conventional or ' fast-track ' perioperative care . METHODS The perioperative care programme and surgical practice in each centre was defined . Patient data were collected by case-note review on an internet-based audit system . Case mix was determined using ASA classification and the P-POSSUM scoring system . RESULTS A total of 451 consecutive patients from units practicing either conventional ( Sweden , n=109 ; UK , n=87 ; Netherl and s , n=76 , Norway , n=61 ) or fast-track surgery ( Denmark , n=118 ) , were studied between 1998 and 2001 . Elements of perioperative practice varied widely both between units practicing ' traditional ' care and the reference ' fast-track ' unit ( Denmark ) . Based on the P-POSSUM scores , the case mix was similar between centres . There were no differences in morbidity or 30-day mortality between the different centres . The median length of stay was 2 days in Denmark and 7 - 9 days in the other centres ( P readmission rate was 22 % in Denmark and 2 - 16 % in the other centres ( P length of hospital stay but may be associated with a higher readmission rate . Morbidity and mortality appears to be similar with either approach . Prospect i ve evaluation of the potential benefits of the fast-track approach in different European centres is merited",
"A carbohydrate‐rich drink ( CHO ) has been shown to reduce preoperative discomfort . It was hypothesized that it may also reduce postoperative nausea and vomiting ( PONV ) ",
"Purpose The purpose of this study is to investigate the influence of anesthetic methods on markers of anti-tumor immunity and intestinal functions in fast-track surgery in colon cancer ( CC ) patients during the perioperative period . Patients and methods A total of 53 patients with American Society of Anesthesiologists ( ASA ) I-II status r and omly received general anesthesia ( G group , n = 27 ) or general anesthesia combined with epidural anesthesia ( E group , n = 26 ) for surgical tumor resection . The recovery times of intestinal function were evaluated in both groups postoperatively . The frequencies of different subsets of CD4 + T cells and myeloid-derived suppressor cells and C-reactive protein ( CRP ) were measured by flow cytometry and enzyme-linked immunosorbent assay , respectively , before anesthesia ( t0 ) , 1 h after the beginning of surgery ( t1 ) , 1 h after the end of surgery ( t2 ) , and on day 2 ( t3 ) and day 5 ( t4 ) post-surgery . Results There was no significant difference in demographic characteristics between the two groups , but the E group of patients received significantly lower amounts of morphine and sevoflurane . In comparison with those in the G group , significantly greater numbers of lymphocytes and elevated frequencies of Th1 cells were detected at t3 and t4 post-surgery in the E group ( p percentages of Th2 cells and regulatory T cells were detected in the E group at t2–4 post-surgery . Whereas the levels of plasma CRP increased post-surgery in both groups , the levels of CRP were significantly lower in the E group than those in the G group at t3–4 post-surgery ( p times to the first flatus and to tolerate a full diet were significantly shorter in the E group than those in the G group ( p General anesthesia combined with epidural anesthesia plays an important role in fast-track surgery , mitigating the surgical stress-related impairment of anti-tumor immune responses and hastening the recovery of intestinal function . This combination might also help to improve long-term outcomes for CC patients",
"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 A prospect i ve , r and omized trial was performed to determine if intra-abdominal drainage catheters are necessary after elective liver resection . PATIENTS AND METHODS Between April 1992 and April 1994 , 120 patients subjected to liver resection , stratified by extent of resection and by surgeon , were r and omized to receive or not receive operative closed-suction drainage . Operative blood loss was not an exclusion criteria , and no patient who consented to the study was excluded . RESULTS Eighty-seven patients ( 73 % ) had resection of one hepatic lobe or more ( 27 lobectomies , 54 trisegmentectomies , and 6 bilobar atypical resections ) and 33 had less than a lobectomy ( 8 wedge resections or enucleations , 9 segmentectomies , and 16 bisegmentectomies ) . Eighty-four patients ( 70 % ) had metastatic cancer and 36 patients ( 30 % ) had primary liver pathology . There were no differences in outcome , including length of hospital stay ( no drain , 13.4 + /- 0.9 days ; drain , 13.1 + /- 0.8 days ; P = not significant [ NS ] ) , mortality ( no drain , 3.3 % ; drain , 3.3 % ) , complication rate ( no drain , 43 % ; drain , 48 % ; P = NS ) , or requirement for subsequent percutaneous drainage ( no drain , 18 % ; drain , 8 % ; P = NS ) . All infected collection s ( n = 3 ) occurred in operatively drained patients . Two other complications were directly related to the operatively placed drains . One patient developed a subcutaneous abscess at the drain site , and a second developed a subcutaneous drain tract tumor recurrence as the only current site of recurrence . CONCLUSION In the first 50 consecutive resections performed since the conclusion of this trial , only 4 patients ( 8 % ) have required subsequent percutaneous drainage . We conclude that abdominal drainage is unnecessary after elective liver resection",
"Abstract Background There is increasing evidence that C-reactive protein is a useful negative predictor of infective complications and anastomotic leak following surgery for colorectal cancer . In particular , C-reactive protein concentrations on postoperative days 3 and 4 have been proposed to be of clinical utility since they aid safe and early discharge of selected patients following colorectal surgery . However , it is not clear whether such thresholds are also applicable in laparoscopic surgery . The aim of the present study was to compare the value of daily C-reactive protein concentrations in the prediction of postoperative infective complications in patients undergoing open versus laparoscopic resection for colon cancer . Methods Patients with histologically proven colon cancer who were considered to have undergone potentially curative resection in one of two university teaching hospitals in Glasgow were included in the study ( n = 344 ) . Patient characteristics were collected in a prospect i ve surgical data base . All resections were elective cases and were performed using either open ( n = 191 ) or laparoscopic surgery ( n = 153 ) . Daily blood sample s to measure C-reactive protein concentrations perioperatively were taken routinely . Patients were assessed for postoperative infective and non-infective complications . Results The majority of patients were aged 65 years or older ( 75 % ) , male ( 52 % ) , had left-sided tumors ( 54 % ) , node negative disease ( 77 % ) , and did not undergo neoadjuvant treatment ( 94 % ) . Patients undergoing open and laparoscopic resection were similar in terms of age , sex , tumor site , TNM stage , comorbidity , and infective complications . In contrast , preoperative and postoperative days 1–3 C-reactive protein concentrations were lower following laparoscopic compared with open resection in the whole cohort ( n = 344 ; all p = 251 ; all p . The median length of hospital stay was shorter in the laparoscopic resection ( p postoperative complication , 93 ( 73 % ) of which were infective complications . In those who developed an infective complication , there was no significant difference in the C-reactive protein concentrations between open and laparoscopic resections on postoperative days 1–4 . C-reactive protein thresholds predictive of infective complications were the same on postoperative days 3 ( 180 mg/l ) and 4 ( 140 mg/l ) following both open and laparoscopic resection for colon cancer . Conclusions The results of the present study show that although the magnitude of the systemic inflammatory response , as evidence d by C-reactive protein , following surgery was greater in open compared with laparoscopic resection , the threshold concentrations of C-reactive protein for the development of postoperative infective complications were remarkably similar on days 3 and 4",
"BACKGROUND Bowel preparation prior to colonic surgery usually includes antibiotic therapy together with mechanical bowel preparation ( MBP ) . Mechanical bowel preparation may cause discomfort to the patient , prolonged hospitalization , and water and electrolyte imbalance . It was assumed that with the improvement in surgical technique together with the use of more effective prophylactic antibiotics , it was possible that MBP would no longer be necessary . HYPOTHESIS There is no statistical difference in the postoperative results of patients who undergo elective colon resection with MBP as compared with those who have no MBP . DESIGN AND PATIENTS The study includes all patients who had elective large bowel resection at Campus Golda between April 1 , 1999 , and March 31 , 2002 . Emergency operations were not included . The patients were r and omly assigned to the 2 study groups ( with or without MBP ) according to identification numbers . All patients were treated with intravenous and oral antibiotics prior to surgery . The patients in the MBP group received Soffodex for bowel preparation . RESULTS A total of 329 patients participated in the study , 165 without MBP and 164 with MBP . The 2 groups were similar in age , sex , and type of surgical procedure . Two hundred sixty-eight patients ( 81.5 % ) underwent surgery owing to colorectal cancer and 61 patients ( 18.5 % ) owing to benign disease . The hospitalization period was longer in the bowel-prepared group ( mean + /- SD , 8.2 + /- 5.1 days ) as compared with the nonprepared group ( mean + /- SD , 8.0 + /- 2.7 days ) . However , this difference was not statistically significant . The time until the first bowel movement was similar between the 2 groups : a mean + /- SD of 4.2 + /- 1.3 days in the nonprepared group as compared with a mean + /- SD of 4.3 + /- 1.1 days in the prepared group ( P = NS ) . Four patients ( 1.2 % ) died in the postoperative course owing to acute myocardial infa rct ion and pulmonary embolism . Sixty-two patients ( 37.6 % ) of the non-MBP group suffered from postoperative complications as compared with 77 patients ( 46.9 % ) of the MBP group . CONCLUSION Our results suggest that no advantage is gained by preoperative MBP in elective colorectal surgery",
"Background We have previously used a magnetic resonance imaging ( MRI ) method to study gastric emptying of liquids . So far , however , it has not possible to assess solid gastric emptying with this technique . Aims To vali date scintigraphically MRI as a method for measuring emptying of a mixed solid/liquid meal . Methods In eight healthy subjects , gastric emptying of a solid/liquid ( SM ) and a liquid meal ( LM ) of identical energy content and macronutrient composition was studied by scintigraphy and MRI for 120 minutes . Results MRI and scintigraphy agreed with respect to emptying profiles ( intraclass correlation coefficient ( RI ) SM : 0.988 , RI , LM : 0.917 ) , t1/2 ( SMMRI : 129 ( 9 ) , SMScinti : 123 ( 11 ) minutes , NS ; LMMRI : 100 ( 7 ) , LMScinti : 110 ( 8) minutes , NS ) and AUC ( SMMRI : 8999 ( 232 ) , SMScinti : 8788 ( 277 ) min% , NS ; LMMRI : 8819 ( 368 ) , LMScinti : 8891 ( 321 ) min% , NS ) . Conclusions MRI can be used to measure reliably gastric emptying not only of liquid but also of mixed solid/liquid meals in humans",
"BACKGROUND : Previous work has shown that the administration of oral dietary supplements to patients who have undergone gastrointestinal surgery results in clinical ly significant short term benefits . AIMS : This study aim ed firstly to re-evaluate these short term effects , and secondly to establish whether there are any long term benefits . SUBJECTS : One hundred patients admitted for elective moderate or major gastrointestinal surgery . METHODS : In the inpatient phase , patients were r and omised to receive a normal ward diet postoperatively , or the same diet supplemented with an oral dietary supplement . In the outpatient phase , patients were further r and omised to receive their home diet , or their home diet supplemented with the oral dietary supplement for four months . RESULTS : During the inpatient phase , patients treated with oral supplements had a significantly improved nutritional intake and lost less weight ( 2.2 , 95 % confidence interval ( 95 % CI ) 0.9 kg ) compared with control patients ( 4.2 ( 0.78 ) kg , p h and grip strength whereas control patients showed a significant reduction in grip strength ( p Subjective levels of fatigue increased significantly above preoperative levels in control patients ( p complications compared with four in the supplemented group ( p nutrient intakes but there were no significant differences in indices of nutritional status or wellbeing between the groups . CONCLUSIONS : The prescription of oral dietary supplements to patients who have undergone gastrointestinal surgery results in clinical ly significant benefits . These benefits , however , are restricted to the inpatient phase",
"BACKGROUND Enhanced Recovery after Surgery ( ERAS ) programs have gained popularity with potential to accelerate recovery and reduce morbidity after colectomy . We were interested in comparing recovery after open right colectomy within an ERAS program compared with laparoscopic right colectomy in a st and ard care perioperative environment . METHODS Between October 2005 and June 2009 , prospect i ve data were collected on consecutive patients undergoing elective open right colectomy within an established ERAS setting ( OpERAS ) . Similarly , between March 2008 and June 2009 , data were collected on consecutive patients undergoing laparoscopic right hemicolectomy with conventional care ( LapCon ) . Exclusion criteria for both groups were : ASA > or= 4 , formation of a stoma , and dementia or mental illness rendering the patient unable to comply with instructions . Perioperative variables were collected . The surgical recovery score ( SRS ) was used as a vali date d means to measure convalescence on d 1 , 3 , 7 , 30 , and 60 postoperatively . RESULTS There were 74 patients in the OpERAS and 39 patients in the LapCon groups . At baseline , there were no significant demographic differences except that more patients had malignancy in OpERAS group . Mean operating time was longer in the LapCon group . Median day stay was 4 ( 3 - 28 ) in OpERAS and 5 ( 2 - 18 ) in LapCon ( P = 0.032 ) . There was no statistical difference in the incidence of complications or the severity of complications . There were no significant differences in SRS after surgery at any time point . CONCLUSION When perioperative care is optimized , recovery after elective open right hemicolectomy is comparable with laparoscopic resection . Studies looking at the combination of laparoscopy and ERAS are warranted",
"The present study was undertaken to investigate the short term clinical efficacy of oral dietary supplements administered post-operatively to patients undergoing predetermined moderate to severe gastrointestinal surgery . Trial end points for comparison included effects of oral dietary supplements on nutritional intake , nutritional status and incidence of serious complications . 54 patients who were scheduled to undergo predetermined moderate to major gastrointestinal surgical procedures entered the study . They were r and omly assigned to receive a normal ward diet post-operatively or the same diet supplemented ad libitum by an oral nutritional sip feed . The study period was defined as commencing from the day patients were adjudged to be capable of ingesting ' free fluids ' to the day of hospital discharge . 40 patients ( 20 in each group ) completed the study . The mean daily energy intake ( KCal/day ) assessed from 7 day food diaries was significantly higher in the treatment group ( 1833 + /- SEM 99 ) than in the control group ( 1108 + /- 56 , p mean daily protein intake g/day in the treatment group ( 66.0 + /- 3.4 ) was also greater than in the control group ( 52.9 + /- 29 p intake in protein from the oral dietary supplements ( 15.7 + /- 1.0 ) , protein intake from the ward diet being similar in the treatment ( 50.1 + /- 3.2 ) and control ( 52.9 + /- 29 ) groups . Patients in the treatment group maintained their pre-operative weight where as control patients had lostsignificant amount of their pre-operative weight by study day 3 ( 4.5 + /- 12 kg and by discharge ( 4.7 + /- 1.2 kg , p Pre-operative muscle function as evidence d by grip strength dynamometry decreased to a greater extent in the control than treatment group patients by study day 3 ( 14.6 + /- 2.2 KPa vs 2.8 + /- 2.4 incidence of serious infections ( pneumonia , wound infection ) was significantly higher in the control group ( 10 ) than in the treatment group ( 3 , p oral dietary supplements on an ad libitum basis to post-operative patients undergoing moderate to major gastrointestinal surgery results in clinical ly significant short term benefits",
"Major surgery is associated with postoperative insulin resistance which is attenuated by preoperative carbohydrate ( CHO ) treatment . The effect of this treatment on clinical outcome after major abdominal surgery has not been assessed in a double‐blind r and omized trial",
"Background : The debate over the correct perioperative fluid management is unresolved . Methods : The impact of two intraoperative fluid regimes on postoperative outcome was prospect ively evaluated in 152 patients with an American Society of Anesthesiologists physical status of I – III who were undergoing elective intraabdominal surgery . Patients were r and omly assigned to receive intraoperatively either liberal ( liberal protocol group [ LPG ] , n = 75 ; bolus of 10 ml/kg followed by 12 ml · kg−1 · h−1 ) or restrictive ( restrictive protocol group [ RPG ] , n = 77 ; 4 ml · kg−1 · h−1 ) amounts of lactated Ringer 's solution . The primary endpoint was the number of patients who died or experienced complications . The secondary endpoints included time to initial passage of flatus and feces , duration of hospital stay , and changes in body weight , hematocrit , and albumin serum concentration in the first 3 postoperative days . Results : The number of patients with complications was lower in the RPG ( P = 0.046 ) . Patients in the LPG passed flatus and feces significantly later ( flatus , median [ range ] : 4 [ 3–7 ] days in the LPG vs. 3 [ 2–7 ] days in the RPG ; P their postoperative hospital stay was significantly longer ( 9 [ 7–24 ] days in the LPG vs. 8 [ 6–21 ] days in the RPG ; P = 0.01 ) . Significantly larger increases in body weight were observed in the LPG compared with the RPG ( P postoperative days , hematocrit and albumin concentrations were significantly higher in the RPG compared with the LPG . Conclusions : In patients undergoing elective intraabdominal surgery , intraoperative use of restrictive fluid management may be advantageous because it reduces postoperative morbidity and shortens hospital stay ",
"BACKGROUND Infections are an important cause of morbidity and mortality in patients with multiple trauma . Studies in both animals and human beings have suggested that glutamine-enriched nutrition decreases the number of infections . METHODS Patients with multiple trauma with an expected survival of more than 48 h , and who had an Injury Severity Score of 20 or more , were r and omly allocated glutamine supplemented enteral nutrition or a balanced , isonitrogenous , isocaloric enteral-feeding regimen along with usual care . Each patient was assessed every 8 h for infection , the primary endpoint . Data were analysed both per protocol , which included enteral feeding for at least 5 days , and by intention to treat . FINDINGS 72 patients were enrolled and 60 received enteral feeding ( 29 glutamine-supplemented ) for at least 5 days . Five ( 17 % ) of 29 patients in the glutamine-supplemented group had pneumonia compared with 14 ( 45 % ) of 31 patients in the control group ( p Bacteraemia occurred in two ( 7 % ) patients in glutamine group and 13 ( 42 % ) in the control group ( p sepsis compared with eight ( 26 % ) patients in the control group ( p pneumonia , sepsis , and bacteraemia in patients with multiple trauma who received glutamine-supplemented enteral nutrition . Larger studies are needed to investigate whether glutamine-supplemented enteral nutrition reduces mortality",
"PURPOSE : We have previously reported the five-year results of a r and omized trial comparing laparoscopic and open resection for cancer of the upper rectum and rectosigmoid junction . The aim of this follow-up study is to report on the long-term morbidity and ten-year oncologic outcomes among the subgroup of patients with upper rectal cancer . METHODS : From September 1993 to October 2002 , 153 patients with upper rectal cancer were r and omly assigned to receive either laparoscopic-assisted ( n = 76 ) or open ( n = 77 ) anterior resection . Patients were last followed up in December 2007 . Long-term morbidity , survival , and disease-free interval were prospect ively recorded . Data were analyzed by intention-to-treat principle . RESULTS : The demographic data of the two groups were comparable . More patients in the open group developed adhesion-related bowel obstruction requiring hospitalization ( P = 0.001 ) and intervention . The overall long-term morbidity rate was also significantly higher in the open group ( P = 0.012 ) . After curative resection , the probabilities of cancer-specific survival at ten years of the laparoscopic-assisted and open groups were 83.5 percent and 78.0 percent , respectively ( P = 0.595 ) , and their probabilities of being disease-free at ten years were 82.9 percent and 80.4 percent , respectively ( P = 0.698 ) . CONCLUSION : Laparoscopic-assisted anterior resection for upper rectal cancer is associated with fewer long-term complications and similar ten-year oncologic outcomes when compared with open surgery",
"Recent studies have suggested that MBP does not lower the risk of postoperative septic complications after elective colorectal surgery . This r and omized clinical trial assessed whether preoperative MBP is beneficial in elective colonic surgery",
"Autonomic behavior is subject to direct suggestion . We found that patients undergoing major operations benefit more from instruction than from information and reassurance . We compared the return of intestinal function after intra-abdominal operations in 2 groups of patients : the suggestion group received specific instructions for the early return of gastrointestinal motility , and the control group received an equal-length interview offering reassurance and nonspecific instructions . The suggestion group had a significantly shorter average time to the return of intestinal motility , 2.6 versus 4.1 days . Time to discharge was 6.5 versus 8.1 days . Covariates including duration of operation , amount of intraoperative bowel manipulation , and amount of postoperative narcotics were also examined using the statistical model analysis of covariance . An average savings of $ 1,200 per patient result ed from this simple 5-minute intervention . In summary , the use of specific physiologically active suggestions given preoperatively in a beleivable manner can reduce the morbidity associated with an intra-abdominal operation by reducing the duration of ileus",
"Objective To compare the absorption of carbon-13 ( C ) acetate – enriched nutrients with D-xylose absorption . Design Prospect i ve cohort observational study . Setting Surgical intensive care unit of a university hospital . Patients A total of 24 critically ill patients requiring enteral nutritional support . InterventionThe patients were divided into three groups according to the route of C acetate administration : 1 ) gastric , 2 ) jejunal , and 3 ) intravenous . D-xylose was administered via the same route as enteral nutrition . Measurements and Main Results C acetate absorption and oxidation were reflected by pulmonary CO2 excretion . Breath CO2 isotopic enrichment was measured by mass spectrometry . C acetate absorption was rapid , and D-xylose absorption was depressed in all three groups , compared with the normal values ( p Breath CO2 isotopic enrichment was similar after intravenous and jejunal administration but slightly delayed during the first 240 mins after gastric administration ( p tolerated : mean energy delivery amounted to 77 % , 88 % , and 86 % of measured resting energy expenditure on days 1–3 . Conclusions Gastric and jejunal C acetate are rapidly absorbed in critically ill surgical patients requiring enteral nutrition , contrasting with a depressed or delayed D-xylose absorption . CO2 recovery kinetics was similar after jejunal or intravenous C acetate and slightly depressed after gastric administration . Further studies are required to determine the value of labeled nutrients to assess gastric emptying and intestinal absorption",
"HYPOTHESIS Perioperative administration of a supplemented enteral formula may decrease postoperative morbidity . DESIGN R and omized clinical trial . SETTING Department of surgery at a university hospital . PATIENTS One hundred ninety-six registered malnourished patients ( weight loss > or = 10 % ) who were c and i date s for major elective surgery for malignancy of the gastrointestinal tract . INTERVENTION After r and omization ( n = 150 ) , one group received postoperative enteral feeding with a st and ard diet within 12 hours of surgery ( control group ; n = 50 ) . Another group orally received 1 L/d for 7 consecutive days of a liquid diet enriched with arginine , omega-3 fatty acids , and RNA ( preoperative group ; n = 50 ) . After surgery , patients were given the same st and ard enteral formula as the control group . A third group orally received 1 L/d for 7 consecutive days of the enriched liquid diet . After surgery , patients were given enteral feeding with the same enriched formula ( perioperative group ; n = 50 ) . MAIN OUTCOME MEASURES Postoperative complications and length of hospital stay . RESULTS The 3 groups were comparable for baseline demographics , biochemical markers , comorbidity factors , and surgical variables . The intent-to-treat analysis showed that the total number of patients with complications was 24 in the control group , 14 in the preoperative group , and 9 in the perioperative group ( P = .02 , control group vs perioperative group ) . Postoperative length of stay was significantly shorter in the preoperative ( 13.2 days ) and perioperative ( 12.0 days ) groups than in the control group ( 15.3 days ) ( P = .01 and P = .001 , respectively , vs the control group ) . CONCLUSION Perioperative immunonutrition seems to be the best approach to support malnourished patients with cancer",
"Objective : To evaluate the efficacy , amount of hemorrhage , biliary leakage , complications , and postoperative evolution after fibrin glue sealant application in patients undergoing liver resection . Summary Background Data : Fibrin sealants have become popular as a means of improving perioperative hemostasis and reducing biliary leakage after liver surgery . However , trials regarding its use in liver surgery remain limited and of poor method ologic quality . Patients and Methods : A total of 300 patients undergoing hepatic resection were r and omly assigned to fibrin glue application or control groups . Characteristics and debit of drainage and postoperative complications were evaluated . The amount of blood loss , measurements of hematologic parameters liver test , and postoperative evolution ( particularly involving biliary fistula and morbidity ) was also recorded . Results : Postoperatively , no differences were observed in the amount of transfusion ( 0.15 ± 0.66 vs. 0.17 ± 0.63 PRCU ; P = 0.7234 ) or in the patients that required transfusion ( 18 % vs. 12 % ; P = 0.2 ) , respectively , for the fibrin glue or control group . There were no differences in overall drainage volumes ( 1180 ± 2528 vs. 960 ± 1253 mL ) or in days of postoperative drainage ( 7.9 ± 5 vs. 7.1 ± 4.7 ) . Incidence of biliary fistula was similar in the fibrin glue and control groups , ( 10 % vs. 11 % ) . There were no differences regarding postoperative morbidity between groups ( 23 % vs. 23 % ; P = 1 ) . Conclusions : Application of fibrin sealant in the raw surface of the liver does not seem justified . Blood loss , transfusion , incidence of biliary fistula , and outcome are comparable to patients without fibrin glue . Therefore , discontinuation of routine use of fibrin sealant would result in significant cost saving",
"Postoperative organ dysfunction contributes to morbidity , hospital stay and convalescence . Multimodal rehabilitation with epidural analgesia , early oral feeding , mobilization and laxative use after colonic resection has reduced ileus and hospital stay ",
"BACKGROUND Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale r and omised trials to support its use . We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes . METHODS Between July , 1996 , and July , 2002 , we undertook a multicentre , r and omised clinical trial in 794 patients with colorectal cancer from 27 UK centres . Patients were allocated to receive laparoscopic-assisted ( n=526 ) or open surgery ( n=268 ) . Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins , proportion of Dukes ' C2 tumours , and in-hospital mortality . Analysis was by intention to treat . This trial has been assigned the International St and ard R and omised Controlled Trial Number IS RCT N74883561 . FINDINGS Six patients ( two [ open ] , four [ laparoscopic ] ) had no surgery , and 23 had missing surgical data ( nine , 14 ) . 253 and 484 patients actually received open and laparoscopic-assisted treatment , respectively . 143 ( 29 % ) patients underwent conversion from laparoscopic to open surgery . Proportion of Dukes ' C2 tumours did not differ between treatments ( 18 [ 7 % ] patients , open vs 34 [ 6 % ] , laparoscopic ; difference -0.3 % , 95 % CI -3.9 to 3.4 % , p=0.89 ) , and neither did in-hospital mortality ( 13 [ 5 % ] vs 21 [ 4 % ] ; -0.9 % , -3.9 to 2.2 % , p=0.57 ) . Apart from patients undergoing laparoscopic anterior resection for rectal cancer , rates of positive resection margins were similar between treatment groups . Patients with converted treatment had raised complication rates . INTERPRETATION Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes . However , impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use",
"Objective : To evaluate the effect of laparoscopic or open colectomy with fast track or st and ard perioperative care on patient 's immune status and stress response after surgery . Methods : Patients with nonmetastasized colon cancer were r and omized to laparoscopic or open colectomy with fast track or st and ard care . Blood sample s were taken preoperatively ( baseline ) , and 1 , 2 , 24 , and 72 hours after surgery . Systemic HLA-DR expression , C-reactive protein , interleukin-6 , growth hormone , prolactin , and cortisol were analyzed . Results : Nineteen patients were r and omized for laparoscopy and fast track care ( LFT ) , 23 for laparoscopy and st and ard care ( LS ) , 17 for open surgery and fast track care ( OFT ) , and 20 for open surgery and st and ard care ( OS ) . Patient characteristics were comparable . Mean HLA-DR was 74.8 in the LFT group , 67.1 in the LS group , 52.8 in the OFT group , and 40.7 in the OS group . Repeated- measures 2-way analysis of variance ( ANOVA ) showed this can be attributed to type of surgery and not aftercare ( P = 0.002 ) . Interleukin-6 levels were highest in the OS group . Repeated- measures 2-way ANOVA showed this can be attributed to type of surgery and not aftercare ( P = 0.001 ) . C-reactive protein levels were highest in the OS group . Following repeated- measures 2-way ANOVA , this can be attributed to type of surgery and not aftercare ( P = 0.022 ) . Growth hormone was lowest in the LFT group . Following repeated- measures 2-way ANOVA , this can be attributed to type of aftercare and not to type of surgery ( P = 0.033 ) . No differences between the groups were seen regarding prolactin or cortisol . No differences in ( infectious ) complication rates were observed between the groups . Conclusions : This r and omized trial showed that immune function of HLA-DR in patients undergoing laparoscopic surgery with fast track care remains highest . This can be attributed to type of surgery and not aftercare . These results may indicate a reason for the accelerated recovery of patients treated laparoscopically within a fast track program as described in the LAparoscopy and /or FAst track multimodal management versus st and ard care ( LAFA-Trial ) ( www.trialregister.nl , protocol NTR222 )",
"Background Protocol s for enhanced recovery provide comprehensive and evidence -based guidelines for best perioperative care . Protocol implementation may reduce complication rates and enhance functional recovery and , as a result of this , also reduce length-of-stay in hospital . There is no comprehensive framework available for pancreaticoduodenectomy . Methods An international working group constructed within the Enhanced Recovery After Surgery ( ERAS ® ) Society constructed a comprehensive and evidence -based framework for best perioperative care for pancreaticoduodenectomy patients . Data were retrieved from st and ard data bases and personal archives . Evidence and recommendations were classified according to the GRADE system and reached through consensus in the group . The quality of evidence was rated “ high ” , “ moderate ” , “ low ” or “ very low ” . Recommendations were grade d as “ strong ” or “ weak ” . Results Comprehensive guidelines are presented . Available evidence is summarised and recommendations given for 27 care items . The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations . Conclusions The present evidence -based guidelines provide the necessary platform upon which to base a unified protocol for perioperative care for pancreaticoduodenectomy . A unified protocol allows for comparison between centres and across national borders . It facilitates multi-institutional prospect i ve cohort registries and adequately powered r and omised trials",
"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"
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OBJECTIVES In the care of patients with type 2 diabetes , self-management is emphasised and studied while theory and observations suggest that patients also benefit from social support . We sought to assess the effect of social network interventions on social support , glycaemic control and quality of life in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS We search ed Ovid MEDLINE , Ovid EBM Review s , Cochrane Central Register of Controlled Trials , EMBASE , PsycINFO and CINAHL through April 2017 for r and omised clinical trials ( RCTs ) of social network interventions in patients with type 2 diabetes . Review ers working independently and in duplicate assessed eligibility and risk of bias , and extracted data from eligible RCTs . We pooled estimates using inverse variance r and om effects meta- analysis . RESULTS We found 19 eligible RCTs enrolling 2319 participants . Social network interventions were commonly based on individual behaviour change rather than social or interpersonal theories of self-management , were educational , and sought to engage social network members for their knowledge and experience . Interventions improved social support ( 0.74 SD ( 95 % CI 0.32 to 1.15 ) , I2=89 % , 8 RCTs ) and haemoglobin A1c at 3 months ( -0.25 percentage points ( 95 % CI -0.40 to -0.11 ) , I2=12 % , 9 RCTs ) , but not quality of life . CONCLUSIONS Despite a compelling theoretical base , research ers have only minimally studied the value of interventions targeting patients ' social networks on diabetes care . Although the body of evidence to date is limited , and based on individual behaviour change theories , the results are promising . This review challenges the scientific community to design and test theory-based interventions that go beyond self-management approaches to focus on the largely untapped potential of social networks to improve diabetes care . PROSPERO REGISTRATION CRD42016036117
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"OBJECTIVE To compare glycemic control and secondary outcomes of a 4-month telephonic couples behavioral intervention to individual intervention , and to education , for adults with type 2 diabetes . RESEARCH DESIGN AND METHODS A r and omized trial with the following three arms : couples calls ( CC ) ( n = 104 ) ; individual calls ( IC ) ( n = 94 ) ; and diabetes education ( DE ) ( n = 82 ) . All arms had self-management education ( two calls ) . CC and IC had 10 additional behavior change calls . CC addressed collaboration and relationships/communication . Participants consisted of 280 couples , among whom one partner had type 2 diabetes and an A1C level ≥7.5 % . Blinded assessment s occurred at 4 , 8 , and 12 months . The primary outcome was change in A1C ; and secondary outcomes were BMI , waist circumference , blood pressure , depressive symptoms , diabetes self-efficacy , and diabetes distress . RESULTS Patients had a mean age of 56.8 years ; 61.6 % were male , and 30.4 % were minorities . The baseline mean A1C level was 9.1 % . Intention-to-treat analyses found significant A1C reductions for all ( 12 months : CC −0.47 % , IC −0.52 % , DE −0.57 % ) , with no differences between arms . Preplanned within-arm analyses were stratified by baseline A1C tertiles : lowest tertile ( 7.5–8.2 % ) , no change from baseline ; middle tertile ( 8.3–9.2 % ) , only CC led to significantly lower A1C level ; and highest tertile ( ≥9.3 % ) , significant improvement for all interventions . For BMI , CC showed significant improvement , and CC and DE led to decreased waist circumference . The IC group showed greater blood pressure improvement . Results for secondary psychosocial outcomes favored the CC group . CONCLUSIONS In adults with poorly controlled type 2 diabetes , a collaborative couples intervention result ed in significant , lasting improvement in A1C levels , obesity measures , and some psychosocial outcomes . For those with exceedingly high A1C levels , education alone was beneficial , but additional intervention is needed to achieve glycemic targets",
"BACKGROUND In a European trial in 8 countries , the subjective well-being of patients on alternative forms of treatment for insulin-dependent diabetes was compared using the 28-item WHO Well-Being Question naire , covering four dimensions of depression , anxiety , energy and positive well-being . The objective of the analysis reported here has been to identify the items of the WHO question naire which belong to an overall index of negative and positive well-being . METHODS Adult patients at 10 study centres in 8 countries who had been on insulin for at least 2 years were invited to participate in a r and omised , cross-over trial to compare insulin pump treatment with injection therapy . At each phase , patients completed questions on well-being and general health . Internal validity of the well-being index was evaluated by Cronbach 's alpha and Loevinger 's and Mokken 's homogeneity coefficients , as well as factor analysis . External validity was evaluated by comparisons with results of the general assessment questions and by the ability to discriminate between the alternative forms of treatment . RESULTS 358 patients had sufficient data for analysis . Ten items were found to constitute a valid index of well-being with respect to internal and external validity . Coefficients of homogeneity were acceptable and there was evidence for both concurrent and discriminant validity . CONCLUSIONS The WHO ( Ten ) well-being index includes negative and positive aspects of well-being in a single uni-dimensional scale . Its advantage lies in its ability to show overall change along the continuum of well-being , thus facilitating comparisons between patient groups and treatments . It is not specific to diabetes , and therefore may be useful as a disease-independent index of well-being in a broad range of health care studies",
"Purpose This study developed and tested a culturally appropriate , church-based intervention to improve diabetes self-management . Research Design and Methods This was a r and omized trial conducted at 24 African American churches in central North Carolina . Churches were r and omized to receive the special intervention ( SI ; 13 churches , 117 participants ) or the minimal intervention ( MI ; 11 churches , 84 participants ) . The SI included an 8-month intensive phase , consisting of 1 individual counseling visit , 12 group sessions , monthly phone contacts , and 3 encouragement postcards , followed by a 4-month reinforcement phase including monthly phone contacts . The MI received st and ard educational pamphlets by mail . Outcomes were assessed at 8 and 12 months ; the primary outcome was comparison of 8-month A1C levels . Results At baseline , the mean age was 59 years , A1C 7.8 % , and body mass index 35.0 kg/m2 ; 64 % of participants were female . For the 174 ( 87 % ) participants returning for 8-month measures , mean A1C ( adjusted for baseline and group r and omization ) was 7.4 % for SI and 7.8 % for MI , with a difference of 0.4 % ( 95 % confidence interval [ CI ] , 0.1 - 0.6 , P = .009 ) . In a larger model adjusting for additional variables , the difference was 0.5 % ( 95 % CI , 0.2 - 0.7 , P Diabetes knowledge and diabetes-related quality of life significantly improved in the SI group compared with the MI group . Among SI participants completing an acceptability question naire , intervention components and material s were rated as highly acceptable . Conclusions The church-based intervention was well received by participants and improved short-term metabolic control",
"Purpose The purpose of the study was to investigate the effects of a family-based self-management support intervention for adults with type 2 diabetes ( T2DM ) . Methods Using a 2-group , experimental repeated measures design , 157 dyads ( participant with T2DM and family member ) were r and omly assigned to an intervention ( education , social support , home visits , and telephone calls ) or a wait list control group . Data were collected at baseline , postintervention ( 3 months ) , and 6 months postintervention . A series of 2 × 3 repeated measures ANOVAs were used to test the hypotheses with interaction contrasts to assess immediate and sustained intervention effects . Results Significant changes over time were reported in diet self-management , exercise self-management , total self-management , diabetes self-efficacy for general health and total diabetes self-efficacy , physician distress , regimen distress , interpersonal distress , and total distress . There were likewise sustained effects for diet self-management , total self-management , diabetes self-efficacy for general health , total self-efficacy , physician distress , regimen distress , and interpersonal distress . Conclusions Results support and extend prior research documenting the value of culturally relevant family-based interventions to improve diabetes self-management and substantiate the need for intensive , longer , tailored interventions to achieve glycemic control ",
"Objective To develop and test a family-centered behavioral weight loss intervention for African American adults with type 2 diabetes . Methods In this r and omized trial , dyads consisting of African American adult with overweight or obesity and type 2 diabetes ( index participant ) paired with a family partner with overweight or obesity , but not diagnosed with diabetes , were assigned in a 2:1 ratio to a 20-week special intervention ( SI ) or delayed intervention ( DI ) control group . The primary outcome was weight loss among index participants at 20 weeks follow-up . Results One hundred-eight participants ( 54 dyads – 36 ( SI ) and 18 ( DI ) dyads ) were enrolled : 81 % females ; mean age , 51 years ; mean weight,103 kg ; and mean BMI , 37 kg/m2 . At post-intervention , 96 participants ( 89 % ) returned for follow-up measures . Among index participants , mean difference in weight loss between groups was −5.0 kg , p improvements in hemoglobin A1c , depressive symptoms , family interactions , and dietary , physical activity , and diabetes self-care behaviors . SI family partners also had significant weight loss ( −3.9 kg ( SI ) vs. −1.0 kg ( DI ) p=0.02 ) . Conclusions A family-centered , behavioral weight loss intervention led to clinical ly significant short-term weight loss among family dyads",
"AIMS We evaluated a theoretically-derived family-oriented intervention aim ed to improve self-efficacy , self-management , glycemic control and quality of life in individuals living with Type 2 diabetes in Thail and . METHODS In a single-blinded r and omized controlled trial , 140 volunteer individuals with Type 2 diabetes , recruited from a diabetes clinic in rural Thail and , were r and omly allocated to intervention and control arms . Those in the intervention arm received routine care plus a family-oriented program that included education classes , group discussion s , a home visit , and a telephone follow-up while the control arm only received routine care . Improvement in outcomes over time ( baseline , Week 3 , and Week 13 following intervention ) was evaluated using Generalized Estimating Equations multivariable analyses . RESULTS Except for age , no between-group significant differences were observed in all other baseline characteristics . Diabetes self-efficacy , self-management , and quality of life improved in the intervention arm but no improvement was observed in the controls . In the risk-adjusted multivariable models , compared to the controls , the intervention arm had significantly better self-efficacy , self-management , outcome expectations , and diabetes knowledge ( p increased the diabetes self-management score by 14.3 points ( β=14.3 , ( 95 % CI 10.7 - 17.9 ) , p ) . Self-management was better in leaner patients and in females . No between-group differences were seen in quality of life or glycemic control , however , in the risk-adjusted multivariable models , higher self-management scores were associated with significantly decreased HbA1c levels ( p improved patient quality of life ( p improved patients ' self-efficacy and self-management , which in turn could decrease HbA1c levels",
"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 Glycaemic control is the main goal of treatment for type 2 diabetic patients . Hyperglycaemia may result in cognitive decline . More family support may increase medication adherence and decrease glycaemic level . The purpose of this study was to determine the impact of family support improvement behavior on anti diabetic medication adherence and cognition in type 2 diabetic patients . Method The r and omized control trial study was conducted on 91 patients from an outpatient diabetes clinic . They were r and omly divided to intervention ( n = 45 ) and control ( n = 46 ) group . Data on the patients ’ demographic information and their family gathered using a question naire , For two groups Morisky Medication Adherence Scale ( MMAS ) , drug administration part of Diabetes Social Support Question naire – family version ( DSSQ ) , Number Connection Test ( NCT ) were applied and hemoglobin A1C was measured two times in the onset of study and three months later for control group and before and after intervention for intervention group . The key family members of the intervention group were taught according to their educational needs in small groups . Result In intervention group mean of NCT score was significantly decreased after intervention ( P = 0.006 ) however in the control group there was no significant difference after three months . In intervention group a significant correlation was noted between DSSQ scores and MMAS scores after intervention(r = 0.67 , P Conclusion Family support instruction based on the educational needs of family members , may improve medication adherence through direct effect and cognitive status with indirect effect",
"OBJECTIVE To determine the effects of a culturally competent diabetes self-management intervention in Mexican Americans with type 2 diabetes . RESEARCH DESIGN AND METHODS A prospect i ve , r and omized , repeated measures study was conducted on the Texas-Mexico border in Starr County . A total of 256 r and omly selected individuals with type 2 diabetes between 35 and 70 years of age , diagnosed with type 2 diabetes after 35 years of age , and accompanied by a family member or friend were included . The intervention consisted of 52 contact hours over 12 months and was provided by bilingual Mexican American nurses , dietitians , and community workers . The intervention involved 3 months of weekly instructional sessions on nutrition , self-monitoring of blood glucose , exercise , and other self-care topics and 6 months of biweekly support group sessions to promote behavior changes . The approach was culturally competent in terms of language , diet , social emphasis , family participation , and incorporation of cultural health beliefs . Outcomes included indicators of metabolic control ( HbA(1c ) and fasting blood glucose ) , diabetes knowledge , and diabetes-related health beliefs . RESULTS Experimental groups showed significantly lower levels of HbA(1c ) and fasting blood glucose at 6 and 12 months and higher diabetes knowledge scores . At 6 months , the mean HbA(1c ) of the experimental subjects was 1.4 % below the mean of the control group ; however , the mean level of the experimental subjects was still high ( > 10 % ) . CONCLUSIONS This study confirms the effectiveness of culturally competent diabetes self-management education on improving health outcomes of Mexican Americans , particularly for those individuals with HbA(1c ) levels > 10 %",
"OBJECTIVE This study sought to evaluate the feasibility of a pilot , dyad-based lifestyle intervention , the Unidas por la Vida program , for improving weight loss and dietary intake among high-risk Mexican American mothers who have Type 2 diabetes and their overweight/obese adult daughters . METHOD Mother-daughter dyads ( N = 89 ) were recruited from two federally qualified health centers and r and omly assigned to either the Unidas intervention or to the control condition . The 16-week Unidas intervention consisted of the following : ( a ) four group meetings , ( b ) eight home visits , and ( c ) booster telephone calls by a lifestyle community coach . The control condition consisted of educational material s mailed to participants ' homes . Participants completed surveys at T1 ( baseline ) and T2 ( 16 weeks ) that assessed various demographic , social network involvement , and dietary variables . RESULTS Unidas participants lost significantly more weight at T2 ( p eating foods with lower glycemic load ( p saturated fat ( p = .004 ) at T2 . Unidas participants also reported a significant increase in health-related social support and social control ( persuasion control only ) and a decrease in undermining . CONCLUSIONS The Unidas program promoted weight loss and improved dietary intake , as well as changes in diet-related involvement of participants ' social networks . The results from this study demonstrate that interventions that draw upon multiple people who share a health-risk have the potential to foster significant changes in lifestyle behaviors and in social network members ' health-related involvement . Future research that builds on these findings is needed to eluci date the specific dyadic and social network processes that may drive health behavior change",
"OBJECTIVE To evaluate the effectiveness of a psychological , family-based intervention to improve diabetes-related outcomes in patients with poorly controlled type 2 diabetes . METHODS This study was a r and omized controlled trial of a psychological family-based intervention targeted at individuals with poorly controlled type 2 diabetes . Recruitment and follow-up occurred at specialist diabetes clinics . Patients were r and omly allocated to an intervention group ( n=60 ) or a control group ( n=61 ) . Poor control was defined as at least 2 of the patient 's last 3 glycated hemoglobin ( A1C ) readings at > 8.0 % . The intervention consisted of 2 sessions delivered by a health psychologist to the patient and a family member in the patient 's home , with a third session involving a 15-minute follow-up telephone call . RESULTS At 6-month follow-up , the intervention group reported significantly lower mean A1C levels than the control group ( 8.4 % [ SD=0.99 % ] vs 8.8 % [ SD=1.36 % ] ; P=.04 ) . The intervention was most effective in those with the poorest control at baseline ( A1C>9.5 % ) ( intervention 8.7 % [ SD=1.16 % , n=15 ] vs control 9.9 % [ SD=1.31 % , n=15 ] ; P=.01 ) . The intervention group also reported statistically significant improvements in beliefs about diabetes , psychological well-being , diet , exercise , and family support . CONCLUSIONS After participating in a family-based intervention targeting negative and /or inaccurate illness perceptions , patients with poorly controlled type 2 diabetes showed improvements in A1C levels and other outcomes . Our results suggest that adding a psychological , family-based component to usual diabetes care may help improve diabetes management",
"ABSTRACT BACKGROUND Churches may provide a familiar and accessible setting for chronic disease self-management education and social support for Latinos with diabetes . OBJECTIVE We assessed the impact of a multi-faceted church-based diabetes self-management intervention on diabetes outcomes among Latino adults . DESIGN This was a community-based , r and omized controlled , pilot study .SUBJECTSOne-hundred adults with self-reported diabetes from a Midwestern , urban , low-income Mexican-American neighborhood were included in the study . INTERVENTIONS Intervention participants were enrolled in a church-based diabetes self-management program that included eight weekly group classes led by trained lay leaders . Enhanced usual care participants attended one 90-minute lecture on diabetes self-management at a local church . OUTCOME MEASURES The primary outcome was change in glycosylated hemoglobin ( A1C ) . Secondary outcomes included changes in low-density lipoproteins ( LDL ) , blood pressure , weight , and diabetes self-care practice s . KEY RESULTS Participants ’ mean age was 54 ± 12 years , 81 % were female , 98 % were Latino , and 51 % were uninsured . At 3 months , study participants in both arms decreased their A1C from baseline ( −0.32 % , 95 % confidence interval [ CI ] : -0.62 , -0.02 % ) . The difference in change in A1C , LDL , blood pressure and weight from baseline to 3-month and 6-month follow-up was not statistically significant between the intervention and enhanced usual care groups . Intervention participants reported fewer days of consuming high fat foods in the previous week ( −1.34 , 95 % CI : -2.22 , -0.46 ) and more days of participating in exercise ( 1.58 , 95 % CI : 0.24 , 2.92 ) compared to enhanced usual care from baseline to 6 months . CONCLUSIONS A pilot church-based diabetes self-management intervention did not reduce A1C , but result ed in decreased high fat food consumption and increased participation in exercise among low-income Latino adults with diabetes . Future church-based interventions may need to strengthen linkages to the healthcare system and provide continued support to participants to impact clinical outcomes",
"Purpose : Test a practice -based intervention to foster involvement of a relative or friend for the reduction of cardiovascular risk in patients with type 2 diabetes . Methods : We enrolled in a r and omized controlled trial 199 patients and 108 support persons ( SPs ) from 18 practice s within a practice -based research network . All patient participants had type 2 diabetes with suboptimal blood pressure control and were prepared to design ate a SP . A subset of the patients also had dyslipidemia . All study visits were conducted at the practice sites where staff took st and ardized blood pressure measurements and collected blood sample s. All patients completed one education session and received newsletters aim ed at improving key health behaviors . Intervention group patients included their chosen SP in the education session and the SPs received newsletters . Results : After 9 to 12 months , the intervention had no significant effect on systolic blood pressure , HbA1C , health-related quality of life , patient satisfaction , medication adherence , or perceived health competence . Power was insufficient to detect an effect on low-density lipoprotein cholesterol . Baseline cardiovascular risk values were not very high , with mean systolic blood pressure at 140 mm Hg ; mean HbA1C at 7.6 % ; and mean low-density lipoprotein at 137 mg/dL. Patient health care satisfaction was high . Conclusion : This practice -based intervention to foster social support for chronic care management among diabetics had no significant impact on the targeted outcomes",
"A pilot study was conducted to assess the feasibility and potential efficacy of a couples focused diabetes intervention in which a collaborative problem-solving approach to diabetes self-care was promoted . Couples ( N = 44 ) , in which one partner had Type 2 diabetes and was in poor blood glucose control were r and omly assigned to one of three groups : a couples intervention , an individual intervention , or individual diabetes education . The intervention included goal - setting , dietary behavior change , and a focus on emotions . For those in the couples arm , this was done within the framework of promoting collaborative communication between the partners . All intervention contacts were over the telephone to increase reach . Results showed that both the individual and couples interventions yielded meaningful clinical improvements in medical outcomes . Diabetes education also result ed in improved blood glucose control . Despite the small number , mixed-model regression analyses found statistically significant treatment effects for total cholesterol . This pilot demonstrates the feasibility and potential efficacy of a telephone intervention for Type 2 diabetes patients and their partners . Information from implementing this pilot led to refinement and further development of the intervention , which is being assessed in a larger , more comprehensive trial",
"Latinas with type 2 diabetes are in need of culturally sensitive interventions to make recommended long-term lifestyle changes and reduce heart disease risk . To test the longer-term ( 24-month ) effects of a previously successful , culturally adapted , multiple-health-behavior-change program , ¡ Viva Bien ! , 280 Latinas were r and omly assigned to usual care or ¡ Viva Bien!. Treatment included group meetings to promote a culturally adapted Mediterranean diet , physical activity , supportive re sources , problem solving , stress-management practice s , and smoking cessation . ¡ Viva Bien ! participants achieved and maintained some lifestyle improvements from baseline through 24 months , including significant improvements for psychosocial outcomes , fat intake , social – environmental support , body mass index , and hemoglobin A1c . Effects tended to diminish over time . The ¡ Viva Bien ! multiple-behavior program was effective in improving and maintaining some psychosocial , behavioral , and biological outcomes related to heart health across 24 months for Latinas with type 2 diabetes , a high-risk , underserved population ( Clinical Trials.gov number , NCT00233259 )",
"Purpose The purpose of this study was to examine the role of self , interpersonal ( ie , family/friend ) , and organizational ( ie , health care ) support in performing diabetes-related self-management behaviors and hemoglobin A1C ( A1C ) levels among rural Latinos with type 2 diabetes . Methods Cross-sectional data from baseline interviews and medical records were used from a r and omized controlled trial conducted in rural Southern California involving a clinic sample of Latinos with type 2 diabetes ( N = 317 ) . Self-management behaviors included fruit and vegetable intake , fat intake , physical activity , glucose monitoring , daily examination of feet , and medication adherence . Multivariate linear and logistic regression models were used to assess the relationships of sources of support with self-management behaviors and A1C . Results Higher levels of self-support were significantly associated with eating fruits and vegetables most days/week , eating high-fat foods few days/week , engaging in physical activity most days/week , daily feet examinations , and self-reported medication adherence . Self-support was also related to A1C . Family/friend support was significantly associated with eating fruits and vegetables and engaging in physical activity most days/week . Health care support was significantly associated with consuming fats most days/week . Conclusions Health care practitioners and future interventions should focus on improving individuals ’ diabetes management behaviors , with the ultimate goal of promoting glycemic control . Eliciting family/friend support should be encouraged to promote fruit and vegetable consumption and physical activity",
" Forty-nine obese diabetic patients with obese spouses ( diabetic or nondiabetic ) were r and omly assigned to an alone or together condition . Patients in the alone group participated by themselves in a 20-week behavioral weight control program ; their spouses attended assessment sessions only . Patients in the together group attended the program with their spouses ; both were targeted for weight loss and taught social support strategies . Weight losses of patients treated alone and together did not differ significantly at posttreatment ( 19.9 vs. 19.1 lb ) or 1-year follow-up ( 11.6 vs. 7.0 lb ) . However , there was a significant interaction of treatment and gender ; women did better when treated with their spouses , whereas men did better when treated alone . A \" family-based \" approach was not effective for these obese Type II diabetic patients as a whole but may be helpful for women",
"Background In this partially r and omised intervention study , we assessed the effect of social networks on the improvement of type 2 diabetes management in a largely African – American population in Baltimore . Methods Patients in the intervention group ( n=68 ) were asked to recruit peers , form small groups , and attend monthly diabetes education sessions , emphasising peer support . Patients in the control group ( n=70 ) were recruited individually to attend st and ard diabetes education sessions . The primary outcomes were changes in haemoglobin A1C ( HbA1c ) and blood glucose . Secondary outcomes included blood pressure , weight , functional status , self-efficacy , perceived cohesion , social network connectedness and diabetes knowledge . General linear mixed models were built to assess mean absolute changes in primary and secondary outcomes at 3 and 6 months . Results At 6 months from baseline , the social network intervention group achieved a larger reduction in HbA1c of −0.32 % ( p for weight , quality of life , self-efficacy , social network scores and diabetes knowledge , compared to the control group . While blood pressure decreased , and perceived cohesion increased in both groups over the duration of the study , the difference between groups was not statistically significant . Conclusions The social networks intervention showed improved integration of patients within their existing networks leading to a greater reduction in HbA1c and blood glucose , as well as improved behaviour mediating outcomes"
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41179326-06ff-11f0-808a-c43d1ab1c353
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The most widely used method for estimating dietary zinc requirements is the factorial approach , in which it is assumed , in adults , that the physiological zinc requirement is the lowest intake that replaces endogenous zinc losses . Presented here are the results of two review s : a narrative review of zinc losses from the human body and a systematic review of factors affecting zinc bioavailability in adult and elderly population s. The narrative review presents data on losses from integumental and excretory routes , obtained from 29 papers published up to April 2013 . The systematic review includes a total of 87 publications describing dietary factors that impact zinc bioavailability , 30 of which examined phytate . A meta- analysis revealed an overall lowering of fractional zinc absorption by 0.14 ( 45 % of control values ) when the phytate : zinc molar ratio of the test meal or diet was greater than 15 . These review s provide a comprehensive re source for use in the setting of human dietary zinc requirements and emphasize the need for more high- quality data to improve estimates of zinc losses and gains
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"Summary Background Long-term consumption of imbalanced diets , poor in dietary fibres , result ed in the prevalence of several nutritional pathologies . However , low digestible carbohydrates ( LDC ) have many beneficial effects , especially on energy intake , digestive physiology , and mineral absorption . Aim of the study To determine the digestive effects of a LDC , called NUTRIOSE ® FB , its metabolisable energy ( ME ) value , and its effects on mineral absorption in humans . Methods Ten healthy young men were fed for 31 d periods a maintenance diet supplemented with either dextrose or the LDC at a level of 100 g DM/d , in six equal doses per d according to a cross-over design . After a 20 d adaptation period , food intake was determined for 11 days using the duplicate meal method , and faeces and urine were collected for 10 d for further analyses . Results Ingestion of the LDC did not cause severe digestive disorders , except excessive gas emission , and flatulence and slight abdominal pain in some subjects for intakes above 50 g DM/d . Wet and dry stool outputs increased by 45 and 70 % , respectively ( P . In vitro enzymatic digestibility of the LDC was 15 ( SD 1.5 ) % , and 9.2 ( SD 8.3 ) % of the LDC was excreted in faeces ( P The ME value of the LDC was 14.1 ( SD 2.3 ) kJ/g DM , that is 14 % less than the tabulated values of sucrose and starch . Its net energy value ( NEV ) , estimated using three prediction equations , was 8.7 , 8.9 , and 11.4 kJ/g DM . Ingestion of the LDC significantly increased the relative apparent absorption of Mg , and Mg retention by 67 % and 31 mg/d , respectively , tended to increase Ca apparent absorption ( P=0.110 ) and Ca retention ( P=0.059 ) , but did not significantly alter Zn parameters . Conclusion NUTRIOSE ® FB can be used as a “ bulking ” agent , and substituted up to 50 g/d for usual maltodextrins without causing digestive disorders in healthy subjects . It would reduce intestinal transit disorders and energy intake , and improve magnesium and calcium absorption and retention ",
"BACKGROUND Iron , zinc , and calcium can interact with each other in a way that inhibits their respective absorption . On the other h and , mineral fortification has been used to improve simultaneous iron and zinc absorption from food supplements . OBJECTIVE We evaluated the effect of a novel fortificant mixture consisting of NaFeEDTA , zinc methionine , ascorbic acid , and citric acid on iron and zinc absorption from a dry food supplement design ed for preschool children . DESIGN The st and ard food supplement contained cereal and legume flour , dried milk , and a mixture of micronutrients including ferrous sulfate and zinc sulfate as sources of supplemental iron and zinc , respectively . St and ard and novel food products were prepared as porridge with or without the addition of 200 mg Ca as calcium phosphate . Iron absorption and zinc absorption from the food products were evaluated simultaneously in 13 nonpregnant , adult women by extrinsically labeling the products with radioisotopes of iron and zinc and carrying out whole-body counting 7 d after the food products were consumed in r and om order . RESULTS The absorption of iron from the NaFeEDTA-containing ( novel ) food product was 1.7 times that from the ferrous sulfate-containing ( st and ard ) product ( P = 0.015 ) . There was no significant effect of dietary calcium on iron absorption . Zinc absorption was not associated with the form of zinc consumed , but higher dietary calcium was marginally associated with lower zinc absorption ( P = 0.071 ) . CONCLUSIONS A mixture of fortificants containing NaFeEDTA , zinc sulfate or zinc methionine , ascorbic acid , and citric acid , but without calcium , can improve iron and zinc absorption from food products . A cost-benefit analysis of the novel fortificant mixture needs to be performed",
"Oat bran has a high phytate content and a low or inactivated phytase activity . A high intake of oat bran could therefore result in an impaired absorption of trace elements . The effect of a mean daily intake of 142 g of oat bran ( 102 g/10 MJ ) on absorption of zinc was evaluated by the use of stable isotopes and fecal monitoring in 12 healthy subjects ( 6 males and 6 females ) . Each subject participated in two separate diet periods each of 21 d with identical low-fiber diets and with oat bran added in one of the periods . The oat bran was incorporated into bread and served at three daily main meals . The intake of zinc and phytate per 10 MJ was 138 micromol ( 9.0 mg ) and 0.5 mmol , respectively , in the low-fiber period and 225 micromol ( 14.7 mg ) and 4.0 mmol , respectively , in the oat bran period . Stable isotopes of zinc ( (70)Zn ) were added to the diets at d 7 of each period . The fractional absorptions ( means + /- SD ) of zinc from the low-fiber and oat bran diets were 0.48 + /- 0.11 and 0.40 + /- 0.15 ( P = 0.07 ) , respectively . The higher zinc content in the oat bran period result ed in a greater amount of zinc absorbed ( 64 + /- 19 micromol and 99 + /- 51 micromol , respectively , P = 0.009 ) . Balance data suggest that the higher absorbed amount of zinc result ed in correspondingly higher intestinal endogenous excretion of zinc . In conclusion , the absorption of zinc was high and not affected by addition of oat bran",
"The search for a reliable , convenient indicator of Zn status was the focus of research for several decades . Plasma Zn concentration is still the most widely used clinical measurement , despite the known problems of interpretation . More recently , research ers suggested that isotopically determined kinetic parameters , such as the exchangeable Zn pool ( EZP ) , may more accurately and reliably reflect body Zn status . The objective of this study was to examine the relationship between net body Zn loss and gain during acute changes in dietary Zn intake with biochemical and kinetic indices of Zn status . Five men participated in an 85-d Zn depletion/repletion study . Net body Zn loss and gain were determined from the difference between dietary plus intravenously administered Zn and Zn excretion . Biochemical indicators of Zn status included plasma Zn , plasma alkaline phosphatase activity , and plasma retinol binding protein concentration . Following intravenous administration of (70)Zn or (67)Zn , a compartmental model was used to determine EZP mass , fractional Zn absorption , endogenous zinc excretion ( EZE ) , and plasma Zn flux . The changes in total body zinc correlated best with changes in plasma Zn ( r(2 ) = 0.826 , P EZE ( r(2 ) = 0.773 , P plasma Zn flux ( r(2 ) = 0.766 , P plasma Zn concentration is a valid indicator of whole-body Zn status in the absence of confounding factors ; however , further research is needed to determine how kinetic parameters respond to conditions where plasma Zn concentration is known to be unreliable",
"Zinc absorption as measured by body retention of [65Zn]zinc chloride or a turkey test meal extrinsically labeled with 65Zn was determined in human subjects by whole body counting after 7 days . Average 65Zn absorption from zinc chloride in persons with a high iron-absorbing capacity was similar to persons with a low capacity to absorb iron . Inorganic iron , 920 mumol ( 51 mg ) , or HB iron , 480 mumol ( 26 mg ) , inhibited 65Zn absorption from 92 mumol ( 6 mg ) of zinc chloride . When 610 mumol of iron ( 34 mg ) was added to a turkey test meal containing 61 mumol of zinc ( 4 mg ) , 65Zn absorption was not inhibited . Tin , 306 mumol ( 36 mg ) , given with zinc chloride or turkey test meals ( 61 mumol , 4 mg , of Zn ) significantly reduced 65Zn absorption . Copper , 79 mumol ( 5 mg ) , had no significant effect on the 65Zn absorption from 7.9 mumol ( 0.5 mg ) of zinc chloride . In summary , the capacity to absorb iron did not influence 65Zn absorption , but both inorganic iron and heme-iron inhibited 65Zn absorption from zinc chloride . Inorganic iron had no effect , however , on 65Zn absorption from the turkey test meal . Tin in a large dose also inhibited 65Zn absorption from both zinc chloride and the turkey test meal",
"The iron fortificant NaFeEDTA could have a potential negative effect on the metabolism of other minerals . We have used stable isotopes to monitor zinc and calcium metabolism in 10 women consuming a single meal of high- extraction wheat rolls ( 100 g flour ) fortified with 5 mg Fe as either FeSO4 or NaFeEDTA . Six-day chemical balances were made simultaneously to study apparent zinc and calcium retention from the complete diet containing the differently iron-fortified breads ( 200 g flour ; 10 mg added Fe/d ) . Mean 70Zn absorption from the bread meal increased from 20.9 % with FeSO4 to 33.5 % with NaFeEDTA ( P mean 44Ca absorption was 53.3 % from both breads . When NaFeEDTA-fortified bread was consumed , there was a small but significant increase in urinary excretion of 70Zn and 44Ca . There was a similar small increase in urinary zinc excretion during the 6-d balance , although the apparent retention of zinc and calcium was not different . Thus , we found no negative overall effect of NaFeEDTA consumption on the metabolism of zinc and calcium . In contrast , the results suggest that NaFeEDTA added to low-bioavailability diets might increase zinc absorption as well as provide iron with high bioavailability",
"Zinc absorption , mineral balance , and blood lipid concentrations were measured in 21 women aged 33 + /- 7 y ( range : 20 - 42 y ) consuming controlled lactoovovegetarian and nonvegetarian diets for 8 wk each in a crossover design . The lactoovovegetarian and nonvegetarian diets , respectively , provided ( by analysis ) 973 and 995 mg Ca , 1.8 and 1.3 mg Cu , 367 and 260 mg Mg , 5.9 and 2.5 mg Mn , 1457 and 1667 mg P , 9.1 and 11.1 mg Zn , and ( by calculation ) 40 and 16 g dietary fiber , 2.5 and 0.8 mmol phytic acid , molar ratios of phytate to Zn of 14 and 5 , and millimolar ratios of ( phytate x Ca ) to Zn of 344 and 111 . Dietary zinc absorption was measured by extrinsic isotopic labeling and whole-body counting . Plasma cholesterol , cholesterol fractions , and lipoproteins were reduced 7 - 12 % with the lactoovovegetarian diet , consistent with predictions based on dietary cholesterol and fat . Blood pressure was unaffected . Calcium , copper , magnesium , and phosphorus balances were not different between diets ; manganese balance tended to be greater with the lactoovovegetarian diet ( P absorptive efficiency that , together with a 14 % reduction in dietary zinc , reduced the amount of zinc absorbed by 35 % ( 2.4 compared with 3.7 mg/d ) and reduced plasma zinc by 5 % within the normal range . Zinc balance was maintained with both diets . Although there is a greater risk of zinc deficiency in persons consuming lactoovovegetarian compared with omnivorous diets , with inclusion of whole grains and legumes zinc requirements can be met and zinc balance maintained",
" The absorption of zinc in man from composite meals of conventional foods with various main protein sources was measured with a radionuclide technique . The meals were extrinsically labeled with 65Zn and the absorption of zinc was determined from a measurement of the whole-body retention of the isotope about 2 weeks after ingestion of the labeled meal . The meals consisted of a meat patty made from either chicken , beef , or soybeans , and included potatoes , tomatoes , and white bread . For meals based on animal protein a positive correlation was found between zinc absorption and zinc content . When 25 % of the animal protein in the chicken meal was replaced by defatted soy flour neither the zinc content nor zinc absorption were significantly influenced . The same substitution in a beef meal result ed in a decrease in zinc content and also a lower zinc absorption . The absorption from a soybean meal did not differ from an animal protein meal with the same zinc content . Lower zinc absorption was found when the calcium content of a soybean meal was increased by the addition of milk . For this study , the total zinc content of the meal was the most important factor influencing the amount of zinc absorbed",
"Mineral utilization was studied by metabolic balance techniques in 10 healthy male volunteers fed diets containing 65 and 94 g protein . Both diets contained approximately 650 mg calcium , 1 mg copper , 16 mg iron , 250 mg magnesium 1000 mg phosphorus , and 7 mg zinc . The diet consisted of conventional foods ; the additional 29 g protein was egg white protein mixed into a beverage and fed twice per day . Plasma mineral levels were not affected by the increase in dietary protein . When the diet provided 94 g of protein , urinary calcium and zinc were slightly , but significantly , increased by an average of 35 mg ( p less than 0.05 ) and 0.15 mg ( p less than 0.001 ) , respectively . Apparent mineral absorption and balance were unchanged by this modest increase in dietary protein",
"The effects of three diets -- high meat ( HM ) , low meat ( LM ) , or low meat with mineral supplements (LS)--on zinc absorption , elemental balance , and related clinical indexes were investigated in a metabolic study of 14 women aged 51 - 70 y. The women ate each of the three diets for 7 wk in r and om order . Lean beef , chicken , ham , and tuna in the HM diet replaced foods with a low mineral content in the LM diet . The LS diet was similar to the HM diet in K , P , Fe , Mg , and Zn contents . Compared with the other diets , the HM diet increased zinc absorption and retention , and slightly increased urinary zinc . Nitrogen and calcium balances and urinary calcium were not different for the HM and LM diets . Iron balance was not different for the HM and LS diets with similar iron content , but the HM diet was unexpectedly associated with lower iron status ( higher iron-binding capacity and lower ferritin than LM and LS diets ) . These results indicate that 0.8 g protein/kg body wt meets protein requirements in older women , and that high meat consumption increases zinc retention without compromising calcium status and may reduce indexes of iron status , in contrast with iron absorption results from studies with radiolabeled test meals",
"BACKGROUND Several chemical forms of zinc have been proposed for food fortification , but information is needed on their absorption from common cereals having varied phytate content . OBJECTIVE The goal was to measure zinc absorption from wheat products fortified with iron sulfate and either zinc sulfate or zinc oxide . DESIGN Adult volunteers received either low-phytate bread ( n = 11 ) or higher-phytate porridge ( n = 11 ) once weekly on 2 or 3 occasions . The foods were fortified with 1 of the 2 zinc salts ( 60 mg elemental Zn/kg wheat flour ) during week 1 and with the other during week 2 , in r and om order . (65)Zn in the same chemical form as the fortificant was incorporated in each food to assess zinc absorption with the use of whole-body counting . The porridge group received an additional test meal fortified with zinc oxide during week 3 , but the (65)Zn tracer was given as an oral solution of (65)ZnCl(2 ) . RESULTS Zinc absorption from bread ( 13.8 % ; 95 % CI : 11.8 % , 16.2 % ) was significantly ( P zinc absorption from meals fortified with zinc sulfate or zinc oxide ( P = 0.24 ) . When the porridge was fortified with zinc oxide and labeled with (65)ZnCl(2 ) , absorption of the tracer ( 8.9 % ; 7.1 % , 11.0 % ) was significantly ( P = 0.007 ) greater than when (65)ZnO was incorporated in the porridge ( 5.6 % ; 4.5 % , 6.9 % ) . CONCLUSIONS Either zinc oxide or zinc sulfate can be used to fortify wheat products consumed by presumably healthy persons . Isotopic tracers used to assess the absorption of mineral fortificants should have the same chemical form as the fortificant",
"BACKGROUND In several countries cereals are now enriched with folic acid to reduce the risk of neural tube defects . Human studies suggest that folic acid interferes with zinc absorption . This raises concerns about the zinc status of high-risk groups such as infants , pregnant women , and older persons . OBJECTIVE We sought to determine the effect of added folic acid on zinc absorption from white bread with high and low zinc contents . DESIGN Zinc absorption was measured in 15 healthy women ( 22 - 33 y ) , each of whom consumed 4 single meals spaced 2 wk apart in a r and omized crossover design . The servings of bread ( 100 g ) differed in zinc and folic acid contents as follows : A , 1.2 mg Zn and 17 microg folic acid ; B , 1.2 mg Zn and 144 microg folic acid ; C , 3.0 mg Zn and 17 microg folic acid ; and D , 2.9 mg Zn and 144 microg folic acid . Meals were extrinsically labeled with 65Zn and absorption was estimated from whole-body retention measurements . Folate status was assessed by measuring plasma and erythrocyte folate and plasma homocysteine concentrations . RESULTS Mean ( + /-SD ) zinc absorption did not differ significantly in relation to the folate content of the breads at either the low zinc content ( 38.8 + /- 13.5 % and 40.6 + /- 16.5 % for A and B , respectively ; P = 0.74 ) or the high zinc content ( 26.7 + /- 9.3 % and 22.7 + /- 6.6 % for C and D , respectively ; P = 0.16 ) . There was no significant correlation between folate status and zinc absorption ( r 0.1 ) . CONCLUSION Fortification of white bread with a commonly used amount of folic acid did not appear to influence zinc absorption at either a high or a low zinc content",
"We measured the effect of calcium carbonate and hydroxyapatite on whole-body retention of zinc-65 in 11 and iron-59 in 13 healthy , postmenopausal women . In a single-blind , controlled , crossover study , each subject , on three occasions , ingested a st and ard test meal supplemented with iron-59 or zinc-65 and capsules containing placebo or 500 mg elemental calcium as calcium carbonate or hydroxyapatite . Whole-body countings were performed prior to , 30 min after , and 2 wk after each meal . Mean ( SEM ) zinc retention was 18.1 + /- 1.0 % with placebo ( control ) and did not vary significantly with calcium carbonate ( 110.0 + /- 8.6 % of control ) or hydroxyapatite ( 106.0 + /- 7.9 % of control ) . Iron retention , 6.3 + /- 2.0 % with placebo , was significantly reduced with both calcium carbonate ( 43.3 + /- 8.8 % of control , p = 0.002 ) and hydroxyapatite ( 45.9 + /- 10.0 % of control , p = 0.003 ) . Iron absorption may be significantly reduced when calcium supplements are taken with meals",
"BACKGROUND Identification of allelic variants in a single gene that determine the phytate content of maize kernels and the subsequent breeding of low-phytate maize have facilitated studies design ed to determine quantitatively the effects of maize phytate on the bioavailability of minerals in maize . OBJECTIVE The objective was to determine the relation between the fractional absorption of zinc ( FAZ ) and the phytate content and phytate : zinc molar ratios of maize tortillas prepared from hybrids with different phytate contents . DESIGN Six healthy adults were fed , as the only food for 2 d , maize tortillas prepared from 1 of 2 low-phytate mutants : lpa1 - 1 ( lpa1 - 1-LP ) or Nutridense Low Phytate ( ND-LP ) , which have phytate reductions of approximately 60 % and approximately 80 % , respectively , compared with their respective wild-type isohybrids . Four additional subjects were fed tortillas prepared from the corresponding wild-type isohybrids ( lpa1 - 1-WT and ND-WT ) according to the same study design . Meals were extrinsically labeled with zinc stable isotopes , and FAZ was determined with a dual-isotope-tracer ratio technique . Overall FAZ values were examined in relation to dietary phytate and phytate : zinc molar ratios by using a mixed nonlinear regression model . RESULTS The mean ( + /-SD ) FAZ values from tortillas prepared from ND-LP , lpa1 - 1-LP , lpa1 - 1-WT , and ND-WT were 0.38 + /- 0.07 , 0.28 + /- 0.04 , 0.15 + /- 0.07 , and 0.13 + /- 0.05 , respectively . A negative relation ( P FAZ and both dietary phytate and the phytate : zinc molar ratio . The effect of dietary zinc ( 8 - 14 mg Zn/d ) under these experimental conditions was not significant . CONCLUSIONS FAZ from maize tortillas is positively related to the extent of phytate reduction achieved with low-phytate hybrids ",
" Nine young men and six elderly men and women ingested low-zinc , low-copper , and adequate diets for 2-wk periods . The Zn-Cu ratios averaged 2:1 , 15:1 , and 5:1 . On day 8 of each period , subjects ingested doses of 70Zn and 65Cu so that net absorption could be determined . Zn absorption on the adequate diet was 39 + /- 3 % ( means + /- SEM ) in young subjects and 21 + /- 1 % ( p less than 0.05 ) in the elderly subjects . During the low-Zn period , Zn absorption was higher as compared with that on the adequate diet in both young ( 64 + /- 5 % , p less than 0.05 ) and elderly subjects ( 43 + /- 7 % , p less than 0.05 ) . Cu absorption on the adequate diet was 60 + /- 4 % and 53 + /- 2 % in young and elderly subjects , respectively . During the low-Cu period , Cu absorption was higher as compared with that on the adequate diet in the elderly subjects ( 67 + /- 4 % , p less than 0.05 ) . Cu absorption was higher in six of seven young subjects on the restricted Cu diet ( p greater than 0.05 ) . The effect upon absorption of the change in the Zn-Cu ratio was less than the effect of dietary restriction",
"The absorption of Zn or Fe from breakfast meals containing oat porridge prepared from malted and soaked oats and a control porridge made from untreated oats was measured in human subjects . The effect on Zn and Fe absorption of reducing the phytate content of oat-porridge meals was examined in each subject by extrinsic labelling of porridge with 65Zn and of bread rolls with 55Fe and 59Fe , and measuring whole-body retention and the erythrocyte uptake of isotopes . Each experiment comprised nine to ten subjects . The absorption of Zn from malted-oat porridge with a phytate ( inositol hexaphosphate ) content of 107 mumol was 18.3 % , and significantly higher ( P control porridge containing 432 mumol phytate ( 11.8 % ) . Fe absorption from the meal containing malted-oat porridge with 107 mumol phytate ( Expt 2 ) was also significantly improved ( P porridge with 437 mumol phytate . The average increase in Fe absorption was 47 % , or from 4.4 to 6.0 % . In the breakfast meal containing malted porridge with 198 mumol phytate ( Expt 3 ) the increase in Fe absorption was not significantly improved . Even though the phytate content was reduced to a greater extent in Expt 3 than Expt 2 , the average increase in Fe absorption in Expt 3 was only 25 % more than that from the meal containing control porridge ( with 599 mumol phytate ) , depending on the higher absolute amount of phytate . In conclusion , an improvement in Zn and Fe absorption from oat products can be achieved by practising malting and soaking in the processing of oats . This may be of importance in the prevention of mineral deficiency in vulnerable groups",
"The absorption of Zn from a lupin ( Lupinus angustifolius ) milk fortified with Ca , a bread containing lupin flour ( 230 g/kg ) , a sauce containing lupin flour and a sauce containing a lupin-protein isolate was determined in humans by measuring the whole-body retention of radioisotope from meals labelled with 0.02 MBq 65Zn , allowing for endogenous excretion of Zn , after 14 d. The absorption of Zn from the Ca-enriched milk ( 16.2 % ) and the bread made with lupin flour ( 27.0 % ) was similar to literature figures for comparable soya-bean products . The absorption from composite meals made with lupin flour ( 28.2 % ) and protein isolate ( 32.7 % ) was significantly higher than that reported for comparable soya-bean products . In a second experiment the absorption of Zn from a lupin-milk base and a soya-bean-milk base was compared with that from Ca-supplemented bases . The absorption of Zn from the lupin-milk base ( 26.3 % ) was significantly higher than from the soya-bean-milk base ( 17.6 % ) , and neither was significantly altered by the addition of Ca . Overall the absorption of Zn from lupin-protein foods was found to be higher than from comparable soya-bean products . Lupin milk could be an attractive alternative to soya-bean milk for infant formulas",
"The dose-dependent inhibitory effect of sodium phytate ( myo-inositol-hexaphosphate ) on absorption of zinc and retention of calcium was studied in man . No systematic study of this dose-response effect has been reported to this time . Forty subjects were served meals containing white wheat rolls without/with additions of phytate . Ten subjects were given test meals containing one or two of the studied levels of phytate and in addition all subjects were served meals to which no phytate was added . The zinc content was 3.1 mg ( 47 micromol ) and the calcium content 266 mg ( 6.6 mmol ) . The rolls were labelled extrinsically with radioisotopes , 65Zn and 47Ca , and whole-body retention of both minerals was measured . Totally 105 meals were served , 36 meals in which no phytate was added and 9 - 10 meals on each level of phytate . The zinc absorption in meals to which either 0 , 25 , 50 , 75 , 100 , 140 , 175 or 250 mg of phytate-P ( 0 , 134 , 269 , 403 , 538 , 753 , 941 or 1344 micromol phytate ) had been added was 22 % , 16 % , 14 % , 11 % , 7 % , 7 % , 7 % and 6 % , respectively ( mean values ) . The addition of 50 mg phytate-P or more significantly decreased zinc absorption ( p=0.01 ) as compared to absorption from the test meals with no added phytate . The calcium retention at day 7 in the same meals was 31 % , 28 % , 27 % , 26 % , 22 % , 19 % , 14 % and 11 % ( mean values ) . The addition of 100 mg phytate-P or more significantly decreased calcium retention ( p=0.03 ) compared to the test meals with no added phytate . It was concluded that the inhibitory effect of phytate on the absorption of zinc and the retention of calcium was dose dependent",
"The influence of different protein sources on Zn absorption was evaluated in healthy adults by radioisotopic labelling of single meals , followed by whole-body retention measurements 14 d after intake . Semi-synthetic liquid diets were used for the evaluation of different animal-protein sources and dephytinized soyabean-protein isolate ( phytic acid/kg ) . Zn absorption was measured in the same subjects from identical test meals containing no added protein . No statistically significant differences were found in the Zn absorption from test meals containing bovine whey , casein or egg albumen when compared with test meals without added protein . Bovine serum albumin ( BSA ) and soyabean-protein isolate ( mean absorption of Zn from 45 - 49 % ( no added protein ) to 38.0 ( SD 10.9 ) ( BSA , P Zn absorption is inhibited by certain protein sources , such as BSA and dephytinized soyabean-protein isolate , while other proteins have little or no effect",
"Objective : This study was carried out to evaluate the effect of short-chain fructooligosaccharides ( sc-FOS ) on the absorption of Cu , Zn , and Se among postmenopausal women who are potential c and i date s to sub clinical trace element deficiencies . Design : A r and omized double blind cross-over study . Setting : This study was carried out at the Human Nutrition Research Center , Clermont-Ferr and , France . Subjects : 11 postmenopausal women aged 53–70 y , not taking hormone replacement therapy were enrolled and completed the study . Interventions : Diets with 10 g/day sc-FOS or placebo were given for 5 weeks each in r and om order followed by a wash-out period of at least 3 weeks . At the end of each period , stable isotopes ( 3.19 mg 67Zn as ZnCl2 , 2.06 mg 65Cu as CuCl2 and 52.3 μg 74Se as sodium selenite ) and radiopaque pellets ( as fecal excretion index ) were administered during lunch . Stools were collected for the next 5–7 days . Isotopes were determined by ICP-MS ( Cu and Zn ) or GC-MS ( Se ) . Results : Copper absorption was significantly enhanced ( p = 0.042 ) by sc-FOS . No effect of sc-FOS was observed on Zn , and Se absorption . Conclusion : To our knowledge , this is the first study on the influence of sc-FOS on trace element metabolism . The observed increase in copper absorption may be of interest regarding daily copper requirements in menopausal women . However , the relevance of this observation remains to be established",
"Objective : To study whether hydrothermal treatment or malting of barley ( cv . Blenheim ) improves zinc and calcium absorption in humans . Design : Two groups of 10 and 12 healthy subjects , respectively , were in a period of 2 months in a fasting state , served two single meals each containing porridge or breakfast cereals prepared from processed or unprocessed ( control ) barley ( 60 g ) . The meals included 200 g of milk , extrinsically labelled with 65Zn and 47Ca . Whole-body retention of both minerals was measured . Setting : The study was carried out at the Department of Radiation Physics , Sahlgrenska University Hospital , Göteborg . Subjects : The subjects were recruited among students at the Göteborg University . None dropped out . Interventions : The activities of 65Zn and 47Ca were measured by whole-body counting four to five times over a 4-week period after each meal . Results : Zinc absorption from hydrothermally treated barley porridge , containing 28 mg P as inositol tri- to hexaphosphates ( InsP3–InsP6 ) , was significantly higher ( P % ( n=12 ) . Calcium absorption did not differ ( P>0.05 ) , 21.1±6.8 vs 19.5±4.7 % ( n=12 ) . Zinc absorption from breakfast cereals of malted barley with phytase activity and containing 70 mg P as InsP3–InsP6 , was significantly higher ( P ) . The calcium absorption was 21.3±6.5 vs 18.5±4.3 % ( n=10 ) and did not differ significantly ( P>0.05 ) . Conclusions : Improvements of zinc absorption in breakfast meals can be achieved by optimised hydrothermal treatment or malting of barley . Calcium absorption was not influenced in the meals in this study .Sponsorship : Supported by Semper AB , Sweden , Oy Lahden Polttimo , Finl and , the SL-Foundation , Sweden , Swedish National Board for Industrial and Technical Development ( NUTEK ) , the Nordic Industrial Foundation , Swedish Council for Forestry and Agricultural Research ( SJFR , project no 50.0306/97 )",
"One of the benefits associated with consumption of vegetarian diets is that these diets usually have lower contents of total fat and cholesterol and have more favorable polyunsaturated-to-saturated fatty acid ratios . Thus , use of vegetarian diets tends to fit recommendations relative to decreasing risk of cardiovascular disease . However , changes in level and kind of dietary fat may result in alterations in utilization of essential minerals . In studies carried out at the University of Nebraska using healthy human subjects , low-fat diets were found to inhibit the absorption of iron , zinc , manganese , and calcium . Further research indicated that both increase in fatty acid chain length and increase in saturation of fatty acids result ed in a decrease in Ca bioavailability . However , increased dietary cholesterol levels tended to increase Ca bioavailability",
"Zn absorption was investigated in healthy elderly subjects aged 71 - 78 years and in young subjects aged 23 - 43 years using serum concentration curve ( SCC ) tests . Both groups had similar Zn and protein status . The increase in serum Zn was monitored for 180 min after ingestion of 200 ml of soya milk enriched with 50 mg of Zn . Three levels of phytic acid were used : 0 g/200 ml ( totally dephytinized soya milk ) , 0.13 g/200 ml ( half dephytinized ) , and 0.26 g/200 ml ( natural phytic acid content ) . In a first study the effect of 0 v. 0.26 g/200 ml phytic acid was compared in 10 elderly and 10 young subjects , each subject receiving both treatments . In a second study soya milks with 0 and 0.13 g/200 ml were tested in nine elderly and ten young subjects , again receiving both treatments . Mean areas under the curve of the SCC tests conducted with the 0 g/200 ml soya milk were found to be the same in both studies . Phytic acid strongly depressed Zn absorption in both studies ( P difference was found between the groups of young and elderly subjects . Therefore , no significant effect of aging on Zn absorption , as evaluated by the SCC test , or on the inhibitory effect of phytic acid was detected",
"The effect of combining a multi-micronutrient supplement with a milk-based cornstarch porridge on the bioavailability of iron , zinc , folate , and vitamin C was evaluated using the plasma curve response over time ( 8 hours ) in healthy women . Three tests were carried out in a crossover design : S ( multi-micronutrient supplement ) , MS ( multi-micronutrient supplement plus test meal ) , and M ( test meal ) . Relative bioavailability was determined as the percent ratio of the area under the curve ( AUC ) in MS corrected by M , and AUC in S. Compared to S , AUC in MS was smaller for iron ( p C. Relative bioavailability was lower ( p bioavailability of these nutrients when the multi-micronutrient supplement is combined with a milk-based cornstarch porridge is small . Therefore , the tested meal is a suitable vehicle for the multi-micronutrient supplement",
"BACKGROUND Casein phosphopeptides ( CPP ) are phosphorus-rich peptide fragments of casein , assumed to contribute to the high bioavailability of calcium from milk . METHODS The effect of casein phosphopeptides on calcium and zinc absorption from infant foods was investigated . Twenty-two men and women were given single test meals extrinsically labeled with Ca and Zn . Absorption was calculated from measurements on whole-body retention of the radioisotopes . Each subject was given either rice-based cereal ( n = 11 ) or whole-grain cereal ( n = 11 ) on three occasions together with 250 ml water and added 0 , 1 , and 2 g CPP in r and om order . One serving of rice-based cereal contained 481 mg Ca and 1.29 mg Zn ; whole-grain cereal contained 541 mg Ca and 1.77 mg Zn . One and 2 g of CPP contributed with additional 69 and 138 mg Ca , respectively . RESULTS From rice-based cereal , fractional calcium absorption was not affected by CPP addition ( mean + /- SD ) : 16.0 + /- 4.0 % ( no CPP ) , 17.6 + /- 4.5 % ( 1 g CPP ) , and 15.8 + /- 4.3 % ( 2 g CPP ) , while the total quantity of calcium absorbed was significantly improved : 7 + /- 19 mg , 97 + /- 25 mg , and 98 + /- 26 mg , respectively ( p = 0.0004 ) . Fractional zinc absorption as well as total quantity of zinc absorbed were increased with addition of CPP : 19.4 + /- 9.0 % ( 0.25 + /- 0.12 mg ) , 25.2 + /- 7.5 % ( 0.33 + /- 0.10 mg ) and 23.9 + /- 5.4 % ( 0.31 + /- 0.07 mg ) at the three CPP levels ( p = 0.04 ) . From whole-grain cereal , CPP had no effect on the percentage or actual quantity of calcium absorbed : 17.0 + /- 3.2 % ( 92 + /- 18 mg ) , 17.2 + /- 4.5 % ( 105 + /- 27 mg ) , and 15.0 + /- 4.6 % ( 102 + /- 31 mg ) , respectively . Zinc absorption was also not influenced by CPP : 16.0 + /- 5.1 % ( 0.28 + /- 0.09 mg ) , 15.3 + /- 3.1 % ( 0.27 + /- 0.06 mg ) and 18.1 + /- 4.4 % ( 0.32 + /- 0.08 mg ) , respectively . CONCLUSIONS CPP addition improved calcium and zinc absorption from rice-based cereal , while no effect was seen from whole-grain cereal",
"The purpose of this study was to determine the utilization of zinc in young adult women fed diets containing varying amounts of lean ground beef . A secondary objective was to determine the utilization of iron . The 28-day study was divided into one 7-day preexperimental period , during which a vegetarian diet was fed , and three r and omly arranged 7-day experimental periods . During the experimental periods , the diets contained 3 , 6 , or 9 oz of beef , supplying varying levels of zinc and iron . Complete collection s of urine and fecal sample s were obtained from each subject . All the diets result ed in positive zinc balance ; however , mean zinc balances were significantly higher when subjects consumed the experimental diets containing beef . When data for all diets containing beef were combined , mean values for apparent zinc absorption and zinc retention were not significantly higher than values that result ed from the vegetarian diet . Consumption of all diets result ed in a positive iron balance ; however , mean iron balances were significantly higher for diets containing beef . As the amount of beef in the diet increased , the bioavailability of iron increased . We found that zinc and iron utilization was enhanced after consumption of a diet including lean ground beef . Results of this study also suggest that little increase in zinc and iron utilization is realized by including more than 3 oz beef per day in the diet",
"Objective : To estimate the micronutrient ( riboflavin , folate , vitamin C , vitamin B12 , iron , zinc and copper ) bioavailability in healthy adults from a multi-micronutrient dietary supplement to assess the possible influence on it by the tablet disintegration properties and by the relative intestinal permeability of subject . Methods : The bioavailability of seven micronutrients from a single br and of multi-micronutrient dietary supplement was measured on two separate occasions in the presence of a st and ardized test meal in 15 healthy adult subjects . Each subject visited the Metabolic Research Unit on four separate r and omized occasions for an absorption test . One test measured the intestinal permeability . The other three tests measured the postpr and ial changes in plasma or serum concentrations after consuming a test meal alone ( control : placebo effect ) , or the test meal with either whole or crushed and powdered dietary supplements . 15 healthy Caucasian adult volunteers , aged 42 ± 14 years . Results : The 12 hour-post-dose AUC for riboflavin , folate and vitamin C ( whole and crushed tablet ) , and that for vitamin B12 ( only for the crushed tablet treatment ) and iron ( only for the whole tablet treatment ) were all significantly ( p the AUC after supplement intake for zinc and copper . Neither the form of the supplement for all micronutrients tested nor intestinal permeability of the subject for riboflavin , folate , vitamin C , iron , zinc and copper influenced the postdose nutrient AUC . In contrast , for vitamin B12 the intestinal permeability of the subject influenced significantly the nutrient AUC ( p = 0.003 ) . Conclusion : Tablet disintegration characteristics of this dietary supplement did not limit absorption of these seven micronutrients . The intestinal permeability of subject was only positively correlated with the B12 bioavailability . Results are suggestive of using multi-micronutrients dietary supplements as a vehicle to decrease the prevalence of multiple micronutrient deficiencies overall for vitamins in healthy adults",
"The effect of wheat bran on zinc absorption was studied in normal volunteers using a zinc tolerance test ( ZTT ) and whole-body monitor to measure the 7-day percentage retention of 65zinc ( 65Zn ) . Twenty-three subjects ( age 21 - 26 years ) were r and omized into three groups . All were given 5 microCi of 65Zn orally in a 10 ml solution of zinc sulphate which contained 15 mg of elemental zinc . In addition , Group A were given 20 g wheat bran , Group B 20 g Rice Krispies ( a low-fibre food ) and Group C had zinc alone . The differences between the retention of 65Zn in the three groups were all statistically significant ( A vs B P less than 0.005 ; B vs C and A vs C P less than 0.001 ) . Similarly the differences in the areas under the ZTT curves in the three groups were all statistically significant ( A vs B P less than 0.005 ; B vs C and A vs C P less than 0.001 ) . We conclude that wheat bran leads to a significant reduction in zinc absorption which could eventually induce a state of zinc deficiency",
"The availabilities of nutrients from a representative rural Mexican diet ( RMD ) and a representative urban Mexican diet ( UMD ) were evaluated by balance experiments in sixteen Mexican women . Compared with UMD , the plant-based RMD led to a higher number of defaecations and higher faecal excretion of dry matter , fat , nitrogen and energy . Apparent digestibility of N from RMD was only 67 % compared with 90 % from UMD . N balance was 0.4 and 2.6 g/d with RMD and UMD respectively ( P Apparent digestibility of energy was 89 and 95 % from RMD and UMD respectively ( P the metabolizable energy ( ME ) using Atwater 's ( Atwater & Bryant , 1900 ) general factors overestimates the determined ME in RMD by 8 % . The Food and Agriculture Organization/World Health Organization/United Nations University ( World Health Organization , 1985 ) recommended factors for correction of digestibility of fibre intake overestimate energy and protein absorption from RMD . The diets provided similar amounts of zinc , and its apparent absorption from RMD was 0.5 mg/d ( 4.6 % ) and its balance was 0.1 mg/d . This compared with values for UMD of 1.6 mg/d ( 16 % ) and 1.2 mg/d respectively . Iron intake was higher from RMD ( 17.4 v. 11.6 mg/d ; P apparent absorption was 17 v. 35 % and balance was 2.7 and 3.8 mg/d ( P calcium ( 745 v. 410 mg/d ) but apparent absorption from RMD was negative ( -136 v. 15 mg/d ) and balance was more negative ( -197 v. -77 mg/d ; P < 0.05 ) . Thus , the content of these minerals is not low in the rural diet but their bioavailabilities are poor",
"One self-selected study ( study A ) and one laboratory-controlled study ( study B ) were conducted to investigate the effect of tea consumption on zinc bioavailability in healthy humans . The 14-day study A consisted of two 7-day experimental periods , while the 28-day study B consisted of two 14-day experimental periods . In study A eight subjects and in study B ten subjects were participated . Subjects of study A consumed self-selected diets and kept a record of foods eaten . In study B , subjects ate a constant and weighed laboratory controlled diet . In both studies , subjects consumed 8 g of instant tea during tea supplementation periods . Complete urine and fecal collection s were made by subjects of both studies . Zinc contents of urine , fecal and food sample s were determined by using Atomic Absorption Spectrophotometer . Mean zinc intakes of humans consuming self-selected diets were below the RDA . Mean urinary zinc excretion , fecal zinc excretion and zinc balance were unaffected by the tea consumption . Negative zinc balances in study A and positive zinc balances in study B were observed in both tea and no tea dietary treatments . Tea consumption showed a small but not statistically significant adverse affect on zinc bioavailability in humans",
"Objectives : This study is aim ed at investigating the effect of feeding a soluble or partly soluble fibre rich-diet on the apparent absorption and balance of calcium , magnesium , iron and zinc in healthy young men , by using a chemical balance technique . Study design : Nine healthy young men were given a control diet or the same diet complemented with either inulin ( soluble ) or sugar beet fibre ( partly soluble ) during 28 d periods according to a 3 × 3 latin square design with three repetitions . During the 20 d adaptation period to fibre ingestion , experimental fibres were incorporated into bread ( 60 % ) and liquid foods ( 40 % ) up to a maximum of 40 g/d . Ca , Mg , Fe and Zn were measured in diets and in a 8 d urine and faecal composites to assess mineral absorption and balance . Results : The dietary mineral intake provided ( mg/d ) 859±196 of Ca ; 311±43 of Mg ; 11.6±1.7 of Fe ; and 11.1±1.6 of Zn from the control diet . The apparent absorption of minerals from the control diet was ( % ) Ca : 21.3±12.5 ; Mg : 46.3±10.9 ; Fe : 21.8±12.3 and Zn : 14.0±14.5 ( mean±s.d . ) . Ingestion of inulin significantly increased the apparent absorption and the balance of Ca . Sugar beet fibre ingestion result ed in a significant increase in Ca intake and balance , without modification its apparent absorption . Apparent absorption and balance of Mg , Fe and Zn were not significantly altered by the ingestion of either experimental fibre . Conclusions : Addition of the two experimental fibres ( inulin or sugar beet fibre ) to normal mixed diets can improve Ca balance without adverse effects on other mineral retention . Sponsorship : This project was supported by the French Ministry of Agriculture , Fisheries and Foods ( programme Aliment # 2002-Aliment Demain ; No. 906335 ) . The authors acknowledge the société Agro Industries , Recherche et Developpement ( Mr R. De Baynast ) who supplied them with the experimental fibres",
"The capacity of wheat bran to impair mineral absorption independent of its phytate content was studied by metabolic balance studies in man . Three breads were prepared , equivalent to white , brown and wholemeal , by adding bran in different quantities to white flour . Calcium , iron , zinc and sodium phytate were added to the loaves to make the amounts equal in all breads . Six healthy volunteers were studied for three consecutive 24-d-periods during which they ate a controlled diet , typical of that normally consumed in the UK but with 200 g bread/d . Only the type of bread changed between each dietary period . The phytate contents ( mmol ) of 200 g of each of the breads after baking were : white 2.3 , brown 2.1 and wholemeal 2.2 ; non-starch polysaccharide contents ( g ) were : white 3.3 , brown 10.9 and wholemeal 18.7 . The increased amount of bran in the breads increased stool output in the expected way but no change was seen in Ca , Zn and Fe balance . Blood levels of these minerals remained unchanged . It is concluded that wheat bran and , in particular , the cell-wall polysaccharides of bran , are unlikely to exert a significant effect on mineral absorption in man , in amounts customarily eaten , independently of the effect of phytate present in the bran",
"The urinary excretion of zinc in individuals with insulin-dependent diabetes mellitus ( IDDM ) is approximately doubled . In the absence of a compensatory mechanism , this hyperzincuria should induce a deficient or marginal Zn status . We examined parameters of Zn status in plasma and in blood cells with respect to urinary Zn losses and Zn supplementation . We measured Zn levels in the urine , plasma , and erythrocytes of 14 IDDM subjects and 15 nondiabetics who kept dietary records for 3 consecutive days . Subsequently , six IDDM subjects and seven nondiabetics were supplemented with 50 mg Zn daily for 28 days . We measured the above parameters , as well as mononuclear leukocyte Zn ( MNL-Zn ) and the plasma subfraction of albumin-bound Zn ( alb-Zn ) . The total plasma Zn-binding capacity was also assessed . Plasma copper and erythrocyte Cu were monitored as indicators of potential Zn toxicity . Individuals with IDDM displayed the expected hyperzincuria , but had normal blood Zn parameters . Zincuria increased by a similar amount in both groups during supplementation , as did the MNL-Zn content . However , erythrocyte Zn ( e-Zn ) was refractory , so a trend toward lower e-Zn among IDDM subjects persisted during Zn supplementation . Hemoglobin A1c ( HbA1c ) increased markedly in the Zn-supplemented IDDM group . Despite their chronic hyperzincuria , individuals with IDDM appear not to be Zn-deficient . Large-dose Zn supplementation increases MNL-Zn and induces an undesirable elevation of HbA1c in all individuals . This is especially disconcerting for those with IDDM , and may reflect an exacerbation of a chronic \" Zn diabetes . \" These data suggest a potential for toxicity from large-dose Zn supplementation",
"The rise in plasma zinc after the ingestion of 765 mumol ( 50 mg ) elemental zinc was measured over 6 h in three groups of healthy subjects who , in a second test , also consumed a st and ard wheat bran , a reduced phytate , high fibre processed bran or rice-based , low phytate , low fibre breakfast cereal ( Rice Krispies ) . St and ard bran , reduced phytate bran and Rice Krispies all significantly decreased the area under the plasma zinc time curve ( AUC ) compared to the zinc alone test . The AUC obtained with st and ard bran was significantly lower than that after reduced phytate bran ( mean + /- s.e . : -5.9 + /- 2.7 vs 18.5 + /- 4.2 mumol.h/l , P less than 0.001 ) . The percentage reductions in AUC produced by the test meals were : st and ard bran 106.4 + /- 2.4 , reduced phytate bran 75.9 + /- 4.8 , Rice Krispies 46.3 + /- 10.4 per cent , P less than 0.01 ) . Histidine , taken with st and ard bran in a small subgroup of subjects , tended to improve zinc absorption but the difference was not statistically significant",
"Objective : To determine if human Zn absorption adapts to chronic high Zn intakes . Methods : Zn absorption was measured at 0 , 8 , and 16 wk in healthy postmenopausal women who consumed controlled diets with ∼5 mg Zn from food , supplemented to 14 ( n = 6 ) , 32 ( n = 3 ) , or 47 ( n = 3 ) mg Zn/d for 22 wk . Zn absorption for 1 day was determined by 65Zn-labeling of meals and whole body scintillation counting . Results : At wk 0 , less Zn was absorbed from diets with 14 , compared with 32 or 47 mg/d ( 4.6 , 8.7 , and 10.3 mg/d , respectively ; pooled SE = 0.9 ; p 5.1 ; NS ) . Plasma Zn concentrations were unaffected . The results are consistent with a saturation response model of Zn absorption . Conclusion : Within several weeks , postmenopausal women biologically adapted to absorb a relatively uniform amount of 5 mg Zn/d when controlled , Zn-supplemented diets supplied consistent Zn intakes between 14 and 47 mg/d",
"The effect of Fe fortification on the absorption of Zn was studied by radioisotopic labelling of single meals , followed by measurements of whole-body retention of 65Zn at 14 d after intake . Healthy adult volunteers participated in the study . Weaning cereal , wheat bread and infant formula , foods that are all frequently Fe-fortified , were evaluated in the study . The amounts of Fe added as FeSO4 were similar to the levels in commercial products in Europe and the USA , and were 200 or 500 mg Fe/kg ( weaning cereal ) , 65 mg Fe/kg ( white wheat flour ) and 12 mg Fe/l ( infant formula ) . For comparison , Zn absorption was measured in the same subjects , from identical test meals containing no added Fe . No statistically significant differences were found when Zn absorption from the Fe-fortified test meals was compared with that from non-Fe-fortified test meals . Fractional Zn-absorption values from Fe-fortified v. non-fortified meals were 31.1 ( SD 11.9 ) v. 30.7 ( SD 7.0)% ( weaning cereal ; 200 mg Fe/kg ) , 37.7 ( SD 16.6 ) v. 30.2 ( SD 9.9)% ( weaning cereal ; 500 mg Fe/kg ) , 36.5 ( SD 14.4 ) v. 38.2 ( SD 18.1)% ( bread ; 65 mg Fe/kg flour ) and 41.6 ( SD 8.1 ) v. 38.9 ( SD 14.5)% ( infant formula ; 12 mg Fe/l ) . The addition of Fe to foods at the currently used fortification levels was thus not associated with impaired absorption of Zn and the consumption of these Fe-fortified foods would not be expected to have a negative effect on Zn nutrition",
"Zn bioavailability is often lower in vegetarian diets mainly due to low Zn and high phytic acid contents . The objective of the present study was to determine the fractional and total absorption of Zn from a vegetarian diet in comparison with meat diets with equal concentrations of phytic acid . A r and omized cross-over design , comprising three whole-day diet periods of 5 d each , with a vegetarian diet or diets containing Polish-produced meat or Danish-produced meat , was conducted . Twelve healthy female subjects completed the study . All diets had a high content of phytic acid ( 1250 micromol/d ) and in the meat diets the main meals contained 60 g pork meat . All main meals were extrinsically labelled with the radioactive isotope 65Zn and absorption of Zn was measured in a whole-body counter . The mean Zn content of the whole-day diet was : Polish meat diet 9.9 ( SE 0.14 ) mg , Danish meat diet 9.4 ( SE 0.19 ) mg and vegetarian diet 7.5 ( SE 0.18 ) mg . No difference was observed in the fractional absorption of Zn ( Polish meat diet : 27 ( SE 1.2 ) % , Danish meat diet : 27 ( SE 1.9 ) % and vegetarian diet : 23 ( SE 2.6 ) % ) . A significantly lower amount of total Zn was absorbed from the vegetarian diet ( mean Zn absorption of Polish meat diet : 2.7 ( SE 0.12 ) mg/d ( P vegetarian diet compared with the meat-based diets result ed in lower amounts of absorbed Zn due to a higher content of Zn in the meat diets , but no difference was observed in the fractional absorption of Zn",
"Single doses of zinc sulfate were given to healthy young volunteers , either in the fasting state or with various types of meals . Dairy products ( milk and cheese ) and brown bread decreased zinc absorption , as indicated by a significant drop in peak serum zinc levels . Zinc absorption was decreased when zinc was given in the fasting state with the same amounts of purified phosphate or phytate as those found in foods above . Experiments in vitro have shown that zinc is precipitated by phosphate and phytate at pR values dose to that of the intestinal lumen . Coffee also seems to inhibit zinc absorption . ",
" Eleven fasted adult men consumed a chicken meat s and wich made with white or wholemeal bread , extrinsically labelled with 2 mg 67Zn , on two different occasions . Immediately after eating the s and wich they were given an intravenous injection of 1.5 mg 70Zn . True Zn absorption ( which was approximately 7 % higher than apparent absorption ) was determined by the faecal balance technique by making an allowance for endogenous excretion from measurements of faecal excretion of 70Zn . There was no significant difference in mean true Zn absorption from the white or wholemeal bread s and wich , 33.6 and 25.4 % respectively . It was concluded that the substitution of wholemeal for white bread does not reduce Zn absorption from meat-based s and wiches"
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Previous studies have supposed that probiotic supplementation led to a positive effect on different health outcomes . Furthermore , several studies indicated that probiotics supplementation improved antioxidant status , while some studies did not indicate these effects . Hence , current systematic review and meta- analysis study was conducted to determine the effect of probiotic supplementation on some oxidative stress biomarkers among adult subjects . We search ed four electronic data bases PubMed , SCOPUS , ISI Web of Science , and the Cochrane Library till November 2017 . Clinical trials that compared the effects of probiotic supplementation with the control group were included . A r and om-effect model was used to pool weighted mean difference ( WMD ) . Finding of 11 included studies ( n = 577 ) indicated that probiotic supplementation increased total antioxidant capacity ( TAC ) ( WMD 77.30 mmol/L ; 95 % confidence interval [ CI ] 2.60 , 152.01 ; I2 = 88.3 % ) and reduced malondialdehyde ( MDA ) ( WMD − 0.31 μmol/L ; 95 % CI − 0.54 , − 0.08 ; I2 = 71.5 % ) significantly compared to the control group . However , its effects on glutathione ( GSH ) was not significant ( WMD = 19.32 μmol/L ; 95 % CI − 18.70 , 57.33 ; I2 = 64.9 % ) . The current meta- analysis revealed that probiotic supplementation may result in increasing TAC and lowering MDA , which improve antioxidant status . However , due to high heterogeneity , findings should be interpreted with caution . Further investigations are required to eluci date the effect of supplementation with probiotics on biomarkers of antioxidants
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"Background : The dramatic increase in the incidence of diabetes and its associated complications require a natural and safe solution to control and delay such complications . The present study tested the hypothesis that probiotics may affect biochemical indices of diabetic patients Methods : Thirty four types 2 diabetic patients aged between 25 to 65 years , and diagnosed with diabetes for less than 15 years were selected for this single- blinded clinical trial . Using balanced block r and om sampling , the patients were divided into two groups of intervention ( probiotics ) and placebo . Blood sample s tested for baseline glucose , insulin , TG , total cholesterol , LDL-C , HDL-C , malondialdehyde , high sensitive CRP ( hs-CRP ) and IL-6 . After six weeks of experiment , fasting blood sample s were re-tested and the data obtained were analyzed using SPSS software . Results : There were no significant differences between anthropometric data including body mass index and waist to hip ratio in placebo and treatment groups . There was no significant difference in FBS , Serum TG concentration total cholesterol and LDL-C levels between placebo and treatment groups . HDL-C levels were slightly elevated after probiotic treatment , which were not statistically significant . Insulin , MDA and IL-6 levels were reduced and high sensitive CRP hs . CRP levels were elevated , although , not statistically significant . Conclusion : The result of this study indicates a non- significant declining trend in the level of TG , MDA and IL-6 and insulin resistance after consumption of probiotics",
"ABSTRACT Modulation of the intestinal microbial ecosystem ( IME ) is a useful target to establish probiotic efficacy in a healthy population . We conducted a r and omized , double-blind , crossover , and placebo-controlled intervention study to determine the impact of Bifidobacterium bifidum strain Bb on the IME of adult healthy volunteers of both sexes . High-throughput 16S rRNA gene sequencing was used to characterize the fecal microbiota before and after 4 weeks of daily probiotic cell consumption . The intake of approximately one billion live B. bifidum cells affected the relative abundance of dominant taxa in the fecal microbiota and modulated fecal butyrate levels . Specifically , Prevotellaceae ( P = 0.041 ) and Prevotella ( P = 0.034 ) were significantly decreased , whereas Ruminococcaceae ( P = 0.039 ) and Rikenellaceae ( P = 0.010 ) were significantly increased . We also observed that the probiotic intervention modulated the fecal concentrations of butyrate in a manner dependent on the initial levels of short-chain fatty acids ( SCFAs ) . In conclusion , our study demonstrates that a single daily administration of Bifidobacterium bifidum strain Bb can significantly modify the IME in healthy ( not diseased ) adults . These findings demonstrate the need to reassess the notion that probiotics do not influence the complex and stable IME of a healthy individual . IMPORTANCE Foods and supplements cl aim ed to contain health-promoting probiotic microorganisms are everywhere these days and mainly intended for consumption by healthy people . However , it is still debated what actual effects probiotic products may have on the healthy population . In this study , we report the results of an intervention trial aim ed at assessing the modifications induced in the intestinal microbial ecosystem of healthy adults from the consumption of a probiotic product . Our results demonstrate that the introduction of a probiotic product in the dietary habits of healthy people may significantly modify dominant taxa of the intestinal microbiota , result ing in the modulation of short-chain fatty acid concentrations in the gut . The overall changes witnessed in the probiotic intervention indicate a mechanism of microbiota modulation that could have potential effects on human health",
"Abstract Throughout life , there is an aging of the immune system that causes impairment of its defense capability . Prevention or delay of this deterioration is considered crucial to maintain general health and increase longevity . We evaluated whether dietary supplementation with Lactobacillus delbrueckii subsp . bulgaricus 8481 could enhance the immune response in the elderly . This multi-center , double-blind , and placebo controlled study enrolled 61 elderly volunteers who were r and omly assigned to receive either placebo or probiotics . Each capsule of probiotics contained at least 3 × 107 L. delbrueckii subsp . bulgaricus 8481 . Individuals in the study were administered three capsules per day for 6 months . Blood sample s were obtained at baseline ( time 0 ) , end of month 3 , and month 6 . We characterized cell sub population s , measured cytokines by flow cytometry , quantified T cell receptor excision circle ( TREC ) by real-time PCR ( RT-PCR ) , and determined human β-defensin-2 ( hBD-2 ) concentrations and human cytomegalovirus ( CMV ) titers by enzyme-linked immunosorbent assay ( ELISA ) . Elderly responded to the intake of probiotic with an increase in the percentage of NK cells , an improvement in the parameters defining the immune risk profile ( IRP ) , and an increase in the T cell subsets that are less differentiated . The probiotic group also showed decreased concentrations of the pro-inflammatory cytokine IL-8 but increased antimicrobial peptide hBD-2 . These effects disappeared within 6 months of stopping the probiotic intake . Immunomodulation induced by L. delbrueckii subsp . bulgaricus 8481 could favor the maintenance of an adequate immune response , mainly by slowing the aging of the T cell sub population s and increasing the number of immature T cells which are potential responders to new antigens",
"OBJECTIVE To investigate whether a probiotic mix has additional effects when compared with an isolated dietary intervention on the body composition , lipid profile , endotoxemia , inflammation , and antioxidant profile . METHODS Women who had excess weight or obesity were recruited to a r and omized , double-blind trial and received a probiotic mix ( Lactobacillus acidophilus and casei ; Lactococcus lactis ; Bifidobacterium bifidum and lactis ; 2 × 1010 colony-forming units/day ) ( n = 21 ) or placebo ( n = 22 ) for 8 weeks . Both groups received a dietary prescription . Body composition was assessed by anthropometry and dual-energy X-ray absorptiometry . The lipid profile , lipid accumulation product , plasma fatty acids , lipopolysaccharide , interleukin-6 , interleukin-10 , tumor necrosis factor-α , adiponectin , and the antioxidant enzymes activities were analyzed . RESULTS In comparison with the dietary intervention group , the dietary intervention + probiotic mix group showed a greater reduction in the waist circumference ( -3.40 % vs. -5.48 % , P = 0.03 ) , waist-height ratio ( -3.27 % vs. -5.00 % , P = 0.02 ) , conicity index ( -2.43 % vs. -4.09 % P = 0.03 ) , and plasma polyunsaturated fatty acids ( 5.65 % vs. -18.63 % , P = 0.04 ) and an increase in the activity of glutathione peroxidase ( -16.67 % vs. 15.62 % , P of a probiotic mix reduced abdominal adiposity and increased antioxidant enzyme activity in a more effective way than an isolated dietary intervention",
"Background : The aim of the current study was to determine effects of probiotic yoghurt and multispecies probiotic capsule supplementation on biomarkers of oxidative stress and inflammatory factors in petrochemical workers . Methods : This r and omized , double-blind , placebo-controlled trial was done among petrochemical workers . Subjects were r and omly divided into three groups to receive 100 g/day probiotic yogurt ( n = 12 ) or one probiotic capsule daily ( n = 13 ) or 100 g/day conventional yogurt ( n = 10 ) for 6 weeks . The probiotic yoghurt was containing two strains of Lactobacillus acidophilus and Bifidobacterium lactis with a total of min 1 × 107 CFU . Multispecies probiotic capsule contains seven probiotic bacteria spices Actobacillus casei 3 × 103 , L. acidophilus 3 × 107 , Lactobacillus rhamnosus 7 × 109 , Lactobacillus bulgaricus 5 × 108 , Bifidobacterium breve 2 × 1010 , Bifidobacterium longum 1 × 109 and Streptococcus thermophilus 3 × 108 CFU/g . Fasting blood sample s were obtained at the beginning and end of the trial to quantify biomarkers of oxidative stress and inflammatory factors . Results : Although a significant within-group decrease in plasma protein carbonyl levels was seen in the probiotic capsule group ( 326.0 ± 308.9 vs. 251.0 ± 176.3 ng/mL , P = 0.02 ) , the changes were similar among the three groups . In addition , significant within-group decreases in plasma iso prostagl and in were observed in the probiotic supplements group ( 111.9 ± 85.4 vs. 88.0 ± 71.0 pg/mL , P = 0.003 ) and in the probiotic yogurt group ( 116.3 ± 93.0 vs. 92.0 ± 66.0 pg/mL , P = 0.02 ) , nevertheless there were no significant change among the three groups . Conclusions : Taken together , consumption of probiotic yogurt or multispecies probiotic capsule had beneficial effects on biomarkers of oxidative stress in petrochemical workers",
"OBJECTIVE Oxidative stress plays a major role in the pathogenesis and progression of diabetes . Among various functional foods with an antioxidant effect , probiotic foods have been reported to repress oxidative stress . The objective of this clinical trial was to assess the effects of probiotic and conventional yogurt on blood glucose and antioxidant status in type 2 diabetic patients . METHODS Sixty-four patients with type 2 diabetes mellitus , 30 to 60 y old , were assigned to two groups in this r and omized , double-blind , controlled clinical trial . The patients in the intervention group consumed 300 g/d of probiotic yogurt containing Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 and those in the control group consumed 300 g/d of conventional yogurt for 6 wk . Fasting blood sample s , 24-h dietary recalls , and anthropometric measurements were collected at the baseline and at the end of the trial . RESULTS Probiotic yogurt significantly decreased fasting blood glucose ( P hemoglobin A1c ( P erythrocyte superoxide dismutase and glutathione peroxidase activities and total antioxidant status ( P serum malondialdehyde concentration significantly decreased compared with the baseline value in both groups ( P insulin concentration and erythrocyte catalase activity within either group ( P > 0.05 ) . CONCLUSION The consumption of probiotic yogurt improved fasting blood glucose and antioxidant status in type 2 diabetic patients . These results suggest that probiotic yogurt is a promising agent for diabetes management",
"Sixteen White children with bronchial asthma were divided into two groups ; one received st and ard anti-asthma chemoprophylaxis ( SAC ) and the other SAC supplemented with 1 g ascorbic acid ( Redoxon ) given as a single daily dose for a 6-month period . In 10 patients the effects of ascorbic acid on exercise-induced bronchoconstriction ( EIB ) were assessed by comparing the pre-ascorbic acid results with those obtained 2 1/2 hours after the intravenous injection of 1 g ascorbic acid . Immunological investigations performed on the two groups were assessment of polymorphonuclear leucocyte ( PMNL ) motility , phagocytosis and nitroblue tetrazolium reduction and measurement of secretory IgA , serum immunoglobulin and total haemolytic complement levels and levels of the components C3 and C4 , alpha 1-antitrypsin , antistreptolysin O ( ASO ) , C-reactive protein and antibodies to certain respiratory viruses . These investigations were performed before and 1 , 3 and 6 months after the commencement of therapy . Radio-allergosorbent testing for sensitivity to four common allergens was carried out at the outset and after 6 months of therapy . Injection of ascorbic acid had no detectable effects on the degree of EIB . Slight but not significant immunological changes were observed in the SAC group over the 6-month study period . However , in the SAC plus ascorbic acid group significantly improved PMNL motility and decreased ASO levels and reduced ( although not to a significant extent ) IgE levels and titres of antibodies to the respiratory viruses were observed",
"Objective : Rheumatoid arthritis ( RA ) is an autoimmune inflammatory disease that causes great pain and disability and increasing oxidative stress in patients . The objective of the present study was to evaluate the effects of probiotics — live microorganisms with many health benefits , including antioxidant properties — on oxidative stress indices of patients with RA . This study is a secondary analysis from a previously published study Methods : In a r and omized double-blind placebo-controlled clinical trial , 46 patients with RA were assigned to one of two groups ; patients in the probiotic group received a daily capsule containing 108 colony forming units ( CFUs ) of Lactobacillus casei 01 ( L. casei 01 ) , while those in the placebo group took identical capsules containing maltodextrin , for 8 weeks . In the baseline and at the end of the study , anxiety , physical activity levels , and dietary intakes were assessed . Anthropometric parameters , serum malondialdehyde ( MDA ) , total antioxidant capacity ( TAC ) , erythrocyte superoxide dismutase ( SOD ) , glutathione peroxidase ( GPx ) , and catalase ( CAT ) activities were measured . Results : There was no significant difference between the two groups for demographic characteristics , anthropometric parameters , physical activity , anxiety levels , or dietary intakes , throughout the course of the study . No significant within- and between-group differences were observed for MDA , TAC , or CAT . SOD activity decreased only in the probiotic group and GPx activity decreased in both study groups ( p enzymes activities at the end of the study ( p > 0.05 ) . Conclusion : No significant effect of L. casei 01 supplementation was observed on the oxidative status of patients with RA , compared to placebo",
"BACKGROUND Clinical trials of probiotic treatment for Crohn 's disease ( CD ) have yielded conflicting results . This study assessed the clinical usefulness of combined probiotic and prebiotic therapy in the treatment of active CD . METHOD Ten active CD out patients without history of operation for CD were enrolled . Their mean ( + /-SD ) age was 27 + /- 7 years and the main symptoms presented were diarrhea and abdominal pain . Patients ' initial therapeutic regimen of aminosalicylates and prednisolone failed to achieve remission . Patients were thus initiated on a synbiotic therapy , consisting of both probiotics ( 75 billion colony forming units [ CFU ] daily ) and prebiotics ( psyllium 9.9 g daily ) . Probiotics mainly comprised Bifidobacterium and Lactobacillus . Patients were free to adjust their intake of probiotics or prebiotics throughout the trial . Crohn 's disease activity index ( CDAI ) , International Organization for the Study of Inflammatory Bowel Disease ( IOIBD ) score and blood sample variables were evaluated and compared before and after the trial . RESULTS The duration of the trial was 13.0 + /- 4.5 months . By the end of therapy , each patient had taken a 45 + /- 24 billion CFU daily probiotic dose , with six patients taking an additional 7.9 + /- 3.6 g daily psyllium dose . Seven patients had improved clinical symptoms following combined probiotic and prebiotic therapy . Both CDAI and IOIBD scores were significantly reduced after therapy ( 255 - 136 , P = 0.009 ; 3.5 - 2.1 , P = 0.03 , respectively ) . Six patients had a complete response , one had a partial response , and three were non-responders . Two patients were able to discontinue their prednisolone therapy , while four patients decreased their intake . There were no adverse events . CONCLUSION High-dose probiotic and prebiotic cotherapy can be safely and effectively used for the treatment of active CD"
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Pharmacological cognitive enhancement refers to improvement in cognitive functions after drug use in healthy individuals . This popular topic attracts attention both from the general public and the scientific community . The objective was to explore innovative mechanisms of psychostimulant 's action , whose potential effectiveness was assessed in r and omized placebo-controlled trials ( RCTs ) . A systematic review was carried out , using the words " attention " , " memory " , " learning " , " executive functions " , and " vigilance/wakefulness " combined to " cognitive enhancer " or " smart drug " . Methylpheni date , amphetamines , modafinil , nicotine , acetylcholine esterase inhibitors and antidepressants were extensively studied in previous meta-analyses and were not included in the present work . Drugs were classified according to their primary mode of action , namely catecholaminergic drugs ( tolcapone , pramipexole , guanfacine ) , cholinergic drugs ( anticholinergics ) , glutamatergic drugs ( ampakines ) , histaminergic drugs , and non-specified ( glucocorticoids ) . Overall , 50 RCTs were included in the present review . In conclusion , a number of new active drugs were found to improve some cognitive functions , in particular verbal episodic memory . However the number of RCTs was limited , and most of the studies found negative results . Future studies should assess both effectiveness and tolerance of repeated doses administration , and individual variability in dose response ( including baseline characteristics and potential genetic polymorphisms ) . One explanation for the limited number of recent RCTs with new psychostimulants seems to be the ethical debate surrounding pharmaceutical cognitive enhancement in healthy subjects
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"INTRODUCTION Reasoning biases such as jumping to conclusions ( JTC ) and overconfidence in errors have been well replicated in patients with delusions . However , their relation to dopaminergic activity , central to pathophysiologic models of psychosis , has not yet been investigated . This study aim ed to examine the effects of a dopaminergic agonist ( L-dopa ) and a dopaminergic antagonist ( haloperidol ) on the JTC bias and overconfidence in errors after single-dose administration in healthy individuals . METHODS The study used a r and omized , double-blind , placebo-controlled , 3-way crossover design . Participants were 36 healthy individuals aged 18 - 36 years . The variables of interest were draws to decision and probability threshold to decision on a computerized variant of the beads task and the number of high-confident incorrect responses on a visual memory task . RESULTS There were no significant effects of substance on draws to decision and probability threshold to decision . A significant effect emerged for high-confident incorrect responses in the memory task ; pairwise comparisons indicated a significant reduction of the number of high-confident incorrect responses after administration of haloperidol vs l-dopa and placebo . CONCLUSIONS This is the first study to investigate the direct effects of dopaminergic drugs on reasoning biases . The JTC bias and overconfidence in errors showed a differential pattern of dopaminergic modulation , suggesting that they represent different facets of reasoning abnormalities that interact with each other to produce delusions in susceptible individuals",
"Rationale The central cholinergic system is implicated in cognitive functioning . The dysfunction of this system is expressed in many diseases like Alzheimer 's disease , dementia of Lewy body , Parkinson 's disease and vascular dementia . In recent animal studies , it was found that selective cholinergic modulation affects visuospatial processes even more than memory function . Objective In the current study , we tried to replicate those findings . In order to investigate the acute effects of cholinergic drugs on memory and visuospatial functions , a selective anticholinergic drug , biperiden , was compared to a selective acetylcholinesterase-inhibiting drug , rivastigmine , in healthy elderly subjects . Methods A double-blind , placebo-controlled , r and omised , cross-over study was performed in 16 healthy , elderly volunteers ( eight men , eight women ; mean age 66.1 , SD 4.46 years ) . All subjects received biperiden ( 2 mg ) , rivastigmine ( 3 mg ) and placebo with an interval of 7 days between them . Testing took place 1 h after drug intake ( which was around Tmax for both drugs ) . Subjects were presented with tests for episodic memory ( wordlist and picture memory ) , working memory tasks ( N-back , symbol recall ) and motor learning ( maze task , pursuit rotor ) . Visuospatial abilities were assessed by tests with high visual scanning components ( tangled lines and Symbol Digit Substitution Test ) . Results Episodic memory was impaired by biperiden . Rivastigmine impaired recognition parts of the episodic memory performance . Working memory was non-significantly impaired by biperiden and not affected by rivastigmine . Motor learning as well as visuospatial processes were impaired by biperiden and improved by rivastigmine . Conclusions These results implicate acetylcholine as a modulator not only of memory but also of visuospatial abilities",
"Rationale Hypothalamic – pituitary – adrenal axis dysregulation predicts poor clinical and biochemical response to antidepressants . Antiglucocorticoids have therapeutic benefits but most have a troublesome adverse event profile . Aspects of neuropsychological performance , notably working memory , are susceptible to corticosteroid modulation and are impaired in depression . Aspirin has been shown to attenuate the adrenocorticotropic hormone ( ACTH ) and cortisol response to physiological challenge suggesting its potential to act as an augmenting agent in depression . Objectives To examine the effect of sub-acute ( 300 mg daily for 7 days ) aspirin pre-treatment on the cortisol awakening response and the effect of acute ( 600 mg ) and sub-acute aspirin on the neuroendocrine and neuropsychological response to the arginine vasopressin analogue , desmopressin . Results We demonstrated that aspirin pre-treatment did not attenuate the cortisol or ACTH response to desmopressin but , as hypothesised , significantly reduced the cortisol awakening response and improved working memory . Conclusions Further studies to examine the impact of aspirin on neuropsychological performance and HPA axis function are warranted",
"Background Surgeons are usually exposed to high workloads leading to fatigue and stress . This not only increases the likelihood of mistakes during surgery but also puts pressure on surgeons to use drugs to counteract fatigue , distress , concentration deficits , burnout or symptoms of depression . The prevalence of surgeons taking pharmacological cognitive enhancement ( CE ) or mood enhancement ( ME ) drugs has not been systematic ally assessed so far . Methods Surgeons who attended five international conferences in 2011 were surveyed with an anonymous self-report question naire ( AQ ) regarding the use of prescription or illicit drugs for CE and ME and factors associated with their use . The R and omized Response Technique ( RRT ) was used in addition . The RRT guarantees a high degree of anonymity and confidentiality when a person is asked about stigmatizing issues , such as drug abuse . Results A total of 3,306 question naires were distributed and 1,145 entered statistical analysis ( response rate : 36.4 % ) . According to the AQ , 8.9 % of all surveyed surgeons confessed to having used a prescription or illicit drug exclusively for CE at least once during lifetime . As one would expect , the prevalence rate assessed by RRT was approximately 2.5-fold higher than that of the AQ ( 19.9 % ; 95 % confidence interval ( CI ) , 15.9 % to 23.9 % , N = 1,105 ) . An even larger discrepancy between the RRT and AQ was observed for the use of antidepressants with a 6-fold higher prevalence ( 15.1 % ; 95 % CI , 11.3 % to 19.0 % , N = 1,099 ) as compared to 2.4 % with the AQ . Finally , logistic regression analysis revealed that pressure to perform at work ( odds ratio ( OR ) : 1.290 ; 95 % CI , 1.000 to 1.666 ; P = 0.05 ) or in private life ( OR : 1.266 ; 95 % CI , 1.038 to 1.543 ; P = 0.02 ) , and gross income ( OR : 1.337 ; 95 % CI , 1.091 to 1.640 ; P = 0.005 ) , were positively associated with the use of drugs for CE or ME . Conclusions The use of illicit and prescription drugs for CE or ME is an underestimated phenomenon among surgeons which is generally attributable to high workload , perceived workload , and private stress . Such intake of drugs is associated with attempts to counteract fatigue and loss of concentration . However , drug use for CE may lead to addiction and to overestimation of one ’s own capabilities , which can put patients at risk . Coping strategies should be taught during medical education",
"BACKGROUND Sedation and functional impairments are side effects associated with the use of first-generation antihistamines that preclude their use in aviation . Selected second-generation antihistamines do not have such side effects and have been proposed for use in aircrew . METHODS Forty-two healthy naval aviation personnel served as subjects in this double-blind , r and omized , placebo-controlled crossover study . Subjective drowsiness , cognitive performance , and vigilance were measured under three conditions : 180 mg fexofenadine ( F ) , 50 mg diphenhydramine ( D ) as a positive control , or placebo ( P ) . RESULTS Subjects receiving F vs. D tended to have a faster mean hit reaction time ( adjusted mean difference + /- SE , -10.5 + /- 6.8 ms , p = 0.127 ) . Subjects performed faster and better with F vs. D on measures of omission errors and commission errors ( p symbol digit coding delayed recall accuracy was better for F vs. D ( p = 0.023 ) , and approached significance for shifting attention and divided attention tasks ( p = 0.062 and p = 0.057 , respectively ) . Subjects reported significantly more drowsiness ( p Diphenhydramine administration result ed in significant psychomotor decrements compared with fexofenadine , while the effects of fexofenadine were similar to placebo . These results provide additional support for the safe use of fexofenadine by aviation personnel",
"OBJECTIVE Overgeneral autobiographical memory has become a well established phenomenon within major depressive disorder ( MDD ) . Neuroendocrinologically , MDD is often characterized by a dysregulation of the hypothalamic-pituitary-adrenal ( HPA ) axis , i.e. hypercortisolemia and reduced feedback sensitivity . In healthy participants cortisol administration has been found to impair autobiographical memory retrieval . The purpose of this study was to compare the effects of acute cortisol administration on autobiographical memory in MDD patients with the effects observed in healthy controls . We hypothesized that in contrast to healthy control subjects acute cortisol administration would not affect autobiographical memory performance in MDD due to reduced central glucocorticoid sensitivity . METHODS In a placebo-controlled , double-blind crossover study , 16 patients with MDD and 16 healthy control subjects received a placebo or 10 mg of hydrocortisone orally before autobiographical memory testing ( AMT ) . RESULTS In the placebo condition depressed patients performed poorer than controls . After hydrocortisone intake , healthy subjects reported significantly fewer specific memories on the AMT compared to placebo treatment . In contrast , memory specificity of MDD patients was not affected by hydrocortisone treatment . CONCLUSIONS The present findings replicate previous findings of impaired autobiographical memory retrieval after hydrocortisone treatment in healthy subjects and of impaired AMT performance in depressed patients . We speculate that the missing acute impairing effect of hydrocortisone on autobiographical memory in depressed patients might reflect reduced central glucocorticoid sensitivity . However alternative explanations can not be ruled out",
"Rationale Guanfacine is an α2-adrenergic receptor agonist that has been shown to have beneficial effects on working memory and attentional functions in monkeys and in patients with attention deficit hyperactivity disorder . Objectives The aim of this study was to further investigate the cognitive-enhancing properties of guanfacine using an established battery of tasks measuring executive and memory functions . Methods Sixty healthy male volunteers were r and omised into three groups . Cognitive testing was performed from + 2 to + 4 h after double-blind administration of a single oral dose of 1 or 2 mg of guanfacine or placebo . Results Systolic blood pressure was significantly reduced by both doses of guanfacine at the end of the testing session . There were no statistically significant effects on any of the cognitive measures . Two trend effects were observed with poorer performance on digit span backward and slower ‘ Go ’ reaction times after guanfacine . Conclusion This study found no improvement of prefrontal memory or executive functions after guanfacine . Negative effects on blood pressure and trend effects on digit span backward and go reaction time indicate a mild sedative effect of guanfacine at these doses , possibly via mechanisms of autoreceptor down-regulation",
"Normal aging is associated with a decrease in dopaminergic function and a reduced ability to form new motor memories with training . This study examined the link between both phenomena . We hypothesized that levodopa would ( a ) ameliorate aging-dependent deficits in motor memory formation , and ( b ) increase dopamine availability at the dopamine type 2-like ( D2 ) receptor during training in task-relevant brain structures . The effects of training plus levodopa ( 100 mg , plus 25 mg carbidopa ) on motor memory formation and striatal dopamine availability were measured with [(11)C]raclopride ( RAC ) positron emission tomography ( PET ) . We found that levodopa did not alter RAC-binding potential at rest but it enhanced training effects on motor memory formation as well as dopamine release in the dorsal cau date nucleus . Motor memory formation during training correlated with the increase of dopamine release in the cau date nucleus . These results demonstrate that levodopa may ameliorate dopamine deficiencies in the elderly by replenishing dopaminergic presynaptic stores , actively engaged in phasic dopamine release during motor training",
"Dopamine is a potent modulator of learning and has been implicated in the encoding of stimulus salience . Repetition , however , as required for the acquisition and reacquisition of sensorimotor or cognitive skills ( e.g. , in aphasia therapy ) , decreases salience . We here tested whether increasing brain levels of dopamine during repetitive training improves learning success . Forty healthy humans took 100 mg of the dopamine precursor levodopa or placebo daily for 5 days in a r and omized double‐blind and parallel‐group design . Ninety minutes later on each day , subjects were trained on an artificial vocabulary using a high‐frequency repetitive approach . Levodopa significantly enhanced the speed , overall success , and long‐term retention of novel word learning in a dose‐dependent manner . These findings indicate new ways to potentiate learning in a variety of domains if conventional training alone fails",
"The catechol O-methyltransferase ( COMT ) gene is essential in the metabolic degradation of dopamine in the prefrontal cortex . In the present study , we examined the effect of a Val158Met polymorphism in the COMT gene on individual differences and changes in cognition ( executive functions and visuospatial ability ) in adulthood and old age . The participants were 292 nondemented men ( initially aged 35 - 85 years ) from a r and om sample of the population ( i.e. , the Betula study ) tested at two occasions with a 5-year interval . Confirmatory factor analyses were used to test the underlying structure of three indicators of executive functions ( verbal fluency , working memory , and Tower of Hanoi ) . Associations between COMT , age , executive functioning , and visuospatial ( block design ) tasks were examined using repeated- measures analyses of variance . Carriers of the Val allele ( with higher enzyme activity ) compared with carriers of the Met/Met genotype ( with low enzyme activity ) performed worse on executive functioning and visuo-spatial tasks . Individuals with the Val/Val genotype declined in executive functioning over the 5-year period , whereas carriers of the Met allele remained stable in performance . An Age COMT interaction for visuospatial ability located the effect for middle-aged men only . This COMT polymorphism is a plausible c and i date gene for executive functioning and fluid intelligence in nondemented middle-aged and older adults",
"Elderly subjects ( 65 - 76 years ) were tested for recall of nonsense syllables prior to and after oral administration of 1-(quinoxalin-6 ylcarbonyl)piperidine ( CX516 ) , a central ly active drug that enhances currents mediated by AMPA-type glutamate receptors . A significant and positive drug effect was found for delayed ( 5 min ) recall at 75 min posttreatment ; average scores for the highest dose group were more than twofold greater than for the placebo group . The drug had no evident influence on heart rate or self- assessment of several psychological variables",
"AIMS To assess the sleepiness induced by pramipexole , a D2/D3-dopamine receptor agonist commonly used in Parkinson 's disease and restless legs syndrome , without the problem of the confounding factors related to the disease . METHODS Placebo , bromocriptine ( 2.5 mg ) , L-dopa ( 100 mg ) and pramipexole ( 0.5 mg ) were administered in a single oral dose on four separate days , with at least a 2-week wash-out period in a r and omized cross-over design . Induced somnolence was assessed using Multiple Sleep Latency Test ( MSLT ) and subjective scaling of vigilance . Twelve male subjects ( 26.3 + /- 5.5 years old ) without anxiety , mood , sleep or sedation disorders were enrolled . RESULTS Pramipexole significantly reduced mean sleep latency compared with placebo 3 h 30 min [ -6.1 min ( -9.8 , -2.4 ) , P = 0.002 ] and 5 h 30 min [ -5.6 min ( -7.7 , -3.5 ) , P = 0.003 ] after administration . In addition , the total duration of sleep during the tests was higher with pramipexole than with placebo [ + 6.0 min ( 2.3 , 9.7 ) , P placebo . The induced sleepiness was not associated with an increase in subjective somnolence scaling , indicating that this adverse event may occur without prior warning . CONCLUSIONS These results show that a single oral dose of pramipexole induces sleepiness as assessed by MSLT in healthy young subjects , independent of disease-related sleep dysfunction",
"The present study compares the effects of two alpha2-agonists , clonidine ( 0.5 , 2 , and 5 μg/kg , PO ) and guanfacine ( 7 and 29 μg/kg , PO ) in young healthy volunteers on their performance in visual paired associates learning ( PAL ) and delayed matching to sample ( DMTS ) visual short-term recognition memory tests . In the PAL test , clonidine 2 and guanfacine 29 μg/kg improved the subjects ’ performance . In the DMTS test , clonidine at 5 μg/kg delay-dependently impaired performance accuracy , and at 2 and 5 μg/kg it also slowed responses . Guanfacine had no effect on DMTS test performance . Clonidine 5 and guanfacine 29 μg/kg equally increased subjective feelings of sedation and reduced blood pressure . The results suggest that both clonidine and guanfacine facilitated PAL learning by improving “ frontal strategies , ” but only clonidine disrupted “ mnemonic processing ” decreasing DMTS accuracy . The greater selectivity of guanfacine for alpha2A-adrenoceptor subtype may explain the different profile of action of the drugs"
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4117942a-06ff-11f0-808a-c43d1ab1c353
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N-acetylcysteine , a sulphur-containing amino acid for the treatment of paracetamol overdose and chronic obstructive pulmonary disease , is a widely available off-the-shelf oral antioxidant supplement in many countries . With the potential to modulate several neurological pathways , including glutamate dysregulation , oxidative stress , and inflammation that can be beneficial to the brain functions , N-acetylcysteine is being explored as an adjunctive therapy for many psychiatric conditions . This narrative review synthesis es and presents the current evidence from systematic review s , meta-analyses , and latest clinical trials on N-acetylcysteine for addiction and substance abuse , schizophrenia , obsessive-compulsive and related disorders , and mood disorders . Good evidence exists to support the use of N-acetylcysteine as an adjunct treatment to reduce the total and negative symptoms of schizophrenia . N-acetylcysteine also appears to be effective in reducing craving in substance use disorders , especially for the treatment of cocaine and cannabis use among young people , in addition to preventing relapse in already abstinent individuals . Effects of N-acetylcysteine on obsessive-compulsive and related disorders , as well as on mood disorders , remain unclear with mixed review s , even though promising evidence does exist . Larger and better- design ed studies are required to further investigate the clinical effectiveness of N-acetylcysteine in these areas . Oral N-acetylcysteine is safe and well tolerated without any considerable adverse effects . Current evidence supports its use as an adjunctive therapy clinical ly for psychiatric conditions , administered concomitantly with existing medications , with a recommended dosage between 2000 and 2400 mg/day
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"Background N-acetyl cysteine ( NAC ) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial . The current study aim ed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder . Method The efficacy of a double blind r and omized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined . Participants ( n = 149 ) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and , after eight weeks of open-label NAC treatment , were r and omized to adjunctive NAC or placebo , in addition to treatment as usual . Participants ( primarily out patients ) were recruited through public and private services and through newspaper advertisements . Time to intervention for a mood episode was the primary endpoint of the study , and changes in mood symptoms , functionality and quality of life measures were secondary outcomes . Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase . During the subsequent double-blind phase , there was minimal further change in outcome measures with scores remaining low . Consequently , from this low plateau , between-group differences did not emerge on recurrence , clinical functioning or quality of life measures . Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial ; however , these findings may be confounded by limitations .Trial Registration The trial was registered with the Australian New Zeal and Clinical Trials Registry ( ACTRN12607000074493 )",
"Glutathione ( GSH ) dysregulation at the gene , protein , and functional levels has been observed in schizophrenia patients . Together with disease-like anomalies in GSH deficit experimental models , it suggests that such redox dysregulation can play a critical role in altering neural connectivity and synchronization , and thus possibly causing schizophrenia symptoms . To determine whether increased GSH levels would modulate EEG synchronization , N-acetyl-cysteine ( NAC ) , a glutathione precursor , was administered to patients in a r and omized , double-blind , crossover protocol for 60 days , followed by placebo for another 60 days ( or vice versa ) . We analyzed whole-head topography of the multivariate phase synchronization ( MPS ) for 128-channel resting-state EEGs that were recorded at the onset , at the point of crossover , and at the end of the protocol . In this proof of concept study , the treatment with NAC significantly increased MPS compared to placebo over the left parieto-temporal , the right temporal , and the bilateral prefrontal regions . These changes were robust both at the group and at the individual level . Although MPS increase was observed in the absence of clinical improvement at a group level , it correlated with individual change estimated by Liddle 's disorganization scale . Therefore , significant changes in EEG synchronization induced by NAC administration may precede clinical ly detectable improvement , highlighting its possible utility as a biomarker of treatment efficacy . Trial Registration Clinical Trials.gov",
"Backgound The purpose of this study was to assess the biological and clinical effects of n-acetyl-cysteine ( NAC ) in Parkinson ’s disease ( PD ) . Methods The overarching goal of this pilot study was to generate additional data about potentially protective properties of NAC in PD , using an in vitro and in vivo approach . In preparation for the clinical study we performed a cell tissue culture study with human embryonic stem cell (hESC)-derived midbrain dopamine ( mDA ) neurons that were treated with rotenone as a model for PD . The primary outcome in the cell tissue cultures was the number of cells that survived the insult with the neurotoxin rotenone . In the clinical study , patients continued their st and ard of care and were r and omized to receive either daily NAC or were a waitlist control . Patients were evaluated before and after 3 months of receiving the NAC with DaTscan to measure dopamine transporter ( DAT ) binding and the Unified Parkinson ’s Disease Rating Scale ( UPDRS ) to measure clinical symptoms . Results The cell line study showed that NAC exposure result ed in significantly more mDA neurons surviving after exposure to rotenone compared to no NAC , consistent with the protective effects of NAC previously observed . The clinical study showed significantly increased DAT binding in the cau date and putamen ( mean increase ranging from 4.4 % to 7.8 % ; p NAC , and no measurable changes in the control group . UPDRS scores were also significantly improved in the NAC group ( mean improvement of 12.9 % , p = 0.01 ) . Conclusions The results of this preliminary study demonstrate for the first time a potential direct effect of NAC on the dopamine system in PD patients , and this observation may be associated with positive clinical effects . A large-scale clinical trial to test the therapeutic efficacy of NAC in this population and to better eluci date the mechanism of action is warranted . Trial Registration Clinical Trials.gov",
"OBJECTIVE To evaluate the efficacy of serotonin reuptake inhibitor ( SRI ) augmentation with N-acetylcysteine ( NAC ) , a glutamate modulator and antioxidant medication , for treatment-resistant obsessive-compulsive disorder ( OCD ) . METHODS We conducted a r and omized , double-blind , placebo-controlled , 16-week trial of NAC ( 3,000 mg daily ) in adults ( aged 18 - 65 years ) with treatment-resistant OCD , established according to DSM-IV criteria . Forty subjects were recruited at an OCD-specialized outpatient clinic at a tertiary hospital ( May 2012-October 2014 ) . The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale ( Y-BOCS ) scores . To evaluate the variables group , time , and interaction effects for Y-BOCS scores at all time points , we used nonparametric analysis of variance with repeated measures . Secondary outcomes were the severity scores for anxiety , depression , specific OCD symptom dimensions , and insight . RESULTS Both groups showed a significant reduction of baseline Y-BOCS scores at week 16 : the NAC group had a reduction of 4.3 points ( 25.6 to 21.3 ) , compared with 3.0 points ( 24.8 to 21.8 ) for the placebo group . However , there were no significant differences between groups ( P = .92 ) . Adding NAC was superior to placebo in reducing anxiety symptoms ( P = .02 ) , but not depression severity or specific OCD symptom dimensions . In general , NAC was well tolerated , despite abdominal pain being more frequently reported in the NAC group ( n [ % ] : NAC = 9 [ 60.0 ] , placebo = 2 [ 13.3 ] ; P of NAC in reducing OCD severity in treatment-resistant OCD adults . Secondary analysis suggested that NAC might have some benefit in reducing anxiety symptoms in treatment-resistant OCD patients . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01555970",
"BACKGROUND Cannabis use disorder ( CUD ) is a prevalent and impairing condition , and established psychosocial treatments convey limited efficacy . In light of recent findings supporting the efficacy of N-acetylcysteine ( NAC ) for CUD in adolescents , the objective of this trial was to evaluate its efficacy in adults . METHODS In a 12-week double-blind r and omized placebo-controlled trial , treatment-seeking adults ages 18 - 50 with CUD ( N=302 ) , enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites , were r and omized in a 1:1 ratio to a 12-week course of NAC 1200 mg ( n=153 ) or placebo ( n=149 ) twice daily . All participants received contingency management ( CM ) and medical management . The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment , compared between NAC and placebo participants . RESULTS There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence ( odds ratio=1.00 , 95 % confidence interval 0.63 - 1.59 , p=0.984 ) . Overall , 22.3 % of urine cannabinoid tests in the NAC group were negative , compared with 22.4 % in the placebo group . Many participants were medication non-adherent ; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group . CONCLUSIONS In contrast with prior findings in adolescents , there is no evidence that NAC 1200 mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM . This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development , cannabis use profiles , responses to embedded behavioral treatment , medication adherence , and other factors",
"BACKGROUND Brain glutathione levels are decreased in schizophrenia , a disorder that often is chronic and refractory to treatment . N-acetyl cysteine ( NAC ) increases brain glutathione in rodents . This study was conducted to evaluate the safety and effectiveness of oral NAC ( 1 g orally twice daily [ b.i.d . ] ) as an add-on to maintenance medication for the treatment of chronic schizophrenia over a 24-week period . METHODS A r and omized , multicenter , double-blind , placebo-controlled study . The primary readout was change from baseline on the Positive and Negative Symptoms Scale ( PANSS ) and its components . Secondary readouts included the Clinical Global Impression ( CGI ) Severity and Improvement scales , as well as general functioning and extrapyramidal rating scales . Changes following a 4-week treatment discontinuation were evaluated . One hundred forty people with chronic schizophrenia on maintenance antipsychotic medication were r and omized ; 84 completed treatment . RESULTS Intent-to-treat analysis revealed that subjects treated with NAC improved more than placebo-treated subjects over the study period in PANSS total [ -5.97 ( -10.44 , -1.51 ) , p = .009 ] , PANSS negative [ mean difference -1.83 ( 95 % confidence interval : -3.33 , -.32 ) , p = .018 ] , and PANSS general [ -2.79 ( -5.38 , -.20 ) , p = .035 ] , CGI-Severity ( CGI-S ) [ -.26 ( -.44 , -.08 ) , p = .004 ] , and CGI-Improvement ( CGI-I ) [ -.22 ( -.41 , -.03 ) , p = .025 ] scores . No significant change on the PANSS positive subscale was seen . N-acetyl cysteine treatment also was associated with an improvement in akathisia ( p = .022 ) . Effect sizes at end point were consistent with moderate benefits . CONCLUSIONS These data suggest that adjunctive NAC has potential as a safe and moderately effective augmentation strategy for chronic schizophrenia",
"Background Clozapine is an effective treatment for a proportion of people with schizophrenia ( SZ ) who are resistant to the beneficial effects of other antipsychotic drugs . However , anything from 40–60 % of people on clozapine experience residual symptoms even on adequate doses of the medication , and thus could be considered ‘ clozapine resistant ’ . Agents that could work alongside clozapine to improve efficacy whilst not increasing the adverse effect burden are both desired and necessary to improve the lives of individuals with clozapine-resistant SZ . N-Acetylcysteine ( NAC ) is one such possible agent . Previous research from our research group provided promising pilot data suggesting the efficacy of NAC in this patient population . The aim of the study reported here is to exp and this work by conducting a large scale clinical trial of NAC in the treatment of clozapine-resistant SZ . Methods This study is an investigator initiated , multi-site , r and omised , placebo-controlled trial . It aims to include 168 patients with clozapine-resistant SZ , divided into an intervention group ( NAC ) and a control group ( placebo ) . Participants in the intervention group will receive 2 g daily of NAC . The primary outcome measures will be the negative symptom scores of the Positive and Negative Syndrome Scale ( PANSS ) . Secondary outcome measures will include : changes in quality of life ( QoL ) as measured by the Lancashire Quality of Life Profile ( LQoLP ) and cognitive functioning as measured by the total score on the MATRICS . Additionally we will examine peripheral and cortical glutathione ( GSH ) concentrations as process outcomes . Discussion This large scale clinical trial will investigate the efficacy of NAC as an adjunctive medication to clozapine . This trial , if successful , will establish a cheap , safe and easy-to-use agent ( NAC ) as a ‘ go to ’ adjunct in patients that are only partly responsive to clozapine . Trial registration Australian and New Zeal and Clinical Trials Registration Number : Current R and omised Controlled Trial ACTRN12615001273572 . The date of registration 23 November 2015",
"Treatment with N-acetylcysteine ( NAC ) normalizes glutamate ( Glu ) homeostasis and prevents relapse in drug-dependent animals . However , the effect of NAC on brain Glu levels in substance-dependent humans has not yet been investigated . Proton magnetic resonance spectroscopy ( 1H MRS ) was used to investigate Glu changes in the dorsal anterior cingulate cortex ( dACC ) after a single dose of NAC in cocaine-dependent patients and normal controls . In an open-label , r and omized , crossover study , 8 cocaine-dependent patients and 14 healthy controls underwent two scan sessions : one group receiving no compound and the other following a single administration of 2400 mg NAC . The Barratt Impulsiveness Scale was administered to examine the relation between dACC Glu levels and impulsivity . In the medication-free condition , Glu levels in the dACC were significantly higher in cocaine-dependent patients compared with healthy controls . After administration of NAC , Glu levels were reduced in the cocaine-dependent group , whereas NAC had no effect in healthy controls . Higher baseline Glu levels were associated with higher impulsivity , and both were predictive of greater NAC-induced Glu reduction . The current findings indicate that NAC can normalize elevated Glu levels in cocaine-dependent patients . These findings may have important implication s for treatment , because abnormal Glu levels are related to relapse , and treatment with NAC prevented relapse in animal studies . Furthermore , clinical studies have indicated beneficial effects of NAC in cocaine-dependent patients , and the current study suggests that these beneficial effects might in part be mediated by the ability of NAC to normalize glutamatergic abnormalities",
"Objective Obsessive compulsive and related disorders are a collection of debilitating psychiatric disorders in which the role of glutamate dysfunction in the underpinning neurobiology is becoming well established . N-acetyl cysteine ( NAC ) is a glutamate modulator with promising therapeutic effect . This paper presents a systematic review of clinical trials and case reports exploring the use of NAC for these disorders . A further objective was to detail the methodology of current clinical trials being conducted in the area . Methods PubMed , Web of Science and Cochrane Library Data base were search ed for human clinical trials or case reports investigating NAC in the treatment of obsessive compulsive disorder ( OCD ) or obsessive compulsive related disorders . Research ers with known involvement in NAC studies were contacted for any unpublished data . Results Four clinical trials and five case reports/series were identified . Study duration s were commonly 12-weeks , using 2,400–3,000 mg/day of NAC . Overall , NAC demonstrates activity in reducing the severity of symptoms , with a good tolerability profile and minimal adverse effects . Currently there are three ongoing r and omized controlled trials using NAC for OCD ( two adults and one pediatric ) , and one for excoriation . Conclusion Encouraging results have been demonstrated from the few pilot studies that have been conducted . These results are detailed , in addition to a discussion of future potential research",
"In this study , we investigated the protective effect of the antioxidant N-acetyl-L-cysteine ( NAC ) on the lung inflammation caused by ozone ( O3 ) exposure in mice . Thirty-two C57BL/6 mice were r and omly divided into control group , O3 group , O3+NAC group and NAC group . Mice were exposed to O3 ( 1.0 ppm ) or fresh air for 3 h on the day 1 , day 3 and day 5 , respectively . NAC ( 100 mg/kg ) was intraperitoneally applied to the mice 1 h before each exposure . At 24 h after the 3-time exposure , the alveolar wall structure was severely damaged and the infiltrated inflammatory cells were apparent perivascularly and peribronchiolarly . Significant increases in the total white blood cell count , macrophage , lymphocyte and neutrophil counts , as well as total protein concentration were observed in the bronchoalveolar lavage fluid ( BALF ) ( P The IL-6 , IL-8 ( P ( P NAC could attenuate the alveolar wall structure damage induced by O3 exposure and reduce the amount of infiltrated inflammatory cells , total and differential leukocyte counts ( P the IL-6 , IL-8 ( P 0.01 ) and MDA release ( P p38 MAPK and NF-κB p65 protein expression in the lung tissue of mice ( P NAC ( P that NAC could protect against O3-induced pulmonary inflammation in mice . The beneficial effect of NAC might be related with the p38 MAPK and NF-κB p65 signal pathway",
"OBJECTIVE To investigate the use of and expenditure on 17 of the most popular forms of complementary and alternative medicine ( CAM ) by adult Australians , sociodemographic characteristics of CAM users , and communication between CAM users and their doctors . METHODS In May-June 2005 , a sample of 1067 adults , 18 years and older , from all Australian states and territories , was recruited by r and om-digit telephone dialing and interviewed about their CAM use in the previous 12 months . RESULTS In the 12-month period , 68.9 % ( 95 % CI : 66.1%-71.7 % ) of those interviewed used at least one of the 17 forms of CAM and 44.1 % ( 95 % confidence interval : 41.1%-47.1 % ) visited a CAM practitioner . The estimated number of visits to CAM practitioners by adult Australians in the 12-month period ( 69.2 million ) was almost identical to the estimated number of visits to medical practitioners ( 69.3 million ) . The annual \" out of pocket \" expenditure on CAM , nationally , was estimated as 4.13 billion Australian dollars ( US $ 3.12 billion ) . Less than half of the users always informed their medical practitioners about their use of CAM . The most common characteristics of CAM users were : age , 18 - 34 ; female ; employed ; well-educated ; private health insurance coverage ; and higher-than-average incomes . CONCLUSIONS CAM use nationally in Australia appears to be considerably higher than estimated from previous Australian studies . This may reflect an increasing popularity of CAM ; however , regional variations in CAM use and the broader range of CAM included in the current study may contribute to the difference . Most frequently , doctors would not appear to be aware of their patient use of CAM",
"BACKGROUND There remains no FDA approved medication for the treatment of cocaine dependence . Pre clinical studies and early pilot clinical investigations have suggested that N-acetylcysteine ( NAC ) may be useful in the treatment of the disorder . OBJECTIVE The present report assessed the efficacy of NAC in the treatment of cocaine dependence . METHODS Cocaine-dependent volunteers ( n = 111 ) were r and omized to receive daily doses of 1,200 mg of NAC , 2,400 mg of NAC , or placebo . Participants were followed for 8 weeks ( up to three visits weekly ) . At each of these visits , urine sample s were collected , along with self-reports of cocaine use . Urine sample s were assessed for quantitative levels of benzoylecognine ( ie , cocaine metabolite ) . RESULTS Overall , the primary results for the clinical trial were negative . However , when considering only subjects who entered the trial having already achieved abstinence , results favored the 2,400 mg NAC group relative to placebo , with the 2,400 mg group having longer times to relapse and lower craving ratings . CONCLUSION While the present trial failed to demonstrate that NAC reduces cocaine use in cocaine-dependent individuals actively using , there was some evidence it prevented return to cocaine use in individuals who had already achieved abstinence from cocaine . SCIENTIFIC SIGNIFICANCE N-acetylcysteine may be useful as a relapse prevention agent in abstinent cocaine-dependent individuals"
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41179484-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND Peripheral arterial disease ( PAD ) is common and is a marker of systemic atherosclerosis . Patients with symptoms of intermittent claudication ( IC ) are at increased risk of cardiovascular events ( myocardial infa rct ion ( MI ) and stroke ) and of both cardiovascular and all cause mortality . OBJECTIVES To determine the effectiveness of antiplatelet agents in reducing mortality ( all cause and cardiovascular ) and cardiovascular events in patients with intermittent claudication . SEARCH METHODS The Cochrane Peripheral Vascular Diseases group search ed their Specialised Register ( last search ed April 2011 ) and CENTRAL ( 2011 , Issue 2 ) for publications on antiplatelet agents and IC . In addition reference lists of relevant articles were also search ed . SELECTION CRITERIA Double-blind r and omised controlled trials comparing oral antiplatelet agents versus placebo , or versus other antiplatelet agents in patients with stable intermittent claudication were included . Patients with asymptomatic PAD ( stage I Fontaine ) , stage III and IV Fontaine PAD , and those undergoing or awaiting endovascular or surgical intervention were excluded . DATA COLLECTION AND ANALYSIS Data on method ological quality , participants , interventions and outcomes including all cause mortality , cardiovascular mortality , cardiovascular events , adverse events , pain free walking distance , need for revascularisation , limb amputation and ankle brachial pressure indices were collected . For each outcome , the pooled risk ratio ( RR ) or mean difference ( MD ) with 95 % confidence intervals ( CI ) was calculated . MAIN RESULTS A total of 12 studies with a combined total of 12,168 patients were included in this review . Antiplatelet agents reduced all cause ( RR 0.76 , 95 % CI 0.60 to 0.98 ) and cardiovascular mortality ( RR 0.54 , 95 % CI 0.32 to 0.93 ) in patients with IC compared with placebo . A reduction in total cardiovascular events was not statistically significant ( RR 0.80 , 95 % CI 0.63 to 1.01 ) . Data from two trials ( which tested clopidogrel and picotamide respectively against aspirin ) showed a significantly lower risk of all cause mortality ( RR 0.73 , 95 % CI 0.58 to 0.93 ) and cardiovascular events ( RR 0.81 , 95 % CI 0.67 to 0.98 ) with antiplatelets other than aspirin compared with aspirin . Antiplatelet therapy was associated with a higher risk of adverse events , including gastrointestinal symptoms ( dyspepsia ) ( RR 2.11 , 95 % CI 1.23 to 3.61 ) and adverse events leading to cessation of therapy ( RR 2.05 , 95 % CI 1.53 to 2.75 ) compared with placebo ; data on major bleeding ( RR 1.73 , 95 % CI 0.51 , 5.83 ) and on adverse events in trials of aspirin versus alternative antiplatelet were limited . Risk of limb deterioration leading to revascularisation was significantly reduced by antiplatelet treatment compared with placebo ( RR 0.65 , 95 % CI 0.43 to 0.97 ) . AUTHORS ' CONCLUSIONS Antiplatelet agents have a beneficial effect in reducing all cause mortality and fatal cardiovascular events in patients with IC . Treatment with antiplatelet agents in this patient group however is associated with an increase in adverse effects , including GI symptoms , and healthcare professionals and patients need to be aware of the potential harm as well as the benefit of therapy ; more data are required on the effect of antiplatelets on major bleeding . Evidence on the effectiveness of aspirin versus either placebo or an alternative antiplatelet agent is lacking . Evidence for thienopyridine antiplatelet agents was particularly compelling and there is an urgent need for multicentre trials to compare the effects of aspirin against thienopyridines
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"Background Evidence from diabetic animal models suggests that cilostazol , a cyclic AMP phosphodiesterase inhibitor used in the treatment of claudication , is efficacious in the treatment of peripheral neuropathy , although this is unproven in humans . The main aim of this study was to assess the effects of cilostazol on neuropathic symptomatology in diabetic patients with peripheral arterial disease ( PAD ) . Methods Diabetic patients with PAD were prospect ively recruited to a r and omized double-blinded placebo-controlled trial . Baseline clinical data were recorded prior to trial commencement following medical optimization . Neurological assessment included the Toronto Clinical Neuropathy Scoring system ( TCNS ) and vibration perception thresholds ( VPT ) with a neurothesiometer at baseline , 6 weeks , and 24 weeks . Results Twenty-six patients were recruited from December 2004 to January 2006 , which included 20 males . Baseline patient allocation to treatment arms was matched for age , sex , and medical comorbidities . There was no significant difference in neurological assessment between the treatment groups using the TCNS and VPT at 6 and 24 weeks . Conclusions Despite extensive animal-based evidence that cilostazol attenuates neuropathic symptomatology , our results do not support this effect in human diabetic PAD patients",
"Cilostazol is an antiplatelet agent and vasodilator marketed in Japan for treatment of ischemic symptoms of peripheral vascular disease . It is currently being evaluated in the United States for treatment of symptomatic intermittent claudication ( IC ) . Cilostazol has been shown to improve walking distance in patients with IC . In addition to its reported vasodilator and antiplatelet effects , cilostazol has been proposed to have beneficial effects on plasma lipoproteins . We examined the effect of cilostazol versus placebo on plasma lipoproteins in 189 patients with IC . After 12 weeks of therapy with 100 mg cilostazol BID , plasma triglycerides decreased 15 % ( P Cilostazol also increased plasma high density lipoprotein cholesterol ( HDL-C ) ( 10 % ) and apolipoprotein ( apo ) A1 ( 5.7 % ) significantly ( P HDL3 and HDL2 subfractions were increased by cilostazol ; however , the greatest percentage increase was observed in HDL2 . Individuals with baseline hypertriglyceridemia ( > 140 mg/dL ) experienced the greatest changes in both HDL-C and triglycerides with cilostazol treatment . In that subset of patients , HDL-C was increased 12.2 % and triglycerides were decreased 23 % . With cilostazol , there was a trend ( 3 % ) toward decreased apoB as well as increased apoA1 , result ing in a significant ( 9.8 % , P apoA1 to apoB ratio . Low density lipoprotein cholesterol and lipoprotein(a ) concentrations were unaffected . Cilostazol treatment result ed in a 35 % increase in treadmill walking time ( P=0.0015 ) and a 9.03 % increase in ankle-brachial index ( P cilostazol also favorably modifies plasma lipoproteins in patients with peripheral arterial disease . The mechanism of this effect is currently unknown",
"EMATAP , a r and omized stratified , placebo-controlled double-blind multicentre trial was performed in Argentina in order to confirm the effect of ticlopidine in the prevention of thrombotic events in patients with intermittent claudication . Twenty-one clinical centres enrolled 615 patients , 304 ( 88 diabetic and 216 non diabetic ) were assigned to the ticlopidine group and 311 ( 95 diabetic and 216 non diabetic ) to the placebo group . Treatments were given for 24 weeks . The baseline characteristics were identical in both groups . The compliance was good and only 34 patients ( 17 in each group ) did not reach the last visit . Their status however was checked and known at that time and according to the protocol , there was no patient lost to follow-up . Twenty-five patients experienced a first event during the follow-up period and the results show a very dramatic reduction of events in the ticlopidine group ( 5 vs 20 ) , the difference being highly significant ( p = 0.002 ) in intention-to-treat analysis . If we consider the subgrouping of outcome events : sudden deaths , myocardial infa rct ions and strokes on the one h and , vascular surgery on the other h and , a significant reduction is found in the ticlopidine group . Taking into account the total deaths plus non-fatal events ( 9 vs 21 ) , the results were also significant ( p = 0.027 ) . These above results therefore demonstrate a consistent reduction in all outcome events . As regard side effects there were fewer gastro-intestinal disturbances and skin reactions than seen in North American trials . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Twenty four male hypertensive patients suffering also from peripheral obstructive arterial disease were r and omly subdivided in two groups and after a period of farmacological wash-out of one month Group I was treated with Captopril ( C 50 mg bid ) or Ticlopidine ( T 250 mg bid ) for three months and then with the association C plus T for three months again . After placebo administration for one month , patients were further treated with C plus T at low doses ( 25 mg bid and respectively 250 mg daily ) . In the first part of the study , patients of Group II received an inverse sequence of the drugs ( before Ticlopidine 250 mg bid and then Captopril 50 bid ) . In both groups of patients C induced a significant decrease of blood pressure and an increase of PFWD , TWD , and WI . T did not modify blood pressure but slightly increased PFWD , TWD , and WI . The improvement was more evident during administration of C plus T , whereas placebo administration induced a trend toward baseline values . Finally , the chronic administration of C plus T for twelve months induced a further improvement of all considered parameters . In conclusion , chronic administration of C plus T may be useful in the treatment of hypertensive patients suffering from intermittent claudication , improving significantly PFWD and TWD",
"BACKGROUND Peripheral arterial occlusion disease ( PAOD ) is caused mainly by chronic inflammation and endothelium dysfunction , and is often treated with cilostazol . However , because this drug 's influence on atherogenic cytokines is still not well known , this study examined the effect of cilostazol on the serum levels of soluble CD40 lig and ( sCD40L ) , adiponectin and high-sensitivity C-reactive protein ( hs-CRP ) in patients with type 2 diabetes and PAOD . METHODS AND RESULTS The 92 type 2 diabetics with PAOD and 100 non-PAOD diabetics were enrolled and r and omly assigned to a group receiving either cilostazol or placebo for 6 months . The atherogenic cytokines were measured at the beginning and completion of the study . In the PAOD groups , those in the cilostazol group had significant changes in the levels of hs-CRP , sCD40L and adiponectin ( P=0.001 , P=0.05 , P=0.004 , respectively ) . Changes in the levels of adiponectin and sCD40L were more significant in the PAOD group treated with cilostazol than in the non-PAOD group also treated with the drug ( P=0.01 and P=0.008 , respectively ) . CONCLUSIONS Cilostazol can decrease hs-CPR and sCD40L levels and increase that of adiponectin , and then delay the progression of atherogenesis and chronic inflammation in type 2 diabetics , especially those with PAOD",
"In a recent double‐blind trial lasting over 6 months , 40 patients suffering from intermittent claudication were r and omly allocated to receive 300 mg of suloctidil per day or exactly matching placebo capsules . In addition to treadmill walking distance , other objective criteria including ankle blood pressure response and muscle blood flow measured by 133Xe clearance were used to assess the effectiveness of therapy",
"CONTEXT Few data document current cardiovascular ( CV ) event rates in stable patients with atherothrombosis in a community setting . Differential event rates for patients with documented coronary artery disease ( CAD ) , cerebrovascular disease ( CVD ) , or peripheral arterial disease ( PAD ) or those at risk of these diseases have not been previously evaluated in a single international cohort . OBJECTIVE To establish contemporary , international , 1-year CV event rates in out patients with established arterial disease or with multiple risk factors for atherothrombosis . DESIGN , SETTING , AND PARTICIPANTS The Reduction of Atherothrombosis for Continued Health ( REACH ) Registry is an international , prospect i ve cohort of 68 236 patients with either established atherosclerotic arterial disease ( CAD , PAD , CVD ; n = 55 814 ) or at least 3 risk factors for atherothrombosis ( n = 12 422 ) , who were enrolled from 5587 physician practice s in 44 countries in 2003 - 2004 . MAIN OUTCOME MEASURES Rates of CV death , myocardial infa rct ion ( MI ) , and stroke . RESULTS As of July 2006 , 1-year outcomes were available for 95.22 % ( n = 64 977 ) of participants . Cardiovascular death , MI , or stroke rates were 4.24 % overall : 4.69 % for those with established atherosclerotic arterial disease vs 2.15 % for patients with multiple risk factors only . Among patients with established disease , CV death , MI , or stroke rates were 4.52 % for patients with CAD , 6.47 % for patients with CVD , and 5.35 % for patients with PAD . The incidences of the end point of CV death , MI , or stroke or of hospitalization for atherothrombotic event(s ) were 15.20 % for CAD , 14.53 % for CVD , and 21.14 % for PAD patients with established disease . These event rates increased with the number of symptomatic arterial disease locations , ranging from 5.31 % for patients with risk factors only to 12.58 % for patients with 1 , 21.14 % for patients with 2 , and 26.27 % for patients with 3 symptomatic arterial disease locations ( P patients with established atherosclerotic arterial disease , or at risk of atherothrombosis , experienced relatively high annual CV event rates . Multiple disease locations increased the 1-year risk of CV events",
"BACKGROUND Clopidogrel is a more potent antiplatelet agent than aspirin , result ing in greater clinical efficacy in patients with atherothrombotic disease . Furthermore , the combination of clopidogrel plus aspirin has been demonstrated to be superior to aspirin alone in the treatment of patients with acute coronary syndromes and after coronary stenting . Whether dual antiplatelet therapy is superior to aspirin monotherapy for high-risk primary prevention and secondary prevention is unknown . METHODS AND RESULTS The Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization , Management , and Avoidance ( CHARISMA ) study was design ed to evaluate the efficacy and safety of clopidogrel plus aspirin versus placebo plus aspirin in patients with established coronary , cerebral , or peripheral arterial disease or in patients with multiple risk factors for atherothrombosis who have not yet sustained an ischemic event . This r and omized , international , multicenter , double-blinded , placebo-controlled study has finished enrolling patients worldwide . A total of 15,603 patients will be followed long term . The primary end point will be the composite of vascular death , myocardial infa rct ion , or stroke . Rates of severe bleeding will also be compared between the two arms of the study . CONCLUSIONS This large-scale trial of patients at high risk for atherothrombotic events will allow determination of the value of a strategy of adding clopidogrel to the current st and ard of care , including low-dose aspirin , for a wide spectrum of patients with atherothrombosis",
"Objective : To assess the effect of bezafibrate on the risk of coronary heart disease and stroke in men with lower extremity arterial disease . Design : Double blind placebo controlled r and omised trial . Setting : 85 general practice s and nine hospital vascular clinics . Participants : 1568 men , mean age 68.2 years ( range 35 to 92 ) at recruitment . Interventions : Bezafibrate 400 mg daily ( 783 men ) or placebo ( 785 men ) . Main outcome measures : Combination of coronary heart disease and of stroke . All coronary events , fatal and non-fatal coronary events separately , and strokes alone ( secondary end points ) . Results : Bezafibrate did not reduce the incidence of coronary heart disease and stroke . There were 150 and 160 events in the active and placebo groups respectively ( relative risk 0.96 , 95 % confidence interval 0.76 to 1.21 ) . There were 90 and 111 major coronary events in the active and placebo groups respectively ( 0.81 , 0.60 to 1.08 ) , of which 64 and 65 were fatal ( 0.95 , 0.66 to 1.37 ) and 26 and 46 non-fatal ( 0.60 , 0.36 to 0.99 ) . Beneficial effects on non-fatal events were greatest in men aged coronary events ( 0.38 , 0.20 to 0.72 ) . There were no significant effects in older men . There were 60 strokes in those on active treatment and 49 in those on placebo ( 1.34 , 0.80 to 2.01 ) . There were 204 and 195 deaths from all causes in the two groups respectively ( 1.03 , 0.83 to 1.26 ) . Bezafibrate reduced the severity of intermittent claudication for up to three years . Conclusions : Bezafibrate has no effect on the incidence of coronary heart disease and of stroke combined but may reduce the incidence of non-fatal coronary events , particularly in those aged coronary events may also be reduced",
"PURPOSE To evaluate the combination of a platelet glycoprotein IIb/IIIa complex receptor inhibitor and urokinase for treatment of recent ( MATERIAL S AND METHODS Seventy patients with lower extremity arterial occlusion of less than 6 weeks duration were r and omly separated into two treatment groups : urokinase plus abciximab or urokinase plus placebo . Primary end points were the rate of major complications at 30 days after r and omization and the rates of amputation-free survival and survival without open surgery or major amputation at follow-up of 90 days . Two readers unaware of the patients ' treatment group assignments analyzed digital subtraction angiograms as they related to the study end points , with a final consensus reading . RESULTS Thrombolysis relative to clot length was faster in the urokinase-plus-abciximab group ( odds ratio , 0.52 ; 95 % CI : 0.35 , 0.76 ; P procedure-related deaths or intracranial hemorrhages , but the rate of nonfatal major bleeding was higher with urokinase plus abciximab ( four of 50 patients ) than with urokinase alone ( none of 20 patients ; P = .32 ) . At 90 days , amputation-free survival was 96 % ( 48 of 50 patients ) in the urokinase-plus-abciximab group compared with 80 % ( 16 of 20 patients ) in the urokinase alone group . The hazard ratio for the two Kaplan-Meier curves was 0.42 ( 95 % CI : 0.16 , 0.96 ; P = .04 ) . CONCLUSION In patients with lower extremity arterial occlusion who were undergoing urokinase thrombolysis , adjunctive abciximab treatment result ed in faster thrombus dissolution and improved amputation-free survival , despite an increase in major bleeding",
"BACKGROUND Intermittent claudication is associated with a poor prognosis , but less is known of the risks associated with asymptomatic peripheral arterial disease . The aims of this study were to determine the incidence and natural history of claudication , and the incidence of cardiovascular events in symptomatic and asymptomatic peripheral arterial disease . METHODS In 1988 , 1592 subjects aged 55 - 74 years were selected r and omly from the age-sex register of 10 general practice s in Edinburgh , Scotl and . The presence of peripheral arterial disease was determined by the World Health Organization question naire on intermittent claudication , the ankle brachial pressure index and a reactive hyperaemia test . This cohort was followed prospect ively over 5 years for subsequent cardiovascular events and death . RESULTS One hundred and sixteen new cases of claudication were identified ( incidence density 15.5 per 1000 person-years ) . Of those with claudication at baseline , 28.8 % and still had pain after 5 years , 8.2 % underwent vascular surgery or amputation , and 1.4 % developed leg ulceration . Claudicants had a significantly increased risk of developing angina compared with normals ( RR : 2.31 , 95 % CI : 1.04 - 5.10 ) , and asymptomatic subjects had a slightly increased risk of myocardial infa rct ion and stroke . Deaths from cardiovascular disease were more likely in both claudicants ( RR : 2.67 , 95 % CI : 1.34 - 5.29 ) and subjects with major ( RR : 2.08 , 95 % CI : 1.13 - 3.83 ) or minor asymptomatic disease ( RR : 1.74 , 95 % CI : 1.09 - 2.76 ) . Subjects with major asymptomatic disease also had an increased risk of non-cardiovascular death ( RR : 2.19 , 95 % CI : 1.33 - 3.59 ) , and therefore had the highest overall risk of death ( RR : 2.44 , 95 % CI : 1.59 - 3.74 ) . CONCLUSIONS Subjects with asymptomatic peripheral arterial disease appear to have the same increased risk of cardiovascular events and death found in claudicants",
"The aim was to test within a r and omized , double-blind trial whether the antiaggregant drug ticlopidine might reduce blood viscosity as has been cl aim ed . Sixteen patients with intermittent claudication were studied before and after three years of treatment with ticlopidine , 500 mg/day , or placebo . At base line , the viscosity values were significantly higher as compared with a reference group of healthy subjects . Whole-blood viscosity , measured at four different shear rates at hematocrit adjusted to a st and ard 40 % , decreased significantly at follow-up , with no difference between ticlopidine treatment and placebo . Hema tocrit showed a slight increase in the placebo group . The viscosity parameters were unrelated to lower limb blood flow variables , ankle/brachial index , and walking distances . The mechanism behind the overall decrease in whole-blood viscosity is obscure but could possibly be explained by lifestyle changes . Smok ing habits were , however , unaltered . Since plasma viscosity remained increased , it might indicate that some erythrocyte factor , notably red cell aggregability and deformability , had improved . It is concluded that ticlopidine had no long-term effect on blood viscosity",
"BACKGROUND Chronic peripheral arterial occlusion ( CPAO ) is a progressive disease that is associated with a variety of symptoms , the 4 most common being a sensation of coolness in the limbs , intermittent claudication ( in which pain occurs on walking ) , limb pain ( which occurs spontaneously at rest ) , and ischemic leg ulcers . Beraprost sodium is an oral prostagl and in I2 analogue that may ameliorate these symptoms . OBJECTIVE The aim of this study was to compare the efficacy and tolerability of beraprost sodium and ticlopidine hydrochloride in the treatment of patients with CPAO in China . METHODS In this multicenter , single-blind , controlled study , patients with CPAO were r and omly assigned to receive beraprost 120-μg tablet TID or ticlopidine 500-mg tablet BID , both administered orally . The clinical efficacy of the drugs was assessed using the 4 main symptoms of CPAO . Ankle-brachial index ( ABI ) also was measured as a clinical pharmacologic procedure . Adverse events were assessed throughout the study . RESULTS A total of 124 patients ( 96 men , 28 women ; mean [ SD ] age , 65 [ 12 ] years ) were enrolled in 3 hospitals . Data from 119 patients ( 93 men , 26 women ; mean [ SD ] age , 65 [ 12 ] years ) were included in the efficacy analysis ( 64 and 55 patients in the beraprost and ticlopidine groups , respectively ) . Although all 4 symptoms of CPAO were ameliorated after 3 and 6 weeks of treatment with both drugs , only the cool sensation was significantly improved with beraprost compared with ticlopidine at 6 weeks ( P ) . ABI was significantly increased with both beraprost and ticlopidine at 6 weeks versus baseline ( P 123 patients ( 65 and 58 patients in the beraprost and ticlopidine groups , respectively ) . The numbers of patients who ( 1 ) experienced adverse events ( AEs ) , ( 2 ) experienced adverse drug reactions , and ( 3 ) withdrew due to AEs were significantly smaller in the beraprost group than in the ticlopidine group ( P patients with CPAO , beraprost ameliorated cool sensation in the limbs , intermittent claudication , limb pain , and ischemic/leg ulcers . Beraprost was more efficacious in relieving CPAO symptoms and was better tolerated than ticlopidine . Beraprost may be useful for the treatment of patients with CPAO , but more studies are needed",
"Ten patients with peripheral atherosclerotic disease(PAD ) treated with 750 mg/d of 5-(2-chlorophenylmethyl)-4,5,6,7-tetrahydrothieno ( 3,5-c-pyridine ) hydrochloride ( ticlopidine , Tiklid ) were studied for three months . As control was studied a similar group of patients treated with a traditional vasodilator ( nicotinate ) . The aim of our study was to evaluate the effect of ticlopidine both on the clinical evolution of the disease and on rheologic , coagulative and platelet parameters . A progressive increase of maximal walking distance was noted during the three months of therapy with ticlopidine and limited to the first 30 days of treatment with nicotinate . The fibrinogen levels result ed significantly lowered during 90 days of treatment with ticlopidine , while that was not evident in the nicotinate group . There was also a slight improvement of blood viscosity in the ticlopidine group ( not evident in the nicotinate group ) , but it was not statistically significant . No further modifications of investigated data were found in the two groups of patients . The clinical benefit of ticlopidine in PAD without adverse reactions can be confirmed at least at the dosage of 750 mg/d instead of the usual dose of 500 mg/d . A direct or indirect action of ticlopidine on plasma fibrinogen is suggested . This observation may supply new clues for the underst and ing of the mechanism of action of this drug",
"The clinical efficacy of ticlopidine , a platelet aggregation inhibitor , was evaluated in a double-blind placebo-controlled study on 193 patients with ischemic ulcers due to chronic arterial occlusion . In the group treated with ticlopidine , significantly better efficacy was noted over the placebo group in terms of judgment on overall improvement by doctors in charge as well as by the committee assessing with color slide films . The drug was particularly effective for the treatment of patients with occlusion in the arteries on the distal side and for the ischemic ulcer with relatively small size . In the group with ticlopidine , granulation was significantly improved compared to the placebo group . Those patients who had pain due to arterial occlusion on the distal side were significantly improved by this agent . The mean diameters of ulcers were clearly reduced . Therefore , this agent could possibly be cl aim ed as an effective remedy against the main symptoms of chronic arterial occlu sion . The frequencies of side effects and abnormalities in laboratory tests were comparable in the group treated with ticlopidine to those of the group with placebo . It was , therefore , concluded that this agent has an outst and ing clinical value as a conservative treatment in chronic arterial occlusion",
"Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects . The present study was undertaken to compare the effects of policosanol and ticlopidine in patients with moderately severe intermittent claudication ( IC ) . The study had a 4-week baseline step , followed by a 20-week double-blinded , r and omized treatment period . Twenty-eight eligible patients were r and omized to policosanol 10 mg or ticlopidine 250 mg tablets twice daily ( bid ) . Walking distances in a treadmill ( constant speed 3.2 km/hr , slope 10 ° , temperature 25 ° C ) were assessed before and after 20 weeks of treatment . Both groups were similar at baseline . Compared with baseline , policosanol significantly increased ( p from 162.1 to 273.2 m and from 255.8 to 401.0 m , respectively . Ticlopidine also raised significantly ( p ( 166.2 to 266.3 m ) and ACD ( 252.9 to 386.4 m ) . Comparisons between groups did not show significant differences . Policosanol , but not ticlopidine , significantly ( p increased the ankle/arm pressure ratio . After 10 weeks , policosanol significantly ( p lowered low-density lipoprotein-cholesterol ( LDL-C ) , total cholesterol ( TC ) ( p . At study completion , policosanol lowered ( p ) LDL-C ( 30.2 % ) , TC ( 16.9 % ) , and TC/HDL-C ( 33.9 % ) , increased ( p ( + 31.7 % ) , and left triglycerides unchanged . Ticlopidine did not affect the lipid profile variable . Policosanol induced modest , but significant , reductions ( p levels compared with baseline and ticlopidine . Treatments were well tolerated and did not impair safety indicators . Three ticlopidine patients ( 21.4 % ) withdrew from the trial , only 1 owing to a serious adverse experience ( AE ) ( unstable angina ) . Three other ticlopidine patients experienced mild AE ( headache , diarrhea , and acidity ) . It is concluded that policosanol ( 10 mg bid ) can be as effective as ticlopidine ( 250 mg bid ) for improving walking distances of claudicant patients , and it could be advantageous for the global risk of these individuals owing to its cholesterol-lowering effects . This study is , however , just a pilot comparison , so that further studies in larger sample sizes are needed for definitive conclusions of the comparative effects of both drugs on patients with IC",
"Objective The objective of this study was to provide a comprehensive comparison of the long term safety and tolerability of clopidogrel , a new adenosine diphosphate ( ADP ) receptor antagonist that inhibits platelet activation induced by ADP , and aspirin ( acetylsalicylic acid ) . Patients and Methods The study population comprised 19 185 patients with symptomatic atherosclerosis manifested as recent ischaemic stroke , recent myocardial infa rct ion or symptomatic peripheral arterial disease . Patients were r and omised to receive clopidogrel 75 mg/day or aspirin 325 mg/day for a minimum of 1 year and a maximum of 3 years . Results Compared with aspirin , clopidogrel reduced the combined risk of ischaemic stroke , myocardial infa rct ion or vascular death by 8.7 % ( p = 0.043 ) . The incidence of early permanent discontinuations of the study drug due to adverse events was almost identical in both treatment groups ( 11.94 % for clopidogrel vs 11.92 % for aspirin ) . Reported neutropenia was similar in the clopidogrel and aspirin groups ( 0.10 vs 0.17 % , respectively ) with corresponding rates ( 0.05 vs 0.04 % , respectively ) for severe neutropenia . Thrombocytopenia was identical in the clopidogrel and aspirin groups ( 0.26 % ) , with the rates of severe thrombocytopenia being 0.19 vs 0.10 % , respectively . None of these observed differences was statistically significant . The overall incidence of haemorrhagic events did not differ statistically significantly between treatment groups ( 9.27 % for clopidogrel vs 9.28 % for aspirin ; p = 0.98 ) . There was a trend towards a lower incidence of intracranial haemorrhage in the clopidogrel group ( 0.31 % ) compared with the aspirin group ( 0.42 % ) . Any reported gastrointestinal haemorrhage was significantly less frequent with clopidogrel ( 1.99 % ) than with aspirin ( 2.66 % ) [ p severe gastrointestinal bleeding were 0.49 vs 0.71 % ; p gastrointestinal adverse events with clopidogrel than with aspirin ( 27.1 vs 29.8 % ; p abdominal pain , dyspepsia , constipation , or peptic , gastric , or duodenal ulceration with clopidogrel . Diarrhoea was significantly more common in the clopidogrel group ( 4.46 vs 3.36 % ; p severe diarrhoea ( 0.23 vs 0.11 % ) was low and was not significantly different between groups . There were significantly more patients with rash in the clopidogrel group ( 6.0 % ) compared with the aspirin group ( 4.6 % ) [ p clopidogrel represents a clinical ly important advance in the treatment of patients with manifest atherosclerotic disease",
"In a double-blind study , 296 patients with intermittent claudication ( Fontaine stage II ) were treated with 250 mg ticlopidine twice daily , 500 mg aspirin every third day plus 75 mg dipyridamole three times daily , or 300 mg xanthinol nicotinate three times daily for 6 months . Ticlopidine and aspirin/dipyridamole , but not xanthinol nicotinate , improved platelet aggregation , reduced β-thromboglobulin , platelet factor IV and fibrinopeptide A concentrations , and increased antithrombin III concentrations and red blood cell filterability . No changes in lipid profiles , platelet count or fibrinogen were recorded following any treatment . The doppler systolic blood pressure ratio was improved in patients treated with ticlopidine or aspirin/dipyridamole , but not with xanthinol nicotinate . It is concluded that antiplatelet treatment is useful for the treatment of limb arteriopathy",
"Objective To determine whether aspirin and antioxidant therapy , combined or alone , are more effective than placebo in reducing the development of cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease . Design Multicentre , r and omised , double blind , 2 × 2 factorial , placebo controlled trial . Setting 16 hospital centres in Scotl and , supported by 188 primary care groups . Participants 1276 adults aged 40 or more with type 1 or type 2 diabetes and an ankle brachial pressure index of 0.99 or less but no symptomatic cardiovascular disease . Interventions Daily , 100 mg aspirin tablet plus antioxidant capsule ( n=320 ) , aspirin tablet plus placebo capsule ( n=318 ) , placebo tablet plus antioxidant capsule ( n=320 ) , or placebo tablet plus placebo capsule ( n=318 ) . Main outcome measures Two hierarchical composite primary end points of death from coronary heart disease or stroke , non-fatal myocardial infa rct ion or stroke , or amputation above the ankle for critical limb ischaemia ; and death from coronary heart disease or stroke . Results No evidence was found of any interaction between aspirin and antioxidant . Overall , 116 of 638 primary events occurred in the aspirin groups compared with 117 of 638 in the no aspirin groups ( 18.2 % v 18.3 % ) : hazard ratio 0.98 ( 95 % confidence interval 0.76 to 1.26 ) . Forty three deaths from coronary heart disease or stroke occurred in the aspirin groups compared with 35 in the no aspirin groups ( 6.7 % v 5.5 % ) : 1.23 ( 0.79 to 1.93 ) . Among the antioxidant groups 117 of 640 ( 18.3 % ) primary events occurred compared with 116 of 636 ( 18.2 % ) in the no antioxidant groups ( 1.03 , 0.79 to 1.33 ) . Forty two ( 6.6 % ) deaths from coronary heart disease or stroke occurred in the antioxidant groups compared with 36 ( 5.7 % ) in the no antioxidant groups ( 1.21 , 0.78 to 1.89 ) . Conclusion This trial does not provide evidence to support the use of aspirin or antioxidants in primary prevention of cardiovascular events and mortality in the population with diabetes studied . Trial registration Current Controlled Trials IS RCT N53295293",
"The effects of dipyridamole in association with acetylsalicylic acid were compared with the effects of acetylsalicylic acid alone in patients with peripheral vascular disease . The following parameters were studied in each patient : symptoms-free interval on the treadmill , ankle-arm arterial pressure gradient , oscillographic index , venous occlusion plethysmography and any untoward reactions . Changes were observed in the pain-free interval ( p less than 0.005 ) , and in the venous occlusion plethysmography ( p less than 0.001 ) in the patients treated with the two drugs in association",
"Peripheral vascular disease ( PVD ) commonly presents with leg claudication during walking and eventually limits the walking distance and daily activities . Aspirin or pentox ifylline are commonly prescribed to improve blood flow . Aspirin works through its antiplatelet aggregation mechanism , and pentoxifylline increases the red blood cell flex ibility , which leads to increased tissue perfusion . Data on comparative studies of these drugs for improving claudication in the elderly are limited . The objective of this study was to compare pain relief offered by either aspirin or pentoxifylline for walking leg pain in the elderly with PVD . Patients sixty-five years or older with claudication were r and omly assigned to receive aspirin or pentoxifylline . Their reported level of walking claudication pain with use of the visual analogue scale ( 0 - 5 ) and the distance walked during exercises were recorded . Six weeks later the same parameters were recorded and results were compared with Student 's t test , and a P value less than 0.05 was considered a statistically significant difference . Of the 90 patients who participated , 45 received aspirin ( 325 mg daily ) and 45 were prescribed pentoxifylline ( 400 mg tid ) for six weeks . Both the aspirin and the pentoxifylline groups reported a moderate level of pain ( 2/5 ) and remained about the same ( 2/5 for aspirin and 1/5 for pentoxifylline , P = 0.9 , NS ) after six weeks . However , the pentoxifylline group reported a farther walking distance of 2 miles compared with the aspirin group of 1.2 miles ( P level of pain did not change significantly with either aspirin or pentoxifylline , but the walking distance was farther with the pentoxi fylline group",
"The anti-aggregating activity of five rising doses of clopidogrel has been compared to that of ticlopidine in atherosclerotic patients . The aim of this study was to determine the dose of clopidogrel which should be tested in a large scale clinical trail of secondary prevention of ischemic events in patients suffering from vascular manifestations of atherosclerosis [ CAPRIE ( Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events ) trial ] . A multicenter study involving 9 haematological laboratories and 29 clinical centers was set up . One hundred and fifty ambulatory patients were r and omized into one of the seven following groups : clopidogrel at doses of 10 , 25 , 50 , 75 or 100 mg OD , ticlopidine 250 mg BID or placebo . ADP and collagen-induced platelet aggregation tests were performed before starting treatment and after 7 and 28 days . Bleeding time was performed on days 0 and 28 . Patients were seen on days 0 , 7 and 28 to check the clinical and biological tolerability of the treatment . Clopidogrel exerted a dose-related inhibition of ADP-induced platelet aggregation and bleeding time prolongation . In the presence of ADP ( 5 microM ) this inhibition ranged between 29 % and 44 % in comparison to pretreatment values . The bleeding times were prolonged by 1.5 to 1.7 times . These effects were non significantly different from those produced by ticlopidine . The clinical tolerability was good or fair in 97.5 % of the patients . No haematological adverse events were recorded . These results allowed the selection of 75 mg once a day to evaluate and compare the antithrombotic activity of clopidogrel to that of aspirin in the CAPRIE trial",
"Indobufen — an inhibitor of platelets aggregation — has been used in 306 pa tients with intermittent claudication due to peripheral vascular disease . Patients were treated and followed up for one year . One patient of every 3 treated with indobufen was treated with ASA , and a control group of patients receiving no treatment was also followed up . The authors studied by means of a treadmill exercise test the pain-free walking distance ( PFWD ) , the global walking distance ( GWD ) , and the recovery time after exercise . The treatment period was com pleted by 290 patients : 204 claudicants , 51 claudicants with diabetes , and 35 with a short PFWD and GWD ( > 150 m ) . Indobufen was more effective than ASA in improving the PFWD and GWD in all groups . There were also fewer side effects with indobufen , and cardiac morbidity and mortality was also reduced . In conclusion indobufen showed its activity and safety in chronic treatment of patients with peripheral disease , and we suggest that it may be used for long periods without side effects",
"We compared the efficacy and safety of three doses of beraprost sodium , an epoprostenol analogue , with placebo in the treatment of intermittent claudication ( Fontaine 's stage II ) . One hundred sixty-four patients were r and omized to receive either placebo , 20 micrograms beraprost sodium ( BPS60 group ) , 40 micrograms beraprost sodium ( BPS120 group ) , or 60 micrograms beraprost sodium ( BPS180 group ) three times daily administered orally in a double-blind manner for 12 weeks . Treadmill exercise tests were performed twice during an initial selection phase ( D-28 and D0 ) at week 10 ( at trough beraprost concentration ) and week 12 ( at peak beraprost concentration ) of the treatment phase . At week 10 , all groups showed an increase in pain-free walking distance , and this distance was greatest in the BPS60 and BPS120 groups ( p = 0.055 ) . At week 12 , a similar pattern was observed , and the difference was significant between the groups ( p = 0.023 ) . The most frequent adverse events reported were gastrointestinal disorders , headaches , skin disorders , and flushes . Patients who received either 60 or 120 micrograms of beraprost sodium daily had an increased pain-free walking distance . Further studies are required to investigate why the highest dose used ( 180 micrograms daily ) showed lower efficacy . Having both vasodilating and antiplatelet properties and being able to increase pain-free walking distance in the short term , beraprost sodium is a promising drug for the treatment of intermittent claudication",
"Forty patients with a mean age of 62.6 ± 6 years , 36 men and 4 women , with peripheral arterial occlusive disease ( PAOD ) at Leriche-Fontaine IIb class , were r and omly allocated to one of two treatment groups , receiving either 12,500 IU/ day of subcutaneous ( sc ) calcium-heparin ( CAE ) or 250 mg/day of oral ticlopi dine , each given for ninety days . The following parameters were evaluated be fore the start of the active treatment period and after thirty and ninety days of treatment : pain-free walking distance ( PWD ) , maximum walking distance ( WDmax ) , systolic and diastolic blood pressure ( BP ) , posterior tibial arterial pressure and Winsor index at rest and after exercise ( treadmill ) , transcutaneous oxygen and carbon dioxide pressures at rest ( TcPO2 and TcPCO2 respectively ) , and time to 50 % TcPo2 recovery after three-minute ischemia . Both treatments induced an improvement in PWD/WDmax , which , at the end of the study , were increased by 50.7/58.7 % and 31.7/36.2 % , respectively , for CAE and ticlopidine treatments , respectively . Statistical analysis did not show any difference between treatments , al though a statistically significant difference was found in comparison with basal measurements for both CAE and ticlopidine treatments ( p by ticlopidine were , on the whole , less impressive than those of CAE . In fact , interestingly , although not in a statistically significant way , the CAE group walked longer in comparison with the ticlopidine group irrespective of the more critical baseline clinical conditions . Moreover , TcPo2 was favorably modified by CAE ( p by ticlopidine treatment while the other parameters remained unchanged . In conclusion , CAE , given at the daily dose of 12,500 IU in patients with PAOD at the Leriche-Fontaine IIb class , showed beneficial clinical effects , which , in turn , could be due both to the removal of the thrombophilic i m balance and to the restoration of the fibrinolytic-coagulatory hemostasis in the involved microvascular circulation",
"BACKGROUND Platelets play a key role in the pathogenesis of atherosclerosis , thrombosis , and acute coronary and cerebrovascular syndromes . Inhibition of platelet function by acetylsalicylic acid ( aspirin ) has been shown to reduce the incidence atherothrombotic events in patients with coronary , cerebrovascular , or peripheral vascular disease . Thienopyridine agents , however , including ticlopidine and clopidogrel , inhibit the adenosine diphosphate receptor and have modestly superior effects compared with aspirin on reduction of death , myocardial infa rct ion , and stroke among a broad group of patients with vascular disease . More effective antithrombotic agents are still required to treat patients at high risk for recurrent vascular events . METHODS Lotrafiban , a selective , nonpeptide antagonist of the human platelet fibrinogen receptor ( glycoprotein [ GP ] IIb/IIIa [ alphaIIb/beta3 integrin ] ) , blocks the binding of fibrinogen to the GP IIb/IIIa receptor , which is the final common pathway of platelet aggregation . Lotrafiban at doses of up to 50 mg twice daily was well-tolerated in a 12-week , double-blind , placebo-controlled , dose-ranging study in patients with recent myocardial infa rct ion , unstable angina , transient ischemic attack , or stroke when added to aspirin therapy . On the basis of these results , a dosing regimen was selected for the phase III Blockage of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion ( BRAVO ) trial based on pharmacodynamics and drug tolerability . In the pivotal BRAVO study , lotrafiban therapy is being evaluated in patients who have had a recent myocardial infa rct ion , unstable angina , transient ischemic attack , or ischemic stroke , or who present at any time after a diagnosis of peripheral vascular disease combined with either cardiovascular or cerebrovascular disease . RESULTS The efficacy evaluation will be based on a composite end point of clinical events ( death by any cause , myocardial infa rct ion , stroke , recurrent ischemia requiring hospitalization , or urgent ischemia-driven revascularization ) . The target enrollment is 9200 patients worldwide . Approximately 700 centers will participate and will be distributed within 30 countries across North America , Europe , Australia , and Asia",
"The Swedish Ticlopidine Multicentre Study ( STIMS ) was a double-blind placebo-controlled trial design ed to determine whether ticlopidine , a platelet antiaggregatory agent , reduces the incidence of myocardial infa rct ion , stroke and transitory ischaemic attacks in patients with intermittent claudication . A total of 687 patients was monitored for a minimum of 5 years or until an end-point was reached . The number of end points ( 99 vs. 89 ) , analysed according to the intention-to-treat principle , was 11.4 % lower in the ticlopidine group ( P = 0.24 ) . The mortality rate was 29.1 % lower in the ticlopidine group ( 64 vs. 89 , P = 0.015 ) ; this observation could be accounted for by a reduced mortality from ischaemic heart disease . On-treatment analysis showed there to be significantly fewer end points in the ticlopidine group ( 47 vs. 76 , P = 0.017 ) . Diarrhoea was the most common side-effect . Reversible leucopenia or thrombocytopenia was reported in seven patients on ticlopidine . It is concluded that the high morbidity and mortality from cardio- and cerebrovascular disease in patients with intermittent claudication can be reduced by long-term treatment with ticlopidine",
"The effect of 7-mono-hydroxyethylrutoside and its combination with acetylsalicylic acid was evaluated in a controlled clinical trial , performed in 105 patients with obliterative atherosclerosis of the lower limbs , and using non-invasive measurement of peripheral haemodynamic parameters -- blood flow during reactive hyperaemia and ankle systolic blood pressure . Patients , r and omized into three groups , received either placebo or 7-mono-hydroxyethylrutoside alone or in combination with acetylsalicylic acid for 12 months . The placebo group showed a decrease in maximum calf blood flow and a decrease in ankle systolic pressure . Administration of 7-mono-hydroxyethylrutoside did not lead to any significant changes in systolic pressure but there was a decrease in the maximum calf blood flow . There were no statistically significant changes in patients receiving the 7-mono-hydroxyethylrutoside and acetylsalicylic acid combination who , by contrast , showed a tendency to increased values of the parameters measured",
" Sixty patients with a mean age of 64 years ( range 57 - 77 years ) , 55 males and 5 females , with peripheral arterial occlusive disease ( PAOD ) at Leriche-Fontaine IIb class were r and omly allocated to receive either subcutaneous calcium-heparin ( 12,500 IU once daily ) or oral acetylsalicylic acid ( ASA ) ( 300 mg twice daily ) , each given for 3 months , followed by a 6-month follow-up period during which no treatment was given . The following parameters were evaluated before r and omization , after 1 and 3 months of therapy and after 1 , 3 and 6 months of follow-up : pain-free walking distance ( PWD ) , maximum walking distance ( WDmax ) , systolic and diastolic blood pressure , posterior tibial arterial pressure and ankle/arm index at rest and after exercise ( treadmill ) , transcutaneous gas analysis at rest ( TcPO2 ) . Under both treatments a statistically significant increase ( p PWD/WDmax was observed after 3 months of therapy . Calcium-heparin was slightly but significantly more effective than ASA in prolonging WDmax ( p improvement after 6 months of follow-up without any difference between each-other . Both treatments result ed in a statistically significant increase in TcPO2 and decrease in plasma fibrinogen but under calcium-heparin treatment these modifications were doubled in comparison with ASA ( p calcium-heparin on microcirculation . ( ABSTRACT TRUNCATED AT 250 WORDS",
"OBJECTIVE To assess the prophylactic efficacy of aspirin and a high-dose antioxidant vitamin combination in patients with peripheral arterial disease ( PAD ) in terms of reduction of the risk of a first vascular event ( myocardial infa rct ion , stroke , vascular death ) and critical limb ischaemia . DESIGN R and omized , placebo-controlled , double-blind clinical trial with 2 x 2 factorial design . SETTING Thirty-seven European angiology/vascular medicine units . SUBJECTS A total of 366 out patients with stage I-II PAD documented by angiography or ultrasound , with ankle/brachial index INTERVENTIONS Four treatment groups : ( i ) oral aspirin ( 100 mg daily ) , ( ii ) oral antioxidant vitamins ( 600 mg vitamin E , 250 mg vitamin C and 20 mg beta-carotene daily ) , ( iii ) both or ( iv ) neither , given for 2 years . MAIN OUTCOME MEASURE Major vascular events ( cardiovascular death , myocardial infa rct ion or stroke ) and critical leg ischaemia . RESULTS Seven of 185 patients allocated aspirin and 20 of 181 allocated placebo suffered a major vascular event ( risk reduction 64 % , P = 0.022 ) ; five and eight patients , respectively , suffered critical leg ischaemia ( total 12 vs. 28 , P = 0.014 ) . There was no evidence that antioxidant vitamins were beneficial ( 16/185 vs. 11/181 vascular events ) . Neither treatment was associated with any significant increase in adverse events . Inclusion of this trial in a meta- analysis of other r and omized trials of anti-platelet therapy in PAD makes the overall results highly significant ( P incidence of vascular events by 26 % . CONCLUSIONS For the first time direct evidence shows that low-dose aspirin should routinely be considered for PAD patients , including those with concomitant type 2 diabetes",
"There is a high risk of reocclusion after successful lower limb angioplasty . Platelets play a central role in this process . The aim of this study was to investigate the antiplatelet effect of a combination of aspirin and clopidogrel compared with aspirin alone in patients with claudication undergoing endovascular revascularization",
"The main aim of medical treatment for intermittent claudication ( IC ) is the reduction of mortality and morbidity from ischemic cardiovascular disease . However , symptomatic treatment with the aim of improving exercise performance and the overall quality of life may also be an important target of the clinical management of patients with intermittent claudication . Cloricromene , a drug with antithrombotic and anti-ischemic activities , has previously shown some promising results in patients with claudication . We have carried out a clinical trial to assess the effect of cloricromene on the claudication distance and on the quality of life of patients with IC chronically treated with aspirin . A total of 159 patients with IC , Stage II ( Fontaine ) , were enrolled in a double-blind , r and omized , prospect i ve , multicenter study comparing cloricromene ( 100 mg orally b.i.d . ) or an identical placebo for 6 months . All patients received 160 mg/day aspirin . The primary end-point was the improvement of initial claudication distance ( ICD ) at 6 months as measured by a st and ardized treadmill test . The secondary end-points were the absolute claudication distance ( ACD ) at 6 months , the percentage of patients defined as responders to treatment ( improvement of ICD of at least 40 % ) , changes in the ischemic window ( IW ) , quality of life as assessed by the SF-36 question naire , and the occurrence of major cardiovascular events . The ICD increased in both treatment groups , with a non-significant difference at 6 months in favor of cloricromene of + 12.3 m. The ACD , percentage of responders to treatment and ischemic window also improved in both groups with a slight , non-significant trend in favor of cloricromene . Pretreatment quality of life scores showed only a slight worsening compared with an age-matched , healthy population and did not change upon treatment . A post hoc subgroup analysis showed a significant benefit from cloricromene in patients with an ICD at enrollment higher than the median of the patient population . In conclusion , treatment with cloricromene for 6 months does not significantly improve claudication in patients with Stage II Fontaine peripheral arteriopathy chronically treated with aspirin . An improvement of 40 - 60 m in the ICD on a st and ardized treadmill test does not translate into a self-perceived improvement in the quality of life as assessed by the SF-36 question naire",
"Twenty-seven patients with peripheral atherosclerotic disease were r and omized into two therapy regimens consisting of indobufen ( Indo ) ( 400 mg/day ) and dipyridamole ( Dip ) ( 225 mg/day ) plus acetylsalicylic acid ( ASA ) ( 1 g/day ) , respectively . Maximal walking distance ( MWD ) and ankle-arm systolic pressure ratios were measured before and after three and six months of therapy ; bleeding time , beta-thromboglobulin ( beta-TG ) , platelet factor 4 ( PF4 ) and serum thromboxane B2 ( TXB2 ) were also assessed . The two treatment groups showed a significant and progressive increase in pain-free walking distance at both three and six months of therapy , but patients taking indobufen showed a greater improvement . On the contrary , the pressure doppler ratio at rest was statistically improved only in the ASA plus Dip group . Basal beta-TG and PF4 levels were normal and no changes occurred during the study in either group , while in all patients bleeding times showed a significant increase above basal values and serum TBX2 decreased ",
"Fifty-one men with atherosclerotic intermittent claudication and haemorheological abnormalities completed a double-blind , one-year r and omised trial of Ticlopidine ( 500 mg/day ) , a new antiplatelet agent . Ticlopidine caused significant inhibition of platelet aggregation but did not fully correct abnormalities of coagulation , viscosity , and fibrinolysis . There was no significant improvement in walking ability , Doppler ankle-pressure indices , or calf blood flow . Sustained platelet inhibition for 12 months was insufficient to correct the prothrombotic abnormality of extensive atherosclerosis",
"BACKGROUND AND METHODS In 359 patients with peripheral arterial occlusive disease who had undergone percutaneous transluminal angioplasty ( PTA ) , a r and omized double-blind , controlled clinical study was done to investigate the tolerability of acetyl salicylic acid ( ASA ) given for reocclusion prophylaxis . A comparison was made between a conventional daily dose of 900 mg ASA and a dose of 50 mg ASA . RESULTS Within an observation period of one year following PTA , 35 patients ( 20 % ) in the 900 mg group , and 32 patients ( 17 % ) in the 50 mg group left the trial because of side effects ( p = NS ) . Under the higher dose , however , severe gastrointestinal side effects ( ulcer , haemorrhagic gastritis requiring transfusion ) were significantly more common ( nine patients delta 5.1 % vs two patients delta 1.1 % , respectively ; p = 0.03 ) . Overall , 107 patients ( 30 % ) reported subjective side effects such as upper abdominal pain , a sensation of fullness or nausea during the course of the trial . 62 of these patients were from the 900 mg group ( 35 % ) as compared with 45 patients ( 24 % ) in the 50 mg group ( p = 0.02 ) . Self-scoring of epigastric pain on the basis of a visual analogue scale revealed a score of 1.3 ( 95 % confidence interval 0.9 to 1.6 ) in the 900 mg group and 0.8 ( 95 % confidence interval 0.6 to 1.0 ) in the 50 mg group . The subjective pain intensity showed a uniform time course for all three types of symptom , with a maximum after three months . CONCLUSION Our results confirm the superior tolerability of the lower dose , in particular in elderly patients . For long-term treatment , the smallest possible effective dose should be chosen",
"This paper evaluates the antiaggregant action of ticlopidine and nifedipine in patients with obliterate arteriopathy in inferior limbs of arteriosclerotic etiology ( OAIL ) . They were established 4 study groups : control , with health volunteers without treatment ( N = 10 ) ; patients treated with placebo ( n = 11 ) ; patients treated with 500 mg/day of ticlopidine ( n = 12 ) and treated with 30 mg/day of nifedipine ( n = 12 ) . The last 3 groups the treatment duration was 30 days . It was studied the platelet aggregatory activity against ADP and collagen , before drug administration and at 15 and 30 days post-treatment . Our results suggest that : Platelet aggregation is increased in patients with AOMI compared with that observed in the control group . Ticlopidine inhibits platelet aggregation induced by ADP , but not that induced by collagen . Nifedipine does n't produce any effect on platelet aggregation",
"This study aims to evaluate the reliability of repeated grade d workload treadmill testing ( G-test ; 2 mph ; 0 % grade , increasing 2 % every 2 min ) and to compare the reliability of a constant workload treadmill protocol ( C-test ; 2 mph ; 12 % grade ) versus the grade d workload treadmill protocol in patients with intermittent claudication , studied longitudinally . A clinical trial investigating an orally stable prostacycline derivative that included 330 patients with intermittent claudication was performed . The trial employed three active treatment groups and one placebo group . Because there were no significant inter-group differences at baseline or after treatment , data from all groups were pooled for the evaluation of treadmill test reliability . Treadmill data were obtained from a 2-week run-in phase where three G-tests were performed , as well as from the beginning and the end of a 3-month double-blind phase where a G-test and a C-test were performed in r and om order . Treadmill test reliability was described through test process-related and between-subject variances and also using variance-derived parameters such as the reliability coefficient ( RC ) and the relative precision ( RP ) . A higher value for the RC and a lower value for the RP indicate that the test variability is predominantly due to between-subject variance and not to test process-related variance . Estimates of variance were described for both the maximal or absolute claudication distance ( ACD ) and the initial claudication distance ( ICD ) with each treadmill test . Reliability estimates are reported for the total study sample and for patients with baseline claudication distances diseased claudicants . Theoretical considerations suggest that reliability measures may differ in these subgroups . With repeated testing during the run-in phase for the measure of ACD , the G-test had an RC of 0.952 and an RP of 21.9 % . With the comparison of both test protocol s in the entire study population for the measurement of ACD , the G-test had an RC of 0.902 and an RP of 31.3 % , while the C-test had an RC of 0.876 and an RP of 35.2 % . The results for ICD on the G-test were an RC of 0.809 and an RP of 43.7 % , while the C-test had an RC of 0.737 and an RP of 51.3 % . The reliability of the ACD measurement for RC and RP was numerically superior to those for the ICD for both protocol s. In patients with a baseline ACD , the RC for ACD on the G-test was 0.827 and the RP was 41.4 % . In contrast , on the C-test the RC decreased to 0.250 and the RP increased to 86.6 % . These changes in RC and RP were due to a marked decrease in the between-subject variance , demonstrating the inability of the C-test to separate appropriately the different claudication distances in population s with highly limited baseline claudication distances . During a run-in phase , the G-test has excellent test characteristics . During the longitudinal phase of a trial , the reliability of G-tests and C-tests are comparable in the entire study population . However , in patients with low claudication distances , the G-test should be given preference over the C-test",
"Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects . The present study was undertaken to compare the effects of policosanol and lovastatin on patients with moderately severe intermittent claudication . The study had a 4-week baseline step , followed by a 20-week double blinded , r and omized treatment period . Twenty-eight patients who met study entry criteria were r and omized to policosanol 10 mg or lovastatin 20 mg tablets once daily . Walking distances in a treadmill ( constant speed 3.2 km/hr , slope 10 ° , temperature 25 ° C ) were assessed before and after 20 weeks of treatment . Both groups were similar at r and om ization . Compared with baseline , policosanol increased significantly ( p the initial claudi cation distance ( ICD ) from 160.39 ±15.82 m to 211.31 ±21.48 m ( + 33.7 % ) and the absolute claudication distance ( ACD ) ( p after lovastatin therapy . Changes in ICD and ACD were significantly larger in the policosanol than in the lovastatin group ( p ) . Policosanol , but not lovastatin , significantly increased ( p , although between-group differences were not significant . The frequency of patients reporting improve ment on quality of life domains was greater in the policosanol than in the lovastatin group . Policosanol significantly ( p by 17.5 % and 31.0 % , respectively , and meanwhile increased ( p levels by 31.5 % . Lovastatin reduced ( p ( 18.0 % ) , LDL-C ( 22.6 % ) , and ( p triglycerides ( 9.8 % ) . In addition , policosanol , but not lovastatin , moderately , but significantly , reduced ( p fibrinogen levels , so that final values and percent changes in both groups were different ( p Only 1 lovastatin patient withdrew from the study because of a nonfatal myocardial infa rct ion . Five lovastatin patients , but none from the policosanol group , experienced 6 adverse events ( AE ) ( p policosanol , but not lovastatin , is a suitable alternative to manage patients with intermittent claudication because of pleiotropic properties beyond its cholesterol-lowering effects",
"In 25 patients ( 19 males and 6 females ) suffering from chronic arteriopathy of lower extremities at Fontaine stage II , the clinical efficacy of picotamide was investigated in double blind , cross over placebo-controlled study . Patients were assigned r and omly to the treatment with placebo or picotamide ( 900 mg/die ) for three months and , after 15 days of wash-out , to the treatment with picotamide or placebo for the same period . Painfree walking distance and ankle/arm systolic pressure ratio improved significantly only during picotamide treatment . Laboratory monitoring revealed a significant decrease in platelet aggregation and an increase of fibrinogen degradation products only during picotamide treatment . Three patients during picotamide treatment referred transient gastrointestinal discomfort ( nausea , vomiting and diarrhoea ) ; however in no case the treatment was suspended because of the appearance of these symptoms . These results indicate that picotamide is an effective drug in the management of chronic arteriopathy of lower extremities",
"Many clinical trials have shown the effectiveness of platelet-antiaggregant drugs in the treatment of obliterative peripheral arteriopathy , both locally and in the system , by improving the claudication symptoms and by preventing major cardiovascular events . In this study we evaluated the effectiveness of a 24-week treatment with triflusal , a comparatively new inhibitor of platelet aggregation , in patients affected by chronic peripheral arteriopathy , comparing twice-daily oral doses of 300 mg triflusal with twice-daily placebo doses . The percentages of successes ( defined as a 40 % increase of total walking distance over the basal control ) were 63.6 % in the triflusal group ( 35/55 patients ) and 22.5 % in the placebo group ( 14/62 patients ) . Patients treated with triflusal showed a more important increase in total walking distance and in pain-free walking distance over the basal values than those treated with placebo , together with an improvement of the symptomatology correlated with claudication . Moreover , in the triflusal group there was an increase in the peak-flow recorded through strain-gauge plethysmography . In conclusion , triflusal significantly increased both the distance which could be walked and the clinical symptoms , presumably by improving microperfusion",
"BACKGROUND Atherosclerotic peripheral arterial disease is associated with an increased risk of myocardial infa rct ion , stroke , and death from cardiovascular causes . Antiplatelet drugs reduce this risk , but the role of oral anticoagulant agents in the prevention of cardiovascular complications in patients with peripheral arterial disease is unclear . METHODS We assigned patients with peripheral arterial disease to combination therapy with an antiplatelet agent and an oral anticoagulant agent ( target international normalized ratio [ INR ] , 2.0 to 3.0 ) or to antiplatelet therapy alone . The first co primary outcome was myocardial infa rct ion , stroke , or death from cardiovascular causes ; the second co primary outcome was myocardial infa rct ion , stroke , severe ischemia of the peripheral or coronary arteries leading to urgent intervention , or death from cardiovascular causes . RESULTS A total of 2161 patients were r and omly assigned to therapy . The mean follow-up time was 35 months . Myocardial infa rct ion , stroke , or death from cardiovascular causes occurred in 132 of 1080 patients receiving combination therapy ( 12.2 % ) and in 144 of 1081 patients receiving antiplatelet therapy alone ( 13.3 % ) ( relative risk , 0.92 ; 95 % confidence interval [ CI ] , 0.73 to 1.16 ; P=0.48 ) . Myocardial infa rct ion , stroke , severe ischemia , or death from cardiovascular causes occurred in 172 patients receiving combination therapy ( 15.9 % ) as compared with 188 patients receiving antiplatelet therapy alone ( 17.4 % ) ( relative risk , 0.91 ; 95 % CI , 0.74 to 1.12 ; P=0.37 ) . Life-threatening bleeding occurred in 43 patients receiving combination therapy ( 4.0 % ) as compared with 13 patients receiving antiplatelet therapy alone ( 1.2 % ) ( relative risk , 3.41 ; 95 % CI , 1.84 to 6.35 ; P patients with peripheral arterial disease , the combination of an oral anticoagulant and antiplatelet therapy was not more effective than antiplatelet therapy alone in preventing major cardiovascular complications and was associated with an increase in life-threatening bleeding . ( Clinical Trials.gov number , NCT00125671 [ Clinical Trials.gov ] . )",
"PURPOSE Patients with lower-extremity peripheral arterial disease ( PAD ) face a high risk of cardiovascular morbidity and mortality . Platelet inhibition ( PI ) significantly reduces this risk . Combination PI is common and increasingly indicated in patients with PAD ; however , the effect on platelet function has not been objective ly evaluated . Aspirin ( ASA ) , clopidogrel ( Clop ) , and cilostazol ( Cilo ) are the three most commonly used PI drugs in patients with PAD . A prospect i ve , sequential evaluation of platelet function using the template bleeding time ( BT ) was performed for PAD patients taking these medications singly and in combination . METHODS Twenty-one patients with PAD , averaging 65.9 years of age , were studied . Patients were placed on sequential two-week regimens of the following therapies : washout ( no PI ) , ASA ( 325 mg daily ) , ASA + Cilo ( 100 mg twice daily ) , washout , Cilo , Cilo + Clop ( 75 mg each day ) , washout , Clop , Clop + ASA , and Clop + ASA + Cilo . At the end of each phase , trained personnel measured the BT . RESULTS Baseline bleeding time for the group was 4.29 + /- 1.69 minutes . ASA ( BT = 6.64 + /- 3.52 ) and Clop ( BT = 10.17 + /- 5.4 ) significantly prolonged bleeding time ( P ASA + Clop ( BT = 17.39 + /- 4.59 ) had a more pronounced effect on BT compared with either agent alone ( P of ASA + Clop ( BT = 17.92 + /- 4.69 ) did not prolong BT . CONCLUSION All patients with PAD require platelet inhibition , and many require pharmacotherapy for intermittent claudication . The platelet inhibitors aspirin and clopidogrel are used for the reduction of ischemic events . They significantly prolong bleeding time individually and to a greater extent in combination . Cilo is used to improve walking distance in patients with intermittent claudication . When Cilo is added to ASA , Clop , or the combination of the two , there is no additional increase in bleeding time . Therefore , Cilo can be used in combination with other platelet inhibitors without an additional effect on platelet function as reflected by the bleeding time",
"In this multicenter trial 169 patients with chronic intermittent claudication due to obstructive peripheral vascular disease were r and omized in a double- blind fashion into two parallel groups receiving either 250 mg ticlopidine or placebo , twice daily . At entry , the two groups ( 83 ticlopidine , 86 placebo ) were well matched for the major clinical features apart from an excess of women in the ticlopidine group . At six months , 167 patients were alive , 2 having died of malignant disease ( 1 from each group ) . At this stage , 39 patients from the ticlo pidine group and 29 from the placebo group ( p = 0.04 ) had increased their walking distance by more than 50 % of baseline values . For the groups as a whole pain-free and total walking distance were greater in the ticlopidine group than in the placebo group ( 194 vs 124 meters , p = 0.03 and 236 vs 170 meters , p = 0.04 , respectively ) . Two patients from the ticlopidine group vs 9 patients from the placebo group ( p = 0.03 ) developed significant cardiovascular events during the study . These results indicate that ticlopidine has a beneficial effect both in the treatment of the symptoms and the prevention of vascular complica tions in patients with intermittent claudication",
"Percutaneous transluminal angioplasty of aortoiliac and femoropopliteal atherosclerotic lesions can provide long-lasting hemodynamic improvement . High-dose aspirin is commonly prescribed as reocclusion prophylaxis , but low doses would be preferable because of fewer adverse effects . We performed a double-blind , r and omized , controlled clinical trial in patients with peripheral vascular disease with lesions appropriate for angioplasty . We compared the efficacy and side effects of two doses of aspirin ( 50 mg vs. 900 mg daily ) during a period of 12 months after angioplasty . A total of 359 patients were evaluated : 175 were r and omly assigned to treatment with 900 mg aspirin daily and 184 to 50 mg aspirin a day . Thirty-nine patients developed restenosis at the angioplasty site ; the cumulative percentage of event-free survival after 1 year ( patency rate ) was 85 % in the 900-mg group and 84 % in the 50-mg group . An equivalence test showed the two groups equivalent with respect to restenosis rates ( P = 0.003 for an equivalence region of serious gastrointestinal side effects ( peptic ulcer , eight ; erosive gastritis requiring transfusion , one ) compared to two ( peptic ulcer ) in the 50-mg group ( P = 0.03 ) . The results of our study show that a dose of 50 mg aspirin a day is as effective as one of 900 mg for the prevention of restenoses after lower limb angioplasty , and that severe gastrointestinal side effects are less frequent",
"Aim of our study was to evaluate the effectiveness of indobufen in the treatment of II degree stage lower limb occlusive arterial disease . Forty patients were r and omly assigned to the iIndobufen ( 400 mg/die ) treatment group or the no treatment control group ( 20 patients each ) . Doppler pressure measurement ( Winsor index ) and subjective symptomatology were evaluated at the time of enrollment and after one month . A significant improvement ( p less than 0.01 ) was noted only in the treated group . We conclude that indobufen may be of therapeutic value in the treatment of peripheral occlusive arterial disease",
"In a r and omized double-blind crossover study in 12 patients with atherosclerotic disease , the effect of 2 dosages ( 100 and 200 mg twice daily ) of indobufen , a new synthetic inhibition of platelet aggregation , on some platelet functions , coagulation and fibrinolysis tests was investigated . Regardless of the dosage used , indobufen was shown to induce a prompt normalization of the enhanced platelet aggregation of these patients . The effect lasted for the entire period of drug administration and in 50 % of patients a normal platelet aggregation was maintained until the fourth day after discontinuation of the drug . Indobufen was also able to reduce platelet adhesiveness and to lengthen bleeding time , especially when the higher dosage was used",
"The objective of the study was to evaluate the efficacy and safety of indobufen compared with placebo in the treatment of moderately severe intermittent claudication . The study consisted of a four-week single-blind , placebo-controlled run-in phase , followed by a six-month double-blind r and omized treatment period . A total of 302 patients were allocated to treatment with either placebo ( 154 patients ) or indobufen ( 148 ) 200 mg twice daily . The results of the overall intention-to-treat analysis of the study population showed statistically significant superiority of indobufen over placebo after six months for both the initial ( ICD ) and absolute claudication distances ( ACD ) . The ICD before treatment with indobufen or placebo averaged 137.9 + /- 68.2 and 136.6 + /- 63.2 m ( mean + /- SD ) , respectively . After six months ' treatment with active drug or placebo , this parameter reached 227.9 + /- 174.4 and 153.1 + /- 86.8 m ( mean + /- SD ) , respectively ( p ACD . The reduction of lower limb symptoms also suggested a greater clinical benefit in the indobufen-treated patients . There was no significant change in either group in the ankle/arm pressure ratio at the end of treatment . Adverse events of any type were reported by 18 patients ( 12.2 % ) in the indobufen group and by 11 patients ( 7.2 % ) in the placebo group . The mechanism whereby the drug is effective in this clinical condition could be related to both its antiplatelet and hemorheologic effects",
"OBJECTIVE To determine the fatal and non-fatal cardiovascular event rate in patients with intermittent claudication treated with antiplatelet agents . METHODS AND DESIGN Patients with PAD-II stage Fontaine ( n=223 ) and sex and age matched controls ( n=446 ) were followed up from 1974 to 1998 . All patients were treated with antiplatelet agents ( aspirin , 325 mg once daily or ticlopidine , 250 mg twice daily ) and for risk factors , if present . The end points were death for any cause ( vascular event , cancer , and others ) and non-fatal vascular events ( myocardial infa rct ion , ischemic/hemorrhagic stroke , and leg amputation ) . RESULTS PAD patients had a significantly higher mortality rate than controls ( 3.99 vs. 2.53 deaths for 100 patients per year , respectively ) , cancer ( mostly lung , stomach and colon ) and vascular mortality accounted for such difference . The incidence of non-fatal vascular events was three times higher in patients than in controls ( 1.7 vs. 0.56 , 100 patients per year , respectively , p Vascular mortality and morbidity , despite the use of antiplatelet agents , are still higher than sex and age matched controls ; however , the commonest cause of death is cancer",
"BACKGROUND The manifestations of atherothrombosis such as myocardial infa rct ion , ischemic stroke , limb ischemia , or cardiovascular death pose a global health care burden . Additional therapies to decrease ischemic events in patients with established vascular disease or at risk for developing vascular disease are necessary . We sought to characterize the risk factors and treatments of a diverse contemporary population of patients with atherothrombosis . METHODS The CHARISMA trial has enrolled 15,603 patients from around the world . Patients with established coronary , cerebrovascular , or peripheral arterial disease , or those at high risk of developing atherothrombosis due to multiple risk factors , have been r and omized to receive either the adenosine diphosphate receptor antagonist clopidogrel or placebo , in addition to background therapy with low- to moderate-dose aspirin . RESULTS A high percentage of enrolled patients are being treated with statins and angiotensin-converting enzyme inhibitors . In the CHARISMA population , a total of 75.6 % of the population had an abnormal body mass index : 42.2 % were overweight and 33.4 % were obese , with particularly high rates in the United States , especially of morbid obesity . Correspondingly , the prevalence of diabetes was 42 % . CONCLUSION The CHARISMA trial will further characterize atherothrombosis and provide insight into the role of dual antiplatelet therapy in improving outcomes in patients with multiple risk factors or established vascular disease . Of note , the rates of obesity and diabetes in patients with atherothrombosis throughout the world are particularly alarming",
"BACKGROUND Previous investigators have observed a doubling of the mortality rate among patients with intermittent claudication , and we have reported a fourfold increase in the overall mortality rate among subjects with large-vessel peripheral arterial disease , as diagnosed by noninvasive testing . In this study , we investigated the association of large-vessel peripheral arterial disease with rates of mortality from all cardiovascular diseases and from coronary heart disease . METHODS We examined 565 men and women ( average age , 66 years ) for the presence of large-vessel peripheral arterial disease by means of two noninvasive techniques -- measurement of segmental blood pressure and determination of flow velocity by Doppler ultrasound . We identified 67 subjects with the disease ( 11.9 percent ) , whom we followed prospect ively for 10 years . RESULTS Twenty-one of the 34 men ( 61.8 percent ) and 11 of the 33 women ( 33.3 percent ) with large-vessel peripheral arterial disease died during follow-up , as compared with 31 of the 183 men ( 16.9 percent ) and 26 of the 225 women ( 11.6 percent ) without evidence of peripheral arterial disease . After multivariate adjustment for age , sex , and other risk factors for cardiovascular disease , the relative risk of dying among subjects with large-vessel peripheral arterial disease as compared with those with no evidence of such disease was 3.1 ( 95 percent confidence interval , 1.9 to 4.9 ) for deaths from all causes , 5.9 ( 95 percent confidence interval , 3.0 to 11.4 ) for all deaths from cardiovascular disease , and 6.6 ( 95 percent confidence interval , 2.9 to 14.9 ) for deaths from coronary heart disease . The relative risk of death from causes other than cardiovascular disease was not significantly increased among the subjects with large-vessel peripheral arterial disease . After the exclusion of subjects who had a history of cardiovascular disease at base line , the relative risks among those with large-vessel peripheral arterial disease remained significantly elevated . Additional analyses revealed a 15-fold increase in rates of mortality due to cardiovascular disease and coronary heart disease among subjects with large-vessel peripheral arterial disease that was both severe and symptomatic . CONCLUSIONS Patients with large-vessel peripheral arterial disease have a high risk of death from cardiovascular causes",
"Intermittent claudication impairs functional status and quality of life in many patients by limiting walking capacity . The aim of this study was to evaluate the effects of a 4-week treatment with prostagl and in E1 ( PGE1 ) , a drug inducing vasodilation and inhibiting platelet aggregation , on improving functional status and health-related quality of life in patients with disabling intermittent claudication . Forty-two untrained out patients ( 37 men and five women , mean age 64 ±8 years ) with intermittent claudication , and maximum walking distance ( MWD ) of at least 50 and no more than 200 m on treadmill test ( 5 % slope , 3 km/hr ) were r and omized to 4 weeks of double-blind treatment either with 60 mcg PGE1 daily given IV in 250 mL saline over a period of 2 hours ( 21 patients ) or placebo ( 250 mL saline , 21 patients ) . Treatment-free follow-up was completed 8 weeks after the final infusion . Pain free walking distance ( PFWD ) , MWD , and question naire evaluation were determined at baseline , after the 4-week treatment period , and at the end of the 8 weeks of the treatment-free follow-up period . After 4 weeks of treatment with PGE1 PFWD and MWD increased from 72 ±16 m to 135 ±33 m ( + 87 % , p the Walking Impairment Question naire responses in the PGE1 group at 4 weeks demonstrated significant improvements in the walking impairment score ( + 19 percentage points , p score ( + 24 percentage points , p score ( + 20 percentage points , p showed improvements in physical function and bodily pain scores ( + 14 percentage points , p weeks , increases in PFWD and MWD were maintained ( 113 ±26 m , + 57 % , p the walking impairment score ( + 16 percentage points , p the distance score ( + 23 percentage points , p , the speed score ( + 22 percentage points , p , the stair climbing score ( + 18 percentage points , p the R AND physical function and bodily pain scores ( + 10 percentage points , p change from baseline was found in all the target parameters in the placebo group after 4 weeks of treatment and at the end of the treatment-free follow-up period . These data show that a 4-week treatment with PGE1 improves functional status and quality of life as well as treadmill performance in patients with disabling intermittent claudication as compared with placebo-treated patients . The improvements are also maintained for a period of 8 weeks beyond the end of the treatment . Additional studies are needed to determine the duration of functional benefits after the end of treatment",
"The clinical efficacy of picotamide was investigated in a r and omized , double- blind , placebo-controlled study in patients with peripheral occlusive arterial disease of the lower limbs at functional stage II of the Fontaine classification . Forty patients with a history of claudication for at least six months were admit ted to the study and were given either 3 x 300 mg tablets of picotamide ( 20 subjects ) or three identical placebo tablets ( 20 subjects ) for six months . The two groups of patients were similar in regard to clinical features and potential risk factors . At the end of treatment painfree walking distance and systolic ankle-arm pressure ratio improved more in the picotamide than in the placebo group ( p=0.05 ) . Systolic ankle pressure curves , determined before and after the six- month treatment , showed a positive trend to a higher postexercise ankle pres sure and a faster return to the preexercise levels in the picotamide group ; however , the difference was not statistically significant . Laboratory monitoring revealed a slight prolongation of bleeding time , a significant decrease in arachi donic acid-induced platelet aggregation , and an enhanced fibrinolysis with ab sence of interference with hemostasis in the picotamide group . One patient in the placebo group developed a major cardiovascular event ( angina pectoris ) during the study . These results indicate that picotamide is an effective drug that may modify the natural course of intermittent claudication and associated vascular prob lems",
"The relationship between risk factors and the onset of cardiovascular events was analyzed in patients suffering from peripheral obstructive arterial disease . One thous and and eleven patients were recruited in 120 Italian centers and participated in a clinical trial on picotamide ( A.D.E.P. study ) , whose results have been previously reported . Patients were followed-up for 18 months and cardiovascular events were recorded . Hypertension ( 35 % ) , smoking ( 34 % ) , and diabetes ( 19 % ) were the most common risk factors at baseline . During the follow-up period , 246 patients ( 11.7 % ) had a cardiovascular event , mainly affecting cerebral , cardiac or peripheral circulation . Thirty-five of these events ( 14.2 % ) were fatal . A logistic regression analysis showed in general that hypertension ( odds ratio 1.48 ) , an ankle arm pressure ratio lower than 0.8 ( odds ratio 1.42 ) , smoking ( odds ratio 1.43 ) , previous vascular surgery ( odds ratio 1.35 ) , high white blood cell ( WBC ) count ( odds ratio 1.15 for a difference of 2.0 x 10(9 ) WBC/1 ) and plasma fibrinogen ( odds ratio 1.16 for a difference of 1.05 g/l ) were significantly associated with a higher incidence of cardiovascular events . In particular , deaths of any origin were more frequent in patients with an ankle/arm pressure ratio below 0.8 . High plasma fibrinogen increased the risk of cerebrovascular events , hypertension or coronary heart events and , to a less evident extent , peripheral vascular complications and cerebrovascular events . A history of vascular surgery increased the risk of peripheral vascular complications . Both smoking and a high WBC count showed to be borderline significant risk factors for coronary heart events and the former also for peripheral vascular complications . In male patients ( 84 % ) , ankle/arm pressure ratio lower than 0.8 , high fibrinogen and hypertension were the most important factors for cardiovascular events . This study helps to identify some categories at higher risk of cardiovascular events among patients with peripheral obstructive arterial disease ; this finding is useful to plan future trials to decrease the frequency of such complications",
"Aims : In humans , little is known about the effects of platelet – leucocyte interactions on blood viscosity and microvascular perfusion . This study tested the hypotheses that ( 1 ) activation and interactions between platelets and leucocytes may have an impact on microvascular blood viscosity and perfusion in patients with stage II peripheral arterial occlusive disease , and ( 2 ) a powerful antiplatelet drug such as Clopidogrel might help to improve microvascular perfusion by reducing platelet – leucocyte activation and blood viscosity . Methods : Plasma concentrations of certain markers of leucocyte and platelet activation , in addition to low and high shear rate blood viscosity , were measured before and after a repeated exercise treadmill test . Functional parameters including maximum walking time , transcutaneous oxygen pressure , and half recovery time were also measured . Results : Blocking platelet activation only with a single dose of Clopidogrel ( 300 mg ) did not improve microvascular blood viscosity and perfusion after repeated exercise , but a significant improvement in microvascular perfusion during controlled ischaemia and a lack of post exercise increase in low shear rate blood viscosity was achieved when both platelet and leucocyte activation were suppressed by a relatively longer treatment with Clopidogrel ( four days ) . Conclusions : Clopidogrel , by inhibiting platelet activation and aggregation , might also block the vicious cycle of leucocyte – platelet activation , thus improving the functioning of the microcirculation",
"240 patients were admitted to a double-blind study to determine the effect of long-term treatment with platelet-function inhibiting agents on occlusive arterial disease in the lower extremities . Patients were r and omised into 1 of 3 treatment groups : aspirin 330 mg ; dipyridamole 75 mg and aspirin 330 mg ; or matching placebo 3 times daily . The duration of treatment was 2 years . Arteriography was carried out at the beginning of the study and 2 years later or before if deterioration was observed . 199 patients completed the study according to the trial protocol . The serial arteriograms were assessed in pairs qualitatively , by means of simple comparative viewing , and semiquantitatively with Bollinger 's score system . Progression of the disease was most pronounced in the placebo-treated group , less so in the aspirin-treated group , and least of all in the dipyridamole- and -aspirin group . Patients who smoke and those with hypertension may benefit most from treatment with the 2 preparations under investigation",
"This study was undertaken to evaluate the efficacy and tolerability of policosanol , a new cholesterol-lowering drug with concomitant antiplatelet effects , in patients with inter mittent claudication . After a baseline period of 6 weeks , 62 patients were r and omized to receive , under double-blind conditions , either placebo ( 31 patients ) or policosanol ( 31 ) , 10 mg twice daily . Walking distances in a treadmill ( constant speed 3.2 km/hr , slope 10 ° ) were assessed before and after 6 months of treatment . Both groups were similar at r and omization . Policosanol increased significantly ( p the initial claudication distance from 132.5 ±13.5 m ( baseline ) to 205.7 ±36.3 m ( after therapy ) and the absolute claudication distance ( p The reduction of lower limb symptoms showed a greater benefit in the policosanol group . There was no significant change in either group in the ankle/arm pressure ratio . The treatment was well tolerated . There were 10 discontinuations ( seven placebo , three poli- cosanol ) from the study . Six withdrawals occurred because of adverse events ( AE ) ; all were in placebo patients . There were five serious vascular AEs in the placebo group but none in the policosanol group ( p % ) placebo patients and 3/31 ( 9.7 % ) policosanol patients experienced AEs after r and omization , which showed a lesser incidence of AEs in the policosanol group ( p beneficial effect of policosanol in patients with intermittent claudication",
"Acute peripheral arterial occlusive disease is an important factor affecting the mobility and mortality rate of elderly patients . Catheter-guided arterial thrombolysis in these patients has its limitations : long lysis times , early occlusions , and high restenosis rates . The study investi gated whether the use of tirofiban has the same favorable effect as the glycoprotein ( GP ) IIb/IIIa receptor antagonist abciximab and whether lysis times can be shortened and the disease course positively influenced by these substances . Sixty patients were r and omly assigned to 2 groups . Each group received 5 mg recombinant tissue-type ( rt-PA ) plasminogen activator by slow intra-arterial injection for 10 minutes followed by 5 mg rt-PA per hour and 500 IU heparin per hour IV . After r and omization 1 group received a bolus of 0.25 mg abciximab per kg body weight followed by 10 mg per minute IV for 12 hours ( heparin was reduced to 250 IU/hr ) . The other group received a bolus of 0.4 μg tirofiban per kg body weight as well as postinterventional medication with 0.1 μg tirofiban per minute and kg body weight for 24 hours . During medication with GP IIb/IIIa inhibitor , the patients received a reduced heparin dosage for 24 hours . After 24 hours both groups received 200 mg aspirin orally and full heparinization controlled on the basis of the partial thromboplastin time . The following efficacy criteria were analyzed : rehospitalization events , reintervention events , and amputations within 6 months . Secondary endpoints were changes in the Fontaine stage , the crurobrachial index , the distance to claudication , and the duration of local arterial lysis . No significant differences were found between the abciximab and tirofiban groups in terms of the rehospitalization , rein tervention , or amputation rates , nor were there any group differences in the total number of events . The secondary parameters , such as the crurobrachial index , distance to claudication , and Fontaine stage , also showed no significant differences between the 2 groups within 6 months . The duration of lysis was significantly shorter in the abciximab group . Major bleeding events did not occur in either group . With regard to the adverse effect rate , there were no significant differences between the 2 groups . Both abciximab and tirofiban can be used successfully in patients with peripheral arterial occlusive disease and arterial thrombosis",
"CONTEXT A low ankle brachial index ( ABI ) indicates atherosclerosis and an increased risk of cardiovascular and cerebrovascular events . Screening for a low ABI can identify an asymptomatic higher risk group potentially amenable to preventive treatments . OBJECTIVE To determine the effectiveness of aspirin in preventing events in people with a low ABI identified on screening the general population . DESIGN , SETTING , AND PARTICIPANTS The Aspirin for Asymptomatic Atherosclerosis trial was an intention-to-treat double-blind r and omized controlled trial conducted from April 1998 to October 2008 , involving 28,980 men and women aged 50 to 75 years living in central Scotl and , free of clinical cardiovascular disease , recruited from a community health registry , and had an ABI screening test . Of those , 3350 with a low ABI ( , which was powered to detect a 25 % proportional risk reduction in events . INTERVENTIONS Once daily 100 mg aspirin ( enteric coated ) or placebo . MAIN OUTCOME MEASURES The primary end point was a composite of initial fatal or nonfatal coronary event or stroke or revascularization . Two secondary end points were ( 1 ) all initial vascular events defined as a composite of a primary end point event or angina , intermittent claudication , or transient ischemic attack ; and ( 2 ) all-cause mortality . RESULTS After a mean ( SD ) follow-up of 8.2 ( 1.6 ) years , 357 participants had a primary end point event ( 13.5 per 1000 person-years , 95 % confidence interval [ CI ] , 12.2 - 15.0 ) . No statistically significant difference was found between groups ( 13.7 events per 1000 person-years in the aspirin group vs 13.3 in the placebo group ; hazard ratio [ HR ] , 1.03 ; 95 % CI , 0.84 - 1.27 ) . A vascular event comprising the secondary end point occurred in 578 participants ( 22.8 per 1000 person-years ; 95 % CI , 21.0 - 24.8 ) and no statistically significant difference between groups ( 22.8 events per 1000 person-years in the aspirin group vs 22.9 in the placebo group ; HR , 1.00 ; 95 % CI , 0.85 - 1.17 ) . There was no significant difference in all-cause mortality between groups ( 176 vs 186 deaths , respectively ; HR , 0.95 ; 95 % CI , 0.77 - 1.16 ) . An initial event of major hemorrhage requiring admission to hospital occurred in 34 participants ( 2.5 per 1000 person-years ) in the aspirin group and 20 ( 1.5 per 1000 person-years ) in the placebo group ( HR , 1.71 ; 95 % CI , 0.99 - 2.97 ) . CONCLUSION Among participants without clinical cardiovascular disease , identified with a low ABI based on screening a general population , the administration of aspirin compared with placebo did not result in a significant reduction in vascular events . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N66587262",
"Ticlopidine ( Ticlodone : CAS 55142 - 85 - 3 ) is able to develop a positive effect on claudication in patients affected by peripheral atherosclerotic disease ( PAD ) . It is also known that ticlopidine decreases fibrinogen levels in plasma . 15 PAD patients treated with ticlopidine for 3 months were studied , evaluating the drug 's effect both on maximum walking distance and on fibrinogen . Plasma fibrinogen as coagulable protein , fibrinogen antigen ( Partigen method ) , 125I-fibrinogen survival , euglobulin lysis time and plasminogen were determined with the aim of clarifying if the decrease of plasma fibrinogen induced by ticlopidine is due to an increased destruction of a decreased production of the molecule . The normal levels of all tests before and after therapy both in ticlopidine treated patients and in the control group ( acetylsalicylic acid + dipyridamol ) indicate that the two hypotheses are not true . It is proposed that ticlopidine developing the known effect in decreasing the binding of fibrinogen to platelets induces a decrease only of activated fibrinogen",
" 20 male patients from 44 to 61 years of age with arteriosclerotic disturbances of the blood supply of the legs ( stage II after Fontaine ) were in the cross-over treated with 3 x 200 mg trapidil or 3 x 200 mg pentoxifylline daily . The duration of the therapy was in each case 6 weeks with a one-week elutriation phase . Statistically ascertained was an increase of the distance of intermittent claudication for the two drugs in patients with initial values lower than 550 m. On the other h and the tibio-brachial Doppler quotient and the submaximal blood supply established by the venous-occlusion plethysmography did not change . The post-ischaemic recovery phase of the transcutaneous oxygen partial pressure at the lower leg shortened in particular under the influence of trapidil . Lipid parameter , haematocrit , fibrinogen and plasma viscosity remained unchanged . The subjective tolerance of the two remedies was good",
"BACKGROUND This paper introduces a proof-of-concept trial in progress , supposedly providing new important information on anti-platelet drugs used in patients with peripheral arterial disease ( PAD ) . The Arteriogenesis Competence Network ( Art . Net . ) of the Universities of Basel , Berlin , and Freiburg could show in animal models that Aspirin ( ASA ) , in contrast to Clopidogrel , inhibits the formation of an appropriate collateral network ( arteriogenesis ) . This trial is supposed to reproduce the animal data in man . MATERIAL S AND METHODS In a prospect i ve , double-blind , parallel-group , bi-national ( D , CH ) , multicentre trial , 250 patients will be r and omised to either 100 mg ASA or 75 mg Clopidogrel once daily . Patients will then enter a three months structured rehabilitation programme with daily physical training supposed to induce arteriogenesis . The claudication distances will be tested as the primary endpoint at baseline , 6 weeks , and at 3 months . Also , the 24h physical activity profile of all patients will be electronically documented . CONCLUSIONS This trial will provide information on potential disadvantages when using ASA in PAD patients . If data emerging from animal pharmacology can be reproduced in man , the present st and ard scheme of anti-aggregant treatment in PAD patients has to be reconsidered",
"OBJECTIVE To study the effect of long-term treatment of the platelet inhibitor ticlopidine as secondary prevention against the need of vascular surgery in patients with intermittent claudication . DESIGN The Swedish Ticlopidine Multicentre Study ( STIMS ) , was conducted in six medical and surgical clinics of university hospitals in Sweden . METHODS 687 claudicants were r and omised to ticlopidine 250 mg bd or placebo and vascular surgery events were recorded prospect ively over a 7-year period . Cox proportional hazards models of risk for leg vascular surgery were constructed using drug treatment and 11 putative risk factors for vascular disease as covariates . Surgical event-free survivals were compared by Kaplan-Meier analysis . RESULTS The overall rate of first operations was 2.4 % per annum . More than half of these operations were in the aortoiliac region . One-quarter of patients operated during the period required further operations but amputation was rare . Ticlopidine treatment reduced the need for vascular reconstructive surgery by about half , both in intention-to-treat and on-treatment analyses ( unadjusted relative risks 0.486 , 95 % CI 0.317 - 0.745 ; p Previous peripheral arterial surgery was the strongest predictor of the need for surgery . None of the risk factors examined interacted statistically with the effect of treatment with ticlopidine . CONCLUSION In patients with intermittent claudication it seems possible to prevent the need for future vascular surgery by the use of platelet inhibition with ticlopidine",
"This was a multinational , multicentre , double-blind Phase II study in Europe to evaluate the efficacy and safety of two dose regimens ( 200 mg bid and 200 mg tid ) of sarpogrelate ( MCI-9042 , 5-HT2A receptor antagonist ) compared to placebo in patients with stable , moderately severe intermittent claudication . Following a single-blind placebo run-in period of 6 weeks , 364 ( 309 male and 55 female ) patients ( 59.2 ± 8.4 years , mean SD ) were r and omized to receive sarpogrelate 200 mg bid , 200 mg tid or placebo for 24 weeks with a follow-up of 8 weeks . The primary objective was the increase of absolute claudication distance ( ACD ) at the end of treatment ( week 24 ) compared to placebo . Analysis of covariance ( ANCOVA ) was performed on the log-transformed percentage of baseline ACD : loge ( ACD/baseline ) . A responder analysis ( defined as a 50 % improvement in ACD ) was also performed . There was a marked training/placebo effect on the ACD which persisted up to 16 weeks . At 24 weeks the primary objective did not reach statistical significance ( 200 mg bid vs placebo , p = 0.225 ; 200 mg tid vs placebo , p = 0.580 ) . In the responder analysis , 200 mg bid showed a statistically significant difference vs placebo ( p = 0.035 ) . In the exploratory analysis with completers ( patients completing all treadmill tests ) , there was a statistical difference in ACD/baseline change for 200 mg bid ( p = 0.035 ) and in the responder analysis for 200 mg tid ( p = 0.044 ) at 24 weeks compared to placebo . Both treatments showed a carry-over effect for ACD during the 8-week follow-up ( weeks 28 - 32 ) . The treatment was well tolerated and no clinical ly significant safety concerns were reported . In conclusion , the study results confirm that sarpogrelate is well tolerated and although the primary endpoint failed to reach statistical significance , the responder analysis showed an increased absolute walking distance , which makes a further trial warranted , including a larger population , and possibly also a longer treatment period",
"The mortality in patients with intermittent claudication can be reduced by treatment with ticlopidine . This is the clinical ly most significant result from STIMS , the Swedish Ticlopidine Multicenter Study . During an average treatment period of 5.6 years , 153 of the 687 patients died , 26.1 % in the placebo group and 18.5 % in the ticlopidine group ( RR0.7 , p=0.015 ) . The incidence of fatal vascular events in the two groups was 12 % and 6 % . In terms of lives saved per years of treatment , STIMS showed that by treating 200 claudicants for 5 years one can save 13 from a cardiovascular death , not merely dying from something else as treatment was associated with a reduced total mortality as well . The interpretation of the on-treatment analysis is that for those who tolerate the drug the combined vascular morbidity and mortality rate is lowered from 24 % to 14 % . The disadvantage is that many patients do not tolerate ticlopidine . In STIMS , 22 % ( 2.5 times as many as in the control group ) had to stop medication because of gastrointestinal side-effects . Although ticlopidine is associated with an increased risk of leukopenia , the risk in absolute numbers is small : according to STIMS , 4 % during 5.6 years . All events were reversible . The 1.4 % incidence of thrombocytopenia did not seem to be associated with ticlopidine treatment",
"Background Patients with peripheral vascular disease ( PVD ) undergo a clinical course that can be complicated by cardiovascular events occurring in several areas of the circulation . Methods and Results In the present study we investigated the ability of picotamide , a substance that inhibits platelet thromboxane A2 ( TxA2 ) synthase and antagonizes TxA2 receptors , to reduce cardiovascular complications in PVD patients . The study was double blind and placebo controlled . After a 1-month run-in period , 2,304 patients were r and omly allocated to either placebo or picotamide ( 300 mg t.i.d . ) and followed for 18 months . Major and minor events were analyzed . Results of an “ intention-to-treat analysis ” were that patients on picotamide suffered 45 major events ( 3.9 % ) and 77 minor events ( 6.7 % ) , whereas those taking placebo suffered 52 major ( 4.5 % ) and 99 minor events ( 8.6 % ) . There was borderline statistical difference between the two groups with respect to the sum of the major and minor events ( risk reduction , 18.9o ; p=0.056 , log-rank test ) . Results of an “ on-treatment ” analysis were that patients on picotamide suffered 40 major ( 3.8 % ) and 66 minor events ( 6.3 % ) , whereas those taking placebo suffered 45 major ( 4.2 % ) and 95 minor events ( 8.9%o ) . The sum of both major and minor events was 106 ( 10.1 % ) in the picotamide group and 140 ( 13.1 % ) in the placebo group . This difference was significant ( risk reduction , 23 % ; p=0.029 , log-rank test ) . Conclusions The results of this study indicate that picotamide reduces cardiovascular complications in PVD patients . The apparently low effect of this drug in reducing major events suggests that further studies be made with picotamide in PVD patients who are at high risk of cardiovascular complications so as to further assess its clinical efficacy",
"The efficacy of physical training alone or combined with antiplatelet thera py ( dipyridamole and aspirin ) was studied in 30 patients with stage II peripheral arterial occlusive disease ( PAOD ) . Patients were r and omly allocated to one of the following groups : Group A— dipyridamole 75 mg three times daily and aspirin 330 mg once daily : Group B— physical exercise ; Group C — physical exercise and dipyridamole 75 mg three time daily and aspirin 330 mg once daily . After six months ' treatment the pain-free walking time ( PFWT ) and the max imum walking time ( MWT ) improved significantly ( p PFWT lengthened by 35 % ( from 101.00 ± 34.56 to 137.32 ± 40.50 s ) and the MWT by 38 % ( from 150.34 ± 55.60 to 207.26 ± 60.67 s ) ; in group B the PFWT lengthened by 90 % ( from 90.65 ± 40.54 to 171.45 ± 55.60 s ) and the MWT by 86 % ( from 145.39 ± 60.50 to 270.63 ± 63.61 s ) . When physical exer cise was associated with drugs as in group C , the PFWT lengthened by 120 % ( from 89.51 ± 43.89 to 196.72 ±51.73 s ) and the MWT by 105 % ( from 160.43 ± 59.84 to 329.05 ± 63.96 s ) . No significant variations were observed at any stage of the study in the ankle/arm pressure ratio at rest and after st and ard treadmill exercise , in the plethysmographic rest and peak flows , or in the trans cutaneous oxygen pressure in basal conditions and in its half recovery time after an induced ischemia . The results confirm the benefits of regular exercise in stage II PAOD pa tients but suggest they may be enhanced by antiplatelet therapy ",
"AIMS Patients with diabetes are at excessive risk of mortality and cardiovascular morbidity . Previous studies suggest that aspirin may be less effective in diabetic patients . In this multi-centre , r and omized , double blind trial picotamide , a dual inhibitor of thromboxane A2 synthase and receptor , was compared with aspirin for the prevention of mortality and major cardiovascular events in diabetics with peripheral arterial disease ( PAD ) . METHODS AND RESULTS A total of 1209 adults aged 40 - 75 years with type 2 diabetes and PAD were r and omized to receive picotamide ( 600 mg bid ) or aspirin ( 320 mg od ) for 24 months . The cumulative incidence of the 2 years overall mortality was significantly lower amongst patients who received picotamide ( 3.0 % ) than in those who received aspirin ( 5.5 % ) with a relative risk ratio for picotamide versus aspirin of 0.55 ( 95 % CI : 0.31 - 0.98 % ) . Events were reported in 43 patients ( 7.1 % ) on picotamide and 53 ( 8.7 % ) on aspirin . The combined endpoint of mortality and morbidity had a slightly lower incidence in the picotamide group but this difference did not reach statistical significance . CONCLUSION Picotamide is significantly more effective than aspirin in reducing overall mortality in type 2 diabetic patients with associated PAD",
"The effect of combined treatment with acetylsalicylic acid and dipyridamole on platelet consumption and aggregation was studied in 9 patients with peripheral atherosclerotic disease . The trial was carried out as a r and omized double-blind , cross-over study . All patients had increased consumption of blood platelets . The treatment produced a marked inhibition of platelet aggregation , increased the bleeding time , but did not reduce the platelet consumption",
"In a r and omized double-blind crossover study in 16 patients with enhanced in vitro spontaneous platelet aggregation , sulfinpyrazone proved to be effective in normalizing platelet aggregability within 4 days after initiation of therapy",
"OBJECTIVE To determine the risk factors for peripheral arterial disease ( PAD ) in a diabetic population and to examine whether different levels of these risk factors might explain why diabetic subjects have an increased risk of PAD compared with normal glucose tolerance subjects . RESEARCH DESIGN AND METHODS There were 1,592 men and women aged 55 - 74 years selected at r and om from the age-sex registers of 11 general practice s in Edinburgh , Scotl and . Subjects underwent a comprehensive medical examination , including assessment for PAD ( intermittent claudication on World Health Organization question naire or major asymptomatic disease on noninvasive testing ) and a glucose tolerance test . RESULTS Of the subjects , 288 ( 18.7 % ) were found to have diabetes or impaired glucose tolerance ( IGT ) . The prevalence of PAD was greater in those with diabetes/IGT ( 20.6 % ) compared with those with normal glucose tolerance ( 12.5 % ) ( odds ratio [ OR ] 1.64 , 95 % CI 1.17 - 2.31 ) . Among the diabetes/IGT group , mean levels of smoking , systolic blood pressure , and triglycerides were higher in subjects with PAD than in those without PAD ( P Mean levels of systolic blood pressure and plasma triglycerides were also higher in diabetic subjects than in nondiabetic subjects with PAD ( P risk of PAD after adjusting separately for systolic blood pressure ( OR 1.22 , 95 % CI 0.85 - 1.73 ) and plasma triglycerides ( OR 1.26 , 95 % CI 0.89 - 1.79 ) . Simultaneous adjustment for both systolic blood pressure and triglycerides reduced the risk of PAD among diabetic subjects to 1.11 ( 95 % CI 0.78 - 1.58 ) . CONCLUSIONS Increased mean levels of triglycerides and systolic blood pressure may help to explain the higher prevalence of PAD in diabetic subjects compared with that in normal glucose tolerance subjects",
"Effects of picotamide on platelet activity and on some hemorheologic , coagu lative , and hemodynamic parameters were investigated in a r and omized , dou ble-blind , placebo-controlled study for eighteen months . Twenty patients , average age 61.5±9.6 ( SD ) years , with peripheral arterial disease ( PAD ) at functional stage 2 of the Fontaine classification and with intermittent claudica tion for at least six months were studied . Ten patients received tablets of picotamide , 300 mg three times a day , and 10 subjects received three identical placebo tablets each day . Similar atheroscler otic disease risk factors were present in both groups . Picotamide induced a significant decrease of plasma viscosity , fibrinogen , and beta-thromboglobulin and an increase of amplitude of the photoplethysmo graphic wave ",
"Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects . This study was undertaken to investigate the long-term effects of policosanol administered to patients with moderately severe intermittent claudication . The study consisted of a 6-week single-blind , placebo-controlled run in phase , followed by a 2-year double-blind , r and omized treatment step . Fifty-six patients who met study entry criteria were r and omized to receive placebo or poli cosanol 10 mg twice daily . Walking distances on a treadmill ( constant speed 3.2 km/h , slope 10 ° , temperature 25 ° C ) were assessed before and after 6 , 12 , 18 , and 24 months of treatment . Both groups were similar at r and omization . After 6 months of therapy , policosanol significantly increased ( p the initial claudication distance from 125.9 ±8.7 m to 201.1 ±24.8 m and the absolute claudication distance from 219.5 ± 14.1 m to 380.7 ±50.2 m. Both variables remained unchanged in the placebo group ( p absolute claudication distance ) ; both significantly greater ( p claudication distance ) and 237.7 ±28.1 m ( absolute claudication distance ) , respectively . At study completion , 21 policosanol and 5 placebo patients attained increases in claudication distance values > 50 % ( p 0.001 ) . Policosanol , but not placebo , significantly increased the ankle/arm pressure index . In addition , from month 6 up to study completion , the frequency of patients reporting improve ment of lower limb symptoms was greater in the policosanol group than in the placebo group . The treatment was tolerated well . There were 16 withdrawals ( 12 placebo , 4 policosanol ) from the study . Eight patients in the placebo group experienced a total of 10 serious adverse events , 8 of which were vascular events , compared with none in the policosanol group ( p the policosanol group and 3 patients in the placebo group reported mild adverse events during the study . The present results demonstrate the long-term usefulness of policosanol therapy to treat patients with intermittent claudication",
"OBJECTIVE The concept of clopidogrel resistance is frequently evoked in the cardiac literature . The variability of antiplatelet response in patients with intermittent claudication has not been investigated . The aim of this study was to describe the effect of the addition of clopidogrel to aspirin using ex vivo measures of platelet activation in patients with life-style limiting intermittent claudication . DESIGN OF STUDY Data from r and omised controlled trial . MATERIAL S Data from 67 patients with intermittent claudication taking part in a r and omised controlled trial and who received clopidogrel in addition to aspirin was analysed . METHODS Platelet activation was measured using whole-blood flow cytometric measurement of ADP-stimulated fibrinogen binding at baseline and 12h after administration of a loading dose of 300 mg clopidogrel . Patients continued to receive 75 mg clopidogrel daily for 30 days and platelet activation was again measured at day 30 . Compliance with treatment was assessed by counting returned tablets . RESULTS Six patients were excluded from analysis because of incomplete compliance with treatment . Six of the sixty-one patients ( 9.8 % ) showed no reduction in platelet activation 12h after administration of the loading dose of clopidogrel . At 30 days these six patients still showed no response to clopidogrel . Amongst the remaining 55 patients , the mean reduction in fibrinogen binding after clopidogrel administration was 51.5 % ( 95 % CI : 43.8 - 59.2 ) . Amongst responders there was a wide variability in reduction of fibrinogen binding in response to clopidogrel ( range 8.11 - 97.7 % ) . Four of these patients ( 6.6 % ) showed a reduction of more than 95 % in fibrinogen binding . CONCLUSIONS Patients with intermittent claudication show a wide variability in their response to clopidogrel . While a small proportion of these patients shows no response at all , another small group appears to respond excessively to clopidogrel . Clinical studies are required to identify whether hyper-responders are at increased risk of bleeding complications and whether hyporesponders are at a higher risk of thrombotic events",
"OBJECTIVE We aim ed to determine whether adding clopidogrel to aspirin in patients at high risk of future cardiovascular events would suppress laboratory measures of the antiplatelet effects of aspirin ; and have greater platelet inhibitory effects in patients with the least inhibition of platelets by aspirin . METHODS We performed a r and omized , double-blind , placebo-controlled , crossover trial , comparing clopidogrel 75 mg day(-1 ) versus placebo , in 36 aspirin-treated patients with symptomatic objective ly confirmed peripheral arterial disease . RESULTS The addition of clopidogrel to aspirin did not suppress platelet aggregation induced by arachidonic acid , urinary 11 dehydro thromboxane B2 concentrations , or soluble markers of platelet activation markers ( P-selectin , CD40-lig and ) and inflammation ( high sensitivity serum C-reactive protein , interleukin-6 ) . Clopidogrel significantly inhibited platelet aggregation induced by ADP ( reduction 26.2 % ; 95 % CI : 21.3 - 31.1 % , P inhibition of collagen-induced platelet aggregation by clopidogrel was seen in patients with the least inhibition of arachidonic acid induced aggregation by aspirin [ lower tertile of arachidonic acid-induced platelet aggregation : 2.8 % ( 95 % CI : -0.8 to 6.3 % ) reduction in mean collagen-induced aggregation by clopidogrel ; middle tertile : 4.0 % ( 95 % CI : 0.4 - 7.6 % ) ; upper tertile 12.6 % ( 95 % CI : 4.5 - 20.8 % ) ; P-value for interaction 0.01 ] . CONCLUSIONS The greatest platelet inhibitory effect of clopidogrel occurs in patients with the least inhibition of arachidonic acid-induced platelet aggregation by aspirin . This raises the possibility that the clinical benefits of adding clopidogrel to aspirin may be greatest in patients whose platelets are least inhibited by aspirin . Confirmation in clinical outcome studies may allow these patients to be targeted with antiplatelet drugs that inhibit the ADP receptor , thereby overcoming the problem of laboratory aspirin resistance",
"OBJECTIVE Coagulation activation markers are significantly elevated in patients with peripheral arterial disease compared with healthy controls . The more severe the disease , the higher the markers . Increased coagulation activation may contribute to the disease process and the risk of complications in patients with peripheral arterial disease , particularly after endovascular intervention . Animal studies have shown that clopidogrel significantly inhibits coagulation activation . The aim of this study was to determine whether combination of aspirin and clopidogrel affects thrombin-antithrombin III and D-dimer in patients with intermittent claudication undergoing angioplasty , compared with aspirin alone . METHODS This was a double blind , r and omized placebo-controlled trial conducted in a vascular unit in a tertiary referral center . One hundred thirty-two patients with intermittent claudication were r and omized to clopidogrel and aspirin or placebo and aspirin , with a loading dose 12 hours before endovascular intervention . D-dimer and thrombin-antithrombin III ( TAT ) levels were measured using enzyme-linked immunosorbent assay at baseline , 1 hour before , and 1 hour , 24 hours , and 30 days after intervention in 103 patients who underwent endovascular intervention . RESULTS There was a significant rise in D-dimer levels at 1 hour and 24 hours after angioplasty in both groups ( placebo group : 63.69 , 141.45 , 122.18 ng/mL ; clopidogrel group : 103.79 , 159.95 , 134.69 ng/mL ) , but no difference between the two groups ( P = .514 ) . Similarly there was a significant rise in TAT levels at 1 hour after angioplasty in both groups ( placebo group : 2.93 , 6.16 microg/L ; clopidogrel group : 3.39 , 5.27 microg/L ) , with no significant difference between the two groups ( P = .746 ) . CONCLUSION Endovascular intervention results in a significant increase in TAT and D-dimer . The addition of clopidogrel to aspirin has no effect on TAT and D-dimer before or after endovascular intervention",
"OBJECTIVES In the current study , we hypothesized that beraprost would : 1 ) improve treadmill exercise performance and quality of life ; and 2 ) decrease rates of ischemic events in patients with intermittent claudication . BACKGROUND Previous trials with beraprost sodium , an orally active prostagl and in I(2 ) analogue , in the treatment of claudication in patients with peripheral arterial disease ( PAD ) have been inconsistent . METHODS Patients with intermittent claudication ( n = 897 ) were r and omized to receive either 40 microg three times a day of beraprost with meals ( n = 385 ) or placebo ( n = 377 ) in a double-blinded manner for one year . The primary efficacy parameter was treadmill-measured maximum walking distance , as assessed at three and six months after r and omization . Secondary efficacy parameters included treadmill-measured pain-free walking distance and change in quality of life . RESULTS There was no significant improvement in maximum walking distance in the beraprost group ( 16.7 % ) as compared with the placebo group ( 14.6 % , p = NS ) . Administration of beraprost did not improve the pain-free walking distance ( p = NS between treatment groups ) , and there was no improvement in the quality -of-life measures between the treatment groups . The incidence of critical cardiovascular events was 7.3 % in the beraprost group and 11.4 % in the placebo group ( p = NS ) . There was a significant reduction in the combination of cardiovascular death and myocardial infa rct ion in the beraprost group ( p = 0.01 ) . CONCLUSIONS Despite previous investigations suggesting efficacy , these results indicate that beraprost is not an effective treatment to improve symptoms of intermittent claudication in patients with PAD . The potential benefit of beraprost on critical cardiovascular events would require confirmation in a larger prospect i ve investigation",
"OBJECTIVES The current study tested the hypothesis that NM-702 improves treadmill exercise performance in peripheral arterial disease patients with claudication-limited exercise performance . BACKGROUND Patients with claudication experience significant disability , owing to their exercise limitation . Therapeutic options to improve exercise performance in these patients are limited . NM-702 is a novel drug that inhibits phosphodiesterase as well as thromboxane A2 synthase . METHODS This study was a r and omized , multi-center , placebo-controlled , double-blind trial . Patients were r and omized to receive 24 weeks of twice-daily treatment with either placebo ( intent to treat population , n = 130 ) , 4 mg NM-702 ( n = 126 ) , or 8 mg NM-702 ( n = 130 ) . RESULTS After 24 weeks of treatment , 8 mg NM-702 was associated with a statistically significant increased peak walking time on a grade d treadmill as compared with placebo ( p = 0.004 ) . Peak walking time after 24 weeks was increased by 17.1 + /- 49.0 % in the placebo arm , 22.1 + /- 60.1 % in the 4-mg NM-702 arm , and 28.1 + /- 50.5 % in the 8-mg NM-702 arm . NM-702 at the 8-mg dose for 24 weeks was associated with statistically significant improvements in the treadmill claudication onset time as compared with placebo . In addition , as compared with placebo , NM-702 improved the physical component and physical functioning scores of the Medical Outcomes Study 36-Item Short Form and the walking distance and stair climbing domains of the Walking Impairment Question naire . NM-702 was generally well tolerated , but adverse events typical of vasodilators were common . CONCLUSIONS NM-702 used for 24 weeks by patients with claudication was associated with improvements in laboratory- and ambulatory-based exercise performance",
"Forty-five patients suffering from intermittent claudication were admitted to a double-blind non-crossover study . Three groups were constituted at r and om and treated for 2 months with either 100 mg suloctidil t.i.d . or 1.5 mg dihydroergotoxine methylate t.i.d . or placebo . From the results of measurements of pain-free walking distance and venous occlusion plethysmography recordings , suloctidil was shown to be active and significantly superior to dehydroergotoxine and placebo : in the two latter groups a decrease in calf blood perfusion after 2 months was also noted . The physician 's overall assessment of response to treatment showed that suloctidil and dihydroergotoxine were significantly superior to placebo , and that suloctidil was significantly better than dihydroergotoxine",
"BACKGROUND The aim of this study has been to assess the efficacy and the safety of heparansulphate administered with indobufen in the treatment of occlusive arterial disease . METHODS In a controlled open study , nineteen out- patients with Fontaine 's stage II occlusive arterial disease since one year were r and omly assigned to treatment with indobufen 200 mg/day or indobufen 200 mg/day and heparansulphate 200 mg/day for 6 months . Efficacy assessment s were based on functional evaluations ( pain-free sub-maximal exercise ergometric test , ankle-arm pressure ratio at rest and after induced ischemia ) , on hemocoagulative parameters and on physical signs and subjective symptoms assessed monthly over the whole period of treatment . All patients but one who was lost to follow-up completed the study treatment period as foreseen by the experimental protocol . RESULTS The results of the study show an improvement of 10.89 % ( day 30 ) , 15.92 % ( day 60 ) , 21.04 % ( day 90 ) , 24.19 % ( day 120 ) , 25.18 ( day 150 ) 28.84 % ( day 180 ) end of study in ergometric test pain-free interval obtained by patients treated with heparansulphate and indobufen with respect to patients receiving indobufen alone . Also hemocoagulative parameters and signs and patients ' subjective symptoms were positively influenced by the association heparansulphate and indobufen . CONCLUSIONS On the whole , the results of the study indicate that heparansulphate in association with antiplatelet therapy with indobufen has a beneficial effect in the treatment of peripheral occlusive arterial disease",
"BACKGROUND Repeat hospitalizations of patients with atherosclerosis represent a considerable burden on the health care system . We sought to determine whether clopidogrel compared with aspirin decreases the need for rehospitalization for ischemia and bleeding . METHODS AND RESULTS The Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events ( CAPRIE ) trial was a r and omized , blinded , multicenter , trial of 19,185 patients with atherosclerotic disease manifested as recent ischemic stroke or myocardial infa rct ion or symptomatic peripheral arterial disease . Without any double-counting of events , the number of rehospitalizations for ischemic events ( defined as angina , transient ischemic attack , or limb ischemia ) or bleeding events was determined for the entire cohort . There was a significant reduction in the total number of rehospitalizations for ischemic events or bleeding with clopidogrel use compared with aspirin ( 1502 vs 1673 ; P = .010 ) over an average of 1.6 years of treatment . This reduction in rehospitalization was consistent across individual outcomes of angina , transient ischemic attack , limb ischemia , and bleeding . Compared with aspirin , clopidogrel also result ed in a 7.9 % relative risk reduction in a combined end point of vascular death , stroke , myocardial infa rct ion , or rehospitalization for ischemic events or bleeding ( 15.1 % to 13.7 % at 1 year ; P = .011 ) . Adjusting for baseline prognostic variables , clopidogrel therapy was an independent predictor for reduction of vascular death , stroke , myocardial infa rct ion , or rehospitalization for ischemic events or bleeding ( P = .009 ) . CONCLUSIONS Treatment with clopidogrel results in a significant decrease in the need for rehospitalization for ischemic events or bleeding compared with aspirin . This meaningful end point tracks well with other , more traditional measures of outcome and has incremental value beyond such end points",
"Platelet survival times were measured twice within 6 months using autologous 111-Indium-labelled platelets in 13 male patients diagnosed as stable intermittent claudicants . Linear , exponential , weighted mean and gamma function ( multiple-hit ) analyses were carried out on the data . Of these methods , exact mathematical models such as linear and exponential are unsuitable for the comparison of curves which may alter with treatment or disease progression . Weighted mean platelet survival correlated ( r = 0.96 ) with platelet survival calculated by the precision reference method of analysis , gamma function . Statistics were expressed from gamma function analyses unless otherwise stated . Severity of claudication was measured by doppler ; the ratio of brachial to mean ankle pressures was directly related to platelet survival ( r = 0.84 ) . In 7 patients , where duration of claudication was greater than 5 years , platelet survival was significantly reduced ( P less than 0.02 ) compared with 6 newly diagnosed claudicants of less than 18 months duration . Six r and omly selected patients were treated with 250 mg b.d . ticlopidine during one of the study periods . Ticlopidine significantly increased platelet survival ( P less than 0.02 ) in all patients irrespective of disease duration or severity . The involvement of platelets in atherosclerosis observed in these claudicants , can be reduced by therapy with ticlopidine , however , the lack of clinical improvement following long-term drug treatment only confirms the platelet 's secondary role in this disabling disease",
"Seventy-one patients with peripheral arterial occlusive disease ( PAOD ) were r and om ized into two groups of different treatment modalities . The diagnosis of PAOD was estab lished by history of intermittent claudication , clinical examination , and by Doppler pressure assessment or lower extremity arteriography . After a three-month washout period , 35 patients ( Group 1 ) started treatment with indobufen ( 400 mg per day ) and 36 patients ( Group 2 ) with pentoxifylline ( 600 mg per day ) . Twenty-nine patients from each group completed six months of treatment . Both of the drugs significantly improved maximal and pain-free walking distances , but the effect of indobufen was more pronounced than that of pentoxifylline . Patients with PAOD exhibited signs of hyperco agulation . Fibrinogen , D-dimer , and b-thromboglobulin concentrations did not change significantly following treatment in both of the groups . The authors observed a decrease of platelet aggregation after treatment with indobufen and a decrease of F1 + 2 fragment and PAI-1 antigen after treatment with pentoxifylline",
"The efficacy of and tolerance to ticlopidine , a platelet inhibitor , in preventing progression of obliterative arterial disease was compared with that of a placebo in a double-blind and r and omized trial in 43 patients ( 22 on placebo , 21 on ticlopidine ) over a period of one year . The course of the disease in both groups was assessed by serial angiography of the lower limbs , both at the beginning and at the end of the study . There was a significantly reduced progression in the ticlopidine group ( P less than 0.01 ) . The results support the hypothesis that platelets are of great importance in the progression of arteriosclerosis and that inhibition of platelet function is an effective principle of prevention . Ticlopidine in this respect is an alternative to the use of acetylsalicylic acid",
"The aim of this trial was to assess the activity of indobufen compared with placebo in peripheral occlusive arterial disease of the lower limbs of atheroscle rotic or diabetic origin . Fifty-two out patients were admitted to the r and omized , double-blind study and were given either an indobufen 200-mg tablet ( 28 sub jects ) or placebo ( 24 ) for six months . Painfree walking distance on a treadmill at a constant speed ( 4 km/h ) and slope ( 10 ° ) was assessed before and after three and six months ' treatment . The painfree walking distance before treatment with indobufen or placebo averaged 153 ± 23.02 ( mean ± SE ) and 199 ± 30.58 ( mean ± SE ) meters respectively . After six months ' treatment with active drug or placebo , this parameter reached 610 ± 115.36 ( p 0.05 ) meters respec tively . The difference between the two treatments was statistically significant in favor of indobufen ( p < 0.01 Dunn 's test )",
"Peripheral arterial disease ( PAD ) is associated with platelet hyperactivity . Aspirin and clopidogrel , two platelet inhibitors , act by different mechanisms . Aspirin inhibits thromboxane A2 synthesis and clopidogrel acts on the P2Y12 platelet ADP receptor . We evaluated the effect of clopidogrel ( 75 mg/day ) , aspirin ( 75 mg/day ) and then both drugs on several platelet function indices in patients with PAD ( n = 20 ) . There was a significant ( P = 0.0001 ) decrease in ADP-induced aggregation , after clopidogrel but not after taking aspirin . Clopidogrel plus aspirin significantly decreased spontaneous platelet aggregation ( SPA ) ( P = 0.01 to P = 0.002 ) but SPA was not significantly altered by either aspirin or clopidogrel monotherapy . Similarly , monotherapy did not inhibit serotonin (5HT)-induced aggregation but there was a significant inhibition ( P = 0.03 to P therapy . ADP ( 0.8 μM)-induced platelet shape change ( PSC ) was significantly inhibited by clopidogrel ( P = 0.004 ) or aspirin ( P = 0.01 ) . This was also true for 5HT-induced PSC ( clopidogrel , P = 0.01 ; aspirin , P = 0.03 ) . Soluble P-selectin decreased significantly ( from 32 ± 24 to 25 ± 17 ng/ml , P = 0.04 ) with combination therapy . Plasma platelet-derived growth factor and intraplatelet 5HT levels were not altered by combination therapy . In PAD , clopidogrel is a more potent inhibitor of ADP-induced platelet activation than aspirin ; combination therapy is more effective than clopidogrel or aspirin monotherapy . These potentially clinical ly relevant findings should be evaluated in appropriately design ed trials",
"After a 3-month , single-blind , run-in period , 151 patients with intermittent claudication were r and omly allocated to receive the antiplatelet agent ticlopidine ( 250 mg twice per day ) or an identical placebo . One hundred and twenty patients completed the double-blind phase of the trial , which lasted 21 months . The primary analysis was performed according to the \" intention-to-treat principle \" in all 151 enrolled patients . There was , continuing on from the third month after r and omization , a progressive and sustained improvement of the pain-free and maximum walking distances in the two treatment groups that was significantly greater in the ticlopidine group . The ankle-arm systolic blood pressure ratio at rest and after exercise increased in a significant manner in the ticlopidine group only . In a secondary analysis , with exclusion of 25 patients because of protocol violations at selection , consistently significant differences in favor of the ticlopidine group were still observed for maximum walking distance and systolic ankle-arm blood pressure ratio , both at rest and after exercise . No major side effects were reported in the treated group . It is concluded that long-term treatment with ticlopidine improves walking ability and ankle systolic blood pressure in patients with claudication",
"32 patients ( mean age 65 years , range 51 - 75 years ) were included in this controlled , double blind study to evaluate the effect of dipyridamole in patients with intermittent claudication . Following a run-in phase of one month , 15 patients received 400 mg dipyridamole per day and 17 patients placebo . Patient characteristics ( risk factors , age , clinical and apparative tests ) of both groups did not differ significantly before and during the study period . Mean pain free und absolute walking distance on the treadmill ( 3.2 km/h , 12.5 degrees gradient ) increased significantly in both groups during study period ( p physical activity and increasing adaptation to treadmill exercise . However , dipyridamole did not induce a significantly longer walking distance in comparison with placebo . The working hypothesis that the drug with inhibiting properties of thrombocyte function prolongs walking distance in intermittent claudication , could not be confirmed",
"Objectives : Cilostazol improves walking in patients with peripheral arterial disease ( PAD ) . We hypothesized that cilostazol reduces diabetic complications in PAD patients . Methods : Diabetic PAD patients were prospect ively recruited to a r and omized double-blinded , placebo-controlled trial , using cilostazol 100 mg twice a day . Clinical assessment included ankle-brachial index , arterial compliance , peripheral transcutaneous oxygenation , treadmill walking distance and vali date d quality of life ( QoL ) question naires . Biochemical analyses included glucose and lipid profiles . All tests were at baseline , 6 , and 24 weeks . Results : 26 diabetic PAD patients ( 20 men ) were recruited . Cilostazol improved absolute walking distance at 6 and 24 weeks ( 86.4 % vs. 14.1 % , P = .049 ; 143 % vs. 23.2 % , P = .086 ) . Arterial compliance and lipid profiles improved as did some QoL indices for cilostazol at 6 and 24 weeks . Blood indices were similar at baseline and at follow-up points for both treatment groups . Conclusions : Cilostazol is a well-tolerated and efficacious treatment , which improves claudication distances in diabetic PAD patients with further benefits in arterial compliance , lipid profiles , and"
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411794de-06ff-11f0-808a-c43d1ab1c353
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Background Population ageing is a worldwide phenomenon that has recently challenged public healthcare systems . The knowledge of the burden of chronic musculoskeletal disorders in elders is still limited , particularly in the developing world . This systematic review aim ed to investigate the prevalence of chronic musculoskeletal disorders in elderly Brazilians . Methods A comprehensive literature search was performed in five electronic data bases ( from inception to January 2012 ) and completed by additional search es in reference lists . Two review authors independently selected the eligible studies and extracted data on participants ’ characteristics and rates of chronic musculoskeletal disorders . One review author extracted method ological quality data . We performed a critical synthesis of the results , which were grouped into the diagnoses “ chronic musculoskeletal pain ” or “ specific musculoskeletal diagnoses ” . Results Twenty five studies reporting on a total of 116,091 elderly Brazilians were included . Eight studies ( 32 % ) were of high method ological quality . There was a large variation in the measure of prevalence used by individual studies and in their definition of chronic pain . Prevalence estimates reached 86 % for chronic musculoskeletal pain in any location . Studies investigating multiple pain sites found the lower limb and the spine to be the most prevalent complaints ( 50 % each ) . Arthritis and rheumatism ( including osteoarthritis ) were the most prevalent specific musculoskeletal diagnoses ( 9 % to 40 % ) , followed by herniated disc ( 6 % to 27 % ) . Conclusions Despite the growth of the elderly population worldwide , high- quality research on the burden of chronic musculoskeletal disorders in the elderly is still scarce . Future healthcare research focusing on this age group should be a priority in developing countries since their public healthcare systems are not yet fully prepared to accommo date the needs of an aging population
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"The prevalence of mild and severe radiological osteoarthritis was investigated in a r and om sample of 6585 inhabitants of a Dutch village . Radiographs were grade d 0 - 4 according to the criteria described by Kellgren and Lawrence . The prevalence of radiological osteoarthritis increased strongly with age and was highest for cervical spine ( peak : men 84.8 % , women 84.3 % ) , lumbar spine ( peak : 71.9 % , women 67.3 % ) , and distal interphalangeal joints of the h and s ( peak : men 64.4 % , women 76 % ) . Prevalence did not exceed 10 % in sacroiliac joints , lateral carpometacarpal joints , and tarsometatarsal joints . Severe radiological osteoarthritis ( grade 3 or grade 4 ) was uncommon under age 45 ; in elderly persons the prevalence of severe radiological osteoarthritis did not exceed 20 % except for the cervical and lumbar spine , distal interphalangeal joints of the h and s and , in women only , metacarpophalangeal joints , first carpometacarpal joints , first metatarsophalangeal joints , and knees . Overall , differences between men and women were small except for hips and knees ; however , severe radiological osteoarthritis was found in a higher proportion in most of the joints in women . Our data were compared with data from similar population surveys . The slope between joint involvement and age was strikingly constant for most of the joints . Differences between population s were mainly differences in level . These differences of prevalence of radiological osteoarthritis may be attributed to interobserver differences -- that is , different criteria used to establish radiological osteoarthritis , in addition to genetic or environmental factors , or both",
"Data from a representative national household survey were used to examine 10-year trends ( 1998 - 2008 ) in health conditions of Brazilian elderly . A r and om sample of 105,254 individuals aged > 60 years participated . The mean age was 69 years and 56 % were women . There was a gradual increase in the prevalence of good or excellent self-rated health ( 39.3 % , 43.5 % and 45.0 % , in 1998 , 2003 and 2008 , respectively ) and a decrease in self-reported arthritis , heart disease , and depression . The prevalence of self-reported hypertension ( 43.9 % , 48.8 % , and 53.3 % , respectively ) and diabetes ( 10.3 % , 13.0 % and 16.1 % respectively ) increased sharply . The prevalence of inability to perform activities of daily living ( eating , bathing or using the toilet ) remained stable ( 6.5 % , 6.4 % and 6.9 % , respectively ) . The achievement of three or more physician visits over the previous 12 months increased by 21 % from 1998 to 2008 . Hospitalization decreased by 10 % in the corresponding period . The above mentioned trends persisted after adjustments for age and sex . The results showed improvements in some health dimensions of the elderly , but not all . Changes in the use of health services occurred as expected with the expansion of primary healthcare activities in Brazil",
"Objectives : The objectives of this study were to provide estimates of the prevalence and strength of association between major depression and chronic pain in a primary care population and to examine the clinical burden associated with the two conditions , singly and together . Methods : A r and om sample of Kaiser Permanente patients who visited a primary care clinic was mailed a question naire assessing major depressive disorder ( MDD ) , chronic pain , pain-related disability , somatic symptom severity , panic disorder , other anxiety , probable alcohol abuse , and health-related quality of life ( HRQL ) . Instruments included the Patient Health Question naire , SF-8 , and Grade d Chronic Pain Question naire . A total of 5808 patients responded ( 54 % of those eligible to participate ) . Results : Among those with MDD , a significantly higher proportion reported chronic ( i.e. , nondisabling or disabling ) pain than those without MDD ( 66 % versus 43 % , respectively ) . Disabling chronic pain was present in 41 % of those with MDD versus 10 % of those without MDD . Respondents with comorbid depression and disabling chronic pain had significantly poorer HRQL , greater somatic symptom severity , and higher prevalence of panic disorder than other respondents . The prevalence of probable alcohol abuse/dependence was significantly higher among persons with MDD compared with individuals without MDD regardless of pain or disability level . Compared with participants without MDD , the prevalence of other anxiety among those with MDD was more than sixfold greater regardless of pain or disability level . Conclusions : Chronic pain is common among those with MDD . Comorbid MDD and disabling chronic pain are associated with greater clinical burden than MDD alone . MDD = major depressive disorder ; HRQL = health-related quality of life ; HMO = health maintenance organization ; PHQ = Patient Health Question naire ; GCPS = Grade d Chronic Pain Scale ; CP = chronic pain ; DCP = disabling chronic pain ; GAD = generalized anxiety disorder ; SCID = Structured Clinical Interview for DSM-III-R ; PRIME-MD = Primary Care Evaluation of Mental Disorders ; CI = confidence interval ; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ; DSM-III-R = Diagnostic and Statistical Manual of Mental Disorders , Third Edition Revised",
"BACKGROUND Reports in the literature have identified a need for internationally st and ardized and reliable measurements to analyse musculoskeletal symptoms . Screening of musculoskeletal disorders may serve as a diagnostic tool to evaluate the work environment . The Nordic general question naire is a st and ardized instrument used to analyse musculoskeletal symptoms in an ergonomic or occupational health context . PURPOSE To translate and adapt a version of the Nordic general question naire into Brazilian Portuguese and evaluate its reliability . METHOD The cross-cultural adaptation was performed according to internationally recommended methodology , using the following guidelines : translation ; back-translation ; committee review ; and pretesting . First , the question naire was independently translated into Portuguese by two teachers and one doctor , and a consensus version was generated . Second , two other translators performed a back-translation independently from one another . This version was then su bmi tted to a committee , consisting of six specialists in the area of knowledge of the instrument , to evaluate its equivalence to the original instrument . The final version was pretested on 20 subjects r and omly selected in an outpatient clinic . Reliability was assessed by a test-retest procedure at 1-day intervals using the Kappa coefficient in a group of 40 subjects . The Kappa agreement values were calculated for each one of the four questions of the question naire . The agreement among the same observers was substantial , varying from 0.88 to 1 , according to the Kappa values . RESULTS these demonstrated strong agreement of the instrument , suggesting that the Brazilian version of the \" St and ardized Nordic Question naire \" offers substantial reliability",
"Study Design . Cross-sectional data were collected in a postal question naire within the framework of a 5-year r and omized , controlled , prospect i ve , population -based study . Objectives . To investigate to what extent associations differ or concur when correlates of low back pain are tested against various subdefinitions of low back pain . Summary of Background Data . Numerous factors have been suspected to cause low back pain , but findings have not been constantly reproduced in epidemiologic studies . Methods . Data were collected on 746 people reporting nonspecific low back pain some time during the year preceding the survey . Six correlates of low back pain ( age , sex , marital status , attitude to a healthy life-style , self-reported physical activity at work , and smoking ) were cross-tabulated against nonspecific low back pain and against four subgroups of low back pain . Results . There was only one statistically significant strong association between the potential risk indicators and the nonspecific definition of low back pain , but several emerged when the low back pain group was split into subgroups . Different subgroups of low back pain did , indeed , relate differently to the various correlates . Conclusions . It is necessary to define some clinical ly relevant subgroups of low back pain to accelerate the search for causal mechanisms"
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4117954c-06ff-11f0-808a-c43d1ab1c353
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Several review s and meta-analyses have examined the effects of iodine on mental development . None focused on young children , so they were incomplete in summarizing the effects on this important age group . The current systematic review therefore examined the relationship between iodine and mental development of children 5 years old and under . A systematic review of articles using Medline ( 1980–November 2011 ) was carried out . We organized studies according to four design s : ( 1 ) r and omized controlled trial with iodine supplementation of mothers ; ( 2 ) non-r and omized trial with iodine supplementation of mothers and /or infants ; ( 3 ) prospect i ve cohort study stratified by pregnant women ’s iodine status ; ( 4 ) prospect i ve cohort study stratified by newborn iodine status . Average effect sizes for these four design s were 0.68 ( 2 RCT studies ) , 0.46 ( 8 non- RCT studies ) , 0.52 ( 9 cohort stratified by mothers ’ iodine status ) , and 0.54 ( 4 cohort stratified by infants ’ iodine status ) . This translates into 6.9 to 10.2 IQ points lower in iodine deficient children compared with iodine replete children . Thus , regardless of study design , iodine deficiency had a substantial impact on mental development . Method ological concerns included weak study design s , the omission of important confounders , small sample sizes , the lack of cluster analyses , and the lack of separate analyses of verbal and non-verbal subtests . Quantifying more precisely the contribution of iodine deficiency to delayed mental development in young children requires more well- design ed r and omized controlled trials , including ones on the role of iodized salt
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"Growth and development of 207 children ( 49 % males ; mean age 5.4 years [ SD 0.2 ] , range 4 to 7.3 years whose mothers received iodine during pregnancy , and children who received iodine first in their 2nd year , were examined in 1996 ; 192 children ( 49 % males ; mean age 6.5 years [ SD 0.2 ] , range 5.8 to 6.9 years ) whose mothers received iodine while pregnant were seen in 1998 . Children were from the southern part of China 's Xinjiang Province which has the lowest levels of iodine in water and soil ever recorded . Head circumference but not height was improved for those who received iodine during pregnancy ( compared with those receiving iodine at age 2 ) and for those supplemented before the end of the 2nd trimester ( relative to those supplemented during the 3rd trimester ) . Iodine before the 3rd trimester predicted higher psychomotor test scores for children relative to those provided iodine later in pregnancy or at 2 years . Results from the test for cognitive development result ed in trend only differences between those children supplemented during pregnancy versus later . The results address the question of when maternal iodine supplements should begin in public health programs world wide . Findings may be relevant to the treatment of maternal and newborn thyroid deficiency in industrialized countries , particularly for those infants delivered before the end of the second trimester",
"Reduced maternal thyroid hormone concentrations during pregnancy can adversely affect fetal neurological development . In the context of national iodine supplementation programmes , concern has been expressed over the theoretical possibility that iodine supplementation during pregnancy might adversely affect fetal development as a result of maternal thyroid inhibition from the Wolff-Chaikoff effect . In a double blind controlled trial in five villages in Papua New Guinea , several measures of motor and cognitive function showed no significant differences at either age 11 or 15 years between those children whose mothers had received supplementary iodine during pregnancy and the control children whose mothers had received the placebo",
"BACKGROUND An adequate iodine supply in utero and shortly after birth is known to be crucial to an individual 's physical and mental development . The question of whether iodine supplementation later in life can exert a favorable influence on the mental performance of iodine-deficient population s was addressed in various studies , but with contradictory results . OBJECTIVE The aim of this study was to examine the effect of an improvement in iodine status on mental and psychomotor performance of schoolchildren ( 7 - 11 y ) who were moderately to severely iodine deficient . DESIGN The study , which was originally planned as a double-blind , r and omized , placebo-controlled intervention , was carried out in an iodine-deficient population of schoolchildren ( n = 196 ) in northern Benin . As the population began to have access to iodized salt during the 1-y intervention period , the study population was split post hoc-on the basis of urinary iodine concentrations-into a group with improved iodine status and a group with unchanged iodine status . Changes in mental and psychomotor performance over the intervention period were compared . RESULTS Children with increased urinary iodine concentrations had a significantly greater increase in performance on the combination of mental tests than did the group with no change in urinary iodine concentrations . CONCLUSIONS An improvement in iodine status , rather than iodine status itself , determined mental performance in this population , which was initially iodine deficient . These findings suggest a \" catch-up \" effect in terms of mental performance",
"One hundred goitrous school children received 475 mg iodized oil by mouth , while 100 controls received mineral oil , on a double-blind basis . On follow-up 22 months later the urinary iodine had increased and goiter size had decreased in both groups , more strikingly in the iodine-treated children . There were no consistent differences between the two treatment groups in rate of somatic growth or performance on the Stanford-Binet and Bender tests . Because of the complexities introduced by increases in urinary iodine in the controls , we compared goiter reduction with improvement in IQ score in all children , regardless of group , and found a significant relationship ( p = 0.014 ) , particularly in girls ( p = 0.029 ) . We conclude that oral iodized oil is an attractive alternative to its injection but we recommend an approximate doubling of the dose used here for more effective control . Also , while our data are not conclusive , they support the possibility that correction of iodine deficiency may improve mental performance in school age children , particularly girls",
"Iodine supplementation before pregnancy in iodine-deficient women prevents cretinism and neuromotor deficits in their offspring . It is unclear whether iodine supplementation benefits cognitive function in iodine-deficient school-aged children . We therefore conducted a double-blind , r and omized , controlled trial of the effects of iodized poppy seed oil ( Lipiodol ) on cognitive and motor function and weight gain of iodine-deficient school children . The study was conducted with 305 children in grade s 1 and 2 from 10 primary schools in two iodine-deficient areas in Bangladesh . The children were stratified by school and grade and r and omly assigned to receive 400 mg of oral Lipiodol or a placebo . All children were given a battery of cognitive and motor function tests and had their weights , serum thyroxine ( T4 ) and thyroid-stimulating hormone ( TSH ) and urinary iodine levels measured before and 4 mo after the intervention . On enrollment , both groups were moderately iodine deficient ( median urinary iodine values : placebo group = 3.3 micromol/L , n = 148 ; iodine group = 3.1 micromol/L , n = 152 ; goiter prevalence in both groups > 95 % ) . However , their T4 and TSH levels were within the normal range . After 4 mo , there was a significant treatment effect on urinary iodine levels ( P T4 and TSH levels , weight gain , cognitive or motor function . The findings suggest that Lipiodol supplementation in moderately iodine-deficient children with normal T4 levels is unlikely to benefit their cognitive function . However , it remains possible that other iodine preparations may have benefits",
"BACKGROUND Iodine is required for the production of thyroid hormones , which are necessary for normal brain development and cognition . Although several r and omized trials examined the effect of iodine supplementation on cognitive performance in schoolchildren , the results were equivocal . OBJECTIVE We aim ed to ascertain whether providing iodized oil to iodine-deficient children would affect their cognitive and motor performance . DESIGN In a double-blind intervention trial , 10 - 12-y-old children ( n = 310 ) in primary schools in rural southeastern Albania were r and omly assigned to receive 400 mg I ( as oral iodized oil ) or placebo . We measured urinary iodine ( UI ) , thyroid-stimulating hormone ( TSH ) , and total thyroxine ( TT4 ) concentrations and thyroid gl and volume ( by ultrasound ) . The children were given a battery of 7 cognitive and motor tests , which included measures of information processing , working memory , visual problem solving , visual search , and fine motor skills . Thyroid ultrasound and the biochemical and psychological tests were repeated after 24 wk . RESULTS At baseline , the children 's median UI concentration was 43 microg/L ; 87 % were goitrous , and nearly one-third had low concentrations of circulating TT4 . Treatment with iodine markedly improved iodine and thyroid status : at 24 wk , median UI in the treated group was 172 microg/L , mean TT4 was approximately 40 % higher , and the prevalence of hypothyroxinemia was placebo , iodine treatment significantly improved performance on 4 of 7 tests : rapid target marking , symbol search , rapid object naming , and Raven 's Coloured Progressive Matrices ( P Information processing , fine motor skills , and visual problem solving are improved by iodine repletion in moderately iodine-deficient schoolchildren",
"BACKGROUND The effects of severe iodine deficiency during critical periods of brain development are well documented . There is little known about the consequences of milder forms of iodine deficiency on neurodevelopment . OBJECTIVE The objective was to determine whether supplementing mildly iodine-deficient children with iodine improves cognition . DESIGN A r and omized , placebo-controlled , double-blind trial was conducted in 184 children aged 10 - 13 y in Dunedin , New Zeal and . Children were r and omly assigned to receive a daily tablet containing either 150 microg I or placebo for 28 wk . Biochemical , anthropometric , and dietary data were collected from each child at baseline and after 28 wk . Cognitive performance was assessed through 4 subtests from the Wechsler Intelligence Scale for Children . RESULTS At baseline , children were mildly iodine deficient [ median urinary iodine concentration ( UIC ) : 63 microg/L ; thyroglobulin concentration : 16.4 microg/L ] . After 28 wk , iodine status improved in the supplemented group ( UIC : 145 microg/L ; thyroglobulin : 8.5 microg/L ) , whereas the placebo group remained iodine deficient ( UIC : 81 microg/L ; thyroglobulin : 11.6 microg/L ) . Iodine supplementation significantly improved scores for 2 of the 4 cognitive subtests [ picture concepts ( P = 0.023 ) and matrix reasoning ( P = 0.040 ) ] but not for letter-number sequencing ( P = 0.480 ) or symbol search ( P = 0.608 ) . The overall cognitive score of the iodine-supplemented group was 0.19 SDs higher than that of the placebo group ( P = 0.011 ) . CONCLUSIONS Iodine supplementation improved perceptual reasoning in mildly iodine-deficient children and suggests that mild iodine deficiency could prevent children from attaining their full intellectual potential . The trial was registered with the Australia New Zeal and Clinical Trials Register as ACTRN12608000222347",
"Abstract Endemic cretinism is characterised by multiple neurological defects including deaf-mutism , diplegia , squint , and mental deficiency . The condition is widely prevalent in the Highl and s of New Guinea in association with severe iodine deficiency . Previous studies have shown that iodised oil provides a very satisfactory correction of severe iodine deficiency in New Guinea . A controlled trial on the use of intramuscular iodised oil in the prevention of endemic cretinism was carried out in the Western Highl and s of New Guinea and involved a population of approximately 8000 . Subsequent follow-up over four years revealed 26 endemic cretins out of a total of 534 children born to mothers who had not received iodised oil ; the mothers of 5 of these cretins were pregnant at the start of the trial . In comparison , 7 cases of endemic cretinism occurred among 498 children born to mothers who had been treated with iodised oil ; in 6 of these 7 cases , the mother was pregnant when the trial commenced . It is concluded that intramuscular iodised oil is effective in the prevention of endemic cretinism and that , for it to be effective , it should be given prior to conception . This suggests that severe iodine deficiency in the mother produces neurological damage during fetal development",
"Motor performance of children born to mothers living in an iodine-deficient region was assessed . The mothers were participants in a controlled trial of intramuscular iodised oil in the prevention of endemic cretinism carried out in the Western Highl and s of Papua New Guinea . Mothers received either iodised oil or placebo saline . Children born to mothers given iodine were significantly faster and more accurate in tests of manual function than children from control mothers . The findings indicate that iodine deficiency may lead to a spectrum of sub clinical deficits which place the children at a developmental disadvantage",
"CONTEXT Mild to moderate iodine deficiency during pregnancy can cause transient maternal hypothyroidism and impaired mental development of the progeny . These unfavorable effects are preventable by iodine supplementation . In Europe , however , less than 50 % pregnant women receive iodine-containing supplements , thus representing dietary iodized salt the only carrier of iodine for most women in this life stage . OBJECTIVE / DESIGN This longitudinal study is aim ed to investigate the effects of long-term iodized salt consumption on maternal thyroid function during gestation . PARTICIPANTS / OUTCOME MEASURES : We prospect ively evaluated thyroid function in 100 consecutive thyroperoxidase antibody-negative pregnant women from a mildly iodine-deficient area . Sixty-two women who had regularly used iodized salt for at least 2 yr prior to becoming pregnant and 38 who commenced iodized salt consumption upon becoming pregnant were classified as long-term ( LT ) and short-term ( ST ) iodine supplemented , respectively . RESULTS Long-term iodized salt consumption result ed in a very low prevalence of maternal thyroid failure ( MTF ) in LT women . Conversely , short-term iodine prophylaxis does not seem to protect against the risk of MTF , the prevalence of which was almost 6-fold higher in ST than LT women ( 36.8 % vs. 6.4 % ; chi(2 ) 14.7 , P relative risk reduction amounted to 82.5 % , this measure indicating the extent to which long-term iodine prophylaxis using iodized salt would reduce the risk of MTF in ST women . CONCLUSIONS Prolonged iodized salt significantly improves maternal thyroid economy and reduces the risk of maternal thyroid insufficiency during gestation , probably because of a nearly restoring intrathyroidal iodine stores",
"Transient neonatal hypothyroxinemia is very common in preterm infants . The literature on the effect of this hypothyroxinemia is , however , controversial , and large or long-term follow-up studies are not available . In a nationwide prospect i ve follow-up study on very preterm and ( or ) very low birth weight infants ( n = 717 ) , we studied the relationship between thyroxine levels in the 1st wk of life and neurodevelopmental outcome at 5 y of age and school performance at 9 y of age . Thyroxine concentrations from filter paper eluates were determined in 717 infants : 32 % had levels of more than 3 SD below the mean ( 60 nmol/L ) . The percentage of infants with such low levels increased with decreasing gestational age . At the age of 5 y , 96 % of survivors(n = 640 ) were available for extensive neurodevelopmental examination : 85 ( 13.3 % ) had a disability and 92 ( 14.3 % ) a h and icap . At the age of 9 y , 83 % of survivors ( n = 552 ) answered a question naire on school performance : 300 ( 54.3 % ) were in mainstream education in a grade appropriate for age , 151 ( 27 % ) were in mainstream education with grade retention , and 101 ( 18.3 % ) were in special education . Both neurologic dysfunction at age 5 y and school failure at age 9 y were significantly related to lower neonatal thyroxine levels even after adjustment for other perinatal factors ( odds ratio , 1.3 ) . Whether this relationship is causal should be investigated . If a causal relationship exists , substitution therapy may at least partially prevent neurologic dysfunction and learning disabilities , both common sequelae of very preterm birth",
" Three And ean villages at altitudes of 3,100 to 3,500 meters above sea level were studied in order to determine the prophylac— ' tic effect of iodized oil administration on endemic goiter \\ and cretinism ( 1 ) . At the time of the study the population in | these villages was approximately 4,000 , with an annual growth ' rate of about three percent . In a group of 3,000 subjects i examined in a house-to-house survey , the visible goiter rate , : as defined in an accompanying paper ( 2 ) , was 55 percent . However , ? when the cccurrence of palpable goiter was considered as well , | the incidence of goiter rose to 83 percent . Fifty percent of * the children in the 0 - 5 yr age group were goitrous and of these , | 20 percent demonstrated visible goiter . Goiter prevalence l increased with age , as did nodularity . An example of this is ‘ shown in Fig. 1 . In some families every member was found with ii goiter as illustrated in Fig. 2 . Goiter was also found among 4 the domestic animals . The percentage of defective persons in the i three villages ranged from 1.0 to 3.6 percent . Although these _ . x villages are accessible by automobile , they are still quite remote * , and isolated",
"Women with antibodies against the enzyme thyroid peroxidase [ TPO-Ab ; formerly microsomal antibodies ( MsAb ) ] are at particular risk for developing postpartum thyroid dysfunction ; the latter is significantly associated with postpartum depression . Although the negative effect of postpartum maternal depression on child development is well documented , the consequences of elevated titers of TPO-Ab during pregnancy and subsequent postpartum thyroid dysfunction on child development are not known . In a prospect i ve study of a cohort of 293 pregnant women , the occurrence of TPO-Ab during gestation , thyroid dysfunction , and depression was investigated . Five years after delivery , child development was assessed in 230 children of the original cohort using the Dutch translation of the McCarthy Scales of Children 's Abilities . Children of women with TPO-Ab during late gestation ( n = 19 , with normal thyroid function ) had significantly lower scores ( by t test ) on the McCarthy Scales of Children 's Abilities than antibody-negative women . The difference on the General Cognitive Scale , which reflects IQ scores , was substantial ( 10.5 points ; t = 2.8 ; P = 0.005 ) . After correction for possibly confounding variables , maternal TPO-Ab during gestation was found to be the most important factor related to the scores on the General Cognitive Scale ( odds ratio = 10.5 ; 95 % confidence interval = 3 - 34 ; P = 0.003 ) . We conclude that children of pregnant women who had elevated titers of TPO-Ab but normal thyroid function are at risk for impaired development",
"A prospect i ve observational study was performed in pregnant women with known thyroid disease . We studied the effect of maternal thyroid function in the first half of pregnancy on the neurologic development of the infant in the first 2 y of life . Clinical and thyroid function data were collected from 20 pregnant women with known thyroid disease and their newborn children . Infants were divided into three groups according to their maternal thyroid function within the first half of pregnancy : Group A ( n = 7 ) : maternal sub clinical hypothyroidism , Group B ( n = 6 ) : maternal euthyroidism , and Group C ( n = 7 ) : maternal hyperthyroidism or sub clinical hyperthyroidism . Neurophysiologic , i.e. motor nerve conduction velocity and somatosensory evoked potentials and neurologic and developmental ( Bayley scales ) assessment s were done . One infant , born to a mother with Graves ' disease , developed transient hyperthyroidism . At the age of 6 and 12 mo , the mean mental developmental index ( MDI ) score was 16 points lower for infants in Group A than for those in Group B ( p = 0.03 and 0.02 , respectively ) . At the age of 24 mo , the mean MDI score was 6 points lower , which was not statistically significant . Neurophysiologic and neurologic assessment s and the mean Psychomotor Developmental scores did not differ among the three groups . In conclusion , maternal sub clinical hypothyroidism in the first half of pregnancy was associated with a lower mean MDI score in their infants during the first year of life"
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CONTEXT Necrotizing enterocolitis ( NEC ) is the most frequent gastrointestinal emergency in neonates . The microbiome of the preterm gut may regulate the integrity of the intestinal mucosa . Probiotics may positively contribute to mucosal integrity , potentially reducing the risk of NEC in neonates . OBJECTIVE To perform an up date d systematic review and meta- analysis on the efficacy and safety of probiotics for the prevention of NEC in premature infants . DATA SOURCES Structured search es were performed in : Medline , Embase , and the Cochrane Central Register of Controlled Trials ( all via Ovid , from 2013 to January 2015 ) . Clinical trial registries and electronically available conference material s were also search ed . An up date d search was conducted June 3 , 2016 . STUDY SELECTION R and omized trials including infants less than 37 weeks gestational age or less than 2,500 g on probiotic vs. st and ard therapy . DATA EXTRACTION Data extraction of the newly-identified trials with a double check of the previously-identified trials was performed using a st and ardized data collection tool . RESULTS Thirteen additional trials ( n = 5,033 ) were found . The incidence of severe NEC ( RR 0.53 95 % CI [ 0.42 - 0.66 ] ) and all-cause mortality ( RR 0.79 95 % CI [ 0.68 - 0.93 ] ) were reduced . No difference was shown in culture-proven sepsis RR 0.88 95 % CI [ 0.77 - 1.00 ] . LIMITATIONS Heterogeneity of organisms and dosing regimens studied prevent a species-specific treatment recommendation from being made . CONCLUSIONS Preterm infants benefit from probiotics to prevent severe NEC and death
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"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 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 Probiotics may reduce necrotising enterocolitis and late-onset sepsis after preterm birth . However , there has been concern about the rigour and generalisability of some trials and there is no agreement about whether or not they should be used routinely . We aim ed to test the effectiveness of the probiotic Bifidobacterium breve BBG-001 to reduce necrotising enterocolitis , late-onset sepsis , and death in preterm infants . METHODS In this multicentre , r and omised controlled phase 3 study ( the PiPS trial ) , we recruited infants born between 23 and 30 weeks ' gestational age within 48 h of birth from 24 hospitals in southeast Engl and . Infants were r and omly assigned ( 1:1 ) to probiotic or placebo via a minimisation algorithm r and omisation programme . The probiotic intervention was B breve BBG-001 suspended in dilute elemental infant formula given enterally in a daily dose of 8·2 to 9·2 log10 CFU ; the placebo was dilute infant formula alone . Clinicians and families were masked to allocation . The primary outcomes were necrotising enterocolitis ( Bell stage 2 or 3 ) , blood culture positive sepsis more than 72 h after birth ; and death before discharge from hospital . All primary analyses were by intention to treat . This trial is registered with IS RCT N , number 05511098 and EudraCT , number 2006 - 003445 - 17 . FINDINGS Between July 1 , 2010 , and July 31 , 2013 , 1315 infants were recruited ; of whom 654 were allocated to probiotic and 661 to placebo . Five infants had consent withdrawn after r and omisation , thus 650 were analysed in the probiotic group and 660 in the placebo group . Rates of the primary outcomes did not differ significantly between the probiotic and placebo groups . 61 infants ( 9 % ) in the probiotic group had necrotising enterocolitis compared with 66 ( 10 % ) in the placebo group ( adjusted risk ratio 0·93 ( 95 % CI 0·68 - 1·27 ) ; 73 ( 11 % ) infants in the probiotics group had sepsis compared with 77 ( 12 % ) in the placebo group ( 0·97 ( 0·73 - 1·29 ) ; and 54 ( 8 % ) deaths occurred before discharge home in the probiotic group compared with 56 ( 9 % ) in the placebo group ( 0·93 [ 0·67 - 1·30 ] ) . No probiotic-associated adverse events were reported . INTERPRETATION There is no evidence of benefit for this intervention in this population ; this result does not support the routine use of B breve BBG-001 for prevention of necrotising enterocolitis and late-onset sepis in very preterm infants . FUNDING UK National Institute for Health Research Health Technology Assessment programme",
"OBJECTIVE The aim of this study was to compare the effect of administration of probiotics on feeding tolerance and growth outcomes of HIV-exposed ( but uninfected ) versus HIV non-exposed preterm infants . The None hypothesis of this study states that there will be no difference in the feeding tolerance and growth outcomes for both probiotic-exposed and unexposed premature very low birth weight infants . METHODS A r and omized , double-blind , placebo-controlled trial was conducted during the period from July 2011 to August 2012 . HIV-exposed and non-exposed premature ( were r and omized to receive either a probiotic mixture or placebo . The multispecies probiotic mixture consisted of 1 × 10(9 ) CFU , Lactobacillus rhamnosus GG and Bifidobacterium infantis per day and was administered for 28 d. Anthropometrical parameters , daily intakes , and feeding tolerance were monitored . RESULTS Seventy-four HIV-exposed and 110 unexposed infants were enrolled and r and omized ( mean birth weight 987 g ± 160 g , range , 560 - 1244 g ; mean gestational age 28.7 wk ) . In all 4227 probiotic doses were administered ( mean 22.9/infant ) . There was no difference in the average daily weight gain for treatment groups or HIV exposure . The HIV-exposed group achieved significantly higher z scores for length and head circumference at day 28 than the unexposed group ( P signs of feeding intolerance and abdominal distension between the groups . CONCLUSION Probiotic supplementation did not affect growth outcomes or the incidence of any signs of feeding intolerance in HIV exposure ",
"Objectives To assess the effect of the probiotic VSL#3 in prevention of neonatal sepsis in low birthweight ( LBW ) infants . Design R and omised , double-blind , placebo-controlled trial . Setting Community setting in rural India . Participants LBW infants aged 3–7 days . Interventions Infants were r and omised to receive probiotic ( VSL#3 , 10 billion colony-forming units ( cfu ) ) or placebo for 30 days , and were followed up for 2 months . Main outcome measure Possible serious bacterial infection ( PSBI ) as per the Integrated Management of Neonatal Childhood Illnesses algorithm , as diagnosed by fieldworkers/physicians . Results 668 infants were r and omised to VSL#3 and 672 to placebo . By intention-to-treat analysis , the risk of PSBI among infants in the overall population of LBW infants was not statistically significant ( RR 0.79 ( 95 % CI 0.56 to 1.03 ) ) . Probiotics reduced median days of hospitalisation ( 6 days vs 3 days in probiotics ) ( p=0.018 ) but not the risk of hospitalisation ( RR 0.66 ( 95 % CI 0.42 to 1.04 ) . The onset of PSBI in 10 % of infants occurred on the 40th day in the probiotics arm versus the 25th day in the control arm ( p=0.063 ) . Conclusions Daily supplementation of LBW infants with probiotics VSL#3 ( 10 billion cfu ) for 30 days led to a non-significant 21 % reduction in risk of neonatal sepsis . A larger study with sufficient power and a more specific primary end point is warranted to confirm the preventive effect of VSL#3 on neonatal sepsis in LBW infants . Trial registration number The study is registered at the Clinical Trial Registry of India ( CTRI/2008/091/000049 )",
"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",
"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 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",
"OBJECTIVE . The goal was to investigate the efficacy of orally administered probiotics in preventing necrotizing enterocolitis for very low birth weight preterm infants . METHODS . A prospect i ve , blinded , r and omized , multicenter controlled trial was conducted at 7 NICUs in Taiwan , to evaluate the beneficial effects of probiotics in necrotizing enterocolitis among very low birth weight infants ( birth weight : and were assigned r and omly to 2 groups after parental informed consent was obtained . Infants in the study group were given Bifidobacterium bifidum and Lactobacillus acidophilus , added to breast milk or mixed feeding ( breast milk and formula ) , twice daily for 6 weeks . Infants in the control group were fed with breast milk or mixed feeding . The clinicians caring for the infants were blinded to the group assignment . The primary outcome measurement was death or necrotizing enterocolitis ( Bell 's stage ≥2 ) . RESULTS . Four hundred thirty-four infants were enrolled , 217 in the study group and 217 in the control group . The incidence of death or necrotizing enterocolitis ( stage ≥2 ) was significantly lower in the study group ( 4 of 217 infants vs 20 of 217 infants ) . The incidence of necrotizing enterocolitis ( stage ≥2 ) was lower in the study group , compared with the control group ( 4 of 217 infants vs 14 of 217 infants ) . No adverse effect , such as sepsis , flatulence , or diarrhea , was noted . CONCLUSION . Probiotics , in the form of Bifidobacterium and Lactobacillus , fed enterally to very low birth weight preterm infants for 6 weeks reduced the incidence of death or necrotizing enterocolitis",
"OBJECTIVE To evaluate the health benefits of an exclusively human milk-based diet compared with a diet of both human milk and bovine milk-based products in extremely premature infants . STUDY DESIGN Infants fed their own mothers ' milk were r and omized to 1 of 3 study groups . Groups HM100 and HM40 received pasteurized donor human milk-based human milk fortifier when the enteral intake was 100 and 40 mL/kg/d , respectively , and both groups received pasteurized donor human milk if no mother 's milk was available . Group BOV received bovine milk-based human milk fortifier when the enteral intake was 100 mL/kg/d and preterm formula if no mother 's milk was available . Outcomes included duration of parenteral nutrition , morbidity , and growth . RESULTS The 3 groups ( total n = 207 infants ) had similar baseline demographic variables , duration of parenteral nutrition , rates of late-onset sepsis , and growth . The groups receiving an exclusively human milk diet had significantly lower rates of necrotizing enterocolitis ( NEC ; P = .02 ) and NEC requiring surgical intervention ( P = .007 ) . CONCLUSIONS For extremely premature infants , an exclusively human milk-based diet is associated with significantly lower rates of NEC and surgical NEC when compared with a mother 's milk-based diet that also includes bovine milk-based products",
"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 OF THE STUDY Preterm infants are managed with antibiotics for sepsis , including suspected or probable sepsis . This leads to a delayed and abnormal colonization of the gut with potentially pathogenic organisms and a microbiome , which lacks biodiversity and increases the risk for late-onset sepsis ( LOS ) . Probiotics have been proven to reduce the risk for necrotizing enterocolitis , but evidence for prevention of LOS is inconclusive . Probiotic effect depends also on the strain used , dose and indication for use . This study evaluated Bacillus clausii probiotic administered prophylactically to preterm neonates for prevention of LOS . OBJECTIVES To study B.clausii given prophylactically to preterm neonates for prevention of LOS . DESIGN Double-blinded , placebo-controlled , r and omized trial . SETTING S Tertiary care neonatal unit in India . PARTICIPANTS Consecutive preterm neonates INTERVENTION R and omized to receive either probiotic or placebo for 6 weeks , discharge from hospital , death or occurrence of sepsis , whichever was earlier . PRIMARY OUTCOME Incidence of definite and probable LOS in probiotic group compared with placebo . RESULTS Of 326 eligible preterm infants , 244 were enrolled and 82 were excluded . Of these , 120 were stratified as extreme preterm and r and omized to receive placebo ( n = 59 ) and probiotic ( n = 61 ) . Of 124 babies stratified as very preterm , an equal number was r and omized to receive placebo ( n = 62 ) and probiotic ( n = 62 ) . There was no significant difference in the incidence of LOS between the two arms in the extreme preterm group [ 29 % vs. 23 % ; relative risk ( RR ) 1.27 ; 95 % confidence interval ( CI ) 0.88 - 1.66 ; p = 0.36 ] and the very preterm group ( 13 % vs. 10 % ; RR 1.33 ; 95 % CI 0.96 - 1.70 ; p = 0.32 ) . Full feeds were achieved significantly faster in the probiotic group in both the extreme preterm ( RR 0.82 ; 95 % CI 0.74 - 0.88 ) and the very preterm ( RR 0.67 ; 95 % 0.32 - 0.77 ) . CONCLUSIONS Prophylactic administration of B.clausii to preterm neonates did not result in a significant difference in the incidence of LOS as compared with placebo ",
"Background : The interrelations between early enteral feeding , necrotising enterocolitis ( NEC ) , and nosocomial sepsis ( NS ) remain unclear . Objective : To evaluate the effect of age at the introduction of enteral feeding on the incidence of NS and NEC in very low birthweight ( VLBW Methods : Data were collected on the pattern of enteral feeding and perinatal and neonatal morbidity on all VLBW infants born in one centre during 1995–2001 . Enteral feeding was compared between infants with and without NS and /or NEC . Results : The study sample included 385 infants . Of these , 163 ( 42 % ) developed NS and 35 ( 9 % ) developed NEC . Enteral feeding was started at a significantly earlier mean ( SD ) age in infants who did not develop nosocomial sepsis ( 2.8 ( 2.6 ) v 4.8 ( 3.7 ) days , p = 0.0001 ) . Enteral feeding was introduced at the same age in babies who did or did not develop NEC ( 3.1 ( 2 ) v 3.7 ( 3 ) days , p = 0.28 ) . Over the study period , the mean annual age at the start of enteral feeding fell consistently , and this correlated with the mean annual incidence of NS ( r2 = 0.891 , p = 0.007 ) . Multiple logistic regression analysis showed age at start of enteral feeding , respiratory distress syndrome , and birth weight to be the most significant predictors of risk of NS ( p = 0.0005 , p = 0.024 , p = 0.011 ) . Conclusions : Early enteral feeding was associated with a reduced risk of NS but no change in the risk of NEC in VLBW infants . These findings support the use of early enteral feeding in this high risk population , but this needs to be confirmed in a large r and omised controlled trial",
"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",
"OBJECTIVE To evaluate the effect of oral administration of probiotics on intestinal colonization with drug-resistant bacteria among preterm infants in the neonatal intensive care unit ( NICU ) . METHODS A double-blind , r and omized , placebo-controlled trial was carried out in the preterm infants who were transferred to the NICU immediately after birth . These infants were stratified by whether they were breastfed and then r and omized into test group and control group . The test group was given probiotics from the day when enteral feeding began , while the control group was treated conventionally without probiotics . The two groups were compared in terms of the colonization with extended-spectrum beta-lactamase-producing bacteria , as assessed by rectal swabs on days 1 , 3 , 7 , and 14 after birth , and the incidence of diseases . RESULTS Rectal colonization with drug-resistant bacteria was found in the test group ( n=119 ) and control group ( n=138 ) on days 1 , 3 , 7 , and 14 after birth . There were no significant differences in the incidence of late-onset sepsis and necrotizing enterocolitis between the two groups ( P>0.05 ) . Among non-breastfed infants , the test group had significantly decreased rectal colonization with drug-resistant bacteria compared with the control group on day 14 after birth ( 71.1 % vs 88.9 % ; P=0.04 ) . No probiotic-related adverse events were observed in the study . CONCLUSIONS Oral administration of probiotics may reduce rectal colonization with drug-resistant bacteria in preterm infants under certain conditions and shows good safety",
"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",
"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 ",
"OBJECTIVE To test the efficacy of probiotic and prebiotic , alone or combined ( synbiotic ) , on the prevention of necrotizing enterocolitis ( NEC ) in very low birth weight ( VLBW ) infants . STUDY DESIGN A prospect i ve , r and omized , controlled trial was conducted at 5 neonatal intensive care units in Turkey . VLBW infants ( n = 400 ) were assigned to a control group and 3 study groups that were given probiotic ( Bifidobacterium lactis ) , prebiotic ( inulin ) , or synbiotic ( Bifidobacterium lactis plus inulin ) added to breastmilk or formula for a maximum of 8 weeks before discharge or death . The primary outcome was NEC ( Bell stage ≥2 ) . RESULTS The rate of NEC was lower in probiotic ( 2.0 % ) and synbiotic ( 4.0 % ) groups compared with prebiotic ( 12.0 % ) and placebo ( 18.0 % ) groups ( P The times to reach full enteral feeding were faster ( P the rates of clinical nosocomial sepsis were lower ( P = .004 ) , stays in the neonatal intensive care unit were shorter , ( P = .002 ) , and mortality rates were lower ( P = .003 ) for infants receiving probiotics , prebiotics , or synbiotic than controls . The use of antenatal steroid ( OR 0.5 , 95 % CI 0.3 - 0.9 ) and postnatal probiotic ( alone or in synbiotic ) ( OR 0.5 , 95 % CI 0.2 - 0.8 ) decreased the risk of NEC , and maternal antibiotic exposure increased this risk ( OR 1.9 , 95 % CI 1.1 - 3.6 ) . CONCLUSIONS In VLBW infants , probiotic ( Bifidobacterium lactis ) and synbiotic ( Bifidobacterium lactis plus inulin ) but not prebiotic ( inulin ) alone decrease NEC",
"Abstract Objective : The aim of the study was to evaluate the neurodevelopment outcomes of very low birth weight ( VLBW ) preterm infants supplemented with oral probiotics for the prevention of necrotizing enterocolitis ( NEC ) . Methods : A prospect i ve follow-up study was performed in a cohort of VLBW preterm infants enrolled in a single center r and omized controlled clinical trial to evaluate the efficacy of oral probiotics for the prevention of NEC . Cognitive and neuromotor developments were assessed by using the Bayley scales of infant development II . Sensory and neurological performance was evaluated by st and ard techniques . The primary outcome was neurodevelopmental impairment at 18–24 months ’ corrected age . Results : A total of 400 infants completed the trial protocol . Of the 370 infants eligible for follow-up , 249 infants ( 124 in the probiotics group and 125 in the control group ) were evaluated . There was no significant difference in any of the neurodevelopmental and sensory outcomes between the two groups . Conclusion : Oral probiotic given to VLBW infants to reduce the incidense and severity of NEC started with the first feed did not affect neuromotor , neurosensory and cognitive outcomes at 18–24 months ’ corrected age",
"OBJECTIVE To test the hypothesis that normalizing the intestinal flora by administration of prophylactic probiotics would provide a natural defense , thereby reducing both the incidence and severity of necrotizing enterocolitis ( NEC ) in preterm neonates . STUDY DESIGN Neonates were r and omized to either receive a daily feeding supplementation with a probiotic mixture ( Bifidobacteria infantis , Streptococcus thermophilus , and Bifidobacteria bifidus ; Solgar , Israel ) of 10(9 ) colony forming units (CFU)/day or to not receive feed supplements . NEC was grade d according to Bell 's criteria . RESULTS For 72 study and 73 control infants , respectively , birth weight ( 1152 + /- 262 g vs 1111 + /- 278 g ) , gestational age ( 30 + /- 3 weeks vs 29 + /- 4 weeks ) , and time to reach full feeds ( 14.6 + /- 8.7 days vs 17.5 + /- 13.6 days ) were not different . The incidence of NEC was reduced in the study group ( 4 % vs 16.4 % ; P=.03 ) . NEC was less severe in the probiotic-supplemented infants ( Bell 's criteria 2.3 + /- 0.5 vs 1.3 + /- 0.5 ; P=.005 ) . Three of 15 babies who developed NEC died , and all NEC-related deaths occurred in control infants . CONCLUSION Probiotic supplementation reduced both the incidence and severity of NEC in our premature neonatal population",
"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",
"IMPORTANCE NEC is a common and severe complication in premature neonates , particularly those with very-low-birth-weight ( VLBW , Probiotics including lactobacillus rhamnosus GG ( LGG ) proved effective in preventing NEC in preterm infants in several RCTs . OBJECTIVE Lactoferrin , a mammalian milk glycoprotein involved in innate immune host defences , can reduce the incidence of NEC in animal models , and its action is enhanced by LGG . We tried to assess whether bovine lactoferrin ( BLF ) , alone or with the probiotic LGG , has a similar effect in human infants , something that has not yet been studied . DESIGN An international , multicenter , r and omized , double-blind , placebo-controlled trial conducted from October 1st , 2007 through July 31st , 2010 . SETTING Thirteen Italian and New Zeal and tertiary neonatal intensive care units . PARTICIPANTS 743 VLBW neonates were assessed until discharge for development of NEC . INTERVENTION Infants were r and omly assigned to receive orally either BLF ( 100 mg/day ) alone ( group LF ; n = 247 ) or with LGG ( at 6 × 10(9 ) CFU/day ; group BLF + LGG ; n = 238 ) , or placebo ( Control group ; n = 258 ) from birth until day 30 of life ( 45 for neonates ≥ stage 2 NEC ; death- and /or-≥ stage 2 NEC prior to discharge . RESULTS Demographics , clinical and management characteristics of the 3 groups were similar , including type of feeding and maternal milk intakes . NEC incidence was significantly lower in groups BLF and BLF + LGG [ 5/247 ( 2.0 % ) ] and 0/238 ( 0 % ) , respectively ] than in controls [ 14/258 ( 5.4 % ) ] ( RR = 0.37 ; 95 % CI : 0.136 - 1.005 ; p = 0.055 for BLF vs. control ; RR = 0.00 ; p control ) . The incidence of death- and /or-NEC was significantly lower in both treatment groups ( 4.0 % and 3.8 % in BLF and BLF + LGG vs. 10.1 % in control ; RR = 0.39 ; 95 % CI : 0.19 - 0.80 ; p = 0.008 . RR = 0.37 ; 95 % CI : 0.18 - 0.77 ; p = 0.006 , respectively ) . No adverse effects or intolerances to treatment occurred . CONCLUSIONS AND RELEVANCE Compared with placebo , BLF supplementation alone or in combination with LGG reduced the incidence of ≥ stage 2 NEC and of death- and /or ≥ stage 2 NEC in VLBW neonates . BLF might be a promising strategy to prevent NEC in NICU setting s. Further data on larger sample sizes are warranted before BLF can be widespreadly used in clinical setting s. TRIAL REGISTRATION IS RCT N53107700-http://www.controlled-_trials.com/IS RCT N53107700",
"OBJECTIVE To assess the effect of probiotics on the incidence of necrotizing enterocolitis ( NEC ) in premature infants born to human immunodeficiency virus (HIV)-positive and HIV-negative women . PATIENTS AND METHODS HIV-exposed and HIV-unexposed premature infants were r and omized to either the probiotic or the placebo group . The probiotic consisted of 1 × 10(9 ) colony-forming units , Lactobacillus rhamnosus GG and Bifidobacterium infantis per day . RESULTS In total , 74 HIV-exposed and 110 HIV-unexposed infants were enrolled and r and omized . The incidence of death [ 4 ( 5.4 % ) vs. 7 ( 6 % ) ; p = 0.79 ] and NEC [ 4 ( 5 % ) vs. 5 ( 5 % ) ; p = 0.76 ] did not differ significantly between the HIV-exposed and HIV-unexposed groups . A significant difference was found for total NEC incidence between the study and control groups [ 3 ( 3 % ) vs. 6 ( 6 % ) ; p = 0.029 ] . The incidence of NEC in the HIV-exposed group differed significantly [ Bells I 2 ( 5 % ) vs. Bells III 2 ( 5 % ) ; p = 0.045 ) . CONCLUSION Probiotic supplementation reduced the incidence of NEC in the premature very low birth weight infants ; however , results failed to show a lower incidence of NEC in HIV-exposed premature infants . A reduction in the severity of disease was found in the HIV-exposed study group",
"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 compare stool colonization among premature infants receiving high-dose probiotics versus st and ard dose . STUDY DESIGN This blinded , r and omized , placebo-controlled trial was conducted in a Level III neonatal unit . Eligibility criteria were gestational age 27 - 33 weeks , age malformations and necrotizing enterocolitis/sepsis were exclusions . A total of 149 subjects were r and omly allocated to groups A through D ( received 12-hourly probiotic supplements of 10(10 ) cells for 21 days , 10(10 ) cells for 14 days , 10(9 ) cells for 21 days and placebo , respectively ) . Key outcome was stool colonization by a probiotic organism at 28 days . RESULTS Colonization with Lactobacillus and Bifidobacterium was significantly higher in groups A , B , and C versus placebo respectively , but groups A through C did not differ from each other . There were trends toward more colony forming unit ( cfu ) of Lactobacillus and Bifidobacterium per milliliter of stool in group A versus B and B versus C. Groups A and B and spontaneous preterm labor ( SPL ) independently predicted high Lactobacillus counts on day 28 ; groups A , B , and C and SPL predicted high Bifidobacterium counts . CONCLUSION Proportion of infants colonized with probiotic species was similar with high-dose and st and ard dose regimes"
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41179614-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND Type 2 diabetes is impacting millions of people globally ; however , many future cases can be prevented through lifestyle changes and interventions . Primary care is an important setting for diabetes prevention , for at-risk population s , because it is a patient 's primary point of contact with the health care system and professionals can provide lifestyle counselling and support , as well as monitoring health outcomes . These are all essential elements for diabetes prevention for at-risk adults . AIM To underst and the factors related to the delivery and uptake of type 2 diabetes prevention interventions within primary care in higher income countries . METHODS For this narrative systematic review , we combined qualitative and quantitative studies of diabetes prevention within a primary care setting for patients at-risk of developing the condition . We used an iterative approach for evidence collection , which included using several data bases ( MEDLINE , Embase , Pysch info , BNI , SSCI , CINAHL , ASSIA ) , where we combined diabetes terms with primary care terms . Narrative and thematic synthesis were utilised to identify the prominent themes emerging from the data . RESULTS A data base of 6646 records was screened by the research team , and 18 papers were included . Three major themes were identified in this review . The first theme of context and setting of diabetes progression includes the risk and progression of diabetes , primary care as a setting , and where the responsibility for change is thought to lie . This review also found mixed views on the value of preventative services within primary care . The second theme focused on the various patient factors associated with diabetes prevention such as a patient 's motivation to modify their current lifestyle , perceptions and knowledge ( or lack thereof ) of the impacts of diabetes , lack of follow-up in healthcare setting s , and trust in healthcare professionals . The third theme was centred on professional factors impacting on diabetes prevention which included workload , time constraints , re sources , self-efficacy and knowledge as well as professionals ' perception of patient motivations towards change . CONCLUSION This review explored the factors influencing diabetes prevention in primary care , and identified the context of prevention , as well as patient and professional factors related to preventative services being offered in primary care . This systematic review complements previous review s of real-world setting s by exploring the significant factors in prevention , and the findings are relevant to academics , policymakers , patients and practitioners interested in underst and ing the factors associated with the delivery and uptake of diabetes prevention interventions
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"The aim of the Finnish Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying type 2 diabetes in individuals with impaired glucose tolerance ( IGT ) and to evaluate the effect of the programme on the risk factors of atherosclerotic vascular diseases and the incidence of cardiovascular events . In this ongoing study , a total of 523 overweight subjects with IGT based on two oral glucose tolerance tests were r and omized to either an intervention group or a control group . The main measure in the intervention group is individual dietary advice aim ed at reducing weight and intake of saturated fat and increasing intake of dietary fibre . The intervention subjects are individually guided to increase their level of physical activity . The control group receives general information about the benefits of weight reduction , physical activity and healthy diet in the prevention of diabetes . A pilot study began in 1993 , and recruitment ended in 1998 . By the end of April 1999 there were 65 new cases of diabetes , 34 drop-outs and one death . The weight reduction was greater ( -4.6 kg ) at 1 year in the intervention group ( n = 152 ) than in the control group ( n = 143 , -0.9 kg , P weight reduction of at least 5 kg , while the corresponding figures for the control subjects were 14.0 and 12.0 % ( P reductions in 2 h glucose , fasting and 2 h insulin , systolic and diastolic blood pressure , and serum triglycerides . Most of the beneficial changes in cardiovascular risk factors were sustained for 2 years . These interim results of the ongoing Finnish Diabetes Prevention Study demonstrate the efficacy and feasibility of the lifestyle intervention programme",
"Background : Research on the translation of efficacious lifestyle change programs to prevent type 2 diabetes into community or clinical setting s is needed . Objective : The objective of this study was to examine the reach , implementation , and efficacy of a 6-month lifestyle program implemented in primary care by nurse practitioners ( NPs ) for adults at risk of type 2 diabetes . Methods : The NP sites ( n = 4 ) were r and omized to an enhanced st and ard care program ( one NP and one nutrition session ) or a lifestyle program ( enhanced st and ard care and six NP sessions ) . These NPs recruited adults at risk of diabetes from their practice ( n = 58 ) , with an acceptance rate of 70 % . Results : The program reached a diverse , obese , and moderately low income sample . The NPs were able to successfully implement the protocol s. The average length of the program was 9.3 months . Attendance was high ( 98 % ) , and attrition was low ( 12 % ) . The NPs were able to adopt the educational , behavioral , and psychosocial strategies of the intervention easily . Motivational interviewing was more difficult for NPs . Mixed-model repeated- measures analysis indicated significant trends or improvement in both groups for nutrition and exercise behavior . Participants of the lifestyle program demonstrated trends for better high-density lipoprotein ( HDL ) and exercise behavior compared with the enhanced st and ard care participants . Twenty-five percent of lifestyle participants met treatment goals of 5 % weight loss compared with 11 % of st and ard care participants . Discussion : A lifestyle program can be implemented in primary care by NPs , reach the targeted population , and be modestly successful . Further research is indicated",
"BACKGROUND In the 2.8 years of the Diabetes Prevention Program ( DPP ) r and omised clinical trial , diabetes incidence in high-risk adults was reduced by 58 % with intensive lifestyle intervention and by 31 % with metformin , compared with placebo . We investigated the persistence of these effects in the long term . METHODS All active DPP participants were eligible for continued follow-up . 2766 of 3150 ( 88 % ) enrolled for a median additional follow-up of 5.7 years ( IQR 5.5 - 5.8 ) . 910 participants were from the lifestyle , 924 from the metformin , and 932 were from the original placebo groups . On the basis of the benefits from the intensive lifestyle intervention in the DPP , all three groups were offered group-implemented lifestyle intervention . Metformin treatment was continued in the original metformin group ( 850 mg twice daily as tolerated ) , with participants unmasked to assignment , and the original lifestyle intervention group was offered additional lifestyle support . The primary outcome was development of diabetes according to American Diabetes Association criteria . Analysis was by intention-to-treat . This study is registered with Clinical Trials.gov , number NCT00038727 . FINDINGS During the 10.0-year ( IQR 9.0 - 10.5 ) follow-up since r and omisation to DPP , the original lifestyle group lost , then partly regained weight . The modest weight loss with metformin was maintained . Diabetes incidence rates during the DPP were 4.8 cases per 100 person-years ( 95 % CI 4.1 - 5.7 ) in the intensive lifestyle intervention group , 7.8 ( 6.8 - 8.8 ) in the metformin group , and 11.0 ( 9.8 - 12.3 ) in the placebo group . Diabetes incidence rates in this follow-up study were similar between treatment groups : 5.9 per 100 person-years ( 5.1 - 6.8 ) for lifestyle , 4.9 ( 4.2 - 5.7 ) for metformin , and 5.6 ( 4.8 - 6.5 ) for placebo . Diabetes incidence in the 10 years since DPP r and omisation was reduced by 34 % ( 24 - 42 ) in the lifestyle group and 18 % ( 7 - 28 ) in the metformin group compared with placebo . INTERPRETATION During follow-up after DPP , incidences in the former placebo and metformin groups fell to equal those in the former lifestyle group , but the cumulative incidence of diabetes remained lowest in the lifestyle group . Prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years . FUNDING National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK )",
"Background Type 2 diabetes is a major public health problem in Australia with prevalence increasing in parallel with increasing obesity . Prevention is an essential component of strategies to reduce the diabetes burden . There is strong and consistent evidence from r and omised controlled trials that type 2 diabetes can be prevented or delayed through lifestyle modification which improves diet , increases physical activity and achieves weight loss in at risk people . The current challenge is to translate this evidence into routine community setting s , determine feasible and effective ways of delivering the intervention and providing on-going support to sustain successful behavioural changes . Methods / Design The Sydney Diabetes Prevention Program ( SDPP ) is a translational study which will be conducted in 1,550 participants aged 50 - 65 years ( including 100 indigenous people aged 18 years and older ) at high risk of future development of diabetes . Participants will be identified through a screening and recruitment program delivered through primary care and will be offered a community-based lifestyle modification intervention . The intervention comprises an initial individual session and three group sessions based on behaviour change principles and focuses on five goals : 5 % weight loss , 210 min/week physical activity ( aerobic and strength training exercise ) , limit dietary fat and saturated fat to less than 30 % and 10 % of energy intake respectively , and at least 15 g/1000 kcal dietary fibre . This is followed by 3-monthly contact with participants to review progress and offer ongoing lifestyle advice for 12 months . The effectiveness and costs of the program on diabetes-related risk factors will be evaluated . Main outcomes include changes in weight , physical activity , and dietary changes ( fat , saturated fat and fibre intake ) . Secondary outcomes include changes in waist circumference , fasting plasma glucose , blood pressure , lipids , quality of life , psychological well being , medication use and health service utilization . Discussion This translational study will ascertain the reach , feasibility , effectiveness and cost-effectiveness of a lifestyle modification program delivered in a community setting through primary health care . If demonstrated to be effective , it will result in recommendations for policy change and practical methods for a wider community program for preventing or delaying the onset of type 2 diabetes in high risk people",
"Clinical trials have demonstrated that lifestyle changes can prevent type 2 diabetes , but the importance of leisure-time physical activity ( LTPA ) is still unclear . We carried out post hoc analyses on the role of LTPA in preventing type 2 diabetes in 487 men and women with impaired glucose tolerance who had completed 12-month LTPA question naires . The subjects were participants in the Finnish Diabetes Prevention Study , a r and omized controlled trial of lifestyle changes including diet , weight loss , and LTPA . There were 107 new cases of diabetes during the 4.1-year follow-up period . Individuals who increased moderate-to-vigorous LTPA or strenuous , structured LTPA the most were 63 - 65 % less likely to develop diabetes . Adjustment for changes in diet and body weight during the study attenuated the association somewhat ( upper versus lower third : moderate-to-vigorous LTPA , relative risk 0.51 , 95 % CI 0.26 - 0.97 ; strenuous , structured LTPA , 0.63 , 0.35 - 1.13 ) . Low-intensity and lifestyle LTPA and walking also conferred benefits , consistent with the finding that the change in total LTPA ( upper versus lower third : 0.34 , 0.19 - 0.62 ) was the most strongly associated with incident diabetes . Thus increasing physical activity may substantially reduce the incidence of type 2 diabetes in high-risk individuals",
"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",
"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",
"Vascular disease is a leading cause of death and disability . While it is preventable , little is known about the feasibility or acceptability of implementing interventions to prevent vascular disease in Australian primary health care . We conducted a cluster r and omised controlled trial assessing prevention of vascular disease in patients aged 40 - 65 by providing a lifestyle modification program in general practice . Interviews with 13 general practice s in the intervention arm of this trial examined their views on implementing the lifestyle modification program in general practice setting s. Qualitative study , involving thematic analysis of semi-structured interviews with 11 general practitioners , four practice nurses and five allied health providers between October 2009 and April 2010 . Providing brief lifestyle intervention fitted well with routine health-check consultations ; however , acceptance and referral to the program was dependent on the level of facilitation provided by program coordinators . Respondents reported that patients engaged with the advice and strategies provided in the program , which helped them make lifestyle changes . Practice nurse involvement was important to sustaining implementation in general practice , while the lack of referral services for people at risk of developing vascular disease threatens maintenance of lifestyle changes as few respondents thought patients would continue lifestyle changes without long-term follow up . Lifestyle modification programs to prevent vascular disease are feasible in general practice but must be provided in a flexible format , such as being offered out of hours to facilitate uptake , with ongoing support and follow up to assist maintenance . The newly formed Medicare Locals may have an important role in facilitating lifestyle modification programs for this target group",
"Objectives : In participatory decision-making ( PDM ) , physicians actively engage patients in treatment and other care decisions . Patients who report that their physicians engage in PDM have better disease self-management and health outcomes . We examined whether physicians ’ diabetes-specific treatment PDM preferences as well as their self-reported practice s are associated with the quality of diabetes care their patients receive . Methods : 2003 cross-sectional survey and medical record review of a r and om sample of diabetes patients ( n = 4198 ) in 10 US health plans across the country and their physicians ( n = 1217 ) . We characterized physicians ’ diabetes care PDM preferences and practice s as ‘ no patient involvement , ’ ‘ physician-dominant , ’ ‘ shared , ’ or ‘ patient-dominant ’ and conducted multivariate analyses examining their effects on the following : ( 1 ) three diabetes care processes ( annual hemoglobin A1c test ; lipid test ; and dilated retinal exam ) ; ( 2 ) patients ’ satisfaction with physician communication ; and ( 3 ) whether patients ’ A1c , systolic blood pressure ( SBP ) , and low-density lipoprotein cholesterol ( LDL ) were in control . Results : Most physicians preferred ‘ shared ’ PDM ( 58 % ) rather than ‘ no patient involvement ’ ( 9 % ) , ‘ physici and ominant ’ ( 28 % ) or ‘ patient dominant ’ PDM ( 5 % ) . However , most reported practicing ‘ physician-dominant ’ PDM ( 43 % ) with most of their patients , rather than ‘ no patient involvement ’ ( 13 % ) , ‘ shared ’ ( 37 % ) or ‘ patient-dominant ’ PDM ( 7 % ) . After adjusting for patient and physician-level characteristics and clustering by health plan , patients of physicians who preferred ‘ shared ’ PDM were more likely to receive A1c tests [ 90 % vs. 82 % , AOR : 2.05 , 95 % CI : 1.03—3.07 ] and patients of physicians who preferred ‘ patient-dominant ’ treatment decision-making were more likely to receive lipid tests [ 60 % vs. 50 % , AOR : 1.58 , 95 % CI : 1.04—2.39 ] than those of providers who preferred ‘ no patient involvement ’ in treatment decision-making . There were no differences in patients ’ satisfaction with their doctor ’s communication or control of A1c , SBP or LDL depending on their physicians ’ PDM preferences . Physicians ’ self-reported PDM practice s were not associated with any of the examined aspects of diabetes care in multivariate analyses . Conclusions : Patients whose physicians prefer more patient involvement in decision-making are more likely than patients whose physicians prefer more physician-directed styles to receive some recommended risk factor screening tests , an important first step toward improved diabetes outcomes . Involving patients in treatment decision-making alone , however , appears not to be sufficient to improve biomedical outcomes",
"BACKGROUND Intensive lifestyle interventions can reduce the incidence of type 2 diabetes in people with impaired glucose tolerance , but how long these benefits extend beyond the period of active intervention , and whether such interventions reduce the risk of cardiovascular disease ( CVD ) and mortality , is unclear . We aim ed to assess whether intensive lifestyle interventions have a long-term effect on the risk of diabetes , diabetes-related macrovascular and microvascular complications , and mortality . METHODS In 1986 , 577 adults with impaired glucose tolerance from 33 clinics in China were r and omly assigned to either the control group or to one of three lifestyle intervention groups ( diet , exercise , or diet plus exercise ) . Active intervention took place over 6 years until 1992 . In 2006 , study participants were followed-up to assess the long-term effect of the interventions . The primary outcomes were diabetes incidence , CVD incidence and mortality , and all-cause mortality . FINDINGS Compared with control participants , those in the combined lifestyle intervention groups had a 51 % lower incidence of diabetes ( hazard rate ratio [ HRR ] 0.49 ; 95 % CI 0.33 - 0.73 ) during the active intervention period and a 43 % lower incidence ( 0.57 ; 0.41 - 0.81 ) over the 20 year period , controlled for age and clustering by clinic . The average annual incidence of diabetes was 7 % for intervention participants versus 11 % in control participants , with 20-year cumulative incidence of 80 % in the intervention groups and 93 % in the control group . Participants in the intervention group spent an average of 3.6 fewer years with diabetes than those in the control group . There was no significant difference between the intervention and control groups in the rate of first CVD events ( HRR 0.98 ; 95 % CI 0.71 - 1.37 ) , CVD mortality ( 0.83 ; 0.48 - 1.40 ) , and all-cause mortality ( 0.96 ; 0.65 - 1.41 ) , but our study had limited statistical power to detect differences for these outcomes . INTERPRETATION Group-based lifestyle interventions over 6 years can prevent or delay diabetes for up to 14 years after the active intervention . However , whether lifestyle intervention also leads to reduced CVD and mortality remains unclear",
"BACKGROUND Intensive lifestyle interventions have been successful in reducing type 2 diabetes incidence . Whether intensive programmes requiring face-to-face contact , trained staff and access to facilities are feasible , on a larger scale , has been debated . OBJECTIVES The aim of this study is to determine the feasibility and efficacy of a lifestyle intervention for type 2 diabetes prevention in men using an assessor-blinded , parallel-group , r and omised controlled trial . The ' Type 2 Diabetes PULSE ( Prevention Using LifeStyle Education ) Programme for Men ' is a 6-month , self-administered , gender-tailored lifestyle intervention , with a multicomponent approach ( weight loss , dietary modification , aerobic exercise and resistance training ) . Eligible men were aged 18 - 65 years , overweight/obese ( BMI 25 - 40 kg·m(-2 ) ) and at high-risk for type 2 diabetes ( score ≥ 12 , Australian diabetes risk tool ) . Men with diagnosed prediabetes were eligible , but those with type 1 and 2 diabetes were ineligible . R and omisation was stratified by age ( intervention or wait-list control group . Data are collected at study entry ( baseline ) , 3 and 6 months . The primary outcome is weight change at 6 months . Secondary outcomes include : fasting plasma glucose , HbA1C , waist circumference , body composition , blood pressure , diet quality , aerobic fitness , muscular fitness and physical activity . Generalised linear mixed models ( intention-to-treat ) will assess outcomes for treatment ( intervention vs. control ) , time ( baseline , 3 and 6-months ) and the treatment-by-time interaction . CONCLUSION The results will determine the efficacy of a type 2 diabetes prevention programme for men with potential for wide reach and dissemination . TRIAL REGISTRATION Australian New Zeal and Clinical Trials Registry ( ACTRN12612000721808 )",
"Aims /hypothesisThis study aim ed to determine whether lifestyle intervention lasting for 4 years affected diabetes incidence , body weight , glycaemia or lifestyle over 13 years among individuals at high risk of type 2 diabetes . Methods Overweight , middle-aged men ( n = 172 ) and women ( n = 350 ) with impaired glucose tolerance were r and omised in 1993–1998 to an intensive lifestyle intervention group ( n = 265 ) , aim ing at weight reduction , dietary modification and increased physical activity , or to a control group ( n = 257 ) that received general lifestyle information . The primary outcome was a diagnosis of diabetes based on annual OGTTs . Secondary outcomes included changes in body weight , glycaemia , physical activity and diet . After active intervention ( median 4 years , range 1–6 years ) , participants still free of diabetes and willing to continue their participation ( 200 in the intervention group and 166 in the control group ) were further followed until diabetes diagnosis , dropout or the end of 2009 , with a median total follow-up of 9 years and a time span of 13 years from baseline . Results During the total follow-up the adjusted HR for diabetes ( intervention group vs control group ) was 0.614 ( 95 % CI 0.478 , 0.789 ; p absolute levels of body weight , fasting and 2 h plasma glucose and a healthier diet . Adherence to lifestyle changes during the intervention period predicted greater risk reduction during the total follow-up . Conclusions /interpretationLifestyle intervention in people at high risk of type 2 diabetes induces sustaining lifestyle change and results in long-term prevention of progression to type 2 diabetes . Trial registration Clinical Trials.gov NCT00518167 Funding The DPS study has been financially supported by the Academy of Finl and ( 128315 , 129330 ) , Ministry of Education , Novo Nordisk Foundation , Yrjö Jahnsson Foundation , Juho Vainio Foundation , Finnish Diabetes Research Foundation , Finnish Foundation for Cardiovascular Research , Unilever , and Competitive Research Funding from Tampere , Kuopio and Oulu University Hospitals . The study sponsors had no role in the design and conduct of the study ; the collection , analysis and interpretation of the data ; or the preparation , review or approval of the manuscript",
"Background As in clinical practice re sources may be limited compared to experimental setting s , translation of evidence -based lifestyle interventions into daily life setting s is challenging . In this study we therefore evaluated the implementation of the APHRODITE lifestyle intervention for the prevention of type 2 diabetes in Dutch primary care . Based on this evaluation we discuss opportunities for refining intervention delivery . Methods A 2.5-year intervention was performed in 14 general practice s in the Netherl and s among individuals at high risk for type 2 diabetes ( FINDRISC-score ≥ 13 ) ( n = 479 ) and was compared to usual care ( n = 446 ) . Intervention consisted of individual lifestyle counselling by nurse practitioners ( n = 24 ) and GPs ( n = 48 ) and group-consultations . Drop-out and attendance were registered during the programme . After the intervention , satisfaction with the programme and perceived implementation barriers were assessed with question naires . Results Drop-out was modest ( intervention : 14.6 % ; usual care : 13.2 % ) and attendance at individual consultations was high ( intervention : 80 - 97 % ; usual care : 86 - 94 % ) . Providers were confident about diabetes prevention by lifestyle intervention in primary care . Participants were more satisfied with counselling from nurse practitioners than from GPs . A major part of the GPs reported low self-efficacy regarding dietary guidance . Lack of counselling time ( 60 % ) , participant motivation ( 12 % ) , and financial reimbursement ( 11 % ) were regarded by providers as important barriers for intervention implementation . Conclusions High participant compliance and a positive attitude of providers make primary care a suitable setting for diabetes prevention by lifestyle counselling . Results support a role for the nurse practitioner as the key player in guiding lifestyle modification . Further research is needed on strategies that could increase cost-effectiveness , such as more stringent criteria for participant inclusion , group-counselling , more tailor-made counselling and integration of screening and / or interventions for different disorders"
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41179682-06ff-11f0-808a-c43d1ab1c353
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Purpose The purpose of this review is to systematic ally explore and summarise the validity and reliability of telerehabilitation (TR)-based physiotherapy assessment for musculoskeletal disorders . Method A comprehensive systematic literature review was conducted using a number of electronic data bases : PubMed , EMBASE , PsycINFO , Cochrane Library and CINAHL , published between January 2000 and May 2015 . The studies examined the validity , inter- and intra-rater reliabilities of TR-based physiotherapy assessment for musculoskeletal conditions were included . Two independent review ers used the Quality Appraisal Tool for studies of diagnostic Reliability ( QAREL ) and the Quality Assessment of Diagnostic Accuracy Studies ( QUADAS ) tool to assess the method ological quality of reliability and validity studies respectively . Results A total of 898 hits were achieved , of which 11 articles based on inclusion criteria were review ed . Nine studies explored the concurrent validity , inter- and intra-rater reliabilities , while two studies examined only the concurrent validity . Review ed studies were moderate to good in method ological quality . The physiotherapy assessment s such as pain , swelling , range of motion , muscle strength , balance , gait and functional assessment demonstrated good concurrent validity . However , the reported concurrent validity of lumbar spine posture , special orthopaedic tests , neurodynamic tests and scar assessment s ranged from low to moderate . Conclusion TR-based physiotherapy assessment was technically feasible with overall good concurrent validity and excellent reliability , except for lumbar spine posture , orthopaedic special tests , neurodynamic testa and scar assessment
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"Objectives : Musculoskeletal conditions have only recently been acknowledged and research on their burden is scarce in the Middle East and North African ( MENA ) region . For the first time , a population based study was conducted in Lebanon to assess the prevalence , level of disability , and health seeking behaviours related to musculoskeletal pain and rheumatic disorders . Methods : A r and om sample of 500 participants aged ≥ 15 years from Southern Lebanon was interviewed using the COPCORD ( Community Oriented Program for Control of Rheumatic Diseases ) question naire . Results : The prevalence of current musculoskeletal pain was 31.2 % [ CI ( 27.0–35.2 % ) ] . Being a female [ OR=1.8 , CI ( 1.2–2.8 ) ] and of advancing age [ OR=1.03 , CI ( 1.01–1.05 ) ] were the only significant factors associated with current musculoskeletal pain . Prevalence of current functional disability was 6.4 % [ CI ( 4.2–8.5 % ) ] . Around quarter ( 26.0 % ) [ CI ( 22.3–30.1 % ) ] of our sample sought some kind of treatment . The overall prevalence rate of rheumatic disease was 17.0 % [ CI ( 13.7–20.3 % ) ] . Discussion : Our findings indicate that musculoskeletal conditions are common in Lebanon . This is a timely public health issue that needs further investigation and solid recognition by health authorities . Community-based interventions should target patients to prompt them to seek early help in order to prevent the development of musculoskeletal pain into disorders",
"Study Design . A descriptive study of repeated measures using a crossover design . Objective . To determine the level of agreement between assessment s obtained via telerehabilitation and those obtained by traditional face-to-face method in a population of individuals with chronic low back pain ( LBP ) in a primary care setting . Summary of Background Data . Musculoskeletal assessment using telerehabilitation has shown adequate inter- and intrarater agreement and concordance with face-to-face clinical assessment in different diseases . There have been no published studies on the reliability of a telerehabilitation system to assess LBP . Methods . Fifteen individuals ( 6 males ; mean age , 37 yr ) with chronic LBP attended a session for a clinical interview , followed by face-to-face and real-time online telerehabilitation evaluations . There was a 30-minute interval between the 2 assessment s , the order of which was r and omly selected for each patient . The telerehabilitation system used an Internet application conducted via Internet connection ( 17 kB/s ) between 2 personal computers . Real-time video connection facilitated communication between the therapist and the subject . Outcome measures included lumbar spine mobility , Sorensen test , anterior straight leg raise test , Oswestry Disability Index , visual analogue scale for pain , 12-Item Short Form Health Survey question naire , and Tampa Kinesiophobia Scale . Results . The & agr ; reliability between face-to-face and telerehabilitation evaluations was more than 0.80 for 7 of the 9 outcome measures . Lowest reliability was for lateral flexion range of motion ( & agr;= 0.75 ) . Very good inter- and intrarater intraclass correlation coefficients ( & rgr ; ) were obtained ( 0.92–0.96 ) . Conclusion . The findings of our pilot study suggest that this telerehabilitation system may be useful to assess individuals with chronic LBP , providing initial support for its implementation in primary care . Level of Evidence :",
"BACKGROUND total knee arthroplasty is an effective means for relieving the symptoms associated with degenerative arthritis of the knee . Rehabilitation is a necessary adjunct to surgery and is important in regaining optimum function . Access to high- quality rehabilitation services is not always possible , especially for those who live in rural or remote areas . The aim of this study was to evaluate the equivalence of an Internet-based telerehabilitation program compared with conventional outpatient physical therapy for patients who have had a total knee arthroplasty . METHODS this investigation was a single-blinded , prospect i ve , r and omized , controlled noninferiority trial . Sixty-five participants were r and omized to receive a six-week program of outpatient physical therapy either in the conventional manner or by means of an Internet-based telerehabilitation program . The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) measured at baseline and six weeks by a blinded independent assessor . Secondary outcomes included the Patient-Specific Functional Scale , the timed up- and -go test , pain intensity , knee flexion and extension , quadriceps muscle strength , limb girth measurements , and an assessment of gait . Noninferiority was assessed through the comparison of group differences with a noninferiority margin and with linear mixed model statistics . RESULTS baseline characteristics between groups were similar , and all participants had significant improvement on all outcome measures with the intervention ( p flexion and extension range of motion , muscle strength , limb girth , pain , timed up- and -go test , quality of life , and clinical gait and WOMAC scores . Better outcomes for the Patient-Specific Functional Scale and the stiffness subscale of the WOMAC were found in the telerehabilitation group ( p < 0.05 ) . The telerehabilitation intervention was well received by participants , who reported a high level of satisfaction with this novel technology . CONCLUSIONS the outcomes achieved via telerehabilitation at six weeks following total knee arthroplasty were comparable with those after conventional rehabilitation . LEVEL OF EVIDENCE therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence",
"summary We investigated the accuracy and reliability of observational kinematic gait assessment s performed via a low-b and width Internet link ( 18 kbit/s ) and a higher-speed Internet link ( 128 kbit/s ) . Twenty-four subjects were r and omized to either b and width group . Gait was assessed with the Gait Assessment Rating Scale ( GARS ) in the traditional manner , which is from video-recordings , and with repeated measurements via the online method . Online assessment was found to provide as accurate a measure of gait performance as the traditional assessment ( limits of agreement51 GARS point ; intraclass correlation coefficient , ICC= 0.96 ) regardless of the speed of the Internet connection . The online assessment also demonstrated high intra-rater ( ICC= 0.96 ) and inter-rater ( ICC= 0.92 ) reliability . Low-b and width telerehabilitation applications appear to be feasible via the Internet",
"Surgery has always been a dynamic discipline . It has a long history of groundbreaking innovations that dramatically improved the way patients were treated and surgery was practice d. However , nothing could have prepared the surgical community for the revolutionary advances of the last 2 decades . Almost overnight , the traditional open approach to surgery was replaced by a minimally invasive surgery ( MIS ) approach [ 2 ] . Practitioners quickly realized that this novel approach would require new types of training . Suddenly , the directors of surgical residency programs had to deal with faculty members who were question ing the training paradigm that had served surgery well for a century . The traditional Halsteadian method did not seem to be suitable for the new types of skills required for MIS . To make matters worse , the length of time allocated to training residents was contracting . In the European Union in 2001 the European Working time Directive was extended to include physicians in training and this year in the United States of America the m and atory 80 hour work week restriction has been instituted , both dramatically reducing work/training hours for residents . At the same time , the practice of surgery came under scrutiny in another , apparently unrelated area when the value and relevance of surgical research became an issue of controversy . In an unprecedented attack , the editor of the Lancet [ 6 ] publically called into question the quality of current surgical research . In an editorial entitled ‘ ‘ Surgical Research or Comic Opera ? ’ ’ Dr. Horton expressed grave reservations about its utility , validity , and usefulness . Although the editorial was met by the surgical community with the predictable indignant response , Horton did make some valid points . Not necessarily in response to this editorial but certainly contiguous to it , surgical research appears to be moving away from reliance on retrospective data to prospect i ve , r and omized , and —where possible— blinded data . It is our contention that these two issues , i.e. , MIS skills and surgical research , have now converged around the very essence of our surgical heritage — the stringent use of the ‘ ‘ scientific method ’’ and objective assessment . Perhaps this is best exemplified by the relatively new editorial practice of prioritizing prospect i ve , r and omized , blinded surgical trials for publication . Although blinded , r and omized , controlled trial design can be employed to answer definitively many surgical research questions , we must remember that this design is only one of a quiver full of research method ologies , and may not always be the experimental design of choice . The function of good science is to show clear cause- and -effect relationships , and this does not always require a prospect i ve , r and omized , double-blind experimental design . Indeed the optimal method may not even be experimental , but statistical , such as Structural Equation Models [ 3 ] . This methodology will almost certainly be required to answer the question of which fundamental psychological abilities predict MIS skills/performance or what factors predict obesity or treatment outcomes in obesity . In both of these examples the answer will be multifactorial , which precludes the use of traditional experimental design . The control exerted with traditional experimental design will be replaced with the equally powerful ( but method ologically more sophisticated ) ‘ ‘ statistical ’ ’ control . The point we want to make here is that there is no ‘ ‘ magic bullet ’ ’ experimental methodology for surgical research ; instead , there is a range of experimental design s that should be applied appropriately to answer the pertinent research question . Research design should therefore vary depending on the circumstances . An eloquent example can be found in a report form the Dundee MIS group , who used four subjects and , in essence , a single-subject design to evaluate the utility of three-dimensional camera systems [ 5 ] . The research design they used answered the question unequivocally , but Correspondence to : A. G. Gallagher Surg Endosc ( 2003 ) 17 : 1525–1529 DOI : 10.1007/s00464 - 003 - 0035 -",
"Telemedicine promises to revolutionize medical care delivery in rural and remote areas . The ability to accurately evaluate physical impairment via the Internet is important to the possible future provision of Internet-based physiotherapy . This study evaluated the reliability and validity of assessing knee range of motion via the Internet . Two therapists evaluated knee angle on a single subject via two methods of assessment : the Internet and the traditional method ( face-to-face ) . Nine r and om positions of the knee were chosen with the principal examiner performing 20 face-to-face and two sets of 20 Internet measures in each position ( n=540 ) . The secondary therapist performed Internet assessment s only . The Internet connection was established at a readily available speed of 17 kbit/s . The Internet-based goniometer was found to be a valid tool for measuring both knee flexion and extension angles . It was shown to possess both high intra and inter-rater reliability . Difference average plots of the scores verified the consistency of measurement between both modes of assessment . The successful evaluation of the physical outcome measure of knee range of motion via the Internet assists the further development of Internet-based physiotherapy applications"
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411796e6-06ff-11f0-808a-c43d1ab1c353
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Use of alcohol , cannabis and opioids is highly prevalent and is associated with global disease burden and high economic costs . The exact pathophysiology of abuse or addiction associated with these sedative substances is not completely understood , but previous research implicates the important role of the striatal dopamine system in the addiction process . Multiple studies investigated changes in the striatal dopamine systems of users of sedative substances , but currently these results are very heterogeneous . Therefore , we conducted a meta- analysis of in vivo neuroimaging studies investigating dopaminergic alterations in the striatum of users of alcohol , opioids or cannabis . Analyses for each substance were conducted separately for the availability of D2/D3 dopamine receptors , dopamine transporters and dopamine synthesis capacity . In total , 723 substance users and 752 healthy controls were included . The results indicated a significant lower striatal D2/D3 receptor availability in alcohol users compared to controls ( g = 0.46 ) but no difference in dopamine transporter availability or dopamine synthesis capacity . Our analysis indicated that changes of dopamine receptors and transporters are moderated by the duration of abstinence . Comparing opioid users with controls revealed a significant lower D2/D3 receptor availability ( g = 1.17 ) and a significantly lower transporter availability ( g = 1.55 ) in opioid users . For cannabis users , there was no significant difference in receptor availability compared to controls and too few studies provided information on dopamine transporter availability or synthesis capacity . Our analysis provides strong evidence for a central role of the striatal dopamine system in use of alcohol or opioids . Further studies are needed to clarify the impact of the dopamine system in cannabis users
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"It has been documented that methadone maintenance treatment is effective in reducing drug craving and relevant risk behaviors in heroin users . However , it is not understood whether methadone maintenance treatment impairs the dopamine transporter in the striatum . To establish whether chronic opiate use might impair brain dopamine neurons in humans , we assessed dopamine transporter ( DAT ) uptake function in the striatum ( cau date and putamen ) , and analyzed the correlation between DAT in the striatum and heroin craving and subjective anxiety in former heroin users with prolonged abstinence and in patients receiving methadone maintenance treatment . Binding of [(11)C]-2beta-carbomethoxy-3beta-aryltropane ( [ (11)C ] CFT ) as a brain dopamine transporter lig and was measured with positron emission tomography ( PET ) in eleven former heroin users with prolonged abstinence , ten patients receiving methadone maintenance treatment and ten healthy control subjects . Heroin craving and subjective anxiety in prolonged abstinence and methadone maintenance treatment groups were assessed and the correlations between DAT of striatum and heroin craving or subjective anxiety were determined . In comparison with healthy control subjects , methadone maintenance treatment subjects had lower DAT uptake function in the bilateral cau date and putamen and prolonged abstinence subjects showed significantly lower DAT uptake function in the bilateral cau date . Moreover , in comparison to the prolonged abstinence subjects , the methadone maintenance treatment subjects showed significant decreases of DAT uptake in the bilateral putamen . DAT uptake function in bilateral striatum was not associated with heroin craving in prolonged abstinence or in methadone maintenance treatment subjects ; however , DAT uptake function in the bilateral cau date was significantly correlated with subjective anxiety in methadone maintenance treatment subjects . Our findings suggest that chronic opioid use induces long-lasting striatum dopamine neuron impairment , and prolonged withdrawal from opioids can benefit the recovery of impaired dopamine neurons in the brain",
"Abstract Rationale : Late onset type 1 alcoholism has been suggested to be associated with an underlying dopaminergic defect . Therefore , it is relevant to study both postsynaptic D2-receptor and presynaptic dopamine transporter ( DAT ) densities among alcoholics . Objective : We investigated DAT densities , along with striatal and extrastriatal dopamine D2-receptor densities , in nine non-violent late-onset male alcoholics , who had no major mental disorder nor antisocial personality disorder ( ASPD ) , and nine healthy controls . Methods : [123I]PE2I and [123I]epidepride were used in SPECT imaging . Results : DAT occupancy ratios ( striatum/cerebellum ) were significantly lower among alcoholics than in controls . Extrastriatal D2-receptor occupancy ratios ( temporal pole/cerebellum ) were not significantly different between the groups . Conclusions : Striatal presynaptic DAT densities are decreased among type 1 alcoholics , and this finding is not associated with recent alcohol abuse",
"BACKGROUND Pre clinical data implicate the reinforcing effects of alcohol to be mediated by interaction between the opioid and dopamine systems of the brain . Specifically , alcohol-induced release of β-endorphins stimulates μ-opioid receptors ( MORs ) , which is believed to cause dopamine release in the brain reward system . Individual differences in opioid or dopamine neurotransmission have been suggested to be responsible for enhanced liability to abuse alcohol . In the present study , a single dose of the MOR agonist remifentanil was administered in detoxified alcohol-dependent patients and healthy control subjects to mimic the β-endorphin-releasing properties of ethanol and to assess the effects of direct MOR stimulation on dopamine release in the mesolimbic reward system . METHODS Availability of D(2/3 ) receptors was assessed before and after single-dose administration of the MOR agonist remifentanil in 11 detoxified alcohol-dependent patients and 11 healthy control subjects with positron emission tomography with the radiotracer [(18)F]fallypride . Severity of dependence as assessed with the Alcohol Use Disorders Identification Test was compared with remifentanil-induced percentage change in [(18)F]fallypride binding ( Δ%BP(ND ) ) . RESULTS The [(18)F]fallypride binding potentials ( BP(ND)s ) were significantly reduced in the ventral striatum , dorsal putamen , and amygdala after remifentanil application in both patients and control subjects . In the patient group , ventral striatum Δ%BP(ND ) was correlated with the Alcohol Use Disorders Identification Test score . CONCLUSIONS The data provide evidence for a MOR-mediated interaction between the opioid and the dopamine system , supporting the assumption that one way by which alcohol unfolds its rewarding effects is via a MOR-(γ-aminobutyric acid)-dopamine pathway . No difference in dopamine release was found between patients and control subjects , but evidence for a patient-specific association between sensitivity to MOR stimulation and severity of alcohol dependence was found",
"BACKGROUND Positron emission tomography ( PET ) imaging studies have shown that addiction to a number of substances of abuse is associated with a decrease in dopamine D(2/3 ) receptor binding and decreased presynaptic dopamine release in the striatum . Some studies have also shown that these reductions are associated with the severity of addiction . For example , in cocaine dependence , low dopamine release is associated with the choice to self-administer cocaine . The goal of the present study was to investigate these parameters of striatal dopamine transmission in heroin dependence and their association with drug seeking behavior . METHODS Heroin-dependent and healthy control subjects were scanned with [(11)C]raclopride before and after stimulant administration ( methylpheni date ) to measure striatal D(2/3 ) receptor binding and presynaptic dopamine release . After the PET scans , the heroin-dependent subjects performed heroin self-administration sessions . RESULTS Both striatal D(2/3 ) receptor binding and dopamine release were reduced in the heroin-dependent subjects compared with healthy control subjects . However , neither PET measure of dopamine transmission predicted the choice to self-administer heroin . CONCLUSIONS These findings show that heroin addiction , like addiction to other drugs of abuse , is associated with low D(2/3 ) receptor binding and low presynaptic dopamine . However , neither of these outcome measures was associated with the choice to self-administer heroin",
"Rationale Previous imaging studies have indicated that the levels of the dopamine transporter ( DAT ) are reduced in the brains of heroin users . However , whether these changes can be reversed by abstinence and /or treatment remains unclear . Objectives This study aims to investigate DAT availability in heroin users and changes in DAT availability after abstinence and treatment with the Jitai tablets , a traditional Chinese medicinal product that is approved for the treatment of opioid addiction . Methods Single-photon emission computed tomography ( SPECT ) with [ 99mTc ] TRODAT-1 was performed on heroin-dependent patients ( n = 64 ) and healthy controls ( n = 15 ) . The patients were r and omly assigned to treatment with either placebo or the Jitai . All patients underwent SPECT imaging both at baseline and after 6 months of treatment . DAT availability was assessed in the cau date and putamen . Depression and anxiety were evaluated at baseline . Results DAT availability remained at low levels during a 6-month period in the placebo-treated group but was increased ( 14–17 % ) in the Jitai-treated group . The ratio of DAT availability at month 6 to that at baseline in the Jitai-treated group was significantly higher than that in the placebo-treated group in both the bilateral cau date and putamen . DAT uptake in the striatum was significantly correlated with daily heroin dose , years of heroin use , and depression . Conclusions These findings suggest that chronic heroin use induces long-lasting striatal DAT reductions . DAT availability remained unchanged during a 6-month period of abstinence . Treatment with Jitai appears to be effective at increasing striatal DAT availability ",
"Rationale Chronic exposure to heroin results in decreased dopamine transporter levels . Jitai tablets , a traditional Chinese medicine , have been effective at increasing striatal dopamine transporter availability after 6 months of treatment . However , it remains unknown how long the heroin-induced impairment persists and whether dopamine transporter can be normalized following long-term abstinence or treatment . Objectives This study was to evaluate the time course of dopamine transporter changes in heroin users undergoing long-term abstinence and treatment with Jitai tablets for 1 year . Methods Single-photon emission computed tomography using [99mTc]TRODAT-1 was performed on 64 heroin users and 20 healthy subjects to assess striatal dopamine transporter availability at baseline , 3 , 6 , and 12 months . Heroin users were r and omly assigned to treatment with either placebo or Jitai tablets . Depression and anxiety scores were measured before each imaging session . Results Compared with healthy controls , significant reduction in dopamine transporter availability was found in heroin users at baseline in both the right ( by ∼31.6 % ) and left striatum ( by ∼33.2 % ) . At 6 months , dopamine transporter availability was significantly higher in Jitai tablet-treated group than placebo group in the bilateral striatum ( p months , dopamine transporter levels in both groups were upregulated substantially from baseline but still not recovered to normal levels in the left striatum ( p scores significantly decreased at 3 , 6 , and 12 months ( p in dopamine transporter . Treatment with Jitai tablets appears to stimulate recovery",
"Imaging studies in patients with Type II alcohol dependence have revealed significant reductions in dopamine ( DA ) D2 receptor availability . Here we assessed the effects of alcohol detoxification in DA D2 receptors in alcoholic subjects . We evaluated 14 patients with Type II alcohol dependence tested within 6 weeks of detoxification and then re-tested 1 - 4 months later while alcohol free . The comparison group comprised 11 healthy controls . PET was used with [11C]raclopride to measure DA D2 receptors . Eight alcoholics and all control subjects were tested with a CTI 931 PET scanner and six alcoholics with a Siemens HR+ PET scanner . Data were analyzed separately for the studies done in the different scanners . Comparisons between early and late alcohol detoxification showed no significant changes in DA D2 receptor availability ( B(max)/K(d ) ) for the studies done with the CTI and the HR+ scanners . Comparison with controls showed lower DA D2 receptor levels in cau date and putamen in alcoholics tested during early detoxification and in cau date during late detoxification . These studies replicate previous findings of lower striatal DA D2 receptors in alcoholics than in controls and absence of significant recovery during alcohol detoxification . These findings suggest that low DA D2 receptor availability in alcoholics is not due to alcohol withdrawal and may reflect a predisposing factor"
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Background Dem and -side financing ( DSF ) interventions , including cash transfers and vouchers , have been introduced to promote maternal and newborn health in a range of low- and middle-income countries . These interventions vary in design but have typically been used to increase health service utilisation by off setting some financial costs for users , or increasing household income and incentivising ‘ healthy behaviours ’ . This article documents experiences and implementation factors associated with use of DSF in maternal and newborn health . Methods A secondary analysis ( using an adapted Supporting the Use of Research Evidence framework – SURE ) was performed on studies that had previously been identified in a systematic review of evidence on DSF interventions in maternal and newborn health . Results The article draws on findings from 49 quantitative and 49 qualitative studies . The studies give insights on difficulties with exclusion of migrants , young and multiparous women , with dem and s for informal fees at facilities , and with challenges maintaining quality of care under increasing dem and . Schemes experienced difficulties if communities faced long distances to reach participating facilities and poor access to transport , and where there was inadequate health infrastructure and human re sources , shortages of medicines and problems with corruption . Studies that documented improved care-seeking indicated the importance of adequate programme scope ( in terms of programme eligibility , size and timing of payments and voucher entitlements ) to address the issue of concern , concurrent investments in supply-side capacity to sustain and /or improve quality of care , and awareness generation using community-based workers , leaders and women ’s groups . Conclusions Evaluations spanning more than 15 years of implementation of DSF programmes reveal a complex picture of experiences that reflect the importance of financial and other social , geographical and health systems factors as barriers to accessing care . Careful design of DSF programmes as part of broader maternal and newborn health initiatives would need to take into account these barriers , the behaviours of staff and the quality of care in health facilities . Research is still needed on the policy context for DSF schemes in order to underst and how they become sustainable and where they fit , or do not fit , with plans to achieve equitable universal health coverage
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"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",
"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"
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411797a4-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND Falls are the leading cause of traumatic brain injury and fractures and the No. 1 cause of emergency department visits by older adults . Although declines in muscle strength and sensory function contribute to increased falls in older adults , skeletal muscle fatigue is often overlooked as an additional contributor to fall risk . In an effort to increase awareness of the detrimental effects of skeletal muscle fatigue on postural control , we sought to systematic ally review research studies examining this issue . PURPOSE The specific purpose of this review was to provide a detailed assessment of how anticipatory and reactive postural control tasks are influenced by acute muscle fatigue in healthy older individuals . METHODS An extensive search was performed using the CINAHL , Scopus , PubMed , SPORTD iscus , and AgeLine data bases for the period from inception of each data base to June 2013 . This systematic review used st and ardized search criteria and quality assessment s via the American Academy for Cerebral Palsy and Developmental Medicine Methodology to Develop Systematic Review s of Treatment Interventions ( 2008 version , revision 1.2 , AACPDM , Milwaukee , Wisconsin ) . RESULTS A total of 334 citations were found . Six studies were selected for inclusion , whereas 328 studies were excluded from the analytical review . The majority of articles ( 5 of 6 ) utilized reactive postural control paradigms . All studies incorporated extrinsic measures of muscle fatigue , such as declines in maximal voluntary contraction or available active range of motion . The most common biomechanical postural control task outcomes were spatial measures , temporal measures , and end-points of lower extremity joint kinetics . CONCLUSION On the basis of systematic review of relevant literature , it appears that muscle fatigue induces clear deteriorations in reactive postural control . A paucity of high- quality studies examining anticipatory postural control supports the need for further research in this area . These results should serve to heighten awareness regarding the potential negative effects of acute muscle fatigue on postural control and support the examination of muscle endurance training as a fall risk intervention in future studies
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"OBJECTIVE To examine the relationship and differences between static and dynamic postural stability in healthy , physically active adults . DESIGN Descriptive laboratory study . SETTING Research laboratory . PARTICIPANTS Ten females ( age : 21.6 ± 1.2 yrs , mass : 60.8 ± 7.6 kg , height : 165.0 ± 5.0 cm ) and ten males ( age : 25.1 ± 3.0 yrs , mass : 73.9 ± 8.7 kg , height : 173.5 ± 9.0 cm ) . MAIN OUTCOME MEASURES Static postural stability was measured during a single-leg st and ing task ( st and ard deviation of the ground reaction forces ) . Dynamic postural stability was measured during a single-leg l and ing task using the Dynamic Postural Stability Index . Pearson 's r-coefficients were calculated to examine relationships between the two tests and a one-way ANOVA was calculated to examine potential differences in test scores ( p that dynamic postural stability scores were significantly higher than static postural stability scores . CONCLUSIONS A lack of a correlation between static and dynamic measures and increase in difficulty during dynamic measures indicates differences in the type and magnitude of challenge imposed by the different postural stability tasks . The more challenging dynamic measures of postural stability may be more suitable for prospect i ve studies examining risk of ankle and knee injury in healthy , physically active individuals",
"AIM The aim of this study was to evaluate the interrater reliability and convergent validity of the American Academy for Cerebral Palsy and Developmental Medicine 's ( AACPDM ) methodology for conducting systematic review s ( group design studies ) . METHOD Four clinicians independently rated 24 articles for the level of evidence and conduct using AACPDM methodology . Study conduct was also assessed using the Effective Public Health Practice Project scale . Raters were r and omly assigned to one of two pairs to resolve discrepancies . The level of agreement between individual raters and pairs was calculated using kappa ( α=0.05 ) and intraclass correlations ( ICCs ; α=0.05 ) . Spearman 's rank correlation coefficient was calculated to evaluate the relationship between raters ' categorization of quality categories using the two tools . RESULTS There was acceptable agreement between raters ( κ=0.77 ; p the level of evidence ratings . There was acceptable agreement between pairs for four of the seven conduct questions ( κ=0.53 - 0.87 ) . ICCs ( all raters ) for conduct category ratings ( weak , moderate , and strong ) also indicated good agreement ( ICC=0.76 ) . Spearman 's rho indicated a significant positive correlation for the overall quality category comparisons of the two tools ( 0.52 ; p interrater reliability . Evaluation of its study quality ratings demonstrated reasonable agreement when compared with a similar tool",
"INTRODUCTION Frequent falls and risk of injury are evident in individuals with Parkinson 's disease ( PD ) as the disease progresses . There have been no reports of any interventions that reduce the incidence of falls in idiopathic PD . PURPOSE Assess the benefit of gait and step perturbation training in individuals with PD . DESIGN R and omized , controlled trial . SETTING Outpatient research , education and clinical center in a tertiary care Veterans Affairs Medical Center . OUTCOME MEASURES Gait parameters , 5-step test , report of falls . SUBJECTS Eighteen men with idiopathic PD in stage 2 or 3 of the Hoehn and Yahr staging . METHODS Subjects were r and omly assigned to a trained or control group . They were asked about any falls 2 weeks prior to and after an 8 week period . Gait speed , cadence , and step length were tested on an instrumented walkway . Subjects were timed while stepping onto and back down from an 8.8 cm step for 5 consecutive steps . Gait training consisted of walking on a treadmill at a speed greater than over ground walking speed while walking in 4 directions and while supported in a harness for safety . Step training consisted of suddenly turning the treadmill on and off while the subject stood in the safety harness facing either forwards , backwards , or sideways . Training occurred 1 hour per day , three times per week for 8 weeks . A two-factor ( time and group ) analysis of variance with repeated measures was used to compare the groups . RESULTS Substantial reduction occurred in falls in the trained group , but not in the control group . Gait speed increased in the trained group from 1.28+/-0.33 meters/sec to 1.45+/-0.37 meters/sec , but not in the control group ( from 1.26 to 1.27 m/s ) . The cadence increased for both groups : from 112.8 to 120.3 steps/min for the trained group and 117.7 to 124.3 steps/min for the control group . Stride lengths increased for the trained group , but not the control group . The 5-step test speed increased in the trained group from 0.40+/-0.08 steps/sec to 0.51+/-0.12 steps/sec , and in the control group ( 0.36+/-0.11 steps/sec to 0.42+/-0.11 steps/sec ) . CONCLUSION Gait and step perturbation training result ed in a reduction in falls and improvements in gait and dynamic balance . This is a promising approach to reduce falls for patients with PD",
"The purpose of this study was to quantify changes in postural stability with fatigue of the frontal and sagittal movers of the lower extremities . There were four test sessions , with a r and omized order assigned according to the muscles tested and the plane of motion . Subjects were 20 healthy men ( age : 22.6+/-2.4 years , height : 173.7+/-3.6 cm , weight : 63.3+/-7.9 kg ) . During each session , one set of muscle groups was fatigued using isokinetic contractions : ankle plantar/dorsi flexors , ankle evertor/invertors , hip flexor/extensors or hip abductor/adductors . The Biodex Stability System was used to assess anterior/posterior and medial/lateral stability before and after muscle fatigue . Repeated measures ANOVAs revealed that fatigue was associated with a significant increase in all stability indices . Fatigue of the hip movers , whether in the frontal or sagittal planes , led to greater increments in stability indices than fatigue of the ankle musculature . Fatigue of the frontal movers result ed in greater increases in the medial/lateral stability index compared to fatigue of the sagittal movers . In conclusion , fatigue of proximal lower extremity muscles affects postural stability and fatigue of the frontal movers is associated with postural instability in the frontal plane",
"BACKGROUND Aging compromises the ability of the central nervous system to maintain body balance and reduces the capacity for adaptive reactions . To prevent falls , the reception conditions for sensory information need to be improved . OBJECTIVES To evaluate the impact of a structured aquatic and a non-aquatic exercise program for lower-limb muscle endurance on the static and dynamic balance of elderly people . METHODS This was a prospect i ve r and omized clinical study in which the variables were assessed before and after the training program . Thirty-six elderly people were evaluated using four tests : the Berg Balance Scale , Dynamic Gait Index , gait speed and t and em gait . The participants were r and omized into three groups : aquatic exercise group , non-aquatic exercise group and control group . The exercise groups underwent a program for lower-limb muscle endurance that consisted of 40-minute sessions twice a week for six weeks . The participants were reevaluated after six weeks . The data were analyzed statistically using the univariate ANOVA test for comparisons between the groups before and after the intervention . RESULTS The program for lower-limb muscle endurance significantly increased balance ( p improvement in static and dynamic balance among community-dwelling elderly people . It was also possible to infer that this improvement occurred regardless of the environment , i.e. aquatic or non-aquatic . Article registered in the Australian New Zeal and Clinical Trials Registry ( ANZCTR ) under the number ACTRN 12609000780257",
"Purpose : Aging is associated with deterioration of the physiologic systems controlling balance . Consequently , a multitude of intervention trials has appeared in the last 2 decades attempting to improve control of balance . Effective programs often require substantial and frequent time commitments , expensive and specialized equipment , professional assistance , and clinical setting s. This investigation reports the effects of a simple , short‐term balance training program on dynamic balance in healthy older women . Methods : Subjects included 11 healthy women ( 75.6 ± 6.4 years ) who participated in biweekly , 15‐minute balance training sessions for 5 weeks , and 10 age‐matched women ( 71.2 ± 9.1 years ) who served as controls . Balance training involved medial‐lateral and anterior‐posterior movements and bilateral partial squats while st and ing on semi‐compressible foam roller‐devices . Dynamic balance was quantified using functional reach in the forward , left , and right directions , and a lower extremity reach test . Results : Significant increases were observed in the balance trained group : 25 % in functional reach right ( P = 0.014 ) and left ( P in lower extremity reach ( P = 0.001 ) . No change was noted in the control group . Conclusions : Improvements in dynamic balance can be realized following 5 weeks of dynamic balance training using this novel , simplistic , and short‐term protocol",
"Tripping over obstacles is a common cause of falls in older adults , and muscle fatigue , which can alter walking patterns , may add to this risk . To date , no study has examined the effect of lower limb muscle fatigue on obstacle negotiation in older adults . 30 older adults ( 13 women , aged 78.3 [ 6.2 ] years ) negotiated a 12 m obstacle course , while completing a visual secondary task , under two r and omized conditions : rested or fatigued . For the fatigue condition , participants performed a repeated sit-to-st and movement , as fast as possible , until they could no longer continue . Participants then immediately began walking trials . Kinematic and kinetic data were collected on approach to , during , and after crossing a height-adjustable target obstacle ( 10 % and 20 % of leg length ) . Repeated measures ANOVA showed a statistically significant increase in lead limb vertical loading rate after stepping over the 10 % obstacle when fatigued , relative to rested ( P=0.046 ) . No other significant between-condition differences ( > 0.05 ) were observed for the other kinematic variables when negotiating the 10 % obstacle . Furthermore , no significant between-condition differences ( P>0.05 ) were observed for any kinetic or kinematic variables when negotiating the 20 % obstacle . This study describes a feasible method for investigating the consequences of lower limb muscle fatigue on obstacle crossing . The current finding of increased vertical loading rate when fatigued supports the need for further investigation into the effect of muscle fatigue on gait under different environmental conditions , fatiguing a range of muscles , analyzing a more comprehensive array of kinetic and kinematic measures , and in healthy and clinical population",
"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",
"OBJECTIVE To quantify changes in balance parameters and ranges of postural control at the ankle after isokinetic fatigue . DESIGN Before-after trials , with a 5 x 6 repeated- measures design . SETTING General community . PARTICIPANTS Twenty-four men ( age , 24.9 + /- 3.92y ; height , 177.79 + /- 6.36 cm ; weight , 80.78 + /- 13.22 kg ) without ankle trauma within 2 years . INTERVENTIONS Fatigue of the plantarflexors and dorsiflexors was induced by isokinetic contractions . Balance was assessed by using a unilateral test ( 15-s quiet stance , 10-s lean test ) on a force platform immediately before and at 0 ( T0 ) , 10 ( T10 ) , 20 ( T20 ) , and 30 ( T30 ) minutes postfatigue . MAIN OUTCOME MEASURE Mediolateral ( ML ) and fore-aft ( FA ) sway as well as ML and FA displacement were analyzed by analysis of variance with repeated measures for time ( alpha = .05 ) . RESULTS In quiet stance , ML sway was greater at T0 , whereas total sway increased at all time points postfatigue ( P test , FA sway increased at T0 and T10 , and total sway increased at all time points ( P ML and FA displacement significantly differed at T0 ( P sway parameters returned to baseline within 20 minutes . CONCLUSIONS Isokinetic fatigue of ankle plantarflexors and dorsiflexors significantly influences sway parameters and ranges of postural control in healthy young men . These perturbations are transient , and recovery occurs within 20 minutes",
"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"
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41179808-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND Although radiofrequency catheter ablation ( RFA ) has evolved from an experimental procedure to an important treatment option for atrial fibrillation , the relative safety and efficacy of catheter ablation relative to that of antiarrhythmic drug ( AAD ) therapy has not been established . METHODS AND RESULTS Two separate systematic review s were conducted : one on RFA and the other on AAD to provide accurate and broadly representative estimates of the clinical efficacy and safety of both therapies in the treatment of atrial fibrillation . Electronic search es were conducted in EMBASE and MEDLINE from 1990 to 2007 . For the RFA review , all study design s were accepted . For the AAD review , articles were limited to prospect i ve studies on the following drugs of interest : amiodarone , dofetilide , sotalol , flecainide , and propafenone . Data were extracted by 1 review er , with a second review er performing independent confirmation of extracted data . Sixty-three RFA and 34 AAD studies were included in the review s. Patients enrolled in RFA studies tended to be younger ( mean age , 55 versus 62 years ) , had longer duration of atrial fibrillation ( 6.0 versus 3.1 years ) , and had failed a greater number of prior drug trials ( 2.6 versus 1.7 ) . The single-procedure success rate of ablation off AAD therapy was 57 % ( 95 % CI , 50 % to 64 % ) , the multiple procedure success rate off AAD was 71 % ( 95 % CI , 65 % to 77 % ) , and the multiple procedure success rate on AAD or with unknown AAD usage was 77 % ( 95 % CI , 73 % to 81 % ) . In comparison , the success rate for AAD therapy was 52 % ( 95 % CI , 47 % to 57 % ) . A major complication of catheter ablation occurred in 4.9 % of patients . Adverse events for AAD studies , although more common ( 30 % versus 5 % ) , were less severe . CONCLUSIONS Studies of RFA for treatment of atrial fibrillation report higher efficacy rates than do studies of AAD therapy and a lower rate of complications
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"Background — The purpose of this study was to reevaluate the ECG features of arrhythmogenic right ventricular dysplasia ( ARVD ) . The second objective was to evaluate the sensitivity and specificity of the st and ard and newly proposed diagnostic ECG markers in the presence of a right bundle-branch block ( RBBB ) . Methods and Results — One hundred patients with ARVD ( 57 men ; aged 39±15 years ) and 57 controls ( 21 men ; aged 40±17 years ) were included . Among the 100 patients with ARVD , a complete RBBB was present in 17 patients , and 15 patients had an incomplete RBBB . T-wave inversion through V3 demonstrated optimal sensitivity and specificity in both ARVD patients without a complete RBBB or incomplete RBBB ( 71 % [ 95 % confidence interval , 58 % to 81 % ] and 96 % [ 95 % confidence interval , 81 % to 100 % ] , respectively ) and in ARVD patients with incomplete RBBB ( 73 % [ 95 % confidence interval , 45 % to 92 % ] and 95 % [ 95 % confidence interval , 77 % to 100 % ] , respectively ) . Between ARVD patients and controls with a complete RBBB , the only 2 parameters that differed were the prevalence of T-wave inversion through V4 ( 59 % versus 12 % , respectively ; P an r′/s ratio in V1 sensitive and specific parameter was an r′/s ratio of QRS morphology being the first step , for ECG evaluation of ARVD patients . Definite criteria are then applied on the basis of the presence of no RBBB , incomplete RBBB , and complete RBBB to obtain the best diagnostic utility of the ECG",
"Background —Left atrioesophageal fistula is a rare but devastating complication that may occur after catheter ablation of atrial fibrillation . We used capsule endoscopy to assess esophageal injury after catheter ablation for atrial fibrillation in a population r and omized to undergo general anesthesia or conscious sedation . Methods and Results —Fifty patients undergoing atrial fibrillation ablation for paroxysmal symptomatic atrial fibrillation refractory to antiarrhythmic drugs were enrolled and r and omized , including those undergoing the procedure under general anesthesia ( 25 patients , group 1 ) and those receiving conscious sedation with fentanyl or midazolam ( 25 patients , group 2 ) . All patients underwent esophageal temperature monitoring during the procedure . The day after ablation , all patients had capsule endoscopy to assess the presence of endoluminal tissue damage of the esophagus . We observed esophageal tissue damage in 12 ( 48 % ) patients of group 1 and 1 esophageal tissue damage in a single patient ( 4 % ) of group 2 ( P maximal esophageal temperature was significantly higher in patients undergoing general anesthesia ( group 1 ) versus patients undergoing conscious sedation ( group 2 ) ( 40.6±1 ° C versus 39.6±0.8 ° C ; P The time to peak temperature was 9±7 seconds in group 1 and 21±9 seconds in group 2 , and this difference was statistically significant ( P complication occurred during or after the administration of the pill cam or during the procedures . All esophageal lesions normalized at the 2-month repeat endoscopic examination . Conclusion —The use of general anesthesia increases the risk of esophageal damage detected by capsule endoscopy",
"Background — Tecarfarin ( ATI-5923 ) is a novel oral vitamin K antagonist . Unlike warfarin , it is metabolized by esterases , escaping metabolism by the cytochrome P450 system and thereby avoiding cytochrome P450–mediated drug-drug or drug-food interactions as well as genetic variations found in the cytochrome P450 system . Both tecarfarin and warfarin can be monitored with the international normalized ratio . We hypothesized that the time in therapeutic range for tecarfarin will exceed values usually experienced with warfarin . Methods and Results — This was a 6- to 12-week open-label , multicenter , phase IIA study of 66 atrial fibrillation patients with a mild to moderate risk of stroke to determine the safety and tolerability of tecarfarin and to ascertain an optimal tecarfarin dosing regimen . Sixty-four subjects ( 97 % ) were taking warfarin at enrollment and were switched to tecarfarin . After the initial 3 weeks of tecarfarin treatment , the mean interpolated time in therapeutic range was 71.4 % . Only 10.9 % of patients had time in therapeutic range of international normalized ratio ranges of 4.0 were 1.2 % and 1.2 % , respectively . The median daily dose ( for an individual patient ) to maintain an international normalized ratio between 2 and 3 was 15.6 mg ( range , 6 to 29 mg ) . Conclusions — This is the first study of tecarfarin in patients with atrial fibrillation . It appears that tecarfarin may possess advantages over the currently available st and ard of care , warfarin , by improving time in therapeutic range . Adequately powered prospect i ve trials are warranted to definitively compare tecarfarin with warfarin in clinical setting s for which warfarin is indicated",
"Background — Atrial arrhythmias are common early after atrial fibrillation ( AF ) ablation . We hypothesized that empirical antiarrhythmic drug ( AAD ) therapy for 6 weeks after AF ablation would reduce the occurrence of atrial arrhythmias . Methods and Results — We r and omized consecutive patients with paroxysmal AF undergoing ablation to empirical antiarrhythmic therapy ( AAD group ) or no antiarrhythmic therapy ( no-AAD group ) for the first 6 weeks after ablation . In the no-AAD group , only atrioventricular nodal blocking agents were prescribed . All patients wore a transtelephonic monitor for 4 weeks after discharge and were reevaluated at 6 weeks . The primary end point of the study was a composite of ( 1 ) atrial arrhythmias lasting more than 24 hours ; ( 2 ) atrial arrhythmias associated with severe symptoms requiring hospital admission , cardioversion , or initiation/change of antiarrhythmic drug therapy ; and ( 3 ) intolerance to antiarrhythmic agent requiring drug cessation . Of 110 enrolled patients ( age 55±9 years , 71 % male ) , 53 were r and omized to AAD and 57 to no-AAD . There was no difference in baseline characteristics between groups . During the 6 weeks after ablation , fewer patients reached the primary end point in the AAD compared with the no-AAD group ( 19 % versus 42 % ; P=0.005 ) . There remained fewer events in the AAD group ( 13 % versus 28 % ; P=0.05 ) when only end points of AF > 24 hours , arrhythmia-related hospitalization , or electrical cardioversion were compared . Conclusions — AAD treatment during the first 6 weeks after AF ablation is well tolerated and reduces the incidence of clinical ly significant atrial arrhythmias and need for cardioversion/hospitalization for arrhythmia management ",
"Background — Postural tachycardia syndrome ( POTS ) induces disabling chronic orthostatic intolerance with an excessive increase in heart rate on st and ing . β-Blockade is an appealing treatment approach , but conflicting preliminary reports are conflicting . We tested the hypothesis that propranolol will attenuate the tachycardia and improve symptom burden in patients with POTS . In protocol 1 , a low dose ( 20 mg ) was compared with placebo , and the dose response was assessed in protocol 2 . Methods and Results — In protocol 1 , patients with POTS ( n=54 ) underwent acute drug trials of propranolol 20 mg orally and placebo , on separate mornings , in a r and omized crossover design . Blood pressure , heart rate , and symptoms were assessed while the patients were seated and after st and ing for up to 10 minutes before and hourly after the study drug . Supine ( P ) heart rates were significantly lower after propranolol compared with placebo . The symptom burden improvement from baseline to 2 hours was greater with propranolol than placebo ( median , −4.5 versus 0 arbitrary units ; P=0.044 ) . In protocol 2 , 18 patients with POTS underwent similar trials of high-dose ( 80 mg ) versus low-dose ( 20 mg ) propranolol . Although the high dose elicited a greater decrease than the low dose in st and ing heart rate ( P ) and orthostatic tachycardia ( P propranolol ( −6 versus −2 arbitrary units ; P=0.041 ) . Conclusions — Low-dose oral propranolol significantly attenuated tachycardia and improved symptoms in POTS . Higher-dose propranolol did not further improve , and may worsen , symptoms",
"Background — Many patients with atrial fibrillation are at high risk for stroke and require antithrombotic therapy . Antiarrhythmic drugs have not previously been shown to reduce the risk of stroke in atrial fibrillation . The effect of dronedarone , a new multichannel-blocking antiarrhythmic drug , on stroke has been evaluated in a r and omized , double-blind clinical trial , ATHENA ( A placebo-controlled , double-blind , parallel-arm Trial to assess the efficacy of dronedarone 400 mg BID for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter ) . Methods and Results — Patients with persistent or paroxysmal atrial fibrillation and at least 1 risk factor for cardiovascular hospitalization were r and omized to receive dronedarone ( 400 mg BID ) or double-blind matching placebo and followed up for a minimum of 1 year to a common termination at 30 months . All strokes that occurred during the study were included in the present post hoc analysis . There were 4628 patients r and omized to placebo or dronedarone . The baseline risk factors for stroke were well balanced between the 2 groups , and the baseline mean CHADS2 score was 2 . The baseline use of either oral anticoagulant therapy or antiplatelet agent alone was 60 % . Dronedarone reduced the risk of stroke from 1.8 % per year to 1.2 % per year ( hazard ratio 0.66 , 95 % confidence interval 0.46 to 0.96 , P=0.027 ) . The effect of dronedarone was similar whether or not patients were receiving oral anticoagulant therapy , and there was a significantly greater effect of dronedarone in patients with higher CHADS2 scores . Conclusions — In this post hoc analysis , a reduction in stroke was observed in patients with atrial fibrillation who were receiving usual care , which included antithrombotic therapy and heart rate control , who were r and omized to dronedarone . Further studies to investigate the effect of dronedarone and other antiarrhythmic agents on stroke are indicated",
"Background — The Sudden Cardiac Death in Heart Failure Trial ( SCD-HeFT ) demonstrated that implantable cardioverter-defibrillator ( ICD ) therapy reduces all-cause mortality in patients with New York Heart Association class II/III heart failure and a left ventricular ejection fraction ≤35 % on optimal medical therapy . Whether ICD therapy reduced sudden death caused by ventricular tachyarrhythmias without affecting heart failure deaths in this population is unknown . Methods and Results — SCD-HeFT r and omized 2521 subjects to placebo , amiodarone , or shock-only , single-lead ICD therapy . Over a median follow-up of 45.5 months , a total of 666 deaths occurred , which were review ed by an Events Committee and initially categorized as cardiac or noncardiac . Cardiac deaths were further adjudicated as result ing from sudden death presumed to be ventricular tachyarrhythmic , bradyarrhythmia , heart failure , or other cardiac causes . ICD therapy significantly reduced cardiac mortality compared with placebo ( adjusted hazard ratio , 0.76 ; 95 % confidence interval , 0.60 to 0.95 ) and tachyarrhythmia mortality ( adjusted hazard ratio , 0.40 ; 95 % confidence interval , 0.27 to 0.59 ) and had no impact on mortality result ing from heart failure or noncardiac causes . The cardiac and tachyarrhythmia mortality reductions were evident in subjects with New York Heart Association class II but not in subjects with class III heart failure . The reduction in tachyarrhythmia mortality with ICD therapy was similar in subjects with ischemic and nonischemic disease . Compared with placebo , amiodarone had no significant effect on any mode of death . Conclusions — ICD therapy reduced cardiac mortality and sudden death presumed to be ventricular tachyarrhythmic in SCD-HeFT and had no effect on heart failure mortality . Amiodarone had no effect on all-cause mortality or its cause-specific components , except an increase in non-cardiac mortality in class III patients . Clinical Trial Registration Information— URL : http://www . clinical trials.gov . Unique identifier : NCT00000609",
"Background — One variable that may influence cardiac resynchronization therapy response is the programmed atrioventricular ( AV ) delay . The SmartDelay Determined AV Optimization : A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy ( SMART-AV ) Trial prospect ively r and omized patients to a fixed empirical AV delay ( 120 milliseconds ) , echocardiographically optimized AV delay , or AV delay optimized with SmartDelay , an electrogram-based algorithm . Methods and Results — A total of 1014 patients ( 68 % men ; mean age , 66±11 years ; mean left ventricular ejection fraction , 25±7 % ) who met enrollment criteria received a cardiac resynchronization therapy defibrillator , and 980 patients were r and omized in a 1:1:1 ratio . All patients were programmed ( DDD-60 or DDDR-60 ) and evaluated after implantation and 3 and 6 months later . The primary end point was left ventricular end-systolic volume . Secondary end points included New York Heart Association class , quality -of-life score , 6-minute walk distance , left ventricular end-diastolic volume , and left ventricular ejection fraction . The medians ( quartiles 1 and 3 ) for change in left ventricular end-systolic volume at 6 months for the SmartDelay , echocardiography , and fixed arms were −21 mL ( −45 and 6 mL ) , −19 mL ( −45 and 6 mL ) , and −15 mL ( −41 and 6 mL ) , respectively . No difference in improvement in left ventricular end-systolic volume at 6 months was observed between the SmartDelay and echocardiography arms ( P=0.52 ) or the SmartDelay and fixed arms ( P=0.66 ) . Secondary end points , including structural ( left ventricular end-diastolic volume and left ventricular ejection fraction ) and functional ( 6-minute walk , quality of life , and New York Heart Association classification ) measures , were not significantly different between arms . Conclusions — Neither SmartDelay nor echocardiography was superior to a fixed AV delay of 120 milliseconds . The routine use of AV optimization techniques assessed in this trial is not warranted . However , these data do not exclude possible utility in selected patients who do not respond to cardiac resynchronization therapy . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00677014",
"BACKGROUND Methods to identify high-risk patients and timing of implantable cardioverter-defibrillator ( ICD ) therapy after ST-elevation myocardial infa rct ion need further optimization . METHODS AND RESULTS We evaluated outcomes of early ICD implantation in patients with inducible ventricular tachycardia . Consecutive patients treated with primary percutaneous coronary intervention for acute ST-elevation myocardial infa rct ion underwent early left ventricular ejection fraction ( LVEF ) assessment . Patients with LVEF > 40 % were discharged ( group 1 ) ; patients with LVEF electrophysiological study . If no ventricular tachycardia was induced , patients were discharged without an ICD ( group 2 ) . If sustained monomorphic ventricular tachycardia ( > or = 200-ms cycle length ) was induced , an ICD was implanted before discharge ( group 3 ) . Follow-up was obtained up to 30 months in all patients and up to 48 months in a subgroup of patients with LVEF total mortality . Group 1 ( n=574 ) had a mean LVEF of 54+/-8 % ; group 2 ( n=83 ) , 32+/-6 % ; and group 3 ( n=32 ) , 29+/-7 % . At a median follow-up of 12 months , there was no significant difference in survival between the 3 groups ( P=0.879 ) , with mortality rates of 3 % , 3 % , and 6 % for groups 1 through 3 , respectively . In the subgroup of group 2 patients with LVEF mortality at a median follow-up of 25 months . In group 3 , 19 % had spontaneous ICD activation result ing from ventricular tachycardia . CONCLUSIONS Early ICD implantation limited to patients with inducible ventricular tachycardia enables a low overall mortality in patients with impaired LVEF after primary percutaneous coronary intervention for ST-elevation myocardial infa rct ion",
"Background — Brugada syndrome is characterized by ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death ( SCD ) . Fundamental questions remain on the best strategy for assessing the real disease-associated arrhythmic risk , especially in asymptomatic patients . The aim of the present study was to evaluate the prognosis and risk factors of SCD in Brugada syndrome patients in the FINGER ( France , Italy , Netherl and s , Germany ) Brugada syndrome registry . Methods and Results — Patients were recruited in 11 tertiary centers in 4 European countries . Inclusion criteria consisted of a type 1 ECG present either at baseline or after drug challenge , after exclusion of diseases that mimic Brugada syndrome . The registry included 1029 consecutive individuals ( 745 men ; 72 % ) with a median age of 45 ( 35 to 55 ) years . Diagnosis was based on ( 1 ) aborted SCD ( 6 % ) ; ( 2 ) syncope , otherwise unexplained ( 30 % ) ; and ( 3 ) asymptomatic patients ( 64 % ) . During a median follow-up of 31.9 ( 14 to 54.4 ) months , 51 cardiac events ( 5 % ) occurred ( 44 patients experienced appropriate implantable cardioverter-defibrillator shocks , and 7 died suddenly ) . The cardiac event rate per year was 7.7 % in patients with aborted SCD , 1.9 % in patients with syncope , and 0.5 % in asymptomatic patients . Symptoms and spontaneous type 1 ECG were predictors of arrhythmic events , whereas gender , familial history of SCD , inducibility of ventricular tachyarrhythmias during electrophysiological study , and the presence of an SCN5A mutation were not predictive of arrhythmic events . Conclusions — In the largest series of Brugada syndrome patients thus far , event rates in asymptomatic patients were low . Inducibility of ventricular tachyarrhythmia and family history of SCD were not predictors of cardiac events",
"Background — Together with pulmonary veins , many extrapulmonary vein areas may be the source of initiation and maintenance of atrial fibrillation . The left atrial appendage ( LAA ) is an underestimated site of initiation of atrial fibrillation . Here , we report the prevalence of triggers from the LAA and the best strategy for successful ablation . Methods and Results — Nine hundred eighty-seven consecutive patients ( 29 % paroxysmal , 71 % nonparoxysmal ) undergoing redo catheter ablation for atrial fibrillation were enrolled . Two hundred sixty-six patients ( 27 % ) showed firing from the LAA and became the study population . In 86 of 987 patients ( 8.7 % ; 5 paroxysmal , 81 nonparoxysmal ) , the LAA was found to be the only source of arrhythmia with no pulmonary veins or other extrapulmonary vein site reconnection . Ablation was performed either with focal lesion ( n=56 ; group 2 ) or to achieve LAA isolation by placement of the circular catheter at the ostium of the LAA guided by intracardiac echocardiography ( 167 patients ; group 3 ) . In the remaining patients , LAA firing was not ablated ( n=43 ; group 1 ) . At the 12±3-month follow-up , 32 patients ( 74 % ) in group 1 had recurrence compared with 38 ( 68 % ) in group 2 and 25 ( 15 % ) in group 3 ( P arrhythmias in 27 % of patients presenting for repeat procedures . Isolation of the LAA could achieve freedom from atrial fibrillation in patients presenting for a repeat procedure when arrhythmias initiating from this structure are demonstrated",
"Background — Prospect i ve studies defining the risk associated with pacemaker or implantable cardioverter-defibrillator replacement surgeries do not exist . These procedures are generally considered low risk despite results from recent retrospective series reporting higher rates . Methods and Results — We prospect ively assessed predefined procedure-related complication rates associated with elective pacemaker or implantable cardioverter-defibrillator generator replacements over 6 months of follow-up . Two groups were studied : those without ( cohort 1 ) and those with ( cohort 2 ) a planned transvenous lead addition for replacement or up grade to a device capable of additional therapies . Complications were adjudicated by an independent events committee . Seventy-two US academic and private practice centers participated . Major complications occurred in 4.0 % ( 95 % confidence interval , 2.9 to 5.4 ) of 1031 cohort 1 patients and 15.3 % ( 95 % confidence interval , 12.7 to 18.1 ) of 713 cohort 2 patients . In both cohorts , major complications were higher with implantable cardioverter-defibrillator compared with pacemaker generator replacements . Complications were highest in patients who had an up grade to or a revised cardiac resynchronization therapy device ( 18.7 % ; 95 % confidence interval , 15.1 to 22.6 ) . No periprocedural deaths occurred in either cohort , although 8 later procedure-related deaths occurred in cohort 2 . The 6-month infection rates were 1.4 % ( 95 % confidence interval , 0.7 to 2.3 ) and 1.1 % ( 95 % confidence interval , 0.5 to 2.2 ) for cohorts 1 and 2 , respectively . Conclusions — Pacemaker and implantable cardioverter-defibrillator generator replacements are associated with a notable complication risk , particularly those with lead additions . These data support careful decision making before device replacement , when managing device advisories , and when considering up grade s to more complex systems . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00395447",
"Background — Reactions to music are considered subjective , but previous studies suggested that cardiorespiratory variables increase with faster tempo independent of individual preference . We tested whether compositions characterized by variable emphasis could produce parallel instantaneous cardiovascular/respiratory responses and whether these changes mirrored music profiles . Methods and Results — Twenty-four young healthy subjects , 12 musicians ( choristers ) and 12 nonmusician control subjects , listened ( in r and om order ) to music with vocal ( Puccini 's “ Tur and ot ” ) or orchestral ( Beethoven 's 9th Symphony adagio ) progressive crescendos , more uniform emphasis ( Bach cantata ) , 10-second period ( ie , similar to Mayer waves ) rhythmic phrases ( Giuseppe Verdi 's arias “ Va pensiero ” and “ Libiam nei lieti calici ” ) , or silence while heart rate , respiration , blood pressures , middle cerebral artery flow velocity , and skin vasomotion were recorded . Common responses were recognized by averaging instantaneous cardiorespiratory responses regressed against changes in music profiles and by coherence analysis during rhythmic phrases . Vocal and orchestral crescendos produced significant ( P=0.05 or better ) correlations between cardiovascular or respiratory signals and music profile , particularly skin vasoconstriction and blood pressures , proportional to crescendo , in contrast to uniform emphasis , which induced skin vasodilation and reduction in blood pressures . Correlations were significant both in individual and group-averaged signals . Phrases at 10-second periods by Verdi entrained the cardiovascular autonomic variables . No qualitative differences in recorded measurements were seen between musicians and nonmusicians . Conclusions — Music emphasis and rhythmic phrases are tracked consistently by physiological variables . Autonomic responses are synchronized with music , which might therefore convey emotions through autonomic arousal during crescendos or rhythmic phrases",
"Background —Current methods for detecting atrial fibrillation ( AF ) have limited diagnostic yield . Continuous monitoring with automatic arrhythmia detection and classification may improve detection of symptomatic and asymptomatic AF and subsequent patient treatment . The study purpose was to quantify the performance of the first implantable leadless cardiac monitor ( ICM ) with dedicated AF detection capabilities . Methods and Results — Patients ( n=247 ) with an implanted ICM ( Reveal XT , Medtronic Inc , Minneapolis , Minn ) who were likely to present with paroxysmal AF were selected . A special Holter device stored 46 hours of subcutaneously recorded ECG , ICM markers , and 2 surface ECG leads . The ICM automatic arrhythmia classification was compared with the core laboratory classification of the surface ECG . Of the 206 analyzable Holter recordings collected , 76 ( 37 % ) contained at least 1 episode of core laboratory classified AF . The sensitivity , specificity , positive predictive value , and negative predictive value for identifying patients with any AF were 96.1 % , 85.4 % , 79.3 % , and 97.4 % , respectively . The AF burden measured with the ICM was very well correlated with the reference value derived from the Holter ( Pearson coefficient=0.97 ) . The overall accuracy of the ICM for detecting AF was 98.5 % . Conclusions —In this ICM validation study , the dedicated AF detection algorithm reliably detected the presence or absence of AF and the AF burden was accurately quantified . The ICM is a promising new diagnostic and monitoring tool for the clinician to treat AF patients independently of symptoms . Long-term studies are needed to evaluate the clinical benefits of the technology . Clinical Trial Registration — clinical trials.gov Identifier NCT00680927",
"Background —Whether different ablation strategies affect paroxysmal atrial fibrillation ( AF ) long-term freedom from AF/atrial tachyarrhythmia is unclear . We sought to compare the effect of 3 different ablation approaches on the long-term success in patients with paroxysmal AF . Methods and Results —One hundred three consecutive patients with paroxysmal AF scheduled for ablation and presenting in the electrophysiology laboratory in AF were selected for this study . Patients were r and omized to pulmonary vein antrum isolation ( PVAI ; n=35 ) versus biatrial ablation of the complex fractionated atrial electrograms ( CFAEs ; n=34 ) versus PVAI followed by CFAEs ( n=34 ) . Patients were given event recorders and followed up at 3 , 6 , 9 , 12 , and 15 months postablation . There was no statistical significant difference between the groups in term of sex , age , AF duration , left atrial size , and ejection fraction . At 1 year follow-up , freedom from AF/atrial tachyarrhythmia was documented in 89 % of patients in the PVAI group , 91 % in the PVAI plus CFAEs group , and 23 % in the CFAEs group ( P success rate was seen between PVAI alone and PVAI associated with defragmentation . CFAEs ablation alone had the smallest impact on AF recurrences at 1-year follow-up . These results suggest that antral isolation is sufficient to treat most patients with paroxysmal AF",
"Background — Although implantable cardioverter-defibrillators ( ICDs ) lower mortality in stable patients with low ejection fraction late after myocardial infa rct ion , r and omized trials of ICD versus control subjects implanted early after myocardial infa rct ion do not show mortality benefit . Our objective was to investigate possible mechanisms underlying the lack of mortality benefit in the Defibrillation in Acute Myocardial Infa rct ion Trial ( DINAMIT ) . Methods and Results — This is a secondary analysis of the prospect i ve r and omized clinical trial . Out patients with recent ( 6 to 40 days ) acute myocardial infa rct ion , left ventricular dysfunction ( ejection fraction ICD ( n=311 ) or to st and ard medical therapy ( n=342 ) . In a competing-risks analysis , those factors that increased the risk of arrhythmic death also increased the risk of nonarrhythmic deaths . After adjustment for these factors , receiving an ICD was associated with a decreased risk of arrhythmic death ( hazard ratio , 0.33 ; 95 % confidence interval , 0.15 to 0.71 ) but an increase in nonarrhythmic death ( hazard ratio , 1.70 ; 95 % confidence interval , 1.00 to 2.80 ) . In an adjusted time-dependent analysis , patients receiving an ICD and having appropriate ICD therapy had a 15.1 % yearly hazard of mortality compared with 5.2 % in ICD patients with no appropriate therapy ( P sudden death in ICD patients was completely offset by increased nonarrhythmic deaths , which were greatest in patients receiving ICD shock therapy ( hazard ratio , 6.0 ; 95 % confidence interval , 2.8 to 12.7 ) . Conclusions — In patients receiving ICDs early after myocardial infa rct ion , those factors that are associated with arrhythmia requiring ICD therapy are also associated with a high risk of nonsudden death , negating the benefit of ICDs in this setting"
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41179876-06ff-11f0-808a-c43d1ab1c353
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CONTEXT More than 50 million US adults take aspirin regularly for long-term prevention of cardiovascular disease , typically either 81 mg/d or 325 mg/d . Controversy remains regarding the most appropriate long-term daily dose . OBJECTIVE To review the mechanism of action of aspirin and the clinical literature for relationships among aspirin dosage , efficacy , and safety . EVIDENCE ACQUISITION A systematic review of the English- language literature was undertaken using MEDLINE and EMBASE ( search ed through February 2007 ) and the search term aspirin or acetylsalicylic acid and dose . The search was limited to clinical trials and was extended by a review of bibliographies of pertinent reports of original data and review articles . Published prospect i ve studies using different aspirin dosages in the setting of cardiovascular disease were included . EVIDENCE SYNTHESIS Although pharmacodynamic data demonstrate that long-term aspirin dosages as low as 30 mg/d are adequate to fully inhibit platelet thromboxane production , dosages as high as 1300 mg/d are approved for use . In the United States , 81 mg/d of aspirin is prescribed most commonly ( 60 % ) , followed by 325 mg/d ( 35 % ) . The available evidence , predominantly from secondary -prevention observational studies , supports that dosages greater than 75 to 81 mg/d do not enhance efficacy , whereas larger dosages are associated with an increased incidence of bleeding events , primarily related to gastrointestinal tract toxicity . CONCLUSIONS Currently available clinical data do not support the routine , long-term use of aspirin dosages greater than 75 to 81 mg/d in the setting of cardiovascular disease prevention . Higher dosages , which may be commonly prescribed , do not better prevent events but are associated with increased risks of gastrointestinal bleeding
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"CONTEXT Recent r and omized trials suggest that women may not accrue the same cardioprotective benefits as men do from low-dose aspirin therapy used in primary prevention . Failure of aspirin to suppress platelet aggregation in women is one hypothesized mechanism . OBJECTIVE To examine differential platelet reactivity to low-dose aspirin therapy by sex . DESIGN , SETTING , AND PARTICIPANTS A clinical trial of aspirin at 81 mg/d for 14 days was conducted in 571 men and 711 women . Baseline and post-aspirin therapy measures included platelet aggregation to arachidonic acid , adenosine diphosphate , epinephrine , and platelet function analyzer closure time . MAIN OUTCOME MEASURE Sex differences in cyclooxygenase 1 ( COX-1 ) direct and indirect platelet activation pathways before and after administration of aspirin . RESULTS In 10 of the 12 platelet agonist exposures , women 's platelets were significantly more reactive at baseline . However , after aspirin therapy , the percent aggregation to arachidonic acid ( the direct COX-1 pathway ) decreased more in women than in men ( P reactivity in both men and women . In COX-1 indirect pathways , women experienced the same or more platelet inhibition than men in 8 of the 9 assays yet retained modestly greater platelet reactivity after aspirin therapy . In multivariable analysis , female sex significantly predicted aggregation to 2 muM and 10 muM of adenosine diphosphate ( P = .02 and platelet reactivity after aspirin therapy , retaining modestly more platelet reactivity compared with men . However , most women achieved total suppression of aggregation in the direct COX-1 pathway , the putative mechanism for aspirin 's cardioprotection",
"The focus of new research efforts to improve the morbidity and mortality associated with acute myocardial infa rct ion ( AMI ) has turned to adjuvant agents that show promise of improving outcomes following coronary thrombolysis . We enrolled 162 patients with AMI in a r and omized trial comparing front-loaded tissue-plasminogen activator ( t-PA ) plus weight-adjusted heparin with anisoylated plasminogen streptokinase activator complex ( APSAC ) without heparin as well as st and ard-dose ( 325 mg ) and low-dose ( 81 mg ) aspirin . The primary end point was an in-hospital morbidity profile ; secondary end points were clinical and angiographic potency and hemorrhagic events . Selected sites performed an electrocardiographic sub study to determine the time to 50 % ST-segment recovery and the time to steady state . Although the trial was terminated when the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries-I trial showed that t-PA had a significant mortality advantage over streptokinase , important trends were evident . Patients given t-PA and heparin were better anticoagulated ( p = 0.001 ) , yet AP-SAC-treated patients had more bleeding complications . The primary end point favored t-PA ( 25.4 % vs 31.3 % ) , and the secondary end points were similar in both groups . In the electrocardiographic sub study , the t-PA group achieved both 50 % ST-segment recovery and steady-state recovery sooner than the APSAC group . Patients taking low-dose aspirin had lower in-hospital mortality and less recurrent ischemia but more strokes than the st and ard-dose aspirin group . Thus , this trial demonstrated trends favoring front-loaded t-PA with weight-adjusted heparin over APSAC without heparin in the treatment of AMI . The use of low-dose aspirin did not appear to impose a loss of protection from adverse events , nor did st and ard-dose aspirin increase serious bleeding",
"Abstract Objective To ascertain the current burden of adverse drug reactions ( ADRs ) through a prospect i ve analysis of all admissions to hospital . Design Prospect i ve observational study . Setting Two large general hospitals in Merseyside , Engl and . Participants 18 820 patients aged > 16 years admitted over six months and assessed for cause of admission . Main outcome measures Prevalence of admissions due to an ADR , length of stay , avoidability , and outcome . Results There were 1225 admissions related to an ADR , giving a prevalence of 6.5 % , with the ADR directly leading to the admission in 80 % of cases . The median bed stay was eight days , accounting for 4 % of the hospital bed capacity . The projected annual cost of such admissions to the NHS is £ 466 m ( € 706 m , $ 847 m ) . The overall fatality was 0.15 % . Most reactions were either definitely or possibly avoidable . Drugs most commonly implicated in causing these admissions included low dose aspirin , diuretics , warfarin , and non-steroidal anti-inflammatory drugs other than aspirin , the most common reaction being gastrointestinal bleeding . Conclusion The burden of ADRs on the NHS is high , accounting for considerable morbidity , mortality , and extra costs . Although many of the implicated drugs have proved benefit , measures need to be put into place to reduce the burden of ADRs and thereby further improve the benefit : harm ratio of the drugs",
"Background —We studied the benefits and risks of adding clopidogrel to different doses of aspirin in the treatment of patients with acute coronary syndrome ( ACS ) . Methods and Results —In the Clopidogrel in Unstable angina to prevent Recurrent Events ( CURE ) trial , 12 562 patients with ACS using aspirin , 75 to 325 mg daily , were r and omized to clopidogrel or placebo for up to 1 year . In this analysis , patients were divided into the following 3 aspirin dose groups : ≤100 mg , 101 through 199 mg , and ≥200 mg . The combined incidence of cardiovascular death , myocardial infa rct ion , or stroke was reduced by clopidogrel regardless of aspirin dose , as follows : ≤100 mg , 10.5 % versus 8.6 % ( relative risk [ RR ] , 0.81 [ 95 % CI , 0.68 to 0.97 ] ) ; 101 to 199 mg , 9.8 % versus 9.5 % ( RR , 0.97 [ 95 % CI 0.77 to 1.22 ] ) ; and ≥200 mg , 13.6 % versus 9.8 % ( RR , 0.71 [ 95 % CI , 0.59 to 0.85 ] ) . The incidence of major bleeding increased with increasing aspirin dose both in the placebo group ( 1.9 % , 2.8 % , and 3.7 % , respectively ; P = 0.0001 ) and the clopidogrel group ( 3.0 % , 3.4 % , and 4.9 % , respectively ; P = 0.0009 ) ; thus , the excess risk with clopidogrel was 1.1 % , 1.2 % , and 1.2 % , respectively . The adjusted hazard ratio for major bleeding for the highest versus the lowest dose of aspirin was 1.9 ( 95 % CI 1.29 to 2.72 ) in the placebo group , 1.6 ( 95 % CI 1.19 to 2.23 ) in the clopidogrel group , and 1.7 ( 95 % CI 1.36 to 2.20 ) in the combined group . Conclusions —In patients with ACS , adding clopidogrel to aspirin is beneficial regardless of aspirin dose . Bleeding risks increase with increasing aspirin dose , with or without clopidogrel , without any increase in efficacy . Our findings suggest that the optimal daily dose of aspirin may be between 75 and 100 mg , with or without clopidogrel ",
" From 1979 to 1985 2435 patients having had transient ischaemic attacks ( TIAs ) or minor ischaemic strokes , were enrolled in the UK TIA trial and were r and omised to receive either aspirin 300 mg , daily or aspirin 1200 mg or placebo . Analysis of reported upper gastrointestinal bleeding events ( defined as haematemesis or melaena , or both ) showed a risk of bleeding in a dose dependent manner , odds ratios ( 95 % CI ) for 300 mg of aspirin = 3.3 ( 1.2 to 9.0 ) and for 1200 mg = 6.4 ( 2.5 to 16.5 ) and , as would be expected , an increased risk of hospitalisation because of bleeding also in a dose dependent manner , odds ratio = 3.6 ( 0.7 to 17.2 ) for 300 mg and 8.7 ( 2.0 to 37.6 ) for 1200 mg . Further analysis suggested greater risks of bleeding from duodenal ulcers than gastric ulcers and that bleeding is more likely early in the course of treatment with aspirin used as secondary prevention . There was also an increased risk of lower gastrointestinal bleeding , defined as fresh blood per rectum for both doses of aspirin , odds ratio 1.8 ( 0.5 to 6.1 ) for 300 mg of aspirin , and 1.5 ( 0.4 to 5.3 ) for 1200 mg of aspirin ",
" From 1979 - 85 , 2435 patients with a transient ischaemic attack or minor ischaemic stroke were r and omly allocated to receive long term \" blind \" treatment with aspirin 600 mg twice daily ( n = 815 ) , aspirin 300 mg once daily ( n = 806 ) or placebo ( n = 814 ) . No patient was lost to follow up . The \" intention to treat \" comparison included all the serious vascular events and deaths which occurred before the end of the follow up period on 30 September 1986 . There was no difference in efficacy between the 300 mg and 1200 mg daily doses of aspirin , but the lower dose was undoubtedly less gastrotoxic . Also , there was no definite difference in the response of males and females to aspirin . The odds of suffering a major stroke , myocardial infa rct ion or vascular death were 15 % less in the combined aspirin groups compared with the placebo group ( 95 % confidence interval 29 % reduction to 3 % increase in odds ) which is compatible with the continuing overview of all the similar trials of antiplatelet drugs where the relative reduction in odds was 25 % . There was no statistically significant reduction in the likelihood of either disabling major stroke and vascular death or vascular death occurring",
"In order to evaluate the efficacy of low dose acetylsalicylic acid ( ASA ) for the secondary prevention of ischemic stroke , this cooperative multicenter clinical trial was conducted on a non-blind basis . Patients having a first transient ischemic attack ( TIA ) , reversible ischemic neurological deficit ( RIND ) or completed ischemic stroke were eligible for this trial . A total of 590 patients including 47 cases of TIA , 23 cases of RIND and 520 cases of completed stroke entered this study . These patients were allocated by the time of admission to one of the following 5 trial regimens : ( 1 ) vasodilators having no known inhibitory effect on platelet function ( control group ) , ( 2 ) dipyridamole ( DP ) 50 mg 3 times a day ( DP group ) , ( 3 ) ASA 300 mg once a day ( ASA 300 mg group ) , ( 4 ) ASA 300 mg once in combination with DP 50 mg 3 times a day ( ASADP group ) , and ( 5 ) ASA 100 mg once a day ( ASA1 group ) . No difference in effect between the control and DP groups was observed , nor between the ASA 300 mg and ASADP groups . Therefore , we combined the control and DP groups to make a non-ASA group , and joined the ASA 300 mg and ASADP groups to make an ASA3 group . The differences in the cumulative event-free rate appeared to be significant between the non-ASA group and the ASA3 group and also between the non-ASA group and the ASA1 group . But the frequency distribution of age , territory of stroke , diabetes mellitus , cardiac disease , hematological disease and hyperuricemia were significantly different among these 3 study groups . We thus included these covariates in the Cox 's proportional hazard model to control their possible confounding effects . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Background —This is the primary report of the large-scale evaluation of lotrafiban , an orally administered IIb/IIIa receptor antagonist , a unique trial with respect to the platelet antagonist , protocol design , and inclusion of cerebrovascular disease in a significant proportion of patients . Methods and Results — Patients with vascular disease were r and omized to lotrafiban 30 or 50 mg BID on the basis of age and predicted creatinine clearance or placebo in addition to aspirin at a dose ranging from 75 to 325 mg/d at the discretion of the physician-investigator . Follow-up was for up to 2 years . The primary end point was the composite of all-cause mortality , myocardial infa rct ion , stroke , recurrent ischemia requiring hospitalization , and urgent revascularization . Of 9190 patients enrolled from 23 countries and 690 hospitals , 41 % had cerebrovascular disease at the time of entry , and 59 % had coronary artery disease . Death occurred in 2.3 % of placebo-assigned patients and 3.0 % of lotrafiban-group patients ( hazard ratio 1.33 , 95 % CI 1.03 to 1.72 , P = 0.026 ) , and the cause of excess death was vascular related . There was no significant difference in the primary end point ( 17.5 % compared with 16.4 % , respectively ; hazard ratio 0.94 , 95 % CI 0.85 to 1.03 , P = 0.19 ) . Serious bleeding was more frequent in the lotrafiban group ( 8.0 % compared with 2.8 % ; P Serious bleeding was more common among patients who received higher doses of aspirin ( > 162 mg/d ) , with or without lotrafiban . Conclusions —Lotrafiban , an orally administered platelet glycoprotein IIb/IIIa blocker , induced a 33 % increase in death rate , which was vascular in origin and not affected by the type of atherosclerotic involvement at entry to the trial . Although the dose of aspirin was not r and omly assigned , the finding of increased bleeding with doses > 162 mg/d is noteworthy",
"Large clinical trials such as the second International Study of Infa rct Survival routinely gave patients with myocardial infa rct ion a chewed aspirin , yet there are no data to show whether chewing of aspirin is better , or worse , than swallowing a whole tablet . We performed a r and omized , placebo-controlled study to determine whether chewing aspirin or administering it in solution accelerates its absorption and antiplatelet activity . On separate days , 12 fasting volunteers ingested 325 mg of buffered aspirin , either by chewing a tablet for 30 seconds before swallowing it with 4 ounces of water , swallowing a whole tablet with 4 ounces of water , or drinking 4 ounces of Alka Seltzer . Frequent blood sample s were obtained for serum aspirin , salicylate , and thromboxane B2 ( TxB2 ) concentrations . With all formulations of aspirin , serum TxB2 decreased 50 % when the plasma aspirin concentration reached approximately 1,000 ng/ml . A 50 % and 90 % decrease in serum TxB2 occurred more quickly after chewing a tablet than after a tablet was swallowed whole . For example , the t 50 % for serum TxB2 inhibition was 5.0 + /- 0.6 minutes with the chewed tablet versus 12.0 + /- 2.3 minutes when the tablet was swallowed ( p = 0.01 ) . A 50 % decrease in serum TxB2 occurred 7.6 + /- 1.2 minutes after Alka Seltzer solution ( p = 0.04 vs chewing a tablet ; p = 0.13 vs swallowing a whole tablet ) . Chewing an aspirin tablet is the most effective way of accelerating absorption of aspirin into the blood and shortening the time required for an antiplatelet effect",
"BACKGROUND Aspirin is known to improve the outcome of patients who have had a cerebral transient ischemic attack , but the optimal dose of aspirin remains uncertain . Experimental evidence indicates that 30 mg of aspirin daily alters platelet aggregation more favorably than the 300-mg dose currently used in patients after transient ischemic attack or minor ischemic stroke . METHODS We assessed the effects of two doses of a water-soluble preparation of acetylsalicylic acid , or aspirin ( 30 mg vs. 283 mg a day ) , on the occurrence of death from all vascular causes , nonfatal stroke , or nonfatal myocardial infa rct ion in a double-blind , r and omized , controlled clinical trial in patients who had had a transient ischemic attack or minor stroke . A total of 3131 patients participated in the study . The mean follow-up was 2.6 years . RESULTS In the group assigned to receive 30 mg of aspirin , the frequency of death from vascular causes , nonfatal stroke , or nonfatal myocardial infa rct ion was 228 of 1555 ( 14.7 percent ) , as compared with 240 of 1576 ( 15.2 percent ) in the group assigned to receive 283 mg . The age- and sex-adjusted hazard ratio for the group receiving the lower dose was 0.91 ( 95 percent confidence interval , 0.76 to 1.09 ) . There were slightly fewer major bleeding complications in the 30-mg group than in the 283-mg group ( 40 vs. 53 ) , and significantly fewer reports of minor bleeding ( 49 vs. 84 ) . Fewer patients receiving 30 mg of aspirin reported gastrointestinal symptoms ( 164 vs. 179 ) and other adverse effects ( 73 vs. 90 ) . CONCLUSIONS Our data indicate that 30 mg of aspirin daily is no less effective in the prevention of vascular events than a 283-mg dose in patients with a transient ischemic attack or minor stroke , and has fewer adverse effects",
"Data describing the pharmacokinetics and pharmacodynamics of low dose aspirin ( acetylsalicylic acid ; ASA ) are limited . This single-center study was design ed to determine the rate and extent of oral absorption of 80-mg ASA tablets in healthy , young male subjects and to assess the intra- and inter-subject variability of ASA pharmacokinetics and platelet aggregation effects . Ten subjects each received a single , open-label , oral 80-mg ASA dose on three separate days . Each dose was separated by a 2-week washout interval . Blood sample s for pharmacokinetic determinations of ASA and its metabolite , salicylic acid ( SA ) and platelet aggregation studies were obtained at scheduled timepoints before and up to 24 hours after each dose . Peak plasma ASA levels of 1 microgram/mL were achieved within 30 minutes . Peak plasma SA levels of approximately 4 micrograms/mL were attained in 1 hour . The terminal half-lives ( t1/2 ) of ASA and SA were 0.4 and 2.1 hours , respectively . Both ASA and SA pharmacokinetics and the platelet aggregation response to ASA exhibited considerable intra- and inter-subject variability . Inhibition of platelet aggregation was found to relate with ASA area under the plasma concentration versus time curve ( AUC )",
"BACKGROUND Aspirin products are known to cause irritation and injury to the gastric mucosa . The belief that enteric-coated and buffered varieties are less likely to occasion major upper-gastrointestinal bleeding ( UGIB ) than plain aspirin was tested in data from a multicentre case-control study . METHODS 550 incident cases of UGIB admitted to hospital with melaena or haematemesis and confirmed by endoscopy , and 1202 controls identified from population census lists , were interviewed about use of aspirin and other non-steroidal anti-inflammatory drugs ( NSAIDs ) during the 7 days before the onset of bleeding ( cases ) or interview ( controls ) . Relative risks of UGIB for each type of aspirin used regularly ( at least every other day ) were calculated overall , and according to dose , by multiple logistic regression , with control for age , sex , marital status , date , education , cigarette smoking , alcohol use , and use of NSAIDs . FINDINGS The relative risks of UGIB for plain , enteric-coated , and buffered aspirin at average daily doses of 325 mg or less were 2.6 , 2.7 , and 3.1 , respectively . At doses greater than 325 mg , the relative risk was 5.8 for plain and 7.0 for buffered aspirin ; there were insufficient data to evaluate enteric-coated aspirin at this dose level . There were no important differences in risk attributable to the three aspirin forms according to bleeding site ( gastric vs duodenal ) , or when users of NSAIDs were excluded . INTERPRETATION Use of low doses of enteric-coated or buffered aspirin carries a three-fold increase in the risk of major UGIB . The assumption that these formulations are less harmful than plain aspirin may be mistaken",
"BACKGROUND Long-term treatment with aspirin is recommended in patients with large-vessel peripheral arterial disease since these patients have a high risk of death from cardiovascular causes . Recent studies have demonstrated the prophylactic effect of low-dose aspirin in reducing the risk of cardiovascular events . Since aspirin is also recommended for prevention of late recurrence after peripheral angioplasty , the present study was undertaken to compare the effects of high-dose ( 1000 mg/d ) and low-dose ( 100 mg/d ) aspirin on long-term patency after femoropopliteal angioplasty . METHODS AND RESULTS Two hundred sixteen patients treated successfully by percutaneous transluminal angioplasty for femoropopliteal lesions were r and omly allocated to therapy with either 1000 or 100 mg aspirin daily . The follow-up was 24 months . The long-term results were analyzed using the Kaplan-Meier method , and differences between curves of cumulative patency were determined with the Wilcoxon and log-rank statistics . Complete follow-up information ( patency after 24 months , restenosis , and death ) was obtained in 207 patients . During the 2-year follow-up period , 72 patients --36 in the high-dose and 36 in the low-dose aspirin group , respectively -- developed angiographically verified reobstruction within the recanalized segment . By intention-to-treat analysis , the cumulative patency rates at 24 months were 62.5 % in the high-dose and 62.6 % in the low-dose aspirin group ( Wilcoxon , P = .97 ; log-rank , P = .97 ) . The cumulative survival at 24 months of follow-up was 86.6 % in the high-dose and 87.7 % in the low-dose aspirin group . The number of patients discontinuing therapy was 30 in the high-dose and 11 in the low-dose aspirin group ( P aspirin discontinued therapy because of gastrointestinal symptoms ( 4 versus 20 ) . CONCLUSIONS The data indicate that 100 mg aspirin is no less effective in the prevention of restenosis after femoropopliteal PTA than a 1000-mg dose and has fewer side effects",
"BACKGROUND Inflammation may be important in the pathogenesis of atherothrombosis . We studied whether inflammation increases the risk of a first thrombotic event and whether treatment with aspirin decreases the risk . METHODS We measured plasma C-reactive protein , a marker for systemic inflammation , in 543 apparently healthy men participating in the Physicians ' Health Study in whom myocardial infa rct ion , stroke , or venous thrombosis subsequently developed , and in 543 study participants who did not report vascular disease during a follow-up period exceeding eight years . Subjects were r and omly assigned to receive aspirin or placebo at the beginning of the trial . RESULTS Base-line plasma C-reactive protein concentrations were higher among men who went on to have myocardial infa rct ion ( 1.51 vs. 1.13 mg per liter , P C-reactive protein values had three times the risk of myocardial infa rct ion ( relative risk , 2.9 ; P risk of ischemic stroke ( relative risk , 1.9 ; P=0.02 ) of the men in the lowest quartile . Risks were stable over long periods , were not modified by smoking , and were independent of other lipid-related and non-lipid-related risk factors . The use of aspirin was associated with significant reductions in the risk of myocardial infa rct ion ( 55.7 percent reduction , P=0.02 ) among men in the highest quartile but with only small , nonsignificant reductions among those in the lowest quartile ( 13.9 percent , P=0.77 ) . CONCLUSIONS The base-line plasma concentration of C-reactive protein predicts the risk of future myocardial infa rct ion and stroke . Moreover , the reduction associated with the use of aspirin in the risk of a first myocardial infa rct ion appears to be directly related to the level of C-reactive protein , raising the possibility that antiinflammatory agents may have clinical benefits in preventing cardiovascular disease",
"OBJECTIVES This study was design ed to compare the efficacy of low and intermediate aspirin doses in acute coronary syndromes . BACKGROUND Little is known of the comparative efficacy of low and intermediate aspirin doses in this setting . METHODS We compared six-month death , myocardial infa rct ion ( MI ) , and stroke in patients with unstable angina or acute MI discharged while receiving low ( or = 150 mg ) aspirin therapy in the GUSTO IIb and PURSUIT trials ( n = 20,521 ) . We used multivariable analysis and performed a propensity analysis in order to adjust for baseline imbalances between the groups . RESULTS Aspirin doses 29.9 % ( 6,128 ) of patients . By six months , 6.4 % of the patients ( 1,310 of 20,521 ) had a primary event , 6.2 % of the patients receiving aspirin doses > or = 150 mg ( hazard ratio [ HR ] 1.06 [ 95 % confidence interval ( CI ) 0.94 to 1.19 ] , p = 0.35 ) . After adjusting for baseline imbalances and the propensity score for discharge aspirin dose , there was no effect of aspirin dose on the composite end point at six months ( HR 0.92 [ 95 % CI 0.79 to 1.07 ] , p = 0.28 ) . However , the higher aspirin dose was associated with a reduction in six-month MI ( HR 0.79 [ 95 % CI 0.64 to 0.98 ] , p = 0.03 ) . The outcome was similar when patients were matched on the basis of the propensity score for aspirin dose ( HR for death/MI/stroke 0.94 [ 95 % CI 0.80 to 1.12 ] , p = 0.51 ) , although stroke occurred significantly more frequently among patients receiving the higher aspirin dose ( HR 1.74 [ 95 % CI 1.01 to 3.02 ] p = 0.05 ) and the effect on MI was no longer apparent . CONCLUSIONS Although these data are non-r and omized , they suggest that the aspirin dose upon discharge may influence the clinical course after unstable angina or acute MI",
"Aim While regular use of low-dose aspirin has been recommended for several groups of patients at risk of vascular occlusion , the optimal dose of aspirin to produce a cardiovascular benefit whilst minimizing side effects is uncertain . Further , while enteric coated preparations may reduce gastrointestinal symptoms , the antiplatelet effects of these formulations have not been completely tested . In addition , exceptionally few data relating to these issues have been available in women . Methods To determine whether a 100 mg alternate day dose of aspirin given in regular and enteric coated formulations for a 2-week period is sufficient to inhibit platelet function in men and women , a r and omized , double-blind , placebo-controlled trial was conducted among 22 healthy volunteers evaluating the effects of these preparations on platelet aggregation induced by arachidonic acid , adenosine diphosphate , and epinephrine , and on plasma concentrations of thromboxane and prostacyclin . Results During the active aspirin phase of the study , all subjects demonstrated a clinical anti-platelet effect as evidence d by failure of the platelets to aggregate in the presence of at least one platelet agonist , and mean thromboxane and prostacyclin levels decreased to 7.5 and 15.6 % of baseline , respectively ( both P recovery of platelet function as well as thromboxane and prostacyclin production . There were virtually no differences between regular and enteric coated formulations , or between men and women . Conclusion These data indicate that an alternate day regimen of 100 mg aspirin given in either regular or enteric coated formulation is adequate to achieve functional platelet inhibition . The clinical efficacy of this dose and formulation of aspirin is being tested in the ongoing Women 's Health Study , a r and omized , double-blind , placebo-controlled trial of 40 000 female health professionals design ed in part to assess the benefits and risks of 100 mg alternate day aspirin in the primary prevention of cardiovascular disease",
"Aspirin interferes with platelet aggregation by inhibiting the metabolism of arachidonic acid to thromboxane A2 . Although both high- and low-dose aspirin therapies are effective for secondary prophylaxis in patients with atherosclerotic vascular disease , the acute response to low-dose aspirin therapy is controversial . Eighteen volunteer subjects ingested 81 , 162 , or 324 mg of aspirin in a longitudinal crossover study design . Initial doses were r and omly assigned and dosing intervals were separated by 2 weeks . Platelet aggregation in response to 0.9 mM arachidonic acid was measured at baseline , 15 , 30 , 60 , and 90 minutes after ingestion . Thromboxane B2 production was assayed on simultaneously obtained sample s after stimulation with arachidonic acid . The median inhibition of aggregation was 97 % , 97 % , and 97 % 15 minutes after ingestion of 81 , 162 , and 324 mg , respectively . Four subjects had 15 minutes after ingesting 81 mg , but all 4 had > 90 % inhibition after 30 minutes . Thromboxane B2 production declined by > 93 % in all subjects at each dose . There was no difference between doses in inhibition of thromboxane B2 production",
"Inhibition of cyclooxygenase by aspirin has been shown to be beneficial in clinical situations such as acute myocardial infa rct ion or unstable angina . The precise effect of various doses of aspirin on acute and long-term inhibition of platelet aggregation and thromboxane synthesis remains unclear . In this study we evaluated the effect of oral aspirin ( 0 , 40 , 100 , 300 , or 500 mg ) as the initial loading dose in combination with different maintenance doses of aspirin ( 0 , 40 , or 100 mg/day ) for 14 days on platelet function in healthy men . Bleeding time 2 or 24 hours after the first aspirin administration was significantly increased for 300 and 500 mg aspirin ( p aspirin , a significant inhibition of collagen-induced platelet aggregation ( ED50 collagen : from 3 + /- 1 to 17 + /- 2 , 24 + /- 3 , 22 + /- 3 micrograms/ml , respectively ) was seen . At the same time serum thromboxane B2 synthesis was inhibited by more than 99 % with 300 and 500 mg aspirin . At the end of the 14-day observation period , bleeding time was significantly prolonged for the different combinations of aspirin doses compared with initial values ( p Collagen-induced platelet aggregation and serum thromboxane B2 synthesis were significantly inhibited for all aspirin combinations tested at 14 days ( p aspirin combination was less effective , because it reached its maximal effect very late at day 7 of the observation period compared with the other combinations . ( ABSTRACT TRUNCATED AT 250 WORDS",
"In this study of healthy middle-aged and elderly subjects , we found that self-reported family history of premature heart attack and sudden death is independently associated with reduced HRV , suggesting that autonomic imbalance may be part of the complex of familial predisposition to premature heart attack",
"BACKGROUND Endarterectomy benefits certain patients with carotid stenosis , but benefits are lessened by perioperative surgical risk . Acetylsalicylic acid lowers the risk of stroke in patients who have experienced transient ischaemic attack and stroke . We investigated appropriate doses and the role of acetylsalicylic acid in patients undergoing carotid endarterectomy . METHODS In a r and omised , double-blind , controlled trial , 2849 patients scheduled for endarterectomy were r and omly assigned 81 mg ( n=709 ) , 325 mg ( n=708 ) , 650 mg ( n=715 ) , or 1300 mg ( n=717 ) acetylsalicylic acid daily , started before surgery and continued for 3 months . We recorded occurrences of stroke , myocardial infa rct ion , and death . We compared patients on the two higher doses of acetylsalicylic acid with patients on the two lower doses . FINDINGS Surgery was cancelled in 45 patients , none were lost to follow-up by 30 days , and two were lost by 3 months . The combined rate of stroke , myocardial infa rct ion , and death was lower in the low-dose groups than in the high-dose groups at 30 days ( 5.4 vs 7.0 % , p=0.07 ) and at 3 months ( 6.2 vs 8.4 % , p=0.03 ) . In an efficacy analysis , which excluded patients taking 650 mg or more acetylsalicylic acid before r and omisation , and patients r and omised within 1 day of surgery , combined rates were 3.7 % and 8.2 % , respectively , at 30 days ( p=0.002 ) and 4.2 % and 10.0 % at 3 months ( p=0.0002 ) . INTERPRETATION The risk of stroke , myocardial infa rct ion , and death within 30 days and 3 months of endarterectomy is lower for patients taking 81 mg or 325 mg acetylsalicylic acid daily than for those taking 650 mg or 1300 mg",
" All 701 heart infa rct ion patients admitted to 15 hospitals in the district of Cottbus between 1981 and 1983 were r and omly administered 30 , 60 or 1000 mg aspirin daily according to the territorial affiliation of their local hospitals . The physical and drug therapy during the 2 years follow-up was highly st and ardized ; deviations -- as far as they occurred -- were documented . Lower all-cause mortality was statistically demonstrated in patients over 60 and a lower fatal reinfa rct ion rate in patients over 50 as well as in men . Deaths and fatal reinfa rct ions were significantly lower among patients with a history of angina pectoris , marked ST-depression , with an infa rct ion location except for the posterior wall and among hypercholesterolemic patients . The preventive effect of 60 mg aspirin daily was less than that of 30 mg in comparison to the 1000 mg group . Side effects were seen in 4 and 8 % ( first and second year ) , respectively , of the patients administered 30 mg aspirin as opposed to 22 and 17 % in patients allocated 1000 mg . We conclude that the optimum dose of aspirin for preventing reinfa rct ions could be as low as 30 mg daily",
"OBJECTIVE We assessed the production of eicosanoids and the effects of very low dose aspirin in patients with stable angina under basal conditions and during rapid atrial pacing . BACKGROUND Platelet activation occurs in acute ischemic syndromes but is still controversial in stable angina . Very low dose aspirin is known to be platelet selective and can be used to test the hypothesis of the platelet origin of increased thromboxane production in stable angina . METHODS Urinary excretion of eicosanoids was measured in 42 patients , including 24 patients with and 18 patients without coronary artery disease . The effects of 50 mg/day of aspirin were measured at rest and during pacing-induced ischemia in 10 patients with stable angina and were compared with a similar group of patients not treated by aspirin . RESULTS Excretion of 11-dehydro-thromboxane B2 was 2.6 times higher in patients with stable angina than in healthy subjects ( mean [ + /- SEM ] 74.8 + /- 13.0 [ 24 patients ] vs. 29.0 + /- 5.4 [ 18 patients ] ng/mmol of creatinine , p Urinary prostacyclin metabolite levels did not differ between the two groups . Treatment for 8 days with 50 mg/day of aspirin inhibited platelet cyclooxygenase , as reflected by the 97 % reduction of in vitro serum thromboxane production . This aspirin regimen normalized the level of urinary thromboxane metabolites in patients with angina ( 17.3 + /- 3.4 ng/mmol of creatinine [ 10 patients ] , p prostacyclin metabolite levels . Atrial pacing in patients with angina not treated with aspirin caused lactate and thromboxane release into the coronary sinus . In patients with very low dose aspirin therapy , pacing did not cause thromboxane release despite inducing myocardial ischemia . However , fractional lactate extraction decreased less sharply in patients with than without aspirin therapy . CONCLUSIONS Thromboxane production is greatly increased in patients with stable angina . Very low dose aspirin administered to these patients reduces thromboxane synthesis to normal levels , preserves prostacyclin bio synthesis and prevents acute thromboxane release into the coronary circulation during pacing-induced ischemia . Our data suggest that platelets ( not monocytes/macrophages ) are activated in stable angina to produce thromboxane",
" Of 1078 patients admitted to the coronary care unit with acute chest pain , 293 who had possible acute myocardial infa rct ion and symptoms of median 4 h duration were r and omized to treatment with acetylsalicylic acid ( ASA ) 100 mg daily , 1000 mg daily or placebo for 3 months . During hospitalization , the combined incidence of cardiac death and non-fatal myocardial infa rct ion on-treatment ( withdrawals not included ) was significantly lower ( P less than 0.02 ) in the 100 mg group ( 7.1 % ) than in both the 1000 mg group ( 20.8 % ) and the placebo group ( 19.7 % ) . During later time periods of treatment and at all time periods analysed according to the intention-to-treat principle ( withdrawals included ) , data suggested the same trend , but differences were not statistically significant . Collagen-induced platelet aggregation and serum thromboxane B2 were reduced to the same degree in the two ASA groups and were normal in the placebo group . The data suggest that low-dose ASA could be cheap and safe as first-aid therapy in myocardial infa rct ion suspects",
"Aspirin is almost certainly the most widely used drug in the world . It is used both therapeutically ( to reduce pain , inflammation , and fever ) and prophylactically ( to prevent thrombotic events ) . Although prophylactic , antithrombotic doses of aspirin are generally lower than therapeutic doses , epidemiologic studies suggest that such doses may still be associated with gastrointestinal damage [ 1 - 3 ] . In a long-term , placebo-controlled study evaluating aspirin for secondary prevention of myocardial infa rct ion , a daily dose of 1000 mg increased the risk for hospitalization for gastric and duodenal ulcers by about eightfold [ 1 ] . In another long-term , placebo-controlled study evaluating aspirin for stroke prevention in patients with transient ischemic attacks , the rate of hospitalization for serious gastrointestinal bleeding was increased approximately threefold with 1200 mg of aspirin per day and twofold with just 300 mg of aspirin per day [ 2 ] . In another long-term study for primary prevention of cardiovascular diseases , an aspirin dose of 325 mg given every other day was associated with a significantly greater risk for duodenal ulcer when compared with placebo [ 3 ] . Few experimental data exist on the risk for gastroduodenal mucosal injury as a function of aspirin dose , and it is not known whether any clinical ly used dose of aspirin is free of risk for gastroduodenal mucosal damage . In a recent endoscopic study of patients with coronary artery disease , most of whom were receiving only 100 mg of aspirin per day , the prevalence of gastric erosions was higher than the prevalence of erosions in a historical control group [ 4 ] . The literature contains little information on the relation between aspirin dosage and suppression of gastroduodenal mucosal prostagl and in synthesis in humans . Because suppression of gastroduodenal mucosal prostagl and in synthesis appears to be one of the important mechanisms for mucosal damage by aspirin [ 5 , 6 ] , it would be useful to determine the threshold dose for gastroduodenal mucosal prostagl and in inhibition in humans because aspirin doses below this threshold may not damage the gastroduodenal mucosa . Our goal was to determine the effects of a wide range of doses of aspirin ( 3 mg/d to 2600 mg/d ) on gastric juice prostagl and ins ( PGE2 and PGF2 ) and on stomach mucosal injury as reflected by gastric juice hemoglobin and DNA , both of which are sensitive indicators of mucosal injury [ 7 , 8 ] . Effects of various doses of aspirin were also related to their effects on gastric acid secretion and serum thromboxane B2 . Methods Healthy volunteers between the ages of 18 and 75 years were solicited through advertisement . All respondents had a screening history , physical examination , complete blood count , and serum electrolyte , creatinine , bilirubin , and liver chemistry tests . Volunteers were excluded for heartburn ; abdominal pain ; indigestion ; bloating ; fullness ; nausea and vomiting ; use ( within the previous 2 weeks ) of aspirin , nonsteroidal anti-inflammatory drugs , glucocorticoids , histamine-2-receptor antagonists , sucralfate , misoprostol , omeprazole , antacids , or Pepto-Bismol ( Procter and Gamble , Cincinnati , Ohio ) ; history of allergy to aspirin or topical tetracaine ; a positive urine pregnancy test ; history of gastric surgery , peptic ulcer , or other gastrointestinal disease ; history of liver disease ( including currently elevated liver chemistry tests ) ; or history or presence of anemia , thrombocytopenia , leukopenia , gout , coagulation disorder , or renal insufficiency . Sixteen people ( 5 men and 11 women ) met all entry criteria and gave written consent to participate as paid volunteers . Use of any medication other than study medication was not allowed during the study . The study was approved by the Human Studies Subcommittee at the Department of Veterans Affairs Medical Center , Dallas , Texas . Part 1 Ten volunteers ( four men and six women ; mean age , 44.2 years ; range , 19 to 73 years ) were enrolled in part 1 of the study . One man was excluded for noncompliance . On 4 separate days at least 1 week apart , each of the other nine participants received placebo ( calcium sulfate , 222 mg ; cellulose , 97 mg ) ; aspirin , 81 mg ( Bayer Children 's Aspirin , Glenbrook Laboratories ; New York , New York ) ; aspirin , 325 mg ( one tablet ) ; or aspirin , 650 mg ( two 325-mg tablets ) . Medication was taken with each of three meals and at bedtime on the day before the study and at 0700 h on the study day . During the course of four visits , each of the nine volunteers took each of the four drug regimens in r and om order . Medications were dispensed by a research pharmacist so that the investigators were blinded to the study regimens . Although the medications differed in appearance , volunteers were blinded to exact ingredients of the medications and were instructed to refrain from discussing their study regimens with the investigators and technical assistants . We used the dosing schedule of the highest dose of aspirin ( 650 mg four times a day ) in a previous study , which result ed in significant inhibition of gastric mucosal PGE2 and PGF2 concentrations [ 9 ] . Each volunteer was instructed to report to the research laboratory on the study day after an overnight fast . At 0800 h ( 1 hour after the fifth and final dose of medication ) , a venous blood sample was taken for determination of serum salicylate concentration . Then , a nasogastric tube was positioned fluoroscopically in the dependent portion of the gastric antrum . Volunteers were trained not to swallow their saliva and to collect saliva through dental suction catheters . Residual gastric secretion was aspirated with the volunteer in the supine position and the fluid was discarded . Beginning at 0830 h , gastric juice was collected by intermittent suction pump aspiration , and the sample s collected were divided into aliquots and placed in separate containers every 15 minutes for the next 2 hours . In our laboratory , typical recovery of gastric juice with a nasogastric tube positioned fluoroscopically is greater than 90 % [ 10 ] . Part 2 Eleven volunteers ( three men and eight women ; mean age , 45.2 years ; range , 25 to 73 years ) were enrolled in part 2 of the study . Two men were excluded for noncompliance . Four of the remaining nine volunteers ( one man and three women ) had participated in part 1 of the study . On five separate occasions at least 14 days apart , each volunteer received placebo ( calcium sulfate , 222 mg ; cellulose , 97 mg ) ; aspirin , 3 mg ; aspirin , 10 mg ; aspirin , 30 mg ; or aspirin , 81 mg for 8 days . Medications were prepared and packaged in identical green opaque gelatin capsules by the Pharmacy Service at Dallas Veterans Affairs Medical Center . Medications were dispensed by a research pharmacist so that the study was double-blinded . Volunteers were instructed to take the medication with breakfast for 7 days before the study and at 0600 h on the study day . During the course of five visits , each volunteer received each of the five drug regimens in r and om order . Each volunteer was instructed to report to the research laboratory after an overnight fast . At 0700 h ( 1 hour after the last dose of medication ) , venous blood sample s were drawn for serum salicylate and serum thromboxane B2 determinations . We chose to monitor serum thromboxane B2 concentrations in part 2 because data from part 1 suggested that aspirin doses of 324 mg/d or less would not result in any detectable serum salicylate level and because the serum thromboxane B2 level has been shown to be a clinical ly relevant and reliable marker of low-dose aspirin therapy [ 11 ] . After venipuncture , a nasogastric tube was positioned fluoroscopically in the gastric antrum , as described above . Beginning at 0730 h , gastric juice was collected by intermittent suction pump aspiration and sample s collected were divided into aliquots and placed in separate containers every 15 minutes for the next 60 minutes . We chose to do this study for 60 minutes because results from part 1 indicated that no substantial fluctuations in gastric juice prostagl and in , hemoglobin , and DNA , or gastric acid outputs occurred throughout the 2-hour study period . The aspirin dosing schedule was chosen based on the following observations : 1 ) Thirty mg of aspirin daily has recently been shown to be as effective as 283 mg daily in the prevention of cerebrovascular events in patients with a transient ischemic attack or minor stroke [ 12 ] ; 2 ) reduction of serum thromboxane B2 by low-dose aspirin is cumulative on repeated daily dosing and has been shown to reach a steady state after 7 days [ 13 ] ; and 3 ) serum thromboxane B2 generally returns to normal by 14 days after cessation of aspirin therapy [ 13 , 14 ] . Processing of Gastric Juice Sample s and Determination of Gastric Acid Output The volume of each 15-minute gastric juice sample was recorded to the nearest 0.2 mL , and indomethacin was added immediately to the sample after collection ( final indomethacin concentration , 50 M ) to prevent further prostagl and in synthesis . The pH of each sample was determined by glass electrode . Acidity was derived from the pH [ 15 ] and expressed as mmol/L. Acid output was calculated by multiplying volume by acidity , expressed as mmol/h . To stabilize prostagl and ins in the specimen , the sample was then titrated to pH 7.0 with 0.2-N NaOH and kept at 4 C. Sample s were processed the same day that they were collected and used in subsequent determinations of PGE2 , PGF2 , hemoglobin , and DNA concentrations . Determination of Gastric Juice PGE2 and PGF2 Output Extraction of prostagl and ins from gastric juice sample s was done according to the method of Peskar and colleagues [ 16 ] . Aliquots of gastric juice that had been titrated to pH 7.0 were homogenized and centrifuged . The result ant supernatant was titrated to pH 3.0 with acetic acid . The acidified supernatant was extracted twice with four volumes of ethyl acetate . The organic extracts were pooled and stored at 70C until radioimmunoassay . Before the assay , organic extracts were"
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Observational studies demonstrating reduced rates of infections , necrotizing enterocolitis ( NEC ) , and mortality in preterm infants fed their own mother ’s milk , as opposed to formula , have prompted endeavors to achieve similar effects with the right choice of food and food additives . In a systematic review of meta-analyses and r and omized controlled trials ( RCTs ) , we considered nutritional interventions aim ed at reducing the rates of infections , NEC , or mortality in very preterm infants . The overall effects of particular interventions were presented as risk ratios with 95 % confidence intervals . In RCTs , pasteurized human donor milk , as opposed to formula , reduced NEC but not infections or mortality . No differences emerged between infants receiving human or bovine milk-based fortifiers . Pooled data of small trials and a recent large RCT suggested that bovine lactoferrin reduced rates of fungal sepsis without impact on other infections , NEC , or mortality . Pooled data of RCTs assessing the use of prebiotic oligosaccharides found reduced infection but not mortality . Enteral L-glutamine ( six RCTs ) lowered infection rates , and enteral L-arginine ( three RCTs ) reduced NEC . A meta- analysis sensitivity approach found multiple-strain ( but not single-strain ) probiotics to be highly effective in reducing NEC and mortality . Thus , selected food components may help to improve outcomes in preterm infants
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"OBJECTIVE To compare the duration of parenteral nutrition , growth , and morbidity in extremely premature infants fed exclusive diets of either bovine milk-based preterm formula ( BOV ) or donor human milk and human milk-based human milk fortifier ( HUM ) , in a r and omized trial of formula vs human milk . STUDY DESIGN Multicenter r and omized controlled trial . The authors studied extremely preterm infants whose mothers did not provide their milk . Infants were fed either BOV or an exclusive human milk diet of pasteurized donor human milk and HUM . The major outcome was duration of parenteral nutrition . Secondary outcomes were growth , respiratory support , and necrotizing enterocolitis ( NEC ) . RESULTS Birth weight ( 983 vs 996 g ) and gestational age ( 27.5 vs 27.7 wk ) , in BOV and HUM , respectively , were similar . There was a significant difference in median parenteral nutrition days : 36 vs 27 , in BOV vs HUM , respectively ( P = .04 ) . The incidence of NEC in BOV was 21 % ( 5 cases ) vs 3 % in HUM ( 1 case ) , P = .08 ; surgical NEC was significantly higher in BOV ( 4 cases ) than HUM ( 0 cases ) , P = .04 . CONCLUSIONS In extremely preterm infants given exclusive diets of preterm formula vs human milk , there was a significantly greater duration of parenteral nutrition and higher rate of surgical NEC in infants receiving preterm formula . This trial supports the use of an exclusive human milk diet to nourish extremely preterm infants in the neonatal intensive care unit",
"Background : C and ida is an important cause of infections in premature infants . Gastrointestinal colonization with C and ida is a common site of entry for disseminated disease . The objective of this study was to determine whether a dietary supplement of medium-chain triglycerides ( MCTs ) reduces C and ida colonization in preterm infants . Methods : Preterm infants with C and ida colonization ( n = 12 ) receiving enteral feedings of either infant formula ( n = 5 ) or breast milk ( n = 7 ) were r and omized to MCT supplementation ( n = 8) or no supplementation ( n = 4 ) . Daily stool sample s were collected to determine fungal burden during a 3-week study period . Infants in the MCT group received supplementation during 1 week of the study period . The primary outcome was fungal burden during the supplementation period as compared with the periods before and after supplementation . Results : Supplementation of MCT led to a marked increase in MCT intake relative to unsupplemented breast milk or formula as measured by capric acid content . In the treatment group , there was a significant reduction in fungal burden during the supplementation period as compared with the period before supplementation ( rate ratio , 0.15 ; P = 0.02 ) , with a significant increase after supplementation was stopped ( rate ratio , 61 ; P Fungal burden in the control group did not show similar changes . Conclusions : Dietary supplementation with MCT may be an effective method to reduce C and ida colonization in preterm infants",
"Background : Feeding preterm infants human milk has a beneficial effect on the risk of late-onset sepsis ( LOS ) . Due to lack of microbiological st and ards , practice s such as pasteurization of mother ’s own milk differ widely among neonatal intensive care units worldwide . Objectives : To investigate whether pasteurization of mother ’s own milk for very-low-birth-weight ( VLBW ) infants influences the incidence and severity of infection-related outcomes . Methods : In this r and omized controlled trial , preterm infants ( gestational age received either raw or pasteurized mother ’s own milk during the first 8 weeks of life . The primary outcome was the incidence of proven LOS . A dose-response relation was verified , i.e. the dependence of the risk of sepsis on the actual and cumulative quantities of mother ’s own milk . Results : This study included 303 VLBW infants ( mean birth weight : 1,276 g ; mean gestational age : 29 weeks ) whose baseline and nutritional characteristics were similar . The incidence of laboratory-confirmed sepsis was not statistically different in infants fed raw milk compared to infants who received pasteurized milk : 22/151 ( 0.15 , CI : 0.08–0.20 ) and 31/152 ( 0.20 , CI : 0.14–0.27 ) , respectively ( RR : 0.71 ; 95 % CI : 0.43–1.17 ) . A significant dose-response relation was observed between the adjusted quantity of enteral feeding and the risk of LOS , regardless of the type of feeding . Conclusion : For preterm infants , pasteurization of mother ’s own milk shows a trend towards an increase in infectious morbidity , although no statistical significance was reached . Practice s should focus on collection , storage and labeling procedures to ensure the safety and quality of expressed milk",
"BACKGROUND Zinc plays a pivotal role in the pathogenesis of many diseases and in body growth . Preterm neonates have high zinc requirements . OBJECTIVE The objective of the study was to investigate the efficacy of zinc supplementation in reducing morbidity and mortality in preterm neonates and to promote growth . DESIGN This was a prospect i ve , double-blind , r and omized controlled study of very-low-birth-weight preterm neonates r and omly allocated on the seventh day of life to receive ( zinc group ) or not receive ( control group ) oral zinc supplementation . Total prescribed zinc intake ranged from 9.7 to 10.7 mg/d in the zinc group and from 1.3 to 1.4 mg/d in the placebo control group . The main endpoint was the rate of neonates with ≥ 1 of the following morbidities : late-onset sepsis , necrotizing enterocolitis , bronchopulmonary dysplasia , periventricular leucomalacia , and retinopathy of prematurity . Secondary outcomes were mortality and body growth . RESULTS We enrolled 97 neonates in the zinc group and 96 in the control group . Morbidities were significantly lower in the zinc group ( 26.8 % compared with 41.7 % ; P = 0.030 ) . The occurrence of necrotizing enterocolitis was significantly higher in the control group ( 6.3 % compared with 0 % ; P = 0.014 ) . Mortality risk was higher in the placebo control group ( RR : 2.37 ; 95 % CI : 1.08 , 5.18 ; P = 0.006 ) . Daily weight gain was similar in the zinc ( 18.2 ± 5.6 g · kg⁻¹ · d⁻¹ ) and control ( 17.0 ± 8.7 g · kg⁻¹ · d⁻¹ ) groups ( P = 0.478 ) . CONCLUSION Oral zinc supplementation given at high doses reduces morbidities and mortality in preterm neonates . This trial was registered in the Australian New Zeal and Clinical Trial Register as ACTRN12612000823875",
"OBJECTIVE To evaluate the health benefits of an exclusively human milk-based diet compared with a diet of both human milk and bovine milk-based products in extremely premature infants . STUDY DESIGN Infants fed their own mothers ' milk were r and omized to 1 of 3 study groups . Groups HM100 and HM40 received pasteurized donor human milk-based human milk fortifier when the enteral intake was 100 and 40 mL/kg/d , respectively , and both groups received pasteurized donor human milk if no mother 's milk was available . Group BOV received bovine milk-based human milk fortifier when the enteral intake was 100 mL/kg/d and preterm formula if no mother 's milk was available . Outcomes included duration of parenteral nutrition , morbidity , and growth . RESULTS The 3 groups ( total n = 207 infants ) had similar baseline demographic variables , duration of parenteral nutrition , rates of late-onset sepsis , and growth . The groups receiving an exclusively human milk diet had significantly lower rates of necrotizing enterocolitis ( NEC ; P = .02 ) and NEC requiring surgical intervention ( P = .007 ) . CONCLUSIONS For extremely premature infants , an exclusively human milk-based diet is associated with significantly lower rates of NEC and surgical NEC when compared with a mother 's milk-based diet that also includes bovine milk-based products",
"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",
"OBJECTIVES To determine whether supplementation with L -arginine reduces the incidence of all stages of necrotizing enterocolitis ( NEC ) in premature infants with birth weight STUDY DESIGN In a r and omized , double-blind , placebo-controlled study , 152 premature infants were prospect ively , r and omly assigned to receive either supplemental L -arginine ( 1.5 mmol/kg per day ; n = 75 [ group A ] ) or placebo ( control group ; n = 77 [ group B ] ) with oral feeds/parenteral nutrition during the first 28 days of life . Nutrient intake , plasma ammonia , arginine , and amino acid concentrations were measured in all infants at days 3 , 14 , and 28 and at the time of diagnosis of NEC . RESULTS NEC developed in 5 infants in group A compared with 21 infants in group B ( P Arginine intake and plasma arginine concentrations were similar in both groups at study entry and ( as expected ) increased in group A at days 14 and 28 . Plasma arginine concentrations were lower in both groups at time of diagnosis of NEC . No significant differences in maternal and neonatal demographics , nutrient intake , plasma ammonia and total and essential amino acid concentrations were present between the two groups . CONCLUSIONS Arginine supplementation ( 1.5 mmol/kg per day ) in premature infants reduces the incidence of all stages of NEC",
"OBJECTIVE To test the efficacy of probiotic and prebiotic , alone or combined ( synbiotic ) , on the prevention of necrotizing enterocolitis ( NEC ) in very low birth weight ( VLBW ) infants . STUDY DESIGN A prospect i ve , r and omized , controlled trial was conducted at 5 neonatal intensive care units in Turkey . VLBW infants ( n = 400 ) were assigned to a control group and 3 study groups that were given probiotic ( Bifidobacterium lactis ) , prebiotic ( inulin ) , or synbiotic ( Bifidobacterium lactis plus inulin ) added to breastmilk or formula for a maximum of 8 weeks before discharge or death . The primary outcome was NEC ( Bell stage ≥2 ) . RESULTS The rate of NEC was lower in probiotic ( 2.0 % ) and synbiotic ( 4.0 % ) groups compared with prebiotic ( 12.0 % ) and placebo ( 18.0 % ) groups ( P The times to reach full enteral feeding were faster ( P the rates of clinical nosocomial sepsis were lower ( P = .004 ) , stays in the neonatal intensive care unit were shorter , ( P = .002 ) , and mortality rates were lower ( P = .003 ) for infants receiving probiotics , prebiotics , or synbiotic than controls . The use of antenatal steroid ( OR 0.5 , 95 % CI 0.3 - 0.9 ) and postnatal probiotic ( alone or in synbiotic ) ( OR 0.5 , 95 % CI 0.2 - 0.8 ) decreased the risk of NEC , and maternal antibiotic exposure increased this risk ( OR 1.9 , 95 % CI 1.1 - 3.6 ) . CONCLUSIONS In VLBW infants , probiotic ( Bifidobacterium lactis ) and synbiotic ( Bifidobacterium lactis plus inulin ) but not prebiotic ( inulin ) alone decrease NEC",
"OBJECTIVE To evaluate the safety and explore the efficacy of recombinant human lactoferrin ( talactoferrin [ TLf ] ) to reduce infection . STUDY DESIGN We conducted a r and omized , double blind , placebo-controlled trial in infants with birth weight of 750 - 1500 g. Infants received enteral TLf ( n = 60 ) or placebo ( n = 60 ) on days 1 through 28 of life ; the TLf dose was 150 mg/kg every 12 hours . Primary outcomes were bacteremia , pneumonia , urinary tract infection , meningitis , and necrotizing enterocolitis ( NEC ) . Secondary outcomes were sepsis syndrome and suspected NEC . We recorded clinical , laboratory , and radiologic findings , along with diseases and adverse events , in a data base used for statistical analyses . RESULTS Demographic data were similar in the 2 groups of infants . We attributed no enteral or organ-specific adverse events to TLf . There were 2 deaths in the TLf group ( 1 each due to posterior fossa hemorrhage and postdischarge sudden infant death ) , and 1 death in the placebo group , due to NEC . The rate of hospital-acquired infections was 50 % lower in the TLf group compared with the placebo group ( P blood or line infections , urinary tract infections , and pneumonia . Fourteen infants in the TLf group weighing had no gram-negative infections , compared with only 3 of 14 such infants in the placebo group . Noninfectious outcomes were not statistically significantly different between the 2 groups , and there were no between-group differences in growth or neurodevelopment over a 1-year posthospitalization period . CONCLUSION We found no clinical or laboratory toxicity and a trend toward less infectious morbidity in the infants treated with TLf . TRIAL REGISTRATION Clinical Trials.gov : NCT00854633",
"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",
"Background Human milk-based fortifiers ( HMBFs ) are being adopted in neonatal care to enrich the nutrients in human milk for very low birth weight ( VLBW ) infants despite being costly and there being limited efficacy data . No r and omized clinical trial has evaluated the use of HMBF compared with bovine milk-based fortifiers ( BMBFs ) in the absence of formula feeding . Objective To determine if HMBF compared with BMBF for routine nutrient enrichment of human milk improves feeding tolerance , reduces morbidity , reduces fecal calprotectin ( a measure of gut inflammation ) , and supports the growth of infants Design In this blinded r and omized clinical trial , infants born weighing The infants were fed mother 's milk and donor milk as required . Fortification commenced at 100 mL/kg per day of HMBF ( 0.81 kcal/mL ) or BMBF ( 0.72 kcal/mL ) and advanced at 140 mL/kg per day to 0.88 and 0.78 kcal/mL , respectively . The primary outcome was percentage of infants with a feeding interruption for ≥12 h or a > 50 % reduction in feeding volume . Secondary outcomes included a dichotomous mortality and morbidity index ( i.e. , affirmative for any one of death , late-onset sepsis , necrotizing enterocolitis , chronic lung disease , or severe retinopathy of prematurity ) , fecal calprotectin , and growth . Results Of 232 eligible infants , 127 ( 54.7 % ) were r and omized ( n = 64 HMBF , n = 63 BMBF ) . Mean ± SD birth weight and gestational age of infants were 888 ± 201 g and 27.7 ± 2.5 wk , respectively . No statistically significant differences were identified in feeding interruptions [ 17/64 HMBF , 20/61 BMBF ; unadjusted risk difference : -6.2 % ( 95 % CI : -22.2 % , 9.8 % ) ] . There was no statistically significant difference in the mortality and morbidity index ( 48.4 % HMBF , 49.2 % BMBF , adjusted P = 0.76 ) , changes in fecal calprotectin , or growth z scores . Conclusions Among infants born weighing , the use of HMBF did not improve feeding tolerance or reduce mortality and morbidity compared with BMBF . This trial was registered at clinical trials.gov as NCT02137473",
"BACKGROUND Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants . Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin , an antimicrobial protein processed from cow 's milk , prevents infections and associated complications . OBJECTIVE To determine whether or not enteral supplementation with bovine lactoferrin ( The Tatua Cooperative Dairy Company Ltd , Morrinsville , New Zeal and ) reduces the risk of late-onset infection ( acquired > 72 hours after birth ) and other morbidity and mortality in very preterm infants . DESIGN R and omised , placebo-controlled , parallel-group trial . R and omisation was via a web-based portal and used an algorithm that minimised for recruitment site , weeks of gestation , sex and single versus multiple births . SETTING UK neonatal units between May 2014 and September 2017 . PARTICIPANTS Infants born at at trial enrolment . INTERVENTIONS Eligible infants were allocated individually ( 1 : 1 ratio ) to receive enteral bovine lactoferrin ( 150 mg/kg/day ; maximum 300 mg/day ) or sucrose ( British Sugar , Peterborough , UK ) placebo ( same dose ) once daily from trial entry until a postmenstrual age of 34 weeks . Parents , caregivers and outcome assessors were unaware of group assignment . OUTCOMES Primary outcome - microbiologically confirmed or clinical ly suspected late-onset infection . Secondary outcomes - microbiologically confirmed infection ; all-cause mortality ; severe necrotising enterocolitis ( NEC ) ; retinopathy of prematurity ( ROP ) ; bronchopulmonary dysplasia ( BPD ) ; a composite of infection , NEC , ROP , BPD and mortality ; days of receipt of antimicrobials until 34 weeks ' postmenstrual age ; length of stay in hospital ; and length of stay in intensive care , high-dependency and special-care setting s. RESULTS Of 2203 enrolled infants , primary outcome data were available for 2182 infants ( 99 % ) . In the intervention group , 316 out of 1093 ( 28.9 % ) infants acquired a late-onset infection versus 334 out of 1089 ( 30.7 % ) infants in the control group [ adjusted risk ratio ( RR ) 0.95 , 95 % confidence interval ( CI ) 0.86 to 1.04 ] . There were no significant differences in any secondary outcomes : microbiologically confirmed infection ( RR 1.05 , 99 % CI 0.87 to 1.26 ) , mortality ( RR 1.05 , 99 % CI 0.66 to 1.68 ) , NEC ( RR 1.13 , 99 % CI 0.68 to 1.89 ) , ROP ( RR 0.89 , 99 % CI 0.62 to 1.28 ) , BPD ( RR 1.01 , 99 % CI 0.90 to 1.13 ) , or a composite of infection , NEC , ROP , BPD and mortality ( RR 1.01 , 99 % CI 0.94 to 1.08 ) . There were no differences in the number of days of receipt of antimicrobials , length of stay in hospital , or length of stay in intensive care , high-dependency or special-care setting s. There were 16 reports of serious adverse events for infants in the lactoferrin group and 10 for infants in the sucrose group . CONCLUSIONS Enteral supplementation with bovine lactoferrin does not reduce the incidence of infection , mortality or other morbidity in very preterm infants . FUTURE WORK Increase the precision of the estimates of effect on rarer secondary outcomes by combining the data in a meta- analysis with data from other trials . A mechanistic study is being conducted in a subgroup of trial participants to explore whether or not lactoferrin supplementation affects the intestinal microbiome and metabolite profile of very preterm infants . TRIAL REGISTRATION Current Controlled Trials IS RCT N88261002 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 22 , No. 74 . See the NIHR Journals Library website for further project information . This trial was also sponsored by the University of Oxford , Oxford , UK . The funder provided advice and support and monitored study progress but did not have a role in study design or data collection , analysis and interpretation",
"Summary Background Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants . Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin , an antimicrobial protein processed from cow 's milk , prevents infections and associated complications . The aim of this large r and omised controlled trial was to collect data to enhance the validity and applicability of the evidence from previous trials to inform practice . Methods In this r and omised placebo-controlled trial , we recruited very preterm infants born before 32 weeks ' gestation in 37 UK hospitals and younger than 72 h at r and omisation . Exclusion criteria were presence of a severe congenital anomaly , anticipated enteral fasting for longer than 14 days , or no realistic prospect of survival . Eligible infants were r and omly assigned ( 1:1 ) to receive either enteral bovine lactoferrin ( 150 mg/kg per day ; maximum 300 mg/day ; lactoferrin group ) or sucrose ( same dose ; control group ) once daily until 34 weeks ' postmenstrual age . Web-based r and omisation minimised for recruitment site , gestation ( completed weeks ) , sex , and single versus multifetal pregnancy . Parents , caregivers , and outcome assessors were unaware of group assignment . The primary outcome was microbiologically confirmed or clinical ly suspected late-onset infection ( occurring > 72 h after birth ) , which was assessed in all participants for whom primary outcome data was available by calculating the relative risk ratio with 95 % CI between the two groups . The trial is registered with the International St and ard R and omised Controlled Trial Number 88261002 . Findings We recruited 2203 participants between May 7 , 2014 , and Sept 28 , 2017 , of whom 1099 were assigned to the lactoferrin group and 1104 to the control group . Four infants had consent withdrawn or unconfirmed , leaving 1098 infants in the lactoferrin group and 1101 in the sucrose group . Primary outcome data for 2182 infants ( 1093 [ 99·5 % ] of 1098 in the lactoferrin group and 1089 [ 99·0 ] of 1101 in the control group ) were available for inclusion in the modified intention-to-treat analyses . 316 ( 29 % ) of 1093 infants in the intervention group acquired a late-onset infection versus 334 ( 31 % ) of 1089 in the control group . The risk ratio adjusted for minimisation factors was 0·95 ( 95 % CI 0·86–1·04 ; p=0·233 ) . During the trial there were 16 serious adverse events for infants in the lactoferrin group and 10 for infants in the control group . Two events in the lactoferrin group ( one case of blood in stool and one death after intestinal perforation ) were assessed as being possibly related to the trial intervention . Interpretation Enteral supplementation with bovine lactoferrin does not reduce the risk of late-onset infection in very preterm infants . These data do not support its routine use to prevent late-onset infection and associated morbidity or mortality in very preterm infants . Funding UK National Institute for Health Research Health Technology Assessment programme ( 10/57/49 )",
"BACKGROUND Lactoferrin is the major antimicrobial protein in human milk . In our r and omized controlled trial ( RCT ) of bovine lactoferrin ( BLF ) supplementation in preterm neonates , BLF reduced late-onset sepsis ( LOS ) . Mother 's own milk ( MM ) contains higher concentrations of lactoferrin than donor milk or formula , but whether BLF is more effective in infants who receive formula or donor milk is uncertain . AIM To evaluate the incidence of LOS in preterm infants fed MM and in those fed formula and /or donor milk . STUDY DESIGN This is a ( A ) post hoc subgroup analysis , in our RCT of BLF , of its effects in preterm infants fed MM , with or without formula , versus those fed formula and /or donor milk ( no-MM ) and ( B ) post hoc meta- analysis , in our RCT of BLF and in the ELFIN ( Enteral Lactoferrin in Neonates ) RCT , of the effect of BLF in subgroups not exclusively fed MM . RESULTS ( A ) Of 472 infants in our RCT , 168 were r and omized to placebo and 304 were r and omized to BLF . Among MM infants , LOS occurred in 22/133 ( 16.5 % ) infants r and omized to placebo and in 14/250 ( 5.6 % ) r and omized to BLF ( relative risk or risk ratio ( RR ) : 0.34 ; relative risk reduction ( RRR ) : 0.66 ; 95 % confidence interval ( 95 % CI ) for RR : 0.18 - 0.64 ; p LOS occurred in 7/35 ( 20.0 % ) r and omized to placebo and in 2/54 ( 3.7 % ) r and omized to BLF ( RR : 0.19 ; RRR : 0.81 ; 95 % CI for RR : 0.16 - 0.96 ; p = 0.026 ) . In multivariable logistic regression analysis , there was no interaction between BLF treatment effect and type of feeding ( p = 0.628 ) . ( B ) In 1,891 infants not exclusively fed MM in our RCT of BLF and in the ELFIN RCT , BLF reduced the RR of LOS by 18 % ( RR : 0.82 ; 95 % CI : 0.71 - 0.96 ; p = 0.01 ) . CONCLUSION Adequately powered studies should address the hypothesis that BLF is more effective in infants fed formula or donor milk than those fed MM . Such studies should evaluate whether a specific threshold of total lactoferrin intake can be identified to protect such patients from LOS"
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Background Developing successful interventions for chronic musculoskeletal pain requires valid , responsive , and reliable outcome measures . The Minneapolis VA Evidence -based Synthesis Program completed a focused evidence review on key psychometric properties of 17 self-report measures of pain severity and pain-related functional impairment suitable for clinical research on chronic musculoskeletal pain . Methods Pain experts of the VA Pain Measurement Outcomes Workgroup identified 17 pain measures to undergo systematic review . In addition to a MEDLINE search on these 17 measures ( 1/2000–1/2017 ) , we h and - search ed ( without publication date limits ) the reference lists of all included studies , prior systematic review s , and —when available — Web sites dedicated to each measure ( PROSPERO registration CRD42017056610 ) . Our primary outcome was the measure ’s minimal important difference ( MID ) . Secondary outcomes included responsiveness , validity , and test-retest reliability . Outcomes were synthesized through evidence mapping and qualitative comparison . Results Of 1635 abstract s identified , 331 articles underwent full-text review , and 43 met inclusion criteria . Five measures ( Oswestry Disability Index ( ODI ) , Rol and -Morris Disability Question naire ( RMDQ ) , SF-36 Bodily Pain Scale ( SF-36 BPS ) , Numeric Rating Scale ( NRS ) , and Visual Analog Scale ( VAS ) ) had data reported on MID , responsiveness , validity , and test-retest reliability . Seven measures had data reported on three of the four psychometric outcomes . Eight measures had reported MIDs , though estimation methods differed substantially and often were not clinical ly anchored . Conclusions In this focused evidence review , the most evidence on key psychometric properties in chronic musculoskeletal pain population s was found for the ODI , RMDQ , SF-36 BPS , NRS , and VAS . Key limitations in the field include substantial variation in methods of estimating psychometric properties , defining chronic musculoskeletal pain , and reporting patient demographics . Trial Registration Registered in the PROSPERO data base :
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"OBJECTIVE The primary goal was to determine whether a composite measure of pain and activity is a more responsive assessment of analgesic effect than pain alone or activity alone in patients with osteoarthritis ( OA ) of the knee . DESIGN We conducted a r and omized , double-blind , placebo-controlled , 2-period , crossover study of celecoxib vs. placebo in subjects with chronic pain due to knee OA . Patients with knee OA and baseline pain intensity score ≥4 on a 0 - 10 numerical rating scale ( NRS ) before each period were r and omized . Pain endpoints included in-clinic pain score ( 24-hour and 1-week recall ) , daily paper diary pain score , current pain on an electronic pain diary ( each on NRS ) , and WOMAC pain subscale . Activity measures included WOMAC function subscale and actigraphy using a device . Three composite pain-activity measures were prespecified . RESULTS Sixty-three patients were r and omized and 47 completed the study . The WOMAC pain subscale was the most responsive of all five pain measures . Pain-activity composites result ed in a statistically significant difference between celecoxib and placebo but were not more responsive than pain measures alone . However , a composite responder defined as having 20 % improvement in pain or 10 % improvement in activity yielded much larger differences between celecoxib and placebo than with pain scores alone . Actigraphy was more responsive than the WOMAC function scale , possibly due to lower placebo responsiveness . CONCLUSION We have identified composite pain-activity measures that are similarly or more responsive than pain-alone measures in patients with OA . Further research is warranted to determine the optimal method for computing these composites",
"BACKGROUND Universal pain screening with a 0–10 pain intensity numeric rating scale ( NRS ) has been widely implemented in primary care . OBJECTIVE To evaluate the accuracy of the NRS as a screening test to identify primary care patients with clinical ly important pain . DESIGN Prospect i ve diagnostic accuracy study PARTICIPANTS 275 adult clinic patients were enrolled from September 2005 to March 2006 . MEASUREMENTS We operationalized clinical ly important pain using two alternate definitions : ( 1 ) pain that interferes with functioning ( Brief Pain Inventory interference scale ≥ 5 ) and ( 2 ) pain that motivates a physician visit ( patient-reported reason for the visit ) . RESULTS 22 % of patients reported a pain symptom as the main reason for the visit . The most common pain locations were lower extremity ( 21 % ) and back/neck ( 18 % ) . The area under the receiver operator characteristic curve for the NRS as a test for pain that interferes with functioning was 0.76 , indicating fair accuracy . A pain screening NRS score of 1 was 69 % sensitive ( 95 % CI 60–78 ) for pain that interferes with functioning . Multilevel likelihood ratios for scores of 0 , 1–3 , 4–6 , and 7–10 were 0.39 ( 0.29–0.53 ) , 0.99 ( 0.38–2.60 ) , 2.67 ( 1.56–4.57 ) , and 5.60 ( 3.06–10.26 ) , respectively . Results were similar when NRS scores were evaluated against the alternate definition of clinical ly important pain ( pain that motivates a physician visit ) . CONCLUSIONS The most commonly used measure for pain screening may have only modest accuracy for identifying patients with clinical ly important pain in primary care . Further research is needed to evaluate whether pain screening improves patient outcomes in primary care",
"& NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies",
"Background The psychometric properties of Patient Reported Outcomes Measurement Information System ( PROMIS ) instruments have been explored in a number of general and clinical sample s. No study , however , has evaluated the psychometric function of these measures in individuals with symptomatic knee osteoarthritis ( KOA ) . The aim of this project was to evaluate the construct ( structural ) validity and floor/ceiling effects of four PROMIS measures in this population . Methods We conducted a secondary analysis of baseline data from a r and omized trial comparing Tai Chi and physical therapy . Participants completed four PROMIS static short-form instruments ( i.e. , Anxiety , Depression , Physical Function , and Pain Interference ) as well as six well-vali date d ( legacy ) measures that assess pain , function , and psychological health . We calculated descriptive statistics and percentages of participants scoring the minimum ( floor ) and maximum ( ceiling ) possible scores for PROMIS and legacy measures . We also estimated the association between PROMIS scores and scores on legacy measures using Spearman ’s rank correlations coefficients . Results Data from 204 participants were analyzed . Mean age of the sample was 60 years ; 70 % were female . The PROMIS Anxiety and Depression had floor effects with 17 and 24 % of participants scoring the minimum , respectively . PROMIS Anxiety and Depression scores had strongest associations with general mental health , including stress ( Perceived Stress Scale , r ≥ 0.65 ) and depression ( Beck Depression Index-II , r = 0.70 ) . PROMIS Pain Interference scores correlated most strongly with measures of whole body pain ( Short-Form 36 Bodily Pain , r = −0.73 ) and physical health ( Short-Form 36 Physical-Component Summary , r = −0.73 ) ; their correlations were lower with other legacy measures , including with the WOMAC knee-specific pain ( r = 0.47 ) . PROMIS Physical Function scores had stronger associations with scores on the Short-Form 36 Physical Function ( r = 0.79 ) than with scores on other legacy measures . Conclusion The four PROMIS static-short forms performed well among individuals with symptomatic knee osteoarthritis as evidence d in correlations with legacy measures . PROMIS Anxiety and Depression target general mental health ( e.g. , stress , depression ) , and PROMIS Pain Interference and Physical Function static-short forms target whole-body outcomes among participants with symptomatic knee osteoarthritis . Floor effects in the PROMIS Anxiety and Depression scores should be considered if needing to distinguish among patients with very low levels of these outcomes .Trial registration Clinical trials.gov NCT01258985 . Registered 10 December",
"UNLABELLED The design used in this study was a prospect i ve cohort . Pain intensity levels recorded by the digital version of the visual analog scale ( VAS-D ) are easy to both score and share with other health care professionals . The purpose of the study was to examine the test-retest reliability , concurrent validity , and responsiveness of the VAS-D. Thirty-three people with upper extremity injuries reported pain intensity levels before and after performing four maximal grip contractions ( pre- and postgripping ) . Our version of the VAS-D had high test-retest reliability ( r=0.96 ) and good concurrent validity ( r=0.84 - 0.97 ) with both the paper version of the VAS ( VAS-P ) and the verbal numerical rating scale ( NRS-V ) . Responsiveness of the VAS-D was indicated by a significant increase in pain levels from pre- to postgripping . Similar responsiveness to that of the VAS-P and NRS-V was indicated by similar effect size coefficients and analysis of variance of pain change scores . In conclusion , the VAS-D is a reliable , valid , and responsive measure of pain intensity for people with upper extremity injuries . However , differences in accuracy ( resolution ) among the VAS-D , VAS-P , or NRS-V may render the three pain scales not fully compatible . LEVEL OF EVIDENCE Not applicable",
"OBJECTIVE To assess reliability , validity , and responsiveness of a 29-item short-form version of the Patient Reported Outcomes Measurement Information System ( PROMIS ) and a novel “ impact score ” calculated from those measures . DESIGN Prospect i ve cohort study . SETTING Rural primary care practice s. SUBJECTS Adults aged ≥ 55 years with chronic musculoskeletal pain , not currently receiving prescription opioids . METHODS Subjects completed the PROMIS short form at baseline and after 3 months . Patient subsets were compared to assess reliability and responsiveness . Construct validity was tested by comparing baseline scores among patients who were or were not applying for Worker 's Compensation ; those with higher or lower catastrophizing scores ; and those with or without recent falls . Responsiveness was assessed with mean score changes , effect sizes , and st and ardized response means . RESULTS Internal consistency was good to excellent , with Cronbach 's alpha between 0.81 and 0.95 for all scales . Among patients who rated their pain as stable , test-retest scores at 3 months were around 0.70 for most scales . PROMIS scores were worse among patients seeking or receiving worker 's compensation , those with high catastrophizing scores , and those with recent falls . Among patients rating pain as “ much less ” at 3 months , absolute effect sizes for the various scales ranged from 0.24 ( Depression ) to 1.93 ( Pain Intensity ) . CONCLUSIONS Results indicate that the PROMIS short 29-item form may be useful for the study of patients with chronic musculoskeletal pain . Our findings also support use of the novel “ impact score ” recommended by the National Institutes of Health ( NIH ) Task Force on Research St and ards for Chronic Low Back Pain",
"OBJECTIVE To determine how well early responses to physical therapy for chronic low back pain predict outcomes at discharge . METHODS A prospect i ve single cohort study of chronic low back pain patients seen at a university spine physical therapy clinic . Self-reported pain severity on a 100-mm visual analog scale was measured before each physical therapy visit . The predictive variables were the change in pain score at the second , third , and fourth visits . The first outcome variable was discharge change in pain severity for a correlation analysis . The second outcome variable was a dichotomous variable of whether the subjects had achieved at least a 30 % reduction in pain severity at discharge for a discriminant analysis . RESULTS Spearman 's rank order correlation coefficient showed that early responses at the second ( r = 0.324 , P = 0.02 ) third ( r = 0.342 , P = 0.01 ) , and fourth visits ( r = 0.615 , P discharge change in pain . The discriminant analysis showed that early responses from the second to fourth visits were able to correctly predict 80.4 % of the discharge outcomes ( P physical therapy help predict discharge outcomes for chronic low back pain",
"Several versions of the 24-item Rol and Morris Disability Question naire ( RMDQ ) have been proposed ; however , their responsiveness has not been extensively explored . The objective of this study was to compare the responsiveness of four versions of the RMDQ . Perceived disability was measured using the 24-item , two 18-item and an 11-item RMDQ on 1,069 low back pain patients from six r and omised controlled trials . Responsiveness was calculated using effect size , Guyatt ’s responsiveness index ( GRI ) and receiver operating characteristics ( ROC ) curves . Effect size analyses showed that both 18-item versions of the RMDQ were superior to the 24- and 11-item versions of the RMDQ . GRI showed that the 24- and 18-item versions of the RMDQ were similar but more responsive than the 11-item . ROC curves revealed that the 11-item was less responsive than the other three versions , which had similar responsiveness . The results of this study demonstrate that the 24-item and both 18-item versions of the RMDQ have similar responsiveness with all having superior responsiveness to the 11-item",
"BACKGROUND The Army Surgeon General released the Pain Management Task Force final report in May 2010 . Among military providers , concerns were raised that the st and ard numeric rating scale ( NRS ) for pain was inconsistently administered and of question able clinical value . In response , the Defense and Veterans Pain Rating Scale ( DVPRS ) was developed . METHODS The instrument design integrates pain rating scale features to improve interpretability of incremental pain intensity levels , and to improve communication and documentation across all transitions of care . A convenience sample of 350 inpatient and outpatient active duty or retired military service members participated in the study at Walter Reed Army Medical Center . Participants completed the five-item DVPRS-one pain intensity NRS with and without word descriptors presented in r and om order and four supplemental items measuring general activity , sleep , mood , and level of stress and the Brief Pain Inventory seven interference items . Using systematic sampling , a r and om sample was selected for a word descriptor validation procedure matching word phases to corresponding pain intensity on the NRS . RESULTS Parallel forms reliability and concurrent validity testing demonstrated a robust correlation . When the DVPRS was presented with the word descriptors first , the correlation between the two ratings was slightly higher , r = 0.929 ( N = 171 ; P Intraclass correlation coefficient was 0.943 showing excellent alignment of word descriptors by respondents ( N = 42 ) , matching them correctly with pain level . CONCLUSIONS The DVPRS tool demonstrated acceptable psychometric properties in a military population",
"The purpose of this prospect i ve , single site cohort quasi-experimental study was to determine the responsiveness of the numerical rating scale ( NRS ) , Rol and –Morris disability question naire ( RMDQ ) , Oswestry disability index ( ODI ) , pain self-efficacy question naire ( PSEQ ) and the patient-specific functional scale ( PSFS ) in order to determine which would best measure clinical ly meaningful change in a chronic low back pain ( LBP ) population . Several patient-based outcome instruments are currently used to measure treatment effect in the chronic LBP population . However , there is a lack of consensus on what constitutes a “ successful ” outcome , how an important improvement/deterioration has been defined and which outcome measure(s ) best captures the effectiveness of therapeutic interventions for the chronic LBP population . Sixty-three consecutive patients with chronic LBP referred to a back exercise and education class participated in this study ; 48 of the 63 patients had complete data . Five question naires were administered initially and after the 5-week back class intervention . Also at 5 weeks , patients completed a global impression of change as a reflection of meaningful change in patient status . Score changes in the five different question naires were subjected to both distribution- and anchor-based methods : st and ard error of measurement ( SEM ) and receiver operating characteristic ( ROC ) curves to define clinical improvement . From these methods , the minimal clinical ly important difference ( MCID ) defined as the smallest difference that patients and clinicians perceive to be worthwhile is presented for each instrument . Based on the SEM , a point score change of 2.4 in the NRS , 5 in the RMDQ , 17 in the ODI , 11 on the PSEQ , and 1.4 on the PSFS corresponded to the MCID . Based on ROC curve analysis , a point score change of 4 points for both the NRS and RMDQ , 8 points for the ODI , 9 points for the PSEQ and 2 points for the PSFS corresponded to the MCID . The ROC analysis demonstrated that both the PSEQ and PSFS are responsive to clinical ly important change over time . The NRS was found to be least responsive . The exact value of the MCID is not a fixed value and is dependent on the assessment method used to calculate the score change . Based on ROC curve analysis the PSFS and PSEQ were more responsive than the other scales in measuring change in patients with chronic LBP following participation in a back class programme . However , due to the small sample size , the lack of observed worsening of symptoms over time , the single centre and intervention studied these results which need to be interpreted with caution",
"Study Design . Cohort study . Objectives . To estimate the Minimal Clinical ly Important Change ( MCIC ) of the pain intensity numerical rating scale ( PI-NRS ) , the Quebec Back Pain Disability Scale ( QBPDS ) , and the Euroqol ( EQ ) in patients with low back pain . Summary of Background Data . MCIC can provide valuable information for research ers , healthcare providers , and policymakers . Methods . Data from a r and omized controlled trial with 442 patients with low back pain were used . The MCIC was estimated over a 12-week period , and three different methods were used : 1 ) mean change scores , 2 ) minimal detectable change , and 3 ) optimal cutoff point in receiver operant curves . The global perceived effect scale ( GPE ) was used as an external criterion . The effect of initial scores on the MCIC was also assessed . Results . The MCIC of the PI-NRS ranged from 3.5 to 4.7 points in (sub)acute patients and 2.5 to 4.5 points in chronic patients with low back pain . The MCIC of the QBPDS was estimated between 17.5 to 32.9 points and 8.5 to 24.6 points for (sub)acute and chronic patients with low back pain . The MCIC for the EQ ranged from 0.07 to 0.58 in (sub)acute patients and 0.09 to 0.28 in patients with chronic low back pain . Conclusion . Reporting the percentage of patients who have made a MCIC adds to the interpretability of study results . We present a range of MCIC values and advocate the choice of a single MCIC value according to the specific context",
"CONTEXT Common pain conditions appear to have an adverse effect on work , but no comprehensive estimates exist on the amount of productive time lost in the US workforce due to pain . OBJECTIVE To measure lost productive time ( absence and reduced performance due to common pain conditions ) during a 2-week period . DESIGN AND SETTING Cross-sectional study using survey data from the American Productivity Audit ( a telephone survey that uses the Work and Health Interview ) of working adults between August 1 , 2001 , and July 30 , 2002 . PARTICIPANTS R and om sample of 28 902 working adults in the United States . MAIN OUTCOME MEASURES Lost productive time due to common pain conditions ( arthritis , back , headache , and other musculoskeletal ) expressed in hours per worker per week and calculated in US dollars . RESULTS Thirteen percent of the total workforce experienced a loss in productive time during a 2-week period due to a common pain condition . Headache was the most common ( 5.4 % ) pain condition result ing in lost productive time . It was followed by back pain ( 3.2 % ) , arthritis pain ( 2.0 % ) , and other musculoskeletal pain ( 2.0 % ) . Workers who experienced lost productive time from a pain condition lost a mean ( SE ) of 4.6 ( 0.09 ) h/wk . Workers who had a headache had a mean ( SE ) loss in productive time of 3.5 ( 0.1 ) h/wk . Workers who reported arthritis or back pain had mean ( SE ) lost productive times of 5.2 ( 0.25 ) h/wk . Other common pain conditions result ed in a mean ( SE ) loss in productive time of 5.5 ( 0.22 ) h/wk . Lost productive time from common pain conditions among active workers costs an estimated 61.2 billion dollars per year . The majority ( 76.6 % ) of the lost productive time was explained by reduced performance while at work and not work absence . CONCLUSIONS Pain is an inordinately common and disabling condition in the US workforce . Most of the pain-related lost productive time occurs while employees are at work and is in the form of reduced performance",
"Background : Comparative responsiveness data are needed to inform choices about pain outcome measures . Objectives : To compare responsiveness of pain intensity , pain-related function , and composite measures , using data from a r and omized trial and observational study . Research Design : Analysis of responsiveness . Subjects : A total of 427 adults with persistent back , hip , or knee pain were recruited from primary care . Methods : Participants completed Brief Pain Inventory , Chronic Pain Grade ( CPG ) , Rol and disability , SF-36 bodily pain , and pain global rating of change measures . We used the global rating as the anchor for st and ardized response mean and receiver operating characteristic curve analyses . We used the distribution-based st and ard error of measurement to estimate minimally important change . To assess responsiveness to the trial intervention , we evaluated st and ardized effect size statistics stratified by trial arm . Results : All measures were responsive to global improvement and all had fair-to-good accuracy in discriminating between participants with and without improvement . SF bodily pain was less responsive than other measures in several analyses . The 3-item PEG was similarly responsive to full Brief Pain Inventory scales . CPG and SF bodily pain were less responsive to the trial intervention and did not perform well among participants with hip/knee pain . Agreement between anchor and distribution-based methods was modest . Conclusions : If a brief measure is desired , the 3-item PEG is more responsive than the SF bodily pain scale . CPG and SF bodily pain scales may be relatively poor choices for trial outcome assessment . Both anchor and distribution-based methods should be considered when determining clinical ly important change",
"BACKGROUND CONTEXT There is a growing dem and to measure the real-world effectiveness and value of care across all specialties and disease states . Prospect i ve registries have emerged as a feasible way to capture real-world care across large patient population s. However , the proven validity of more robust and cumbersome patient-reported outcome instruments ( PROi ) must be balanced with what is feasible to apply in large-scale registry efforts . Hence , commercial registry efforts that measure quality and effectiveness of care in an attempt to guide quality improvement , pay for performance , or value-based purchasing should incorporate measures that most accurately represent patient-centered improvement . PURPOSE We set out to establish the relative validity and responsiveness of common PROi in accurately determining effectiveness of cervical surgery for neck and arm pain in registry efforts . STUDY DESIGN Prospect i ve cohort study . PATIENT SAMPLE Eighty-eight patients undergoing primary anterior cervical discectomy and fusion ( ACDF ) for neck and arm pain . OUTCOME MEASURES Patient-reported outcome measures for pain ( numeric rating scale for neck pain [ NRS-NP ] and arm pain [ NRS-AP ] ) , disability ( neck disability index [ NDI ] ) , general health ( short-form 12-item survey physical component summary [ SF-12 PCS ] and mental component summary [ SF-12 MCS ] ) , and quality of life ( Euro-Qol-5D [ EQ-5D ] ) were assessed . METHODS Eighty-eight patients undergoing primary ACDF for neck and arm pain were entered into a Web-based prospect i ve registry . Baseline and 12-month patient-reported outcomes ( NRS-NP , NRS-AP , NDI , SF-12 PCS , SF-12 MCS , and EQ-5D ) were assessed . Patients were also asked whether they experienced a level of improvement after ACDF that met their expectation ( meaningful improvement ) . To assess the validity of NRS-NP , NRS-AP , and NDI ( measures of pain and disability ) to discriminate between meaningful and nonmeaningful improvement and the validity of SF-12 PCS , SF-12 MCS , and EQ-5D ( measures of general health and quality of life ) to discriminate between meaningful and nonmeaningful improvement , receiver-operating characteristic curves were generated for each outcome instrument . The greater the area under the curve ( AUC ) , the more valid the discriminator . The difference between st and ardized response means ( SRMs ) in patients reporting meaningful improvement versus not was calculated to determine the relative responsiveness of each outcome instrument to changes in pain and QOL after surgery . RESULTS For pain and disability , both NDI ( AUC=0.75 ) and NRS-AP ( AUC=0.74 ) were valid discriminators of meaningful improvement . Numeric rating scale for neck pain ( AUC=0.69 ) was a poor discriminator . Neck disability index was also most responsive to postoperative improvement ( SRM difference 0.78 ) , followed by NRS-AP ( SRM difference 0.59 ) and NRS-NP ( SRM difference 0.46 ) . For general health and quality of life , SF-12 PCS ( AUC=0.79 ) was the only valid discriminator of meaningful improvement . Euro-Qol-5D ( AUC=0.68 ) and SF-12 MCS ( AUC=0.44 ) were poor discriminators . Short-form 12 physical component summary ( SRM difference 1.08 ) was also most responsive compared with EQ-5D ( SRM difference 0.89 ) and SF-12 MCS ( SRM difference 0.01 ) . CONCLUSIONS For pain and disability , NDI is the most valid and responsive measure of improvement after surgery for neck and arm pain . Numeric rating scale for neck pain and NRS-AP are poor substitutes for NDI when measuring effectiveness of care in registry efforts . For health-related quality of life , only SF-12 PCS could accurately discriminate meaningful improvement after cervical surgery and was found to be most valid and responsive . Large-scale registry efforts aim ed at measuring effectiveness of cervical spine surgery should use NDI and SF-12 to accurately assess improvements in pain , disability , and quality of life",
"Objective The Patient-Reported Outcomes Measurement Information System ( PROMIS ) was developed to st and ardize measurement of clinical ly relevant patient-reported outcomes . This study evaluated the reliability and construct validity of select PROMIS static short-form ( SF ) instruments in women with fibromyalgia . Design Analysis of baseline data from the Fibromyalgia Activity Study with TENS ( FAST ) , a r and omized controlled trial of the efficacy of transcutaneous electrical nerve stimulation . Setting Dual site , university-based outpatient clinics . Subjects Women aged 20 to 67 years diagnosed with fibromyalgia . Methods Participants completed the Revised Fibromyalgia Impact Question naire ( FIQR ) and 10 PROMIS static SF instruments . Internal consistency was calculated using Cronbach alpha . Convergent validity was examined against the FIQR using Pearson correlation and multiple regression analysis . Results PROMIS static SF instruments had fair to high internal consistency ( Cronbach α = 0.58 to 0.94 , P . PROMIS ' physical function ' domain score was highly correlated with FIQR ' function ' score ( r = -0.73 ) . The PROMIS ' total ' score was highly correlated with the FIQR total score ( r = -0.72 ) . Correlations with FIQR total score of each of the three PROMIS domain scores were r = -0.65 for ' physical function , ' r = -0.63 for ' global , ' and r = -0.57 for ' symptom ' domain . PROMIS ' physical function , ' ' global , ' and ' symptom ' scores explained 58 % of the FIQR total score variance . Conclusions Select PROMIS static SF instruments demonstrate convergent validity with the FIQR , a legacy measure of fibromyalgia disease severity . These results highlight the potential utility of select PROMIS static SFs for assessment and tracking of patient-reported outcomes in fibromyalgia",
"Purpose : To compare the sensitivity to change and the responsiveness to intervention of the PROMIS Pain Interference short forms , Brief Pain Inventory ( BPI ) , 3-item PEG scale , and SF-36 Bodily Pain subscale in a sample of patients with persistent musculoskeletal pain of moderate severity . Methods : St and ardized response means , st and ardized effect sizes , and receiver operating curve analyses were used to assess change between baseline and 3-month assessment s in 250 participants who participated in a r and omized clinical effectiveness trial of collaborative telecare management for moderate to severe and persistent musculoskeletal pain . Results : The BPI , PEG , and SF-36 Bodily Pain measures were more sensitive to patient-reported global change than the PROMIS Pain Interference short forms , especially for the clinical ly improved group , for which the change detected by the PROMIS short forms was not statistically significant . The BPI was more responsive to the clinical intervention than the SF-36 Bodily Pain and PROMIS Pain Interference measures . Post hoc analyses exploring these findings did not suggest that differences in content or rating scale structure ( number of response options or anchoring language ) adequately explained the observed differences in the detection of change . Conclusions : In this clinical trial , the BPI and PEG measures were better able to detect change than the SF-36 Bodily Pain and PROMIS Pain Interference measures ",
"Background : Patient-reported outcome measures are increasingly used evaluating clinical care . Many measures used to assess operative hindfoot interventions vary in content , and some have not been psychometrically vali date d in this population . The purpose of this study was to compare measurement properties of 6 lower-extremity patient-reported outcome measures , and to evaluate their reliability and validity in light of patients ’ preferences . Methods : Cross-sectional survey of 42 preoperative and 100 postoperative patients completed 6 lower-extremity outcome measures on 2 occasions : Foot Function Index ( FFI ) , Ankle Osteoarthritis Scale ( AOS ) , patient-reported items of the American Orthopaedic Foot & Ankle Society Question naire ( AOFAS ) , Lower Extremity Functional Scale ( LEFS ) , Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , and the Short Musculoskeletal Function Assessment ( SMFA ) , as well as measures of preference , and symptoms . Results : Internal consistency was good to excellent for all scales and subscales ( α = .84-.97 ; ICC [ 2,1 ] = .81-.96 ) . Correlations between scales ranged from .50 ( WOMACStiffness and FFIActivity Limitations ) to .92 ( LEFS and SMFAOverall , WOMACPain and AOSOverall , FFIOverall and AOFASOverall ) . Higher correlations occurred within instruments ( r = .97 AOSPain and AOSOverall ) and between similar subscales from different instruments ( r = .91 WOMACPain and AOSPain ) . Construct validity showed moderate to high correlations to global ratings of Pain , Stiffness , and difficulty performing Daily Activities . The highest correlations ( r > .75 ) occurred between Pain and AOSOverall ( r = .84 ) , stiffness and WOMACStiffness ( r = .81 ) , and Daily Activities and AOSDisability ( r = .87 ) . Patients rated instruments by preference . FFI , WOMAC , LEFS , and SMFA rated favorably for length . FFI , WOMAC , LEFS , and AOFAS rated high for underst and ability . FFI was rated by postoperative patients as most likely to capture change due to surgery . SMFA rated the best overall . Conclusions : Direct comparison of instruments revealed similarity between scales in construct validity and reliability . Patient preferences supported the use of these scales . Foot-specific instruments offered no clear advantage over lower-extremity instruments . Level of Evidence : Level II , prospect i ve comparative study"
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This study aims to determine osteoporosis ( OP ) investigation and treatment within post-fracture initiatives conducted in fracture clinics and other orthopedic environments . A systematic review was conducted . Eligibility criteria were : hip fracture patients plus all other fracture patients presenting with a fragility fracture , orthopedic setting where orthopedic physicians/staff were involved , intervention to improve OP management , primary data on ≥20 patients from r and omized controlled trials ( RCTs ) and other study design s. We calculated outcome data within 6 months of screening from an intention-to-treat principle to derive an equated proportion ( EP ) across interventions . Outcomes were : ( 1 ) proportion of patients investigated with bone densitometry , ( 2 ) proportion of patients initiating OP medication , and ( 3 ) proportion of patients taking OP medication . We identified 2,259 citations , of which 57 articles that included 64 intervention groups were eligible . The median EP for patients investigated was 43 % and the 75th percentile was 71 % . The median EP for medication initiation was 22 % and the 75th percentile was 34 % . The median EP for medication taking was 27.5 % and the 75th percentile was 43 % . The EPs for all outcomes were higher for interventions with dedicated personnel to implement the intervention and those within which bone mineral density testing and /or treatment were included . In studies with an EP , up to 71 % of patients were investigated for OP , but < 35 % initiated medication , and < 45 % were taking medication within 6 months of screening . Calculating an EP allowed us to compare outcomes across the studies , therefore capturing both RCTs and other study design s typical of real-world setting
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"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",
"Objectives To establish a protocol for the treatment of fragility fractures in the hospital setting based on treatment of osteoporosis . Material s and methods An intervention protocol was implemented in patients with fragility fractures based on ( 1 ) indicating the diagnosis of osteoporotic fracture in the summary of discharge ; ( 2 ) “ lifestyle recommendations ” ; and ( 3 ) therapy for osteoporosis . Thirty-one hospitals were involved and they were informed of the importance of protocol compliance . In the first phase , a retrospective study was conducted to establish the number of low-energy fractures treated and the percentage of them that had complied with the protocol ( n = 887 ) . Then , prospect ively , the same data were collected for the patients managed for 1 year ( n = 6,826 ) in three sections of 4-month intervals . Results The percentage of compliance increased from 8.2 to 57.2 % in the first point , from 12.6 to 42.4 % in the second , and from 10.3 to 43.2 % in the third . Conclusion The implementation of programs to improve osteoporosis treatment is very useful for ensuring adherence in the management of osteoporosis following admission due to fragility fracture",
"BACKGROUND Although osteoporosis is strongly associated with hip fractures , the initiation of osteoporosis treatment following hip fractures occurs at surprisingly low rates of between 5 % and 30 % . Currently , most patients receiving treatment have been referred back to their primary care physician for osteoporosis management . The purpose of this study was to compare the effect of osteoporosis management initiated by the orthopaedic team and osteoporosis management initiated by the primary care physician on the rates of treatment at six months . METHODS A prospect i ve r and omized trial was conducted to assess the difference in the rate of osteoporosis treatment when an in-house assessment of osteoporosis was initiated by the orthopaedic surgeon and follow-up was conducted in a specialized orthopaedic osteoporosis clinic compared with osteoporosis education and \" usual \" care . RESULTS Sixty-two patients were enrolled in the study . Thirty-one patients each were in the control and intervention groups . The percentage of patients who were on pharmacologic treatment for osteoporosis at six months after the fracture was significantly greater when the evaluation was initiated by the orthopaedic surgeon and was managed in a specialized orthopaedic osteoporosis clinic ( 58 % ) than when treatment was managed by a primary care physician ( 29 % ) ( p = 0.04 ) . CONCLUSIONS An active role by orthopaedic surgeons in the management of osteoporosis improves the rate of treatment at six months following a hip fracture",
"BACKGROUND In a r and omized trial of patients with hip fractures , we previously demonstrated that a hospital-based case manager could increase rates of appropriate osteoporosis treatment to 51 % compared with 22 % for usual care ( P Patients with hip fractures were r and omized to usual care ( n = 110 ) or a case manager ( n = 110 ) and followed up for 1 year . Time-motion studies were used to determine intervention costs . From a third-party health care payer perspective and over the patient 's remaining lifetime , a Markov decision-analytic model was constructed to determine cost-effectiveness of the intervention compared with usual care . Costs and benefits were discounted at 3 % and expressed in 2006 Canadian dollars . RESULTS The intervention cost CaD $ 56 per patient . Compared with usual care , the intervention strategy was dominant : for every 100 patients case managed , 6 fractures ( 4 hip fractures ) were prevented , 4 quality -adjusted life-years were gained , and CaD $ 260 000 was saved by the health care system . Irrespective of the number of patients case managed , the intervention reached a break-even threshold within 2 years . The intervention dominated usual care over the entire spectrum of 1-way sensitivity analyses and was cost-saving in 82 % of probabilistic model simulations . CONCLUSIONS Compared with usual care , we found that using a case manager for patients with hip fractures increased rates of appropriate osteoporosis treatment . The intervention dominated usual care , and the analysis suggests that systems implementing an intervention similar to ours should expect to see a reduction in fractures , gains in life expectancy , and substantial cost savings . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00175175",
"Background : Osteoporosis is a common disease characterized by decreased bone mass and increased fracture risk in postmenopausal women and the elderly . Hip fractures are among the most common consequences of osteoporosis and unfortunately usually occur late in the course of the disease . When a patient is admitted to the hospital with a fragility hip fracture , a unique opportunity for diagnosis and treatment presents itself . Fortunately , several medications have proven to be effective in lowering the risk of future fractures . The purpose s of the present study were to test the hypothesis that most fragility hip fractures go untreated and to determine whether educational efforts to raise physician awareness have led to an improvement in osteoporosis treatment rates . Methods : A retrospective cohort study was performed with use of the patient data bases at two university medical centers and one university-affiliated community hospital . The charts of 300 r and omly selected patients were sorted with use of ICD-9 ( International Classification of Diseases , Ninth Revision ) codes for femoral neck fractures . There were 100 patients from each center , with twenty-five patients from each year between 1997 and 2000 . The admitting diagnosis , mechanism of injury , admission medications , procedures performed during hospitalization , and discharge medications were then extracted and analyzed . During this period , the National Osteoporosis Foundation established guiding principles for the treatment of fragility fractures . Results : Of the seventy-five patients from all centers for each year from 1997 to 2000 , 11 % , 13 % , 24 % , and 29 % , respectively , were discharged with a prescription for some medication targeting osteopenia , either supplemental calcium or an antiosteoporotic medication ( estrogen , calcitonin , a bisphosphonate , or raloxifene ) . A trended chi-square analysis of this increase revealed a p value of prescription at the time of discharge . However , forty of these patients ( 13.3 % of the overall group ) received calcium and only eighteen ( 6.0 % of the overall group ) received a medication to actively prevent bone resorption and treat osteoporosis . In addition , no patient underwent a bone density scan while in the hospital . Conclusions : Elderly patients and postmenopausal women who are admitted to the hospital and diagnosed with a low-energy femoral neck fracture have been undertreated for osteoporosis . However , over the four years of the present study , there was a significant increase in the rate of treatment . It is hoped that treatment rates will continue to increase in the future with continued educational efforts",
"Background : Missed opportunities for osteoporosis detection and treatment following fractures , especially in the elderly , are common . Clinical pharmacy specialist ( CPS ) intervention may positively impact this deficiency . Objective : To examine the impact of a CPS-managed intervention to identify , screen , and initiate appropriate osteoporosis pharmacotherapy in elderly patients after an atraumatic fracture . Methods : This was a prospect i ve quality improvement analysis . Hospitalized and ambulatory patients who had a diagnosis of atraumatic fracture between July 2002 through August 2003 but were not on osteoporosis pharmacotherapy were identified by CPSs . Bone mineral density ( BMD ) screening and osteoporosis pharmacotherapy recommendations were made by a CPS when appropriate . Descriptive analyses were performed to determine the proportion of patients initiated on osteoporosis pharmacotherapy or receiving a recommended BMD evaluation . Results : A total of 137 ( 40 inpatient and 97 ambulatory ) female patients were included . The mean ages ± SD of inpatient and ambulatory patients were 83 ± 8 and 70 ± 7 years , respectively . Overall , 50 % ( n = 69 ) of patients either initiated their recommended osteoporosis pharmacotherapy ( 48 % [ n = 19 ] and 30 % [ n = 29 ] of inpatient and ambulatory patients , respectively ) or received a recommended BMD screening ( 42 ambulatory patients were recommended and 50 % [ n = 21 ] completed a BMD test ) . Of the patients who completed a BMD test , 17 ( 81 % ) were osteoporotic . All 17 were initiated on osteoporosis pharmacotherapy . Conclusions : Using a systematic approach to identify patients in need of osteoporosis pharmacotherapy , a CPS-managed intervention result ed in clinical ly meaningful osteoporosis treatment initiation rates ",
"Introduction Older patients with fragility fractures are not commonly tested or treated for osteoporosis . Compared to usual care , a previously reported intervention led to 30 % absolute increases in osteoporosis treatment within 6 months of wrist fracture . Our objective was to examine longer-term outcomes , reproducibility , and cost-effectiveness of this intervention . Methods We conducted an extended analysis of a non-r and omized controlled trial with blinded ascertainment of outcomes that compared a multifaceted intervention to usual care controls . Patients > 50 years with a wrist fracture treated in two Emergency Departments in the province of Alberta , Canada were included ; those already treated for osteoporosis were excluded . Overall , 102 patients participated in this study ( 55 intervention and 47 controls ; median age : 66 years ; 78 % were women ) . The interventions consisted of faxed physician reminders that contained osteoporosis treatment guidelines endorsed by opinion leaders and patient counseling . Controls received usual care ; at 6-months post-fracture , when the original trial was completed , all controls were crossed-over to intervention . The main outcomes were rates of osteoporosis testing and treatment within 6 months ( original study ) and 1 year ( delayed intervention ) of fracture , and 1-year persistence with treatments started . From the perspective of the healthcare payer , the cost-effectiveness ( using a Markov decision-analytic model ) of the intervention was compared with usual care over a lifetime horizon . Results Overall , 40 % of the intervention patients ( vs. 10 % of the controls ) started treatment within 6 months post-fracture , and 82 % ( 95%CI : 67–96 % ) had persisted with it at 1-year post-fracture . Delaying the intervention to controls for 6 months still led to equivalent rates of bone mineral density ( BMD ) testing ( 64 vs. 60 % in the original study ; p = 0.72 ) and osteoporosis treatment ( 43 vs. 40 % ; p = 0.77 ) as previously reported . Compared with usual care , the intervention strategy was dominant – per patient , it led to a $ 13 Canadian ( U.S. $ 9 ) cost savings and a gain of 0.012 quality -adjusted life years . Base-case results were most sensitive to assumptions about treatment cost ; for example , a 50 % increase in the price of osteoporosis medication led to an incremental cost-effectiveness ratio of $ 24,250 Canadian ( U.S. $ 17,218 ) per quality -adjusted life year gained . Conclusions A pragmatic intervention directed at patients and physicians led to substantial improvements in osteoporosis treatment , even when delivered 6-months post-fracture . From the healthcare payer ’s perspective , the intervention appears to have led to both cost-savings and gains in life expectancy",
"In an attempt to identify a high-risk cohort of patients , who could be offered preventive therapy , we assessed patients who had suffered one hip fracture . A total of 394 patients were prospect ively followed to determine those who had suffered a second fracture . Entry bone mass of the unfractured hip and total body was examined by dual X-ray absorptiometry ( DXA ) and of the os calcis , by quantitative ultrasound ( QUS ) , along with various clinical parameters . The relative risks in the QUS parameters did not reach significance , except for broadb and ultrasound attentuation as measured by the McCue CUBA Clinical , whereas femoral neck and total body bone mineral density also reached significance . Lowest quartile body weight was also a significant risk factor as were occurrence of a new fall and poor mobility score . Using Receiver Operator Characteristic curves , we found no significant differences between DXA trochanter or for the Mini Mental State Examination score in predicting those who sustained a second hip fracture . In this elderly group risk factors are almost as good as bone mass at predicting those who will sustain a second hip fracture . Low body weight and poor mobility could be used as triggers for the use of preventive therapy without the use of bone mass measurements and to target expensive preventive therapy to reduce fracture risk",
"OBJECTIVE To review the 3-year performance of an established osteoporosis care service and consider further improvements in an effort to reduce fragility fractures . METHODS Osteoporosis care has been coordinated for all willing and able patients with orthopedic fragility fractures in our health system by a nurse and medical director since 2003 , using a guideline -based care algorithm and task management software . Patients were followed by telephone for 2 years to monitor their status and optimize adherence to treatment . Demographics , management recommendations , clinical data , and adherence to treatment were review ed for the 2003 - 2005 patient population . RESULTS Of 1,019 patients with fragility fractures , 61 % underwent osteoporosis evaluation and treatment . The remainder included 15 % who refused to participate and 24 % who were unable to participate for various logistical and health reasons . More patients age > 80 years were unwilling or unable to participate . Bone densities ( dual x-ray absorptiometry [ DXA ] ) were normal , low , or osteoporotic in 24 % , 55 % , and 21 % of patients , respectively , and 60 % of the osteoporotic group had > or = 1 abnormal metabolic bone laboratory result . Only 17 % of the total reported a previous fracture , and 47 % had ever undergone DXA . Few experienced bone loss , a new fracture , or bisphosphonate intolerance during treatment . CONCLUSION An osteoporosis care service has coordinated care for every willing and able fragility fracture patient with positive outcomes . In addition , the results suggest a high priority for earlier proactive diagnosis and intervention of the at-risk population if fractures are to be reduced",
"This study compares the investigation of and treatment for osteoporosis in two groups of fracture patients at two orthopaedic centres in the UK . One centre had a formal fracture liaison service ( FLS ) responsible for screening fracture patients for osteoporosis . The other centre relied upon individual clinicians to initiate investigation or treatment for osteoporosis in patients following fracture . Patients who had been treated in either centre for a proximal humeral or hip fracture during a 6-month period were followed up 6 months later to identify how many had received screening or treatment for osteoporosis . Information was retrieved from a prospect ively compiled data base or by postal question naire . The study revealed that in the centre with an FLS 85 % of patients with a proximal humeral fracture and 20 % with a hip fracture had been offered a dual-energy X-ray absorptiometry ( DEXA ) scan . Approximately 50 % and 85 % , respectively , were receiving treatment for osteoporosis 6 months following their fracture . This compared with DEXA being offered to only 6 % and 9.7 % of humeral and hip fracture patients , respectively , and 20 % ( hip ) and 27 % ( proximal humerus ) receiving osteoporosis treatment in the other centre . The presence of an FLS result ed in a considerably higher proportion of patients receiving investigation and treatment for osteoporosis following a hip or proximal humeral fracture",
"BACKGROUND Measurement of bone mineral density is widely used to diagnose osteoporosis . The objectives of this study are to determine how bone densitometry affects subsequent treatment of osteopenia and osteoporosis with either hormone replacement therapy or bisphosphonates and to examine clinical factors associated with starting either therapy after bone densitometry . METHODS We conducted a prospect i ve study involving women over 50 years of age who were referred to a tertiary care hospital for the first time to undergo bone density measurement using dual-energy x-ray absorptiometry ( DXA ) . Baseline clinical data were collected through face-to-face interviews before the test . Subsequently , the scans were review ed and categorized as showing no bone loss , osteopenia or osteoporosis , based on World Health Organization criteria . Three months after DXA , subjects were contacted by telephone to determine their underst and ing of the test results and any new treatments started or recommended since the scan . RESULTS Of 383 women recruited at the time of their DXA , 335 ( 87.5 % ) completed the 3-month follow-up . Among those reached at follow-up , DXA results showed no bone loss in 119 ( 35.5 % ) , osteopenia in 137 ( 40.9 % ) and osteoporosis in 79 ( 23.6 % ) . The proportion of subjects with osteoporosis receiving either hormone replacement therapy or bisphosphonate therapy was 15.2 % before the test , increasing to 63.3 % after the scan . The following factors were independently associated with the initiation of either therapy : actual DXA result showing osteoporosis ( odds ratio [ OR ] 7.2 ; 95 % confidence interval [ CI ] 1.7 - 30.3 ) , compared with a normal scan ; subjects ' perception that their scan showed bone loss ( osteopenia , or osteoporosis ) ( OR 13.5 ; 95 % CI 4.0 - 45.5 ) or that they were unclear about the results ( OR 5.4 ; 95 % CI 1.6 - 18.8 ) , compared with the perception that the results were normal ; and discussion of the DXA results with a physician ( OR 5.5 ; 95 % CI 1.9 - 16.0 ) . INTERPRETATION The proportion of women with osteoporosis receiving hormone replacement therapy or bisphosphonate therapy increases after diagnosis with densitometry . However , communication by physicians so that patients underst and their test results is a critical component in the initiation of therapy after bone densitometry",
"UNLABELLED A low-impact fracture in a postmenopausal woman should prompt investigations for osteoporosis followed , if needed , by appropriate treatment . OBJECTIVES To evaluate the impact of information alerting general practitioners to the need for osteoporosis treatment in postmenopausal women with a recent history of peripheral fracture . METHODS We conducted a prospect i ve 7-month follow-up study of 78 postmenopausal women , with a mean age of 81.5 years , admitted to the emergency department for peripheral fractures . Three months after the fracture , we sent a letter to the general practitioner of each patient emphasizing the probable contribution of osteoporosis to the fracture and the need for osteoporosis treatment . Six months after the fracture , we interviewed the patients by telephone , and one month later we mailed a question naire to those physicians who had not followed the treatment recommendation . RESULTS At emergency room admission , 9 patients were receiving treatment for osteoporosis ( hormone replacement therapy in one patient and calcium and vitamin D supplementation in eight patients ) . Admission to a ward was required in 66 ( 85 % ) patients . No treatment for osteoporosis was given at discharge . Six months after discharge , seven patients reported recent initiation of calcium and vitamin D supplementation , and none reported other osteoporosis treatments . The response rate to the physician question naire mailed 7 months after discharge was 54 % ( n=28 ) ; responses showed treatment of 11 additional patients , by calcium and vitamin D supplementation in six cases and by bisphosphonates with or without calcium and vitamin D supplementation in five cases . Treatment initiation rates were similar in patients younger and older than 80 years . CONCLUSIONS Despite information of general practitioners about the need for osteoporosis treatment , such treatment was initiated in only 30.5 % of patients . General practitioners may be reluctant to initiate osteoporosis treatment in patients who are very old or have multiple comorbidities",
"OBJECTIVES Osteoporosis treatment rates after a fracture are low . This study evaluated methods to increase guideline -recommended osteoporosis care postfracture . DESIGN Participants were r and omly assigned to usual care or one of two interventions . Analysis of primary outcomes used electronic data and linear regression . SETTING A Pacific Northwest nonprofit health maintenance organization . PARTICIPANTS Female patients aged 50 to 89 who suffered a fracture in 1999 and had not received bone mineral density ( BMD ) measurement or medication for osteoporosis ( n=311 ) and their primary care providers ( n=159 ) . INTERVENTION Patient-specific clinical guideline advice to the primary care provider delivered by electronic medical record ( EMR ) message or electronic reminder to the provider plus an educational letter mailed to the patient . MEASUREMENTS BMD measurement and osteoporosis medication . RESULTS At 6 months , provider reminder result ed in 51.5 % of patients receiving BMD measurement or osteoporosis medication , provider reminder plus patient education result ed in 43.1 % , and usual care result ed in 5.9 % ( P Patients aged 60 to 69 were 18 % ( 95 % confidence interval=3 - 34 ) more likely to receive BMD measurement or an osteoporosis medication than those aged 80 to 89 . CONCLUSION Patient-specific postfracture advice to the provider through an EMR message significantly increased BMD measurement and osteoporosis medication . As EMRs become more widespread , this intervention could improve osteoporosis management for many postfracture patients . Future research should identify barriers to and facilitators of care for older , high-risk patients",
"Introduction Despite the high risk for subsequent fracture following an initial osteoporotic fracture , the majority of subjects with minimal trauma fractures receive no treatment for osteoporosis . The primary aim of this investigation was to determine whether an information-based intervention could change post-fracture management of osteoporosis . A secondary aim was to define participant- and doctor-related barriers to osteoporosis management . Methods Consecutive fracture patients ( n=254 ) from the outpatient fracture clinic at St Vincent ’s Hospital , Sydney were interviewed over a 15-month period ( February 2002–July 2003 ) . Fracture risk factors , prior investigation and treatment for osteoporosis were collected at baseline . Participants were initially contacted after 3 months to ascertain follow-up management . All those not investigated or treated by their primary care physician were then r and omized to either a personalized letter or the same letter plus an offer of a free bone mineral density ( BMD ) test . Participants were contacted after 9 months to record further investigations or treatment for osteoporosis . Results Less than 20 % of the participants had a primary care physician follow-up 3 months after the fracture , leaving 159 who were r and omized to a personalized letter ( n=79 ) and a personalized letter plus the offer of a free BMD test ( n=80 ) . There was a significant increase in the number of people investigated for osteoporosis in the group receiving the letter plus BMD offer [ 38 % ( letter + BMD ) vs. 7 % ( letter only ) ; p=0.001 ) . A high proportion of those tested had low BMD ( 49 % osteopenia and 17 % osteoporosis ) . However , the rates of treatment in both groups were very low ( 6 % ) . Furthermore , even among the few individuals ( 23 % ) who contacted their primary care physician , only 25 % were recommended treatment . The belief that the fracture was osteoporotic was an independent predictor of having a BMD test , a primary care physician follow-up and treatment . Other independent predictors were age over 50 years for a primary care physician follow-up , female sex for having a BMD test and having had a BMD test for treatment . Conclusion This study demonstrates that an information-based intervention led to a modest increase in the proportion of people investigated for osteoporosis ; however . there was no significant effect on treatment rates . The offer of a free BMD assessment was associated with a significantly higher rate of investigation than a personalized letter alone ( odds ratio : 8.5 ; 95 % confidence interval : 3.1–24.5 ) , but this investigation did not affect treatment rate . The low uptake of either a BMD or a visit to a primary care physician together with low rates of treatment recommendation even among people who contacted their primary care physician reflects significant participant and doctor-related barriers to osteoporosis management",
"Summary In a cluster r and omized trial , we evaluated the effect of a multifaceted intervention ( directed at both patient and primary care physician ) on the rates of testing and treatment of osteoporosis in postmenopausal women within six months of their wrist fracture . Compared to usual care , women in the intervention practice s were three times more likely to receive bone mineral density testing and prescribed osteoporosis treatments . Introduction Postmenopausal women with wrist fractures are at increased risk of future fragility fractures , yet they frequently do not receive evaluation and treatment for osteoporosis . We set out to evaluate a multifaceted intervention design ed to improve management of osteoporosis in older women with recent wrist fractures . Methods Cluster r and omized trial of 270 women cared for in 119 primary care practice s. We recruited postmenopausal women with an acute wrist fracture from the emergency departments of hospitals in southeastern Ontario , Canada . Family practice s were r and omly assigned to either the intervention or usual care . The intervention consisted of a mailed reminder with a summary of treatment guidelines and letter sent to the primary care physician , in addition to an educational package and letter to the women . The primary outcome was the proportion of women prescribed osteoporosis therapy within 6 months of their fracture . Results The mean age of women was 69(10.9 ) years . The intervention increased the proportion of women started on osteoporosis medications ( 28 % vs. 10 % ) of controls , adjusted OR 3.45 , 95 % CI , 1.58–7.56 , p = 0.002 ) and the proportion who had a bone mineral density ( BMD ) test ( 53.3 % vs. 26 % ) of controls , OR 3.38 , 95 % CI , 1.83–6.26 , p testing and treatment rates . Conclusion A multifaceted intervention significantly improved rates of osteoporosis treatment and BMD testing in postmenopausal women with wrist fractures",
"OBJECTIVE We aim ed to determine whether a novel Patient Empowerment and Physician Alerting ( PEPA ) intervention would improve the proportion of seniors who were investigated and treated for osteoporosis after hip fracture . METHODS We undertook a 6-month r and omized controlled trial ( RCT ) in 48 women and men > /= 60 years old who had suffered a hip fracture and were admitted to a tertiary-care university hospital . The primary outcome measure was the proportion of participants offered one or more osteoporosis-specific ' best practice s ' measured using the Diagnosis and Management Question naire ( DMQ ) . Participant responses were vali date d in part by physician report . RESULTS In the PEPA intervention group , 19 ( 68 % ) were offered one or more components of best practice care compared with 7 ( 35 % ) in the ' usual care ' group ( p PEPA group , 15 ( 54 % ) ( p bisphosphonate therapy , 8 ( 29 % ) ( p bone mineral density scan , 11 ( 39 % ) were prescribed calcium and vitamin D ( p = .32 ) , and 9 ( 32 % ) ( p exercise . In the usual care group , 0 ( 0 % ) were prescribed bisphosphonate therapy , a bone mineral density assessment , or exercise and 6 ( 30 % ) were prescribed calcium and vitamin D. CONCLUSIONS This simple , inexpensive PEPA intervention result ed in far superior clinical management than did usual care in a population at high risk of future hip fracture",
"Context Many patients who sustain fragility fractures do not receive subsequent testing and treatment for osteoporosis . Contribution This study shows that faxed reminders to physicians , treatment guidelines endorsed by opinion leaders , and patient education about osteoporosis can increase the testing and therapy for osteoporosis among patients who present to an emergency department with wrist fracture . Caution s This study did not r and omly assign persons to the intervention group and did not examine improvements in bone density or repeated fractures . The Editors Osteoporosis , a chronic and progressive condition that leads to decreased bone mass and skeletal fragility , may result in fractures , disability , pain , deformity , and even death ( 1 - 3 ) . The condition is common , affecting an estimated 1.4 million Canadians and 10 million Americans ( 1 , 2 ) . These figures represent 25 % of women and 12 % of men older than 50 years of age ( 1 , 2 ) . In the United States , the annual cost of treating osteoporosis and its sequelae has been estimated at $ 13.8 billion ( 2 ) , compared with $ 7.5 billion for congestive heart failure and $ 6.2 billion for asthma ( 3 ) . Without better preventive strategies , the rate of osteoporotic fractures is expected to double over the next 15 years ( 4 ) . Several experts ( 5 ) and guidelines ( 1 , 2 ) suggest a preventive strategy of identifying people with typical osteoporosis-related fractures ( for example , fractures of the hip , spine , or wrist [ often called fragility fractures ] ) and targeting them for treatment . They recommend this strategy because this population is at the greatest risk for subsequent fracture and may derive the greatest absolute benefit from treatment . Numerous safe and effective treatments can reduce the risk for recurrent fracture by 40 % to 60 % ( 1 - 3 , 6 ) . In addition , with the use of bisphosphonates and raloxifene , all subgroups of examined patients may obtain beneficial effects ( 3 , 7 - 9 ) within a year ( 7 , 8) . People 50 years of age and older with a fracture of the wrist may be particularly well suited to a strategy of case finding and secondary prevention . Fractures of the wrist are the most common symptomatic fracture related to osteoporosis ( 3 ) , and 70 % to 80 % of persons with wrist fractures have low bone mass ( 10 , 11 ) . Observational studies suggest that a wrist fracture is a sentinel event in the natural history of osteoporosis because this type of fracture forecasts an increased risk for fractures of the hip and spine over the next 10 to 20 years ( 12 - 14 ) . Best practice ( clinical practice consistent with current evidence and expert consensus ) would be to identify people 50 years of age or older with a fragility fracture of the wrist , to measure their bone mineral density , and to treat those with low bone mass or osteoporosis ( 1 , 2 , 5 ) . However , the gap between best practice and everyday clinical practice is wide . Over the past 5 to 10 years , studies from the United States ( 3 , 15 , 16 ) , Canada ( 17 , 18 ) , and elsewhere ( 5 , 19 ) report that rates of testing for and treating osteoporosis a year or longer after a fracture of the wrist are less than 10 % to 20 % . This is an important failure in the process of knowledge translation and indicates that benefits within our reach are not being achieved . We design ed a pragmatic , multifaceted osteoporosis intervention strategy directed at people 50 years of age or older with a fracture of the wrist and at their primary care physicians . The intervention consisted of physician reminders , treatment guidelines endorsed by local opinion leaders , and patient education . Our primary objective was to examine whether this intervention improved the diagnosis and treatment of osteoporosis in this high-risk population . Secondary objectives included examining the effect of this intervention on patients ' knowledge , satisfaction , and quality of life . Methods Setting and Participants Capital Health ( Edmonton , Alberta ) is one of the largest integrated health service delivery organizations in Canada ( 20 ) . It provides comprehensive health services for about 1 million people and has an annual budget of almost $ 2 billion ( Canadian ) ( 20 ) . Primary care is delivered by approximately 900 fee-for-service physicians . We enrolled participants from the 2 largest emergency departments in the region : the University of Alberta Hospital ( a university-based teaching hospital ) and the Royal Alex and ra Hospital ( a university-affiliated community teaching hospital ) . These emergency departments provide most of the fracture care and emergency orthopedic services to the region . Consecutive patients presenting to the emergency department with a wrist fracture were potentially eligible . Inclusion criteria were as follows : age 50 years or older ; any simple , closed fracture of the distal forearm ; and discharge home . We excluded patients who were already taking prescription treatments for osteoporosis . Because we did not ask patients whether they had a diagnosis of osteoporosis until study closeout , a patient with a history of osteoporosis who was not being treated with prescription medication was potentially eligible for inclusion . We also excluded patients who were unable to provide consent , were unwilling to participate , were admitted to the hospital , resided in a long-term care facility , resided outside the Capital Health region , or could not read and converse in English . Study Design and Patient Enrollment We conducted a prospect i ve controlled trial with blinded ascertainment of outcomes . To allocate patients to the intervention or usual care control groups , we adapted and modified an onoff 1-site study design for 2 sites ( 21 ) . For 1 month at a time , in sequential order , the intervention was on at 1 emergency department while it was off at the other . At the end of each month , research nurses alternated intervention status from on to off or vice versa . Patients with wrist fractures were treated , as appropriate , by emergency department physicians and then approached by research nurses or orthopedic technicians for enrollment in the study before discharge home . We obtained informed consent from each patient , and all data were maintained outside the emergency departments in a central ized secure file system . The University of Alberta Health Research Ethics Board approved the study . Intervention We design ed an intervention to overcome the many barriers that exist for primary care physicians who are trying to adopt evidence -based treatments for their patients with osteoporosis . Each of the 3 components of the intervention had published evidence of effectiveness ( 22 - 24 ) . Physician Reminders A reminder was generated for each patient and faxed to the primary care physician of record . The reminder notified physicians that their patient had recently been seen and treated in the emergency department for a wrist fracture and reminded them that their patient was now considered to be at increased risk for osteoporosis . Generating and sending the personalized and patient-specific reminder took about 6 minutes for each patient . Treatment Guidelines Generated and Endorsed by Opinion Leaders As part of the reminder , we provided brief evidence -based treatment recommendations . These guidelines were design ed to fit on the same page and emphasized 3 points : 1 ) The patient is at very high risk for osteoporosis and needs a bone mineral density measurement if one has not been performed in the past year ; 2 ) without treatment , the patient may be at increased risk for another fracture within the year ; and 3 ) bisphosphonate treatment will reduce the patient 's risk for fracture by about 50 % . Bisphosphonate alternatives ( for example , calcitonin , raloxifene , and hormone therapy ) were mentioned as second-line approved treatments because , at the time of study design , only the bisphosphonates had been demonstrated to prevent both vertebral and nonvertebral fractures . Using previously vali date d methods ( 25 , 26 ) , we recruited 5 osteoporosis opinion leaders who had been nominated by local primary care providers . The opinion leaders helped develop and then endorsed the guidelines by attaching their names and signatures . Patient Education We provided patients in the intervention group with a tailored , single-page summary of osteoporosis information that mirrored the physician material s described in the preceding paragraph . We reinforced these written material s with a brief telephone counseling session that took place within 1 week of the fracture . This counseling ( approximately 4 minutes per session ) reiterated the content of the written material s and encouraged patients to seek further information and counseling from their primary care physician . We did not provide intervention patients with any written material s or counseling regarding fall prevention or home safety . Control Patients ( Usual Care ) On the basis of surveys and in-depth interviews with emergency department physicians in Canada and the United States , the current st and ard of care for patients treated for a wrist fracture usually consists of 1 ) notification to the primary care physician of record that the patient was seen and treated and 2 ) information on follow-up plans . We ensured that such notifications occurred for all control patients . In addition , we enhanced usual care by ensuring that control patients received educational material s and telephone counseling regarding fall prevention and home safety . During the call , patients were encouraged to visit their primary care physician for more detailed advice and a medication review . They did not receive any counseling or educational material s about osteoporosis . Thus , control patients received the same amount of attention and care as the intervention patients . After the main study was completed , all control patients were crossed over to the osteoporosis intervention , and all intervention patients were provided with counseling regarding fall prevention and home safety . Outcomes and Measurements The primary study outcome was",
"BACKGROUND Treatment of osteoporosis following a hip fracture has been notoriously poor . Many efforts have been made to improve treatment rates . The purpose of this study was to determine whether a perioperative inpatient intervention program , involving patient education and providing a list of questions for the primary care physician , increased the percentage of patients in whom osteoporosis was addressed following a hip fracture . METHODS A prospect i ve , r and omized trial involving eighty patients who had been admitted to an academic medical center with a low-energy hip fracture was conducted . During their hospitalization , the study group patients were engaged in a fifteen-minute discussion regarding the association between osteoporosis and hip fractures , the efficacy of dual-energy x-ray absorptiometry scans in the diagnosis of osteoporosis and of bisphosphonates in its treatment , and the importance of medical follow-up for osteoporosis management . These patients were also provided with five questions regarding osteoporosis treatment to be given to their primary medical physician , and they were reminded about the questions during a follow-up telephone call six weeks later . The patients in the control group received a brochure describing methods for preventing falls . Both groups were contacted by telephone at six months after discharge to determine whether osteoporosis had been addressed . Positive indicators of intervention included assessment of bone mineral density with dual-energy x-ray absorptiometry and initiation of antiresorptive therapy . RESULTS The average age in each group was eighty-two years , and 78 % of the patients were female . Four patients in each group did not survive through the six-month follow-up period and were excluded from the trial . Fifteen ( 42 % ) of the thirty-six patients who had been r and omized to the study group , compared with only seven ( 19 % ) of the thirty-six patients in the control group , had their osteoporosis addressed by their primary physician . This difference between the groups was significant ( p = 0.036 ) . CONCLUSIONS Patients who were provided with information and questions for their primary care physician about osteoporosis were more likely to receive appropriate therapeutic intervention than were patients who had not received the information and questions . Orthopaedic surgeons have a unique opportunity to improve the rate of osteoporosis treatment in the perioperative period following a hip fracture by educating patients and directing them toward channels for long-term osteoporosis management",
"Background : Older patients who experience a fragility fracture are at high risk of future fractures but are rarely tested or treated for osteoporosis . We developed a multifaceted intervention directed at older patients with wrist fractures ( in the form of telephone-based education ) and their physicians ( in the form of guidelines endorsed by opinion leaders , supported by reminders ) to improve the quality of osteoporosis care . Methods : In a r and omized controlled trial with blinded ascertainment of outcomes , we compared our intervention with usual care ( provision of printed educational material s to patients ) . Eligible patients were those older than 50 years of age who had experienced a wrist fracture and were seen in emergency departments and fracture clinics ; we excluded those who were already being treated for osteoporosis . The primary outcome was bisphosphonate treatment within 6 months after the fracture . Secondary outcomes included bone mineral density testing , “ appropriate care ” ( consisting of bone mineral density testing with treatment if bone mass was low ) and quality of life . Results : We screened 795 patients for eligibility and r and omly assigned 272 to the intervention ( 137 patients ) or control ( 135 patients ) group . The median age was 60 years ; 210 ( 77 % ) of the subjects were women , and 130 ( 48 % ) reported a previous fracture as an adult . Six months after the fracture , 30 ( 22 % ) of the intervention patients , as compared with 10 ( 7 % ) of the control patients , were receiving bisphosphonate therapy for osteoporosis ( adjusted relative risk [ RR ] 2.6 , 95 % confidence interval [ CI ] 1.3–5.1 , p = 0.008 ) . Intervention patients were more likely than control patients to undergo bone mineral density testing ( 71/137 [ 52 % ] v. 24/135 [ 18 % ] ; adjusted RR 2.8 , 95 % CI 1.9–4.2 , p receive appropriate care ( 52/137 [ 38 % ] v. 15/135 [ 11 % ] ; adjusted RR 3.1 , 95 % CI 1.8–5.3 , p died , and 4 others experienced recurrent fracture . Interpretation : A multifaceted intervention directed at high-risk patients and their physicians substantially increased rates of testing and treatment for osteoporosis . Nevertheless , more than half of the patients in the intervention group were not receiving appropriate care 6 months after their fracture , which suggests that additional strategies should be explored . ( Clinical Trials.gov trial register no. NCT00152321 .",
"BACKGROUND Patients who survive hip fracture are at high risk of recurrent fractures , but rates of osteoporosis treatment 1 year after sustaining a fracture are less than 10 % to 20 % . We have developed an osteoporosis case manager intervention . The case manager educated patients , arranged bone mineral density tests , provided prescriptions , and communicated with primary care physicians . The intervention was compared with usual care in a r and omized controlled trial . METHODS We recruited from all hospitals that participate in the Capital Health system ( Alberta , Canada ) , including patients 50 years or older who had sustained a hip fracture and excluding those who were receiving osteoporosis treatment or who lived in a long-term care facility . Primary outcome was bisphosphonate therapy 6 months after fracture ; secondary outcomes included bone mineral density testing , appropriate care ( bone mineral density testing and treatment if bone mass was low ) , and intervention costs . RESULTS We screened 2219 patients and allocated 220 , as follows : 110 to the intervention group and 110 to the control group . Median age was 74 years , 60 % were women , and 37 % reported having had previous fractures . Six months after hip fracture , 56 patients in the intervention group ( 51 % ) were receiving bisphosphonate therapy compared with 24 patients in the control group ( 22 % ) ( adjusted odds ratio , 4.7 ; 95 % confidence interval , 2.4 - 8.9 ; P Bone mineral density tests were performed in 88 patients in the intervention group ( 80 % ) vs 32 patients in the control group ( 29 % ) ( P bone mineral density testing , 25 ( 21 % ) had normal bone mass . Patients in the intervention group were more likely to receive appropriate care than were patients in the control group ( 67 % vs 26 % ; P intervention cost was $ 50.00 per patient . CONCLUSION For a modest cost , a case manager was able to substantially increase rates of osteoporosis treatment in a vulnerable elderly population at high risk of future fractures",
"Recognizing Osteoporosis and its Consequences in Quebec ( ROCQ ) is an ongoing patient health-management programme aim ed at evaluating the diagnostic and treatment care gaps for osteoporosis following a fragility fracture , and subsequently initiating and measuring interventions to decrease these gaps in women 50 years of age and over . Hospitals servicing approximately half of the population of the Province of Quebec ( Canada ) are participating in the ROCQ programme . Women with fragility and traumatic fractures are approached during their visit to a cast or outpatient clinic and are subsequently contacted by telephone 0 to 16 weeks after their fracture ( phase 1 ) . During the first phone contact , they are invited to answer a question naire aim ed at identifying the specific circumstances of their fracture and asked to participate in an observational study that could last up to 18 months . Based on this initial question naire , patients are classified as having either experienced a fragility or traumatic fracture . During the first phone contact , there is no reference about the possible association between the fracture and osteoporosis and no investigation or intervention is proposed . Six to eight months after the fracture event ( phase 2 ) , women are again contacted by phone to complete a question naire that evaluates the diagnostic and treatment rates for osteoporosis . At this phase of the programme , women with fragility fractures are r and omized to one of the three following intervention groups : 1 ) Educational Video Group , 2 ) Documentation Group and 3 ) Control Group . Participants are contacted 12 to 14 months after the intervention ( phase 3 ) to evaluate the efficacy of the interventions on the diagnosis and treatment rates of osteoporosis . All participants with fragility or traumatic fractures who consent will be followed for 20 years using data from the Québec Ministry of Health data base to measure the association between the index fracture and future fracture risk",
"This article reports a controlled trial to investigate the effectiveness of patient education and a physician alerting system in altering secondary osteoporosis prevention after a low-trauma ( fragility ) wrist fracture and to record the current rate of osteoporosis investigation following such fractures . Fifty-one women and men aged 50 years or older with a low-trauma wrist fracture were identified ( 41 women and 10 men ; mean age [ 95 % CI ] , 71.51 [ 67.31 - 74.81 ] ) . The intervention group received a four-part intervention aim ed at both the patient and the family physician in addition to the usual care for the fracture . The control group only received usual care for the fracture . Data were collected for both groups at six weeks and six months . Results indicate that 92 % of the intervention subjects were investigated for osteoporosis , compared with the usual-care group , in which only 23 % were investigated . Early osteoporosis intervention has the potential to limit disease impact , and h and therapists can play a key role in early identification of osteoporosis",
"OBJECTIVE We previously demonstrated that a case manager intervention improved osteoporosis ( OP ) treatment within 6 months of hip fracture compared with usual care . The second phase of the r and omized trial compared a less intensive intervention , facilitated bone mineral density ( BMD ) testing , with usual care and the case manager intervention . METHODS We initially r and omized 220 hip fracture patients to either an OP case manager intervention or usual care . After completing the original trial at 6 months postfracture , usual care patients were reallocated to facilitated BMD testing ; BMD tests were arranged and results sent to primary care physicians . Main outcomes ( bisphosphonate treatment , BMD tests , receipt of appropriate care ) were reascertained 1 year following hip fracture and compared with outcomes achieved by the OP case manager intervention and usual care . RESULTS Compared with usual care , facilitated BMD testing increased testing from 29 % to 68 % ( P bisphosphonate use from 22 % to 38 % ( P of appropriate care from 26 % to 45 % ( P OP case manager intervention led to significantly higher bisphosphonate use ( 54 % versus 38 % ; P = 0.03 ) , receipt of appropriate care ( 71 % versus 45 % ; P BMD testing ( 80 % versus 68 % ; P = 0.06 ) than usual care followed by facilitated BMD testing . CONCLUSION Compared with usual care , 2 different inexpensive interventions result ed in significant increases in appropriate management of OP after hip fracture . The magnitude of improvements achieved was directly related to the intensity of the interventions"
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411799ca-06ff-11f0-808a-c43d1ab1c353
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OBJECTIVE Sedentary behaviour ( SB ) has distinct deleterious health outcomes , yet there is no consensus on best practice for measurement . This study aim ed to identify the optimal self-report tool for population surveillance of SB , using a systematic framework . DESIGN A framework , TAxonomy of Self-reported Sedentary behaviour Tools ( TASST ) , consisting of four domains ( type of assessment , recall period , temporal unit and assessment period ) , was developed based on a systematic inventory of existing tools . The inventory was achieved through a systematic review of studies reporting SB and tracing back to the original description . A systematic review of the accuracy and sensitivity to change of these tools was then mapped against TASST domains . DATA SOURCES Systematic search es were conducted via EBSCO , reference lists and expert opinion . ELIGIBILITY CRITERIA FOR SELECTING STUDIES The inventory included tools measuring SB in adults that could be self-completed at one sitting , and excluded tools measuring SB in specific population s or context s. The systematic review included studies reporting on the accuracy against an objective measure of SB and /or sensitivity to change of a tool in the inventory . RESULTS The systematic review initially identified 32 distinct tools ( 141 questions ) , which were used to develop the TASST framework . Twenty-two studies evaluated accuracy and /or sensitivity to change representing only eight taxa . Assessing SB as a sum of behaviours and using a previous day recall were the most promising features of existing tools . Accuracy was poor for all existing tools , with underestimation and overestimation of SB . There was a lack of evidence about sensitivity to change . CONCLUSIONS Despite the limited evidence , mapping existing SB tools onto the TASST framework has enabled informed recommendations to be made about the most promising features for a surveillance tool , identified aspects on which future research and development of SB surveillance tools should focus . TRIAL REGISTRATION NUMBER International prospect i ve register of systematic review s (PROPSPERO)/CRD42014009851
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"Purpose Imprecise measurement of physical activity variables might attenuate estimates of the beneficial effects of activity on health-related outcomes . We aim ed to compare the cardiometabolic risk factor dose-response relationships for physical activity and sedentary behaviour between accelerometer- and question naire-based activity measures . Methods Physical activity and sedentary behaviour were assessed in 317 adults by 7-day accelerometry and International Physical Activity Question naire ( IPAQ ) . Fasting blood was taken to determine insulin , glucose , triglyceride and total , LDL and HDL cholesterol concentrations and homeostasis model-estimated insulin resistance ( HOMAIR ) . Waist circumference , BMI , body fat percentage and blood pressure were also measured . Results For both accelerometer-derived sedentary time ( sedentary behaviour was associated with increased risk ( all p≤0.01 ) . However , for HOMAIR and insulin the regression coefficients were > 50 % lower for the IPAQ-reported compared to the accelerometer-derived measure ( p moderate-to-vigorous physical activity ( MVPA ) and risk factors were less strong than those observed for sedentary behaviours , but significant negative relationships were observed for both accelerometer and IPAQ MVPA measures with glucose , and insulin and HOMAIR values ( all p with triglyceride , total cholesterol and LDL cholesterol concentrations , BMI , waist circumference and percentage body fat , and a positive relationship was evident with HDL cholesterol ( p = 0.0002 ) . Regression coefficients for HOMAIR , insulin and triglyceride were 43–50 % lower for the IPAQ-reported compared to the accelerometer-derived MVPA measure ( all p≤0.01 ) . Conclusion Using the IPAQ to determine sitting time and MVPA reveals some , but not all , relationships between these activity measures and metabolic and vascular disease risk factors . Using this self-report method to quantify activity can therefore underestimate the strength of some relationships with risk factors",
"Supplemental digital content is available in the text .",
"OBJECTIVES : To investigate the effect of physical activity on the association between television viewing and overweight ( body mass index ( BMI ) ≥25 kg/m2 ) . DESIGN : Cross-sectional study administered by interview to adults r and omly selected from the electronic white pages . SUBJECTS : 3392 adults ( 64 % response rate ) from a representative population sample in the State of New South Wales , Australia . MEASUREMENTS : Self-reported height and weight , two-week leisure-time physical activity recall , one-week average television viewing recall . RESULTS : BMI and physical activity patterns were both associated with hours of television watched . Compared to those participants who reported watching less than one hour of television per day , those watching 1 to 2.5 hours were 93 % more likely to be overweight ( BMI ≥25 kg/m2 ) , those watching 2.5 to 4 hours were 183 % more likely to be overweight , those watching more than 4 hours per day were four times more likely to be overweight . Physical activity was not directly associated with being overweight , but an interaction between activity and television watching was present . Respondents in the low , moderate and high physical activity categories who reported watching more than 4 hours of television per day were twice as likely to be overweight compared to those who watched less than one hour of television per day , irrespective of physical activity participation . CONCLUSIONS : With approximately half the Australian adult population overweight or obese , these findings indicate that public health strategies to reduce overweight and prevent weight gain may need to focus on reducing sedentary behaviours such as television viewing in addition to increasing physical activity ",
"PURPOSE Although moderate-to-vigorous physical activity is related to premature mortality , the relationship between sedentary behaviors and mortality has not been fully explored and may represent a different paradigm than that associated with lack of exercise . We prospect ively examined sitting time and mortality in a representative sample of 17,013 Canadians 18 - 90 yr of age . METHODS Evaluation of daily sitting time ( almost none of the time , one fourth of the time , half of the time , three fourths of the time , almost all of the time ) , leisure time physical activity , smoking status , and alcohol consumption was conducted at baseline . Participants were followed prospect ively for an average of 12.0 yr for the ascertainment of mortality status . RESULTS There were 1832 deaths ( 759 of cardiovascular disease ( CVD ) and 547 of cancer ) during 204,732 person-yr of follow-up . After adjustment for potential confounders , there was a progressively higher risk of mortality across higher levels of sitting time from all causes ( hazard ratios ( HR ) : 1.00 , 1.00 , 1.11 , 1.36 , 1.54 ; P for trend Age-adjusted all-cause mortality rates per 10,000 person-yr of follow-up were 87 , 86 , 105 , 130 , and 161 ( P for trend sitting time and mortality from all causes and CVD , independent of leisure time physical activity . In addition to the promotion of moderate-to-vigorous physical activity and a healthy weight , physicians should discourage sitting for extended periods",
"Background Sarcopenia is associated with loss of independence and ill-health in the elderly although the causes remain poorly understood . We examined the association between two screen-based leisure time sedentary activities ( daily TV viewing time and internet use ) and muscle strength . Methods and Results We studied 6228 men and women ( aged 64.9±9.1 yrs ) from wave 4 ( 2008 - 09 ) of the English Longitudinal Study of Ageing , a prospect i ve study of community dwelling older adults . Muscle strength was assessed by a h and grip test and the time required to complete five chair rises . TV viewing and internet usage were inversely associated with one another . Participants viewing TV ≥6hrs/d had lower grip strength ( Men , B = −1.20 kg , 95 % CI , −2.26 , −0.14 ; Women , −0.75 kg , 95 % CI , −1.48 , −0.03 ) in comparison to contrast , internet use was associated with higher grip strength ( Men , B = 2.43 kg , 95 % CI , 1.74 , 3.12 ; Women , 0.76 kg , 95 % CI , 0.32 , 1.20 ) . These associations persisted after mutual adjustment for both types of sedentary behaviour . Conclusions In older adults , the association between sedentary activities and physical function is context specific ( TV viewing vs. computer use ) . Adverse effects of TV viewing might reflect the prolonged sedentary nature of this behavior",
"Background Evidence on the relation between leisure-time physical activity ( LTPA ) and health-related quality of life ( HRQoL ) in older adults is based primarily on clinical trials of physical exercise programs in institutionalized persons and on cross-sectional studies of community-dwelling persons . Moreover , there is no evidence on whether leisure-time sedentary behavior ( LTSB ) is associated with HRQoL independently of LTPA . This study examined the longitudinal association between LTPA , LTSB , and HRQoL in older community-dwelling adults in Spain . Methods Prospect i ve cohort study of 1,097 persons aged 62 and over . In 2003 LTPA in MET-hr/week was measured with a vali date d question naire , and LTSB was estimated by the number of sitting hours per week . In 2009 HRQoL was measured with the SF-36 question naire . Analyses were done with linear regression and adjusted for the main confounders . Results Compared with those who did no LTPA , subjects in the upper quartile of LTPA had better scores on the SF-36 scales of physical functioning ( β 5.65 ; 95 % confidence interval [ CI ] 1.32 - 9.98 ; p linear trend ( β 7.38 ; 95 % CI 0.16 - 14.93 ; p linear trend ( β 6.92 ; 95 % CI 1.86 - 11.98 ; p linear trend ( β 5.09 ; 95 % CI 0.76 - 9.41 ; p linear trend ( β 7.83 ; 95 % CI 2.89 - 12.75 ; p linear trend ( β 8.59 ; 95 % CI 1.97 - 15.21 ; p linear trend ( β 4.20 ; 95 % CI 0.26 - 8.13 ; p linear trend the number of sitting hours showed a gradual and inverse relation with the scores on most of the SF-36 scales , which was also clinical ly relevant . Conclusions Greater LTPA and less LTSB were independently associated with better long-term HRQoL in older adults",
"BACKGROUND Physical activity is an important lifestyle which is often poorly assessed in epidemiological studies . The European Prospect i ve Investigation into Cancer Study -Norfolk cohort ( EPIC-Norfolk ) , a large population -based cohort study , has developed a comprehensive question naire to assess activity in different domains of life aim ed at assessing total energy expenditure . We report the repeatability of this instrument and its validity against repeated objective measures of fitness and energy expenditure undertaken throughout the time frame of reference of the question naire . METHODS The validity of the instrument was measured in 173 individuals r and omly selected from a continuing population -based cohort study . Energy expenditure was assessed by four separate episodes of 4-day heart-rate monitoring , a method previously vali date d against whole body calorimetry and doubly-labelled water . Cardio-respiratory fitness was assessed by four repeated measures of sub-maximum oxygen uptake . At the end of the 12-month period , participants completed the physical activity question naire that assesses past-year activity at home , work and in recreation . Repeatability was assessed in a separate group of 399 r and omly selected participants in EPIC who completed the physical activity question naire twice with a 3-month interval . RESULTS The age- and sex-adjusted correlation between the objective measure of daytime energy expenditure and the sum of recreational and occupational reported physical activity ( in MET h per week ) was 0.28 ( P time spent in vigorous activity was correlated with cardio-respiratory fitness ( 0.16 , P energy expenditure was more than five times basal ( 0.17 , P repeatability of the sum of recreational and occupational reported activity was high , r = 0.73 . CONCLUSIONS The indices of physical activity derived from this question naire have levels of validity and repeatability comparable to other physical activity instruments that are used in large epidemiological studies and which have undergone such intense development and testing",
"The obesity epidemic is attributed in part to reduced physical activity . Evidence supports that reducing time spent sitting , regardless of activity , may improve the metabolic consequences of obesity . Analyses were conducted in a large prospect i ve study of US adults enrolled by the American Cancer Society to examine leisure time spent sitting and physical activity in relation to mortality . Time spent sitting and physical activity were queried by question naire on 53,440 men and 69,776 women who were disease free at enrollment . The authors identified 11,307 deaths in men and 7,923 deaths in women during the 14-year follow-up . After adjustment for smoking , body mass index , and other factors , time spent sitting ( > or = 6 vs. mortality in both women ( relative risk = 1.34 , 95 % confidence interval ( CI ) : 1.25 , 1.44 ) and men ( relative risk = 1.17 , 95 % CI : 1.11 , 1.24 ) . Relative risks for sitting ( > or = 6 hours/day ) and physical activity ( cardiovascular disease mortality . The time spent sitting was independently associated with total mortality , regardless of physical activity level . Public health messages should include both being physically active and reducing time spent sitting",
"Background There is currently no vali date d question naire available to assess total sedentary time in older adults . Most studies only used TV viewing time as an indicator of sedentary time . The first aim of our study was to investigate the self-reported time spent by older persons on a set of sedentary activities , and to compare this with objective sedentary time measured by accelerometry . The second aim was to determine what set of self-reported sedentary activities should be used to validly rank people ’s total sedentary time . Finally we tested the reliability of our newly developed question naire using the best performing set of sedentary activities . Methods The study sample included 83 men and women aged 65–92 y , a r and om sample of Longitudinal Aging Study Amsterdam participants , who completed a question naire including ten sedentary activities and wore an Actigraph GT3X accelerometer for 8 days . Spearman correlation coefficients were calculated to examine the association between self-reported time and objective sedentary time . The test-retest reliability was calculated using the intraclass correlation coefficient ( ICC ) . Results Mean total self-reported sedentary time was 10.4 ( SD 3.5 ) h/d and was not significantly different from mean total objective sedentary time ( 10.2 ( 1.2 ) h/d , p = 0.63 ) . Total self-reported sedentary time on an average day ( sum of ten activities ) correlated moderately ( Spearman ’s r = 0.35 , p total objective sedentary time . The correlation improved when using the sum of six activities ( r = 0.46 , p The test-retest reliability of the sum of six sedentary activities was 0.71 ( 95 % CI 0.57 - 0.81 ) . Conclusions A question naire including six sedentary activities was moderately associated with accelerometry-derived sedentary time and can be used to reliably rank sedentary time in older persons",
"PURPOSE Past-day recall rather than recall of past week or a usual/typical day may improve the validity of self-reported sedentary time measures . This study examined the test-retest reliability , criterion validity , and responsiveness of the seven-item question naire , Past-day Adults ' Sedentary Time ( PAST ) . METHODS Participants ( breast cancer survivors , n = 90 , age = 33 - 75 yr , body mass index = 25 - 40 kg·m ) in a 6-month r and omized controlled trial of a lifestyle-based weight loss intervention completed the interviewer-administered PAST question naire about time spent sitting/lying on the previous day for work , transport , television viewing , nonwork computer use , reading , hobbies , and other purpose s ( summed for total sedentary time ) . The instrument was administered at baseline , 7 d later for test-retest reliability ( n = 86 ) , and at follow-up . ActivPAL3-assessed sit/lie time in bouts of ≥5 min during waking hours on the recall day was used as the validity criterion measure at both baseline ( n = 72 ) and follow-up ( n = 68 ) . Analyses included intraclass correlation coefficients , Pearson 's correlations ( r ) , and Bl and -Altman plots and responsiveness index . RESULTS The PAST had fair to good test-retest reliability ( intraclass correlation coefficient = 0.50 , 95 % confidence interval [ CI ] = 0.32 - 0.64 ) . At baseline , the correlation between PAST and activPAL sit/lie time was r = 0.57 ( 95 % CI = 0.39 - 0.71 ) . The mean difference between PAST at baseline and retest was -25 min ( 5.2 % ) , 95 % limits of agreement = -5.9 to 5.0 h , and the activPAL sit/lie time was -9 min ( 1.8 % ) , 95 % limits of agreement = -4.9 to 4.6 h. The PAST showed small but significant responsiveness ( -0.44 , 95 % CI = -0.92 to -0.04 ) ; responsiveness of activPAL sit/lie time was not significant . CONCLUSION The PAST question naire provided an easy-to-administer measure of sedentary time in this sample . Validity and reliability findings compare favorably with other sedentary time question naires . Past-day recall of sedentary time shows promise for use in future health behavior , epidemiological , and population surveillance studies",
"We assessed the validity of the Physical Activity Scale for the Elderly ( PASE ) in a sample of sedentary adults ( 56 men , 134 women , mean age + /- [ SD ] 66.5+/-5.3 years ) who volunteered to participate in a r and omized controlled trial on the effect of aerobic conditioning on psychological function . Construct validity was established by correlating PASE scores with physiologic and performance characteristics : peak oxygen uptake , resting heart rate and blood pressure , percent body fat , and balance . The mean PASE scores were higher in men than in women ( men = 145.8+/-78.0 ; women = 123.9+/-66.3 , P PASE scores were also significantly higher in those who did not report a chronic health condition ( cardiovascular disease , hypertension , cancer , or recent surgery ) . PASE scores were significantly associated ( P peak oxygen uptake ( r = 0.20 ) , systolic blood pressure ( r = -0.18 ) and balance score ( r = 0.20 ) . No significant associations of PASE score and diastolic blood pressure , resting heart rate , or percent body fat were noted . These results provide additional evidence for the validity of the PASE as a measure of physical activity suitable for use in epidemiology studies on the association of physical activity , health , and physical function in older individuals",
"BACKGROUND The reproducibility and validity of self-administered question naires on physical activity and inactivity were examined in a r and om ( representative ) sample of the Nurses ' Health Study II cohort and a r and om sample of African-American women in that cohort . METHODS Repeat question naires were administered 2 years apart . Past-week activity recalls and 7-day activity diaries were the referent methods ; these instruments were sent to participants four times over a 1-year period . RESULTS The 2-year test-retest correlation for activity was 0.59 for the representative sample ( n = 147 ) and 0.39 for the African-American sample ( n = 84 ) . Correlations between activity reported on recalls and that reported on question naire were 0.79 and 0.83 for the representative and African-American sample s , respectively . Correlations between activity reported in diaries and that reported on question naire were 0.62 and 0.59 , respectively . Test-retest coefficients for inactivity were 0.52 and 0.55 , respectively . Correlations between inactivity reported in diaries and that reported on question naire were 0.41 and 0.44 , respectively . CONCLUSION The simple , short question naires on activity and inactivity used in the Nurses ' Health Study II are reasonably valid measures for epidemiological research"
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41179a06-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND Geriatric assessment is a multidisciplinary diagnostic process that evaluates the older adult 's medical , psychological , social , and functional capacity . No systematic review of the use of geriatric assessment in oncology has been conducted . The goals of this systematic review were : 1 ) to provide an overview of all geriatric assessment instruments used in the oncology setting ; 2 ) to examine the feasibility and psychometric properties of those instruments ; and 3 ) to systematic ally evaluate the effectiveness of geriatric assessment in predicting or modifying outcomes ( including the impact on treatment decision making , toxicity of treatment , and mortality ) . METHODS We search ed Medline , Embase , Psychinfo , Cinahl , and the Cochrane Library for articles published in English , French , Dutch , or German between January 1 , 1996 , and November 16 , 2010 , reporting on cross-sectional , longitudinal , interventional , or observational studies that assessed the feasibility or effectiveness of geriatric assessment instruments . The quality of articles was evaluated using relevant quality assessment frameworks . RESULTS We identified 83 articles that reported on 73 studies . The quality of most studies was poor to moderate . Eleven studies examined psychometric properties or diagnostic accuracy of the geriatric assessment instruments used . The assessment generally took 10 - 45 min . Geriatric assessment was most often completed to describe a patient 's health and functional status . Specific domains of geriatric assessment were associated with treatment toxicity in 6 of 9 studies and with mortality in 8 of 16 studies . Of the four studies that examined the impact of geriatric assessment on the cancer treatment decision , two found that geriatric assessment impacted 40%-50 % of treatment decisions . CONCLUSION Geriatric assessment in the oncology setting is feasible , and some domains are associated with adverse outcomes . However , there is limited evidence that geriatric assessment impacted treatment decision making . Further research examining the effectiveness of geriatric assessment on treatment decisions and outcomes is needed
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[
"Objective : The study aim ed at evaluating the activity and toxicity of gemcitabine monochemotherapy in a unselected series of elderly patients with advanced bladder cancer . The secondary objectives were to establish whether there is a correlation between treatment and Comprehensive Geriatric Assessment ( CGA ) and , in addition , to determine overall patient survival . Methods : Treatment consisted of six courses of chemotherapy with gemcitabine at a dosage of 1,200 mg/m2 on days 1 and 8 , every 21 days . CGA , as described by Gruppo Italiano di Oncologia Geriatrica , was assessed for evaluating the functional status of patients before , during , and after treatment . Results : Twenty-five patients were enrolled ( M/F 22/3 ) , 22 of these were evaluable for response and 23 for toxicity . Characteristics of patients : median age 76 years ( range 71–87 ) ; ECOG performance status ( PS ) 1 in 12 patients and 2 in 13 patients ; clinical stage III in 6 patients and IV in 19 patients . At the end of the therapy the parameters of CGA improved in 4 cases ( 17 % ) , remained unchanged in 17 cases ( 74 % ) and worsened only in 2 cases ( 9 % ) . Two patients were not evaluable . Response evaluation showed 3 ( 13.5 % ) complete responses ( CRs ) and 7 ( 32 % ) partial responses ( PRs ) , for an overall response rate of 45.5 % [ 95 % confidence interval ( CI ) , 24.3–65.7 % ] . Three ( 13.5 % ) patients had stable disease ( SD ) and 9 ( 41 % ) disease progression ( DP ) . Median overall survival was 8 months and median time to progression was 5 months . Treatment was generally well tolerated , with 1 patient having grade 3 gastrointestinal toxicity and 3 having grade 4 neutropenia . Conclusions : We conclude that gemcitabine can be safely administered in monochemotherapy , is effective and does not worsen the functional status of elderly patients with advanced bladder cancer",
" Abstract Seventeen elderly patients with advanced progressive non small cell lung cancer ( NSCLC ) were treated with oral etoposide at the daily dose of 100 mg for 14 days every 3 - 4 weeks with pharmacokinetic monitoring . One partial response and 6 stabilizations were documented with a median overall duration of 13 weeks ( range 8 - 32 ) . The median survival was 24 weeks with an apparent advantage for non-progressive patients ( 40 weeks vs. 18 weeks ) . The treatment was well tolerated especially by those patients without concomitant illness , suggesting the crucial role of a careful selection of the geriatric population . Toxicity was not related to the etoposide plasma level , but was clearly dependent on comorbidity . A geriatric assessment rather than chronological age therefore appears to be more reliable in the selection of elderly patients for clinical trials . The easy self-management , favorable toxicity profile and synergy with other compounds makes oral etoposide suitable for further clinical -pharmacological studies in elderly patients",
"OBJECTIVES To test the hypothesis that early and rogen deprivation therapy ( ADT ) has no proven survival advantage in older men with biochemical recurrence ( BCR ) of prostate cancer ( PCa ) , and it may contribute to geriatric frailty . METHODS We conducted a case-control study of men aged 60 + years with BCR on ADT ( n = 63 ) vs PCa survivors without recurrence ( n = 71 ) . Frailty prevalence , \" obese \" frailty , Short Physical Performance Battery ( SPPB ) scores , and falls were compared . An exploratory analysis of frailty biomarkers ( C-reactive protein , erythrocyte sedimentation rate , hemoglobin , albumin , and total cholesterol ) was performed . Summary statistics and univariate and multivariate regression analyses were conducted . RESULTS More patients on ADT were obese ( body mass index > 30 ; 46.2 % vs 20.6 % ; P = .03 ) . There were no statistical differences in SPPB ( P = .41 ) or frailty ( P = .20 ) . Using a proposed \" obese \" frailty criteria , 8.7 % in ADT group were frail and 56.5 % were \" prefrail , \" compared with 2.9 % and 48.8 % of controls ( P = .02 ) . Falls in the last year were higher in the ADT group ( 14.3 % vs 2.8 % ; P = .02 ) . In analyses controlling for age , clinical characteristics , and comorbidities , the ADT group trended toward significance for \" obese \" frailty ( P = .14 ) and falls ( OR = 4.74 , P = .11 ) . Comorbidity significantly increased the likelihood of \" obese \" frailty ( P = .01 ) and falls ( OR 2.02 , P = .01 ) . CONCLUSIONS Men with BCR on ADT are frailer using proposed modified \" obese \" frailty criteria . They may have lower performance status and more falls . A larger , prospect i ve trial is necessary to establish a causal link between ADT use and progression of frailty and disability",
"BACKGROUND Development of a geriatric screening tool is necessary to identify elderly cancer patients who would benefit from comprehensive geriatric assessment ( CGA ) . We develop and evaluate the G-8 screening tool against various reference tests . PATIENTS AND METHODS Analyses were based on 364 cancer patients aged>70 years scheduled to receive first-line chemotherapy included in a multicenter prospect i ve study . The G-8 consists of seven items from the Mini Nutritional Assessment ( MNA ) question naire and age . Our primary reference test is based on a set of seven CGA scales : Activities Daily Living ( ADL ) , Instrumental ADL , MNA , Mini-Mental State Exam , Geriatric Depression Scale , Cumulative Illness Rating Scale-Geriatrics , and Timed Get Up and Go . We considered the presence of at least one question naire with an impaired score as an abnormal reference exam . Additional reference exams are also discussed . RESULTS The prevalence of being at risk varied from 60 % to 94 % according to the various definitions of the reference test . When considering the primary reference test , a cut-off value of 14 for the G-8 tool provided a good sensitivity estimate ( 85 % ) without deteriorating the specificity excessively ( 65 % ) . CONCLUSION The G-8 shows good screening properties for identifying elderly cancer patients who could benefit from CGA",
"This prospect i ve cohort study of consecutive elderly cancer patients was undertaken to evaluate the role of the multidimensional geriatric assessment ( MGA ) as an aid in treatment decision-making . A total of 571 cancer patients ( aged > or = 70 ) were enrolled during 6-year ( 1999 - 2005 ) . All underwent MGA as part of the first evaluation . In multivariate analysis , the probability of receiving active , instead of palliative , treatment was negatively associated with increasing age ( odds ratio=0.69 every 5 years , p=0.005 ) , living alone ( OR=0.54 , p=0.031 ) , dependence in activities of daily living ( ADL score > 0 , OR=0.41 , p=0.003 ) and a low body-mass index ( BMI ) ( OR=0.51 , p=0.061 ) ; while a positive association emerged for instrumental activities of daily living ( IADL ) score ( OR=1.12 per point , p=0.019 ) . Our data suggest that MGA , in addition to age , is a useful tool in clinical practice for deciding cancer treatment in elderly patients , with a major independent role played by living alone , ADL , IADL and BMI",
"Background Growing evidence suggests that a comprehensive geriatric assessment ( CGA ) in older patients with cancer can detect unsuspected health problems , predict survival , and predict tolerance to chemotherapy . However , studies regarding CGA in cancer patients are scarce in Asia . Methods We prospect ively enrolled 65 elderly cancer patients who were c and i date s of systemic chemotherapy between July 2006 and March 2008 . Baseline CGA data including demographic information , comorbidity , functional status by means of Activities of Daily Living ( ADL ) , and Instrumental Activities of Daily Living ( IADL ) , cognition , psychological state , nutritional status , and medication were collected and analyzed . Quality of life ( QoL ) was assessed by the EORTC question naire QLQ-C30 . Results Of the 65 patients , the median age was 71 years ( range , 65–80 ) , 49 ( 75 % ) were males , and 58 ( 89 % ) had Eastern Cooperative Oncology Group performance status ( ECOG PS ) 0 or 1 . All patients had solid tumor , 74 % received palliative chemotherapy , and 18 % received adjuvant chemotherapy . Twenty-five percent of patients had Charlson ’s comorbidity index score of 2 or more , 23 % were ADL dependent , and 14 % were IADL dependent . Using Mini-Mental Status Exam ( MMSE ) , it was found that 51 % of patients had mild cognitive impairment ( MMSE score 17–24 ) , and 5 % had cognitive impairment ( ≤16 ) . Forty percent of patients had depression by Short form Geriatric Depression Scale ( SGDS ) , 19 % had malnutrition by Mini-Nutritional Assessment ( MNA ) , and 23 % had body mass index ( BMI ) less than 19.4 kg/m2 ( lowest 10 % ) . Global health status/ quality of life ( QoL ) was less than 50 % in 39 % of patients . Frail patients according to the Balducci classification had significantly poor ECOG PS and worse global health status/QoL. Conclusion CGA was feasible and could detect multiple unsuspected health problems including functional impairment and malnutrition in Korean elderly cancer patients receiving chemotherapy ",
"This prospect i ve study evaluated components of a comprehensive geriatric assessment ( CGA ) to identify rates and predictors of falls in older patients . Fall rates and scores on components of the CGA were compared among adults aged 70 or older in three groups : patients with cancer receiving chemotherapy , patients with cancer not receiving chemotherapy , and community-dwelling adults without cancer . Older adults in the chemotherapy group were hypothesized to fall significantly more often than those in the nonchemotherapy group . Among the patients with cancer , scores on the Activities of Daily Living Scale were a significant predictor of falls . The scores were the only domain of the CGA found to be a significant predictor ; therefore , more research is needed to better underst and fall risk assessment among older patients with cancer . Nurses should conduct fall risk assessment s with measures of functional status as included in a CGA",
"INTRODUCTION Demographic aging poses a problem of management in patients over 65 years old with lung cancer ( LC ) . Performance status ( PS ) is an index of global activity that , in part , determines treatment . Geriatric indices allow a multifactorial assessment of the elderly subject . The aim of our study is to evaluate whether PS correlates with the geriatric indices in elderly patients with lung cancer . METHODS In a single centre prospect i ve study the geriatric indices ( ADL , IADL , PINI , MMS ) and the Charlson score ( CS ) were measured before treatment . RESULTS Forty one patients aged 75.7 + /- 6.6 years were included in the study . PS 3 - 4 was found in 15 % of patients and 44 % had stage IV disease . Half of them were ADL dependent and 95 % were IADL dependent . A MMS was found in 29 % and 17 % had a PINI > 20 . The CS was 2.7 + /- 2.1 . There was a correlation between PS and the geriatric indices but no correlation between PS and CS . CONCLUSION PS is significantly correlated with the geriatric indices but is independent of CS . PS appears to be a good parameter for the assessment of global activity in the elderly subject with LC",
"UNLABELLED Studies of comprehensive geriatric assessment ( CGA ) have shown the importance of follow-up for effectiveness , but this has not been tested in an oncology clinic . In this pilot study , we enrolled 15 early breast cancer patients , aged 70 and older . They received a multidisciplinary CGA every 3 months and structured follow-up from the SAOP nurse practitioner , dietitian , social worker , and pharmacist according to risk . Total follow-up was 6 months . Median age of evaluable patients was 79 years ( range 72 - 87 ) . Median number of comorbidities by Cumulative Index Rating Scale-Geriatric ( CIRS-G ) was 5 ( 3 - 9 ) at baseline . Ten patients were at pharmacological risk , five at psychosocial risk , and eight at nutritional risk . Patients presented on average six problems initially , and three new problems during follow-up . The intervention directly influenced oncological treatment in four cases . It ensured continuity/coordination of care in seven cases . Success rate in addressing problems was 87 % . Mean Functional Assessment of Cancer Treatment-Breast ( FACT-B ) scores improved from 110.5 ( S.D. 16.7 ) to 116.3 ( S.D. 16.5 ) ( t=0.025 ) . Function and independence were maintained . CONCLUSIONS Older patients with early breast cancer have a high prevalence of comorbidity . A CGA with follow-up has potential for improving the treatment and prognosis of these patients and is feasible in an academic oncology setting",
"BACKGROUND Geriatric assessment has been suggested as a possibly useful approach in dealing with frail elderly cancer patients . METHODS This was a secondary subset analysis from a r and omized 2 x 2 factorial trial in 11 Department of Veterans Affairs medical centers . Hospitalized , frail patients at least 65 years old , after stabilization of their acute illness , were r and omized to receive care in a geriatric inpatient unit , a geriatric outpatient clinic , both , or neither . The interventions involved core teams that provided geriatric assessment and patient management . We identified 99 patients with a diagnosis of cancer by The International Classification of Diseases , 9th Revision ( ICD-9 ) codes , excluding all nonmelanoma skin cancers . Outcomes collected at discharge , 6 months , and 1 year after r and omization were survival , changes in health-related quality of life ( using the Medical Outcomes Study 36-Item Short-Form general health survey [ SF-36 ] ) , activities of daily living , physical performance , health service utilization , and costs . RESULTS There was no effect on mortality ( 1-year survival 59.6 % ) . The changes in the SF-36 scores from r and omization for emotional limitation , mental health and bodily pain ( also sustained at 1 year ) on the SF-36 were better for geriatric inpatient care cancer patients at discharge . There was no difference in SF-36 scores between geriatric outpatient and usual outpatient care . Days of hospitalization and overall costs were equivalent for the interventions and usual care over the 1-year study . CONCLUSIONS This study suggests that inpatient geriatric assessment and management may be an effective approach to the management of pain and psychological status in the elderly cancer inpatient at no greater length of hospitalization or extra cost than usual care",
"INTRODUCTION Elderly cancer patients are a very heterogeneous population . A comprehensive geriatric assessment ( CGA ) shall help to identify more precisely those patients who are fit , compared to those who are vulnerable or frail , when deciding on chemotherapeutical treatment . METHODS In a prospect i ve trial , 200 cancer patients treated in an out-patient setting were judged by their physician for their fitness for chemotherapy as fit , vulnerable or frail . A CGA was performed thereafter . We determined the feasibility of a CGA in an out-patient setting and the frequency of changes within the different assessment tools and compared physicians ' judgement with the CGA results . RESULTS Physicians judged 64.3 % of their patients as fit , 32.4 % as vulnerable , and 3.2 % as frail . A CGA was completed by 97.5 % of patients and lasted 20min per patients ( range : 9 - 47min ) . 26.5 % of all patients had no deficits in the CGA . The CGA identified a mean of 1.7 problems per patient , 1.3 in patients judged as fit , 2.3 in those judged as vulnerable , and 4.2 in those judged as frail . A CGA is more sensitive in classifying patients as fit compared to vulnerable or frail than physicians ' judgement . CONCLUSION A CGA is feasible and detects more elderly cancer patients as being unfit for chemotherapy than physicians ' judgement . Further trials including disease and treatment related end-points are needed",
"BACKGROUND Carboplatin/paclitaxel every 3 weeks is the st and ard for patients with ovarian cancer , but elderly patients frequently receive modified schedules or single agent chemotherapy to avoid toxicity . A phase II study was conducted to describe tolerability of a weekly schedule of both drugs in elderly patients . METHODS Patients aged > or=70 years with stage IC-IV ovarian cancer , performance status Treatment was carboplatin ( AUC 2)+paclitaxel ( 60 mg/m2 ) on days 1 , 8 , 15 every 4 weeks , up to six cycles . A two-stage design was applied with lack of unacceptable toxicity as primary endpoint ; 26 patients were required at the final stage , with at least 23 of them without unacceptable toxicity to conclude for a positive result . Geriatric assessment was performed by activity daily living ( ADL ) and instrumental ADL ( IADL ) scales . RESULTS Twenty-six patients were analysed ( median age 77 years , range 70 - 84 ) . Performance status was 0 in 10 and 1 in 16 patients ; 14 patients had two or more comorbidities ; 8 and 18 patients had some dependency in ADL or IADL . Twenty-three patients ( 88.5 % ) were treated without suffering unacceptable toxicity . Unacceptable toxic events were grade 3 heart rhythm , grade 3 increase of liver transaminases and prolonged haematological toxicity . Grade 1 neuropathy was reported in four cases . Out of 13 patients evaluable by RECIST , 5 partial responses were observed ( response rate 38.5 % ) . Two complete responses were observed among six patients with non-target lesions . Eight patients eligible for CA-125 response assessment had a response after six cycles . Median estimated progression-free survival was 13.6 months , and median overall survival was 32.0 months . CONCLUSIONS In a series of elderly ovarian cancer patients , characterized by a high incidence of comorbidities and functional impairment , weekly carboplatin and paclitaxel demonstrated a favourable toxicity profile",
"Purpose With the increasing number of elderly patients suffering from cancer , comorbidity and functional impairment become common problems in patients with cancer . Both comorbidity and functional impairment are associated with a shorter survival time in cancer patients , but their independent role has rarely been addressed before . Methods Within a prospect i ve trial we recruited 427 cancer patients , irrespective of age and type of cancer , admitted as in patients prior to the start of chemotherapy . Comorbidity was assessed with the cumulative illness rating scale ( CIRS-G ) , functional impairment with WHO performance status ( WHO-PS ) , basal ( ADL ) and instrumental ( IADL ) activities of daily living . Results Median follow-up was 34.2 months . A total , 61.4 % . of patients died . Median survival time was 21.0 months . Age , kind of tumour ( solid vs. haematological ) , treatment approach ( non-curative vs. curative ) , WHO-PS ( 2–4 vs. 0–1 ) , IADL ( severe comorbidity ( CIRS-level 3–4 vs. none ) were significantly associated with shorter survival time in univariate analysis . In a multivariate Cox-regression- analysis , age ( HR 1.019 ; 95%-CI 1.007–1.032 ; P = 0.003 ) , kind of tumour ( HR 1.832 ; 95%-CI 1.314–2.554 ; P severe comorbidity , functional impairment , and kind of tumour are independently related to shorter survival time in cancer patients",
"BACKGROUND To determine the feasibility of two chemotherapy regimens in elderly patients with advanced ovarian carcinoma ( AOC ) . PATIENTS AND METHODS Eighty-three patients > or=70 years were previously enrolled in a trial evaluating carboplatin and cyclophosphamide ( CC ) . On the basis of identical eligibility criteria , 75 further patients were enrolled in a trial evaluating carboplatin and paclitaxel ( Taxol ) ( CP ) . The primary end point of these studies was the feasibility of six courses of chemotherapy . Comprehensive geriatric assessment ( CGA ) parameters were assessed in terms of prognostic factors . RESULTS More patients in the CC group presented with performance status of two or more , depression symptoms , use of co-medications , hypoalbuminemia , abnormal Mini-Mental Status score , or sub-optimal surgery . Both regimens appeared feasible : 75.6 % in the CC group and 68.1 % in the CP group completed six courses . CC and CP groups had similar overall survival ( OS ) . Independent prognostic factors of poorer OS were the following : increasing age ( P = 0.013 ) , depression symptoms at baseline ( P paclitaxel ( P = 0.025 ) . CONCLUSION As this is a non-r and omised retrospective review of two consecutive studies , no firm conclusion can be drawn . It seems , however , that in elderly patients with AOC the use of paclitaxel results in more toxicity . CGA parameters and particularly emotional disorders might help to determine a priori the risk/benefit ratio of chemotherapy in this patient population",
"BACKGROUND Elderly patients with advanced non-small-cell lung cancer ( NSCLC ) may derive similar benefit from platinum-based chemotherapy as younger patients . Quality of life ( QoL ) and comprehensive geriatric assessment ( CGA ) is often advocated to assess benefits and risks . PATIENTS AND METHODS A total of 181 chemotherapy-naive patients [ ≥70 years , performance score ( PS ) of 0 - 2 ] with stage III-IV NSCLC received carboplatin and gemcitabine ( CG ) ( n = 90 ) or carboplatin and paclitaxel ( CP ) ( n = 91 ) every 3 weeks for up to four cycles . Primary end point was change in global QoL from baseline compared with week 18 . Pretreatment CGA and mini geriatric assessment during and after treatment were undertaken . A principal component ( PC ) analysis was carried out to determine the underlying dimensions of CGA and QoL and subsequently related to survival . RESULTS There were no changes in QoL after treatment . The number of QoL responders ( CG arm , 12 % ; CP arm , 5 % ) was not significantly different . CGA items were only associated with neuropsychiatric toxicity . Quality -adjusted survival was not different between treatment arms . The PC analysis derived from nine CGA , six QoL and one PS score indicated only one dominant dimension . This dimension was strongly prognostic , and physical and role functioning , Groningen Frailty Indicator and Geriatric Depression Scale were its largest contributors . CONCLUSIONS Paclitaxel or gemcitabine added to carboplatin did not have a differential effect on global QoL. CGA was associated with toxic effects in a very limited manner . CGA and QoL items measure one underlying dimension , which is highly prognostic",
"PURPOSE / OBJECTIVES To determine the extent to which falls occur in older adult patients with cancer ; to identify how falls relate to depression , age , functional status , and cognition ; and to develop a model for predicting falls . DESIGN Descriptive , prospect i ve , quantitative . SETTING Patients in the Senior Adult Oncology Program at the H. Lee Moffitt Cancer Center and Research Institute . SAMPLE 165 patients aged 70 years or older with any diagnosis of cancer , treatment type , and stage . METHODS Data were collected during a one-time interview using a comprehensive geriatric assessment consisting of the Instrumental Activities of Daily Living ( IADL ) Scale , Activities of Daily Living ( ADL ) Scale , Geriatric Depression Scale , Mini-Mental State Examination , and a fall assessment . MAIN RESEARCH VARIABLES Falls , functional status , depression , cognition , age , and gender . FINDINGS IADL scores were found to be a predictor of falls while controlling for age and ADL status . An IADL score of 22 predicts a 21 % risk of a fall . Fall risk increases to 81 % at an IADL score of 9 . CONCLUSIONS IADL score is a predictor of falls in this older adult population with cancer . ADL scores are not a predictor of falls when IADL is included in the model . IMPLICATION S FOR NURSING Nurses must play a vital role in conducting fall screening and risk assessment s for older adults with cancer",
"OBJECTIVE To examine the association between the outcomes of a pre-operative comprehensive geriatric assessment ( CGA ) and the risk of severe post-operative complications in elderly patients electively operated for colorectal cancer . METHODS One hundred seventy-eight consecutive patients ≥ 70 years electively operated for all stages of colorectal cancer were prospect ively examined . A pre-operative CGA was performed , and patients were categorized as fit , intermediate , or frail . The main outcome measure was severe complications within 30 days of surgery . RESULTS Twenty-one patients ( 12 % ) were categorized as fit , 81 ( 46 % ) as intermediate , and 76 ( 43 % ) as frail . Eighty-three patients experienced severe complications , including three deaths ; 7/21 ( 33 % ) of fit patients , 29/81 ( 36 % ) of intermediate patients and 47/76 ( 62 % ) of frail patients ( p=0.002 ) . Increasing age and ASA classification were not associated with complications in this series . CONCLUSION CGA can identify frail patients who have a significantly increased risk of severe complications after elective surgery for colorectal cancer",
"Several instruments have been proposed to improve treatment decisions in elderly cancer patients , but evidence of their impact in clinical practice is limited . The aim of this study was to analyze the role of clinical and functional factors in predicting serious adverse events , including death , severe toxicity or treatment interruption , during chemotherapy in elderly cancer patients . The survey evaluated elderly with lung or colon or breast cancer treated with chemotherapy , followed by S. Giovanni Battista Hospital . We enrolled 110 consecutive patients older than 70 years of age with lung ( n=45 ) , colon ( n=50 ) and breast ( n=15 ) cancer between October 2004 and October 2005 . Overall , 73/110 patients ( 66.4 % ) experienced adverse events as death ( n=14 ) , grade s III and IV toxicity ( n=40 ) , or treatment interruption for other reasons ( n=19 ) . The variables with stronger predictivity were advanced stage , toxicity of treatment , level of comorbidity and Karnofsky performance status ( KPS ) . instrumental activities of daily living ( IADL ) index and age itself were not independent predictors . In conclusion our results confirm the need of a careful selection of elderly patients suitable for chemotherapy , giving more weight to comorbidity and KPS scores than to age itself . The potential role of other functional evaluations need to be further assessed in r and omized controlled trials",
"OBJECTIVES To examine the toxicity experienced by a cohort of older women receiving adjuvant chemotherapy for breast cancer and the longitudinal effect on their functional status and quality of life ( QOL ) . DESIGN A geriatric assessment measuring functional status , comorbidity , mood , nutritional status , and QOL was performed before chemotherapy , at the end of chemotherapy , and 6 months later . SETTING This prospect i ve longitudinal study was conducted at Memorial Sloan-Kettering Cancer Center , New York , New York . PARTICIPANTS Fifty patients aged 65 and older with Stage I to III breast cancer receiving any adjuvant chemotherapy ; 49 were evaluable . MEASUREMENTS The chemotherapy regimen and the toxicity to chemotherapy were recorded . A geriatric assessment was performed before the start of chemotherapy , on completion of chemotherapy , and 6 months after completion of chemotherapy . QOL testing was performed at the same times . RESULTS Patients ( mean age 68 , range 65 - 84 ) received an anthracycline-based chemotherapy regimen ( n=15 ) or cyclophosphamide 600 mg/m2 intravenously ( i.v . ) , methotrexate 40 mg/m2 i.v . , 5-fluorouracil 600 mg/m2 i.v . every 3 weeks for eight cycles ( n=34 ) . Grade 3 or 4 toxicity occurred in 53 % ( n=26 ) , hematological toxicity in 27 % ( n=13 ) , and nonhematological toxicity in 31 % ( n=15 ) . Despite toxicity , there was no significant longitudinal change in functional status or QOL . CONCLUSION Despite toxicity from adjuvant chemotherapy , this cohort of relatively young older patients maintained their functional status and QOL from before chemotherapy to 6 months postchemotherapy . Subtle changes in higher-order functioning would require assessment using different geriatric assessment tools",
"BACKGROUND The prevalence of comorbidities and functional impairment among elderly patients may enhance the risk of operation-related complications , but the importance of these conditions in elderly patients undergoing thoracic surgery remains unclear . METHODS One hundred twenty patients > /= 60 years of age who underwent thoracic surgery were registered prospect ively and examined . A comprehensive geriatric assessment ( CGA ) that evaluated such diverse areas as functional status ( ie , performance status and activities of daily living [ ADLs ] using the Barthel index ) , comorbidity , nutrition ( ie , body mass index , arm-muscle circumference , albumin level , transferrin level , lymphocyte count , and cholinesterase level ) , and cognitive function ( ie , mini-mental state examination [ MMSE ] and negative emotions for operation ) was performed in the 2 weeks before patients underwent the operation . RESULTS The diseases of the 120 patients were as follows : lung cancer , 85 patients ; mediastinal tumor , 14 patients ; bullas , 12 patients ; and other diseases , 9 patients . Postoperative complications developed in 20 patients ( 16.7 % ) . The patients with dependence for performing the ADLs , and dementia were more likely to develop postoperative complications ( p = 0.041 , and p = 0.0065 , respectively ) . The patients who experienced longer operation times ( ie , > /= 300 min ; p = 0.018 ) were more likely to have complications . The incidence of prolonged air leak in the patients with malnutrition increased seven-fold ( p = 0.045 ) and that of postoperative infectious diseases in those patients with obesity increased 24-fold ( p = 0.0013 ) , while all patients who developed delirium had low scores in the MMSE preoperatively ( p = 0.0003 ) . Using multiple logistic regression , the best model was obtained with a combination of MMSE ( p = 0.031 ) and the Barthel index ( p = 0.04 ) . When the operation variables were added to this model , the operation time had the strongest effect ( p = 0.016 ) . CONCLUSIONS Dependence for the performance of ADLs and impaired cognitive conditions are important predictors of postoperative complications , especially when the operation time is long . CGA is necessary in addition to the conventional cardiopulmonary functional assessment in elderly patients",
"BACKGROUND Cancer is a disease that particularly affects the elderly and , although surgery is the first treatment choice , many elderly cancer patients do not receive st and ard surgery because they are considered unfit for treatment due to an inaccurate estimation of operative risk . Pre-operative Assessment of Cancer in the Elderly ( PACE ) was developed in order to address the need to provide detailed information about the functional reserve of the elderly cancer patient to aid individualised management . METHODS PACE incorporates a battery of vali date d instruments including the Comprehensive Geriatric Assessment ( CGA ) , Brief Fatigue Inventory ( BFI ) , Eastern Cooperative Oncology Group Performance Status ( ECOG-PS ) , and American Society Anesthesiologists ( ASA ) grade . An international prospect i ve study was conducted with 460 consecutive elderly cancer patients ( 216 breast , 146 GIT , 71 GUT , 27 other ) receiving PACE prior to receiving elective surgery . RESULTS Three hundred and eighty four patients ( 83.4 % ) were observed to have at least one co-morbidity ; the most common being hypertension ( n=246 , 53.5 % ) . More than two thirds of the patients had good functional and mental status according to PACE . After adjusting for age , sex and type of cancer , six of the seven items of PACE were found to be significantly associated with co-morbidities ( according to the Satariano 's Index of Co-morbidities ( SIC ) ) . A multivariate analysis identified IADL , BFI and ASA to be the most important instruments in explaining SIC . DISCUSSION PACE has been effectively used to describe the functional capacity and health status in an international cohort of elderly cancer patients . The majority of PACE instruments have been found to be significantly associated with co-morbidities ( SIC ) and can distinguish between type and severity of cancer . PACE represents a useful tool in evaluating onco-geriatric fitness for surgery",
"As a result of demographic evolution , oncologists will treat more and more elderly patients with prostate cancer . Aging is frequently associated with the coexistence of several medical complications that can increase the complexity of cancer treatment decision-making . Unfortunately , clinical oncologists need to be more familiar with the multidimensional assessment of elderly patients . To acquire this skill , we implemented a multidimensional geriatric assessment program at our cancer center . This instrument prospect ively assessed 60 elderly patients with prostate cancer . Herein , we describe geriatric aspects detected in our patient sample and report treatment options proposed to elderly patients with prostate cancer at different disease stages . The minimal comprehensive geriatric assessment ( mini-CGA ) procedure revealed that 66 % of our patient population was dependent in one or more of the Katz Activities of Daily Living and 87 % were dependent in 1 or more of the Lawton Instrumental Activities of Daily Living ; all patients had significant comorbidity according to the Cumulative Illness Rating Scale-Geriatrics , 75 % having at least one severe comorbidity . We identified 19 cases of drug interaction . We also observed that half of these patients had a risk of falling and some physical disability ; 45 % had cognitive disorders requiring more investigation ; one third had depressive symptoms . Finally , 65 % of the patients were either malnourished or at risk of malnutrition . Many of these problems were unknown before the mini-CGA processing and may interfere with cancer and cancer treatment . Thus , the correct management of elderly patients with cancer requires comprehensive geriatric assessment as well as relevant disease staging at diagnosis . This approach will help us to propose the most appropriate treatment with the main aim of preserving quality of life",
"BACKGROUND Age > 60 years and impaired performance status ( PS ) are adverse prognostic features in the International Prognostic Index for non-Hodgkin 's lymphoma ; however , patients aged > 60 years compose a heterogeneous population , and commonly used PS measures are subjective and incomplete . PATIENTS AND METHODS Vali date d tests are used in geriatric population s to predict mortality and functional decline . The timed \" up and go \" test measures the time required to st and , walk a set distance , and return . The Tinetti Gait and Balance test measures gait and balance , and the h and grip assesses grip strength . We evaluated these tests in a heterogeneous cohort of older patients with lymphoma , as a first step in identifying prognostic subsets that might differ in the ability to tolerate disease and treatment . The mean age of the patients ( N = 25 ) was 70 years , with 13 men and 12 women . Five patients were newly diagnosed , 15 had aggressive histology , and 10 had indolent disease . Two subjects had Eastern Cooperative Oncology Group PS 0 , 20 had PS 1 , and 3 had PS 2 . Assessment s could be conducted in of functional status measures . RESULTS The interquartile range/median ( higher values reflect greater variance ) was 73.1 for the h and grip , 42.3 for the \" up and go , \" and 1.8 for the Tinetti test . CONCLUSION Accepted geriatric assessment tools can identify subgroups of older patients with lymphoma with distinct functional status . Prospect i ve trials in larger and more homogeneous patient population s will define the potential of these tools to assist in guiding therapy and predicting outcomes",
"PURPOSE To identify Comprehensive Geriatric Assessment ( CGA ) components independently associated with changes in planned cancer treatment . PATIENTS AND METHODS We prospect ively included 375 consecutive elderly patients with cancer ( ELCAPA01 study ) assessed by geriatricians using the CGA . Multivariate analysis was used to identify factors associated with changes in the cancer treatment ( intensification , decrease , or delayed > 2 weeks ) . Change was defined as a difference between the initial treatment proposal and the final treatment selected in a multidisciplinary meeting . RESULTS Mean age was 79.6 years ( st and ard deviation [ SD ] , 5.6 years ) , and 197 ( 52.5 % ) were women . The most common tumor location was the digestive system ( 58.7 % ) . The mean number of comorbidities was 4.2 ( SD , 2.7 ) per patient , and the mean Cumulative Illness Rating Scale for Geriatrics score was 11.8 ( SD , 5.3 ) . After the CGA , the initial cancer treatment plan was modified for 78 ( 20.8 % ) of 375 patients ( 95 % CI , 16.8 to 25.3 ) , usually to decrease treatment intensity ( 63 [ 80.8 % ] of 78 patients ) . By univariate analysis , cancer treatment changes were associated with Eastern Cooperative Oncology Group performance status ≥ 2 ( 73.3 % in the group with changes v 41.1 % in the in the group without changes ; P , dependency for one or more activities of daily living ( ADL ; 59.0 % v 24.2 % ; P malnutrition ( 81.8 % v 51.2 % ; P , cognitive impairment ( 38.5 % v 24.9 % ; P = .023 ) , depression ( 52.6 % v 21.7 % ; P greater number of comorbidities ( mean , 4.8 [ SD , 2.9 ] v 4.0 [ SD , 2.6 ] ; P = .02 ) . By multivariate analysis , factors independently associated with cancer treatment changes were a lower ADL score ( odds ratio [ OR ] , 1.25 per 0.5-point decrease ; CI , 1.04 to 1.49 ; P = .016 ) and malnutrition ( OR , 2.99 ; CI , 1.36 to 6.58 ; P = .007 ) . CONCLUSION Functional status assessed by the ADL score and malnutrition were independently associated with changes in cancer treatment ",
"This study is part of a larger multicenter prospect i ve study conducted in Italy to assess the efficacy of the comprehensive geriatric assessment ( CGA ) among elderly patients with cancer ( i.e. aged 65 years or older ) . The prevalence of functional limitations , and its association with selected characteristics , was investigated among 303 elderly patients consecutively admitted at the Department of Medical Oncology , IRCCS Centro di Riferimento Oncologico , Aviano ( Northeast Italy ) , between 1995 and 1998 . These patients had a median age of 72 years ( range , 65 - 94 ) , and were affected by haematological ( n=182 ) or solid tumours ( n=121 ) . At baseline , their physical function was assessed , in addition to performance status ( PS ) , by means of the activity of daily living ( ADL ) and the instrumental activities of daily living ( IADL ) scales . Overall , 17 % of the patients had a limitation for ADL , and 59 % for IADL , the prevalence of functional disabilities increased with age . Specifically , 8 % of patients had continence limitations and 13 % had limitations in taking the prescribed drugs . By multivariate analysis , a poor PS turned out to be a strong independent determinant of both ADL and IADL disabilities",
"BACKGROUND A number of elderly cancer patients do not receive st and ard surgery for solid tumors because they are considered unfit for treatment as a consequence of inaccurate estimation of the operative risk . To tailor treatment to onco-geriatric series , oncologists are now beginning to use a comprehensive geriatric assessment ( CGA ) . This study investigates the value of an extended CGA in assessing the suitability of elderly patients for surgical intervention . PATIENTS AND METHODS Preoperative assessment of cancer in the elderly ( PACE ) incorporates vali date d instruments including the CGA , an assessment of fatigue and performance status and an anaesthesiologist 's evaluation of operative risk . An international prospect i ve study was conducted using 460 consecutively recruited elderly cancer patients who received PACE prior to elective surgery . Mortality , post-operative complications ( morbidity ) and length of hospital stay were recorded up to 30 days after surgery . RESULTS Poor health in relation to disability ( assessed using the instrumental activities of daily living ( IADL ) ) , fatigue and performance status ( PS ) were associated with a 50 % increase in the relative risk of post-operative complications . Multivariate analysis identified moderate/severe fatigue , a dependent IADL and an abnormal PS as the most important independent predictors of post-surgical complications . Disability assessed by activities of daily living ( ADL ) , IADL and PS were associated with an extended hospital stay . CONCLUSION PACE represents a valuable tool in enhancing the decision process concerning the c and idacy of elderly cancer patients for surgical intervention and can reduce inappropriate age-related inequity in access to surgical intervention . It is recommended that PACE be used routinely in surgical practice",
"Research on the use of health care by older newly-diagnosed cancer patients is sparse . We investigated whether frailty predicts hospitalization , emergency department ( ED ) and general practitioner ( GP ) visits in older cancer patients in a prospect i ve pilot study . Newly-diagnosed cancer patients aged 65 years and over were recruited in the Segal Cancer Centre , Jewish General Hospital , Montreal , Canada . One hundred ten patients participated , mean age 74.1 , 70 % women . During 1 year follow-up , 52 patients ( 47.3 % ) had cancer-related hospitalizations , 23 patients ( 20.9 % ) had ED visit and 17 patients ( 15.5 % ) had GP visit . No frailty marker predicted hospitalization or visits to the GP . Cognitive impairment suspicion was the only frailty marker that predicted ED visits ( odds ratio 4.97 ; 95%CI 1.14 - 21.69 ) . Although health care use was considerable in this sample , most frailty markers were not associated with health care use in this pilot study",
"OBJECTIVES To report on the longitudinal cognitive functioning of older women receiving adjuvant chemotherapy for breast cancer . DESIGN Neuropsychological and functional status testing were performed before chemotherapy and 6 months after chemotherapy . SETTING Cancer center . PARTICIPANTS Thirty-one patients aged 65 and older with Stage I to III breast cancer . Of the 31 patients enrolled , three refused post-testing , and 28 were evaluable . MEASUREMENTS The following domains of cognitive function were examined : attention ; verbal memory ; visual memory ; and verbal , spatial , psychomotor , and executive functions . RESULTS Participants had a mean age of 71 ( range 65 - 84 ) : 39 % Stage I , 50 % Stage II , and 11 % Stage III . The number of scores 2 st and ard deviations ( SDs ) below the norm were calculated for each patient before and 6 months after chemotherapy ; 14 ( 50 % ) had no change , 11 ( 39 % ) worsened , and three ( 11 % ) improved ( P=.05 ) . Seven patients ( 25 % ) experienced a decline in cognitive function , defined as a 1-SD decline from pre- to post-testing in two or more neuropsychological domains . Exploratory analyses revealed no significant difference between functional status , comorbidity , and depression scale scores and change in overall quality -of-life scores before and after chemotherapy . CONCLUSION In this cohort of older women receiving adjuvant chemotherapy , a subset experienced a decline in cognitive function from before chemotherapy to 6 months after chemotherapy . Further prospect i ve study is needed to confirm these observations and to identify the subgroup at special risk",
"PURPOSE Older patients are underrepresented in many areas of cancer services utilization and in clinical trial enrollment . This study evaluates whether age , when adjusted for sex , comorbidity , stage , tumor site , geography , and time period , is predictive of cancer treatment practice . METHODS First , we used the Ontario Cancer Registry ( OCR ) to examine for any apparent differences in treatment practice s between elderly ( > or = 70 years ) and younger patients in the last three decades . Second , we performed a chart review of 1,505 patients with lung , breast , and colorectal cancers seen in Ontario either at an urban center , the Princess Margaret Hospital , or at a rural center , the Northwestern Regional Cancer Centre . Patients were r and omly selected from two time periods , 1977 to 1978 and 1997 ; and the study population was to comprise at least 50 % elderly patients . RESULTS OCR data demonstrated that , in some setting s , such as colorectal cancer , the proportions of elderly cancer patients who were referred to cancer centers and who received any cancer treatment were lower than their younger counterparts . The chart review data showed that increasing age was a significant negative predictor for receiving any cancer treatment ( P having a clinical trial discussion with the treating specialist ( P elderly cancer patients in clinical trials , a better underst and ing of appropriate therapies for this patient population can be obtained and may , thereby , impact on their cancer-related morbidity and mortality",
"PURPOSE Older adults are vulnerable to chemotherapy toxicity ; however , there are limited data to identify those at risk . The goals of this study are to identify risk factors for chemotherapy toxicity in older adults and develop a risk stratification schema for chemotherapy toxicity . PATIENTS AND METHODS Patients age ≥ 65 years with cancer from seven institutions completed a prechemotherapy assessment that captured sociodemographics , tumor/treatment variables , laboratory test results , and geriatric assessment variables ( function , comorbidity , cognition , psychological state , social activity/support , and nutritional status ) . Patients were followed through the chemotherapy course to capture grade 3 ( severe ) , grade 4 ( life-threatening or disabling ) , and grade 5 ( death ) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events . RESULTS In total , 500 patients with a mean age of 73 years ( range , 65 to 91 years ) with stage I to IV lung ( 29 % ) , GI ( 27 % ) , gynecologic ( 17 % ) , breast ( 11 % ) , genitourinary ( 10 % ) , or other ( 6 % ) cancer joined this prospect i ve study . Grade 3 to 5 toxicity occurred in 53 % of the patients ( 39 % grade 3 , 12 % grade 4 , 2 % grade 5 ) . A predictive model for grade 3 to 5 toxicity was developed that consisted of geriatric assessment variables , laboratory test values , and patient , tumor , and treatment characteristics . A scoring system in which the median risk score was 7 ( range , 0 to 19 ) and risk stratification schema ( risk score : percent incidence of grade 3 to 5 toxicity ) identified older adults at low ( 0 to 5 points ; 30 % ) , intermediate ( 6 to 9 points ; 52 % ) , or high risk ( 10 to 19 points ; 83 % ) of chemotherapy toxicity ( P the risk of chemotherapy toxicity in older adults . Geriatric assessment variables independently predicted the risk of toxicity ",
"Purpose The prevalence of elderly and comorbid patients ( pts ) with malignant lymphoma ( ML ) will steadily increase in future . Elderly patients comprise a heterogeneous population . Comprehensive geriatric assessment ( CGA ) is an established diagnostic tool in geriatric medicine . However , the prognostic value in patients with ML is unclear . We sought to establish a relationship between results of CGA and survival time in patients with ML . Methods Newly diagnosed patients with ML and indication for chemotherapeutical treatment were prospect ively recruited in an observational trial . In addition to usual diagnostic work up , a CGA including activities of daily living ( ADL ) , instrumental activities of daily living ( IADL ) and comorbidities was performed . Association of patients ’ characteristics and results of CGA with survival were analysed according to Kaplan – Meier method and in a multivariate Cox-regression analysis . Results About 143 patients were included , median age was 63 years , 63 patients were women . Median follow-up of surviving patients was 62 months . Sixty-six patients died within this time . Advanced age , poor Karnofsky performance status , dependence in ADL and IADL and presence of severe comorbidity were significantly associated with shorter survival time . In a Cox-regression analysis , IADL ( HR 2.1 ; 95 % CI 1.1–3.9 ) and comorbidity ( HR 1.9 ; 95 % CI 0.9–3.9 ) were independent and strongest associated with survival time . Conclusion Results of CGA , such as IADL and comorbidities , are prognostic variables for survival of patients with ML . Results should be vali date d in homogeneous clinical groups and if confirmed included in diagnostic and therapeutic algorithm",
"OBJECTIVES To establish a correlation between a specific MGA category , an appropriate preventively established treatment and clinical outcome in a population of elderly cancer patients . The ultimate goal was to verify whether the appropriate treatment given to elderly cancer patients according to their MGA category could translate into a better clinical outcome assessed as clinical response and toxicity , i.e whether this process might achieve a clinical ly meaningful impact . PATIENTS AND METHODS We carried out a phase II open , prospect i ve non-r and omized study in 75 elderly cancer patients ( lung , head and neck , colorectal , gynecologic and breast ) hospitalized at the Department of Medical Oncology , University of Cagliari , Italy . All patients underwent MGA evaluation and were assigned to three different categories : fit , intermediate and frail . Thereafter , an appropriate preventively established treatment was administered and the clinical outcome was assessed . The clinical outcome after 3 month treatment was defined on the basis of objective clinical response and toxicity . The difference of clinical outcome in the MGA categories was assessed by ANOVA test . Moreover , the correlation between MGA category and the clinical outcome ( clinical response and toxicity ) was assessed by Spearman 's correlation test . RESULTS A better clinical response was observed in fit patients as compared both to intermediate and frail patients . Treatment toxicity was comparable in the different MGA categories . The correlation analysis between MGA category , clinical response to treatment and toxicity showed that there was a significant direct correlation with clinical response and no correlation with toxicity . Overall , the regression analysis showed that MGA was predictive of clinical outcome , in the sense that it is truly predictive for clinical response and no predictive for toxicity . CONCLUSION Our study demonstrates that the MGA , although time-consuming , is a useful and cost-benefit effective tool to appropriately select elderly cancer patients to be treated effectively in terms of a survival advantage and those who would benefit mainly in terms of improvement of quality of life . Moreover , the treatment preventively established for each MGA category was shown to be adequate and accomplished the most appropriate performances in terms of effectiveness and toxicity ",
"We r and omly assigned frail elderly in patients with a high probability of nursing-home placement to an innovative geriatric evaluation unit intended to provide improved diagnostic assessment , therapy , rehabilitation , and placement . Patients r and omly assigned to the experimental ( n = 63 ) and control ( n = 60 ) groups were equivalent at entry . At one year , patients who had been assigned to the geriatric unit had much lower mortality than controls ( 23.8 vs. 48.3 per cent , P less than 0.005 ) and were less likely to have initially been discharged to a nursing home ( 12.7 vs. 30.0 per cent , P less than 0.05 ) or to have spent any time in nursing home during the follow-up period ( 26.9 vs. 46.7 per cent , P less than 0.05 ) . The control-group patients had substantially more acute-care hospital days , nursing-home days , and acute-care hospital readmissions . Patients in the geriatric unit were significantly more likely to have improvement in functional status and morale than controls ( P less than 0.05 ) . Direct costs for institutional care were lower for the experimental group , especially after adjustment for survival . We conclude that geriatric evaluation units can provide substantial benefits at minimal cost for appropriate groups of elderly patients , over and above the benefits of traditional hospital approaches",
"BACKGROUND No tool currently exists to rapidly allow surgeons to objective ly quantify surgical risk in geriatric patients . The goal of our prospect i ve study was to determine if individual questions extracted from vali date d screens for common geriatric syndromes would have predictive value for surgical risk in geriatric patients with thoracic neoplasms . METHODS Patients ≥ 70 y old were recruited to participate in a prospect i ve , IRB-approved study involving the preoperative administration of vali date d screening tests . Patients were given the geriatric depression scale ( GDS ) , nutrition screening initiative nutritional health checklist ( NSI NHC ) , mini mental status exam ( MMSE ) , brief fatigue inventory ( BFI ) , and assessed for activities of daily living ( ADLs ) and instrumental activities of daily living ( IADLs ) . All patients enrolled in this study were scheduled for thoracic surgery . RESULTS Patients who responded to having a dependency in the IADL \" shopping \" were more likely to have major complications and to be discharged to a non-home location than those without a dependency ( P = 0.011 , 0.003 ) . Patients who answered \" yes \" to questions 1 , 9 , and 10 of the NSI NHC had a longer mean length of stay compared with patients who answered \" no \" ( P = 0.039 , 0.010 , 0.031 ) . Answering \" yes \" to GDS question 2 correlated with the incidence of major complications ( r = 0.270 P = 0.037 ) . Answering \" yes \" to GDS question 12 increased the likelihood of being discharged to a non-home location postoperatively ( odds ratio = 11.64 , 95 % CI , 0.68 - 202.86 , P = 0.047 ) . CONCLUSIONS Our data indicate that an abbreviated , rapid presurgical assessment can be developed for estimating operative risk , length of stay , and discharge destination in geriatric patients with thoracic malignancies using individual questions from previously vali date d screening tools",
"Aims and background Cancer is an age-related disease , and the increase in life expectancy will lead to a progressive increase of cancer cases in the elderly ( ≥70 years of age ) . We have created a group called GONG ( Gruppo Oncologico Geriatrico ) to apply cancer geriatric assessment in elderly cancer patients , in order to select which of them are eligible for oncological treatment or supportive care only . Patients and methods We applied this model to evaluate 153 patients from March 2004 to August 2005 . Our model included three categories of patients : frail ( at least one of the following items : Activities of Daily Living scale Results Applying the aforementioned criteria , we found 30 borderline , 14 frail and 109 non-frail patients . Statistical analysis showed a significant difference in mortality between frail and non-frail patients ( P at higher risk of death . These results confirm the importance of cancer geriatric assessment also for the clinical evaluation of oncological patients . Additional r and omized studies with a larger number of patients , also in an adjuvant setting , should be performed to confirm the effectiveness of this approach",
"BACKGROUND Data from prospect i ve clinical trials are needed to better define st and ards of care in elderly patients with advanced ovarian carcinoma and to demonstrate the interest of Comprehensive Geriatric Assessment ( CGA ) in this fragile and heterogeneous population . PATIENTS AND METHODS From July 1998 to October 2000 , 83 advanced ovarian carcinoma patients > 70 years old received carboplatin AUC 5 and cyclophosphamide 600 mg/m2 , on day 1 of six 28-day cycles . The clinical and biological geriatric covariates prospect ively studied were : comorbidities , comedications , cognitive functions ( Mini-Mental test ) , nutritional status and autonomy . RESULTS Patient characteristics were : median age 76 years , serous histology ( 73 % ) , FIGO stage III ( 75 % ) , optimal initial surgery ( 21 % ) and performance status ( PS ) > or = 2 ( 44 % ) . Sixty patients ( 72 % ) received six chemotherapy cycles without severe toxicity ( STox ) or tumor progression . Multivariate analysis retained three factors as independent predictors of STox : symptoms of depression at baseline ( P = 0.006 ) , dependence ( P = 0.048 ) and PS > or = 2 ( P = 0.026 ) . Independent prognostic factors identified for overall survival ( Cox model ) were depression ( P = 0.003 ) , FIGO stage IV ( P = 0.007 ) and more than six different comedications per day ( P = 0.043 ) . CONCLUSION CGA could predict STox and overall survival of elderly advanced ovarian carcinoma patients",
"PURPOSE Factors captured in a geriatric assessment can predict morbidity and mortality in older adults , but are not routinely measured in cancer clinical trials . This study evaluated the implementation of a geriatric assessment tool in the cooperative group setting . PATIENTS AND METHODS Patients age ≥ 65 with cancer , who enrolled on cooperative group cancer trials , were eligible to enroll on Cancer and Leukemia Group B ( CALGB ) 360401 . They completed a geriatric assessment tool before initiation of protocol therapy , consisting of valid and reliable geriatric assessment measures which are primarily self-administered and require minimal re sources and time by healthcare providers . The assessment measures functional status , comorbidity , cognitive function , psychological state , social support , and nutritional status . The protocol specified criteria for incorporation of the tool in future cooperative group trials was based on the time to completion and percent of patients who could complete their portion without assistance . Patient satisfaction with the tool was captured . RESULTS Of the 93 patients who enrolled in this study , five ( 5 % ) met criteria for cognitive impairment and three did not complete the cognitive screen , leaving 85 assessable patients ( median age , 72 years ) . The median time to complete the geriatric assessment tool was 22 minutes , 87 % of patients ( n = 74 ) completed their portion without assistance , 92 % ( n = 78 ) were satisfied with the question naire length , 95 % ( n = 81 ) reported no difficult questions , and 96 % ( n = 82 ) reported no up setting questions . One hundred percent of health care professionals completed their portion . CONCLUSION This brief , primarily self-administered geriatric assessment tool met the protocol specified criteria for inclusion in future cooperative group clinical trials",
"OBJECTIVES To integrate the principles of geriatric assessment into the care of older patients with cancer in order to identify vulnerable older adults and develop interventions to optimize cancer treatment . DESIGN A brief , comprehensive , self-administered question naire and intervention algorithm were developed consisting of measures of geriatric assessment that are brief , reliable , vali date d , and predictive of mortality and morbidity in older patients . SETTING Academic tertiary care cancer center and community-based satellite practice . PARTICIPANTS Patients aged 65 and older with cancer . MEASUREMENTS The question naire solicits information about the patient 's functional status , comorbidity , psychological status , nutritional status , and social support . A scoring algorithm for referral to a multidisciplinary team was developed . RESULTS Two hundred forty-five of 250 patients completed the question naire ( mean age 76 , range 65 - 95 ) . The majority of patients were women ( 71 % ) , white ( 95 % ) , married ( 52 % ) , and retired ( 90 % ) , with a variety of tumor types and stages . Most patients ( 78 % ) completed the question naire on their own and reported acceptance of question naire length ( 91 % ) , no difficult questions ( 94 % ) , no up setting questions ( 96 % ) , and no missing questions ( 89 % ) . The mean time to completion was 15 minutes , with a median of 12.5 ( st and ard deviation 10 , range 2 - 60 ) . Information from this question naire helped identify physical and psychological impairments , poor nutrition , lack of social support , and untreated comorbidities . Appropriate referrals to a multidisciplinary team were made . CONCLUSION This brief , comprehensive , self-administered question naire is feasible for use in the outpatient oncology setting and helped identify the needs of geriatric oncology patients . Prospect i ve trials are needed to determine the effectiveness of the interventions offered",
"The primary aim of the present study was to examine the relationship of changes in hemoglobin levels following recombinant human erythropoietin ( rHuEPO ) treatment to changes in cognitive functioning studied by Mini Mental State Examination ( MMSE ) in elderly cancer patients undergoing chemotherapy treatment . The secondary aim was that to assess the relationship of changes in hemoglobin levels following rHuEPO treatment to changes in functions studied by Comprehensive Geriatic Assessment ( CGA ) , such as Activity of Daily Living ( ADL ) , Instrumental Activities of Daily Living ( IADL ) , Geriatric Depression Scale ( GDS ) and the Mini Nutritional Assessment ( MNA ) . To this end , hemoglobin levels and cognitive functioning were evaluated in a sample of cancer patients prior to the start of chemotherapy treatment and again after 4 , 8 and 12 weeks of treatment with chemotherapy plus rHuEPO . Ten elderly patients ( mean age 71.4 years ) were enrolled . At baseline , enrolled patients had a mean Hb value of 10.3g/dl . After 4 weeks of rHuEPO treatment , Hb values increased significantly ( p Hb levels > or=1g/dl in comparison to baseline and therefore were considered responders . At baseline , four patients ( 40 % ) showed a moderate cognitive impairment , whilst six patients ( 60 % ) showed a normal cognitive function . After 4 weeks of rHuEPO treatment nine patients ( 90 % ) showed a significant improvement of cognitive functions in comparison to baseline ( p rHuEPO in terms of correction of anemia . The Spearman 's rank correlation test showed a statistical significant correlation between Hb increase and increase in cognitive functioning assessed by MMSE after 4 weeks ( p=0.049 ) , 8 weeks ( p=0.044 ) and 12 weeks ( p=0.031 ) of rHuEPO treatment . Therefore , the findings of this study provide support for the hypothesis that significant increases in hemoglobin over the course of chemotherapy supplemented with rHuEPO administration would be accompanied by significant improvement in cognitive performance over the same interval"
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41179a42-06ff-11f0-808a-c43d1ab1c353
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Purpose The objective of this systematic review was to identify , collate and analyse the current available evidence on the effectiveness of workplace-based rehabilitative interventions in workers with upper limb conditions on work performance , pain , absenteeism , productivity and other outcomes . Methods We search ed Medline , Cochrane Library , Scopus , Web of Science , Academic Search Premier , Africa-Wide Information , CINAHL , OTSeeker and PEDro with search terms in four broad areas : upper limb , intervention , workplace and clinical trial ( no date limits ) . Studies including neck pain only or musculoskeletal pain in other areas were not included . Results Initial search located 1071 articles , of which 80 were full text review ed . Twenty-eight articles were included , reporting on various outcomes relating to a total of seventeen studies . Nine studies were of high method ological quality , seven of medium quality , and one of low quality . Studies were sorted into intervention categories : Ergonomic controls ( n = 3 ) , ergonomic training and workstation adjustments ( n = 4 ) , exercise and resistance training ( n = 6 ) , clinic-based versus workplace-based work hardening ( n = 1 ) , nurse case manager training ( n = 1 ) , physiotherapy versus Feldenkrais ( n = 1 ) , and ambulant myofeedback training ( n = 1 ) . The largest body of evidence supported workplace exercise programs , with positive effects for ergonomic training and workstation adjustments , and mixed effects for ergonomic controls . Ambulant myofeedback training had no effect . The remaining three categories had positive effects in the single study on each intervention . Conclusion While there is substantial evidence for workplace exercise programs , other workplace-based interventions require further high quality research . Systematic review registration PROSPERO CRD42017059708
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"Abstract While workplace physical exercise can help manage musculoskeletal disorders , less is known about psychosocial effects of such interventions . This aim of this study was to investigate the effect of workplace physical exercise on psychosocial factors among workers with chronic musculoskeletal pain . The trial design was a 2-armed parallel-group r and omized controlled trial with allocation concealment . A total of 66 slaughterhouse workers ( 51 men and 15 women , mean age 45 years [ st and ard deviation ( SD ) 10 ] ) with upper limb chronic musculoskeletal pain were r and omly allocated to group-based strength training ( physical exercise group ) or individual ergonomic training and education ( reference group ) for 10 weeks . Social climate was assessed with the General Nordic Question naire for Psychological and Social Factors at Work , and vitality and mental health were assessed with the 36-item Short Form Health Survey . All scales were converted to 0 to 100 ( higher scores are better ) . Between-group differences from baseline to follow-up were determined using linear mixed models adjusted for workplace , age , gender , and baseline values of the outcome . Mean baseline scores of social climate , mental health , and vitality were 52.2 ( SD 14.9 ) , 79.5 ( SD 13.7 ) , and 53.9 ( SD 19.7 ) , respectively . Complete baseline and follow-up data were obtained from 30 and 31 from the physical exercise and reference groups , respectively . The between-group differences from baseline to follow-up between physical exercise and reference were 7.6 ( 95 % CI 0.3 to 14.9 ) , −2.3 ( 95 % CI -10.3 to 5.8 ) , and 10.1 ( 95 % CI 0.6 to 19.5 ) for social climate , mental health , and vitality , respectively . For social climate and vitality , this corresponded to moderate effect sizes ( Cohen d = 0.51 for both ) in favor of physical exercise . There were no reported adverse events . In conclusion , workplace physical exercise performed together with colleagues improves social climate and vitality among workers with chronic musculoskeletal pain . Mental health remained unchanged",
"OBJECTIVES The aim of this study was to investigate the effectiveness of an ergonomic intervention on productivity loss at work caused by upper-extremity disorders ( UED ) . METHODS Workers with medically verified UED were invited to participate . The intervention consisted of a physician contacting the worker 's supervisor and an occupational physiotherapist conducting an ergonomic assessment at the worksite . Before and after the intervention , the employees self-assessed UED-related productivity loss ( ie , decreased quality and quantity of the daily work output ) . We tested for differences between groups at 8 and sub-sequently 12 weeks . We also applied generalized estimating equation ( GEE ) to analyze repeated measures data . RESULTS Altogether 177 employees were r and omized . The overall participation rate was 88 % . At baseline , 54 % of the intervention group and 58 % of the control group reported productivity loss . The magnitude of productivity loss was 17 % and 20 % , respectively . At 8 weeks , both the proportion and magnitude of productivity loss were lower in the intervention than the control group , but the differences were statistically significant only at 12 weeks ( proportion 25 % versus 51 % , magnitude 7 % versus 18 % , P=0.001 for both ) . Using GEE analyses , we also found the differences to be statistically significant ( proportion 38 % versus 52 % , magnitude 12 % versus 18 % ) . The intervention only benefitted employees with 0 - 20 % loss of productivity at baseline , not those with a higher initial productivity loss . CONCLUSIONS Early ergonomic intervention , in addition to adequate medical care , is effective in preventing and restoring self-reported productivity loss associated with UED",
"Background Office computer workers are at increased risk for neck/upper extremity ( UE ) musculoskeletal pain . Methods A seven-month office ergonomic intervention study evaluated the effect of two engineering controls plus training on neck/UE pain and mechanical exposures in 113 computer workers , including a 3-month follow-up period . Participants were r and omised into an intervention group , who received a keyboard/mouse tray ( KBT ) , touch pad ( TP ) for the non-dominant h and and keyboard shortcuts , and a control group who received keyboard shortcuts . Participants continued to have available a mouse at the dominant h and . Outcomes were pain severity , computer rapid upper limb assessment ( RULA ) , and h and activity level . Prevalence ratios ( PRs ) evaluated intervention effects using dichotomised pain and exposure scores . Results In the intervention group , the dominnt proximal UE pain PR=0.9 , 95 % CI 0.7 to 1.2 and the dominant distal UE PR=0.8 , 95 % CI 0.5 to 1.3 , postintervention . The non-dominant proximal UE pain PR=1.0 , 95 % CI 0.8 to 1.4 , while the non-dominant distal UE PR=1.2 , 95 % CI 0.6 to 2.2 , postintervention . Decreases in non-neutral postures were found in two RULA elements ( non-dominant UE PR=0.9 , 95 % CI 0.8 to 0.9 and full non-dominant RULA PR=0.8 , 95 % CI 0.8 to 0.9 ) of the intervention group . H and activity increased on the non-dominant side ( PR=1.4 , 95 % CI 1.2 to 1.6 ) in this group . Conclusions While the intervention reduced non-neutral postures in the non-dominant UE , it increased h and activity in the distal region of this extremity . To achieve lower h and activity , a KBT and TP used in the non-dominant h and may not be the best devices to use",
"Process evaluation is important to explain success or failure of workplace interventions . This study performs a summative process evaluation of workplace interventions with physical exercise . As part of a r and omized controlled trial 132 office workers with neck and shoulder pain were to participate in 10 weeks of elastic resistance training five times a week at the workplace ; the 2 min group performed a single set of lateral raise to failure , and the 12 min group performed 5 - 6 sets with 8–12 repetitions . Participants received a single instructional session together with a training diary and manual at baseline ( 100 % dose delivered and 100 % dose received ) , and 59 and 57 participants , respectively , replied to the process evaluation question naire at 10-week follow-up . Results showed that in the 2 and 12 min groups , respectively , 82 % and 81 % of the participants completed more than 30 training sessions . However , two-thirds of the participants would have preferred more than a single exercise to vary between . In the 12 versus 2 min group more participants experienced the training sessions as too long ( 30 % versus 5 % ) . Most participants ( 67–92 % ) found the training diary and manual helpful , adequacy in a single instructional session , and satisfaction with the type of training . Among those with low adherence , lack of time ( 51 % ) and difficulties in starting exercising after illness ( 26 % ) were common barriers for regular training . Among those with low adherence , 52 % felt that five training sessions per week were too much , and 29 % would rather have trained a completely different kind of exercise . In conclusion , resistance training at the workplace is generally well received among office workers with neck-shoulder pain , but a one-size-fits-all approach is not feasible for all employees",
"Background Neck and shoulder complaints are common among employees in sedentary occupations characterized by intensive computer use . Such musculoskeletal pain - which is often associated with restricted range of motion and loss of muscle strength - is one of the most common conditions treated by physical therapists . The exact mechanism of neck pain is rarely revealed by clinical examination and the treatment has varied from passive rest to active treatments . Active treatments have often been divided into either training of the painful area or the surrounding musculature avoiding direct training of the painful area . Our study investigates the effect of the latter approach . Methods / Design A r and omized controlled trial of 10 weeks duration is currently being conducted . Employed office workers with severe neck-shoulder pain are r and omized to 3 × 20 min shoulder function training with training supervision or to a reference group receiving advice to stay physically active . Shoulder function training primarily focuses on the serratus anterior and lower trapezius muscle with only minimal activation the upper trapezius . An announcement was sent to the administrative section of the university including jobs characterized by intensive computer work . The first 100 positive replies entered the study . Among these inclusion criteria were pain intensity in the neck/shoulder of at least 3 on a 0 - 9 scale . Exclusion criteria were cardiovascular disease , trauma , hypertension , or serious chronic disease . Before and after the intervention period the participants replied to a question naire about musculoskeletal disorders and work disability , and underwent a st and ardized clinical examination of the neck and shoulder girdle . Further , on a weekly basis the participants log pain intensity of the neck and shoulder during the previous week . The primary outcome measure is pain in the neck and shoulders at week 10 based on the weekly pain registration and results from the clinical examination . Secondary outcomes are strength and work disability . Trial Registration Clinical Trials ( NCT ) :",
"In practice the secondary prevention of work-related upper extremity ( WRUE ) symptoms generally targets biomechanical risk factors . Psychosocial risk factors have also been shown to play an important role in the development of WRUE symptom severity and future disability . The addition of a stress management component to biomechanically focused interventions may result in greater improvements in WRUE symptoms and functional limitations than intervening in the biomechanical risk factors alone . Seventy office workers with WRUE symptoms were r and omly assigned to an ergonomics intervention group ( assessment and modification of work station and stretching exercises ) or a combined ergonomic and job stress intervention group ( ergonomic intervention plus two 1-h workshops on the identification and management of workplace stress ) . Baseline , 3- and 12-month follow-up measures of observed ergonomic risks and self-reported ergonomic risks , job stress , pain , symptoms , functional limitation , and general physical and mental health were obtained from all participants . While both groups experienced significant decreases in pain , symptoms , and functional limitation from baseline to three months with improvements continuing to 12 months post baseline , no significant differences between groups were observed for any outcome measures . Findings indicate that the additional two-session job stress management component did not significantly enhance the short- or long-term improvements brought about by the ergonomic intervention alone",
"Background The prevalence of health risk behaviours is growing amongst South African employees . Health risk behaviours have been identified as a major contributor to reduced health related quality of life ( HRQoL ) and the increased prevalence of non-communicable diseases . Worksite wellness programmes promise to promote behaviour changes amongst employees and to improve their HRQoL. The aim of this study was to evaluate the short-term effects of an employee wellness programme on HRQoL , health behaviour change , body mass index ( BMI ) and absenteeism amongst clothing and textile manufacturing employees . Methods The study used a r and omised control trial design . The sample consisted of 80 subjects from three clothing manufacturing companies in Cape Town , South Africa . The experimental group was subjected to a wellness programme based on the principles of cognitive behaviour therapy ( CBT ) as well as weekly supervised exercise classes over six weeks . The control group received a once-off health promotion talk and various educational pamphlets , with no further intervention . Measurements were recorded at baseline and at six weeks post-intervention . Outcome measures included the EQ-5D , Stanford Exercise Behaviours Scale , body mass index and absenteeism . Data was analysed with the Statistica-8 software program . Non-parametric tests were used to evaluate the differences in the medians between the two groups and to determine the level of significance . The Sign test was used to determine the within group changes . The Mann – Whitney U test was used to determine the difference between the two groups . Results At six weeks post intervention the experimental group ( 39 subjects ) demonstrated improvement in almost every parameter . In contrast , apart from an overall decrease in time off work and a reduction in BMI for all study participants , there was no significant change noted in the behaviour of the control group ( 41 subjects ) . Seventy percent of the experimental group had improved HRQoL EQ-5D VAS scores post intervention , indicating improved perceived HRQoL. In comparison , only 58 % of the control group had improved HRQoL EQ-5D VAS scores post intervention . There was no significant difference between the two groups at baseline or at six weeks post intervention . Conclusion An employee wellness programme based on the principles of CBT combined with weekly aerobic exercise class was beneficial in improving the perceived HRQoL and changing health-related behaviours of clothing manufacturing employees . However , it can not be concluded that the EWP was more effective than the once off health promotion talk as no significant changes were noted between the two groups at 6-weeks post intervention . This trial has been registered with Clinical Trials.gov ( trial registration number NCT01625039 )",
"Introduction Return to work following an occupational injury is a multifactoral process although many traditional clinic-based rehabilitation programs do not appreciate the importance of workplace factors . A r and omized controlled trial was conducted to investigate the effect of workplace-based rehabilitation program on the return to work outcome of work-related rotator cuff disorder , which is based on the therapeutic use of actual work facilities and work environment . Methods A total of 103 workers were recruited and r and omly assigned into Clinic-based Work Hardening ( CWH ) or Workplace-based Work Hardening ( WWH ) groups . The CWH group were given traditional generic work hardening training while WWH group received workplace-based work hardening training with rehabilitative principles of athletic rotator cuff pathology , biomechanics and specific job activities . Results After four weeks , a higher return to work rate was obtained in WWH group compared to CWH group ( 71.4 % vs. 37 % , p lowering of self-reported shoulder problems and functional work capabilities in the WWH group versus the CWH group . Conclusion Workplace-based rehabilitation program appeared to be more effective in facilitating the return to work process of the injured worker as assessed immediately following intervention . In particular this approached was associated with many of the psychosocial workplace factors related to separation from the work routine . The influence of peer group and /or employer could be minimized . This initial attempt with rotator cuff injuries appears promising however long-term outcome needs to be determined",
"Purpose The aim of the study was to determine effects of ergonomic intervention on work-related upper extremity musculoskeletal disorders ( WUEMSDs ) among computer workers . Methods Four hundred computer workers answered a question naire on work-related upper extremity musculoskeletal symptoms ( WUEMSS ) . Ninety-four subjects with WUEMSS using computers at least 3 h a day participated in a prospect i ve , r and omized controlled 6-month intervention . Body posture and workstation layouts were assessed by the Ergonomic Question naire . We used the Visual Analogue Scale to assess the intensity of WUEMSS . The Upper Extremity Function Scale was used to evaluate functional limitations at the neck and upper extremities . Health-related quality of life was assessed with the Short Form-36 . After baseline assessment , those in the intervention group participated in a multicomponent ergonomic intervention program including a comprehensive ergonomic training consisting of two interactive sessions , an ergonomic training brochure , and workplace visits with workstation adjustments . Follow-up assessment was conducted after 6 months . Results In the intervention group , body posture ( p workstation layout ( p = 0.002 ) improved over 6 months ; furthermore , intensity ( p duration ( p frequency ( p = 0.009 ) of WUEMSS decreased significantly in the intervention group compared with the control group . Additionally , the functional status ( p = 0.001 ) , and physical ( p and mental ( p = 0.035 ) health-related quality of life improved significantly compared with the controls . There was no improvement of work day loss due to WUEMSS ( p > 0.05 ) . Conclusions Ergonomic intervention programs may be effective in reducing ergonomic risk factors among computer workers and consequently in the secondary prevention of WUEMSDs",
"Background Neck and upper limb symptoms are frequently reported by computer workers . Work style interventions are most commonly used to reduce work-related neck and upper limb symptoms but lifestyle physical activity interventions are becoming more popular to enhance workers health and reduce work-related symptoms . A combined approach targeting work style and lifestyle physical activity seems promising , but little is known on the effectiveness of such combined interventions . Methods / design The RSI@Work study is a r and omised controlled trial that aims to assess the added value of a lifestyle physical activity intervention in addition to a work style intervention to reduce neck and upper limb symptoms in computer workers . Computer workers from seven Dutch companies with frequent or long-term neck and upper limb symptoms in the preceding six months and /or the last two weeks are r and omised into three groups : ( 1 ) work style group , ( 2 ) work style and physical activity group , or ( 3 ) control group . The work style intervention consists of six group meetings in a six month period that take place at the workplace , during work time , and under the supervision of a specially trained counsellor . The goal of this intervention is to stimulate workplace adjustment and to improve body posture , the number and quality of breaks and coping behaviour with regard to high work dem and s. In the combined ( work style and physical activity ) intervention the additional goal is to increase moderate to heavy physical activity . The control group receives usual care . Primary outcome measures are degree of recovery , pain intensity , disability , number of days with neck and upper limb symptoms , and number of months without neck and upper limb symptoms . Outcome measures will be assessed at baseline and six and 12 months after r and omisation . Cost-effectiveness of the group meetings will be assessed using an employer 's perspective . Discussion This study will be one of the first to assess the added value of a lifestyle physical activity intervention in addition to a work style intervention in reducing neck and upper limb symptoms of computer workers . The results of the study are expected in 2007",
"Purpose Neck and shoulder complaints are common among employees in occupations characterized by intensive computer use . Treatment has varied from passive rest to active treatments and active treatments have often been divided into either training of the painful area or the surrounding musculature avoiding direct training of the painful area . Our study investigates the effect of the latter approach . The purpose of this study was in a r and omised controlled trial to investigate if intensive scapular function training (SFT)—in terms of training of the lower trapezius and the serratus anterior muscle while minimizing direct training of the upper trapezius — is effective in reducing pain in adults with chronic non-specific pain in the neck/shoulder region . Methods 47 office workers with chronic non-specific pain in the neck/shoulder region were r and omized to 10 weeks 3 × 20 min SFT with training supervision or to a control group . At baseline and at follow-up the participants were tested for maximum isometric shoulder strength by a blinded tester . Further , once a week participants reported pain intensity of the neck/shoulder during the previous week . Results In intention-to-treat analysis neck- and shoulder pain decreased 2.0 ( 95 % CI 0.35 ; 3.64 ) in SFT compared with control group ( p 0.05 ) . Pressure Pain Threshold ( PPT ) increased 129 kPa in the lower trapezius in SFT compared with the control group ( p 0.01 ) . Shoulder elevation strength increased 7.7 kg in SFT compared with the control group ( p change in shoulder protraction strength . Conclusions SFT reduces pain intensity and increases shoulder elevation strength in adults with chronic non-specific pain in the neck/shoulder region . The magnitude of improvement in pain intensity was clinical ly relevant",
"Chronic musculoskeletal pain is widespread in the working population and leads to muscular fatigue , reduced work capacity , and fear of movement . While ergonomic intervention is the traditional approach to the problem , physical exercise may be an alternative strategy . This secondary analysis of a r and omized controlled trial investigates the effect of strength training on muscular fatigue resistance and self-rated health among workers with chronic pain . Sixty-six slaughterhouse workers with chronic upper limb pain and work disability were r and omly allocated to 10 weeks of strength training or usual care ergonomic training ( control ) . At baseline and follow-up , participants performed a h and grip muscular fatigue test ( time above 50 % of maximal voluntary contraction force ) with simultaneous recording of electromyography . Additionally , participants replied to a question naire regarding self-rated health and pain . Time to fatigue , muscle strength , h and /wrist pain , and self-rated health improved significantly more following strength training than usual care ( all P Time to fatigue increased by 97 % following strength training and this change was correlated to the reduction in fear avoidance ( Spearman 's rho = −0.40 ; P = 0.01 ) . In conclusion , specific strength training improves muscular fatigue resistance and self-rated health and reduces pain of the h and /wrist in manual workers with chronic upper limb pain . This trial is registered with Clinical Trials.gov NCT01671267",
"Objective : To investigate the effects of ambulant myofeedback training including ergonomic counselling ( Mfb ) and ergonomic counselling alone ( EC ) , on work-related neck-shoulder pain and disability . Methods : Seventy-nine female computer workers reporting neck-shoulder complaints were r and omly assigned to Mfb or EC and received four weeks of intervention . Pain intensity in neck , shoulders , and upper back , and pain disability , were measured at baseline , immediately after intervention , and at three and six months follow-up . Results : Pain intensity and disability had significantly decreased immediately after four weeks Mfb or EC , and the effects remained at follow up . No differences were observed between the Mfb and EC group for outcome and subjects in both intervention groups showed comparable chances for improvement in pain intensity and disability . Conclusions : Pain intensity and disability significantly reduced after both interventions and this effect remained at follow-up . No differences were observed between the two intervention groups",
"& 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",
"Introduction The goal of this study was to assess the effectiveness of a group-based interactive work style intervention in improving work style behavior . Methods Computer workers with neck and upper limb symptoms were r and omised into the work style group ( WS , N = 152 ) , the work style and physical activity group ( WSPA , N = 156 ) , or the usual care group ( N = 158 ) . Both intervention groups received the same work style intervention but the WSPA group also received a lifestyle physical activity intervention . Participants from the intervention groups attended six group meetings which focused on behavioral change with regard to body posture and workstation adjustment , breaks , and coping with high work dem and s in order to reduce work stress . Stage of change , breaks and exercise behavior , and stress outcomes were assessed by question naire at baseline ( T0 ) and after 6 ( T1 ) and 12 months ( T2 ) . Body posture and workstation adjustment were assessed by observation and by question naire at T0 , T1 , and T2 . Multilevel analyses were used to study differences in work style behavior between study groups . Results The work style intervention was effective in improving stage of change with regard to body posture , workstation adjustment , and the use of sufficient breaks during computer work . These findings were confirmed by higher self-reported use of breaks and exercise reminder software and less working hours without breaks . However , self-reported changes in body posture and workstation adjustment were less consistent . The work style intervention was ineffective in changing stress outcomes . Conclusion A group-based work style intervention seems to be effective in improving some elements of work style behavior . Future studies should investigate the effectiveness of work style interventions on all dimensions of the Feuerstein work style model",
"Management of the return-to-work process in cl aim ants with work-related upper extremity disorders often poses challenges to the health care provider , cl aim ant , and employer . Modifying workplace ergonomic risk factors as a component of the workplace accommodation process may improve return-to-work outcomes by reducing recurrent pain and discomfort . The present study is a case-control evaluation of the effects of a 2-day training program for nurse case managers that was design ed to facilitate the implementation of workplace accommodations within a workers ’ compensation health care delivery system . After the training , 101 cl aim ants with compensable upper extremity disorders were r and omly assigned to case mangers with and without training . Overall , 208 accommodations were recommended and 155 of these were implemented ( 75 % ) . Cl aim ants of trained nurses received 1.5 times as many recommendations for accommodations as cl aim ants managed by nurses not trained in the process , and 1.4 times as many accommodations were implemented , although no differences were found between the two groups in implementation rates . Trained nurses were more likely to recommend accommodations addressing workstation layout , computer-related improvements , furnishings , accessories , and lifting/carrying aids , whereas the untrained nurses were more likely to suggest light duty and lifting restrictions . This study indicates that the training was associated with a change in the practice behavior of case managers regarding the workplace accommodation process . More research is needed to identify barriers to implementation and develop more effective approaches to facilitate worksite accommodations in disabled workers with carpal tunnel syndrome and other persistent upper extremity disorders",
"BACKGROUND Chronic pain and disability of the arm , shoulder , and h and severely affect labor market participation . Ergonomic training and education is the default strategy to reduce physical exposure and thereby prevent aggravation of pain . An alternative strategy could be to increase physical capacity of the worker by physical conditioning . OBJECTIVES To investigate the effect of 2 contrasting interventions , conventional ergonomic training ( usual care ) versus resistance training , on pain and disability in individuals with upper limb chronic pain exposed to highly repetitive and forceful manual work . STUDY DESIGN Examiner-blinded , parallel-group r and omized controlled trial with allocation concealment . SETTING Slaughterhouses located in Denmark , Europe . METHODS Sixty-six adults with chronic pain in the shoulder , elbow/forearm , or h and /wrist and work disability were r and omly allocated to 10 weeks of specific resistance training for the shoulder , arm , and h and muscles for 3 x 10 minutes per week , or ergonomic training and education ( usual care control group ) . Pain intensity ( average of shoulder , arm , and h and , scale 0 - 10 ) was the primary outcome , and disability ( Work module of DASH question naire ) as well as isometric shoulder and wrist muscle strength were secondary outcomes . RESULTS Pain intensity , disability , and muscle strength improved more following resistance training than usual care ( P Pain intensity decreased by 1.5 points ( 95 % confidence interval -2.0 to -0.9 ) following resistance training compared with usual care , corresponding to an effect size of 0.91 ( Cohen 's d ) . LIMITATIONS Blinding of participants is not possible in behavioral interventions . However , at baseline outcome expectations of the 2 interventions were similar . CONCLUSION Resistance training at the workplace results in clinical relevant improvements in pain , disability , and muscle strength in adults with upper limb chronic pain exposed to highly repetitive and forceful manual work . TRIAL REGISTRATION NCT01671267",
"OBJECTIVE Imbalance between work dem and s and individual re sources can lead to musculoskeletal disorders and reduced work ability . The aim of this study was to evaluate the effect of two contrasting interventions on work ability among slaughterhouse workers with chronic pain and work disability . METHODS Sixty-six slaughterhouse workers with upper-limb chronic pain and work disability were r and omly allocated to 10 weeks of either strength training for the shoulder , arm , and h and muscles ( 3 times per week , 10 minutes per session ) or ergonomic training ( usual care control group ) from September to December 2012 . The outcome measure was the change from baseline to 10-week follow-up in the work ability index ( WAI ) . RESULTS A priori hypothesis testing showed a group × time interaction for WAI ( P , WAI increased 2.3 [ 95 % confidence interval ( 95 % CI ) 0.9 - 3.7 ] in the strength training group corresponding to a moderate effect size ( Cohen 's d 0.52 ) . Within-group changes indicated that between-group differences were mainly caused by a reduction in WAI in the ergonomic group . Of the 7 items of WAI , item 2 ( work ability in relation to the dem and s of the job ) and item 7 ( mental re sources ) increased following strength training compared with ergonomic training ( P Implementation of strength training at the workplace prevents deterioration of work ability among manual workers with chronic pain and disability exposed to forceful and repetitive job tasks . Thus , strength training performed at the workplace may in fact be regarded as a complex biopsychosocial intervention modality that reaches further than the specific physiological benefits of training per se",
"OBJECTIVES The aim of this study was to assess the effect of an ergonomic intervention on pain and sickness absence caused by upper-extremity musculoskeletal disorders . METHODS In this r and omized controlled study , subjects aged 18 - 60 years ( N=177 ) seeking medical advice due to upper-extremity symptoms were included if their symptoms , or the exacerbation of symptoms , had started Workplace ergonomic improvements were made in the intervention group . Data on symptoms and sickness absences were gathered during one-year follow-up . RESULTS Pain intensity , pain interference with work , leisure time , or sleep did not differ between the intervention and control group during the one-year follow-up . During the first three months of follow-up , the percentage of employees with sickness absence due to upper-extremity or other musculoskeletal disorders did not differ between the intervention ( N=89 ) and control ( N=84 ) group , but the total number of sickness absence days in the intervention group was about half of that in the control group ( mean 6.2 versus 9.8 days for upper-extremity disorder and 6.0 versus 11.5 days for upper-extremity and other musculoskeletal disorders combined ) . During 4 - 12 months of follow-up , the percentage of employees with sickness absence due to upper-extremity disorder ( 10.1 % versus 16.7 % , P=0.20 ) or upper-extremity and other musculoskeletal disorders combined ( 20.2 % versus 32.1 % , P=0.07 ) was lower in the intervention than the control group . CONCLUSIONS Our findings suggest that an early ergonomic intervention reduces sickness absence due to upper-extremity or other musculoskeletal disorders",
"There is evidence that performing job tasks involving repetition , vibration , sustained posture or forceful movement may contribute to symptoms of work related upper extremity disorders . Typing is one such activity ; symptoms that develop as a result of this activity can affect performance of work , self-care and leisure occupations . Studies investigating the impact of ergonomic keyboards on symptom reduction are limited , and little research exists regarding the reduction of key activation force as an intervention . Methods : This r and omized , prospect i ve study used a sample of 68 symptomatic workers employed by a single company . One group received a commercially available ergonomic keyboard , a second group used a modified version of the same keyboard design ed to reduce activation force , vibration and key travel . We measured symptoms and clinical signs , functional status , and device satisfaction in both groups over a six-month study period . Results : Between-groups analyses indicated that the groups performed similarly on the outcomes of interest . Repeated-measure analysis identified a reduction of symptoms , an improvement in functional status , preference for and increased satisfaction with the intervention keyboards , and maintenance of typing speed and accuracy for both groups . Conclusions",
"OBJECTIVES To study whether isometric shoulder endurance was more advantageous than isometric shoulder strength training in reducing pain and perceived exertion and to increase shoulder function through improved muscle endurance and strength . DESIGN R and omized trial . SETTING Three occupational health care centers . PARTICIPANTS Women industrial workers with nonspecific neck-shoulder pain . The International Classification of Diseases , 10th Revision ( ICD-10 ) diagnosis was \" cervicobrachial syndrome \" ( M53.1 ) . Thirty-eight patients completed the isometric shoulder endurance training and 31 patients completed the isometric shoulder strength training . INTERVENTION Twelve weeks of training . MAIN OUTCOME MEASURES Self-reported pain and rating of perceived exertion ( RPE ) , arm motion performance test , shoulder muscle strength , shoulder muscle endurance , and shoulder functional tests , as well as follow-up after supervised training had ended . RESULTS The isometric shoulder strength training result ed in an almost one-scale step decrease in RPE at work and a 5 % to 15 % improvement of arm motion performance compared with the endurance training . The isometric shoulder strength training more effectively improved left side shoulder abduction strength ( p isometric shoulder endurance training was not more successful than the strength training in the endurance test ( p .51 to .81 ) . CONCLUSIONS Physical training programs for neck-shoulder pain may include isometric shoulder muscular strength exercise in addition to isometric shoulder endurance training , rather than endurance training only"
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The numbers of quality -adjusted life years ( QALYs ) gained are increasingly being used to represent the gains in individual utility from treatment . This requires that the value of a health improvement to an individual is a simple product of gains in quality of life and length of life . The article reports on a systematic review of the literature on 2 issues : whether the value of a state is affected by how long the state lasts , and by states that come before or after it . It was found that individual preferences over health are influenced by the duration of health states and their sequence . However , although there is much variation across individual respondents , the assumptions tend to hold much better when valuations are aggregated across respondents , which is encouraging for economic evaluations that rely on using average ( mean or median ) values
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[
"The time-tradeoff ( TTO ) test is widely used to measure quality of life for different health states . Subjects are asked to equate the value of living a given period in an inferior health state to the value of living a shorter period in good health . Applications of TTOs have been criticized based on the fact that the value of future life duration is taken as the future life duration itself . The authors show that for a health state in which a subject does not want to live longer than a specified amount of time , subjects ' responses do not comply with the assumption that the value of the period in inferior health is equated to the value of the shorter period in good health Actually , preference reversals with respect to such a health state point to the use of a proportional heuristic in the TTO test . Comparisons of the TTO test in these subjects with category scaling and difference measurements also favor a proportional inter pretation of the TTO test . In tests based on conjoint measurement , these subjects also appear to use a proportional heuristic . Consequences of the use of the TTO test and conjoint measurement m quality -of-life models are discussed Key words : utility assessment , QALY , conjoint measurement ; preference reversals ; compatibility effect . ( Med Decis Making 1996;16:36 - 44",
"This paper reports a comparative study of three formulations of the time-tradeoff ( TTO ) method of health valuation . One asks people to consider giving up time each day in exchange for better health . The second asks people to consider giving up time during a 12-month interval . The third is the more conventional TTO in which people are asked to contemplate a reduction in life expectancy . Question naires were sent to 4,087 adults selected at r and om from the population of Scotl and . Each respondent provided a de scription of his or her health , and was asked to value an improvement in that health , using all three formulations of the TTO . The daily TTO appeared to be an improvement on the conventional formulation , correlating more strongly with health , eliciting re sponses that appeared to be more precise , and obtaining information about the value of health from a far greater number of respondents . The performance of the annual TTO appeared to be only slightly inferior to that of the daily TTO . Key words : time tradeoff ; quality of life ; health valuation . ( Med Decis Making 1996;16:335 - 347",
"The techniques of cost utility analysis ( CUA ) were used to evaluate the treatment of gallstone disease by open and laparoscopic cholecystectomy and by extracorporeal shockwave lithotripsy ( ESWL ) . The application of the techniques in this context raised three method ological questions which are not satisfactorily resolved in the literature . The first is whether an ex ante or ex post perspective is best adopted for the measurement of quality of life ( QoL ) . The second is the method for converting a short term deterioration in QoL followed by full health into QALYs and the reliability of the methods available . The third is the issue of indirect costs which , in the context of a temporary disease state , can not be easily avoided . The economic evaluation found laparoscopic cholecystectomy to be generally superior than the competitor technologies ( entailing lower costs and better outcomes ) . However , the results were sensitive to assumptions about the perspective for measuring benefits and the inclusion of indirect costs",
"The author presents evidence for the descriptive adequacy of the quality -adjusted life years ( QALY ) model as applied to health profiles . One important assumption of the model is preferential independence : if two profiles have the same health state during year X , then preference between them does not switch if the level of health changes during year X. In experiment 1 , 30-year health profiles were used to perform 27 em pirical tests of independence with 98 subjects . Independence was reliably satisfied in all 27 tests . In experiment 2 , 15 additional tests were conducted . These tests had been specifically design ed to be more sensitive to independence violations , but indepen dence was still mostly satisfied . In both experiments , the conclusions about indepen dence hold regardless of what discount rate is used . These results act as a \" lower bound \" on the validity of the QALY model for health profiles . Key words : quality -ad justed life years ; QALY model ; health profiles ; preferential independence . ( Med Decis Making 1998;18:418 - 428",
"A series of ‘ scenarios ’ describing the physical , social and emotional characteristics , limitations and duration of different health states have been successfully applied to a r and om sample of the general public in order to determine their social utility . The result ing mean daily health state utilities differ among disorders and vary with age , the duration of the disorder , the ‘ label ’ used to describe the disorder and the health status of the respondent . These health state utilities have considerable potential application in the planning and financing of health services"
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Introduction Type 2 diabetes mellitus ( T2DM ) affects more than 1.1 million Canadians aged ≥65 years . Group Medical Visits are an emerging health service delivery method . Recent systematic review s show that they can significantly reduce glycated haemoglobin ( HbA1c ) levels , but Group Visits have not been evaluated within primary care . We intend to determine the clinical effectiveness , quality of life and economic implication s of Group Medical Visits within a primary care setting for older people with T2DM . Methods and analysis A 2-year proof-of-concept , single-blinded ( measurement team ) r and omised control trial to test the efficacy of Group Medical Visits in an urban Canadian primary care setting . Participants ≥65 years old with T2DM ( N=128 ) will be equally r and omised to either eight groups of eight patients each ( Group Medical Visits ; Intervention ) or to Individual visits ( St and ard Care ; Controls ) . Those administering co interventions are not blinded to group assignment . Our sample size is based on estimates of variance ( ±1.4 % for HbA1c ) and effect size ( 0.9/1.4=0.6 ) from the literature and from our own preliminary data . Forty participants per group will provide a β likelihood of 0.80 , assuming an α of 0.05 . A conservative estimation of an effect size of 0.7/1.4 changes the N in the power calculation to 59 per group . Hence , we aim to enrol 64 participants in each study arm . We will use intention-to-treat analysis and compare mean HbA1c ( % glycosylated HbA1c ) ( primary outcome ) of Intervention/Control participants at 12 months , 24 months and 1 year postintervention on selected clinical , patient-rated and economic measures . Trial registration number NCT02002143
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"Background and Objective Current policy directions place increasing expectations on patients to actively engage in their care , especially in chronic disease management . We examined relationships between patient activation and multiple dimensions of primary healthcare ( PHC ) , including access , utilization , responsiveness , interpersonal communication , and satisfaction for patients with and without chronic illness . Research Design Cross-sectional , r and om digit dial survey conducted in British Columbia ( BC ) , Canada . SubjectsStratified sample of adults ( n=504 ) , aged 19 to 90 years , who had visited their regular provider within the past 24 months . All data were weighted to represent residents living in BC . Measures Patient activation and PHC experiences include accessibility , continuity , whole-person care , interpersonal communication , responsiveness , chronic disease management , and satisfaction . Results The multivariate models provide evidence that both quantity of time and quality of interactions with one 's regular provider are associated with higher patient activation . Those with no chronic illness had higher activation scores when they spent more time talking with their regular provider , experienced less hurried communication , or if their test results were explained . The more time people with chronic illness are able to spend with their physician , the more activated they were . Chronic illness respondents also had higher activation scores if they reported higher whole-person care or if they were more satisfied . Conclusions Positive interactions between the patient and the provider can influence the patient 's abilities to engage in and be confident in maintaining/improving his/her health . Supporting patients in becoming actively engaged , in ways that work for them , is essential to providing high quality care , especially among those with a chronic condition",
"Summary We estimated the incremental cost-effectiveness of a once-weekly or twice-weekly resistance training intervention compared with balance and tone classes in terms of falls prevented and quality -adjusted life years ( QALYs ) gained . Both resistance training interventions were more likely to save health care re source money and offer better health outcomes for falls prevention than balance and tone classes . Introduction This study aims to estimate the incremental cost-effectiveness and cost-utility of a once-weekly or twice-weekly resistance training intervention compared with twice-weekly balance and tone classes in terms of falls prevented and QALYs gained . Methods Economic evaluation was conducted concurrently with a three-arm r and omized controlled trial including 155 community-dwelling women aged 65 to 75 years , Mini Mental State Examination ≥24 , and visual acuity 20/40 or better . Participants received the once-weekly resistance training ( n = 54 ) , the twice-weekly resistance training ( n = 51 ) or the twice-weekly balance and tone ( the comparator ) classes ( n = 50 ) for 1 year . Measurements included the number of falls for each participant , healthcare re source utilization , and associated costs over 9 months ; health status was assessed using the EQ-5D and SF-6D to calculate QALYs . Results Based on the point estimates from our base case analysis , we found that both once- and twice-weekly resistance training groups were less costly ( p balance and tone classes . The incremental QALYs assessed using the SF-6D were 0.003 for both the once- and twice-weekly resistance training groups , compared with the twice-weekly balance and tone classes . The incremental QALYs assessed using the EQ-5D were 0.084 for the once-weekly and 0.179 for the twice-weekly resistance training groups , respectively , compared with the twice-weekly balance and tone classes . Conclusions An individually tailored resistance training intervention delivered once or twice weekly provided better value for money for falls prevention than balance and tone classes",
"OBJECTIVE To study time course changes in knowledge , problem solving ability , and quality of life in patients with type 2 diabetes managed by group compared with individual care and education . RESEARCH DESIGN AND METHODS We conducted a 5-year r and omized controlled clinical trial of continuing systemic education delivered by group versus individual diabetes care in a hospital-based secondary care diabetes unit . There were 120 patients with non-insulin-treated type 2 diabetes enrolled and r and omly allocated to group or individual care . Eight did not start and 28 did not complete the study . The main outcome measures were knowledge of diabetes , problem solving ability , quality of life , HbA1c , BMI , and HDL cholesterol . RESULTS Knowledge of diabetes and problem solving ability improved from year 1 with group care and worsened among control subjects ( P Quality of life improved from year 2 with group care but worsened with individual care ( P HbA1c level progressively increased over 5 years among control subjects ( + 1.7 % , 95 % CI 1.1 - 2.2 ) but not group care patients ( + 0.1 % , -0.5 to 0.4 ) , in whom BMI decreased ( -1.4 , -2.0 to -0.7 ) and HDL cholesterol increased ( + 0.14 mmol/l , 0.07 - 0.22 ) . CONCLUSIONS Adults with type 2 diabetes can acquire specific knowledge and conscious behaviors if exposed to educational procedures and setting s tailored to their needs . Traditional one-to-one care , although delivered according to optimized criteria , is associated with progressive deterioration of knowledge , problem solving ability , and quality of life . Better cognitive and psychosocial results are associated with more favorable clinical outcomes",
"Summary Using two instruments ( SF-6D and EQ-5D ) to estimate quality adjusted life years ( QALYs ) , we conducted an economic evaluation of a 12-month r and omized controlled trial with a 12-month follow-up study in older women to evaluate the value for money of two doses of resistance training compared with balance and tone classes . We found that the incremental QALYs estimated from the SF-6D were two- to threefold greater than those estimated from the EQ-5D . Introduction Decision makers must continually choose between existing and new interventions . Hence , economic evaluations are increasingly prevalent . The impact of quality -adjusted life year ( QALY ) estimates using different instruments on the incremental cost-effectiveness ratios ( ICERs ) is not well understood in older adults . Thus , we compared ICERs , in older women , estimated by the EuroQol-5D ( EQ-5D ) and the Short Form-6D ( SF-6D ) to discuss implication s on decision making . Methods Using both the EQ-5D and the SF-6D , we compared the incremental cost per QALY gained in a r and omized controlled trial of resistance training in 155 community-dwelling women aged 65 to 75 years . The 12-month r and omized controlled trial included a subsequent 12-month follow-up . Our focus , the follow-up study , included 123 of the 155 participants from the Brain Power study ; 98 took part in the economic evaluation ( twice-weekly balance and tone exercises , n = 28 ; once-weekly resistance training , n = 35 ; twice-weekly resistance training , n = 35 ) . Our primary outcome measure was the incremental cost per QALY gained of once- or twice-weekly resistance training compared with balance and tone exercises . Results At cessation of the follow-up study , the incremental QALY was −0.051 ( EQ-5D ) and −0.144 ( SF-6D ) for the once-weekly resistance training group and −0.081 ( EQ-5D ) and −0.127 ( SF-6D ) for the twice-weekly resistance training group compared with balance and tone classes . Conclusion The incremental QALYs estimated from the SF-6D were two- to threefold greater than those estimated from the EQ-5D . Given the large magnitude of difference , the choice of preference-based utility instrument may substantially impact health care decisions",
"We assessed the validity of the Physical Activity Scale for the Elderly ( PASE ) in a sample of sedentary adults ( 56 men , 134 women , mean age + /- [ SD ] 66.5+/-5.3 years ) who volunteered to participate in a r and omized controlled trial on the effect of aerobic conditioning on psychological function . Construct validity was established by correlating PASE scores with physiologic and performance characteristics : peak oxygen uptake , resting heart rate and blood pressure , percent body fat , and balance . The mean PASE scores were higher in men than in women ( men = 145.8+/-78.0 ; women = 123.9+/-66.3 , P PASE scores were also significantly higher in those who did not report a chronic health condition ( cardiovascular disease , hypertension , cancer , or recent surgery ) . PASE scores were significantly associated ( P peak oxygen uptake ( r = 0.20 ) , systolic blood pressure ( r = -0.18 ) and balance score ( r = 0.20 ) . No significant associations of PASE score and diastolic blood pressure , resting heart rate , or percent body fat were noted . These results provide additional evidence for the validity of the PASE as a measure of physical activity suitable for use in epidemiology studies on the association of physical activity , health , and physical function in older individuals",
"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",
"We have developed a diabetes quality -of-life ( DQOL ) measure oriented toward the patient with insulin-dependent diabetes mellitus ( IDDM ) . The DQOL was assessed for its reliability and validity in a group of patients with IDDM ( n = 192 ) . We found that the DQOL and its four scales had high degrees of internal consistency ( Cronbach 's r = .66-.92 ) and excellent test-retest reliability ( r = .78-.92 ) . Using conceptually relevant measures of psychiatric symptoms , perceived well-being and adjustment to illness , we also demonstrated convergent validity of the DQOL . This instrument was initially design ed for use in the Diabetes Control and Complications Trial , a multicenter controlled clinical trial evaluating the effects of two different diabetes treatment regimens on the appearance and progression of early vascular complications . However , the DQOL may also be useful in evaluating the quality of life in other groups of patients with IDDM",
"Context Anxiety and depression are both common in primary care patients , but much less attention has been paid to anxiety . Contribution The authors administered a 7-item anxiety scale ( Generalized Anxiety Disorder [GAD]-7 ) to 965 primary care patients , who also had a structured interview , to detect an anxiety disorder . Of these patients , 19.5 % had at least 1 anxiety disorder . Patients with anxiety had worse functional status , more disability days , and more physician visits , but 41 % were not being treated for any anxiety disorder . The GAD-7 had high sensitivity and good specificity for detecting a generalized anxiety disorder , panic disorder , social anxiety disorder , and posttraumatic stress disorder . Implication s Anxiety disorders are common , underrecognized , and undertreated , but they are easy to detect with a brief question naire . The Editors Anxiety and depression are the 2 most common mental health problems seen in the general medical setting ( 15 ) . Although increasing attention has been paid to anxiety , it still lags far behind depression in terms of research as well as clinical and public health efforts in screening , diagnosis , and treating affected individuals . This is unfortunate given the prevalence of anxiety and its substantial impact on patient functioning , work productivity , and health care costs ( 614 ) . More than 30 million Americans have a lifetime history of anxiety ( 15 ) , and anxiety disorders cost an estimated $ 42 billion dollars per year in the United States alone , counting direct and indirect costs ( 16 ) . The 4 most common anxiety disorders ( excluding simple phobias that seldom present clinical ly ) are generalized anxiety disorder , panic disorder , social anxiety disorder , and posttraumatic stress disorder ( PTSD ) ( 1723 ) . However , despite the substantial disability associated with each anxiety disorder and the availability of effective treatments , only a minority of patients ( 15 % to 36 % ) with anxiety are recognized in primary care ( 24 , 25 ) . In our paper , we analyze results from a large primary carebased anxiety study ( 26 ) to answer several questions . First , what is the prevalence of these 4 anxiety disorders , both individually and concurrent with one another ? Second , how do these disorders compare in functional impairment , health care use , and comorbid depressive and somatic symptom burden ? Third , how effective is a brief anxiety measure in screening for each disorder ? Compared with previous research , our study is particularly well-positioned to ascertain commonalities among anxiety diagnoses that are traditionally considered to be discrete and to determine whether a single measure can be used as a first step , common metric . This is especially salient for the busy , complex primary care setting , in which simplifying initial recognition of mental disorders may in fact make wider efforts at recognition more feasible . Methods Patient Sample The Patient Health Question naire ( PHQ ) anxiety study ( 26 ) was conducted to develop a short measure to assess generalized anxiety disorder . Patients were enrolled from a research network of 15 primary care sites ( 13 family practice and 2 internal medicine sites ) located in 12 states and administered central ly by Clinvest , Inc. , Springfield , Missouri , from November 2004 to June 2005 . The Generalized Anxiety Disorder (GAD)-7 scale was developed and vali date d in 2149 patients . In the original study , 2982 persons were invited to participate ; of these , 2740 ( 92 % ) completed the 4-page question naire and had no or minimal missing data ( 26 ) . To minimize sampling bias , consecutive patients were approached at each site in clinic sessions until the target quota for that week was achieved . Of the 2740 participants , the first 2149 were used for development and validation of the GAD-7 scale , whereas the last 591 were used to determine the testretest reliability of the scale . Of the 2149 patients in the validation group , 1654 agreed to a telephone interview , of whom 965 were r and omly selected to undergo this interview within 1 week of their clinic visit by 1 of 2 mental health professionals : a clinical psychologist ( with a PhD ) or a senior psychiatric social worker . Contact information was sent by fax to each interviewer , who shuffled the fax sheets received each day and then drew from the stack several participants to interview that day . The 965 interviewed patients comprise the study population for this paper , and compared with the 1184 participants who did not undergo a mental health professional interview , these were more often women ( 69 % vs. 63 % ; P= 0.003 ) and had slightly higher GAD-7 anxiety scores ( 5.7 vs. 5.1 ; P= 0.010 ) but were similar in age , race , and education . Of note , we only used data from the 1184 participants not undergoing a mental health professional interview to derive the GAD-7 ( 26 ) . The study was approved by the Sterling Institutional Review Board . Study Question naire Before seeing their physicians , patients completed a 4-page question naire that included the GAD-7 ( Appendix Figure ) . This scale was shown to have good internal and testretest reliability , as well as convergent , construct , criterion , procedural , and factorial validity for the diagnosis of generalized anxiety disorder ( 26 ) . Scores on the GAD-7 range from 0 to 21 ; scores of 5 , 10 , and 15 represent mild , moderate , and severe anxiety symptoms , respectively . The first 2 items of the GAD-7 represent core anxiety symptoms , and scores on this GAD-2 subscale range from 0 to 6 . Appendix Figure . The Generalized Anxiety Disorder (GAD)-7 scale . The first 2 items constitute the GAD-2 subscale . GAD-7 2006 Pfizer Inc. All rights reserved . Used with permission . The study question naire also included questions about age , sex , education , race or ethnicity , and marital status ; the Medical Outcomes Study Short Form-20 ( SF-20 ) , which measures functional status in 6 domains ( 27 ) ; the 10-item anxiety subscale from the Hopkins Symptom Checklist ( 28 ) ; the PHQ-8 depression scale ( 29 ) ; a 3-item version of the Social Phobia Inventory ( Mini-SPIN ) ( 30 ) ; the 5-item PHQ panic module ( 25 ) ; and the PHQ-15 somatic symptom scale ( 31 ) . Also , single-item global assessment s of anxiety , depression , and pain based on a scale of 0 ( none ) to 10 ( as bad as you can imagine ) were included . Finally , patients reported the number of physician visits and disability days during the previous 3 months . Structured Psychiatric Interview The 2 mental health professionals , while blinded to the results of the self-report research question naire , conducted structured psychiatric interviews by telephone to establish independent criteria -based diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders , fourth edition ( DSM-IV ) ( 32 ) . The interview consisted of the generalized anxiety disorder , social anxiety disorder , and PTSD sections of the Structured Clinical Interview for DSM-IV ( SCID ) ( 33 ) . Reinterview by telephone was used because of its feasibility in our multisite study and its demonstrated comparability with face-to-face research interviews ( 3436 ) . The 2 mental health professionals based diagnoses of generalized anxiety disorder and PTSD on the SCID interview . For generalized anxiety disorder , some questions were slightly modified to better assess each DSM-IV criterion . They based a diagnosis of social anxiety disorder on whether the patient met SCID diagnostic criteria and had a Mini-SPIN score of 8 or greater , because this improves the accuracy of social anxiety disorder diagnoses ( 37 ) . They based a diagnosis of panic disorder on answering yes to all 5 questions on the PHQ panic module , a threshold that reflects DSM-IV criteria and has been vali date d in both clinical ( 25 ) and population -based ( 38 ) sample s. Statistical Analysis We estimated sample size with respect to sensitivity of the GAD-7 scale for diagnosing the target disease ( generalized anxiety disorder ) . We needed 60 participants with generalized anxiety disorder to ensure that the total width of the 95 % CI around a sensitivity proportion of 0.80 was no greater than 0.20 . Given that the estimated prevalence of generalized anxiety disorder in the primary care population was 6 % ( 18 ) , we needed a total of 1000 unselected primary care patients to have approximately 60 patients with generalized anxiety disorder . We determined the prevalence of each of the 4 anxiety disorders and compared them in patient demographic characteristics , functional status , psychiatric comorbidity , disability days , and physician visits . Consistent with previous work ( 1 , 26 , 29 , 39 ) , we replaced missing values in a scale with the mean value of the remaining items if 25 % or fewer items were missing . If more than 25 % of items were missing , the sum score was not computed and was counted as missing . The amount of missing data for any individual variable or scale score was very low ( 15 sites did not differ in missing data . In addition to descriptive statistics , we used analysis of covariance to examine associations among each anxiety disorder and the 6 SF-20 functional status scales , self-reported disability days , and physician visitscontrolling for demographic variables ( sex , age , race , and educational level ) and study site . We ran similar models to examine the effect of the number of anxiety disorders . In all models , patients with no anxiety disorder were the reference group . We adjusted pairwise statistical comparisons by using the Bonferroni correction . Because some dependent variables displayed a skewed ( but unimodal ) distribution , we also reran the models using the rank transformation of the dependent variables . We examined the operating characteristics ( sensitivity , specificity , and positive likelihood ratio ) for a range of cutoff scores of the GAD-7 and GAD-2 for each anxiety disorder . We conducted receiver-operating characteristic curve analyses to determine the area under the curve ( AUC ) for each anxiety disorder . We calculated AUCs and performed statistical comparisons ( GAD-7 vs.",
"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",
"The Diabetes Control and Complications Trial ( DCCT ) provided much information towards settling the long-running controversy about the effectiveness of improving control of diabetes on the risk of its major complications . With the appearance or the advance of clinical ly significant retinopathy as its major outcome variable , DCCT r and omised 1,441 insulin-dependent diabetic patients to conventional or intensified control groups . In both primary prevention and secondary intervention arms of the trial , intensified control reduced retinopathy risk by half or more , and also reduced nephropathy and neuropathy risks -- however , risk of severe hypoglycaemic episodes was increased about three-fold . By contrast , there were no differences in quality of life , neurocognitive or emotional assessment s between the two groups . The application of trial findings to ' real life ' care is considered",
"Abstract Patient activation , defined as one ’s attitudes and confidence toward managing illness , has been not been thoroughly studied in consumers with schizophrenia . The current study sought to underst and the relationship between patient activation and symptoms , medication adherence , recovery attitudes , and hope in a sample of 119 adults with schizophrenia . The participants were enrolled in an 18-month r and omized controlled study of the Illness Management and Recovery program . Data were collected at baseline ; correlations and stepwise multiple regressions were used to examine the relationships and determine the unique contribution of variables . Higher patient activation was most strongly associated with positive recovery attitudes , higher levels of hope , and fewer emotional discomfort symptoms . Patient activation was significantly related to a broad measure of illness self-management , providing evidence for the construct validity of the patient activation measure . Our findings emphasize the importance of recovery-based mental health services that recognize level of patient activation as a potential factor in consumer outcomes",
"BACKGROUND Hemoglobin A1c ( HbA1c ) is a marker of cumulative glycemic exposure over the preceding 2- to 3-month period . Whether mild elevations of this biomarker provide prognostic information for development of clinical ly evident type 2 diabetes and cardiovascular disease among individuals at usual risk for these disorders is uncertain . METHODS We examined baseline HbA1c levels as a predictor of incident clinical diabetes and cardiovascular disease ( nonfatal myocardial infa rct ion , coronary revascularization procedure , ischemic stroke , or death from cardiovascular causes ) in a prospect i ve cohort study beginning in 1992 of 26,563 US female health professionals aged 45 years or more without diagnosed diabetes or vascular disease ( median follow-up 10.1 years ) . RESULTS During follow-up , 1238 cases of diabetes and 684 cardiovascular events occurred . In age-adjusted analyses using quintiles of HbA1c , a risk gradient was observed for both incident diabetes and cardiovascular disease . After multivariable adjustment , HbA1c remained a strong predictor of diabetes but was no longer significantly associated with incident cardiovascular disease . In analyses of threshold effects , adjusted relative risks for incident diabetes in HbA1c categories of less than 5.0 % , 5.0 % to 5.4 % , 5.5 % to 5.9 % , 6.0 % to 6.4 % , 6.5 % to 6.9 % , and 7.0 % or more were 1.0 , 2.9 , 12.1 , 29.3 , 28.2 , and 81.2 , respectively . Risk associations persisted after additional adjustment for C-reactive protein and after excluding individuals developing diabetes within 2 and 5 years of follow-up . CONCLUSIONS These prospect i ve findings suggest that HbA1c levels are elevated well in advance of the clinical development of type 2 diabetes , supporting recent recommendations for lowering of diagnostic thresholds for glucose metabolic disorders . In contrast , the association of HbA1c with incident cardiovascular events is modest and largely attributable to coexistent traditional risk factors",
"OBJECTIVE This study explores a range of relevant socio-demographic , physical and psychological factors in a unique examination of the risk factors for frequent attendance at primary care . The impact of patient activation for self-management on health service utilisation is of particular interest . METHODS A population -based sample of people with chronic disease from Queensl and , Australia , was interviewed using computer assisted telephone surveying . Data were collected from a r and om sample of 1470 people with either diabetes or a cardiovascular condition . RESULTS As participants became more activated they were less likely to frequently attend their main health care provider for assistance with their chronic condition . For both conditions the association was graduated and for participants with a cardiovascular condition this association remained statistically significant even after controlling for other potentially influential factors such as disease severity , length of time since diagnosis , and psychological distress . CONCLUSION Characteristics of the individual , including patient activation and psychological functioning , as well as disease factors contribute to primary care consulting patterns among people with chronic illness . PRACTICAL IMPLICATION S Efforts to improve patient activation for self-management should remain a central element of chronic care",
"OBJECTIVE A trial was performed to establish whether our group care model for lifestyle intervention in type 2 diabetes can be exported to other clinics . RESEARCH DESIGN AND METHODS This study was a 4-year , two-armed , multicenter controlled trial in 13 hospital-based diabetes clinics in Italy ( current controlled trials no. IS RCT N19509463 ) . A total of 815 non – insulin-treated patients aged were r and omized to either group or individual care . RESULTS After 4 years , patients in group care had lower A1C , total cholesterol , LDL cholesterol , triglycerides , systolic and diastolic blood pressure , BMI , and serum creatinine and higher HDL cholesterol ( P prescriptions . Health behaviors , quality of life , and knowledge of diabetes had become better in group care patients than in control subjects ( P < 0.001 , for all ) . CONCLUSIONS The favorable clinical , cognitive , and psychological outcomes of group care can be reproduced in different clinical setting",
"Context Several studies suggest that blood glucose levels are associated with cardiovascular disease , even at blood glucose values that do not meet diagnostic criteria for diabetes . Contribution Among adult residents of Norfolk , United Kingdom , there was a continuous relationship between hemoglobin A1c levels and cardiovascular disease and total mortality . This relationship was apparent even among persons without diabetes . Implication s These observations justify the need for studies that address whether improvements in glycemic control might improve health outcomes in persons who do not have diabetes . The Editors Diabetes mellitus is of major and increasing global public health importance ( 1 ) . Persons with diabetes are at increased risk for premature disability and death associated with vascular , renal , retinal , and neuropathic complications . Raised fasting and postchallenge blood glucose levels in an oral glucose tolerance test are used to diagnose diabetes . The diagnostic threshold is based on the shape of the risk curve between glucose levels and specific microvascular complications of diabetes ( 2 - 6 ) . Diabetes also increases the risk for macrovascular diseases , such as coronary heart disease and stroke ( 7 ) . In contrast to microvascular disease , increasing evidence suggests that the relationship between blood glucose level and macrovascular disease is continuous and does not have an obvious threshold ( 2 , 8 , 9 ) . Hemoglobin A1c concentration is an indicator of average blood glucose concentrations over the preceding 3 months ; it is useful for characterizing dysglycemia in population studies because it is simpler to perform than the oral glucose tolerance test ( 10 ) . In a 3-year follow-up of men in a prospect i ve study , we previously reported that hemoglobin A1c concentrations were related to cardiovascular disease and all-cause mortality ( 11 ) . However , we had insufficient power to examine risk relationships at concentrations close to the diagnostic threshold of 7 % or to examine the relationship in women . We report the relation between hemoglobin A1c concentrations and fatal and nonfatal coronary heart disease , cardiovascular disease events , and all-cause mortality in men and women after an average of 6 years of follow-up . Methods The European Prospect i ve Investigation into Cancer in Norfolk ( EPICNorfolk ) is a prospect i ve population study of 25 623 men and women who were between 40 and 79 years of age and who resided in Norfolk , United Kingdom . Participants were recruited from general practice registers . Information on the recruitment process is available elsewhere ( 12 ) . Between 1993 and 1997 , participants completed a health and lifestyle question naire . Participants were asked whether a doctor had ever told them that they have any of the conditions contained in a list that included diabetes , heart attack , and stroke . People with known diabetes were defined as those who responded yes to the diabetes option of this question . Smoking history was derived from responses ( yes or no ) to the questions : Have you ever smoked as much as 1 cigarette a day for as long as a year ? and Do you smoke cigarettes now ? At a clinic , trained nurses performed a health examination for each participant . Body mass index was estimated as weight (kg)/height ( m2 ) , and waist-to-hip ratio was determined by measurements of the circumference of the waist and hips . Blood pressure was measured by using an Accutorr ( Data scope , Mahwah , New Jersey ) noninvasive blood pressure monitor after the participant had been seated for 5 minutes . The mean of 2 readings was used for analysis . Nonfasting blood sample s were taken ; sample s for assay were stored in a refrigerator at 4 C until transport within 1 week of sampling to the Department of Clinical Biochemistry , University of Cambridge . Starting in 1995 , hemoglobin A1c was measured on fresh EDTA blood sample s by using high-performance liquid chromatography ( BioRad Diamat Automated Glycosylated Haemoglobin Analyser , Hemel Hempstead , United Kingdom ) . We report results for follow-up to January 2003 , an average of about 6 years . All participants were flagged for death certification at the Office of National Statistics ; vital status was obtained for the entire cohort . Trained nosologists coded death certificates according to the International Classification of Diseases , Ninth or Tenth Revisions ( ICD-9 or ICD-10 ) . Cardiovascular death ( stroke , coronary heart disease , and other vascular causes ) was defined as those whose underlying cause of death was coded as ICD-9 400448 or ICD-10 I10I79 . Death from coronary heart disease was defined as those whose cause of death was coded as ICD-9 410414 or ICD-10 I22I25 . Participants admitted to a hospital were identified by their National Health Service number . Hospitals were linked to the East Norfolk Health Authority data base , which identifies all hospital contacts throughout Engl and and Wales for Norfolk residents . We used the same ICD diagnostic codes described in the preceding paragraphs to ascertain hospital episodes of cardiovascular disease and coronary heart disease in our cohort . Participants were identified as having a coronary heart disease event during follow-up if they had a hospital admission or died with coronary heart disease as the cause of death . Of the coronary heart disease events identified , 21 % ( 112 of 529 ) were fatal ; of the cardiovascular disease events , 23 % ( 197 of 806 ) were fatal . In men , 24 % ( 76 of 321 ) of deaths were attributed to heart disease and 29 % ( 117 of 321 ) were attributed to cardiovascular disease . In women , 18 % ( 36 of 200 ) of deaths were attributed to heart disease and 35 % ( 70 of 200 ) were attributed to cardiovascular causes . The Norwich Ethics Committee approved the study , and participants gave signed informed consent . Statistical Analysis These analyses , undertaken by using SPSS software , version 10.0 ( SPSS , Inc. , Chicago , Illinois ) , included 10 232 men and women age 45 to 79 years who completed the health and lifestyle question naire and had available hemoglobin A1c measurements . We divided the cohort into 7 categories on the basis of baseline data : known diabetes , high likelihood of previously undiagnosed diabetes ( no personal history of diabetes but a hemoglobin A1c concentration 7 % ) , and hemoglobin A1c concentrations in 0.5percentage point intervals ( risk factor distributions and then coronary heart disease , cardiovascular disease , and all-cause mortality rates by hemoglobin A1c and diabetes category . Age-adjusted odds ratios were calculated by using logistic regression models . We used a Cox proportional hazards model to determine the independent contribution of hemoglobin A1c to total mortality and cardiovascular and coronary heart disease after adjustment for age , body mass index , waist-to-hip ratio , systolic blood pressure , blood cholesterol concentrations , cigarette smoking , and history of heart attack or stroke . Participants with missing baseline data for 1 or more risk factors ( 130 men and 186 women ) were excluded from the multivariate analyses . Role of the Funding Sources The funding sources had no role in the design , conduct , and reporting of the study or in the decision to su bmi t the manuscript for publication . Results Table 1 presents characteristics of the participants according to hemoglobin A1c concentration and self-reported diabetes . Those with known diabetes had higher mean ( SD ) hemoglobin A1c concentrations ( 8.0 % 1.9 % ) than the rest of the study sample ( 5.3 % 0.7 % ) . They were older and had a higher body mass index , waist-to-hip ratio , and systolic blood pressure ; they were also more likely to report having had a previous heart attack or stroke . Participants with probable but previously undiagnosed diabetes ( hemoglobin A1c 7 % ) shared these characteristics . Mean risk factor levels rose with increasing concentration of hemoglobin A1c less than 7 % . Table 1 . Distribution of Variables by Hemoglobin A1c Concentration and Known Diabetes in 4662 Men and 5570 Women Age 45 to 79 Years ( European Prospect i ve Investigation into Cancer in Norfolk , 1995 to 1997 ) Table 2 shows adjusted odds ratios for hemoglobin A1c concentrations , diabetes status , and outcomes . Persons with known or undiagnosed diabetes had a greater risk for all-cause mortality and cardiovascular or coronary heart disease than those without diabetes . Risk for coronary heart or cardiovascular disease and total mortality increased throughout the whole range of hemoglobin A1c concentrations ; those with hemoglobin A1c concentrations less than 5 % had the lowest rates . For men , a gradient of increasing rates through the distribution was apparent for all end points . For women , odds ratios for cardiovascular or coronary heart disease did not increase significantly until the hemoglobin A1c concentration reached 6 % ; odds ratios were very high in women with concentrations greater than 7 % . Table 2 . Rates and Age-Adjusted Relative Risks for Total Coronary Heart Disease Events , Cardiovascular Disease Events , and All-cause Mortality by Category of Hemoglobin A1c Concentration and Known Diabetes in 4462 Men and 5570 Women Age 45 to 79 Years ( European Prospect i ve Investigation into Cancer in Norfolk , 1995 to 2003 ) Table 3 shows outcomes after adjustment for age alone and then after adjustment for age and other risk factors . In men , known diabetes predicted coronary heart and cardiovascular disease events and total mortality with approximate 2-fold relative risks . These relative risks were only slightly attenuated after adjustment for known risk factors . In women , known diabetes status predicted an approximate 5-fold increase in risk for coronary heart and 3-fold increase in risk for cardiovascular disease events ; these increases were attenuated after adjustment for known risk factors to 3-fold and 2-fold risk , respectively . In men and women , hemoglobin A1c concentrations predicted an increased risk for"
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Background The purpose was to conduct systematic review s of the relationship between physical activity of healthy community-dwelling older ( > 65 years ) adults and outcomes of functional limitations , disability , or loss of independence . Methods Prospect i ve cohort studies with an outcome related to functional independence or to cognitive function were search ed , as well as exercise training interventions that reported a functional outcome . Electronic data base search strategies were used to identify citations which were screened ( title and abstract ) for inclusion . Included articles were review ed to complete st and ardized data extraction tables , and assess study quality . An established system of assessing the level and grade of evidence for recommendations was employed . Results Sixty-six studies met inclusion criteria for the relationship between physical activity and functional independence , and 34 were included with a cognitive function outcome . Greater physical activity of an aerobic nature ( categorized by a variety of methods ) was associated with higher functional status ( expressed by a host of outcome measures ) in older age . For functional independence , moderate ( and high ) levels of physical activity appeared effective in conferring a reduced risk ( odds ratio ~0.5 ) of functional limitations or disability . Limitation in higher level performance outcomes was reduced ( odds ratio ~0.5 ) with vigorous ( or high ) activity with an apparent dose-response of moderate through to high activity . Exercise training interventions ( including aerobic and resistance ) of older adults showed improvement in physiological and functional measures , and suggestion of longer-term reduction in incidence of mobility disability . A relatively high level of physical activity was related to better cognitive function and reduced risk of developing dementia ; however , there were mixed results of the effects of exercise interventions on cognitive function indices . Conclusions There is a consistency of findings across studies and a range of outcome measures related to functional independence ; regular aerobic activity and short-term exercise programmes confer a reduced risk of functional limitations and disability in older age . Although a precise characterization of a minimal or effective physical activity dose to maintain functional independence is difficult , it appears moderate to higher levels of activity are effective and there may be a threshold of at least moderate activity for significant outcomes
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"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 The relationship between obesity and physical function is not well understood . Physical activity may be a key factor impacting on the relationship between obesity and physical function . METHODS Subjects included 171 community-dwelling women ( mean age = 74.3 , SD = 4.3 ) participating in a 14-year follow-up study to a walking intervention trial . Measures of obesity [ body mass index ( BMI ) ] and physical activity ( Modified Paffenbarger Question naire ) were collected in 1982 , 1985 , 1995 , and 1999 . Physical function was assessed in 1999 using the Functional Status Question naire ( FSQ ) and gait speed . RESULTS Measures of obesity from 1982 to 1995 and measures of physical activity from 1982 to 1995 were related to physical function in 1999 . However , hierarchical regression analysis to predict physical function in 1999 controlling for the presence of chronic conditions indicated that physical activity from 1982 to 1995 , and not obesity from 1982 to 1995 , was an independent predictor of physical function ( FSQ : adjusted R2 = 0.09 , F = 4.68 , P Physical activity appears to be as important if not more important than body weight in predicting future physical function",
"This paper describes a quasi-experimental study of a musical exercise intervention to improve the physical , cognitive , behavioral status and life satisfaction of older residents in a long-term care facility in the United Kingdom . Twenty long-term care residents from three different units ( n=60 ) were recruited and assigned to one of three groups : a control ( C ) group ( no intervention ) , an occupational therapy ( OT ) group ( comparison group ) and a music exercise group ( intervention group ) . Assessment s of physical and cognitive status were made pre-intervention and repeated at the end of the 10-week exercise program and again 10 weeks after the completion of the program . The results show that both OT and exercise participation is associated with improvement in physical and cognitive function . However , the exercise group showed significant improvement in more areas than the OT group . The functional benefits from OT and exercise were not sustainable after these activities ceased and showed significant decline 10 weeks after the end of the programs",
"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 It is important to determine if permanent lifestyle changes may result from physical activity interventions and whether health may be affected by these changes . OBJECTIVE To conduct a 10-year follow-up of physical activity and self-reported health status in participants of a r and omized clinical trial of walking intervention . METHODS Of the original 229 volunteer postmenopausal women who participated in the original clinical trial , 196 ( N = 96 intervention and 100 controls ) completed the 10-year follow-up telephone interview . The interview protocol included questions on self-reported walking for exercise and purpose s other than exercise , the Paffenbarger sport and exercise index , functional status , and various chronic diseases and conditions . RESULTS The median values for both usual walking for exercise and total walking were significantly higher for walkers compared with controls ( for both , P = .01 ) , with median differences of 706 and 420 kcal/wk , respectively . After excluding women who reported heart disease during the original trial , 2 women in the walking group ( 2 % ) and 11 women in the control group ( 12 % ) reported physician-diagnosed heart disease over the last 10 years ( P = .07 ) . There were also fewer hospitalizations , surgeries , and falls among women in the walking group , although these differences were not statistically significant ( P>.05 ) . CONCLUSIONS Although limited by self-report , this study may be the first to demonstrate long-term exercise compliance to a r and omized control trial in older women and to suggest that health benefits may have ensued as a result of these increased activity levels",
"The goal was to determine the existence of differential effects of long-term moderate- or low-intensity exercise on selected bio-behavioral variables in 72 community-dwelling persons over 60 years of age . After screening , subjects were r and omly assigned to a moderate ( n = 39 , 60 - 70 % heart rate reserve [ HRR ] ) or low ( n = 33 , 30 - 40 % HRR ) intensity exercise protocol . Both groups exercised three times per week for 9 months and dependent measures were taken at baseline , 4.5 months and after 9 months . Repeated measures ANOVA with Tukey post hoc comparisons constituted the analysis approach . Moderate exercise showed no superiority over low-intensity exercise ; both groups improved about equally . Variables that significantly improved included : self-reported sleep ( sleep quantity and dream recall ) , mental status ( attention/concentration , short-term memory and higher cognitive functioning ) , health perceptions ( health outlook , health worry , rejection of the sick role ) , and cardiovascular fitness indicators ( submaximum stress test heart rate , maximum oxygen consumption ( VO2max ) , maximum work capacity and maximum exercise time ) . Similarity of outcomes in both groups may mean that the moderate exercise protocol was too conservative . Conversely , the findings may indicate that lower levels of exercise , which may be safer and more feasible over time , do improve fitness levels , prolong independent functioning , and promote positive perceptions of well-being in older adults",
"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",
"PURPOSE Lifestyle Interventions and Independence for Elders Pilot ( LIFE-P ) was a trial to examine the effects of a physical activity intervention ( PA ) compared with a health education control ( SA ) on measures of disability risk in sedentary older adults ( N = 424 ) . We examined adherence to the LIFE-P PA intervention for the first 12 months of the trial . METHODS The PA intervention consisted of walking , strength , flexibility , and balance training supplemented with behavioral skills training modules , and it used a phased , center-based schedule of adoption ( 3x wk(-1 ) , weeks 1 - 8 ) , transition ( 2x wk(-1 ) , weeks 9 - 24 ) , and maintenance ( 1x wk(-1 ) , weeks 25 to end of trial ) while transitioning to primarily home-based physical activity . SA consisted of weekly ( weeks 1 - 26 ) transitioning to monthly health education workshops . RESULTS Participation in moderate-intensity physical activity increased from baseline to months 6 and 12 in PA compared with SA ( P PA participants who reported > or = 150 min x wk(-1 ) of moderate activity demonstrated a significantly greater improvement in their Short Physical Performance Battery score compared with participants who reported PA arm , center-based attendance was 76.3 + /- 24.5 , 65.4 + /- 28.6 , and 49.8 + /- 35.8 % in the adoption , transition , and maintenance phases , respectively . CONCLUSIONS Adherence to physical activity in LIFE-P was associated with greater improvement in SPPB score and was consistent with adherence in physical activity trials of shorter duration in this subgroup of older adults . Older individuals at risk for disability can adhere to a regular program of physical activity in a long-term r and omized trial",
"Increasing physical activity is currently considered to be a possible prevention strategy for cancer , obesity , and cardiovascular disease , either alone or in combination with dietary changes . This paper presents results of a r and omized trial of moderate-to-vigorous intensity exercise in middle aged , sedentary women ; specifically , we report changes in and correlates of quality of life and functional status of this exercise intervention program for both the short ( three months ) and longer term ( 12 months ) . The intervention group showed a significant increase in Mental Health score from baseline to 3 months ( p General Health score ( p Change in Social Support – Affection were predictors of the changes in quality of life variables . This study documented improvements in quality of life and general functioning that occurred as a result of participating in an exercise intervention in sedentary middle-aged women",
"Background : Few studies have considered the neighborhood as a context in which to examine the physical activity and quality of life relationship . Purpose : The goal of this study was to evaluate the effects of a neighborhood walking program on quality of life among older adults . It was design ed as a r and omized trial involving a multilevel design with neighborhoods corresponding to primary sampling units and residents to secondary units . Methods : Five hundred eighty-two communitydwelling senior residents ( 65 years of age or older ) in neighborhoods in the northeast metropolitan area of Portl and , Oregon , were recruited through telephone , direct mail , and referrals . The walking intervention was delivered at the neighborhood level . Neighborhoods ( N = 56 ) were r and omly assigned to a 6-month , 3 times per week , leader-led walking group activity ( n = 28 ) or an information-only control group ( n = 28 ) . Primary outcome measures included SF-12 ( Physical , Mental summary scores ) and life satisfaction ( SWLS ) ; the secondary outcome measure was neighborhood walking activity , assessed at baseline , 3 months , and 6 months of the study period . Results : Compared to the control neighborhoods , results from multilevel , longitudinal analyses indicated significant improvements in the primary outcomes of SF-12 Physical ( p SF-12 Mental ( p ( p of walking activity ( p neighborhood-based walking program of low to moderate intensity is feasible and beneficial for promoting quality of life among senior residents at a community level",
"Six-year predictors of successful aging were analyzed for 356 Alameda County Study men and women aged 65 - 95 years measured prospect ively in 1984 and followed to 1990 . Successful aging was defined as needing no assistance nor having difficulty on any of 13 activity/mobility measures plus little or no difficulty on five physical performance measures . After adjusting for baseline successful aging , sex , and age , the authors found that 1984 predictors of 1990 successful aging included income above the lowest quintile ( odds ratio ( OR ) = 2.01 , 95 % confidence interval ( CI ) 0.99 - 4.11 ) , > or = 12 years of education ( OR = 1.67 , 95 % CI 0.98 - 2.84 ) , white ethnicity ( OR = 2.12 , 95 % CI 0.93 - 4.86 ) , diabetes ( OR = 0.10 , 95 % CI 0.01 - 0.79 ) , chronic obstructive pulmonary disease ( OR = 0.41 , 95 % CI 0.17 - 0.97 ) , arthritis ( OR = 0.43 , 95 % CI 0.26 - 0.71 ) , and hearing problems ( OR = 0.48 , 95 % CI 0.25 - 0.89 ) . Adjusting for all variables , the authors found that behavioral and psychosocial predictors included the absence of depression ( OR = 1.94 , 95 % CI 1.10 - 3.42 ) , having close personal contacts ( OR = 1.82 , 95 % CI 1.05 - 3.18 ) , and often walks for exercise ( OR = 1.77 , 95 % CI 1.00 - 3.12 ) . Cross-sectional comparisons at follow-up revealed significantly higher community involvement , physical activity , and mental health for those aging successfully",
"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",
"CONTEXT Evidence suggests that physical activity may be related to the clinical expression of dementia . Whether the association includes low-intensity activity such as walking is not known . OBJECTIVE To examine the association between walking and future risk of dementia in older men . DESIGN Prospect i ve cohort study . SETTING AND PARTICIPANTS Distance walked per day was assessed from 1991 to 1993 in 2257 physically capable men aged 71 to 93 years in the Honolulu-Asia Aging Study . Follow-up for incident dementia was based on neurological assessment at 2 repeat examinations ( 1994 - 1996 and 1997 - 1999 ) . MAIN OUTCOME MEASURES Overall dementia , Alzheimer disease , and vascular dementia . RESULTS During the course of follow-up , 158 cases of dementia were identified ( 15.6/1000 person-years ) . After adjusting for age , men who walked the least ( excess risk of dementia compared with those who walked more than 2 mile/d ( 17.8 vs 10.3/1000 person-years ; relative hazard [ RH ] , 1.77 ; 95 % confidence interval [ CI ] , 1.04 - 3.01 ) . Compared with men who walked the most ( > 2 mile/d ) , an excess risk of dementia was also observed in those who walked 0.25 to 1 mile/d ( 17.6 vs 10.3/1000 person-years ; RH , 1.71 ; 95 % CI , 1.02 - 2.86 ) . These associations persisted after accounting for other factors , including the possibility that limited amounts of walking could be the result of a decline in physical function due to pre clinical dementia . CONCLUSIONS Findings suggest that walking is associated with a reduced risk of dementia . Promoting active lifestyles in physically capable men could help late-life cognitive function",
"Background and aims : Little is known about muscle strength as a predictor of disability among older Mexican Americans . The aim of this study was to examine the association between h and grip strength and 7-year incidence of ADL disability in older Mexican American men and women . Methods : A 7-year prospect i ve cohort study of 2493 non-institutionalized Mexican American men and women aged 65 or older residing in five south-western states . Maximal h and grip strength test , body mass index , cognitive function , activities of daily living , self-reports of medical conditions ( arthritis , diabetes , heart attack , stroke , cancer , hip fracture ) , and depressive symptoms were obtained . Results : In a Cox proportional regression analysis , there was a linear relationship between h and grip strength at baseline and risk of incident ADL disability over a 7-year follow-up . Among non-disabled men at baseline , the hazard ratio of any new ADL limitation was 1.90(95 % CI 1.14–3.17 ) for those in the lowest quartile , when compared with men in the highest h and grip strength quartile , after controlling for age , marital status , medical conditions , high depressive symptoms , MMSE score , and BMI at baseline . Among non-disabled women at baseline , the hazard ratio of any new ADL limitation was 2.28 ( 95 % CI 1.59–3.27 ) for those in the lowest quartile , when compared with women in the highest h and grip strength quartile . Conclusions : H and grip strength is an independent predictor of ADL disability among older Mexican American men and women . The h and grip strength test is an easy , reliable , valid , inexpensive method of screening to identify older adults at risk of disability",
"OBJECTIVES To assess the extent to which physical activity and leg strength are associated with change in mobility in older persons . DESIGN Prospect i ve , observational cohort study . SETTING Retirement communities across the Chicago metropolitan area participating in the Rush Memory and Aging Project . PARTICIPANTS Eight hundred eighty-six ambulatory older persons without dementia . MEASUREMENT Rate of change in mobility . RESULTS In a linear mixed-effects model that controlled for age , sex , education , and a term for baseline physical activity , a higher level of physical activity was associated with a slower rate of mobility decline ( estimate=0.006 , st and ard error (SE)=0.003 , P=.03 ) ; each additional hour of physical activity at baseline was associated with an approximately 3 % decrease in the rate of mobility decline . In a similar model , a higher level of baseline leg strength was associated with a slower rate of mobility decline ( estimate=0.031 , SE=0.132 , P=.02 ) ; each additional unit of leg strength at baseline was associated with an approximately 20 % decrease in the rate of mobility decline . In a final model , which included terms for physical activity and leg strength together , both were associated with decline in mobility . Furthermore , both remained associated with mobility even after controlling for body composition , balance , pulmonary function , cognition , history of joint pain , cardiovascular diseases and risk factors , and medications . CONCLUSION Physical activity and leg strength are relatively independent predictors of mobility decline in older persons . Although physical activity may improve strength , the beneficial effect of physical activity on mobility is likely to involve other pathways",
"CONTEXT There are potential benefits of mind-body techniques on cognitive function because the techniques involve an active attentional or mindfulness component , but this has not been fully explored . OBJECTIVE To determine the effect of yoga on cognitive function , fatigue , mood , and quality of life in seniors . DESIGN R and omized , controlled trial comparing yoga , exercise , and wait-list control groups . PARTICIPANTS One hundred thirty-five generally healthy men and women aged 65 - 85 years . INTERVENTION Participants were r and omized to 6 months of Hatha yoga class , walking exercise class , or wait-list control . Subjects assigned to classes also were asked to practice at home . MAIN OUTCOME MEASURES Outcome assessment s performed at baseline and after the 6-month period included a battery of cognitive measures focused on attention and alertness , the primary outcome measures being performance on the Stroop Test and a quantitative electroencephalogram ( EEG ) measure of alertness ; SF-36 health-related quality of life ; Profile of Mood States ; Multi-Dimensional Fatigue Inventory ; and physical measures related to the interventions . RESULTS One hundred thirty-five subjects were recruited and r and omized . Seventeen subjects did not finish the 6-month intervention . There were no effects from either of the active interventions on any of the cognitive and alertness outcome measures . The yoga intervention produced improvements in physical measures ( eg , timed 1-legged st and ing , forward flexibility ) as well as a number of quality -of-life measures related to sense of well-being and energy and fatigue compared to controls . CONCLUSIONS There were no relative improvements of cognitive function among healthy seniors in the yoga or exercise group compared to the wait-list control group . Those in the yoga group showed significant improvement in quality -of-life and physical measures compared to exercise and wait-list control groups",
"Abstract : A r and omised controlled trial was conducted to determine whether a 12–month program of group exercise had beneficial effects on physiological and cognitive functioning and mood in 187 older community – dwelling women . The exercisers ( n= 94 ) and controls ( n= 93 ) were well matched in terms of the test measures and a number of health and life – style assessment s. The mean number of classes attended by the 71 exercise subjects who completed the program was 59.0 ( range 26 to 82 ) . At the end of the trial , the exercisers showed significant improvements in reaction time , strength , memory span and measures of wellbeing when compared with the controls . There was also an indication that anxiety had been reduced in the exercisers . Within the exercise group , improvements in memory span were associated with concomitant improvements in both reaction time and muscle strength . Also , within this group , initial mood measures were significantly inversely associated with improvements at retest , which suggests that the program may have normalised mood states in subjects who had high initial depression , anxiety and stress levels , rather than inducing improvements in all subjects . These findings suggest that group exercise has beneficial effects on physiological and cognitive functioning and wellbeing in older people",
"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",
"CONTEXT Poor muscle strength , functional limitations , and disability often coexist , but whether muscle strength during midlife predicts old age functional ability is not known . OBJECTIVE To determine whether h and grip strength measured during midlife predicts old age functional limitations and disability in initially healthy men . DESIGN AND SETTING A 25-year prospect i ve cohort study , the Honolulu Heart Program , which began in 1965 among Japanese-American men living on Oahu , Hawaii . PARTICIPANTS A total of 608945- to 68-year-old men who were healthy at baseline and whose maximal h and grip strength was measured from 1965 through 1970 . Altogether , 2259 men died over the follow-up period and 3218 survivors participated in the disability assessment in 1991 through 1993 . MAIN OUTCOME MEASURES Functional limitations including slow customary walking speed ( or = 0.4 m/s ) and inability to rise from a seated position without using the arms , and multiple self-reported upper extremity , mobility , and self-care disability outcomes . RESULTS After adjustment for multiple potential confounders , risk of functional limitations and disability 25 years later increased as baseline h and grip strength , divided into tertiles , declined . The odds ratio ( OR ) of walking speed of 0.4 m/s or slower was 2.87 ( 95 % confidence interval [ CI ] , 1.76 - 4.67 ) in those in the lowest third and 1.79 ( 95 % CI , 1.14 - 2.81 ) in the middle third of grip strength vs those in the highest third . The risk of self-care disability was more than 2 times greater in the lowest vs the highest grip strength tertile . Adding chronic conditions identified at follow-up to the models predicting disability reduced the ORs related to grip strength only minimally . CONCLUSIONS Among healthy 45- to 68-year-old men , h and grip strength was highly predictive of functional limitations and disability 25 years later . Good muscle strength in midlife may protect people from old age disability by providing a greater safety margin above the threshold of disability",
"Low bone mass , functional impairment , low muscle strength , and postural instability are predictors of the risk of fracture in an elderly person . The purpose of this study was to investigate the functional impact of an unvarying long-term exercise program to be carried out at home . The exercises had been shown to delay bone loss in an elderly population . At the Department of Physical Medicine and Rehabilitation , University of Vienna , postmenopausal women who had been stratified into exercise or control groups 5 to 10 yr ago were called in for a follow-up examination . Frequency of training , habits , and pain causing disability in activities of daily living were recorded . Walking velocity , muscle strength , and postural stability were measured . Functional assessment , blood analysis , and x-rays of the spine were performed additionally . One hundred twenty-four women aged 68.3 + /- 6.8 yr ( mean + /- SD ) underwent a follow-up investigation at the outpatient clinic . After 7.7 + /- 1.1 yr the compliance of the training group was still 36 % . Self-chosen gait velocity was slightly higher in the regular exercisers than in the controls . No intergroup differences were found for pain induced disability , muscle strength , body sway , and fracture rate . The pain disability index was significantly associated with corrected self-chosen gait velocity . The results suggest that an unvarying home-based exercise program may support general agility but does not yield enough force to improve muscle strength and postural stability in healthy , nondisabled , postmenopausal women who start exercising at the age of 60 yr . Further studies are needed to define more appropriate exercise programs for a comprehensive improvement of functional outcome in a population at high risk for osteoporosis",
"BACKGROUND The Short Physical Performance Battery ( SPPB ) , which includes walking , balance , and chair st and s tests , independently predicts mobility disability and activities of daily living disability . To date , however , there is no definitive evidence from r and omized controlled trials that SPPB scores can be improved . Our objective was to assess the effect of a comprehensive physical activity ( PA ) intervention on the SPPB and other physical performance measures . METHODS A total of 424 sedentary persons at risk for disability ( ages 70 - 89 years ) were r and omized to a moderate-intensity PA intervention or a successful aging ( SA ) health education intervention and were followed for an average of 1.2 years . RESULTS The mean baseline SPPB score on a scale of 0 - 12 , with 12 corresponding to highest performance , was 7.5 . At 6 and 12 months , the PA versus SA group adjusted SPPB ( + /- st and ard error ) scores were 8.7 + /- 0.1 versus 8.0 + /- 0.1 , and 8.5 + /- 0.1 versus 7.9 + /- 0.2 , respectively ( p 400-meter walking speed was also significantly improved in the PA group . The PA group had a lower incidence of major mobility disability defined as incapacity to complete a 400-meter walk ( hazard ratio = 0.71 , 95 % confidence interval = 0.44 - 1.20 ) . CONCLUSIONS A structured PA intervention improved the SPPB score and other measures of physical performance . An intervention that improves the SPPB performance may also offer benefit on more distal health outcomes , such as mobility disability",
"BACKGROUND The effect of changes in physical exercise on progression of musculoskeletal disability in seniors has rarely been studied . METHODS We studied a prospect i ve cohort annually from 1984 to 2000 using the Health Assessment Question naire Disability Index ( HAQ-DI ) . The cohort included 549 participants , 73 % men , with average end-of- study age of 74 years . At baseline and at the end of the study , participants were classified as \" High \" or \" Low \" vigorous exercisers using a cut-point of 60 min/wk . Four groups were formed : \" Sedentary \" ( Low-->Low ; N = 71 ) , \" Exercise Increasers \" ( Low-->High ; N = 27 ) , \" Exercise Decreasers \" ( High-->Low ; N = 73 ) , and \" Exercisers \" ( High-->High ; N = 378 ) . The primary dependent variable was change in HAQ-DI score ( scored 0 - 3 ) from 1984 to 2000 . Multivariate statistical adjustments using analysis of covariance included age , gender , and changes in three risk factors , body mass index , smoking status , and number of comorbid conditions . Participants also prospect ively provided reasons for exercise changes . RESULTS At baseline , Sedentary and Increasers averaged little exercise ( 16 and 22 exercise min/wk ) , whereas Exercisers and Decreasers averaged over 10 times more ( 285 and 212 exercise min/wk ; p initial HAQ-DI scores , ranging from 0.03 to 0.08 . Increasers and Exercisers achieved the smallest increments in HAQ-DI score ( 0.17 and 0.11 ) over 16 years , whereas Decreasers and Sedentary fared more poorly ( increments 0.27 and 0.37 ) . Changes in HAQ-DI score for Increasers compared to Sedentary were significantly more favorable ( p end-of- study values with increments in disability similar to those participants who were more active throughout . These results suggest a beneficial effect of exercise , even when begun later in life , on postponement of disability",
"CONTEXT Dementia is common , costly , and highly age related . Little attention has been paid to the identification of modifiable lifestyle habits for its prevention . OBJECTIVE To explore the association between physical activity and the risk of cognitive impairment and dementia . DESIGN , SETTING , AND SUBJECTS Data come from a community sample of 9008 r and omly selected men and women 65 years or older , who were evaluated in the 1991 - 1992 Canadian Study of Health and Aging , a prospect i ve cohort study of dementia . Of the 6434 eligible subjects who were cognitively normal at baseline , 4615 completed a 5-year follow-up . Screening and clinical evaluations were done at both waves of the study . In 1996 - 1997 , 3894 remained without cognitive impairment , 436 were diagnosed as having cognitive impairment-no dementia , and 285 were diagnosed as having dementia . MAIN OUTCOME MEASURE Incident cognitive impairment and dementia by levels of physical activity at baseline . RESULTS Compared with no exercise , physical activity was associated with lower risks of cognitive impairment , Alzheimer disease , and dementia of any type . Significant trends for increased protection with greater physical activity were observed . High levels of physical activity were associated with reduced risks of cognitive impairment ( age- , sex- , and education-adjusted odds ratio , 0.58 ; 95 % confidence interval , 0.41 - 0.83 ) , Alzheimer disease ( odds ratio , 0.50 ; 95 % confidence interval , 0.28 - 0.90 ) , and dementia of any type ( odds ratio , 0.63 ; 95 % confidence interval , 0.40 - 0.98 ) . CONCLUSION Regular physical activity could represent an important and potent protective factor for cognitive decline and dementia in elderly persons",
"Objective : To test the hypothesis that physical fitness is associated with more successful cognitive aging . Methods : Surviving participants ( N = 460 ) of the Scottish Mental Survey of 1932 were tested on the same general cognitive test at age 11 and 79 years . Measures of grip strength , 6-meter walk time , and lung function ( forced expiratory volume from the lungs in 1 second [ FEV1 ] ) were assessed at age 79 years . Results : A latent physical fitness trait , derived by principal components analysis of the three fitness measures , was significantly associated with successful cognitive aging . Cognitive score at age 11 , sex , social class , and APOE-ε4 genotype were included as covariables . Higher childhood IQ was associated with better lung function in old age . Conclusions : Physical fitness is associated with cognitive reserve . Intervention studies aim ed at making older people fitter are good c and i date s to improve cognitive aging ",
"A prospect i ve analysis of risk factors for Alzheimer 's disease was a major objective of the Canadian Study of Health and Aging , a nationwide , population -based study . Of 6,434 eligible subjects aged 65 years or older in 1991 , 4,615 were alive in 1996 and participated in the follow-up study . All participants were cognitively normal in 1991 when they completed a risk factor question naire . Their cognitive status was reassessed 5 years later by using a similar two-phase procedure , including a screening interview , followed by a clinical examination when indicated . The analysis included 194 Alzheimer 's disease cases and 3,894 cognitively normal controls . Increasing age , fewer years of education , and the apolipoprotein E epsilon4 allele were significantly associated with increased risk of Alzheimer 's disease . Use of nonsteroidal anti-inflammatory drugs , wine consumption , coffee consumption , and regular physical activity were associated with a reduced risk of Alzheimer 's disease . No statistically significant association was found for family history of dementia , sex , history of depression , estrogen replacement therapy , head trauma , antiperspirant or antacid use , smoking , high blood pressure , heart disease , or stroke . The protective associations warrant further study . In particular , regular physical activity could be an important component of a preventive strategy against Alzheimer 's disease and many other conditions",
"Physical activity may help preserve cognitive function and decrease dementia risk , but epidemiologic findings are inconsistent . The authors conducted a prospect i ve study to determine the association between physical activity and risk of dementia , Alzheimer 's disease , and vascular dementia . The US study population comprised 3,375 men and women aged 65 years or older , free of dementia at baseline , who participated in the Cardiovascular Health Cognition Study in 1992 - 2000 . Leisure-time energy expenditure and an activity index reflecting number of different physical activities were calculated . Analyses were based on Cox proportional hazards models . There were 480 incident cases of dementia over an average of 5.4 years of follow-up . After multivariate adjustment , participants in the highest quartile of physical energy expenditure had a relative risk of dementia of 0.85 ( 95 % confidence interval : 0.61 , 1.19 ) compared with those in the lowest quartile , and participants engaging in > or=4 activities had a relative risk of dementia of 0.51 ( 95 % confidence interval : 0.33 , 0.79 ) compared with those engaging in 0 - 1 activity . These associations were more marked in apolipoprotein E genotype ( APOE ) epsilon4 allele noncarriers but were absent in carriers . A similar pattern was observed for Alzheimer 's disease and vascular dementia . Mechanisms to explain the observed relations deserve further study",
" Older and younger aerobically trained and sedentary adults participated in an S1-S2-S3 paradigm design ed to elicit event-related potential ( ERP ) and behavioral responses to determine the influence of cardiovascular fitness on cognitive and motor processes . The paradigm provided warning ( S1 ) as to the difficulty level of an upcoming decision task ( S2 ) . Participants had to decide the taller of two bars on presentation of S2 but hold their response until S3 , to which they indicated their choice motorically . Results revealed age-related differences for ERP measures as older participants showed increased amplitude of the stimulus preceding negativity ( SPN ) prior to S2 , and longer latencies and equipotentiality of P3 in response to S2 . Fitness effects were also observed for the contingent negative variation ( CNV ) with decreased amplitude for fit relative to sedentary individuals . Age interacted with fitness for P3 latency to S2 as older sedentary individuals showed the longest latency followed by older fit and both younger groups . No significant group differences were observed for reaction time ( RT ) to S3 . Therefore , physical fitness is associated with attenuation of cognitive decline in older individuals and greater economy of motor preparation for both young and older participants",
"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 this study was to estimate the prevalence of having no disability in the year prior to death in very old age and to examine factors associated with this outcome . Participants were men and women aged 65 years and older who were followed prospect ively between 1981 and 1991 from three communities : New Haven , Connecticut ; Iowa and Washington counties , Iowa ; and East Boston , Massachusetts . Persons who died in late old age with known disability status within 15 months of death ( n = 1,097 ) were studied for predictors of dying without disability at the last follow-up interview prior to death . The probability of a nondisabled 65-year-old man 's surviving to age 80 and then being nondisabled prior to death was 26 % and , for a 65-year-old woman , the probability of surviving to age 85 and being nondisabled before death was 18 % . Physical activity was a key factor predicting nondisability before death . There was nearly a twofold increased likelihood of dying without disability among the most physically active group compared with sedentary adults ( adjusted odds ratio = 1.86 , 95 % confidence interval 1.24 - 2.79 ) . These findings provide encouraging evidence that disability prior to death is not an inevitable part of a long life but may be prevented by moderate physical activity",
"OBJECTIVES To examine the association between physical activity and the risk of incident disability , including impairment in activities of daily living ( ADLs ) and instrumental activities of daily living ( IADLs ) , in community-based older persons free of dementia . DESIGN Prospect i ve , observational cohort study . SETTING Approximately 40 retirement communities across the Chicago metropolitan area . PARTICIPANTS More than 1,000 older persons from the Rush Memory and Aging Project , an ongoing longitudinal clinical -pathological study of common chronic conditions of old age . MEASUREMENTS All participants underwent detailed annual clinical evaluations that included assessment s of physical activity , ADLs , IADLs , and gait performance . The associations between physical activity , mortality , and incident disability were examined using a series of Cox proportional hazards models controlled for age , sex , education , and baseline gait . RESULTS At baseline , participants spent a mean+/-st and ard deviation of 3.0+/-3.5 hours per week engaging in physical activity ( range 0 - 35 ) . In a proportional hazards model , the risk of death decreased 11 % ( hazard ratio (HR)=0.89 , 95 % confidence interval (CI)=0.83 - 0.95 ) for each additional hour of physical activity per week . For those who were not disabled at baseline , the risk of developing disability in ADLs decreased 7 % ( HR=0.93 , 95 % CI=0.88 - 0.98 ) for each additional hour of physical activity per week . Similarly , the risk of disability in IADLs decreased 7 % ( HR=0.93 , 95 % CI=0.89 - 0.99 ) for each additional hour of physical activity . CONCLUSION For community-based older persons without dementia , physical activity is associated with maintenance of functional status , including a reduced risk of developing impairment in ADLs and IADLs",
"OBJECTIVES To assess the association between physical activity and subsequent physical functioning in middle-aged adults across a range of body mass index ( BMI ) categories . DESIGN Prospect i ve nationally representative cohort studies . SETTING The United States and Engl and . PARTICIPANTS Eight thous and seven hundred two individuals in the United States and 1,507 in Engl and aged 50 to 69 and free of impairment at baseline , followed up for 6 years . MEASUREMENTS Self-reported and measured BMI and self-reported level of physical activity . Outcome measures were score on a physical performance battery and self-reported mobility impairment . RESULTS In both studies , being overweight and being obese were associated with greater risk of impairment ( than being of recommended weight ) . In all weight categories and both countries , higher levels of physical activity were associated with lower risks of mobility impairment . For example , U.S. respondents of recommended weight ( BMI 20 - 25 ) who were active on 3 or more days per week had a relative risk ( RR ) of incident mobility difficulties , compared with those who were less active , of 0.56 ( 95 % confidence interval (CI)=0.40 - 0.78 ) ; for those who were obese ( BMI > /=30 ) the corresponding RR was 0.59 ( 95 % CI=0.45 - 0.76 ) . CONCLUSION Excess bodyweight is a risk factor for impaired physical function in middle-aged and older people . Physical activity is protective of impaired physical functioning in this age group in subjects with recommended weight , overweight , and obesity . Older adults should be encouraged to engage in appropriate levels of physical activity irrespective of their weight",
"BACKGROUND Short-term prospect i ve studies have shown physical activity to be related to functional status . To our knowledge , the association between physical activity levels and functional status over a longer period has not been established . METHODS Two hundred twenty-nine older women ( mean age , 74.2 years ) who were involved in a r and omized controlled walking intervention from 1982 to 1985 were subsequently followed up until December 1999 . Physical activity was assessed in 1985 , 1995 , and 1999 using a physical activity question naire and a physical activity monitor . In 1999 , functional status was assessed by self-report and performance-based measures . RESULTS Subjective and objective measures of physical activity in 1985 independently predicted gait speed in 1999 after controlling for age , chronic conditions , and activity limitation ( subjective model-adjusted R2 = 0.09 [ P=.03 ] ; and objective model-adjusted R2 = 0.13 [ P=.008 ] ) . The consistency of physical activity participation from 1985 to 1995 was also related to functional status in 1999 . Women who were always active had the best functional status and women who were always inactive had the worst functional status . For difficulty with activities of daily living : those always active , 17 ( 37.8 % ) of 45 women ; those inconsistently active , 24 ( 40.0 % ) of 60 women ; and those always inactive , 39 ( 59.1 % ) of 66 women ( chi2 for trend P=.02 ) . For score on the Physical Performance Test : those always active , 24.9 ; those inconsistently active , 24.5 ; and those always inactive , 23.8 ( analysis of variance with linear contrasts P=.04 ) . For gait speed : those always active , 1.17 m/s ; those inconsistently active , 1.15 m/s ; and those always inactive , 1.03 m/s ( analysis of variance with linear contrasts P=.002 ) . CONCLUSION We demonstrated a significant relation between physical activity during a 14-year period and current functional status in older women , thus suggesting that physical activity plays a role in maintaining functional ability later in life",
"Context Some studies suggest that people with high levels of physical activity are less likely to develop dementia . Content All 1740 participants in this cohort study were 65 years of age or older and were cognitively intact at baseline . Over 6.2 years , the rate of dementia was 13.0 per 1000 person-years in those who exercised 3 or more times per week and 19.7 per 1000 person-years in those who exercised less than 3 times per week . Limitations The only measure of exercise intensity was self-reported frequency . The cohort was largely white and well-educated . Implication s This study adds to the evidence that regular exercise is associated with a lower risk for dementia . However , the existing evidence does not prove that regular exercise is associated with a lower dementia risk . The Editors Alzheimer disease and other dementing illnesses are major sources of morbidity and mortality ( 1 - 3 ) that affect millions of persons in the increasingly aging society of the United States . Research design ed to discover strategies to delay onset and progression of these potentially devastating illnesses is ongoing worldwide . Effective prevention strategies would result in substantial benefits through improved quality of life , prolonged independent life expectancy , and reduced economic cost and social burdens . Regular physical exercise is an important element in overall health promotion ( 4 ) and might also be an effective strategy to delay onset of dementia ( 5 ) . A biological basis for how physical exercise might preserve brain function includes improved cerebral blood flow and oxygen delivery ( 6 ) and inducing fibroblast growth factor in the hippocampus ( 7 ) . More recent evidence suggests that reduced loss of hippocampal brain tissue in the aging brain is related to level of physical fitness ( 8) . Evidence from some longitudinal studies and r and omized trials suggests that physical exercise enhances cognitive function in older adults ( 9 - 15 ) , whereas other studies have failed to observe the benefits of physical exercise in preserving cognitive function ( 16 - 19 ) . Many people regard Alzheimer disease as one of the most dreaded consequences of aging . If regular physical exercise were shown to be effective in reducing the risk or delaying the onset of dementing illnesses , it would be another compelling reason to promote physical exercise . Few population -based longitudinal studies have examined the role of physical exercise on the risk for dementia in elderly persons . One recent longitudinal study showed that physical exercise was associated with decreased risk for decline in cognitive function ( odds ratio [ OR ] , 0.58 ) , Alzheimer disease ( OR , 0.50 ) , and any dementia ( OR , 0.63 ) ( 11 ) , whereas another longitudinal study showed no association between physical exercise and dementia ( 16 ) . More recent studies showed that walking was associated with a reduced risk for dementia and Alzheimer disease in a cohort of Japanese-American men ( 20 ) and that engaging in more diverse physical activities was associated with a reduced risk for dementia in the Cardiovascular Health Study ( 21 ) . The purpose of this study was 2-fold : 1 ) to determine whether regular exercise is associated with a reduced risk for incidence of dementia ( in particular , Alzheimer disease ) in a cohort followed biennially over 6 years and 2 ) to examine whether the association of physical exercise with incident dementia is modulated by other potential risk factors , such as depression , cardiovascular and cerebrovascular disease , diabetes , apolipoprotein E 4 allele , cognitive function , physical function , self-rated health , and lifestyle characteristics . Methods Study Sample The Adult Changes in Thought ( ACT ) study is a population -based , longitudinal study of aging and dementia . The ACT study was design ed to determine the incidence of Alzheimer disease , other types of dementia , and cognitive impairment as well as to determine risk factors for these conditions . The details of the ACT study have been described elsewhere ( 22 , 23 ) . Briefly , a r and om sample of 6782 individuals was drawn from Seattle-area members of Group Health Cooperative ( GHC ) , a consumer-governed health maintenance organization . The participants were 65 years of age and older when the study began in 1994 to 1996 . Those who had an existing diagnosis of dementia , were current residents of a nursing home , or were participating in other studies were ineligible ( n= 1360 ) . Of 5422 eligible persons , 2581 participated and 2841 declined participation . Age , sex , and ethnicity of the remaining 2581 participants did not differ significantly from those who were excluded . Nonresponse has been described elsewhere ( 22 ) . Declining to participate was more common among the oldest age group ( > 85 years ) , women , and African-American and minority groups ( 22 ) . Additional details regarding the incident rates of dementia and Alzheimer disease from the ACT study have been published elsewhere and are consistent with rates reported in U.S. and European cohort studies ( 22 ) . The institutional review boards of the University of Washington and Group Health Cooperative approved the ACT study . Participants received the Cognitive Ability Screening Instrument ( CASI ) ( 24 ) as initial screening for cognitive function and were interviewed with structured question naires to obtain data , including demographic characteristics , medical history , memory and general functioning , and potential epidemiologic risk factors . Persons scoring 86 or higher on the CASI were entered directly into the ACT cohort as being cognitively intact . ( The CASI scores range from 0 to 100 ; a score of 86 corresponds to a Mini-Mental State Examination score of 25 to 26 . ) Persons with a score lower than 86 had additional medical record review and st and ardized clinical and neuropsychological evaluation for dementia . Persons who did not meet established criteria for dementia ( 25 ) were included in the ACT cohort . The current study sample was selected from the 2581 ACT participants to examine the temporal relationship of physical exercise preceding development of dementia . By design , we selected the 1895 persons whose CASI scores were above the 25th percentileCASI scores 91 to 100 . We excluded 686 persons whose CASI scores were in the lowest quartileCASI scores 62 to 90because the lowest quartile group might include persons who had mild cognitive impairment or impending dementia ( 26 ) . We did not collect information about the history of exercise before the participants entered the study . Therefore , in the group with low CASI scores , we could not be certain whether a reported low level of physical exercise preceded the development of dementia or was a consequence of the development of cognitive impairment or dementia . Of 1895 participants selected , 155 withdrew after the baseline visit and did not have a follow-up examination and were thus excluded from the analyses , leaving the analytic sample of 1740 persons . Incident Dementia We conducted biennial examinations to identify cases of incident dementia , when participants were rescreened with the CASI . Those who scored 86 or higher on the CASI remained in the ACT cohort . Scores on the CASI that were less than 86 at follow-up prompted a full st and ardized clinical examination . The results of rescreening by the CASI and by the clinical and neuropsychological examinations were review ed at a consensus diagnosis conference that included at least the examining physician , a neuropsychologist , another study physician , and the study nurse . Persons who did not meet the criteria for dementia were considered as not having dementia and were followed in the ACT cohort ( 22 , 23 ) . Persons who met the Diagnostic and Statistical Manual of Mental Disorders , fourth edition ( DSM-IV ) , criteria ( 25 ) for dementia were considered to have incident dementia . Dementia type was determined by the National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer 's Disease and Related Disorders Association ( NINCDS-ADRDA ) criteria ( 27 ) for Alzheimer disease and by the DSM-IV criteria ( 25 ) for other types of dementia . Level of physical activity was not considered at the consensus conference . Physical Exercise Physical exercise was assessed at baseline by asking participants the number of days per week they did each of the following activities for at least 15 minutes at a time during the past year : walking , hiking , bicycling , aerobics or calisthenics , swimming , water aerobics , weight training or stretching , or other exercise . The frequency of exercise was calculated by the times per week that participants engaged in any of these forms of exercise . In this study , persons who exercised at least 3 times a week , above the lowest quartile , were classified as exercising regularly . Baseline Variables as Potential Confounders Numerous factors may influence the relationship between exercise and risk for dementia , including physical functioning , cognitive function , depression , health conditions , and lifestyle characteristics . Physical function was assessed by a performance-based physical function ( PPF ) test ( 23 ) , which consisted of 4 performance tests : 10-foot timed walk , time to st and from a seated position in a chair to a st and ing position 5 times , balance test , and grip strength in the dominant h and . Each test was scored from 0 to 4 points . The final PPF score was the sum of the scores for the 4 performance tests and ranged from 0 to 16 ; higher scores indicated better physical function . Details of the PPF test have been reported elsewhere ( 23 ) . Cognitive function was assessed by using the CASI , which provides quantitative assessment of attention , concentration , orientation , short-term memory , long-term memory , language ability , visual construction , list-generating fluency , abstract ion , and judgment ( 24 ) . At baseline , depression was measured by using the 11-item Center for Epidemiologic Studies Depression ( CES-D ) scale ( 28 ) . The CES-D scores ranged from 0 to 33 , with higher scores",
"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",
"OBJECTIVES To estimate the incidence of chronic activities of daily living ( ADL ) disability and to analyze the sociodemographic , health status , adverse lifestyle , and leisure-time physical activity predictors for chronic ADL disability . DESIGN We recruited a cohort of community-dwelling older people in Taipei , Taiwan , who were not ADL disabled in August 1993 , and we followed them until August 1996 . SETTING S AND PARTICIPANTS The study subjects were 1321 community-dwelling people aged 65 years or older who were ADL intact at the initial interview in August 1993 . The study sample was a subset of a probability sample ( n = 1583 ) r and omly selected from household registration s in the four districts of the Taipei metropolitan area . MEASUREMENTS Baseline information regarding various factors potentially associated with the development of chronic ADL disability was assessed and collected at the beginning of the study . Study participants were assessed annually for ADL function by a structured home interview using a six-item scale . Participants who were unable to perform independently at least one of the six items -- eating , bathing , dressing , toileting , transfers , and walking inside the house -- for more than 3 months were considered chronically ADL disabled . Cox proportional hazard regression models were utilized to examine the independent effect of the potential predictors on risk of chronic ADL disability . RESULTS During the 3-year study period , 145 ( 11.0 % ) participants developed chronic ADL disability , 58 ( 4.4 % ) participants were lost to follow-up , and 83 ( 6.3 % ) participants died . Multiple hazard regression analysis showed that individuals aged 70 to 79 years or older than age 80 had increased risk of ADL disability ( relative risk : 2.05 ( 95 % confidence interval ( CI ) , 1.35 - 3.11 ) and 3.89 ( 95%CI , 2.33 - 6.50 ) , respectively ) compared with those participants younger than age 70 . Risk of chronic ADL disability was inversely associated with routine exercise ( RR = 0.52 ; 95 % CI , 0.39 - 0.68 ) . CONCLUSIONS Age is the most significant predictor of chronic ADL disability . Lack of routine exercise is also a significant predictor of ADL disability in older adults",
"UNLABELLED This review over previously published articles , describes physical activity changes during ageing from age 50 - 85 in the 1914-cohort in Glostrup , Denmark , and analyses the association between physical activity and mortality , myocardial infa rct ion , hip fractures and functional ability . The 1914-cohort in Glostrup was examined at age 50 in 1964 and re-examined 1974 , 1984 , 1989 , 1994 and 1999 . Some analyses were based on pooled data ( CCPPS : Copenhagen Centre for Prospect i ve Population Studies ) from three longitudinal population studies conducted in Copenhagen , Denmark : The Copenhagen County Centre for Preventive Medicine in Glostrup , The Copenhagen City Heart Study and The Copenhagen Male Study . Physical activity of work and leisure time was classified into four levels based on questions originally constructed by Saltin and Grimby . MAIN OUTCOME MEASURES all-cause mortality , fatal and non-fatal myocardial infa rct ion , hip fracture and functional ability ( Avlund mobility index of dependency ) . The lifetime risk from a sedentary leisure time was analysed in multivariate regression analyses controlling for covariates describing gender , age , life style , education and chronic diseases . Less than one third of the population had a sedentary leisure time . Physical activity definitely influenced health and quality of life over the life course in a positive way : compared to the group of inactive men and women , the mortality was about 60 % , the incidence of myocardial infa rct ion 70 % and the incidence of hip fractures 75 % in the moderate active groups . On top the physically active persons gained independency in activities of daily living",
"Objective : To investigate the association between potentially modifiable lifestyle factors and cognitive abilities/depressive symptoms in community-dwelling women aged 70 years and over . Method : Cross-sectional study of community-dwelling women aged 70 years and over ( n = 278 ; mean age = 74.6 years ) . Lifestyle variables assessed included smoking , alcohol consumption , physical activity , nutrition and education . The mental health measures of interest were depression , anxiety , quality of life and cognitive function , as assessed by the Beck Depression Inventory ( BDI ) , Beck Anxiety Inventory ( BAI ) , SF-36 , and the Cambridge Cognitive Examination for Mental Disorders of the Elderly ( CAMCOG ) , respectively . Results : Physically active women were half as likely to be depressed ( BDI score ≥ 10 ) and anxious ( BAI score ≥ 8) when compared to their physically inactive counterparts ( OR = 0.5 , 95 % CI = 0.3–0.8 for both , adjusted for marital status and smoking in the case of depression ) . Having ever smoked more than 20 cigarettes per day was associated with increased risk of depression ( OR = 2.8 , 95 % CI = 1.4–5.5 , adjusted for marital status and physical activity ) . Moderate alcohol use was associated with increased likelihood of having a CAMCOG score within the highest 50 percentile ( OR = 2.0 , 95 % CI = 1.1–3.5 , adjusted for age and education ) , as was more than minimum statutory education ( OR = 2.0 , 95 % CI = 1.1–3.5 , adjusted for age and alcohol consumption ) . There was no obvious association between vitamin B12/folate deficiency or obesity with any of the measures of interest . Conclusions : The results of this study are consistent with the hypothesis that depression is directly associated with heavy smoking and inversely associated with physical activity . They also support the idea that non-harmful alcohol consumption is associated with better cognitive performance . R and omised clinical trials should be now design ed to clarify whether management of lifestyle factors reduces the incidence of mood disorders and cognitive impairment in later life",
"OBJECTIVES To investigate the association between different types of physical activity behavior and incident mobility limitation in older men and women and to examine whether muscle parameters mediate these associations . DESIGN Cohort study with 4.5-year follow-up . SETTING Metropolitan areas surrounding Pittsburgh , Pennsylvania , and Memphis , Tennessee . A r and om sample of white Medicare beneficiaries and all age-eligible blacks . PARTICIPANTS Three thous and seventy-five black and white men and women aged 70 to 79 with no self-reported difficulty walking one-quarter of a mile or climbing 10 steps , enrolled in the Health , Aging and Body Composition ( Health ABC ) Study . MEASUREMENTS Participants were classified as exercisers ( reporting > or = 1,000 kcal/wk of exercise activity ) , lifestyle active ( reporting activity and > or = 2,719 kcal/wk of total physical activity ) , or inactive ( reporting exercise activity and incident mobility limitation , was defined as two consecutive , semiannual self-reports of any difficulty walking one quarter of a mile or climbing 10 steps . Thigh muscle area , thigh muscle attenuation ( a marker of fat infiltration in muscle ) , appendicular lean soft tissue mass , and isokinetic knee extensor strength were examined as potential mediators . RESULTS Over 4.5 years , 34.3 % of men and 47.4 % of women developed mobility limitation . Inactive persons had twice the risk of incident mobility limitation as exercisers ( hazard ratio (HR)=2.08 , 95 % confidence interval (CI)=1.60 - 2.70 , for men , HR=1.98 , 95 % CI=1.51 - 2.60 , for women ) . Lifestyle-active men and women had an intermediate risk ( HR=1.47 and 1.44 , respectively ) . For the lifestyle active and inactive , absence of walking activity conferred an additional risk of mobility limitation . Muscle parameters did not mediate the relationship between physical activity and mobility limitation , except for knee extensor strength in men . CONCLUSION Exercise and an active lifestyle that includes walking protect against mobility loss in older men and women . Activity effects on muscle parameters do not explain this association",
"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",
"The cardiovascular and behavioral adaptations associated with a 4-month program of aerobic exercise training were examined in 101 older men and women ( mean age = 67 years ) . Subjects were r and omly assigned to an Aerobic Exercise group , a Yoga and Flexibility control group , or a Waiting List control group . Prior to and following the 4-month program , subjects underwent comprehensive physiological and psychological evaluations . Physiological measures included measurement of blood pressure , lipids , bone density , and cardiorespiratory fitness including direct measurements of peak oxygen consumption ( VO2 ) and anaerobic threshold . Psychological measures included measures of mood , psychiatric symptoms , and neuropsychological functioning . This study demonstrated that 4 months of aerobic exercise training produced an overall 11.6 % improvement in peak VO2 and a 13 % increase in anaerobic threshold . In contrast , the Yoga and Waiting List control groups experienced no change in cardiorespiratory fitness . Other favorable physiological changes observed among aerobic exercise participants included lower cholesterol levels , diastolic blood pressure levels , and for subjects at risk for bone fracture , a trend toward an increase in bone mineral content . Although few significant psychological changes could be attributed to aerobic exercise training , participants in the two active treatment groups perceived themselves as improving on a number of psychological and behavioral dimensions",
"OBJECTIVES To verify if h and -grip performance in older men is a predictor of disability . DESIGN Population -based prospect i ve study . SETTING A sample from the Italian rural cohorts of the FINE study ( Finl and , Italy , Netherl and s Elderly ) , representative of the general population of elderly men surveyed in 1991 and 1995 . PARTICIPANTS 140 men aged 71 - 91 years who reported no disability in performing activities of daily living ( ADLs ) , instrumental activity of daily living ( IADLs ) and mobility activities at baseline examination and provided information on their functional status at follow-up 4 years later . MEASUREMENTS Disability was defined as needing help in performing ADLs , IADLs and mobility . H and -grip strength was evaluated at baseline by a mechanical dynamometer . RESULTS After adjusting for potential confounding variables , a lower concentration of high-density lipoprotein cholesterol was the only factor predicting disability in men aged 76 years or younger and only reduced h and -grip strength predicted incident disability in men 77 years or older . CONCLUSION Poor h and strength as measured by h and -grip is a predictor of disability in older people . The h and -grip test is an easy and inexpensive screening tool to identify elderly people at risk of disability",
"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",
"Kalapotharakos VI , Michalopoulos M , Strimpakos N , Diamantopoulos K , Tokmakidis SP : Functional and neuromotor performance in older adults : Effect of 12 wks of aerobic exercise . Am J Phys Med Rehabil 2006;85:61–67 . Objective : There is little information regarding the effect of aerobic exercise on physical and neuromotor performance in older adults . The aim of this r and omized , controlled trial was to determine the effects of a 12-wk aerobic exercise program on functional and neuromotor performance in inactive healthy older adults . Design : A total of 22 inactive healthy older adults , aged 60–75 yrs , voluntarily participated in the study and were r and omly assigned to a progressively increased high-intensity aerobic exercise group ( n = 12 ) or to a control group ( n = 10 ) . The aerobic exercise group exercised three times per week for 12 wks on nonconsecutive days . Both groups were evaluated before and after the exercise period in the one-repetition maximum of knee extensors and flexors , 6-min walk distance , chair-rising time , and whole-body reaction time . Results : Multivariate analysis of variance repeated measures ( 2 × 2 ) revealed significant ( P interaction for one-repetition maximum knee extension and flexion strength , 6-min walk distance , chair-rising time , and whole-body reaction time . For the aerobic exercise group , the following variables improved significantly ( P : the one-repetition maximum knee extensors ( 12 % ) and flexors ( 19 % ) muscle strength , 6-min walk distance ( 17 % ) , chair-rising time ( 8 % ) , and whole-body reaction time ( 20 % ) . No significant differences were observed in the control group . Conclusions : The results of the present study show that short-term progressively increased high-intensity aerobic exercise improved the physical and neuromotor performance in inactive healthy older adults . These findings suggest that the participation in a progressively increased high-intensity aerobic exercise program may improve mobility and ability to carry out activities of daily living in older adults",
"Purpose : The purpose of this study was to determine the effects of 9-week multicomponent training on the functional fitness of healthy older adults in different age groups . Method : Forty-two participants were r and omly assigned and stratified by their age group : Training and Control Young Old Groups ( TYOG , CYOG ) ( between 60 – 73 years ) , Training and Control Old Groups ( TOG , COG ) ( between 74 – 86 years ) . The training programme consisted of three sessions per week of walking , strengthening , and flexibility exercises . A recently developed Functional Fitness Test battery to assess the physical parameters associated with independent functioning in older adults was performed before and after training . Results : Training caused significant increases in all functional fitness tests in the TYOG and also in the TOG . There was no difference according to the absolute changes between TYOG and TOG due to the training ( p > 0.05 ) . Training produced a significant improvement in chair sit and reach , arm curl , chair st and and 6 min walk test scores in the TYOG and TOG when they were compared to the control groups ( p Multicomponent training can produce substantial increase in functional fitness tests in young old adults and older adults and the rate of restoration of function is approximately similar in the two old age groups",
"BACKGROUND Concern exists that certain types of exercise , particularly vigorous activity , may increase physical disability among older individuals . We investigated the prevalence of , and risk factors for , physical disability in active older persons ( runners ) , and examined factors influencing the progression of physical disability with age . METHODS Physical disability , measured using the Health Assessment Question naire Disability Index , was assessed prospect ively in 454 runners , age 50 or greater , over five to seven years by annual mailed question naires . Baseline sociodemographic , clinical , and life-style characteristics associated with the presence of any disability over the course of the study were determined and contrasted with those in 292 older non-runners who had been similarly followed . RESULTS Two hundred twenty-two runners ( 49 % ) reported some physical disability during the study . The presence of arthritis symptoms at baseline was the most important risk factor for physical disability ; older age , greater body mass index , strenuous work-related physical activity , and the use of more medications were also associated with a greater likelihood of physical disability . Among the non-runners , 224 ( 77 % ) reported some physical disability , and the presence of arthritis symptoms was also the most important risk factor for physical disability in this group . Age-related changes in physical disability differed between those with and without arthritis symptoms in both the runner and non-runner groups . CONCLUSIONS The presence of arthritis symptoms was an important risk factor for physical disability among both older runners and non-runners , and also identified subgroups of individuals with different progressions of disability with age",
"BACKGROUND The magnitude and duration of the benefit of running and other aerobic exercise on disability and mortality in elderly persons are not well understood . We sought to quantify the benefits of aerobic exercise , including running , on disability and mortality in elderly persons and to examine whether morbidity can be compressed into later years of life by regular exercise . METHODS A 13-year prospect i ve cohort study of 370 members of a runners ' club for persons aged 50 and older and 249 control subjects initially aged 50 to 72 years ( mean , 59 years ) , with annual ascertainment of the Health Assessment Question naire disability score , noting any deaths and their causes . Linear mixed models were used to compute postponement in disability , and survival analysis was conducted to determine the time to and causes of death . RESULTS Significantly ( P disability levels in runners ' club members vs controls and in ever runners vs never runners were sustained for at least 13 years . Reaching a Health Assessment Question naire disability level of 0.075 was postponed by 8.7 ( 95 % confidence interval [ CI ] , 5.5 - 13.7 ) years in runners ' club members vs controls . Running club membership and participation in other aerobic exercise protected against mortality ( rate ratio , 0.36 [ 95 % CI , 0.20 - 0.65 ] and 0.88 [ 95 % CI , 0.77 - 0.99 ] , respectively ) , while male sex and smoking were detrimental ( rate ratio , 2.4 [ 95 % CI , 1.4 - 4.2 ] and 2.2 [ 95 % CI , 1.1 - 4.6 ] , respectively ) . Controls had a 3.3 times higher rate of death than runners ' club members , with higher death rates in every disease category . Accelerated rates of disability and mortality were still not seen in the runners ' club members ; true compression of morbidity was not yet observable through an average age of 72 years . CONCLUSION Running and other aerobic exercise in elderly persons protect against disability and early mortality , and are associated with prolongation of a disability-free life",
"Objective : Few studies have investigated the relationships between body composition , functional ability , and age-related disability in postmenopausal women . We investigated the relative role of fat mass , lean mass , and muscle strength in the development of disability in a group of healthy postmenopausal women younger than 75 years . Design : We performed a cross-sectional study among 396 independently living women aged 56 - 73 years , r and omly selected between 8 and 30 years after menopause . Lean mass and fat mass were assessed by dual-energy x-ray absorptiometry . Muscle strength ( grip and leg extensors ) was assessed using dynamometry . Functional ability was estimated by Physical Performance Score , physical activity during the preceding year , and impairment in activities of daily living . Results : Of the participants , 43.7 % were overweight ( 25 ≥ BMI . Higher muscle strength was observed with increasing lean body mass , and participants with higher muscle strength scored better in the physical performance score and activities of daily living . Higher fat mass was significantly associated with a lower physical performance score , lower physical activity , and a higher frequency of disability . Increasing fat mass was associated with increasing lean mass and decreasing lean/fat ratio . The increase in lean mass and muscle strength associated with higher fat mass was mainly localized in the legs . Conclusions : Our results support the role of fat mass as the primary risk marker for disability , which might later accelerate by the age-related decrease in lean mass and the development of sarcopenia after the age of 75 years",
"OBJECTIVES To examine joint associations of physical activity and adiposity measures ( body mass index ( BMI ) , waist circumference , percentage body fat ) with incident mobility limitation . DESIGN Prospect i ve observational cohort study . SETTING Memphis , Tennessee and Pittsburgh , Pennsylvania . PARTICIPANTS Two thous and nine hundred and eighty-two black and white men and women aged 70 to 79 participating in the Health , Aging and Body Composition ( Health ABC ) study . MEASUREMENTS Mobility limitation was defined as reported difficulty walking one-quarter of a mile or climbing 10 steps during two consecutive semiannual assessment s over 6.5 years . Three measures of adiposity were included in this study : BMI , total percentage body fat , and waist circumference . Physical activity was assessed using a modified leisure-time physical activity question naire . RESULTS Forty-six percent of the cohort developed mobility limitation . White and black men with a high BMI ( > or = 30 kg/m(2 ) ) , high total percentage body fat ( > 31.3 % ) , or high waist circumference ( > or = 102 cm ) had an approximately 60 % , 40 % , and 40 % , respectively , higher risk of incident mobility limitation than those with low adiposity . In women , high adiposity was also associated with a significantly higher mobility limitation risk than in those with low adiposity . Low physical activity ( lowest quartile ) was associated with a 70 % higher risk of mobility limitation in all groups . Persons with high adiposity and low physical activity were at particularly high risk of mobility limitation . People with high adiposity who were physically active had an equally high risk of mobility limitation as inactive people with low adiposity . CONCLUSION High adiposity and low self-reported physical activity predicted the onset of mobility limitation in well-functioning older persons . Preventing weight gain in old age and promoting physical activity in obese and non-obese older persons may therefore be effective strategies to prevent mobility loss and future disability",
"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",
"OBJECTIVE In older people , mobility impairments and physical inactivity are risk factors for further disability and death . We studied the interaction of physical activity and mobility impairment as a predictor of dependence and mortality . DESIGN A population -based , prospect i ve study . The data were collected in structured interviews in the year 1988 and 8 years later in the year 1996 as part of the Evergreen Project . PARTICIPANTS Subjects were 1109 independently living , at baseline 65- to 84-year-old people in the city of Jyvaskyla , in central Finl and . METHODS Participants were ranked into four groups : ( 1 ) Intact mobility and physically active ( Mobile-Active ) , ( 2 ) Intact mobility and sedentary ( Mobile-Sedentary ) , ( 3 ) Impaired mobility and physically active ( Impaired-Active ) , and ( 4 ) Impaired mobility and sedentary ( Impaired-Sedentary ) . The confounders adjusted for in the models included age , marital status , education , chronic conditions , smoking , and physical exercise earlier in life . RESULTS In men and women , the relative risk of death was two times greater in Impaired-Active and three times greater in Impaired-Sedentary groups than the risk of death in Mobile-Active groups . However , the risk of death did not differ between Mobile-Active and Mobile-Sedentary groups . The odds ratio for dependency ( 95 % confidence interval ) in Impaired-Sedentary men was 5.21 ( 1.44 - 18.70 ) and in Impaired-Sedentary women was 2.92 ( 1.52 - 5.60 ) compared to Mobile-Active groups . The risk of dependence did not differ significantly between Mobile-Active , Mobile-Sedentary , and Impaired-Active groups . CONCLUSIONS Mobility impairments predicted mortality and dependence . However , among people with impaired mobility , physical activity was associated with lower risks , whereas the risk did not differ according to activity level among those with intact mobility . Despite of their overall greater risk , mobility-impaired people may be able to prevent further disability and mortality by physical exercise",
"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",
"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",
"The aim of the Odense training studies is to eluci date if regular physical training influences the expected decline in physical functional ability in order to assess capacity for postponing dependence in old age . All participants were healthy community-dwelling women representing three different age-cohorts of 65 , 75 and 85 year-old subjects . The 65 and 85 year-old participants of the training group took part in physical class-based exercises for eight months with one session of 60 min a week , whereas the 75 year-old women trained twice a week over eight months . The multicomponent training consisted of various exercises typically involving body awareness , rhythm , aerobic performance ( walking ) , muscle strength and muscle endurance , flexibility , reaction and balance exercises . Physical ability was measured as physical performance test ( PPT ) , isometric muscle strength of the trunk , hip and leg , aerobic capacity and walking speed . This shows that regular training can significantly improve physical ability of elderly women with regard to PPT , maximal oxygen uptake and maximal walking speed , suggesting that both young-old and old-old women are able to benefit from regular tailored exercise training . Thus , physical training of old community-dwelling women appears to represent a prophylactic remedy that merits further research aim ed at evaluating the preliminary findings of the present studies in larger , less selective groups of participants",
"Physical exercise is commonly promoted as a panacea . However many of the cl aim ed benefits , in particular any positive effects on bone density , have not been scientifically proved . We assessed the effects of a twice-weekly aerobic weight-bearing exercise program on bone density in postmenopausal women . We tested bone density at the spine and hip in 19 exercisers with a mean age of 66.4 years ( SEM + /- 1.2 ) before and after a two-year exercise program , and in 11 controls , mean age 65.4 years ( SEM + /- 1.5 ) . We also assessed risk factors for cardiovascular disease and tested wellbeing and cognitive function . The mean percentage change in lumbar bone mineral density was -0.8 in exercisers and -3.8 in controls ( difference 3.0 per cent ; 95 per cent confidence interval ( CI ) 0.3 to 5.7 per cent ; P = 0.031 ) . The mean percentage change in trochanteric bone mineral concentration was + 9.6 in exercisers and -4.4 in controls ( difference 14.0 per cent ; CI 4.6 to 23.5 ; P = 0.0049 ) . The exercisers also had significantly higher wellbeing and diastolic blood pressure . This study adds strong evidence that twice-weekly weight-bearing aerobic exercise has a protective effect on bone density in postmenopausal women as well as being associated with other measurable benefits",
"OBJECTIVES To determine whether cardiorespiratory fitness at baseline is associated with maintenance of cognitive function over 6 years or with level of cognitive function on tests performed 6 years later in a longitudinal study of healthy older people . DESIGN Prospect i ve cohort . SETTING Community-based study of noninstitutionalized adults aged 55 and older living in Sonoma , California . PARTICIPANTS Three hundred forty-nine cohort members without evidence of cardiovascular disease , musculoskeletal disability , or cognitive impairment at baseline . MEASUREMENTS Cardiorespiratory fitness measures were based on a st and ard treadmill exercise test protocol and included peak oxygen consumption ( peak VO2 ) , treadmill exercise duration , and oxygen uptake efficiency slope ( OUES ) . Cognitive function was evaluated at baseline with a modified Mini-Mental State Examination ( mMMSE ) and after 6 years of follow-up with a detailed cognitive test battery that included the full MMSE , three tests of attention/executive function , two measures of verbal memory , and two tests of verbal fluency . RESULTS Participants with worse cardiorespiratory fitness at baseline experienced greater decline on the mMMSE over 6 years ( mean mMMSE decline ( 95 % confidence interval ) by baseline peak VO2 tertile : lowest = -0.5 ( -0.8 to -0.3 ) , middle = -0.2 ( -0.5 - 0.0 ) , highest = 0.0 ( -0.3 - 0.2 ) , P = .002 for trend over tertiles ) . Participants with worse baseline cardiorespiratory fitness also performed worse on all cognitive tests conducted 6 years later . Results were similar for analyses based on peak VO2 , treadmill exercise duration , and OUES . After adjustment for demographic and health-related covariates , measures of cardiorespiratory fitness were associated most strongly with measures of global cognitive function and attention/executive function . CONCLUSION Baseline measures of cardiorespiratory fitness are positively associated with preservation of cognitive function over a 6-year period and with levels of performance on cognitive tests conducted 6 years later in healthy older adults . High cardiorespiratory fitness may protect against cognitive dysfunction in older people"
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OBJECTIVE To identify self-reported sport concussion symptom scales and to describe the psychometric properties of these identified scales . DESIGN Systematic review . INTERVENTION PubMed , Medline , CINAHL , Scopus , Web of Science , Sport Discus , PsycINFO and AMED were search ed from their establishment until December 2008 . The medical subject heading terms " brain concussion " , " signs or symptoms " and " athletic injuries " . The search was limited to articles published in English . An additional search of the reference lists of the retrieved articles was conducted . Only full-text articles were considered for this study and these were retrieved to determine whether they met the inclusion criteria . RESULTS The initial search result ed in 421 articles , which were reduced to 290 articles after removing duplicates . The h and search result ed in 17 articles , thus giving a total of 307 articles . Full text was available for 295 articles of which 60 met the criteria for inclusion . The excluded 235 articles were case reports , review s and guidelines on concussion management or studies that had not used a symptom scale or checklist . CONCLUSIONS Six core scales were identified with a broad range of symptom items but with limited information on their psychometric properties . There were numerous derivative scales reported , most of which have not been method ically developed or subjected to scientific scrutiny . Despite this , they do make a contribution to the detection , assessment and return to play decisions but there is a need for the clinical user to be aware that many of these scales have " evolved " rather than being scientifically developed
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"Background Neurocognitive testing has been endorsed as a “ cornerstone ’ of concussion management by recent Vienna and Prague meetings of the Concussion in Sport Group . Neurocognitive testing is important given the potential unreliability of athlete self-report after injury . Relying only on athletes'ormalities after injury . Study Design Case control study ; Level of evidence , 3 . Methods High school and college athletes with a diagnosed concussion were tested 2 days after injury . Postinjury neurocognitive performance ( Immediate Postconcussion Assessment and Cognitive Testing ) and symptom ( postconcussion symptom ) scores were compared with preinjury ( baseline ) scores and with those of an agex and education-matched noninjured athlete control group . “ Abnormal ” test performance was determined statistically with Reliable Change Index scores . Results Sixty-four percent of concussed athletes reported a significant increase in symptoms , as judged by postconcussion symptom scores , compared with preinjury baseline at 2 days after injury . Eighty-three percent of the concussed sample demonstrated significantly poorer neurocognitive test results relative to their own baseline performance . The addition of neurocognitive testing result ed in a net increase in sensitivity of 19 % . Ninety-three percent of the sample had either abnormal neurocognitive test results or a significant increase in symptoms , relative to their own baseline ; 30 % of a control group demonstrated either abnormalities in neurocognitive testing or elevated symptoms , as judged by postconcussion symptom scores . For the concussed group , use of symptom and neurocognitive test results result ed in an increased yield of 29 % overreliance on symptoms alone . In contrast , 0 % of the control group had both symptoms and abnormal neurocognitive testing . Conclusion Reliance on patients ’ self-reported symptoms after concussion is likely to result in underdiagnosis of concussion and may result in premature return to play . Neurocognitive testing increases diagnostic accuracy when used in conjunction with self-reported symptoms",
"CONTEXT The return-to-play decision after sport-related cerebral concussion depends in part on knowing when an athlete has fully recovered postural control after injury . OBJECTIVE To describe the postconcussion recovery of postural control using approximate entropy ( ApEn ) , a regularity statistic from nonlinear dynamics . DESIGN Retrospective case series analysis . SETTING Sports medicine research laboratory . PATIENTS OR OTHER PARTICIPANTS Collegiate athletes from whom center-of-pressure and symptom data were collected at preseason , less than 48 hours after injury , and 48 to 96 hours after injury . MAIN OUTCOME MEASURE(S ) Approximate entropy values reflecting the amount of r and omness contained in center-of-pressure oscillations were calculated for anterior-posterior ( AP ) and medial-lateral ( ML ) time series . Equilibrium scores reflecting the amplitude of center-of-pressure AP oscillations were used to indicate postural stability . The number and severity of symptoms were described . RESULTS Compared with the healthy preseason state , ApEn values for the AP and ML time series generally declined immediately after injury in both steady and unsteady injured athletes . At 48 to 96 hours after injury , ApEn values for the ML time series remained significantly depressed ( mean difference compared with preseason = -0.268 , st and ard error = 0.072 ) , even among athletes whose initial postural instability had resolved . We found few significant relationships between changes in ApEn values and changes in symptoms before and after injury . CONCLUSIONS The effects of cerebral concussion on postural control appear to persist for longer than 3 to 4 days , even among athletes with no signs of unsteadiness . Our results may reflect changes in neurophysiologic or mechanical constraints on postural control . Approximate entropy provides a theoretically distinct , valuable measurement alternative that may prove useful for reducing uncertainty in the return-to-play decision",
"CONTEXT Approximately 300 000 sport-related concussions occur annually in the United States , and the likelihood of serious sequelae may increase with repeated head injury . OBJECTIVE To estimate the incidence of concussion and time to recovery after concussion in collegiate football players . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 2905 football players from 25 US colleges were tested at preseason baseline in 1999 , 2000 , and 2001 on a variety of measures and followed up prospect ively to ascertain concussion occurrence . Players injured with a concussion were monitored until their concussion symptoms resolved and were followed up for repeat concussions until completion of their collegiate football career or until the end of the 2001 football season . MAIN OUTCOME MEASURES Incidence of concussion and repeat concussion ; type and duration of symptoms and course of recovery among players who were injured with a concussion during the seasons . RESULTS During follow-up of 4251 player-seasons , 184 players ( 6.3 % ) had a concussion , and 12 ( 6.5 % ) of these players had a repeat concussion within the same season . There was an association between reported number of previous concussions and likelihood of incident concussion . Players reporting a history of 3 or more previous concussions were 3.0 ( 95 % confidence interval , 1.6 - 5.6 ) times more likely to have an incident concussion than players with no concussion history . Headache was the most commonly reported symptom at the time of injury ( 85.2 % ) , and mean overall symptom duration was 82 hours . Slowed recovery was associated with a history of multiple previous concussions ( 30.0 % of those with > or =3 previous concussions had symptoms lasting > 1 week compared with 14.6 % of those with 1 previous concussion ) . Of the 12 incident within-season repeat concussions , 11 ( 91.7 % ) occurred within 10 days of the first injury , and 9 ( 75.0 % ) occurred within 7 days of the first injury . CONCLUSIONS Our study suggests that players with a history of previous concussions are more likely to have future concussive injuries than those with no history ; 1 in 15 players with a concussion may have additional concussions in the same playing season ; and previous concussions may be associated with slower recovery of neurological function",
"This study explored the diagnostic utility of the composite scores of Immediate Post-Concussion Assessment and Cognitive Testing ( ImPACT ) and Post Concussion Symptom Scale scores ( PCSS ) . Recently concussed high school athletes ( N=72 ) were tested within 72 h of sustaining a concussion , and data were compared to non-concussed high school athletes with no history of concussion ( N=66 ) . Between-groups MANOVA revealed a significant multivariate effect of concussion on test performance ( p ImPACT composite scores , as well as the PCSS to classify concussion status . One discriminant function was identified that consisted of the Visual Memory , Processing Speed , and Impulse Control composite scores PCSS , which correctly classified 85.5 % of the cases . Approximately 82 % of participants in the concussion group and 89 % of participants in the control group were correctly classified . Using these data , the sensitivity of ImPACT was 81.9 % , and the specificity was 89.4 % . As part of a formal concussion management program , ImPACT is a useful tool for the assessment of the neurocognitive and neurobehavioral sequelae of concussion , and can also provide post-injury cognitive and symptom data that can assist a practitioner in making safer return to play decisions",
"Objective The purpose of this pilot study was to document the nature and temporal profile of the clinical symptoms of acute sport-related concussion . Design Prospect i ve cohort study Patient Population A total of 303 elite Australian football players participating in a national competition during a single season . Outcome Measures Number and duration of symptoms , digit symbol substitution test ( DSST ) scores , time of return to play post injury . Results A total of 23 concussions were recorded over the course of the 20-week football season . No catastrophic head injuries occurred . Headache was the most common symptom and the most persistent , with 40 % of players reporting headache symptoms lasting more than 15 minutes . Ten of the players ( 43 % ) returned to sport on the day of the injury with the remainder resuming play within 2 weeks . A low likelihood of return to play on the day of injury was found where 3 or more symptoms were present or where the symptoms lasted more than 15 minutes . These findings were significantly correlated with poor DSST performance . Conclusions This pilot study suggests that both the number of postconcussive symptoms and their duration may be used as a measure of injury severity and a guide for return to play",
"Primary objective : To examine the relationship between the occurrence of whiplash-associated disorders and concussion symptoms in hockey players . Research design : Prospect i ve cohort observational study to examine the relationship between whiplash associated disorders and concussion in actual hockey play . Methods and procedures : Twenty hockey teams were followed prospect ively for one season . Team therapists completed acute and 7–10 day follow-up evaluation question naires for all of the players who received either a whiplash mechanism or a concussion . Main outcomes and results : 183 players were registered for this study ; 13 received either a whiplash mechanistic injury or a concussion injury . Initial injuries ranged from WAD I to WAD III and all subjects reported concussion symptoms . Only three subjects reported full resolution of bothWAD and concussion symptoms at the 7–10 day follow-up evaluation . Conclusions : There is a strong association between whiplash induced neck injuries and the symptoms of concussion in hockey injuries . Both should be evaluated when dealing with athletes/ patients suffering from either injury",
"OBJECTIVE : The purpose of this study was to compare concussion rates and recovery times for athletes wearing newer helmet technology compared to traditional helmet design . METHODS : This was a three-year , prospect i ve , naturalistic , cohort study . Participants were 2,141 high school athletes from Western Pennsylvania . Approximately half of the sample wore the Revolution helmet manufactured by Riddell , Inc. ( n = 1,173 ) and the remainder of the sample used st and ard helmets ( n = 968 ) . Athletes underwent computerized neurocognitive testing through the use of ImPACT at the beginning of the study . Following a concussion , players were reevaluated at various time intervals until recovery was complete . RESULTS : In the total sample , the concussion rate in athletes wearing the Revolution was 5.3 % and in athletes wearing st and ard helmets was 7.6 % [ & khgr;2 ( 1 , 2 , 141 ) = 4.96 , P relative risk estimate was 0.69 ( 95 % confidence interval = 0.499– 0.958 ) . Wearing the Revolution helmet was associated with approximately a 31 % decreased relative risk and 2.3 % decreased absolute risk for sustaining a concussion in this cohort study . The athletes wearing the Revolution did not differ from athletes wearing st and ard helmets on the mechanism of injury ( e.g. , head-to-head strike ) , on-field concussion markers ( e.g. , amnesia or loss of consciousness ) , or on-field presentation of symptoms ( e.g. , headaches , dizziness , or balance problems ) . CONCLUSION : Recent sophisticated laboratory research has better eluci date d injury biomechanics associated with concussion in professional football players . This data has led to changes in helmet design and new helmet technology , which appears to have beneficial effects in reducing the incidence of cerebral concussion in high school football players",
"Context With increasing knowledge and research about concussion , there have been few objective studies that have used neuropsychological domain scores and postural stability to assess concussion . Objective To evaluate the recovery curve of athletes who incur sport-related concussion from repeated serial testing of neuropsychological and posturography testing . Design A prospect i ve epidemiological model was used for the course of the study . Setting Division I intercollegiate athletics . Participants Athletes participating in football , soccer , basketball , softball , and cheerleading . Main Outcome Measures Neuropsychological scores and posturography measures were obtained preseason and serially at day 1 , day 2 , day 3 , and day 10 postconcussion . Control participants were tested at the same intervals . Neuropsychological scores were converted to st and ards score and then into domains of attention , learning , speed of information processing , concentration , memory , and verbal fluency . Analysis of covariance with the baseline test as the covariate was used to analyze the data with univariate post hoc tests performed . Results Significant group differences were found for self reported symptoms ( P = 0.001 ) , speed of information processing ( P = 0.005 ) , mean stability ( P = 0.002 ) , and vestibular function ( P = 0.003 ) between injured and control participants . A group , by day , planned comparison found that speed of information processing and composite balance measures demonstrated significant differences through day 10 postinjury , while symptoms and the vestibular ratio remained significant only through day 3 . Conclusions The concussion recovery curve demonstrated short-term neuropsychological and posturography deficits following injury . A comprehensive approach to concussion management should be used to assess the injury and make return-to-play decisions",
"OBJECTIVE Our purpose was to determine whether sex differences exist with respect to post-concussion symptoms and neurocognitive function in concussed collegiate athletes . METHODS A prospect i ve dependent- sample cohort design was used to compare baseline and post-concussion neuropsychological test scores and endorsed symptoms as functions of serial post-concussion assessment with respect to time and sex . The Immediate Post-concussion Assessment and Cognitive Testing ( ImPACT ) battery was administered to a multicenter analysis group of 79 concussed athletes . This computerized neuropsychological test was given to the athletes during the preseason and , on average , 2 and 8 days postinjury . RESULTS Multivariate analyses revealed no significant between-group differences on baseline test performance with respect to sex on any of the ImPACT composite scores or on the total symptom score . Multivariate analyses of post-concussion data revealed a significant main effect of time on ImPACT scores , but no main effect of sex was identified , and no time-by-sex interaction existed . Post hoc analysis revealed that concussed female athletes performed significantly worse than concussed male athletes on visual memory tasks ( P = 0.001 ) , and analysis of endorsed post-concussion symptoms revealed that concussed men were significantly more likely than concussed women to report post-concussion symptoms of vomiting ( P = 0.001 ) and sadness ( P = 0.017 ) . Athletes ' scores were examined individually using the reliable-change methodology . At 2 days post-injury , 58 % of concussed athletes had one or more reliable incidents of performance decline or increases in symptom reporting . At 8 days post-concussion , 30 % of concussed athletes were still showing one or more reliable change from preseason values . CONCLUSIONS College athletes exhibit differences on visual memory composite scores and symptoms post-concussion as a function of sex . These data support the importance of evaluating neuropsychological status and post-concussion symptoms in concussed athletes . In addition , these data illustrate the importance of analyzing an individual athlete 's recovery pattern , because individual differences in recovery trajectories may be overshadowed by global norm-group comparisons",
"OBJECTIVE The relationship between athlete reports of symptoms , neurophysiological activation , and neuropsychological functioning is investigated in a sample of high school athletes . METHODS All athletes were evaluated using functional magnetic resonance imaging ( fMRI ) , a computer-based battery of neurocognitive tests , and a subjective symptom scale . Athletes were evaluated within approximately 1 week of injury and again after clinical recovery using all assessment modalities . RESULTS This study found that abnormal fMRI results during the first week of recovery predicted clinical recovery . As a group , athletes who demonstrated hyperactivation on fMRI scans at the time of their first fMRI scan demonstrated a more prolonged clinical recovery than athletes who did not demonstrate hyperactivation at the time of their first fMRI scan . CONCLUSION These results demonstrate the relationship between neurophysiological , neuropsychological , and subjective symptom data in a relatively large sample composed primarily of concussed high school athletes . fMRI represents an important evolving technology for the underst and ing of brain recovery after concussion and may help shape return-to-play guidelines in the future",
"The purpose of this study was to examine the relation between the subjective report of feeling foggy at one-week post concussion and acute neuropsychological outcome . The outcome variables were derived from a computerized neuropsychological screening battery , Immediate Post-Concussion Assessment and Cognitive Testing ( ImPACT ) . Participants were 110 high school students who sustained a sports-related concussion and were evaluated 5 - 10 days post injury ( M = 6.8 days ) . Athletes were divided into two groups on the basis of self-reported fogginess . The first group reported no fogginess ( n = 91 ) , whereas the second group reported experiencing some degree of fogginess ( n = 19 ) on a 6-point scale . The athletes with persistent fogginess experienced a large number of other post-concussion symptoms , compared to the athletes with no reported fogginess . In addition , the athletes with persistent fogginess had significantly slower reaction times , reduced memory performance , and slower processing speed . Thus , athletes with any degree of self-reported fogginess at one-week post injury are likely to have adverse effects from their concussions in multiple domains",
"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 Recent concussion management guidelines have suggested that athletes with mild ( grade 1 ) concussions may be returned to play if asymptomatic for 15 minutes . The purpose of this study was to assess the utility of a current concussion management guideline in classifying and managing mild concussion . Hypothesis High school athletes diagnosed with a grade 1 concussion will demonstrate measurable decline in neuropsychological functioning that persists during the 1st week of recovery . Study Design Prospect i ve study design ed to evaluate neuropsychological functioning both prior to and following concussion . Methods Forty-three high school athletes completed neuropsychological test performance and symptom ratings prior to the season and at two times during the 1st week following mild concussion . Results Thirty-six hours after injury , mildly concussed high school athletes demonstrated a decline in memory ( P self-reported symptoms ( P Athletes with grade 1 concussion demonstrated memory deficits and symptoms that persisted beyond the context in which they were injured . These data suggest that current grade 1 return-to-play recommendations that allow for immediate return to play may be too liberal . Clinical Relevance A reconsideration of current concussion grading systems appears to be warranted",
"Background : The relevance of headache to outcome after sports-related concussion is poorly understood . Hypotheses : High school athletes reporting headache approximately 1 week after injury will have significantly more other concussion symptoms and will perform more poorly on neuropsychological tests than athletes not experiencing headache . Study Design : Prospect i ve cohort study . Methods : Study participants included 109 high school athletes who had sustained concussion and who were divided into two groups : those reporting headache 7 days after injury and those reporting no headaches . The two groups were compared regarding on-field markers of concussion severity at the time of injury and symptoms and neurocognitive test results collected via ImPACT , a computerized neuropsychological test battery and postconcussion symptom scale , at a mean of 6.8 days after injury . Results : Athletes reporting posttraumatic headache demonstrated significantly worse performance on reaction time and memory ImPACT neurocognitive composite scores . These athletes also reported significantly more symptoms other than headache and were more likely to have demonstrated on-field antero grade amnesia . Conclusions : Findings suggest that any degree of postconcussion headache in high school athletes 7 days after injury is likely associated with an incomplete recovery after concussion",
"Mild head injury has been recognized as producing numerous \" postconcussive \" symptoms that temporarily reduce an individual 's ability to function . Controversy exists over the short- and long-term effects of mild head injuries , and the effects of repeated concussive blows to the head have not been sufficiently studied . Amateur and professional athletes provide an excellent population for the examination of many aspects of postconcussive syndrome . The nature , incidence , and cognitive and emotional symptoms of mild head injury , are review ed within , the framework of professional and amateur sports . Particular attention is paid to the few available prospect i ve studies of amateur boxers and collegiate football players",
"Objective : Following the Second International Conference on Concussion in Sport in 2005 , a summary agreement statement was published that introduced new terminology for sport-related concussions . This new classification system is binary ( ie , “ simple ” versus “ complex ” concussions ) . Athletes who are slow to recover ( ie , > 10 days ) are classified as having complex concussions . The purpose of this study was to determine if high school football players , retrospectively classified as having a simple or a complex concussion , could be differentiated in the first 48 after injury on the basis of symptom reporting or neuropsychological testing . Design : Case-control study . Setting : Pennsylvania high school football programs . Participants : The total sample consisted of 114 concussed high school football players who were identified through a 3 year prospect i ve cohort study . Interventions : All completed a computerized neuropsychological screening evaluation within 72 hours of injury . They were followed clinical ly until they recovered and were cleared to return to play . They were classified retrospectively as having a simple ( n = 55 ) or complex ( n = 59 ) concussion based on their recovery times . Main Outcome Measurements : Neurocognitive test performance and symptom ratings . Results : Within 72 hours after injury , athletes with complex concussions performed more poorly on neuropsychological testing and reported more symptoms than those with simple concussions . Athletes with complex concussions who were slow to recover were 18 times more likely to have 3 unusually low neuropsychological test scores than those with simple concussions ( 95 % CI = 2.3 - 144.9 ) . Athletes with previous concussions did not recover more slowly . Conclusions : This study provides evidence that supports and refutes the clinical usefulness of the new simple-complex concussion classification system",
"CONTEXT Lack of empirical data on recovery time following sport-related concussion hampers clinical decision making about return to play after injury . OBJECTIVE To prospect ively measure immediate effects and natural recovery course relating to symptoms , cognitive functioning , and postural stability following sport-related concussion . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 1631 football players from 15 US colleges . All players underwent preseason baseline testing on concussion assessment measures in 1999 , 2000 , and 2001 . Ninety-four players with concussion ( based on American Academy of Neurology criteria ) and 56 noninjured controls underwent assessment of symptoms , cognitive functioning , and postural stability immediately , 3 hours , and 1 , 2 , 3 , 5 , 7 , and 90 days after injury . MAIN OUTCOME MEASURES Scores on the Grade d Symptom Checklist ( GSC ) , St and ardized Assessment of Concussion ( SAC ) , Balance Error Scoring System ( BESS ) , and a neuropsychological test battery . RESULTS No player with concussion was excluded from participation ; 79 players with concussion ( 84 % ) completed the protocol through day 90 . Players with concussion exhibited more severe symptoms ( mean GSC score 20.93 [ 95 % confidence interval [ CI ] , 15.65 - 26.21 ] points higher than that of controls ) , cognitive impairment ( mean SAC score 2.94 [ 95 % CI , 1.50 - 4.38 ] points lower than that of controls ) , and balance problems ( mean BESS score 5.81 [ 95 % CI , -0.67 to 12.30 ] points higher than that of controls ) immediately after concussion . On average , symptoms gradually resolved by day 7 ( GSC mean difference , 0.33 ; 95 % CI , -1.41 to 2.06 ) , cognitive functioning improved to baseline levels within 5 to 7 days ( day 7 SAC mean difference , -0.03 ; 95 % CI , -1.33 to 1.26 ) , and balance deficits dissipated within 3 to 5 days after injury ( day 5 BESS mean difference , -0.31 ; 95 % CI , -3.02 to 2.40 ) . Mild impairments in cognitive processing and verbal memory evident on neuropsychological testing 2 days after concussion resolved by day 7 . There were no significant differences in symptoms or functional impairments in the concussion and control groups 90 days after concussion . CONCLUSIONS Collegiate football players may require several days for recovery of symptoms , cognitive dysfunction , and postural instability after concussion . Further research is required to determine factors that predict variability in recovery time after concussion . St and ardized measurement of postconcussive symptoms , cognitive functioning , and postural stability may enhance clinical management of athletes recovering from concussion",
"OBJECTIVE To determine the relationship between recorded head accelerations and impact locations and acute clinical outcome of symptomatology , neuropsychological , and postural stability tests after cerebral concussion in Division I collegiate football players . METHODS A prospect i ve field study was used in which accelerometers were embedded in the football helmets of 88 collegiate football players . Linear and rotational accelerations of all head impacts sustained over the course of 2004 to 2006 National Collegiate Athletic Association football seasons were collected in real-time . Change scores were calculated on clinical measures from the players ' preseason baseline to postinjury ( within 48 h ) and regressed against the recorded linear and rotational accelerations of the head at the time of the concussion . RESULTS Thirteen concussions were recorded ranging in impact magnitudes of 60.51 to 168.71 g. Linear regression showed no significant relationships between impact magnitude ( linear or rotational acceleration ) or impact location and change scores for symptom severity , postural stability , or neurocognitive function ( P > 0.05 ) . CONCLUSION Our findings suggest that football players are concussed by impacts to the head that occur at a wide range of magnitudes and that clinical measures of acute symptom severity , postural stability , and neuropsychological function all appear to be largely independent of impact magnitude and location . Because of the varying magnitudes and locations of impacts result ing in concussion as well as other factors such as the frequency of subconcussive impacts and number of previous concussions , it may be difficult to establish a threshold for concussive injury that can be applied to all football players",
"OBJECTIVE This study prospect ively examined neuropsychological functioning in 2300 collegiate football players from 10 National Collegiate Athletic Association Division A universities . The study was design ed to determine the presence and duration of neuropsychological symptoms after mild head injury . METHODS A nonequivalent repeated measures control group design was used to compare the neuropsychological test scores and symptoms of injured players ( n = 183 ) with those of gender , age , and education matched controls . A number of neuropsychological tests , including the Paced Auditory Serial Addition Test , the Digit Symbol Test , and the Trail Making Test , as well as a symptom checklist were used . TECHNIQUE Players and controls were assessed before engaging in game activity and 24 hours , 5 days , and 10 days after injury , using the st and ardized test battery and symptom checklist . RESULTS Players with head injuries displayed impaired performance and increased symptoms in comparison to controls , but this impairment resolved within 5 days in most players . Players with head injuries showed significant improvement between 24 hours and 5 days , as well as between 5 and 10 days . CONCLUSION Although single , uncomplicated mild head injuries do cause limited neuropsychological impairment , injured players generally experience rapid resolution of symptoms with minimal prolonged sequelae",
"Objective To determine the repeatability of a computerized cognitive test design ed to monitor recovery from concussion and assist team physicians make return to play decisions ( CogSport ™ ) . To determine the correlation between CogSport and two conventional neuropsychological tests . Design Prospect i ve , serial investigation of cognitive function . Setting Professional and semi-professional Australian Football clubs and a university affiliated research institute in Melbourne , Australia . Participants Three-hundred healthy young adults , including 240 elite athletes . Main Outcome Measures Intra-class correlation ( ICC ) coefficients for CogSport performance measures administered serially . ICC between CogSport performance measures and conventional neuropsychological tests . Normative data for CogSport performance measures . Results Measures of psychomotor function , decision making , working memory and learning were highly reliable . Some measures also displayed high correlations with conventional neuropsychological tests of information processing and attention . Preliminary normative data is described . Conclusions CogSport is a highly reliable cognitive function test when administered to healthy young adults and elite athletes . CogSport measures similar cognitive functions as conventional tests used commonly in concussion research",
"The purpose of this study was to investigate the sensitivity of orientation and recent memory questions in the diagnosis of concussion . In a prospect i ve study over 7 consecutive years ( 1985 - 1991 ) , all players at a professional Australian Rules Football club who sustained a concussive injury ( n = 28 ) were administered a set of questions evaluating orientation and recent memory . Concussion was diagnosed independently on the basis of loss or disturbance of consciousness and clinical symptoms . A control group of age-matched nonconcussed players was administered the same set of questions . The results showed that items evaluating recently acquired information were more sensitive in the assessment of concussion than st and ard orientation items . The relative sensitivity of orientation questions must be considered when they are used in the clinical diagnosis of concussion in sport",
"Objective To identify an objective evaluation technique to guide return-to-play decisions following mild brain injury ( MBI ) using an agility task that incorporates cognitive and motor performance . Design Prospect i ve , controlled , repeated measures study . Setting Collegiate athletic training facility . Participants 84 athletes ( 25 male rugby players , 34 female rugby players , 25 male ice hockey players ) from 3 intercollegiate club teams participated . 9 athletes who suffered MBI during their competitive seasons and 9 matched controls completed the entire study protocol . Main Outcome Measures Time to complete an agility task on the Cybex Reactor and a postconcussive symptoms scale score were assessed in all subjects during the preseason . Injured subjects and matched controls were also assessed 1 , 3 , 5 , and 10 days postinjury . Results Repeated measures analyses of variance revealed significant differences between injured subjects and controls in postconcussion symptoms , but not agility performance . Post hoc testing revealed that injured subjects reported significantly more postconcussion symptoms on Day 1 after injury . Conclusion The methods of agility assessment used in this study appear to not be sensitive enough to detect functional impairment following MBI"
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41179b8c-06ff-11f0-808a-c43d1ab1c353
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AIMS Left atrial ( LA ) enlargement is associated with atrial fibrillation ( AF ) . However , it is controversial whether dilated atrium can predict post-ablation AF recurrence . We undertook a systematic review and meta- analysis to analyse the association between LA diameter and AF recurrence after single circumferential pulmonary vein isolation ( CPVI ) and explore the potential mechanism . METHODS AND RESULTS Electronic data bases and bibliographies of retrieved studies were search ed . The anteroposterior diameters of LA were available in all included studies , which were measured at end-systole by M-mode transthoracic echocardiography . Subgroup analysis was conducted based on the duration of follow-up . Weighted mean difference ( WMD ) and 95 % confidence interval ( CI ) were calculated using r and om-effect or fixed-effect model , depending on statistical heterogeneity . Twenty-two studies with a total of 3750 individuals met the inclusion criteria . The summary WMD of LA diameter between patients with and without recurrence was 1.87 mm ( 95 % CI 1.26 - 2.48 , P follow-up , and measurement of asymptomatic recurrences were significant sources of heterogeneity . Sensitivity analysis suggested that the difference in LA diameter between patients with and without recurrences persisted regardless of the duration of follow-up . CONCLUSION Dilated LA significantly increases the risk of AF recurrence after single CPVI . This is especially applicable to the patients with long-term follow-up
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"Background — Data regarding the long-term efficacy of atrial fibrillation ( AF ) ablation are still lacking . Methods and Results —Two hundred four consecutive patients symptomatic for paroxysmal or persistent/permanent AF were r and omly assigned to 2 different ablation schemes : pulmonary vein isolation ( PVI ) and PVI plus left linear lesions ( LL ) . Primary end point was to assess the maintenance of sinus rhythm ( SR ) after procedures 1 and 2 in the absence of antiarrhythmic drugs in a long-term follow-up of at least 3 years . Paroxysmal AF — With a single procedure at 12-month follow-up , 46 % of patients treated with PVI maintained SR , whereas at 3-year follow-up , 29 % were in SR ; using the “ PVI plus LL ” at the 12-month follow-up , 57 % of patients were in SR , whereas at the 3-year follow-up , 53 % remained in SR . After a second procedure , the long-term overall success rate without antiarrhythmic drugs was 62 % with PVI and 85 % with PVI plus LL . Persistent/Permanent AF — With a single procedure at the 12-month follow-up , 27 % of patients treated with PVI were in SR , whereas at the 3-year follow-up , 19 % maintained SR ; using the PVI plus LL with a single procedure at the 12-month follow-up 45 % of patients were in SR , whereas at the 3-year follow-up , 41 % remained in SR . After a second procedure , the long-term overall success rate without antiarrhythmic drugs was 39 % with PVI and 75 % with PVI plus LL . Conclusions —A long-term follow-up of AF ablation shows that short-term results can not be considered permanent because AF recurrences are still present after the first year especially in patients who have had “ PVI ” strategy . PVI isolation plus LL is superior to the PVI strategy in maintaining SR without antiarrhythmic drugs after procedures 1 and 2 both in paroxysmal and persistent AF",
"BACKGROUND Although atrial fibrillation ( AF ) is a risk factor for endothelial dysfunction ( ED ) , the effect of catheter ablation ( CA ) on AF-associated ED has not been evaluated . The aims of this study are to determine if the degree of ED predicts the outcome of AF ablation and to evaluate whether ED can be improved through restoring sinus rhythm ( SR ) by successful CA . METHODS This study prospect ively enrolled 80 subjects who underwent CA for AF ( paroxysmal AF = 61 , persistent AF = 19 ) . Eighty subjects with no history of AF were enrolled as controls , all of whom were matched by age , gender , body mass index , and atherosclerotic risk factor distribution . Brachial artery flow-mediated dilatation ( FMD ) was measured at baseline , and at 1 month and 6 months post CA in AF subjects who remained in SR . Among controls , FMD was measured at baseline and at 6 months . We used high sensitivity C-reactive protein ( hs-CRP ) , interleukin-6 , soluble E- or P-selectin , and endothelin-1 as biomarker indices for inflammation and /or ED . RESULTS Compared with controls , AF subjects had lower FMD at baseline ( FMD(baseline ) , P CA , FMD was significantly improved at 1 month and 6 months , nearly approaching control levels . A multivariate analysis revealed that FMD(baseline ) , hs-CRP , and left atrial volume ( LAV ) were independent predictors for arrhythmia recurrence after CA . Other biomarkers were not related to rhythm outcome . CONCLUSION AF subjects have significantly impaired FMD , which can be reversed through maintenance of SR by successful CA . FMD(baseline ) , hs-CRP , and LAV are important predictors for AF recurrence after CA",
"AIMS This study examined the difference in autonomic modification ( AM ) and its effect on paroxysmal atrial fibrillation ( PAF ) recurrence between segmental pulmonary vein isolation ( S-PVI ) and circumferential PVI ( C-PVI ) . METHODS AND RESULTS Successful S-PVI or C-PVI with a basket catheter was achieved in 120 consecutive PAF patients . Serial 24 Holter-recordings were obtained before , immediately , and 1 , 3 , 6 , 12 months after the PVI to analyse the heart rate variability ( HRV ) . Nineteen patients were excluded from analysis because of additional ablation for recurrent PAF after successful PVI . Among the residual 101 patients , 33 had PAF recurrences ( S-PVI = 44.0 % , C-PVI = 21.6 % ) at 1 year of follow-up . The root mean square of successive differences and high-frequency power reflecting parasympathetic nervous activity were significantly lower in patients with and without PAF recurrences after C-PVI and patients without PAF recurrences after S-PVI than patients with PAF recurrences after S-PVI ( P HRV parameters in the immediate aftermath of PVI among the patients without PAF recurrences after S-PVI and those with and without PAF recurrences after C-PVI . CONCLUSION Although additional radiofrequency ablation for AM may be recommended after S-PVI to reduce PAF recurrences , it should be carefully determined after C-PVI",
"INTRODUCTION Ablation has emerged as a major treatment option for atrial fibrillation ( AF ) . However , this procedure is limited by a significant rate of AF recurrence . We aim ed to examine the effects of statins , angiotensin-converting enzyme inhibitors ( ACE-I ) , and angiotensin receptor blockers ( ARB ) on the recurrence rate of AF following ablation . METHODS We conducted a retrospective study of 177 consecutive patients ( mean age = 56 + /- 11 yrs , 69 % males ) who underwent ablation for paroxysmal ( n = 132 ) or persistent AF ( n = 45 ) . Patients were treated with ACE-I ( n = 31 ) or ARB ( n = 18 ) or statins ( n = 50 ) prior to ablation and for the duration of follow-up . RESULTS After a mean follow-up of 13.8 + /- 8.6 months , 72 % of patients were free of AF . For patients taking statins , 33 of 50 ( 60 % ) were free of AF . In patients treated with ACE-I , 17 of 31 ( 55 % ) were free from AF , while in the group of patients treated with ARB , 17 of 18 ( 94 % ) were free from AF . Using Cox regression analysis to correct for baseline variables , treatment with statins did not decrease the recurrence rate ( HR = 1.10 [ 95 % CI : 0.55 - 2.27 ] p = 0.79 ) ; nor did treatment with renin angiotensin system ( RAS ) blockers ( HR 0.94 [ 95 % CI : 0.46 - 1.93 ] p = 0.87 ) . However , subgroup analysis showed that treatment with ARB was associated with a trend towards lower AF recurrence [ HR 0.17 , ( 95 % CI : 0.02 - 1.34 ) p = 0.09 ] . CONCLUSIONS Even though statins and RAS blockers possess anti-inflammatory properties , they did not decrease the recurrence of AF following ablation . However , the subset of patients taking ARB exhibited a trend towards lower AF recurrence . Larger , r and omized studies are needed to address this observation",
"Background — Atrial fibrillation ( AF ) is associated with diffuse left atrial fibrosis and a reduction in endocardial voltage . These changes are indicators of AF severity and appear to be predictors of treatment outcome . In this study , we report the utility of delayed-enhancement magnetic resonance imaging ( DE-MRI ) in detecting abnormal atrial tissue before radiofrequency ablation and in predicting procedural outcome . Methods and Results — Eighty-one patients presenting for pulmonary vein antrum isolation for treatment of AF underwent 3-dimensional DE-MRI of the left atrium before the ablation . Six healthy volunteers also were scanned . DE-MRI images were manually segmented to isolate the left atrium , and custom software was implemented to quantify the spatial extent of delayed enhancement , which was then compared with the regions of low voltage from electroanatomic maps from the pulmonary vein antrum isolation procedure . Patients were assessed for AF recurrence at least 6 months after pulmonary vein antrum isolation , with an average follow-up of 9.6±3.7 months ( range , 6 to 19 months ) . On the basis of the extent of preablation enhancement , 43 patients were classified as having minimal enhancement ( average enhancement , 8.0±4.2 % ) , 30 as having moderate enhancement ( 21.3±5.8 % ) , and 8 as having extensive enhancement ( 50.1±15.4 % ) . The rate of AF recurrence was 6 patients ( 14.0 % ) with minimal enhancement , 13 ( 43.3 % ) with moderate enhancement , and 6 ( 75 % ) with extensive enhancement ( P patients suffering from AF and might provide insight into the progress of the disease . Preablation DE-MRI holds promise for predicting responders to AF ablation and may provide a metric of overall disease progression",
"Background — The mainstay of treatment for atrial fibrillation ( AF ) remains pharmacological ; however , catheter ablation has increasingly been used over the last decade . The relative merits of each strategy have not been extensively studied . Methods and Results — We conducted a r and omized multicenter comparison of these 2 treatment strategies in patients with paroxysmal AF resistant to at least 1 antiarrhythmic drug . The primary end point was absence of recurrent AF between months 3 and 12 , absence of recurrent AF after up to 3 ablation procedures , or changes in antiarrhythmic drugs during the first 3 months . Ablation consisted of pulmonary vein isolation in all cases , whereas additional extrapulmonary vein lesions were at the discretion of the physician . Crossover was permitted at 3 months in case of failure . Echocardiographic data , symptom score , exercise capacity , quality of life , and AF burden were evaluated at 3 , 6 , and 12 months by the supervising committee . Of 149 eligible patients , 112 ( 18 women [ 16 % ] ; age , 51.1±11.1 years ) were enrolled and r and omized to ablation ( n=53 ) or “ new ” antiarrhythmic drugs alone or in combination ( n=59 ) . Crossover from the antiarrhythmic drugs and ablation groups occurred in 37 ( 63 % ) and 5 patients ( 9 % ) , respectively ( P=0.0001 ) . At the 1-year follow-up , 13 of 55 patients ( 23 % ) and 46 of 52 patients ( 89 % ) had no recurrence of AF in the antiarrhythmic drug and ablation groups , respectively ( P were significantly higher in the ablation group . Conclusion — This r and omized multicenter study demonstrates the superiority of catheter ablation over antiarrhythmic drugs in patients with AF with regard to maintenance of sinus rhythm and improvement in symptoms , exercise capacity , and quality of life",
"OBJECTIVES The purpose of this study was to evaluate the associations of transthoracic echocardiographic parameters with recurrent atrial fibrillation ( AF ) and /or stroke . BACKGROUND The Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) study , an evaluation of elderly patients with AF at risk for stroke , provided an opportunity to evaluate the implication s of echocardiographic parameters in patients with AF . METHODS Transthoracic echocardiographic measures of mitral regurgitation ( MR ) , left atrial ( LA ) diameter , and left ventricular ( LV ) function were evaluated in the AFFIRM rate- and rhythm-control patients who had sinus rhythm resume and had these data available . Risk for recurrent AF or stroke was evaluated with respect to transthoracic echocardiographic measures . RESULTS Of 2,474 patients studied , 457 had > or = 2(+)/4(+ ) MR , and 726 had a LA diameter > 4.5 cm . The LV ejection fraction was abnormal in 543 patients . The cumulative probabilities of at least one AF recurrence/stroke were 46%/1 % after 1 year and 84%/5 % by the end of the trial ( > 5 years ) , respectively . Multivariate analysis showed that r and omization to the rhythm-control arm ( hazard ratio [ HR ] = 0.64 ; p risk . Duration of qualifying AF episode > 48 h ( HR = 1.55 ; p risk of recurrent AF . Recurrent AF was more likely with larger LA diameters ( HR = 1.21 , 1.16 , and 1.32 for mild , moderate , and severe enlargement , respectively ) . No transthoracic echocardiographic measures were associated with risk of stroke . CONCLUSIONS In the AFFIRM study , large transthoracic echocardiographic LA diameters were associated with recurrent AF , but no measured echocardiographic parameter was associated with stroke",
"Aims The objective of the study was to analyse the influence of left ventricular ( LV ) ejection fraction ( EF ) on the outcomes of atrial fibrillation ( AF ) ablation after a first procedure . Pre-procedural predictors of recurrences after AF ablation can be useful for patient information and selection of c and i date s. The independent influence of LV systolic dysfunction on recurrence rate has not been studied . Methods and results A case – control study ( 1:1 ) was conducted with a total of 72 patients : 36 cases ( depressed LVEF ) and 36 controls ( normal LVEF ) . Patients were matched by left atrial diameter ( LAD ) , the presence of arterial hypertension , and other variables that might influence the results ( age , gender and paroxysmal vs. persistent AF ) . There were no statistical differences in the variables used to perform the matching . Patients with depressed LVEF had higher LV end diastolic diameter ( 55.6 ± 6.2 vs. 52.4 ± 5.5 , P = 0.03 ) , higher LV end systolic diameter ( 40.3 ± 6.9 vs. 32.6 ± 4.3 , P months , survival analysis for AF recurrences showed no differences between patients with depressed vs. normal LVEF ( 50.0 vs. 55.6 % , log rank = 0.82 ) . Cox regression analysis revealed LAD to be the only variable correlated to recurrence [ OR 1.11 ( 1.01–1.22 ) , P = 0.03 ] . Analysis at 6 months showed a significant increase in LVEF ( 43.23 ± 7.61 to 51.12 ± 13.53 % , P = 0.01 ) for the case group . Conclusion LV systolic dysfunction by itself is not a predictor of outcome after AF ablation . LAD independently correlates with outcome in patients with low or normal LVEF",
"BACKGROUND We conducted a r and omized , controlled trial of circumferential pulmonary-vein ablation for the treatment of chronic atrial fibrillation . METHODS A total of 146 patients with a mean ( + /-SD ) age of 57+/-9 years who had chronic atrial fibrillation were r and omly assigned to receive amiodarone and undergo two cardioversions during the first three months alone ( the control group ) or in combination with circumferential pulmonary-vein ablation . Cardiac rhythm was assessed with daily telephonic transmissions for one year . The left atrial diameter and the severity of symptoms were assessed at 12 months . RESULTS Among the 77 patients assigned to undergo circumferential pulmonary-vein ablation , ablation was repeated because of recurrent atrial fibrillation in 26 percent of patients and atypical atrial flutter in 6 percent . An intention-to-treat analysis showed that 74 percent of patients in the ablation group and 58 percent of those in the control group were free of recurrent atrial fibrillation or flutter without antiarrhythmic-drug therapy at one year ( P=0.05 ) . Among the 69 patients in the control group , 53 ( 77 percent ) crossed over to undergo circumferential pulmonary-vein ablation for recurrent atrial fibrillation by one year and only 3 ( 4 percent ) were in sinus rhythm without antiarrhythmic-drug therapy or ablation . There were significant decreases in the left atrial diameter ( 12+/-11 percent , P symptom severity score ( 59+/-21 percent , P Sinus rhythm can be maintained long term in the majority of patients with chronic atrial fibrillation by means of circumferential pulmonary-vein ablation independently of the effects of antiarrhythmic-drug therapy , cardioversion , or both . The maintenance of sinus rhythm is associated with a significant decrease in both the severity of symptoms and the left atrial diameter",
"Aims This multicentre , r and omized trial compared three strategies of AF ablation : ablation of complex fractionated electrograms ( CFE ) alone , pulmonary vein isolation ( PVI ) alone , and combined PVI + CFE ablation , using st and ardized automated mapping software . Methods and results Patients with drug-refractory , high-burden paroxysmal ( episodes > 6 h , > 4 in 6 months ) or persistent atrial fibrillation ( AF ) were enrolled at eight centres . Patients ( n = 100 ) were r and omized to one of three arms . For CFE alone ( n = 34 ) , spontaneous/induced AF was mapped using vali date d , automated CFE software and all sites . Atrial fibrillation symptoms were confirmed by loop recording . Repeat procedures were allowed within the first 6 months . The primary endpoint was freedom from AF > 30 s at 1 year . Patients ( age 57 ± 10 years , LA size 42 ± 6 mm ) were 35 % persistent AF . In CFE , ablation terminated AF in 68 % . Only 0.4 PVs per patient were isolated as a result of CFE . In PVI , 94 % had all four PVs successfully isolated . In PVI + CFE , 94 % had all four PVs isolated , 76 % had inducible AF with additional CFE ablation , with 73 % termination of AF . There were significantly more repeat procedures in the CFE arm ( 47 % ) vs. PVI ( 31 % ) or PVI + CFE ( 15 % ) ( P = 0.01 ) . After one procedure , PVI + CFE had a significantly higher freedom from AF ( 74 % ) compared with PVI ( 48 % ) and CFE ( 29 % ) ( P = 0.004 ) . After two procedures , PVI + CFE still had the highest success ( 88 % ) compared with PVI ( 68 % ) and CFE ( 38 % ) ( P = 0.001 ) . Ninety-six percent of these patients were off anti-arrhythmics . Complications were two tamponades , no PV stenosis , and no mortality . Conclusion In high-burden paroxysmal/persistent AF , PVI + CFE has the highest freedom from AF vs. PVI or CFE alone after one or two procedures . Complex fractionated electrogram alone has the lowest one and two procedure success rates with a higher incidence of repeat procedures . Clinical Trials.gov identifier number NCT00367757",
"BACKGROUND Radiofrequency catheter ablation ( RFCA ) for curing atrial fibrillation ( AF ) is often followed by early recurrence and delayed cure , so the present study investigate the predictive factors this in patients with chronic AF . METHODS AND RESULTS Ninety-two consecutive patients ( 70 males ; mean age , 58.7+/-6.4 years ) with chronic AF who underwent RFCA for treatment of symptomatic AF were enrolled . Early recurrence of AF ( ERAF ) occurred in 45 patients after ablation . Not achieving AF termination could predict ERAF ( odds ratio ( OR ) 0.95 ; 95 % confidence interval ( CI ) 0.84 - 1.13 ; p=0.02 ) in multivariate analysis . During a follow-up of 12+/-11 ( range , 5 - 25 ) months , delayed cure occurred in 35.6 % ( 16/45 ) of the patients with ERAF . Left atrial size and AF termination during ablation were related to delayed cure . AF termination was the only independent predictive factor for delayed cure ( OR 1.47 ; 95 % CI 1.05 - 1.87 ; p=0.02 ) . CONCLUSION Not achieving AF termination is the only independent predictor of ERAF . Among patients with ERAF , those with a smaller left atrium and AF termination have a higher probability of delayed cure . AF termination can independently predict delayed cure . These results emphasize the importance of AF termination during ablation for patients with chronic AF",
"AIMS The aim of this study was to identify the impact of obstructive sleep apnoea ( OSA ) on recurrence after catheter ablation of paroxysmal atrial fibrillation ( AF ) . METHODS AND RESULTS One hundred and seventy-eight consecutive patients with paroxysmal AF who underwent index circumferential pulmonary vein ( PV ) isolation were prospect ively enrolled . The patients were divided into high risk ( HR group ) and low risk ( LR group ) for OSA group with Berlin question naire . Of the 178 patients , 104 ( 58.4 % ) were in the HR group and 74 ( 41.6 % ) were in the LR group . After a mean follow-up of 344 + /- 137 ( 91 - 572 ) days , 44 patients ( 24.7 % ) experienced recurrence , and the recurrence rate did not differ between the HR ( 25.0 % ) and LR groups ( 24.3 % , P = 0.855 ) . Cox analysis revealed that PV isolation was the only independent predictor of recurrence ( hazard ratio 5.11 , 95 % confidence interval 1.42 - 18.47 , P = 0.013 ) . There was no significant difference in the incidence of complications between the HR and LR groups ( 2.9 vs. 1.9 % , P = 0.729 ) . CONCLUSION The recurrence rate and incidence of complications did not differ in patients with different risk profiles for OSA . The presence of OSA should not lower the decision threshold to choose an ablative procedure in paroxysmal AF",
"AIMS To assess whether treatment with statins or renin-angiotensin-aldosterone system ( RAAS ) inhibitors as potential procedural ' augmenting agents ' improved atrial fibrillation ( AF ) catheter ablation recurrence rates in post-menopausal females ( PMFS ) . METHODS AND RESULTS Five hundred and eighteen consecutive female patients had undergone AF catheter ablation from January 2005 to May 2008 . Post-menopausal females were selected and procedure outcomes were compared between cohorts of PMFS treated with statins or RAAS inhibitors to untreated PMFS . Out of 408 PMFS , 36 ( 8.8 % ) were treated with a combination of RAAS inhibitors and statins , thus were excluded leaving a total of 372 ( 91.2 % ) patients in the study . Out of 372 patients , 111 ( 29.8 % ) were on statins ( Group 1 ) , 59 ( 15.9 % ) on RAAS inhibitors ( Group 2 ) , and 202 ( 54.3 % ) without RAAS inhibitors or statins [ ( Group 3 ) control population ] . Over a mean follow-up time of 24 + /- 8.3 ( median 25 ) months , 78 ( 70.6 % ) in Group 1 , 38 ( 65.4 % ) in Group 2 , and 139 ( 68.8 % ) in Group 3 had procedural success . Statin or RAAS inhibitor use did not predict lower recurrence rates [ hazard ratio ( HR ) : 1.26 , P = 0.282 and HR : 1.14 , P = 0.728 , respectively ] . When compared with controls , no difference in the cumulative incidence of recurrence was found with statin or RAAS inhibitors use ( P = 0.385 and P = 0.761 , respectively ) . CONCLUSION Treatment with statins or RAAS inhibitors did not improve catheter ablation success rates among PMFS . Thereby , from a clinical st and point , PMFS should not be started on these treatments as a procedural ' augmenting agent ' at this time",
"Background and objective Little is known about the outcome of catheter ablation of atrial fibrillation ( AF ) in patients with diabetes mellitus ( DM ) . We investigated the safety and efficacy of catheter ablation of AF in patients with DM . Material s and methods Thirty one patients with DM from a group of 263 consecutive patients undergoing a first-time catheter ablation of AF procedure were enrolled in a prospect i ve study . The ablation protocol ( guided by CARTO system ) consisted in two continuous circular lesions around ipsilateral pulmonary veins . Results The following clinical characteristics differed between DM and no-DM patients : age ( 62.0 ± 10.8 vs. 56.1 ± 10.6 years , P = 0.004 ) , longer AF history ( 9.6 ± 9.3 vs. 6.7 ± 6.3 years , P = 0.024 ) , significantly larger left atrium size ( 41.1 ± 7.8 vs. 38.3 ± 5.8 mm , P = 0.021 ) , hypertension ( 58.1 vs. 35.8 % , P = 0.018 ) and structural heart disease ( 67.7 vs. 43.5 % , P = 0.011 ) . Despite a similar AF recurrence rate in DM and no-DM patients ( 32.3 vs. 22.4 % , P = 0.240 ) , the ablation procedure was complicated in 28 patients ( 11 hematomas , three cardiac tamponades and three strokes ) and the incidence of complications was significantly higher in DM than in no-DM patients ( 29.0 vs. 8.2 % , respectively , P = 0.002 ) . Multivariate analysis showed that DM was an independent risk factor for complications occurrence ( odd ratio 5.936 , 95 % confidence interval 2.059 to 17.112 , P = 0.001 ) . Conclusions First catheter ablation of AF procedure in DM patients was equally efficacious than in no-DM patients . However , DM patients had a higher incidence of complications , mostly thrombotic or hemorrhagic"
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41179bc8-06ff-11f0-808a-c43d1ab1c353
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OBJECTIVE To present a summary of the 2016 version of the European Association of Urology ( EAU ) - European Society for Radiotherapy & Oncology ( ESTRO ) - International Society of Geriatric Oncology ( SIOG ) Guidelines on the treatment of relapsing , metastatic , and castration-resistant prostate cancer ( CRPC ) . EVIDENCE ACQUISITION The working panel performed a literature review of the new data ( 2013 - 2015 ) . The guidelines were up date d , and the levels of evidence and /or grade s of recommendation were added based on a systematic review of the literature . EVIDENCE SYNTHESIS Relapse after local therapy is defined by a rising prostate-specific antigen ( PSA ) level > 0.2ng/ml following radical prostatectomy ( RP ) and > 2ng/ml above the nadir after radiation therapy ( RT ) . 11C-choline positron emission tomography/computed tomography is of limited importance if PSA is 10ng/ml . Multiparametric magnetic resonance imaging and biopsy are important to assess biochemical failure following RT . Therapy for PSA relapse after RP includes salvage RT at PSA levels salvage RP , high-intensity focused ultrasound , cryosurgical ablation or salvage brachytherapy of the prostate in radiation failures . And rogen deprivation therapy ( ADT ) remains the basis for treatment of men with metastatic prostate cancer ( PCa ) . However , docetaxel combined with ADT should be considered the st and ard of care for men with metastases at first presentation , provided they are fit enough to receive the drug . Follow-up of ADT should include analysis of PSA , testosterone levels , and screening for cardiovascular disease and metabolic syndrome . Level 1 evidence for the treatment of metastatic CRPC ( mCRPC ) includes , abiraterone acetate plus prednisone ( AA/P ) , enzalutamide , radium 223 ( Ra 223 ) , docetaxel at 75 mg/m2 every 3 wk and sipuleucel-T. Cabazitaxel , AA/P , enzalutamide , and radium are approved for second-line treatment of CRPC following docetaxel . Zoledronic acid and denosumab can be used in men with mCRPC and osseous metastases to prevent skeletal-related complications . CONCLUSIONS The knowledge in the field of advanced and metastatic PCa and CRPC is changing rapidly . The 2016 EAU-ESTRO-SIOG Guidelines on PCa summarise the most recent findings and advice for use in clinical practice . These PCa guidelines are the first endorsed by the European Society for Therapeutic Radiology and Oncology and the International Society of Geriatric Oncology and reflect the multidisciplinary nature of PCa management . A full version is available from the EAU office or online ( http://uroweb.org/ guideline /prostate-cancer/ ) . PATIENT SUMMARY In men with a rise in their PSA levels after prior local treatment for prostate cancer only , it is important to balance overtreatment against further progression of the disease since survival and quality of life may never be affected in many of these patients . For patients diagnosed with metastatic castrate-resistant prostate cancer , several new drugs have become available which may provide a clear survival benefit but the optimal choice will have to be made on an individual basis
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[
"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 . )",
"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",
"Introduction Tissue cryoablation is a potential curative option for solid malignancies , including radiation recurrent prostate cancer ( RRPC ) . Case series of salvage cryotherapy ( SCT ) in RRPC have reported promising disease free survival ( DFS ) outcomes and acceptable toxicity profile . While many men receive SCT , no predictive factors for treatment induced side effects are known . The aim of this study is to vali date the oncologic outcome of SCT in a large multi-centre patient cohort and to identify potential parameters associated with an increased risk of micturition symptoms . Patients and Methods In this retrospective analysis , we studied 283 consecutive patients with RRPC treated by SCT in three independent U.K. centres ( between 2001 and 2011 ) . Two freeze-thaw cycles of transperineal cryotherapy were performed under transrectal ultrasound guidance by a single surgeon in each of the 3 sites . We analysed clinico-pathological factors against tumour response . Functional outcomes were assessed by continence status and IPSS question naire . Predictive factors for SCT-induced micturition symptoms were analysed in a sub-group ( n = 42 ) of consecutive cases . Results We found that nadir post-SCT PSA levels strongly associated with DFS . The DFS rates at 12- and 36-month were 84 % and 67 % for the ≤1 ng/ml group and 56 % and 14 % for the > 1 ng/ml group , respectively ( p between patients ' post-SCT micturition status with prostate gl and and iceball lengths following SCT . Finally , in a reduction model , both gl and length and maximal length of iceball were highly associated with patients ' IPSS outcome ( p<0.001 ) . Conclusion We report the largest European patient cohort treated with SCT for RRPC . Oncologic outcome guided by nadir PSA of < 1 ng/ml is consistent with earlier single-centre series . For the first time , we identified physical parameters to predict micturition symptoms following SCT . Our data will directly assist on-going and future trial design in cryotherapy in prostate cancer",
"BACKGROUND Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies",
"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 The aim of this retrospective two-centre study was to investigate the clinical impact of 11C-choline PET/CT on treatment management decisions in patients with recurrent prostate cancer ( rPCa ) after radical therapy . Methods Enrolled in this retrospective study were 150 patients ( 95 from Bologna , 55 from Würzburg ) with rPCa and biochemical relapse ( PSA mean ± SD 4.3 ± 5.5 ng/mL , range 0.2–39.4 ng/mL ) after radical therapy . The intended treatment before PET/CT was salvage radiotherapy of the prostatic bed in 95 patients and palliative and rogen deprivation therapy ( ADT ) in 55 patients . The effective clinical impact of 11C-choline PET/CT was rated as major ( change in therapeutic approach ) , minor ( same treatment , but modified therapeutic strategy ) or none . Multivariate binary logistic regression analysis included PSA level , PSA kinetics , ongoing ADT , Gleason score , TNM , age and time to relapse . Results Changes in therapy after 11C-choline PET/CT were implemented in 70 of the 150 patients ( 46.7 % ) . A major clinical impact was observed in 27 patients ( 18 % ) and a minor clinical impact in 43 ( 28.7 % ) . 11C-choline PET/CT was positive in 109 patients ( 72.7 % ) detecting local relapse ( prostate bed and /or iliac lymph nodes and /or pararectal lymph nodes ) in 64 patients ( 42.7 % ) . Distant relapse ( paraaortic and /or retroperitoneal lymph nodes and /or bone lesions ) was seen in 31 patients ( 20.7 % ) , and both local and distant relapse in 14 ( 9.3 % ) . A significant difference was observed in PSA level and PSA kinetics between PET-positive and PET-negative patients ( p multivariate analysis , PSA level , PSA doubling time and ongoing ADT were significant predictors of a positive scan ( p Bologna and Würzburg patients ( p > 0.05 ) . In both centres the same criteria to vali date PET-positive findings were used : in 17.3 % of patients by histology and in 82.7 % of patients by correlative imaging and /or clinical follow-up ( follow-up mean 20.5 months , median 18.3 months , range 6.2–60 months ) . Conclusion 11C-Choline PET/CT had a significant impact on therapeutic management in rPCa patients . It led to an overall change in 46.7 % of patients , with a major clinical change implemented in 18 % of patients . Further prospect i ve studies are needed to evaluate the effect of such treatment changes on patient survival",
"Summary Background Long-term hormone therapy has been the st and ard of care for advanced prostate cancer since the 1940s . STAMPEDE is a r and omised controlled trial using a multiarm , multistage platform design . It recruits men with high-risk , locally advanced , metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy . We report primary survival results for three research comparisons testing the addition of zoledronic acid , docetaxel , or their combination to st and ard of care versus st and ard of care alone . Methods St and ard of care was hormone therapy for at least 2 years ; radiotherapy was encouraged for men with N0M0 disease to November , 2011 , then m and ated ; radiotherapy was optional for men with node-positive non-metastatic ( N+M0 ) disease . Stratified r and omisation ( via minimisation ) allocated men 2:1:1:1 to st and ard of care only ( SOC-only ; control ) , st and ard of care plus zoledronic acid ( SOC + ZA ) , st and ard of care plus docetaxel ( SOC + Doc ) , or st and ard of care with both zoledronic acid and docetaxel ( SOC + ZA + Doc ) . Zoledronic acid ( 4 mg ) was given for six 3-weekly cycles , then 4-weekly until 2 years , and docetaxel ( 75 mg/m2 ) for six 3-weekly cycles with prednisolone 10 mg daily . There was no blinding to treatment allocation . The primary outcome measure was overall survival . Pairwise comparisons of research versus control had 90 % power at 2·5 % one-sided α for hazard ratio ( HR ) 0·75 , requiring roughly 400 control arm deaths . Statistical analyses were undertaken with st and ard log-rank-type methods for time-to-event data , with hazard ratios ( HRs ) and 95 % CIs derived from adjusted Cox models . This trial is registered at Clinical Trials.gov ( NCT00268476 ) and ControlledTrials.com ( IS RCT N78818544 ) . Findings 2962 men were r and omly assigned to four groups between Oct 5 , 2005 , and March 31 , 2013 . Median age was 65 years ( IQR 60–71 ) . 1817 ( 61 % ) men had M+ disease , 448 ( 15 % ) had N+/X M0 , and 697 ( 24 % ) had N0M0 . 165 ( 6 % ) men were previously treated with local therapy , and median prostate-specific antigen was 65 ng/mL ( IQR 23–184 ) . Median follow-up was 43 months ( IQR 30–60 ) . There were 415 deaths in the control group ( 347 [ 84 % ] prostate cancer ) . Median overall survival was 71 months ( IQR 32 to not reached ) for SOC-only , not reached ( 32 to not reached ) for SOC + ZA ( HR 0·94 , 95 % CI 0·79–1·11 ; p=0·450 ) , 81 months ( 41 to not reached ) for SOC + Doc ( 0·78 , 0·66–0·93 ; p=0·006 ) , and 76 months ( 39 to not reached ) for SOC + ZA + Doc ( 0·82 , 0·69–0·97 ; p=0·022 ) . There was no evidence of heterogeneity in treatment effect ( for any of the treatments ) across prespecified subsets . Grade 3–5 adverse events were reported for 399 ( 32 % ) patients receiving SOC , 197 ( 32 % ) receiving SOC + ZA , 288 ( 52 % ) receiving SOC + Doc , and 269 ( 52 % ) receiving SOC + ZA + Doc . Interpretation Zoledronic acid showed no evidence of survival improvement and should not be part of st and ard of care for this population . Docetaxel chemotherapy , given at the time of long-term hormone therapy initiation , showed evidence of improved survival accompanied by an increase in adverse events . Docetaxel treatment should become part of st and ard of care for adequately fit men commencing long-term hormone therapy . Funding Cancer Research UK , Medical Research Council , Novartis , Sanofi-Aventis , Pfizer , Janssen , Astellas , NIHR Clinical Research Network , Swiss Group for Clinical Cancer Research",
"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 . )",
"OBJECTIVE To demonstrate the safety and efficacy of up to 5 years of degarelix treatment and the effects of crossing over from leuprolide to degarelix in the extension phase of a phase III pivotal 1-year trial . METHODS Patients receiving degarelix who completed the 1-year trial continued on 80 mg ( n = 125 ) or 160 mg ( n = 126 ) maintenance doses . Patients who received leuprolide were rer and omized to degarelix 240/80 mg ( n = 69 ) or 240/160 mg ( n = 65 ) . Safety and tolerability were assessed ( primary end point ) , as well as testosterone and prostate-specific antigen levels and prostate-specific antigen progression-free survival ( secondary end points ) . RESULTS Adverse event frequency was similar between both the groups . Adverse events included initial injection site reactions , hot flushes , and increased weight . Testosterone and prostate-specific antigen values during the extension study were similar to those seen during the 1-year trial in patients who continued on degarelix or crossed over from leuprolide . The prostate-specific antigen progression-free survival hazard rate was decreased significantly after the crossover in the leuprolide to degarelix group ( from 0.20 to 0.09 ; P = .002 ) , whereas in patients who continued on degarelix , the rate did not change significantly . In patients with baseline prostate-specific antigen > 20 ng/mL , the same hazard rate change pattern was observed on crossover ( from 0.38 to 0.19 ; P = .019 ) . CONCLUSION Degarelix was well tolerated ; no safety concerns were identified . The significant prostate-specific antigen progression-free survival benefit established for degarelix over leuprolide during year 1 remained consistent at 5 years",
"PURPOSE Patients in whom prostate cancer progresses despite testicular and rogen ablation are generally said to have cancers that have become resistant to hormonal maneuvers . If and rogen suppression has been pharmacologic , this therapy is often stopped before consideration of other systemic treatments . This exploratory study sought clinical correlates of experimental evidence that there may be substantial acceleration of tumor growth after cessation of and rogen suppression . MATERIAL S AND METHODS A retrospective multivariate analysis was performed on survival data for 341 patients treated on four clinical trials of secondary therapy for hormone-refractory prostate cancer . Factors included in the model were recent weight loss , age , performance status , disease site ( soft tissue v bone-dominant ) , prior radiotherapy , and continued and rogen suppression v discontinued exogenous endocrine therapy . RESULTS Recent weight loss , age , performance status , and disease site were important prognostic factors for survival duration in hormone-refractory prostate cancer . Correcting for these factors , continued testicular and rogen suppression was also an important predictor of survival duration in all data sets examined . CONCLUSION This retrospective study showed a modest advantage in survival duration for men with hormone-refractory prostate cancer who continued to receive testicular and rogen suppression . The hypothesis that continued hormonal maneuvers can still affect survival in this group warrants examination in prospect i ve trials",
"PURPOSE Gonadotropin-releasing hormone agonists decrease bone mineral density , lean mass , and muscle size and increase fat mass in men with prostate cancer . Less is known about the effects of bicalutamide monotherapy on bone mineral density and body composition . PATIENTS AND METHODS In a 12-month , open-label study , we r and omly assigned 52 men with prostate cancer and no bone metastases to receive either leuprolide or bicalutamide ( 150 mg by mouth daily ) . Bone mineral density and body composition were measured by dual energy x-ray absorptiometry and quantitative computed tomography . RESULTS Mean ( + /- st and ard error ) bone mineral density of the posterior-anterior lumbar spine decreased by 2.5 % + /- 0.5 % in the leuprolide group and increased by 2.5 + /- 0.5 in the bicalutamide group from baseline to 12 months ( P Mean changes in bone mineral density of the total body , total hip , femoral neck , and trabecular bone of the lumbar spine also differed significantly between groups ( P Fat mass increased by 11.1 % + /- 1.3 % in the leuprolide group and by 6.4 % + /- 1.1 % in the bicalutamide group ( P = .01 ) . Changes in lean mass , muscle size , and muscle strength were similar between the groups . Breast tenderness and enlargement were more common in the bicalutamide group than in the leuprolide group . Fatigue , loss of sexual interest , and vasomotor flushing were less common in the bicalutamide group than in the leuprolide group . CONCLUSION In men with prostate cancer , bicalutamide monotherapy increases bone mineral density , lessens fat accumulation , and has fewer bothersome side effects than treatment with a gonadotropin-releasing hormone agonist",
"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",
"PURPOSE To assess the impact of prognostic factors , including continued ( orchiectomy ) versus discontinued and rogen-suppression ( nonorchiectomy ) therapy , on chemotherapy response and survival of patients with hormone-refractory prostate cancer . METHODS Analysis of five consecutive Southwest Oncology Group ( SWOG ) phase II chemotherapy trials was undertaken . RESULTS Two hundred five hormone-refractory patients were evaluated . Eighty-four percent had been orchiectomized . The median survival duration s for the nonorchiectomy and orchiectomy patients were 6 and 7 months , respectively ( P = .73 ) . In a univariate analysis , orchiectomy patients had a significantly longer median time from diagnosis to first hormone therapy ( 1.1 v 0.1 years , P = .003 ) , were more likely to have had chemotherapy initiated > or = 2 years from diagnosis ( 75 % v 56 % , P = .03 ) , had a lower incidence of liver metastases ( 16 % v 30 % , P = .05 ) , and had lower likelihood of being black ( 8 % v 18 % , P = .05 ) when compared with the nonorchiectomy group . Orchiectomy patients had a marginally significant longer median time from initial hormone treatment , more prior endocrine manipulations , lower median baseline alkaline phosphatase levels , and a lower likelihood of response to chemotherapy when compared with the nonorchiectomy group . Absence of liver metastases ( P = .004 ) , hemoglobin level > or = 10 g/dL ( P acid phosphatase level > or = 1.2 IU/L ( P = .05 ) , response to chemotherapy ( P = .001 ) , and > or = 2 years from initial hormone treatment ( P = .01 ) are important factors for survival . CONCLUSION This study failed to show obvious advantages in response to chemotherapy or survival for patients with continued gonadal suppression . A prospect i ve r and omized trial is suggested to evaluate the effect of this factor on progression-free and overall survival of patients with hormone-refractory prostate cancer receiving chemotherapy",
"PURPOSE We report salvage lymph node dissections for prostate cancer nodal recurrence detected by (11)C-choline positron emission tomography/computerized tomography in the setting of increasing prostate specific antigen after radical prostatectomy . MATERIAL S AND METHODS Retrospective chart review was performed for all patients who underwent salvage lymph node dissection for prostate cancer nodal recurrence . Only patients previously treated with radical prostatectomy were included in the study and those with evidence of local recurrence were excluded from analysis . Primary end points included biochemical recurrence , systemic progression and cancer specific mortality . RESULTS From 2009 to 2013 , 52 men underwent salvage lymph node dissection . Before salvage lymph node dissection 78.8 % ( 41 of 52 ) had some form of therapy after radical prostatectomy . Median age at salvage lymph node dissection was 60 years and median prostate specific antigen was 2.2 ng/ml ( IQR 1.4 - 3.7 ) . The median number of lymph nodes dissected was 21.5 ( IQR 16 - 30 ) and the median number of positive nodes was 3.5 ( IQR 1.2 - 6.5 ) . Since salvage lymph node dissection 46.2 % of the men ( 24 of 52 ) have had no further treatment , 34.6 % ( 18 of 52 ) are on hormonal therapy and 19.2 % ( 10 of 52 ) have received multiple different treatments . At the last followup at a median of 20 months ( IQR 8 - 33 ) , 57.7 % ( 30 of 52 ) had prostate specific antigen remain less than 0.2 ng/ml , 75 % ( 39 of 52 ) remained free of systemic progression and 96.2 % of the men ( 50 of 52 ) were alive . Two patients died of prostate cancer . Three-year biochemical recurrence-free , systemic progression-free and cancer specific survival was 45.5 % , 46.9 % and 92.5 % , respectively . CONCLUSIONS This represents the largest U.S. series of salvage lymph node dissection in the setting of lymph node metastatic prostate cancer after radical prostatectomy . Although followup was short and the study lacked a r and omized control group , salvage lymph node dissection may represent a valid treatment option",
"BACKGROUND Docetaxel administered every 3 weeks is a st and ard treatment for castration-resistant advanced prostate cancer . We hypothesised that 2-weekly administration of docetaxel would be better tolerated than 3-weekly docetaxel in patients with castration-resistant advanced prostate cancer , and did a prospect i ve , multicentre , r and omised , phase 3 study to compare efficacy and safety . METHODS Eligible patients had advanced prostate cancer ( metastasis , a prostate-specific-antigen test result of more than 10·0 ng/mL , and WHO performance status score of 0 - 2 ) , had received no chemotherapy ( except with estramustine ) , had undergone surgical or chemical castration , and had been referred to a treatment centre in Finl and , Irel and , or Sweden . Enrolment and treatment were done between March 1 , 2004 , and May 31 , 2009 . R and omisation was done central ly and stratified by centre and WHO performance status score of 0 - 1 vs 2 . Patients were assigned 75 mg/m(2 ) docetaxel intravenously on day 1 of a 3-week cycle , or 50 mg/m(2 ) docetaxel intravenously on days 1 and 15 of a 4-week cycle . 10 mg oral prednisolone was administered daily to all patients . The primary endpoint was time to treatment failure ( TTTF ) . We assessed data in the per- protocol population . This study is registered with Clinical Trials.gov , number NCT00255606 . FINDINGS 177 patients were r and omly assigned to the 2-weekly docetaxel group and 184 to the 3-weekly group . 170 patients in the 2-weekly group and 176 in the 3-weekly group were included in the analysis . The 2-weekly administration was associated with significantly longer TTTF than was 3-weekly administration ( 5·6 months , 95 % CI 5·0 - 6·2 vs 4·9 months , 4·5 - 5·4 ; hazard ratio 1·3 , 95 % CI 1·1 - 1·6 , p=0·014 ) . Grade 3 - 4 adverse events occurred more frequently in the 3-weekly than in the 2-weekly administration group , including neutropenia ( 93 [ 53 % ] vs 61 [ 36 % ] ) , leucopenia ( 51 [ 29 % ] vs 22 [ 13 % ] ) , and febrile neutropenia ( 25 [ 14 % ] vs six [ 4 % ] ) . Neutropenic infections were reported more frequently in patients who received docetaxel every 3 weeks ( 43 [ 24 % ] vs 11 [ 6 % ] , p=0·002 ) . INTERPRETATION Administration of docetaxel every 2 weeks seems to be well tolerated in patients with castration-resistant advanced prostate cancer and could be a useful option when 3-weekly single-dose administration is unlikely to be tolerated . FUNDING Sanofi",
"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",
"Purpose To up date the Potentially Curable Pancreatic Cancer : American Society of Clinical Oncology Clinical Practice Guideline published on May 31 , 2016 . The October 2016 up date focuses solely on new evidence that pertains to clinical question 4 of the guideline : What is the appropriate adjuvant regimen for patients with pancreatic cancer who have undergone an R0 or R1 resection of their primary tumor ? Methods The recently published results of a r and omized phase III study prompted an up date of this guideline . The high quality of the reported evidence and the potential for its clinical impact prompted the Expert Panel to revise one of the guideline recommendations . Results The ESPAC-4 study , a multicenter , international , open-label r and omized controlled phase III trial of adjuvant combination chemotherapy compared gemcitabine and capecitabine with gemcitabine monotherapy in 730 evaluable patients with resected pancreatic ductal adenocarcinoma . Median overall survival was improved in the doublet arm to 28.0 months ( 95 % CI , 23.5 to 31.5 months ) versus 25.5 months ( 95 % CI , 22.7 to 27.9 months ) for gemcitabine alone ( hazard ratio , 0.82 ; 95 % CI , 0.68 to 0.98 ; P = .032 ) . Grade 3 and 4 adverse events were similar in both arms , although higher rates of h and -foot syndrome and diarrhea occurred in patients r and omly assigned to the doublet arm . Recommendations All patients with resected pancreatic cancer who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of medical or surgical contraindications . The doublet regimen of gemcitabine and capecitabine is preferred in the absence of concerns for toxicity or tolerance ; alternatively , monotherapy with gemcitabine or fluorouracil plus folinic acid can be offered . Adjuvant treatment should be initiated within 8 weeks of surgical resection , assuming complete recovery . The remaining recommendations from the original 2016 ASCO guideline are unchanged",
"BACKGROUND The management of patients with clinical recurrence of prostate cancer after radical prostatectomy ( RP ) remains challenging . OBJECTIVE To determine whether the removal of positive lymph nodes at [11C]choline positron emission tomography/computed tomography ( PET/CT ) scan may have an impact on the prognosis of patients with biochemical recurrence ( BCR ) and nodal recurrence after RP . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve analysis of 72 patients affected by BCR after RP associated with a nodal pathologic [11C]choline PET/CT scan . INTERVENTION Patients underwent salvage lymph node dissection ( LND ) . MEASUREMENTS Biochemical response ( BR ) to treatment was defined as prostate-specific antigen ( PSA ) clinical recurrence ( CR ) after salvage LND , respectively . RESULTS AND LIMITATIONS Overall , 56.9 % of patients achieved BR . Mean and median follow-up after LND were 39.4 and 39.8 mo , respectively . The 5-yr BCR-free survival rate was 19 % . Preoperative PSA time to BCR lymph nodes at previous RP ( HR : 0.19 ; p=0.04 ) represented independent predictors of BR . Overall , 5-yr CR-free and cancer-specific survival were 34 % and 75 % , respectively . At multivariable analyses , only PSA > 4 ng/ml ( HR : 2.13 ; p=0.03 ) and the presence of retroperitoneal uptake at PET/CT scan ( HR=2.92 ; p=0.004 ) represented independent preoperative predictors of CR . Similarly , the presence of pathologic nodes in the retroperitoneum ( HR : 2.78 ; p=0.02 ) , higher number of positive lymph nodes ( HR : 1.04 ; p=0.006 ) , and complete BR to salvage LND ( HR : 0.31 ; p=0.002 ) represented postoperative independent predictors of CR . Main limitations consisted of the lack of a control group and the heterogeneity of patients included in the analyses . CONCLUSIONS Salvage LND is feasible in patients with BCR after RP and nodal pathologic uptake at [11C]choline PET/CT scan . Biochemical response after surgery can be achieved in a consistent proportion of patients . Although most patients invariably progressed to BCR after surgery at longer follow-up , 35 % of patients showed the absence of CR at 5 yr",
"OBJECTIVES Based on methods introduced in the late 1960s and no longer used , serum testosterone level in men after surgical castration was reported to be 50 ng/dL or less . Radioimmunoassay and , subsequently , chemiluminescent methods have supplanted the early analytic methods because of their improved accuracy and ease of testing . The purpose of this study was to define the castrate testosterone level in the era of chemiluminescent testing . METHODS After bilateral orchiectomy , serum testosterone ( total ) levels were measured prospect ively in 35 prostate cancer patients . RESULTS The median testosterone value in this patient cohort was 15 ng/dL ( 0.5 nmol/L ; 95 % confidence interval 12 to 17 ng/dL ) . CONCLUSIONS In a contemporary series , castrate testosterone should be defined as less than 20 ng/dL ( 0.7 nmol/L ) . The important biologic and economic implication s are discussed",
"Objective : Flare-up phenomena , such as an increase in prostate-specific antigen ( PSA ) and /or deterioration of symptoms , are observed in some patients undergoing gonadotropin-releasing hormone ( GnRH ) agonist therapy . This study was carried out to determine the optimal time for starting the administration of flutamide to prevent flare-up phenomena . Patients and Methods : Twenty-six patients with prostate cancer and elevated serum levels of PSA were r and omly assigned to 5 groups . Group A patients ( n = 6 ) were treated with a subcutaneous injection of 3.75 mg leuprorelin acetate depot alone . Group B , C , D and E patients ( 5 patients in each group ) were treated with 375 mg/day of orally administered flutamide combined with leuprorelin . Flutamide was initiated on the day of leuprorelin injection in group B , and at 1 , 2 and 4 weeks before leuprorelin injection in groups C , D and E , respectively . Serum PSA and testosterone levels were measured in each patient . Results : Pretreatment with flutamide increased the serum testosterone level , but the testosterone surge after leuprorelin administration was almost the same in all 5 treatment groups . In patients who had been treated with flutamide in combination with leuprorelin , the mean PSA level did not exceed the pretreatment levels after leuprorelin administration . The rate of decrease in PSA in the group receiving simultaneous administration of flutamide with leuprorelin showed a decline comparable to that during the period before leuprorelin administration in the flutamide pretreatment groups . Conclusion : Simultaneous administration of flutamide with a GnRH agonist is sufficient to prevent flare-up phenomena",
"PURPOSE We report the toxicity and biochemical tumor control outcome of a prospect i ve Phase II study using high-dose-rate brachytherapy ( HDR ) alone as a salvage therapy for recurrent disease after external beam radiotherapy ( EBRT ) . METHODS Forty-two patients with biopsy-proven recurrence were enrolled on a Phase II study of salvage HDR monotherapy using iridium-192 . Median pretreatment EBRT dose was 8100 cGy ( 6840–8640 cGy ) and the median time from completion of EBRT to salvage HDR was 73 months . The protocol prescription dose of 3200 cGy was delivered in four fractions over 30 hours in a single insertion . Median followup after salvage HDR was 36 months ( 6–67 months ) . RESULTS The actuarial prostate-specific antigen biochemical relapse-free survival and distant metastases-free survival rates at 5 years were 68.5 % and 81.5 % , respectively . Cause-specific survival was 90.3 % . Late genitourinary Grade 1 and 2 toxicities were found in 38 % and 48 % , respectively , and one patient developed Grade 3 urinary incontinence . Late Grade 1 and 2 gastrointestinal toxicity was noted in 17 % and 8 % of patients , respectively . Three patients ( 7 % ) developed Grade 2 late urinary toxicity ( urethral stricture ) , which were corrected with urethral dilatation , and one patient developed Grade 3 urinary incontinence . No Grade 4 toxicities were observed . CONCLUSIONS Genitourinary toxicity was the most commonly encountered toxicity observed after salvage HDR but severe toxicities were uncommon . Salvage HDR is an effective and well-tolerated modality for locally recurrent prostate cancer and should be considered even for patients who have previously been treated with ultra-high dose levels of EBRT",
"BACKGROUND The and rogen-receptor isoform encoded by splice variant 7 lacks the lig and -binding domain , which is the target of enzalutamide and abiraterone , but remains constitutively active as a transcription factor . We hypothesized that detection of and rogen-receptor splice variant 7 messenger RNA ( AR-V7 ) in circulating tumor cells from men with advanced prostate cancer would be associated with resistance to enzalutamide and abiraterone . METHODS We used a quantitative reverse-transcriptase-polymerase-chain-reaction assay to evaluate AR-V7 in circulating tumor cells from prospect ively enrolled patients with metastatic castration-resistant prostate cancer who were initiating treatment with either enzalutamide or abiraterone . We examined associations between AR-V7 status ( positive vs. negative ) and prostate-specific antigen ( PSA ) response rates ( the primary end point ) , freedom from PSA progression ( PSA progression-free survival ) , clinical or radiographic progression-free survival , and overall survival . RESULTS A total of 31 enzalutamide-treated patients and 31 abiraterone-treated patients were enrolled , of whom 39 % and 19 % , respectively , had detectable AR-V7 in circulating tumor cells . Among men receiving enzalutamide , AR-V7-positive patients had lower PSA response rates than AR-V7-negative patients ( 0 % vs. 53 % , P=0.004 ) and shorter PSA progression-free survival ( median , 1.4 months vs. 6.0 months ; P clinical or radiographic progression-free survival ( median , 2.1 months vs. 6.1 months ; P overall survival ( median , 5.5 months vs. not reached ; P=0.002 ) . Similarly , among men receiving abiraterone , AR-V7-positive patients had lower PSA response rates than AR-V7-negative patients ( 0 % vs. 68 % , P=0.004 ) and shorter PSA progression-free survival ( median , 1.3 months vs. not reached ; P clinical or radiographic progression-free survival ( median , 2.3 months vs. not reached ; P overall survival ( median , 10.6 months vs. not reached , P=0.006 ) . The association between AR-V7 detection and therapeutic resistance was maintained after adjustment for expression of full-length and rogen receptor messenger RNA . CONCLUSIONS Detection of AR-V7 in circulating tumor cells from patients with castration-resistant prostate cancer may be associated with resistance to enzalutamide and abiraterone . These findings require large-scale prospect i ve validation . ( Funded by the Prostate Cancer Foundation and others . )",
"A previously reported , double‐blind , r and omized , multicenter phase 3 trial in 205 patients with stage C/D prostate cancer compared combined and rogen blockade ( CAB ) with luteinizing hormone‐releasing hormone agonist ( LHRH‐A ) plus bicalutamide 80 mg versus LHRH‐A plus bicalutamide‐matching placebo ( LHRH‐A monotherapy ) . The analysis at a median follow‐up of 2.4 years indicated that CAB significantly ( P prolonged the time to progression and the time to treatment failure . In the current report , survival data from a long‐term follow‐up ( median , 5.2 years ) were analyzed",
"BACKGROUND How best to treat rising prostate-specific antigen ( PSA ) concentration after radical prostatectomy is an urgent clinical question . Salvage radiotherapy delays the need for more aggressive treatment such as long-term and rogen suppression , but fewer than half of patients benefit from it . We aim ed to establish the effect of adding short-term and rogen suppression at the time of salvage radiotherapy on biochemical outcome and overall survival in men with rising PSA following radical prostatectomy . METHODS This open-label , multicentre , phase 3 , r and omised controlled trial , was done in 43 French study centres . We enrolled men ( aged ≥18 years ) who had received previous treatment for a histologically confirmed adenocarcinoma of the prostate ( but no previous and rogen deprivation therapy or pelvic radiotherapy ) , and who had stage pT2 , pT3 , or pT4a ( bladder neck involvement only ) in patients who had rising PSA of 0·2 to less than 2·0 μg/L following radical prostatectomy , without evidence of clinical disease . Patients were r and omly assigned ( 1:1 ) central ly via an interactive web response system to st and ard salvage radiotherapy ( three-dimensional [ 3D ] conformal radiotherapy or intensity modulated radiotherapy , of 66 Gy in 33 fractions 5 days a week for 7 weeks ) or radiotherapy plus short-term and rogen suppression using 10·8 mg goserelin by subcutaneous injection on the first day of irradiation and 3 months later . R and omisation was stratified using a permuted block method according to investigational site , radiotherapy modality , and prognosis . The primary endpoint was progression-free survival , analysed in the intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT00423475 . FINDINGS Between Oct 19 , 2006 , and March 30 , 2010 , 743 patients were r and omly assigned , 374 to radiotherapy alone and 369 to radiotherapy plus goserelin . Patients assigned to radiotherapy plus goserelin were significantly more likely than patients in the radiotherapy alone group to be free of biochemical progression or clinical progression at 5 years ( 80 % [ 95 % CI 75 - 84 ] vs 62 % [ 57 - 67 ] ; hazard ratio [ HR ] 0·50 , 95 % CI 0·38 - 0·66 ; p occurred in patients receiving short-term and rogen suppression compared with those who received radiotherapy alone . The most frequently occuring acute adverse events related to goserelin were hot flushes , sweating , or both ( 30 [ 8 % ] of 366 patients had a grade 2 or worse event ; 30 patients [ 8 % ] had hot flushes and five patients [ 1 % ] had sweating in the radiotherapy plus goserelin group vs none of 372 patients in the radiotherapy alone group ) . Three ( 8 % ) of 366 patients had grade 3 or worse hot flushes and one patient had grade 3 or worse sweating in the radiotherapy plus goserelin group versus none of 372 patients in the radiotherapy alone group . The most common late adverse events of grade 3 or worse were genitourinary events ( 29 [ 8 % ] in the radiotherapy alone group vs 26 [ 7 % ] in the radiotherapy plus goserelin group ) and sexual disorders ( 20 [ 5 % ] vs 30 [ 8 % ] ) . No treatment-related deaths occurred . INTERPRETATION Adding short-term and rogen suppression to salvage radiotherapy benefits men who have had radical prostatectomy and whose PSA rises after a postsurgical period when it is undetectable . Radiotherapy combined with short-term and rogen suppression could be considered as a reasonable option in this population . FUNDING French Ministry of Health , AstraZeneca , and La Ligue Contre le Cancer"
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41179c04-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND Electroconvulsive therapy ( ECT ) is a medical treatment that is most effective for mood disorders ( Bipolar Disorder and Major Depression ) . It has also been shown to be an effective treatment for schizophrenia accompanied by catatonia , extreme depression , mania and other affective components . ECT is currently under-used in many psychiatric setting s due to its stigmatized perception by patients and mental health professionals . However , many unanswered questions remain regarding its role in the management of patients with schizophrenia . AIM Evaluate the main indications of ECT in subjects suffering from schizophrenia . OBJECTIVES Investigate the efficacy and the main indications of ECT in the treatment of schizophrenic patients , evaluate its effects in the short-term and the long-term , compare ECT treatment with pharmacotherapy , and assess the effects of treatment with ECT . METHODS A systematic review of the literature was conducted on the use of ECT for schizophrenia . Thirty one articles from peer- review ed journals were identified , and the most relevant articles were selected for this review . RESULTS The most common indication for using ECT for schizophrenia patients was to augment pharmacotherapy , while the most common accompanying symptoms were , in order , catatonia , aggression and suicide . Catatonic patients responded significantly better to ECT than patients with any other subtype of schizophrenia . The combination of ECT with pharmacotherapy can be useful for drug-resistant patients . The use of an ECT-risperidone combination or ECT-clozapine combination in patients non-responsive to prior pharmacotherapy was found to be most effective . CONCLUSIONS This review indicates that ECT , combined with pharmacotherapy , may be a viable option for a selected group of patients with schizophrenia . In particular , the use of ECT is recommended for drug-resistant patients , for schizophrenic patients with catatonia , aggression or suicidal behavior , and when rapid global improvement and reduction of acute symptomatology are required
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"Electroconvulsive therapy ( ECT ) is prescribed for schizophrenia patients for various indications , in our country . However , official guidelines in other countries have been cautious in prescribing ECT for schizophrenia . To study the indications for which patients with schizophrenia receive ECT . We studied records of schizophrenia in patients receiving ECT in one year ( 2005 ) ( n=101 ) retrospectively , as well as the consecutive data of patients between May 2007 and June 2008 ( n=101 ) prospect ively . The various indications for ECT in schizophrenia were studied by frequency analysis . Of the 202 schizophrenia patients who received ECT , the most common reason was ‘ to augment pharmacotherapy ’ in ( n=116 ) cases . The target symptoms for which ECT was prescribed the most was catatonia ( n=72 ) . The mean number of ECTs ( SD ) received was 8.4 ( 2.8 ) . Augmentation of pharmacotherapy was the most common indication of ECT in patients with schizophrenia",
"OBJECTIVE Previous studies have demonstrated the effectiveness of electroconvulsive therapy ( ECT ) in pharmacotherapy-resistant neuropsychiatric conditions . This study aim ed to evaluate the efficacy and safety of ECT in adolescents with first-episode psychosis . METHOD This case-control study was conducted in in patients aged 13 - 20 years with first-episode psychosis . Every three similar age and same gender patients consecutively recruited were r and omly allocated to control and ECT group at a ratio of 1:2 , while they had antipsychotic treatment . ECT treatment was performed for 3 sessions per week with a maximum of 14 sessions . The endpoint was discharge from hospital . Clinical outcomes were measured using hospital stay days , the Positive and Negative Syndrome Scale ( PANSS ) and response rate . Polysomnography ( PSG ) was conducted at baseline and at week 2 . Safety and tolerability were also evaluated . RESULTS Between March 2004 and November 2009 , 112 eligible patients were allocated to control ( n=38 ) and ECT ( n=74 ) group . Additional ECT treatment significantly reduced hospital stay compared to controls ( 23.2±8.2 days versus 27.3±9.3 days , mean±SD , P=0.018 ) . Survival analysis revealed that the ECT-treated group had a significantly higher cumulative response rate than controls ( 74.3 % versus 50 % , relative risk (RR)=1.961 , P=0.001 ) . Additional ECT also produced significantly greater improvement in sleep efficiency , rapid eye movement ( REM ) latency and density than control condition . The PSG improvement significantly correlated with reduction in scores on overall PANSS , positive symptoms , and general psychopathology . No patients discontinued ECT treatment regimen during hospital stay . The incidence of most adverse events was not different in the two groups , but ECT-treated group had more complaints of transient headache and dizziness than controls . CONCLUSIONS ECT is an effective and safe intervention used in adolescents with first-episode psychosis . Its antipsychotic effects are associated with improved PSG variables . ECT can be considered as an early psychosis intervention",
"Schizophrenia is a serious psychiatric disorder that develops mainly in young adults . Electroconvulsive therapy ( ECT ) is known to be effective and safe in patients with schizophrenia with acute psychotic exacerbation . Because of the shortage of systematic studies , we conducted a prospect i ve naturalistic study to examine the short-term effects of acute ECT and its safety in young adults with medically intractable first-episode schizophrenia . Subjects were seven consecutive patients , 15 - 35 years of age , with first-episode schizophrenia or schizophreniform disorder ( Diagnostic and Statistical Manual of Mental Disorders , 4th edition ; DSM-IV ) , who had failed to respond to neuroleptics . The seven patients were treated with a first course of ECT , and their clinical symptoms were evaluated on the basis of the Brief Psychiatric Rating Scale ( BPRS ) ( 18 items , rated 0 - 6 ) and Global Assessment of Functioning ( GAF ) Scale . The GAF Scale is presented in DSM-IV as a means of assessing global functioning of a psychiatric patient . Scores range from 1 - 100 ; the higher GAF score indicates the higher global functioning . Adverse effects result ing from acute ECT were also evaluated . The total BPRS score 1 week after the final session improved significantly compared to the total pre-ECT BPRS score . The GAF score also improved significantly compared to the pre-ECT GAF score . There were no adverse effects during the acute ECT course , except for mild delirium . We conclude that ECT may be an effective and safe treatment option for young adults with intractable first-episode schizophrenia",
"Background & objectives : In recent years , health-related quality of life ( QOL ) has been regarded as the most important dimension of outcome in schizophrenia . Recent research has shown that atypical antipsychotics improve QOL in patients with schizophrenia . Importance of electroconvulsive therapy ( ECT ) has been demonstrated in restoring function and health related quality of life in depressed patients . However , there are no data on patients of schizophrenia . The objective of the present study was therefore , to assess the improvement in quality of life after ECT in treatment resistant schizophrenia . Methods : Thirty consecutive patients of treatment resistant schizophrenia were given ECT sessions twice a week and assessment s were made with Positive and Negative Syndrome Scale of Schizophrenia ( PANSS ) , WHO QOL Bref , Global Assessment of Functioning Scale and Clinical Global Impressions . Results : The group improved significantly on all the domains of quality of life scale except the domain named satisfaction with social relations . There was also significant change in the total score of PANSS after 6 ECT sessions ( mean at baseline = 86.7 , mean after 6 ECT = 65.5 , P score on the global assessment of functioning also changed significantly ( mean 26.3 at baseline to 44.5 after 6 ECT sessions ) . Interpretation & conclusions : The present findings showed that ECT in addition to improvement in symptomatology led to improvement in QOL in patients of treatment resistant schizophrenia",
"This is the second article from a study of the outcome of five different methods of treatment for schizophrenia ; patients were followed up over a period of two to five years after first admission and the first release . Patients who had been originally treated in hospital with psychotherapy alone stayed longer in hospital over the follow-up period than those who had received electroconvulsive therapy ( ECT ) , drug alone , or drug plus psychotherapy . Those who had been treated with milieu therapy also had a longer stay date d from the time of admission . Patients treated initially with drugs or ECT showed a trend toward spending less time in hospital after their release",
"In a double-blind , prospect i ve study , 30 consecutive treatment-naive adult men with first-onset psychosis and DSM-IIIR provisional schizophreniform disorder ( without good prognostic features ) were r and omized into true electroconvulsive therapy ( ECT ) and sham ECT groups . Both groups received haloperidol in a fixed dose of 15 mg at night . The ECT schedule comprised six bilateral , sinusoidal wave treatments administered on alternate days , thrice a week . Weekly ratings for the first 6 weeks showed an absence of significant difference between the groups in the number of patients responding and in the rate of attenuation of psychosis ; severity of depression , while less in the true ECT group after the first 3 weeks , did not differ between the groups at any subsequent time point . Clinical ratings were repeated at 6 months , and social functioning was assessed ; again , no group differences emerged . It is concluded that ECT does not meaningfully improve response in unselected schizophreniform disorder that is treated with an adequate dose of neuroleptic",
"The efficacy of ECT was investigated in a double-blind trial . Twenty-two patients with schizophrenia received trifluoperazine and were r and omly allocated to receive eight real or eight simulated ECTs . In the first eight weeks , the group receiving real ECTs showed significantly more improvement as measured on the Brief Psychiatric Rating Scale . However , the groups showed no significant differences from the twelfth week onwards . The superiority of real ECT was not confirmed at the end of six months",
"Electroconvulsive therapy ( ECT ) in the treatment of schizophrenia was evaluated in a double-blind trial ; the clinical change after ECT was compared with that after a treatment procedure identical to it but for two exceptions -- no electricity was used and no convulsion was induced . All patients had paranoid schizophrenia according to Present State Examination criteria and all received st and ard doses of neuroleptics for at least 2 weeks before r and om assignment to the two groups . 20 patients completed the trial : 10 had ECT and 10 were in the control group . Treatment was given three times a week , with a minimum of eight treatments and a maximum of twelve . Clinical change was assessed by the Comprehensive Psychiatric Rating Scale . Both groups improved but the improvement of patients receiving ECT was significantly greater than that of controls both after six treatments ( p=0.02 ) and at the end of treatment ( p=0.004 ) . Thus the group receiving ECT gained a clear and early advantage compared with the control group , although by 16 weeks there was little difference between the two groups . Possible reasons for this are discussed",
"BACKGROUND Several studies show that bifrontal electrode placement produces relatively fewer cognitive adverse effects than bitemporal placement during electroconvulsive therapy ( ECT ) in depression . There are no reports comparing these electrode placements in schizophrenia . OBJECTIVES This study compared the clinical and cognitive effects of bifrontal and bitemporal electrode placements in schizophrenia patients referred for electroconvulsive therapy ( ECT ) . METHODS 122 schizophrenia patients who were prescribed ECT were r and omized to receive ECT with either bifrontal ( BFECT ; n = 62 ) or bitemporal ( BTECT ; n = 60 ) placement . Their concomitant anti-psychotic medications and the number of ECT sessions were not controlled . Psychopathology was assessed using the Brief Psychiatric Rating Scale ( BPRS ) , Bush-Francis Catatonia Rating Scale ( BFCRS ) , and the Nurse Observation Scale for Inpatient Evaluation ( NOSIE ) . Cognitive functions were assessed 24-h after the final ECT using a battery of tests . Clinical improvement was compared using chi-square test , repeated measures ANOVA and analysis of covariance ( ANCOVA ) . Cognitive adverse effects were compared using t-test . RESULTS At the end of 2 weeks ( after 6 ECT sessions ) 63 % and 13.2 % of BFECT and BTECT patients respectively had met the response criterion for BPRS ( 40 % reduction in total score ; OR = 20.8 ; 95 % CI = 3.61 - 34.33 ) . BFECT patients showed significantly faster clinical response on BPRS ( Time × Group interaction effect : P = 0.001 ) , BFCRS ( P the NOSIE total assets score ( P = 0.003 ) . ANCOVA using baseline scores as covariates and treatment-resistance status as between-subject factor showed that BFECT patients had significantly greater improvement in all measures . BFECT patients had significantly higher PGI-memory-scale total score than BTECT patients ( t = 5.16 ; P superior performance in other cognitive measures . CONCLUSIONS BFECT results in superior clinical and cognitive outcomes than BTECT in schizophrenia patients referred for ECT",
"As part of the Leicester electroconvulsive therapy ( ECT ) study , the role of ECT in schizophrenia was investigated in a double-blind trial . The Present State Examination criteria for schizophrenia were fulfilled by 22 patients , of whom 19 gave consent and entered the trial . Neuroleptic medication was restricted during the trial period . Patients were r and omly allocated to eight real ECT or eight simulated ECT . At the end of the four-week trial period , patients receiving real ECT showed a significantly greater improvement when measured on the Montgomery-Asberg Schizophrenia Scale ( MASS ) , the visual analogue global psychopathology scale , and the depression scale . The differences on the MASS and visual analogue global psychopathology scale were not due to improvement in depressive symptoms . The superiority of real ECT was not demonstrated at the 12- and 28-week follow-up , when treatment was not controlled",
"BACKGROUND In treatment-resistant schizophrenia a combination of ECT with antipsychotics has been reported to have superior outcomes compared to other strategies , however the results were inconsistent . We investigated the long-term effects of the combination of unilateral , non-dominant hemisphere ECT with three antipsychotics . SUBJECTS AND METHODS The clinical study was a naturalistic , prospect i ve , open-labeled , active-controlled study in adult out patients of both genders suffering from treatment-resistant schizophrenia with a follow up of 2 years . The patients received sulpiride ( n=17 , 100 - 400mg/day , PO ) , risperidone ( n=26 , 2 - 8 mg/day , PO ) or olanzapine ( n=27 , 5 - 10mg/day , PO ) . Unilateral ECT was applied in 1 unit ( 0.5A , 0.8 mS ) in six single applications , once a week and further according to the clinical need , in fortnight steps . Clinical efficacy was established using the PANSS and CGI psychometric scales . RESULTS According to the results , the most effective treatment mode was olanzapine plus ECT , then risperidone plus ECT , while sulpiride plus ECT had lower clinical efficacy . Olanzapine plus ECT was significantly superior in all scale scores vs sulpiride plus ECT , as well as risperidone plus ECT except for PANSS-P ( t=1.85 , p>0.05 ) . During the study , 38 of 70 patients were withdrawn due to treatment failure ( n=21 ) , side effects ( n=6 ) and non-compliance ( n=11 ) . CONCLUSION The combination of novel antipsychotics and ECT can be used safely and effectively in treatment-resistant schizophrenia"
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41179c40-06ff-11f0-808a-c43d1ab1c353
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Anxiety disorders are chronic and functionally disabling conditions with high psychological stress , characterised by cognitive symptoms of excessive worry and focus difficulties and physiological symptoms such as muscle tension and insomnia . Gamma-aminobutyric acid ( GABA ) is an inhibitory neurotransmitter within the central nervous system and is a key target of pharmacotherapies in the treatment of anxiety . Although current pharmaceutical treatments are often efficacious , they may cause undesirable side effects including cognitive decrements and withdrawal symptoms . Plant-based " phytomedicines " may provide novel treatment options , to act as an adjunctive or alternative to existing anxiolytic medications . As such , we conducted a systematic review to assess the current body of literature on anxiolytic phytomedicines and /or phytoconstituents . An open-ended search to 5 July 2017 was conducted using MEDLINE ( PubMed ) , Scopus , and Cochrane library online data bases and performed in a stepped format from pre clinical to clinical investigations . Eligible studies must have had ( a ) in vitro evidence of GABA-modulating activity , ( b ) animal studies using anxiety models to test an anxiolytic effect , and ( c ) human clinical trials . Ten phytomedicines were identified as having pre clinical investigations showing interaction with the GABA system , in addition to human clinical trials : kava , valerian , pennywort , hops , chamomile , Ginkgo biloba , passionflower , ashwag and ha , skullcap , and lemon balm . Collectively , the literature reveals pre clinical and clinical evidence for various phytomedicines modulating GABA-pathways , with comparative anxiolytic effect to the current array of pharmaceuticals , along with good safety and tolerability profiles
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"Background Generalised anxiety disorder ( GAD ) is a chronic and pervasive condition that generates high levels of psychological stress , and it is difficult to treat in the long term . Current pharmacotherapeutic options for GAD are in some cases only modestly effective , and may elicit undesirable side effects . Through targeted actions on the gamma-aminobutyric acid ( GABA ) pathway , the South Pacific medicinal plant kava ( Piper methysticum ) is a non-addictive , non-hypnotic anxiolytic with the potential to treat GAD . The evidence for the efficacy of kava for treating anxiety has been affirmed through clinical trials and meta-analyses . Recent research has also served to lessen safety concerns regarding the use of kava due to hepatotoxic risk , which is reflected in a recent German court overturning the previous kava ban in that country ( which may in turn influence a reinstatement by the European Union ) . The aim of current research is to assess the efficacy of an ‘ aqueous noble cultivar rootstock extract ’ of kava in GAD in a larger longer term study . In addition , we plan to investigate the pharmacogenomic influence of GABA transporters on response , effects of kava on gene expression , and for the first time , the neurobiological correlates of treatment response via functional and metabolic imaging . Methods / Design This clinical trial is funded by the Australian National Health and Medical Research Council ( APP1063383 ) and co-funded by MediHerb ( Integria Healthcare ( Australia ) Pty . Ltd ) . The study is a phase III , multi-site , two-arm , 18-week , r and omised , double-blind , placebo-controlled study using an aqueous extract of noble kava cultivar ( st and ardised to 240 mg of kavalactones per day ) versus matching placebo in 210 currently anxious participants with diagnosed GAD who are non-medicated . The study takes place at two sites : the Centre for Human Psychopharmacology ( Swinburne University of Technology ) , Hawthorn , Melbourne , Australia ; and the Academic Discipline of Psychiatry ( The University of Queensl and ) based at the Royal Brisbane and Women ’s Hospital , Herston , Brisbane , Australia . Written informed consent will be obtained from each participant prior to commencement in the study . The primary outcome is the Structured Interview Guide for the Hamilton Anxiety Rating Scale ( SIGH-A ) . The secondary outcomes involve a range of scales that assess affective disorder symptoms and quality of life outcomes , in addition to the study of mediating biomarkers of response ( assessed via genomics and neuroimaging ) . Discussion If this study demonstrates positive findings in support of the superiority of kava over placebo in the treatment of GAD , and also is shown to be safe , then this plant-medicine can be considered a ’ first-line ‘ therapy for GAD . Genomic and neuroimaging data may reveal clinical response patterns and provide more evidence of the neurobiological activity of the plant extract . Trial Registration Information Clinical Trials.gov : NCT02219880 Date : 13 August 2014",
"Background Anxiety symptoms are frequently observed in dental patients , whether they are undergoing simple or more invasive procedures such as surgery . This research aim ed to compare the effects of Passiflora incarnata and midazolam for the control of anxiety in patients undergoing m and ibular third molar extraction . Material and Methods Forty volunteers underwent bilateral extraction of their m and ibular third molars in a r and omized , controlled , double-blind , crossover clinical trial . Passiflora incarnata ( 260 mg ) or midazolam ( 15 mg ) were orally administered 30 minutes before surgery . The anxiety level of participants was evaluated by question naires and measurement of physical parameters , including heart rate ( HR ) , blood pressure ( BP ) , and oxygen saturation ( SpO2 ) . Results Considering each procedure independently , there were no significant differences between the protocol s in BP , HR , and SpO2 . Over 70 % of the volunteers responded that they felt quiet or a little anxious under both protocol s. With midazolam , 20 % of the participants reported amnesia ( not remembering anything at all ) , while Passiflora showed little or no ability to interfere with memory formation . Conclusions Passiflora incarnata showed an anxiolytic effect similar to midazolam , and was safe and effective for conscious sedation in adult patients who underwent extraction of their m and ibular third molars . Key words : Passiflora incarnata , midazolam , anxiety , oral surgery",
"Chronic stress has been associated with a number of illnesses , including obesity . Ashwag and ha is a well-known adaptogen and known for reducing stress and anxiety in humans . The objective of this study was to evaluate the safety and efficacy of a st and ardized root extract of Ashwag and ha through a double-blind , r and omized , placebo-controlled trial . A total of 52 subjects under chronic stress received either Ashwag and ha ( 300 mg ) or placebo twice daily . Primary efficacy measures were Perceived Stress Scale and Food Cravings Question naire . Secondary efficacy measures were Oxford Happiness Question naire , Three-Factor Eating Question naire , serum cortisol , body weight , and body mass index . Each subject was assessed at the start and at 4 and 8 weeks . The treatment with Ashwag and ha result ed in significant improvements in primary and secondary measures . Also , the extract was found to be safe and tolerable . The outcome of this study suggests that Ashwag and ha root extract can be used for body weight management in adults under chronic stress",
"Context : Stress is a state of mental or emotional strain or tension , which can lead to underperformance and adverse clinical conditions . Adaptogens are herbs that help in combating stress . Ayurvedic classical texts , animal studies and clinical studies describe Ashwag and ha as a safe and effective adaptogen . Aims : The aim of the study was to evaluate the safety and efficacy of a high-concentration full-spectrum extract of Ashwag and ha roots in reducing stress and anxiety and in improving the general well-being of adults who were under stress . Setting s and Design : Single center , prospect i ve , double-blind , r and omized , placebo-controlled trial . Material s and Methods : A total of 64 subjects with a history of chronic stress were enrolled into the study after performing relevant clinical examinations and laboratory tests . These included a measurement of serum cortisol , and assessing their scores on st and ard stress- assessment question naires . They were r and omized to either the placebo control group or the study drug treatment group , and were asked to take one capsule twice a day for a period of 60 days . In the study drug treatment group , each capsule contained 300 mg of high-concentration full-spectrum extract from the root of the Ashwag and ha plant . During the treatment period ( on Day 15 , Day 30 and Day 45 ) , a follow-up telephone call was made to all subjects to check for treatment compliance and to note any adverse reactions . Final safety and efficacy assessment s were done on Day 60 . Statistical Analysis : t-test , Mann-Whitney test . Results : The treatment group that was given the high-concentration full-spectrum Ashwag and ha root extract exhibited a significant reduction ( P stress- assessment scales on Day 60 , relative to the placebo group . The serum cortisol levels were substantially reduced ( P=0.0006 ) in the Ashwag and ha group , relative to the placebo group . The adverse effects were mild in nature and were comparable in both the groups . No serious adverse events were reported . Conclusion : The findings of this study suggest that a high-concentration full-spectrum Ashwag and ha root extract safely and effectively improves an individual 's resistance towards stress and thereby improves self-assessed quality of life",
"Purpose Patients who undergo regional anesthesia experience anxiety in the preoperative period . Passiflora incarnata Linneaus is a plant that has traditionally been used as an anxiolytic and sedative . We aim ed to investigate the effect of preoperative oral administration of Passiflora incarnata Linneaus on anxiety , psychomotor functions , sedation , and hemodynamics in patients undergoing spinal anesthesia . Methods Under local ethics committee approval , 60 patients who were aged 25–55 years and ASAI – II and who were scheduled for spinal anesthesia were enrolled in this prospect i ve , r and omized , double-blind and placebo-controlled study . Thirty minutes before spinal anesthesia , baseline hemodynamic parameters , State-Trait Anxiety Inventory ( STAI ) score , sedation score , and psychomotor function test results were measured , then patients were r and omly assigned to two groups : oral Passiflora incarnata Linneaus extract or placebo was given to the patients . Tests were repeated just before spinal anesthesia . Hemodynamics , sedation score , sensory-motor block and side effects were assessed during the operation . Psychomotor function tests were repeated at the end of the operation and 60 min after the operation . Results There was a statistically significant difference between the two groups for the increase in State Anxiety Inventory ( STAI-S ) score obtained just before spinal anesthesia when compared to the baseline . There was no statistically significant difference in psychomotor function from the baseline for either group . A significant difference was not found between the two groups in demographics , psychomotor function , sedation score , hemodynamics , and side effects . Conclusion Oral preoperative administration of Passiflora incarnata Linneaus suppresses the increase in anxiety before spinal anesthesia without changing psychomotor function test results , sedation level , or hemodynamics",
"Background Despite being the most commonly used herbal for sleep disorders , chamomile 's ( Matricaria recutita ) efficacy and safety for treating chronic primary insomnia is unknown . We examined the preliminary efficacy and safety of chamomile for improving subjective sleep and daytime symptoms in patients with chronic insomnia . Methods We performed a r and omized , double-blind , placebo-controlled pilot trial in 34 patients aged 18 - 65 years with DSM-IV primary insomnia for ≥ 6-months . Patients were r and omized to 270 mg of chamomile twice daily or placebo for 28-days . The primary outcomes were sleep diary measures . Secondary outcomes included daytime symptoms , safety assessment s , and effect size of these measures . Results There were no significant differences between groups in changes in sleep diary measures , including total sleep time ( TST ) , sleep efficiency , sleep latency , wake after sleep onset ( WASO ) , sleep quality , and number of awakenings . Chamomile did show modest advantage on daytime functioning , although these did not reach statistical significance . Effect sizes were generally small to moderate ( Cohen 's d ≤ 0.20 to with sleep latency , night time awakenings , and Fatigue Severity Scale ( FSS ) , having moderate effect sizes in favor of chamomile . However , TST demonstrated a moderate effect size in favor of placebo . There were no differences in adverse events reported by the chamomile group compared to placebo . Conclusion Chamomile could provide modest benefits of daytime functioning and mixed benefits on sleep diary measures relative to placebo in adults with chronic primary insomnia . However , further studies in select insomnia patients would be needed to investigate these conclusions .Trial Registration Clinical Trials.gov Identifier",
"Scutellaria lateriflora , a traditional herbal remedy for stress and anxiety , was tested on human volunteers for its effects on mood . In a placebo-controlled , double-blind , crossover study , 43 healthy participants were r and omised to a sequence of three times daily S. lateriflora ( 350 mg ) or placebo , each over two weeks . In this relatively non-anxious population ( 81 % were mildly anxious or less , i.e. Beck Anxiety Inventory ( BAI ) scores ≤ 15 ) , there was no significant difference between skullcap and placebo with BAI ( p = 0.191 ) . However , there was a significant group effect ( p = 0.049 ) , suggesting a carryover effect of skullcap . For Total Mood Disturbance measured by the Profile of Mood States , there was a highly significant ( p = with skullcap but not placebo ( p = 0.072 ) . The limitations of carryover effect , generally low anxiety scores and differences in anxiety levels between groups at baseline ( p = 0.022 ) , may have reduced the chances of statistical significance in this study . However , as S. lateriflora significantly enhanced global mood without a reduction in energy or cognition , further study assessing its putative anxiolytic effects in notably anxious subjects with co-morbid depression is warranted",
"Introduction The hop ( Humulus lupulus L. ) , a component of beer , is a sedative plant whose pharmacological activity is principally due to its bitter resins , in particular to the α-acid degradation product 2-methyl-3-buten-2-ol . The mechanism of action of hop resin consists of raising the levels of the neurotransmitter γ-aminobutyric acid ( GABA ) , an inhibitory neurotransmitter acting in the central nervous system ( CNS ) . Objectives To analyze the sedative effect of hops as a component of non-alcoholic beer on the sleep/wake rhythm in a work-stressed population . Methods The experiment was conducted with healthy female nurses ( n = 17 ) working rotating and /or night shifts . Overnight sleep and chronobiological parameters were assessed by actigraphy ( Actiwatch ® ) after moderate ingestion of non-alcoholic beer containing hops ( 333 ml with 0,0 % alcohol ) with supper for 14 days ( treatment ) . Data were obtained in comparison with her own control group without consumption of beer during supper . Results Actigraphy results demonstrated improvement of night sleep quality as regards the most important parameters : Sleep Latency diminished ( p≤0.05 ) in the Treatment group ( 12.01±1.19 min ) when compared to the Control group ( 20.50±4.21 min ) , as also did Total Activity ( p≤0.05 ; Treatment group = 5284.78±836.99 activity pulses vs Control = 7258.78±898.89 activity pulses ) . In addition , anxiety as indexed by the State-Trait Anxiety Inventory ( STAI ) decreased in the Treatment group ( State Anxiety 18.09±3.8 vs Control 20.69±2.14 ) . Conclusion The moderate consumption of non-alcoholic beer will favour night-time rest , due in particular to its hop components , in addition to its other confirmed benefits for the organism",
"CONTEXT Anxiety and depression are the most commonly reported psychiatric conditions and frequently occur as comorbid disorders . While the advent of conventional drug therapies has simplified treatment , a large segment of the population goes untreated or declines conventional therapy for financial , cultural , or personal reasons . Therefore , the identification of inexpensive and effective alternative therapies for anxiety and depression is of relevance to public health . OBJECTIVE The current study explores data from a 2009 clinical chamomile trial in humans to determine if chamomile provides clinical ly meaningful antidepressant activity versus a placebo . DESIGN In the 2009 r and omized , double-blind , placebo-controlled study , the research team examined the antianxiety and antidepressant action of oral chamomile ( Matricaria recutita ) extract in participants with symptoms of comorbid anxiety and depression . SETTING In the 2009 study , all of participants ' evaluations took place at the Depression Research Unit at the University of Pennsylvania . The study drew participants from patients at the Department of Family Medicine and Community Health 's primary care clinic at the University of Pennsylvania , Philadelphia . PARTICIPANTS Of the 57 participants in the 2009 trial , 19 had anxiety with comorbid depression ; 16 had anxiety with a past history of depression ; and 22 had anxiety with no current or past depression . INTERVENTION The intervention and placebo groups in the 2009 trial received identically appearing 220-mg capsules containing either pharmaceutical- grade chamomile extract st and ardized to a content of 1.2 % apigenin or a placebo ( ie , lactose monohydrate NF ) , respectively . OUTCOME MEASURES In the current study , the research team used generalized estimating equations analysis to identify clinical ly meaningful changes over time in scores from the Hamilton Depression Rating ( HAM-D ) question naire among treatment groups . RESULTS In the current study , the research team observed a significantly greater reduction over time in total HAM-D scores for chamomile vs placebo in all participants ( P total HAM-D scores for chamomile vs placebo in participants with current comorbid depression ( P = .062 ) . When the team examined the HAM-D core mood item scores , it observed a significantly greater reduction over time for chamomile vs placebo in all participants ( P Chamomile may provide clinical ly meaningful antidepressant activity that occurs in addition to its previously observed anxiolytic activity",
"Statement of Problem : Oral premedication used to reduce the anxiety in patients undergoing dental treatment . Passion flower has been used as a sedative that can control the dental anxiety . Purpose : This study determines the efficacy of Passion flower , in reducing anxiety during the dental procedures . Material and Methods : In this r and omized- one sided blind clinical trial , 63 patients , with moderate , high and severe anxiety(according to VAS score ) in need of periodontal treatment were r and omly divided into 3 groups of 21.The first group was given the drop Passion flower drop and the second group were given the drop of placebo and the third group ; neither drug nor placebo were given ( negative control group ) . Results were analyzed by Chi Square , Variance Analysis , Tucky and Paired-T using SPSS software . Results : Mean anxiety level prior to the drug administration was 12.09±2.42 for the Passion flower group , 12.00±2.66 for the placebo group and 11.66±2.39 for the negative control group . After premedication , these values were : 8.47±2.58 for the Passion flower group , 10.52±2.11 for the placebo group and 11.23±2.34 for the negative control group . These results demonstrated a significant difference ( p the anxiety levels before and after the Passion flower administration in the Passion flower group and also between the Passion flower group and the other two groups . Conclusion : Results indicated that administration of Passion flower , as a premedication , is significantly effective in reducing the anxiety . Since this study is a pioneer on the subject , further trials with greater number of subjects are required to confirm our results",
"Background Anxiety is a serious personal health condition and represents a substantial burden to overall quality of life . Additionally anxiety disorders represent a significant cost to the health care system as well as employers through benefits coverage and days missed due to incapacity . This study sought to explore the effectiveness of naturopathic care on anxiety symptoms using a r and omized trial . Methods Employees with moderate to severe anxiety of longer than 6 weeks duration were r and omized based on age and gender to receive naturopathic care ( NC ) ( n = 41 ) or st and ardized psychotherapy intervention ( PT ) ( n = 40 ) over a period of 12 weeks . Blinding of investigators and participants during r and omization and allocation was maintained . Participants in the NC group received dietary counseling , deep breathing relaxation techniques , a st and ard multi-vitamin , and the herbal medicine , ashwag and ha ( Withania somnifera ) ( 300 mg b.i.d . st and ardized to 1.5 % withanolides , prepared from root ) . The PT intervention received psychotherapy , and matched deep breathing relaxation techniques , and placebo . The primary outcome measure was the Beck Anxiety Inventory ( BAI ) and secondary outcome measures included the Short Form 36 ( SF-36 ) , Fatigue Symptom Inventory ( FSI ) , and Measure Yourself Medical Outcomes Profile ( MY-MOP ) to measure anxiety , mental health , and quality of life respectively . Participants were blinded to the placebo-controlled intervention . Results Seventy-five participants ( 93 % ) were followed for 8 or more weeks on the trial . Final BAI scores decreased by 56.5 % ( p BAI group scores were significantly decreased in the NC group compared to PT group ( p = 0.003 ) . Significant differences between groups were also observed in mental health , concentration , fatigue , social functioning , vitality , and overall quality of life with the NC group exhibiting greater clinical benefit . No serious adverse reactions were observed in either group . Relevance Many patients seek alternatives and /or complementary care to conventional anxiety treatments . To date , no study has evaluated the potential of a naturopathic treatment protocol to effectively treat anxiety . Knowledge of the efficacy , safety or risk of natural health products , and naturopathic treatments is important for physicians and the public in order to make informed decisions . Interpretation Both NC and PT led to significant improvements in patients ' anxiety . Group comparison demonstrated a significant decrease in anxiety levels in the NC group over the PT group . Significant improvements in secondary quality of life measures were also observed in the NC group as compared to PT . The whole system of naturopathic care for anxiety needs to be investigated further including a closer examination of the individual components within the context of their additive effect . Trial Registration Controlled-Trials.com IS RCT",
"Background : Several studies are conducted on Premenstrual Syndrome ( PMS ) . However , a few herbal surveys exist on the treatment of PMS in Iran . Due to the sedative effects of Melissa officinalis ( M. officinalis ) , this question comes to mind that “ can it be used in the treatment of PMS symptoms ? ” Objectives : The current study aim ed to assess the effect of M. officinalis capsule on the intensity of PMS in high-school girls . Material s and Methods : A double-blind r and omized , placebo-controlled trial was performed on 100 high school girls from 2013 to 2014 . The intervention group ( n = 50 ) received 1200 mg of M. officinalis essence daily from the first to the last day of their menstrual cycle for three consecutive cycles . The second group ( n = 50 ) received the placebo . The premenstrual symptoms screening tool was used to assess the intensity of PMS symptoms in the two groups before and one , two , and three months after the intervention . The data were analyzed using paired t-test and repeated measures analysis of variance . Results : The results of repeated measures test revealed a significant reduction ( P 0.001 ) in PMS symptoms . Overall , the mean score of PMS intensity in the intervention group was 42.56 + 15.73 before the intervention and changed to 32.72 ± 13.24 , 30.02 ± 12.08 , and 13.90 ± 10.22 at the three consecutive months after the intervention , respectively ( P = 0.001 ) . Conclusions : M. officinalis capsules were effective in reduction of the PMS symptoms . Yet , application of this medication requires further investigations",
"Background Passiflora incarnata is widely used as an anxiolytic and sedative due to its putative GABAergic properties . Passiflora incarnata L. methanolic extract ( PI-ME ) was evaluated in an animal model of streptozotocin-induced diabetic neuropathic allodynia and vulvodynia in rats along with antinociceptive , anxiolytic and sedative activities in mice in order to examine possible underlying mechanisms . Methods PI-ME was tested preliminary for qualitative phytochemical analysis and then quantitatively by proximate and GC-MS analysis . The antinociceptive property was evaluated using the abdominal constriction assay and hot plate test . The anxiolytic activity was performed in a stair case model and sedative activity in an open field test . The antagonistic activities were evaluated using naloxone and /or pentylenetetrazole ( PTZ ) . PI-ME was evaluated for prospect i ve anti-allodynic and anti-vulvodynic properties in a rat model of streptozotocin induced neuropathic pain using the static and dynamic testing paradigms of mechanical allodynia and vulvodynia . Results GC-MS analysis revealed that PI-ME contained predominant quantities of oleamide ( 9-octadecenamide ) , palmitic acid ( hexadecanoic acid ) and 3-hydroxy-dodecanoic acid , among other active constituents . In the abdominal constriction assay and hot plate test , PI-ME produced dose dependant , naloxone and pentylenetetrazole reversible antinociception suggesting an involvement of opioidergic and GABAergic mechanisms . In the stair case test , PI-ME at 200 mg/kg increased the number of steps climbed while at 600 mg/kg a significant decrease was observed . The rearing incidence was diminished by PI-ME at all tested doses and in the open field test , PI-ME decreased locomotor activity to an extent that was analagous to diazepam . The effects of PI-ME were antagonized by PTZ in both the staircase and open field tests implicating GABAergic mechanisms in its anxiolytic and sedative activities . In the streptozotocin-induced neuropathic nociceptive model , PI-ME ( 200 and 300 mg/kg ) exhibited static and dynamic anti-allodynic effects exemplified by an increase in paw withdrawal threshold and paw withdrawal latency . PI-ME relieved only the dynamic component of vulvodynia by increasing flinching response latency . Conclusions These findings suggest that Passiflora incarnata might be useful for treating neuropathic pain . The antinociceptive and behavioural findings inferring that its activity may stem from underlying opioidergic and GABAergic mechanisms though a potential oleamide- source d cannabimimetic involvement is also discussed",
"INTRODUCTION The availability of herbal medicines over-the-counter ( OTC ) has increased the use of natural products for self-treatment . Valerian has been used to effectively treat generalized anxiety disorder and insomnia . Studies suggest that valerenic acid may increase gamma-aminobutyric acid ( GABA ) modulation in the brain . Benzodiazepines have a similar mechanism of action and have been linked to an increased risk of hospitalizations due to traffic accidents . Despite the risk of somnolence , the safety of driving while under the influence of valerian remains unknown . PURPOSE The purpose of the study was to determine the effects of a one-time valerian 1600 mg dose on subjective sedation effects , st and ardized field sobriety testing ( SFST ) and driving simulator performance parameters . METHODS The study design was a r and omized , placebo-controlled , double-blind , cross-over trial . For each session , participants received either a dose of valerian or placebo . The outcome measures included a simple visual reaction test ( SVRT ) , subjective sleepiness scales , SFST performance scores , and driving simulator performance parameters . RESULTS There were no significant differences in the SVRT or sleepiness scales between placebo and valerian exposures , but the study may have been underpowered . SFST total and individual test failure rates were not significantly different between the two exposures . The driving simulator performance parameters were equivalent between the two exposure conditions . CONCLUSIONS A one-time valerian 1600 mg dose , often used to treat insomnia , does not appear to impair driving simulator performance after acute ingestion",
"Melissa officinalis ( Lemon balm ) is a herbal medicine that has traditionally been attributed with memory-enhancing properties , but which is currently more widely used as a mild sedative and sleep aid . In a previous study it was demonstrated that a commercial Melissa extract led to dose-specific increases in calmness , and dose-dependent decrements in timed memory task performance . However , the extract utilized in that study did not exhibit in vitro cholinergic receptor-binding properties . The current study involved an initial screening of sample s of M. officinalis for human acetylcholinesterase inhibition and cholinergic receptor-binding properties . The cognitive and mood effects of single doses of the most cholinergically active dried leaf were then assessed in a r and omized , placebo-controlled , double-blind , balanced crossover study . Following the in vitro analysis , 20 healthy , young participants received single doses of 600 , 1000 , and 1600 mg of encapsulated dried leaf , or a matching placebo , at 7-day intervals . Cognitive performance and mood were assessed predose and at 1 , 3 , and 6 h postdose using the Cognitive Drug Research computerized assessment battery and Bond – Lader visual analog scales , respectively . In vitro analysis of the chosen extract established IC50 concentrations of 0.18 and 3.47 mg ml−1 , respectively , for the displacement of [3H]-(N)-nicotine and [3H]-(N)-scopolamine from nicotinic and muscarinic receptors in the human cerebral cortex tissue . However , no cholinesterase inhibitory properties were detected . The most notable cognitive and mood effects were improved memory performance and increased ‘ calmness ’ at all postdose time points for the highest ( 1600 mg ) dose . However , while the profile of results was overwhelmingly favorable for the highest dose , decrements in the speed of timed memory task performance and on a rapid visual information-processing task increased with decreasing dose . These results suggest that doses of Melissa officinalis at or above the maximum employed here can improve cognitive performance and mood and may therefore be a valuable adjunct in the treatment of Alzheimer 's disease . The results also suggest that different preparations derived from the same plant species may exhibit different properties depending on the process used for the sample preparation",
"Ginkgo biloba special extract EGb 761 , an anti-dementia drug , enhances cognitive functioning and stabilizes mood in cognitively impaired elderly subjects . Moreover , EGb 761 had been found to alleviate symptoms of anxiety in people with mental decline , therefore it was now tested for clinical efficacy in younger patients suffering from anxiety . One hundred and seven patients with generalized anxiety disorder ( GAD , n=82 ) or adjustment disorder with anxious mood ( ADWAM , n=25 ) according to the diagnostic and statistical manual of mental disorders , third edition - revised ( DSM-III-R ) were r and omized to daily doses of 480 mg EGb 761 , 240 mg EGb 761 or placebo for 4 weeks . Intention-to-treat ( ITT ) analyses were performed on the primary outcome measure , the Hamilton rating scale for anxiety ( HAMA ) , and the secondary variables , the clinical global impression of change ( CGI-C ) , the Erlangen anxiety tension and aggression scale ( EAAS ) , the list of complaints ( B-L ' ) , and the patient 's global rating of change . The HAMA total scores decreased by -14.3 ( + /-8.1 ) , -12.1 ( + /-9.0 ) and -7.8 ( + /-9.2 ) in the high-dose EGb 761 , the low-dose EGb 761 and the placebo group , respectively . Changes were significantly different from placebo for both treatment groups with p=0.0003 ( high-dose group ) and p=0.01 ( low-dose ) . Regression analyses revealed a dose-response trend ( p=0.003 ) . EGb 761 was significantly superior to placebo on all secondary outcome measures . It was safe and well tolerated and may thus be of particular value in elderly patients with anxiety related to cognitive decline",
"BACKGROUND : Many patients have preoperative anxiety ; therefore , the development of a strong anxiolytic with minimal psychomotor impairment for premedication may be desirable . METHODS : In this study , 60 patients were r and omized into two groups to receive either oral Passiflora incarnata ( 500 mg , Passipy ™ Ir anD arouk ) ( n = 30 ) or placebo ( n = 30 ) as premedication , 90 min before surgery . A numerical rating scale ( NRS ) was used for each patient to assess anxiety and sedation before , and 10 , 30 , 60 , and 90 min after premedication . Psychomotor function was assessed with the Trieger Dot Test and the Digit-Symbol Substitution Test at arrival in the operating room , 30 and 90 min after tracheal extubation . The time interval between arrival in the postanesthesia care unit and discharge to home ( discharge time ) was recorded for each patient . RESULTS : The demographic characteristics of patients , ASA physical status , duration of surgery , basal NRS score , sedation at the preset time intervals , and discharge time were similar in the two groups . The NRS anxiety scores were significantly lower in the passiflora group than in the control group ( P differences in psychological variables in the postanesthesia care unit and recovery of psychomotor function was comparable in both groups . CONCLUSIONS : In outpatient surgery , administration of oral Passiflora incarnata as a premedication reduces anxiety without inducing sedation ",
"Objective : Melissa officinalis ( lemon balm ) is contemporaneously used as a mild sedative and /or calming agent . Although recent research has demonstrated modulation of mood in keeping with these roles , no studies to date have directly investigated the effects of this herbal medication on laboratory-induced psychological stress . Methods : In this double-blind , placebo-controlled , r and omized , balanced crossover experiment , 18 healthy volunteers received two separate single doses of a st and ardized M. officinalis extract ( 300 mg , 600 mg ) and a placebo , on separate days separated by a 7-day washout period . Modulation of mood was assessed during predose and 1-hour postdose completions of a 20-minute version of the Defined Intensity Stressor Simulation ( DISS ) battery . Cognitive performance on the four concurrent tasks of the battery was also assessed . Results : The results showed that the 600-mg dose of Melissa ameliorated the negative mood effects of the DISS , with significantly increased self-ratings of calmness and reduced self-ratings of alertness . In addition , a significant increase in the speed of mathematical processing , with no reduction in accuracy , was observed after ingestion of the 300-mg dose . Conclusion : These results suggest that the potential for M. officinalis to mitigate the effects of stress deserves further investigation",
"Background : Several neuropsychiatric adverse effects of efavirenz are known . Preventing these adverse effects may improve patients ’ adherence to antiretroviral therapy ( ART ) . Objectives : To evaluate the efficacy and safety of valerian in preventing neuropsychiatric adverse effects of efavirenz in HIV-positive patients . Method : In this pilot r and omized , double-blinded , placebo-controlled , clinical trial , 51 HIV-positive patients who were receiving efavirenz were recruited into the valerian ( n = 25 ) or placebo ( n = 26 ) group . Patients received valerian ( 530 mg ) or placebo nightly 1 hour before sleep for 4 weeks . The neuropsychiatric status ( sleep , anxiety , depression , suicidal thought , and psychosis ) of patients was assessed at baseline and week 4 using vali date d question naires . Results : Sleep ( P ≤ 0.001 ) and anxiety ( P = 0.001 ) significantly improved in the valerian group compared with the placebo group . Dizziness was the most common complaint of patients in first days of the intervention . In the valerian and placebo groups , 92 % and 84.6 % of patients experienced dizziness , respectively ( P = 0.35 ) . Nausea was the second common adverse effect that 84 % and 76.9 % of patients in the valerian and placebo groups experienced ( P = 0.39 ) . Conclusion : In the first 4 weeks of ART including efavirenz , valerian significantly improved sleep and anxiety in HIV-positive patients . Valerian may be considered as a potential option in preventing neuropsychiatric adverse effects of efavirenz in HIV-positive patients",
"Valerian is the common name given to the genus Valeriana , an odiferous , herbaceous perennial plant widely distributed in the temperate regions of Asia , Europe , and North America . It is among the most widely used herbal medicines in the world . Numerous clinical studies have demonstrated valerian 's ability to improve sleep ; however , to the best of our knowledge , no study has systematic ally assessed subjective and psychomotor/cognitive effects of valerian in young healthy adults across a range of doses . In the present study , we sought to determine whether valerian extract ( Valeriana officinalis ) altered mood and /or impaired psychomotor/cognitive performance in young healthy volunteers . We examined the effects of valerian extract ( 600 , 1200 , and 1800 mg ) and 10 mg diazepam ( positive control ) compared to placebo in 10 young healthy volunteers . Dependent measures included subjective and psychomotor variables . The valerian extract had no significant effects on any of the dependent measures . Diazepam , though , produced subjective effects as measured by four different rating scales , and impaired psychomotor/cognitive performance . The data suggest that acute administration of valerian does not have mood-altering or psychomotor/cognitive effects in young healthy volunteers",
"OBJECTIVE Passionflower ( Passiflora incarnata ) is a folk remedy for anxiety . A double-blind r and omized trial compared the efficacy of Passiflora incarnata extract with oxazepam in the treatment of generalized anxiety disorder . METHODS The study was performed on 36 out- patients diagnosed with GAD using DSM IV criteria . Patients were allocated in a r and om fashion : 18 to the Passiflora extract 45 drops/day plus placebo tablet group , and 18 to oxazepam 30 mg/day plus placebo drops for a 4-week trial . RESULTS Passiflora extract and oxazepam were effective in the treatment of generalized anxiety disorder . No significant difference was observed between the two protocol s at the end of trial . Oxazepam showed a rapid onset of action . On the other h and , significantly more problems relating to impairment of job performance were encountered with subjects on oxazepam . CONCLUSION The results suggest that Passiflora extract is an effective drug for the management of generalized anxiety disorder , and the low incidence of impairment of job performance with Passiflora extract compared to oxazepam is an advantage . A large-scale trial is justified",
"The purpose of this study was to investigate the anxiolytic effects of xanthohumol , a component of Humulus lupulus ( hops ) , and its potential interaction with the benzodiazepine binding site on the y-aminobutyric acid ( GABAA ) receptor in the male Sprague-Dawley rat . This was a prospect i ve , r and omized , between-subjects experimental study . Fifty-five rats were assigned to 1 Sof 5 groups with 11 rats per group : control ( vehicle ) , xanthohumol , midazolam , midazolam with xanthohumol , and flumazenil with xanthohumol . In this study the elevated plus maze measured the behavioral components of anxiety and motor movements . A 2-tailed multivariate analysis of variance and least significant difference post hoc test was used to determine if a significant difference existed . Our data suggest that xanthohumol does not produce anxiolysis by modulation of the GABAA receptor ; however , there may be a possible interaction between xanthohumol and midazolam , or xanthohumol may influence the modulation of another neurotransmitter site in the central nervous system . Alone , xanthohumol does not show significant modulation of the benzodiazepine receptor . Additional research should investigate if xanthohumol acts as a benzodiazepine GABAA partial agonist or antagonist or if it modulates another neurotransmitter system in the central nervous system",
"The aim of the present study was to carry out a controlled pilot study on the putative anxiolytic effect of valepotriates . Thirty-six out patients with generalized anxiety disorder ( DSM III-R ) , after a 2-week wash-out , were r and omized to one of the following three treatments for 4 weeks ( n = 12 per group ) : valepotriates ( mean daily dose : 81.3 mg ) , diazepam ( mean daily dose : 6.5 mg ) , or placebo . A parallel , double-blind , flexible-dose , placebo-controlled design was employed . No significant difference was observed among the three groups at baseline or in the change from baseline on the Hamilton anxiety scale ( HAM-A ) or in the trait part of the state-trait anxiety inventory ( STAI-trait ) . Moreover , the three groups presented a significant reduction in the total HAM-A scores . On the other h and , only the diazepam and valepotriates groups showed a significant reduction in the psychic factor of HAM-A. The diazepam group also presented a significant reduction of the STAI-trait . Although the principal analysis ( HAM-A between group comparison ) found negative results ( probably due to the small sample size in each group ) , the preliminary data obtained in the present study suggest that the valepotriates may have a potential anxiolytic effect on the psychic symptoms of anxiety . However , since the number of subjects per group was very small , the present results must be viewed as preliminary . Thus , further studies addressing this issue are warranted",
"OBJECTIVE The authors sought to observe the long-term clinical course of anxiety disorders over 12 years and to examine the influence of comorbid psychiatric disorders on recovery from or recurrence of panic disorder , generalized anxiety disorder , and social phobia . METHOD Data were drawn from the Harvard/Brown Anxiety Disorders Research Program , a prospect i ve , naturalistic , longitudinal , multicenter study of adults with a current or past history of anxiety disorders . Probabilities of recovery and recurrence were calculated by using st and ard survival analysis methods . Proportional hazards regression analyses with time-varying covariates were conducted to determine risk ratios for possible comorbid psychiatric predictors of recovery and recurrence . RESULTS Survival analyses revealed an overall chronic course for the majority of the anxiety disorders . Social phobia had the smallest probability of recovery after 12 years of follow-up . Moreover , patients who had prospect ively observed recovery from their intake anxiety disorder had a high probability of recurrence over the follow-up period . The overall clinical course was worsened by several comorbid psychiatric conditions , including major depression and alcohol and other substance use disorders , and by comorbidity of generalized anxiety disorder and panic disorder with agoraphobia . CONCLUSIONS These data depict the anxiety disorders as insidious , with a chronic clinical course , low rates of recovery , and relatively high probabilities of recurrence . The presence of particular comorbid psychiatric disorders significantly lowered the likelihood of recovery from anxiety disorders and increased the likelihood of their recurrence . The findings add to the underst and ing of the nosology and treatment of these disorders",
"BACKGROUND Conventional drug treatments for Generalized Anxiety Disorder ( GAD ) are often accompanied by substantial side effects , dependence , and /or withdrawal syndrome . A prior controlled study of oral chamomile ( Matricaria chamomilla L. ) extract showed significant efficacy versus placebo , and suggested that chamomile may have anxiolytic activity for individuals with GAD . HYPOTHESIS We hypothesized that treatment with chamomile extract would result in a significant reduction in GAD severity ratings , and would be associated with a favorable adverse event and tolerability profile . STUDY DESIGN We report on the open-label phase of a two-phase r and omized controlled trial of chamomile versus placebo for relapse-prevention of recurrent GAD . METHODS Subjects with moderate to severe GAD received open-label treatment with pharmaceutical- grade chamomile extract 1500mg/day for up to 8 weeks . Primary outcomes were the frequency of clinical response and change in GAD-7 symptom scores by week 8 . Secondary outcomes included the change over time on the Hamilton Rating Scale for Anxiety , the Beck Anxiety Inventory , and the Psychological General Well Being Index . Frequency of treatment-emergent adverse events and premature treatment discontinuation were also examined . RESULTS Of 179 subjects , 58.1 % ( 95 % CI : 50.9 % to 65.5 % ) met criteria for response , while 15.6 % prematurely discontinued treatment . Significant improvement over time was also observed on the GAD-7 rating ( β=-8.4 [ 95 % CI=-9.1 to -7.7 ] ) . A similar proportion of subjects demonstrated statistically significant and clinical ly meaningful reductions in secondary outcome ratings of anxiety and well-being . Adverse events occurred in 11.7 % of subjects , although no serious adverse events occurred . CONCLUSION Chamomile extract produced a clinical ly meaningful reduction in GAD symptoms over 8 weeks , with a response rate comparable to those observed during conventional anxiolytic drug therapy and a favorable adverse event profile . Future comparative effectiveness trials between chamomile and conventional drugs may help determine the optimal risk/benefit of these therapies for patients suffering from GAD",
"Scutellaria lateriflora is an herbal medicine with long-st and ing traditional use as a relaxing nervine . There has been controversy in the literature with regards to its efficacy , and this study was design ed to clarify its effectiveness in reducing anxiety , one of the phytotherapeutic indications . A double blind , placebo-controlled study of healthy subjects demonstrated noteworthy anxiolytic effects . The use of phytomedicines for the treatment of anxiety is review ed , as is the published literature on S. lateriflora and its putative toxicity",
"BACKGROUND Generalized Anxiety Disorder ( GAD ) is one of the most common anxiety disorders treated in primary care , yet current therapies have limited efficacy and substantial side effects . PURPOSE To evaluate long-term chamomile ( Matricaria chamomilla L. ) use for prevention of GAD symptom relapse . METHODS Out patients from primary care practice s and local communities with a primary diagnosis of moderate-to-severe GAD were enrolled for this two-phase study at a large US academic medical center . During Phase 1 , eligible participants received 12 weeks of open-label therapy with chamomile pharmaceutical grade extract 1500 mg ( 500 mg capsule 3 times daily ) . During Phase 2 , treatment responders were r and omized to either 26 weeks of continuation chamomile therapy or placebo in a double-blinded , placebo-substitution design . The primary outcome was time to relapse during continuation therapy , analyzed using Cox proportional hazards . Secondary outcomes included the proportion who relapsed , treatment-emergent adverse events , and vital sign changes . This study is registered at Clinical Trials.gov , identifier NCT01072344 . RESULTS Between March 1 , 2010 , and June 30 , 2015 , we enrolled 179 participants . Of those , 93 ( 51.9 % ) were responders and agreed to continue in the double-blind r and omized controlled trial . A numerically greater number of placebo-switched ( n=12/47 ; 25.5 % ) versus chamomile-continuation ( n = 7/46 ; 15.2 % ) participants relapsed during follow-up . Mean time to relapse was 11.4 ± 8.4 weeks for chamomile and 6.3 ± 3.9 weeks for placebo . Hazard of relapse was non-significantly lower for chamomile ( hazard ratio , 0.52 ; 95 % CI , 0.20 - 1.33 ; P = 0.16 ) . During follow-up , chamomile participants maintained significantly lower GAD symptoms than placebo ( P = 0.0032 ) , with significant reductions in body weight ( P = 0.046 ) and mean arterial blood pressure ( P = 0.0063 ) . Both treatments had similar low adverse event rates . CONCLUSIONS Long-term chamomile was safe and significantly reduced moderate-to-severe GAD symptoms , but did not significantly reduce rate of relapse . Our limited sample size and lower than expected rate of placebo group relapse likely contributed to the non-significant primary outcome finding . Possible chamomile superiority over placebo requires further examination in large-scale studies",
"Objective : We conducted a r and omized , double-blind , placebo-controlled efficacy and tolerability trial of Matricaria recutita ( chamomile ) extract therapy in patients with mild to moderate generalized anxiety disorder ( GAD ) . We hypothesized that chamomile would be superior to placebo in reducing GAD symptoms with a comparable tolerability profile . Material s and Methods : Sixty-one out patients with mild to moderate GAD were enrolled , and 57 were r and omized to either double-blind chamomile extract ( n = 28 ) or placebo therapy ( n = 29 ) for 8 weeks . The study was powered to detect a statistically significant and clinical ly meaningful group difference in change over time in total Hamilton Anxiety Rating ( HAM-A ) scores . Secondary outcomes included change in the Beck Anxiety Inventory , Psychological Well Being , and Clinical Global Impression Severity scores and the proportion of patients with 50 % reduction or more in baseline HAM-A score . Results : We observed a significantly greater reduction in mean total HAM-A score during chamomile versus placebo therapy ( P = 0.047 ) . Although the study was not powered to identify small to moderate differences in secondary outcomes , we observed a positive change in all secondary outcomes in the same direction as the primary outcome measure . One patient in each treatment group discontinued therapy for adverse events . The proportion of patients experiencing 0 , 1 , 2 , or 3 adverse events or more was not significantly different between groups ( P = 0.417 ) . Conclusions : This is the first controlled clinical trial of chamomile extract for GAD . The results suggest that chamomile may have modest anxiolytic activity in patients with mild to moderate GAD . Future studies are needed to replicate these observations",
"Euphytose ( EUP ) is a combination of six extracts : Crataegus , Ballota , Passiflora and Valeriana , which have mild sedative effects , and Cola and Paullinia , which mainly act as mild stimulants . This multicenter , double-blind , placebo-controlled general practice study was carried out patients with adjustment disorder with anxious mood . The study was coordinated by psychiatrists . Ninety-one patients were included in the EUP group and 91 patients in the placebo group . They all received two tablets three times a day over 28 days ( D ) . Evaluation using the Hamilton-anxiety ( HAM-A ) rating scale were carried out on D0 , D7 , D14 and on D28 . Comparing the two groups , 42.9 % of the patients ( EUP group ) had a HAM-A score of less than 10 at D28 versus 25.3 % in the placebo group ( P = 0.012 ) . Changes in the HAM-A score between D0 and D28 were as follows : D0 ( EUP : 26.12 + /- 4.0 , placebo : 26.27 + /- 4.5 ) , D7 ( EUP : 19.65 + /- 5.7 , placebo : 21.37 + /- 5.6 ) , D14 ( EUP : 15.36 + /- 5.7 , placebo : 17.48 + /- 6.7 ) , D28 ( EUP : 12.63 + /- 7.3 , placebo : 15.2 + /- 8.1 ) . From D7 to D28 there was a statistically significant difference ( P = 0.042 ) between the two treatments , indicating that EUP is better than placebo in the treatment of adjustment disorder with anxious mood",
"Centella asiatica is reputed for its beneficial effects in various neurological disorders . The present investigation was undertaken to evaluate the role of 70 % hydro-ethanolic extract of Centella asiatica ( CA ) on generalized anxiety disorder ( GAD ) in man . Hamilton 's Brief Psychiatric Rating Scale ( BPRS ) was used to screen the subjects . Thirty-three participants ( 18 male and 15 female ; average age 33 yrs ) were medicated with the CA in a fixed dose regime ( 500 mg/capsule , twice daily , after meal ) . They were thoroughly investigated using st and ard question naires based on psychological rating scale at baseline ( day 0 ) , mid-term ( day 30 ) and final ( day 60 ) . The scale also includes a number of direct queries about current levels of experienced stress . The observations revealed that , CA not only significantly ( p attenuated anxiety related disorders but it also significantly ( p reduced stress phenomenon and its correlated depression . CA further significantly ( p willingness for adjustment and cognition . Results indicated that Centella asiatica may be useful in the treatment of GAD and may be used as a promising anxiolytic agent in near future",
"Investigations of the pharmacologic profile of medicinal plants have revealed that a number of plants with purported anxiolytic activity bind to cholecystokinin ( CCK ) receptors . This finding is intriguing in view of the proposed involvement of CCK in the pathophysiology of fear and anxiety . This double-blind , placebo-controlled study was undertaken to evaluate the anxiolytic activity of Gotu Kola ( Centella asiatica ) in healthy subjects . Gotu Kola has been used for centuries in Ayurvedic and traditional Chinese medicine to alleviate symptoms of depression and anxiety . Recent studies in the rat have shown that long-term pretreatment with Gotu Kola decreases locomotor activity , enhances elevated-plus maze performance , and attenuates the acoustic startle response ( ASR ) . In this study , the authors evaluated the effects of Gotu Kola on the ASR in humans . Subjects were r and omly assigned to receive either a single 12-g orally administered dose of Gotu Kola ( N = 20 ) or placebo ( N = 20 ) . The results revealed that compared with placebo , Gotu Kola significantly attenuated the peak ASR amplitude 30 and 60 minutes after treatment . Gotu Kola had no significant effect on self-rated mood , heart rate , or blood pressure . These preliminary findings suggest that Gotu Kola has anxiolytic activity in humans as revealed by the ASR . It remains to be seen whether this herb has therapeutic efficacy in the treatment of anxiety syndromes ",
"OBJECTIVE Cognitive impairments contribute significantly to inadequate functional recovery following illness episodes in bipolar disorder , yet data on treatment interventions are sparse . We assessed the cognitive effects of a st and ardized extract of the medicinal herb Withania somnifera ( WSE ) in bipolar disorder . METHOD Sixty euthymic subjects with DSM-IV bipolar disorder were enrolled in an 8-week , double-blind , placebo-controlled , r and omized study of WSE ( 500 mg/d ) as a procognitive agent added adjunctively to the medications being used as maintenance treatment for bipolar disorder . Study enrollment and data analyses were completed between December 2008 and September 2012 . Cognitive testing at baseline and 8 weeks assessed primary efficacy outcomes . Psychopathology and adverse events were monitored at scheduled visits . RESULTS Fifty-three patients completed the study ( WSE , n = 24 ; placebo , n = 29 ) , and the 2 groups were matched in terms of demographic , illness , and treatment characteristics . Compared to placebo , WSE provided significant benefits for 3 cognitive tasks : digit span backward ( P = .035 ) , Flanker neutral response time ( P = .033 ) , and the social cognition response rating of the Penn Emotional Acuity Test ( P = .045 ) . The size of the WSE treatment effect for digit span backward was in the medium range ( Cohen d = 0.51 ; 95 % CI , 0.25 - 0.77 ) . None of the other cognitive tasks showed significant between-group differences . Mood and anxiety scale scores remained stable , and adverse events were minor . CONCLUSIONS Although results are preliminary , WSE appears to improve auditory-verbal working memory ( digit span backward ) , a measure of reaction time , and a measure of social cognition in bipolar disorder . Given the paucity of data for improving cognitive capacity in bipolar disorder , WSE offers promise , appears to have a benign side-effects profile , and merits further study . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00761761",
"Objective : Obsessive – Compulsive Disorder ( OCD ) is a common neuropsychiatric condition . Many herbs with psychotropic effects exist which can have fewer side effects compared to more conventional medications . Valeriana Officinalis L. is a well-known medicinal plant with a long history of usage in the world with an effect on GABA . This plant is reported to be safe on humans . Our objective in this study was to compare the efficacy of the extract of Valeriana Officinalis L. with placebo in the treatment of OCD . Methods : The study was an 8-week pilot double-blind r and omized trial . Thirty-one adult out patients who met the DSM-IV-TR criteria for OCD based on the structured clinical interview participated in the trial . In this double-blind and r and omized trial , patients were r and omly assigned to receive either capsule of the extract ( 765 mg/day ) or placebo ( 30 mg/day ) for 8 weeks . Results : The results showed significant difference between the extract and placebo in the end of treatment ( P=0.000 ) . Somnolence was the only significant difference between the two groups in terms of observed side effects ( P=0.02 ) . Conclusion : The results suggest that Valeriana Officinalis L. has some antiobsessive and compulsive effects . However , further studies are needed to confirm these findings . Psychiatrists often find that many patients can not tolerate the side effects of psychiatry medicine Valeriana Officinalis L. is a well-known medicinal plant with a long history of usage in world with effect on GABA.The results showed significant difference between the extract and placebo in the treatment of OCD . There was also no significant difference between the two groups in terms of observed side effects ",
"Melissa officinalis ( lemon balm ) is a traditional herbal medicine , which enjoys contemporary usage as a mild sedative , spasmolytic and antibacterial agent . It has been suggested , in light of in vitro cholinergic binding properties , that Melissa extracts may effectively ameliorate the cognitive deficits associated with Alzheimer 's disease . To date , no study has investigated the effects on cognition and mood of administration of Melissa to healthy humans . The present r and omised , placebo-controlled , double-blind , balanced-crossover study investigated the acute effects on cognition and mood of a st and ardised extract of M. officinalis . Twenty healthy , young participants received single doses of 300 , 600 and 900 mg of M. officinalis ( Pharmaton ) or a matching placebo at 7-day intervals . Cognitive performance was assessed using the Cognitive Drug Research ( CDR ) computerised test battery and two serial subtraction tasks immediately prior to dosing and at 1 , 2.5 , 4 and 6 h thereafter . In vitro IC(50 ) concentrations for the displacement of [3H]-(N)-nicotine and [3H]-(N)-scopolamine from nicotinic and muscarinic receptors in human occipital cortex tissue were also calculated . Results , utilising the cognitive factors previously derived from the CDR battery , included a sustained improvement in Accuracy of Attention following 600 mg of Melissa and time- and dose-specific reductions in both Secondary Memory and Working Memory factors . Self-rated \" calmness , \" as assessed by Bond-Lader mood scales , was elevated at the earliest time points by the lowest dose , whilst \" alertness \" was significantly reduced at all time points following the highest dose . Both nicotinic and muscarinic binding were found to be low in comparison to the levels found in previous studies"
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Problems with timing and time perception have been suggested as key characteristics of autism spectrum condition ( ASC ) . Studies and personal accounts from clinicians , parents , caregivers , and self-reports from autistic people themselves often refer to problems with time . Although a number of empirical studies have examined aspects relating to time in autistic individuals , there remains no clear consensus on whether or how timing mechanisms may be affected in autism . A key reason for this lack of clarity is the wide range of timing processes that exist and subsequently the wide range of method ologies , research paradigms , and sample s that time-based studies have used with autism population s. In order to summarize and organize the available literature on this issue , a systematic review was conducted . Five electronic data bases were consulted . From an initial 597 records ( after duplicates were removed ) , 45 papers were selected and review ed . The studies are review ed within different sections based on the different types of timing ability that have been explored in the neurotypical ( NT ) population : time sensitivity , interval timing , and higher-order time perception . Within each section cognitive models , method ologies , possible clinical implication s , and research results are discussed . The results show different consistency across studies between the three types of timing ability . The highest consistency of results showing atypical time perception abilities is found in high-level time perception studies . It remains unclear if autism is characterized by a fundamental time perception impairment . Suggestions for future research are discussed . Autism Res 2019 , © 2019 International Society for Autism Research , Wiley Periodicals , Inc. LAY SUMMARY : This systematic review examines the different types of timing and time perception behavior that have been investigated in autism . Overall , there are a number of studies that show differences between autistic and non-autistic individuals , but some studies do not find such differences . Group differences are more consistent across studies using complex tasks rather than simpler more fundamental timing tasks . We suggest that experiments across a range of timing tasks would be fruitful to address gaps in our knowledge
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"Considerable evidence suggests that the episodic memory system operates abnormally in autism spectrum disorder ( ASD ) whereas the functions of the semantic memory system are relatively preserved . Here we show that the same dissociation also applies to the domain of order memory . We asked adult participants to order the names of famous historical figures either according to their chronological order in history ( probing semantic memory ) or according to a r and om sequence shown once on a screen ( probing episodic memory ) . As predicted , adults with ASD performed less well than age- and IQ-matched comparison individuals only on the episodic task . This observation is of considerable importance in the context of developmental theory because semantic and episodic order memory abilities can be dissociated in typically developing infants before they reach the age at which the behavioural markers associated with ASD are first apparent . This raises the possibility that early emerging memory abnormalities play a role in shaping the developmental trajectory of the disorder . We discuss the broader implication s of this possibility and highlight the urgent need for greater scrutiny of memory competences in ASD early in development",
"This study examined , for the first time , the impact of implementation intentions on prospect i ve memory ( PM ) performance in adults with autism spectrum disorders ( ASD ) and further explored the role of retrospective memory for PM in ASD . PM was assessed with Virtual Week , a computerized game simulating upcoming everyday-life tasks . Twenty-seven adults with ASD and 27 age- and ability-matched controls were included . Half of the participants were instructed to form implementation intentions ( i.e. , encoding PM tasks in form of if-then statements ) , while the rest received simple PM instructions . Results provide first tentative evidence for beneficial effects of implementation intentions and PM tasks with low dem and s on retrospective memory for adults with ASD 's PM . Overall , results point to the importance of planning and retrospective memory for successful prospect i ve remembering in ASD",
"Objective : Prospect i ve memory ( PM ) is the ability to remember to carry out an intended action . Working memory is the ability to store information in mind while processing potentially distracting information . The few previous studies of PM in autism spectrum disorder ( ASD ) have yielded inconsistent findings . Studies of working memory ability in ASD have suggested a selective impairment of “ visual working memory . ” However , it remains unclear whether any such impairment is the result of diminished ( domain-specific ; visual/verbal ) storage capacity or diminished ( domain-general ) processing capacity . We aim to clarify these issues and explore the relation between PM and working memory in ASD . Method : Seventeen adults with ASD and 17 age- and IQ-matched comparison participants completed experimental measures of both event-based ( perform action x when event y occurs ) and time-based ( perform action a at time b ) PM , plus a self-report measure of PM skills . Participants also completed a working memory test battery . Results : Participants with ASD self-reported diminished PM skill , and showed diminished performance on the time-based , but not event-based , PM task . On the working memory test battery , visual but not verbal storage capacity was diminished among participants with ASD , as was processing ability . Whereas visual storage was associated with event-based PM task performance among comparison participants , verbal storage was associated among ASD participants . Conclusions : ASD appears to involve a selective deficit in time-based PM and a selective difficulty with aspects of working memory that depend on the storage of visual information . However , event-based PM may be achieved through compensatory strategies in ASD",
"Three experiments compared the timing performance of humans on a modified temporal generalization task with 1 , 3 , or 5 presentations of the st and ard duration . In all three experiments subjects received presentations of a st and ard duration at the beginning of a trial block and then had to judge whether each of a number of comparison stimuli was or was not the st and ard . The duration of the st and ard changed between blocks . The three experiments varied the experimental design ( between or within subjects ) , task difficulty ( how closely the comparison stimuli were spaced around the st and ards ) , and presence or absence of feedback on performance accuracy . Number of presentations of the st and ard never affected the proportion of identification s of the st and ard when it was presented , nor other features of the temporal generalization gradients observed . The implication s for the operation of reference memories within the scalar timing system were explored via models that made different assumptions about how the individual presentations of the st and ard were stored and used",
"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",
"Prospect i ve memory ( PM ) refers to the implementation of delayed intentions , a cognitive ability that plays a critical role in daily life because of its involvement in goal -directed behavior and consequently the development and maintenance of independence . Emerging evidence indicates that PM may be disrupted in autism spectrum disorders ( ASDs ) , potentially contributing to the functional difficulties that characterize this group . However , the degree , nature , and specificity of ASD-related impairment remains poorly understood . In the current study , children between 8 and 12 years of age who were diagnosed with ASDs ( n=30 ) were compared with typically developing children ( n=30 ) on a child-appropriate version of the Virtual Week board game . This measure provides an opportunity to investigate the different sorts of PM failures that occur . The ASD group showed significant PM impairment on measures of time-based ( but not event-based ) prospect i ve remembering . However , only a subtle difference emerged between regular and irregular PM tasks , and group differences were consistent across these tasks . Because regular and irregular tasks differentially load retrospective memory , these data imply that the PM difficulties seen in ASDs may primarily reflect a monitoring deficit and not an encoding and memory storage deficit . PM performance was poorer under conditions of high ongoing task absorption , but the magnitude of this effect did not vary as a function of group . In both groups , time-based ( but not event-based ) PM difficulties were associated with functional outcomes in daily life , but only an inconsistent association with executive control emerged",
"Three experiments compared human performance on temporal generalization tasks with either one or two different , and distinct , st and ard duration s encoded . In the first two experiments participants received presentations of two different st and ards at the beginning of each trial block and were instructed to encode either one or both of them . When instructed to encode one st and ard they then had to judge whether each of a number of comparison stimuli was or was not that st and ard . When instructed to encode both they were then tested using just one of the st and ards but the participants were unaware , at the time of encoding , which st and ard would later be used as a reference . No marked effect of the number of temporal st and ards encoded was found . In Experiment 3 participants received either one or two temporal st and ards and had to use both when two were presented . This manipulation produced flatter generalization gradients when two st and ards were encoded than when just one was , and modelling attributed this difference mainly to an increase in reference memory variability in the double-st and ard case . This suggests that the variability of representation of duration s in temporal reference memory can be systematic ally increased by increasing temporal reference memory load",
"Children aged 3 , 5 , and 8 years were tested on temporal generalization with visual stimuli . Different groups received 4- and 8-s st and ards . Gradients at all ages superimposed when plotted on the same relative scale , indicating underlying scalar timing . The principal developmental changes were ( i ) increasing sharpness of the generalization gradient with increasing age and ( ii ) a change from symmetrical ( 3 and 5 years ) to adultlike asymmetrical generalization gradients in the oldest children . Theoretical modeling attributed these changes to increasing precision of the reference memory of the st and ard with increasing age , as well as a decreased tendency to \" misremember \" the st and ard as being shorter than it actually was , as the children developed",
"Prospect i ve memory ( remembering to carry out an action in the future ) has been studied relatively little in ASD . We explored time-based ( carry out an action at a pre-specified time ) and event-based ( carry out an action upon the occurrence of a pre-specified event ) prospect i ve memory , as well as possible cognitive correlates , among 21 intellectually high-functioning children with ASD , and 21 age- and IQ-matched neurotypical comparison children . We found impaired time-based , but undiminished event-based , prospect i ve memory among children with ASD . In the ASD group , time-based prospect i ve memory performance was associated significantly with diminished theory of mind , but not with diminished cognitive flexibility . There was no evidence that time-estimation ability contributed to time-based prospect i ve memory impairment in ASD",
"The present study aim ed to find out how different stages of cortical auditory processing ( sound encoding , discrimination , and orienting ) are affected in children with autism . To this end , auditory event-related potentials ( ERP ) were studied in 15 children with autism and their controls . Their responses were recorded for pitch , duration , and vowel changes in speech stimuli , and for corresponding changes in the non-speech counterparts of the stimuli , while the children watched silent videos and ignored the stimuli . The responses to sound repetition were diminished in amplitude in the children with autism , reflecting impaired sound encoding . The mismatch negativity ( MMN ) , an ERP indexing sound discrimination , was enhanced in the children with autism as far as pitch changes were concerned . This is consistent with earlier studies reporting auditory hypersensitivity and good pitch-processing abilities , as well as with theories proposing enhanced perception of local stimulus features in individuals with autism . The discrimination of duration changes was impaired in these children , however . Finally , involuntary orienting to sound changes , as reflected by the P3a ERP , was more impaired for speech than non-speech sounds in the children with autism , suggesting deficits particularly in social orienting . This has been proposed to be one of the earliest symptoms to emerge , with pervasive effects on later development",
"This study investigated the role of the basal ganglia in timing operations . Nondemented , medicated Parkinson 's disease ( PD ) patients and controls were tested on 2 motor-timing tasks ( paced finger tapping at a 300- or 600-ms target interval ) , 2 time perception tasks ( duration perception wherein the interval between the st and ard tone pair was 300 or 600 ms ) , and 2 tasks that controlled for the auditory processing ( frequency perception ) dem and s of the time perception task and the movement rate ( rapid tapping ) in the motor-timing task . Using A.M. Wing and A.B. Kristofferson 's ( 1973 ) model , the total variability in motor timing was partitioned into a clock component , which reflects central timekeeping operations , and a motor delay component , which estimates r and om variability due to response implementation processes . The PD group was impaired at both target intervals of the time perception and motor-timing tasks . Impaired motor timing was due to elevated clock but not motor delay variability . The findings implicate the basal ganglia and its thalamocortical connections in timing operations ",
"The present study is the first to directly compare event- and time-based prospect i ve memory in Autism Spectrum Disorders ( ASD ) using a context ual task mirroring real life dem and s of prospect i ve memory . Twenty-five individuals with ASD and 25 age- and ability-matched controls completed the Dresden Breakfast task which required participants to prepare breakfast following a set of rules and time restrictions . Overall , adults with ASD had less correct time- and event-based prospect i ve memory responses in comparison to controls , which is consistent with previous research in children with ASD . Moreover , ASD participants completed fewer tasks , followed rules less closely , and monitored the elapsing time less closely than controls . Individuals with ASD seem not to be compensating in naturalistic prospect i ve memory tasks"
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Vitamin D deficiency is associated with the risk of tuberculosis ( TB ) infection [ 1,2 ] . Vitamin D deficient individuals have a greater susceptibility to developing TB [ 3 ] and worse disease progression if infected with TB [ 4,5 ] . The likely mechanism through which vitamin D may prevent or limit infection by Mycobacterium Tuberculosis is through the binding of the bioactive form of vitamin D ( 1,25-dihydroxycholecalciferol ) to the vitamin D receptor ( VDR ) , a polymorphic nuclear receptor that regulates the expression of genes important for immune function and involved in cytokine production [ 6–8 ] . The VDR is present in immune cells [ 9,10 ] and bronchial and pulmonary epithelial cells [ 11,12 ] , and is up-regulated following the ligation of specific toll-like receptors ( TLRs ) during an antimicrobial response [ 13,14 ] . Through this mechanism , calcitriol induces several endogenous antimicrobial peptides [ 15,16 ] , specifically cathelicidin LL-37 and b defensin [ 13,16 ] , and suppresses matrix metalloproteinase enzymes that de grade the pulmonary extracellular matrix [ 17 ] . Though vitamin D was used to treat TB during the pre-antibiotic era , trials in recent years have continued to assess its role in the treatment and prevention of TB . A systematic review published this month in the Journal of Clinical and Translational Endocrinology by Sutaria et al. [ 18 ] evaluated the results from 21 r and omized , controlled trials in order to assess : the relationship between low vitamin D status and TB , the link between VDR polymorphisms and TB susceptibility , and the role of vitamin D supplementation in TB treatment and prevention . Sutaria et al. concluded that : 1 ) individuals with TB had lower vitamin D status ( lower serum levels of 25(OH)D [ 19 ] ) than healthy , age-matched , and sex-matched controls , 2 ) people with certain VDR polymorphisms ( BsmI and FokI ) had increased susceptibility to TB , and 3 ) TB patients receiving vitamin D supplementation had improved outcomes in a majority of studies [ 18 ] . Similar to Sutaria et al. [ 18 ] , our recent systematic review regarding vitamin D supplementation in infectious disease [ 20 ] found 9 of 11 prospect i ve , controlled trials in TB patients to have at least 1 positive outcome in response to vitamin D therapy . Vitamin D supplements promoted anti-mycobacterial activity [ 21 ] , improved clinical outcomes ( improved weight gain [ 22,23 ] and decreased tissue involvement on imaging studies [ 22,23 ] ) , increased sputum smear and culture conversion [ 24,25 ] , reduced inflammation [ 26 ] , and increased mediators of anti-microbial activity ( cathelicidin LL37 [ 27 ] and IFN-g [ 22 ] ) . However , these results were not necessarily primary endpoints in their respective studies or applicableoutsideof specific subgroups . Furthermore , other studies had negative
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"RATIONALE Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis . OBJECTIVES To test whether vitamin D supplementation of patients with tuberculosis ( TB ) improved clinical outcome and reduced mortality . METHODS We conducted a r and omized , double-blind , placebo-controlled trial in TB clinics at a demographic surveillance site in Guinea-Bissau . We included 365 adult patients with TB starting antituberculosis treatment ; 281 completed the 12-month follow-up . The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment . MEASUREMENTS AND MAIN RESULTS The primary outcome was reduction in a clinical severity score ( TBscore ) for all patients with pulmonary TB . The secondary outcome was 12-month mortality . No serious adverse effects were reported ; mild hypercalcemia was rare and present in both arms . Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo . Overall mortality was 15 % ( 54 of 365 ) at 1 year of follow-up and similar in both arms ( 30 of 187 for vitamin D treated and 24 of 178 for placebo ; relative risk , 1.19 [ 0.58 - 1.95 ] ) . HIV infection was seen in 36 % ( 131 of 359 ) : 21 % ( 76 of 359 ) HIV-1 , 10 % ( 36 of 359 ) HIV-2 , and 5 % ( 19 of 357 ) HIV-1 + 2 . CONCLUSIONS Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB ; it is possible that the dose used was insufficient . Clinical trial registered with www.controlled-trials.com/is rct n ( IS RCT N35212132 )",
"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 Indirect evidence suggests that optimal vitamin D status is achieved with a serum 25-hydroxyvitamin D [ 25(OH)D ] concentration > 75 nmol/L. OBJECTIVE We aim ed to determine the intake of vitamin D(3 ) needed to raise serum 25(OH)D to > 75 nmol/L. DESIGN The design was a 6-mo , prospect i ve , r and omized , double-blinded , double-dummy , placebo-controlled study of vitamin D(3 ) supplementation . Serum 25(OH)D was measured by radioimmunoassay . Vitamin D(3 ) intake was adjusted every 2 mo by use of an algorithm based on serum 25(OH)D concentration . RESULTS A total of 138 subjects entered the study . After 2 dose adjustments , almost all active subjects attained concentrations of 25(OH)D > 75 nmol/L , and no subjects exceeded 220 nmol/L. The mean ( + /-SD ) slope at 9 wk [ defined as 25(OH)D change/baseline dose ] was 0.66 + /- 0.35 (nmol/L)/(microg/d ) and did not differ statistically between blacks and whites . The mean daily dose was 86 microg ( 3440 IU ) . The use of computer simulations to obtain the most participants within the range of 75 - 220 nmol/L predicted an optimal daily dose of 115 microg/d ( 4600 IU ) . No hypercalcemia or hypercalciuria was observed . CONCLUSIONS Determination of the intake required to attain serum 25(OH)D concentrations > 75 nmol/L must consider the wide variability in the dose-response curve and basal 25(OH)D concentrations . Projection of the dose-response curves observed in this convenience sample onto the population of the third National Health and Nutrition Examination Survey suggests a dose of 95 microg/d ( 3800 IU ) for those above a 25(OH)D threshold of 55 nmol/L and a dose of 125 microg/d ( 5000 IU ) for those below that threshold",
"In all species tested , except humans , biological differences between vitamins D2 and D3 are accepted as fact . To test the presumption of equivalence in humans , we compared the ability of equal molar quantities of vitamin D2 or D3 to increase serum 25-hydroxyvitamin D [ 25(OH)D ] , the measure of vitamin D nutrition . Subjects took 260 nmol ( approximately 4000 IU ) vitamin D2 ( n=17 ) or vitamin D3 ( n=55 ) daily for 14 d. 25(OH)D was assayed with a method that detects both the vitamin D2 and D3 forms . With vitamin D3 , mean ( + /-SD ) serum 25(OH)D increased from 41.3+/-17.7 nmol/L before to 64.6+/-17.2 nmol/L after treatment . With vitamin D2 , the 25(OH)D concentration went from 43.7+/-17.7 nmol/L before to 57.4+/-13.0 nmol/L after . The increase in 25(OH)D with vitamin D3 was 23.3+/-15.7 nmol/L , or 1.7 times the increase obtained with vitamin D2 ( 13.7+/-11.4 nmol/L ; P=0.03 ) . There was an inverse relation between the increase in 25(OH)D and the initial 25(OH)D concentration . The lowest 2 tertiles for basal 25(OH)D showed larger increases in 25(OH)D : 30.6 and 25.5 nmol/L , respectively , for the first and second tertiles . In the highest tertile [ 25(OH)D > 49 nmol/L ] the mean increase in 25(OH)D was 13.3 nmol/L ( P vitamin D3 shown here may seem small , it is more than what others have shown for 25(OH)D increases when comparing 2-fold differences in vitamin D3 dose . The assumption that vitamins D2 and D3 have equal nutritional value is probably wrong and should be reconsidered",
"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",
"Calcidiol , the major circulating metabolite of vitamin D , supports induction of pleiotropic antimicrobial responses in vitro . Vitamin D supplementation elevates circulating calcidiol concentrations , and thus has a potential role in the prevention and treatment of infection . The immunomodulatory effects of administering vitamin D to humans with an infectious disease have not previously been reported . To characterize these effects , we conducted a detailed longitudinal study of circulating and antigen-stimulated immune responses in ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis who were r and omized to receive adjunctive high-dose vitamin D or placebo in a clinical trial , and who fulfilled criteria for per- protocol analysis . Vitamin D supplementation accelerated sputum smear conversion and enhanced treatment-induced resolution of lymphopaenia , monocytosis , hypercytokinaemia , and hyperchemokinaemia . Administration of vitamin D also suppressed antigen-stimulated proinflammatory cytokine responses , but attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4 , CC chemokine lig and 5 , and IFN-α . We demonstrate a previously unappreciated role for vitamin D supplementation in accelerating resolution of inflammatory responses during tuberculosis treatment . Our findings suggest a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality",
"For most people in Australia , the primary source of vitamin D is casual exposure to sunlight . Hypovitaminosis D has been reported for high-risk population s , but little has been documented for women of all ages living in the community . Using cross-sectional data , we aim ed to describe physical and behavioural characteristics associated with serum 25-hydroxyvitamin D ( 25OHD ) for such women and to determine the association of serum 25OHD with hypertension and bone health . Serum 25OHD , parathyroid hormone ( PTH ) , blood pressure , bone mineral density ( BMD ) and anthropometry were measured in a r and om sample of 861 women aged 20 - 92 years enrolled in the Geelong Osteoporosis Study , set in a temperate region at latitude 38 - 39 degrees S. Lifestyle factors ( including diet , smoking , medication use , socio-economic status , residence , education , occupation , and physical activity ) were documented by question naire . In season-adjusted models for women aged 20 - 54 years , physical activity and living with a partner were independently and positively associated with serum 25OHD ; associations with weight and waist-hip ratio were negative . Among older women , physical activity , vitamin D intake and urban dwelling were positively associated with serum 25OHD ; age , weight and smoking were negative . Compared with the lowest tertile , those in the highest serum 25OHD tertile were less likely to have elevated serum PTH ( adjusted OR=0.25 , 95 % CI 0.16 - 0.41 ) and high blood pressure ( adjusted OR=0.40 , 95 % CI 0.22 - 0.72 ) , and more likely to have normal hip and spine BMD ( adjusted OR=1.65 , 95 % CI 1.08 - 2.52 ) . In multivariable models adjusting for season , age , weight ( and height ) , BMD was associated with serum 25OHD at the spine , hip and whole body ; no associations were detected at the forearm and no other characteristics were identified as confounders . Factors associated with high vitamin D status generally reflected healthy body habitus and active lifestyles . In contrast , excessive weight and smoking were associated with poorer vitamin D status . Women with high vitamin D were less likely to have elevated PTH , hypertension or bone deficits than women with poor levels",
"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 )",
"Background We earlier showed that 4-phenylbutyrate ( PB ) can induce cathelicidin LL-37 expression synergistically with 1,25-dihydroxyvitamin D3 in a lung epithelial cell line . We aim ed to evaluate a therapeutic dose of PB alone or in combination with vitamin D3 for induction of LL-37 expression in immune cells and enhancement of antimycobacterial activity in monocyte-derived macrophages ( MDM ) . Methods Healthy volunteers were enrolled in an 8-days open trial with three doses of PB [ 250 mg ( Group-I ) , 500 mg ( Group-II ) or 1000 mg ( Group-III ) ] twice daily ( b.d . ) together with vitamin D3 { 5000 IU once daily ( o.d . ) } , PB ( 500 mg b.d . ) ( Group-IV ) or vitamin D3 ( 5000 IU o.d . ) ( Group-V ) , given orally for 4 days . Blood was collected on day-0 , day-4 and day-8 ; plasma was separated , peripheral blood mononuclear cells ( P BMC ) , non-adherent lymphocytes ( NAL ) and MDM were cultured . LL-37 transcript in cells and peptide concentrations in supernatant were determined by qPCR and ELISA , respectively . In plasma , 25-hydorxyvitamin D3 levels were determined by ELISA . MDM-mediated killing of Mycobacterium tuberculosis ( Mtb ) ( H37Rv ) was performed by conventional culture method . Results MDM from Group-II had increased concentration of LL-37 peptide and transcript at day-4 , while Group-I showed increased transcript at day-4 and day-8 compared to day-0 ( p levels of transcript on day-4 compared to Group-III and Group-V ( p induction of peptide was observed in lymphocytes from Group-II on day-4 compared to Group-I and Group-IV ( p levels on day-8 compared to Group-I and Group-III ( p Intracellular killing of Mtb on day-4 was significantly increased compared to day-0 in Group-I , -II and -V ( p b.d . PB with 5000 IU o.d . vitamin D3 is the optimal dose for the induction of LL-37 in macrophages and lymphocytes and intracellular killing of Mtb by macrophages . Hence , this dose has potential application in the treatment of TB and is now being used in a clinical trial of adults with active pulmonary TB ( NCT01580007 )",
"AIM to compare the vitamin D group of pulmonary tuberculosis patients with a placebo group in terms of clinical improvement , nutritional status , sputum conversion , and radiological improvement . METHODS sixty seven tuberculosis patient visiting the Pulmonary Clinic , of Cipto Mangunkusumo Hospital , Jakarta , from January 1st to August 31st , 2001 were included in this study . The subjects were r and omised to receive vitamin D ( 0.25 mg/day ) or placebo in a double blind method , during the 6th initial week of Tb treatment . The rate of sputum conversion , complete blood counts , blood chemistry as well as radiologic examination were evaluated . RESULTS there were more male patients than females ( 39:28 ) , 78.7 % were in the productive age group , 71.6 % had low nutritional status , 62.4 % with low education level , and 67.2 % with low income . One hundred percent of the vitamin D group and only 76.7 % of the placebo group had sputum conversion . This difference is statistically significant ( p=0.002 ) . CONCLUSION the sputum conversion had no correlation with the hemoglobin level , blood clotting time , calcium level , lymphocyte count , age , sex , and nutritional status . There were more subjects with radiological improvement in the vitamin D group",
"The serum 25-hydroxyvitamin D [ 25(OH)D ] response to daily supplementation with 20 microg cholecalciferol ( D3 ) during winter in predominantly white premenopausal women living in Maine was measured and the effects of body composition and hormonal contraceptive use on baseline serum 25(OH)D concentrations and the response to supplementation were examined . A total of 112 women ( 22.2 + /- 3.7 y old ) received placebo from March 2005 until September 2005 when they were r and omized to receive either placebo or 20 microg/d D3 through February 2006 . Eighty-six women completed the study . Actual mean D3 content of the supplements was 22 microg per capsule . In February 2005 the serum 25(OH)D concentration was 62.0 + /- 23.4 nmol/L ( mean + /- SD ) . Serum 25(OH)D concentrations increased by 35.3 + /- 23.2 nmol/L from February 2005 to February 2006 in the treatment group , significantly more than the 10.9 + /- 16.9 nmol/L increase in the placebo group . Treatment group , magnitude of summer increase in 25(OH)D , estrogen dose , and baseline serum 25(OH)D concentrations , but not body fat , were significant predictors of the 1-y change in 25(OH)D concentrations used to assess the magnitude of the response to supplementation . Daily supplementation with 20 microg D3 during winter achieved optimal 25(OH)D concentrations ( > or = 75 nmol/L ) in 80 % of participants , indicating that this dose is adequate to optimize vitamin D status in most young women in Maine",
"Objective To investigate the impacts of vitamin D status , supplementation and vitamin D receptor ( VDR ) gene polymorphisms on tuberculosis ( TB ) . Methods We conducted a systematic review of published studies pertaining to case – control and r and omized-control trials from 2002 to 2014 using the PubMed data base . Results and conclusion Individuals with TB have lower vitamin D status than healthy individuals . Some VDR gene polymorphisms are associated with increased susceptibility to TB while others may not . Supplementation with vitamin D leads to improved clinical outcomes . However , further studies with a larger patient population and different ethnicities are needed to confirm these effects",
"Our study was done to assess the value of administration of vitamin D to tuberculous children . The study included twenty four newly diagnosed tuberculous children ; eleven males and thirteen females . Their age ranged from one and half to thirteen years . Thirteen patients were extra thoracic type of T.B. , while only seven were intrathoracic and the rest were mixed . They were r and omly divided into two Groups according to the treatment administered : Group A patients were given Rifampicin , Isoniazid and Streptomycin . Group B received in addition vitamin D. After eight weeks therapy , the patients of each group were evaluated regarding clinical , laboratory , and radiological improvement . Vitamin D level is raised after treatment in both Groups A and B , but this rise is not significant . It also showed insignificant difference between the two groups . Vitamin D level showed very high significant decrease in tuberculous children than matched healthy controls ( non tuberculous children ) . Calcium was significantly elevated after treatment in Group A whereas no significant change was detected in Group B. Phosphorous was highly significantly elevated after treatment in Group A , whereas in Group B it is just significantly elevated . Alkaline phosphatase level in both groups A and B were slightly decreased after treatment . However , this decrease was not significant . Clinical improvement was more evident in Group B patients ( those taking vitamin D ) as compared to Group A patients . The same was noted with X-ray and Sonographic findings . We concluded that vitamin D therapy may be of great value in addition to antituberculous drugs in the treatment of tuberculous children , and its use is highly recommended",
"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"
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Background Discrete choice experiments ( DCEs ) are increasingly used in health economics to address a wide range of health policy-related concerns . Objective Broadly adopting the methodology of an earlier systematic review of health-related DCEs , which covered the period 2001–2008 , we report whether earlier trends continued during 2009–2012 . Methods This paper systematic ally review s health-related DCEs published between 2009 and 2012 , using the same data base as the earlier published review ( PubMed ) to obtain citations , and the same range of search terms . Results A total of 179 health-related DCEs for 2009–2012 met the inclusion criteria for the review . We found a continuing trend towards conducting DCEs across a broader range of countries . However , the trend towards including fewer attributes was reversed , whilst the trend towards interview-based DCEs reversed because of increased computer administration . The trend towards using more flexible econometric models , including mixed logit and latent class , has also continued . Reporting of monetary values has fallen compared with earlier periods , but the proportion of studies estimating trade-offs between health outcomes and experience factors , or valuing outcomes in terms of utility scores , has increased , although use of odds ratios and probabilities has declined . The reassuring trend towards the use of more flexible and appropriate DCE design s and econometric methods has been reinforced by the increased use of qualitative methods to inform DCE processes and results . However , qualitative research methods are being used less often to inform attribute selection , which may make DCEs more susceptible to omitted variable bias if the decision framework is not known prior to the research project . Conclusions The use of DCEs in healthcare continues to grow dramatically , as does the scope of applications across an exp and ing range of countries . There is increasing evidence that more sophisticated approaches to DCE design and analytical techniques are improving the quality of final outputs . That said , recent evidence that the use of qualitative methods to inform attribute selection has declined is of concern
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"Background The currently recommended approach for preventing malaria in pregnancy ( MiP ) , intermittent preventive treatment with sulphadoxine-pyrimethamine ( SP-IPT ) , has been question ed due to the spread of resistance to SP . Whilst trials are underway to test the efficacy of future alternative approaches , it is important to start exploring the feasibility of their implementation . Methods and Findings This study uses a discrete choice experiment ( DCE ) method to assess the potential resistance of health workers to changing strategies for control of MiP. In Ashanti region in Ghana , 133 antenatal clinic health workers were presented with 16 choice sets of two alternative policy options , each consisting of a bundle of six attributes representing certain clinical guidelines for controlling MiP ( type of approach and drug used ) , possible associated maternal and neo-natal outcomes , workload and financial incentives . The data were analysed using a r and om effects logit model . Overall , staff showed a preference for a curative approach with pregnant women tested for malaria parasites and treated only if positive , compared to a preventive approach ( OR 1.6 ; p = 0.001 ) . Increasing the incidence of low birth weight or severe anaemia by 1 % would reduce the odds of preferring an approach by 18 % and 10 % respectively . Midwives were more resistant to potential changes to current guidelines than lower-level cadres . Conclusions In Ashanti Region , resistance to change by antenatal clinic workers from a policy of SP-IPT to IST would generally be low , and it would disappear amongst midwives if health outcomes for the mother and baby were improved by the new strategy . DCEs are a promising approach to identifying factors that will increase the likelihood of effective implementation of new interventions immediately after their efficacy has been proven",
"Background Bacterial and fungal infections in pediatric oncology patients cause morbidity and mortality . The clinical utility of antimicrobial prophylaxis in children is uncertain and the personal utility of these agents is disputed . Objectives were to use a discrete choice experiment to : ( 1 ) describe the importance of attributes to parents and healthcare providers when deciding between use and non-use of antibacterial and antifungal prophylaxis ; and ( 2 ) estimate willingness-to-pay for prophylactic strategies . Methods Attributes were chances of infection , death and side effects , route of administration and cost of pharmacotherapy . Respondents were r and omized to a discrete choice experiment outlining hypothetical treatment options to prevent antibacterial or antifungal infections . Each respondent was presented 16 choice tasks and was asked to choose between two unlabeled treatment options and an opt-out alternative ( no prophylaxis ) . Results 102 parents and 60 healthcare providers participated . For the antibacterial discrete choice experiment , frequency of administration was significantly associated with utility for parents but not for healthcare providers . Increasing chances of infection , death , side effects and cost were all significantly associated with decreased utility for parents and healthcare providers in both the antibacterial and antifungal discrete choice experiment . Parental willingness-to-pay was higher than healthcare providers for both strategies . Conclusion Chances of infection , death , side effects and costs were all significantly associated with utility . Parents have higher willingness-to-pay for these strategies compared with healthcare providers . This knowledge can help to develop prophylaxis programs",
"Study Design . Survey to all orthopedic and neurosurgeons , a r and om sample of family physicians ( FPs ) and patients in Ontario , Canada . Objective . To identify the dominant clinical factors influencing patient and physician preferences for lumbar spinal surgery . Summary of Background Data . Surgery on the degenerative lumbar spine offers significant benefit for patients with moderate-severe symptoms failing nonoperative treatment . Referring FPs have little appreciation of factors that identify the ideal surgical c and i date . Differences in preferences may lead to wide variation in referrals and impedes the shared decision-making process . Methods . We used conjoint analysis , a rigorous method for eliciting preferences , to determine the importance that respondents place on decisions for lumbar spinal surgery . We identified 6 clinical factors ( walking tolerance , pain duration , severity , neurologic symptoms , typical onset , and dominant location of pain ) and presented hypothetical vignettes to participants who rated their preference for surgery . Data were analyzed using r and om-effects ordered probit regression models and the importance of each clinical factor relative to the others was determined . Results . We obtained responses from 131 surgeons , 202 FPs , and 164 patients . We found that FPs had the highest overall preferences for surgery and surgeons had the lowest . Surgeons placed the highest importance on the location of pain . FPs considered neurologic symptoms , walking tolerance , and severity to be of similar importance . Pain severity , walking tolerance , and duration of pain were the most important factors for patients in deciding for surgery . Orthopedic ( over neurosurgical ) surgeons had a lower preference for surgery ( P . Older patients ( P preferences for surgery . Conclusion . Different preferences for surgery exist between surgeons , FPs , and patients . FPs may reduce over- and under-referrals by appreciating surgeons ' importance on location of pain ( leg vs. back ) . Surgeons and FPs may improve the shared decision-making process by underst and ing that patients place high importance on quality of life symptoms",
"Health systems worldwide are grappling with the need to control costs to maintain system viability . With the combination of worsening economic conditions , an aging population and reductions in tax revenues , the pressures to make structural changes are expected to continue growing . Common cost control mechanisms , e.g. curtailment of patient access and treatment prioritization , are likely to be adversely viewed by citizens . It seems therefore wise to include them in the decision making processes that lead up to policy changes . In the context of a multilevel iterative mixed- method design a quantitative survey representative of the German population ( N = 2031 ) was conducted to probe the acceptance of priority setting in medicine and to explore the practicability of direct public involvement . Here we focus on preferences for patients ' characteristics ( medical aspects , lifestyle and socio-economic status ) as possible criteria for prioritizing medical services . A question naire with closed response options was fielded to gain insight into attitudes toward broad prioritization criteria of patient groups . Furthermore , a discrete choice experiment was used as a rigorous approach to investigate citizens ' preferences toward specific criteria level in context of other criteria . Both the question naire and the discrete choice experiment were performed with the same sample . The citizens ' own health and social situation are included as explanatory variables . Data were evaluated using corresponding analysis , contingency analysis , logistic regression and a multinomial exploded logit model . The results show that some medical criteria are highly accepted for prioritizing patients whereas socio-economic criteria are rejected",
"Abstract Objectives : The purpose was to quantify patient and parent preferences for administration attributes of immunoglobulin ( IG ) treatments ; and determine which administration attributes were most important to users of IG treatment and whether patients and parents have similar preferences for administration attributes . Methods : US adult patients and parents of children with a self-reported physician diagnosis of a primary immunodeficiency disorder completed a best- practice web-enabled choice-format conjoint survey that presented a series of 12 choice questions , each including a pair of hypothetical IG-treatment profiles . After review ing current therapies , each profile was defined by mode of administration , frequency , location , number of needle sticks , and treatment duration . Before answering the choice questions , respondents were told to assume all treatments worked equally well . Choice questions were based on a D-efficient experimental design . Preference weights for attribute levels were estimated using r and om-parameters logit for each sample ( adult patients and parents ) . Tests were performed to determine potential interactions among the administration attributes . All respondents provided online informed consent . Results : In total , 252 patients and 66 parents completed the choice questions appropriately . Overall , both groups preferred a home setting , monthly frequency , fewer needle sticks , and shorter treatment duration s of IG treatment relative to alternative choices ( p Mode of administration was the least important attribute to both sample s ; however , parents strongly preferred self-administration to an appointment with a healthcare professional ( p self-administration but were indifferent to the two modes . Limitations : Respondents evaluate hypothetical treatments and differences can arise between stated and actual choices . Conclusions : Considering the hypothetical treatments evaluated , IG treatments that provide the option of a home setting , monthly frequency , fewer needle sticks , and shorter treatment duration s may address the needs of both patients and parents . Patients and parents have different preferences for administration attributes of IG treatments",
"Purpose : To quantify gastrointestinal stromal tumor ( GIST ) patients ’ preferences for reducing treatment toxicities and the likely effect of toxicities on patients ’ stated adherence . Methods : English-speaking members of the Life Raft Group , a GIST patient advocacy and research organization , aged 18 years and older , completed a web-enabled survey including a series of treatment-choice questions , each presenting a pair of hypothetical GIST medication toxicity profiles . Each profile was defined by common or concerning toxicities verified via pretest interviews including : severity of edema , diarrhea , nausea , fatigue , rash , h and -foot syndrome , and heart failure ; and risk of serious infection . Each subject answered 13 choice-format questions based on a predetermined experimental design with known statistical properties . Subjects were asked to rate the likelihood that they would miss or skip doses of medications with different toxicity profiles . R and om-parameters logit was used to estimate a relative preference weight for each level of toxicity . Results : 173 subjects completed the survey . Over the ranges of toxicity levels included in the study , heart failure was the most important toxicity . Edema was the least important . For all toxicities , reducing severity from severe to moderate was more important to subjects than reducing severity from moderate to mild . Reducing heart failure from moderate to mild and diarrhea from severe to moderate had the largest effects on subjects ’ evaluation of adherence . Conclusions : All toxicities included in the study are important to patients . Treating or reducing severe toxicities is much more important to patients than treating or reducing moderate toxicities . Focused reductions of certain toxicities may improve treatment adherence",
"Summary In Spain , various treatments are available to prevent osteoporotic fractures . A discrete choice experiment ( DCE ) was used to investigate the importance of different treatment aspects and its influence on patients ’ preferences . All attributes included as type and place of drug administration as well as costs showed to be significant predictors of choice . Spanish osteoporosis patients have well-defined preferences and accept trade-offs among attributes . Introduction This study was design ed to identify patient preferences for different aspects of osteoporosis treatments in Spain . Methods Main attributes of severe osteoporosis treatments were determined by literature review and consultations with nurses . The discrete choice experiment included three attributes : type of drug administration , place of administration , plus a cost attribute in order to estimate willingness to pay for improvements in attribute levels . A pilot study with 50 patients was performed to identify the areas of misunderst and ing . One hundred sixty-six patients with a diagnosis of osteoporosis and severe osteoporosis were presented with pairs of hypothetical treatment profiles with different type of administration levels , places of administration and costs . Questions to collect socio-demographic and disease-related treatment data were also included . Data were analysed using a r and om effects probit model . Results All attributes had the expected polarity and were significant predictors of choice . Patients were willing to pay 183 € /month to have a subcutaneous injection once per day rather than an intravenous injection once per year . Patients with osteoporosis were willing to pay 121 € /month to have medical support when administering the drug treatment at home rather than being admitted several hours to a hospital for drug administration . ConclusionS panish osteoporosis patients have well-defined preferences among treatment attributes and are willing to accept trade-offs among attributes . Participants indicated that they are willing to accept self medication with medical support rather than being hospitalised for several hours . The perspective of the patients should be taken into account when making treatment decisions",
"Introduction . The implementation of mass colorectal cancer ( CRC ) screening is a public health priority . Population participation is fundamental for the success of CRC screening as for any cancer screening program . The preferences of the population may influence their likelihood of participation . Objectives . The authors sought to elicit population preferences for CRC screening test characteristics to improve the design of CRC screening campaigns . Methods . A discrete choice experiment was used . Question naires were compiled with a set of pairs of hypothetical CRC screening scenarios . The survey was conducted by mail from June 2006 to October 2006 on a representative sample of 2000 inhabitants , aged 50 to 74 years from the northwest of France , who were r and omly selected from electoral lists . Question naires were sent to 2000 individuals , each of whom made 3 or 4 discrete choices between hypothetical tests that differed in 7 attributes : how screening is offered , process , sensitivity , rate of unnecessary colonoscopy , expected mortality reduction , method of screening test result transmission , and cost . Results . Complete responses were received from 656 individuals ( 32.8 % ) . The attributes that influenced population preferences included expected mortality reduction , sensitivity , cost , and process . Participants from high social classes were particularly influenced by sensitivity . Conclusions . The results demonstrate that the discrete choice experiment provides information on patient preferences for CRC screening : improving screening program effectiveness , for instance , by improving test sensitivity ( the most valued attribute ) would increase satisfaction among the general population with regard to CRC screening programs . Additional studies are required to study how patient preferences actually affect adherence to regular screening programs",
"Background The SINS trial ( Controlled Clinical Trials IS RCT N48755084 ; Eudract No. 2004 - 004506 - 24 ) is a r and omised controlled trial evaluating long term success of excisional surgery vs. imiquimod 5 % cream for low risk nodular and superficial basal cell carcinoma ( BCC ) . The trial included a discrete choice experiment question naire to explore patient preferences of a cream versus surgery for the treatment of their skin cancer . Methods The self-completed question naire was administered at baseline to 183 participants , measuring patients ’ strength of preferences when choosing either alternative ‘ surgery ’ or ‘ imiquimod cream ’ instead of a fixed ‘ current situation ’ option ( of surgical excision as st and ard practice in UK ) . The treatments were described according to : cost , chance of complete clearance , side effects and appearance . Participants had to choose between various scenarios . Analysis was performed using a mixed logit model , which took into account the impact of previous BCC treatment and sample preference variability . Results The analysis showed that respondents preferred ‘ imiquimod cream ’ to their ‘ current situation ’ or ‘ surgery ’ , regardless of previous experience of BCC symptoms and treatment . Respondents were more likely to be worried about their cosmetic outcomes and side effects they might experience over and above their chance of clearance and cost . Those with no experience of surgery ( compared with experience ) valued more the choice of ‘ imiquimod cream ’ ( £ 1013 vs £ 781 ) . All treatment characteristics were significant determinants of treatment choice , and there was significant variability in the population preferences for all of them . Conclusions Patients with BCC valued more ‘ imiquimod cream ’ than alternative ‘ surgery ’ options , and all treatment characteristics were important for their choice of care . Underst and ing how people with a BCC value alternative interventions may better inform the development of health care interventions",
"Pain Management Programmes ( PMPs ) are a multi-disciplinary approach to the management of chronic low back pain ( CLBP ) . Notwithst and ing evidence of effectiveness , successful take-up of programmes requires acceptability to patients . We used a discrete choice experiment to investigate patient preferences for alternative PMPs for managing CLBP in primary care . Specifically , we estimated the probability of uptake of alternative configurations of PMPs . Potential attributes and associated levels influencing take-up were identified through a systematic literature review , survey of current PMPs , expert consultation , and focus groups . Five attributes were included : content ; provider ; schedule ; group size ; and travel time to clinic . Four hundred and fourteen question naires were mailed to patients attending clinics and 124 question naires were returned suitable for analysis . Method of delivery influenced probability of take-up , with small group sizes and low intensity programmes over a prolonged period increasing the probabilities . Travel time was also important . However , providers and contents of PMPs were not main drivers of preferences , though those with more severe pain did prefer PMPs provided by more specialists . Probability of take-up increases when PMPs better reflect patient preferences . Given preferences , re source constraints , and evidence on clinical outcomes of alternative configurations it is suggested more re source -intensive PMPs be reserved for those with the most severe and disabling pain and less intensive programmes delivered over a longer time period in smaller groups for those with less severe pain . These findings can inform future r and omised trials to evaluate acceptable PMPs in primary care",
"BACKGROUND While the application of conjoint analysis and discrete-choice experiments in health are now widely accepted , a healthy debate exists around competing approaches to experimental design . There remains , however , a paucity of experimental evidence comparing competing design approaches and their impact on the application of these methods in patient-centered outcomes research . OBJECTIVES Our objectives were to directly compare the choice-model parameters and predictions of an orthogonal and a D-efficient experimental design using a r and omized trial ( i.e. , an experiment on experiments ) within an application of conjoint analysis study ing patient-centered outcomes among out patients diagnosed with schizophrenia in Germany . METHODS Out patients diagnosed with schizophrenia were surveyed and r and omized to receive choice tasks developed using either an orthogonal or a D-efficient experimental design . The choice tasks elicited judgments from the respondents as to which of two patient profiles ( varying across seven outcomes and process attributes ) was preferable from their own perspective . The results from the two survey design s were analyzed using the multinomial logit model , and the result ing parameter estimates and their robust st and ard errors were compared across the two arms of the study ( i.e. , the orthogonal and D-efficient design s ) . The predictive performances of the two result ing models were also compared by computing their percentage of survey responses classified correctly , and the potential for variation in scale between the two design s of the experiments was tested statistically and explored graphically . RESULTS The results of the two models were statistically identical . No difference was found using an overall chi-squared test of e quality for the seven parameters ( p = 0.69 ) or via uncorrected pairwise comparisons of the parameter estimates ( p-values ranged from 0.30 to 0.98 ) . The D-efficient design result ed in directionally smaller st and ard errors for six of the seven parameters , of which only two were statistically significant , and no differences were found in the observed D-efficiencies of their st and ard errors ( p = 0.62 ) . The D-efficient design result ed in poorer predictive performance , but this was not significant ( p = 0.73 ) ; there was some evidence that the parameters of the D-efficient design were biased marginally towards the None . While no statistical difference in scale was detected between the two design s ( p = 0.74 ) , the D-efficient design had a higher relative scale ( 1.06 ) . This could be observed when the parameters were explored graphically , as the D-efficient parameters were lower . CONCLUSIONS Our results indicate that orthogonal and D-efficient experimental design s have produced results that are statistically equivalent . This said , we have identified several qualitative findings that speak to the potential differences in these results that may have been statistically identified in a larger sample . While more comparative studies focused on the statistical efficiency of competing design strategies are needed , a more pressing research problem is to document the impact the experimental design has on respondent efficiency",
"Objective To quantify physicians ’ preferences among possible outcomes associated with chronic hepatitis B treatments and to determine which outcomes are most important to physicians in making treatment decisions . Methods Physicians in five countries who treat chronic hepatitis B patients completed a web-enabled , choice-format , conjoint- analysis survey . The survey presented physicians with four treatment-choice questions for three different patient types . Each treatment-choice question included a pair of hypothetical medication profiles . Medication outcomes included how long the medication has been studied ( weight of evidence ) ; the probability that a patient ’s viral load remains undetectable for 5 years , with a possible histological improvement or reversal of disease progression ( long-term efficacy ) ; the 5-year treatment-related risk of fracture ; the 5-year treatment-related risk of renal dysfunction ; and patient cost . Treatment-choice questions were derived from a predetermined experimental design with known statistical properties . For each country , the r and om-parameters logit was used to estimate preference weights for all outcome levels and the mean relative importance of each outcome . Results Long-term efficacy and risk of renal dysfunction were the most important outcomes for the 788 physicians completing the survey , whereas weight of evidence was the least important . However , physicians perceived significant differences in weight of evidence timeframes . Physicians in Germany and France ranked efficacy above side-effect risk , whereas physicians in Spain , Italy , and Turkey ranked side-effect risk above efficacy in importance . Conclusion Physician preferences among treatment profiles indicate systematic differences in the relative importance of treatment outcomes . Physicians require higher efficacy for treatments with higher side-effect risk but somewhat less efficacy for treatments with longer evidence",
"Abstract Background : The aims of this study were to quantify and contrast patient preferences between second-line advanced renal cell carcinoma ( RCC ) medication profiles and their associated benefits and toxicities , and to help frame the doctor – patient discussion about selecting appropriate RCC therapies . Research design and methods : Adult residents of the US with a diagnosis of RCC completed a Web-enabled choice-format conjoint survey consisting of a series of 10 treatment-choice questions , each of which included a pair of hypothetical RCC medication profiles . Each profile was described by various medication attributes ( features or outcomes ) with varying levels . The attributes included efficacy ( progression-free survival [ PFS ] ) , tolerability ( fatigue , stomach problems , mucositis or stomatitis , h and –foot syndrome [ HFS ] ) , serious but rare adverse events ( pneumonitis , hepatic impairment ) , and mode of administration . Treatment-choice questions were based on an experimental design with known statistical properties . R and om-parameters logit regression was used to estimate relative preference weights for each attribute level . Benefit equivalent measures ( additional months of PFS in exchange for toxicities ) were also calculated . Results : Of the 272 patients who completed the survey , the majority were female ( 53 % ) , white ( 92 % ) , and had at least a college degree ( 66 % ) . The mean age was 57 years ( st and ard deviation : 10 years ) . Over the range of attributes and attribute levels included in the survey , PFS was the most important attribute , followed by fatigue , stomach problems , hepatic impairment , mucositis or stomatitis , HFS , pneumonitis , and mode of administration . To reduce severe fatigue to mild-to-moderate fatigue , patients on average would be willing to forego 4.4 months of PFS . To reduce hepatic impairment risk from 0.5 % to 0.0 % , patients on average would be willing to forego 1.0 month of PFS . The main study limitation was that patients answered hypothetical treatment-choice questions . Conclusions : This study provides information to physicians about patient priorities when review ing and selecting RCC therapies with patients",
" Subjects with rheumatoid arthritis ( RA ) enrolled in an online panel were asked to evaluate pairs of treatment alternatives with different attributes . Half of the sample saw a cheap-talk text . Preference parameters were estimated using r and om-parameters logit models to account for unobserved taste heterogeneity . The models also were estimated in willingness-to-pay ( WTP ) space instead of conventional utility space . Cheap talk not only affected the coefficient on the cost attribute , but also preferences for other attributes . WTP estimates were generally lower in cheap talk sample , except for the most important attribute and a 2-level attribute . Subjects who were presented with cheap talk discriminated between the adjoning attribute levels better than the subjects in the control sample",
"Background A discrete choice experiment ( DCE ) is a preference survey which asks participants to make a choice among product portfolios comparing the key product characteristics by performing several choice tasks . Analyzing DCE data needs to account for within-participant correlation because choices from the same participant are likely to be similar . In this study , we empirically compared some commonly-used statistical methods for analyzing DCE data while accounting for within-participant correlation based on a survey of patient preference for colorectal cancer ( CRC ) screening tests conducted in Hamilton , Ontario , Canada in 2002 . Methods A two-stage DCE design was used to investigate the impact of six attributes on participants ' preferences for CRC screening test and willingness to undertake the test . We compared six models for clustered binary outcomes ( logistic and probit regressions using cluster-robust st and ard error ( SE ) , r and om-effects and generalized estimating equation approaches ) and three models for clustered nominal outcomes ( multinomial logistic and probit regressions with cluster-robust SE and r and om-effects multinomial logistic model ) . We also fitted a bivariate probit model with cluster-robust SE treating the choices from two stages as two correlated binary outcomes . The rank of relative importance between attributes and the estimates of βcoefficient within attributes were used to assess the model robustness . Results In total 468 participants with each completing 10 choices were analyzed . Similar results were reported for the rank of relative importance and βcoefficients across models for stage-one data on evaluating participants ' preferences for the test . The six attributes ranked from high to low as follows : cost , specificity , process , sensitivity , preparation and pain . However , the results differed across models for stage-two data on evaluating participants ' willingness to undertake the tests . Little within-patient correlation ( ICC ≈ 0 ) was found in stage-one data , but substantial within-patient correlation existed ( ICC = 0.659 ) in stage-two data . Conclusions When small clustering effect presented in DCE data , results remained robust across statistical models . However , results varied when larger clustering effect presented . Therefore , it is important to assess the robustness of the estimates via sensitivity analysis using different models for analyzing clustered data from DCE studies",
"Abstract Background : Male circumcision ( MC ) has become an important weapon in the fight against HIV/AIDS in many Sub-Saharan African countries . The successful implementation of a national MC program requires the design of circumcision services that are attractive to young men of various ages . For many potential clients , mothers and /or fathers will play an important role in the decision to be circumcised , and hence services will need to be design ed with the preferences of mothers , fathers , and sons in mind . Objective : Our objective was to value multiple design characteristics of potential community-based MC services from the perspectives of mothers , fathers , and sons in Johannesburg , South Africa , and to test for concordance between their values for the design characteristics . Methods : Potential design characteristics of MC services were identified through open-ended interviews with key informants ( n=25 ) . Preferences were estimated using conjoint analysis implemented as part of a cluster r and omized household survey . Each participant was r and omized to receive one of two possible blocks of conjoint analysis , each consisting of six forced-choice tasks comparing two possible MC services varying on 11 design characteristics . With only two levels for each attribute , our experimental design utilized a main effects orthogonal array . Data were analyzed using linear probability models , with tests of concordance of values using Wald tests generated from stratified estimates calculated using restricted least square estimation . Results : A racially and geographically diverse sample consisting of 204 fathers , 204 mothers , and 237 sons completed the survey . In aggregate , requiring a follow-up visit was the most valued design factor ( p lower infection rate ( p having less pain ( p = 0.001 ) , and a private waiting room ( p = 0.001 ) . Based on stratified analysis , sons also valued having the risks and benefits of MC explained ( p = 0.01 ) and mothers valued requiring an HIV test as part of the procedure . Requiring an HIV test was the most significant difference between the respondents ( p = 0.03 ) , with sons finding it somewhat repulsive ( p = 0.30 ) . Conclusion : Our findings suggest that valuation of aspects of MC clinic design can diverge by decision maker . To better ensure utilization of services , these variations should be taken into account to prior to implementation of a national strategy in South Africa",
"Attribute generation for discrete choice experiments ( DCEs ) is often poorly reported , and it is unclear whether this element of research is conducted rigorously . This paper explores issues associated with developing attributes for DCEs and contrasts different qualitative approaches . The paper draws on eight studies , four developed attributes for measures , and four developed attributes for more ad hoc policy questions . Issues that have become apparent through these studies include the following : the theoretical framework for r and om utility theory and the need for attributes that are neither too close to the latent construct nor too intrinsic to people 's personality ; the need to think about attribute development as a two-stage process involving conceptual development followed by refinement of language to convey the intended meaning ; and the difficulty in resolving tensions inherent in the reductiveness of condensing complex and nuanced qualitative findings into precise terms . The comparison of alternative qualitative approaches suggests that the nature of data collection will depend both on the characteristics of the question ( its sensitivity , for example ) and the availability of existing qualitative information . An iterative , constant comparative approach to analysis is recommended . Finally , the paper provides a series of recommendations for improving the reporting of this element of DCE studies",
"Purpose : To estimate consumer utilities associated with major attributes of retail clinics ( RCs ) . Data sources : A discrete choice experiment ( DCE ) with 383 adult residents of the metropolitan statistical areas in Georgia conducted via R and om Digit Dial survey of households . The DCE had two levels each of four attributes : price ( $ 59 ; $ 75 ) , appointment wait time ( same day ; 1 day or more ) , care setting ‐provider combination ( nurse practitioner [NP]‐RC ; physician‐private office ) , and acute illness ( urinary tract infection ; influenza ) , result ing in 16 choice scenarios . The respondents indicated whether they would seek care under each scenario . Conclusions : Cost savings and convenience offered by RCs are attractive to urban patients , and given sufficient cost savings they are likely to seek care there . All else equal , one would require cost savings of at least $ 30.21 to seek care from an NP at RC rather than a physician at private office , and $ 83.20 to wait one day or more . Implication s for practice : Appointment wait time is a major determinant of careseeking decisions for minor illnesses . The size of the consumer utility associated with the convenience feature of RCs indicates that there is likely to be further growth and employment opportunities for NPs in these clinics",
"OBJECTIVES Little is known about doctors ' preferences regarding public report card design . Taiwan just announced the first diabetes report card on April 2008 . The aim of this study was to investigate the Diabetes Mellitus ( DM ) providers ' preferences towards four report card attributes : up date frequency , risk adjustment , content information and display format . METHODS A discrete choice question naire was mailed to hospital and primary care doctors in the northern part of Taiwan , with 221 study targets . The response rate was 29 % . RESULTS Using r and om effect logistic regression , doctors ' preference attribute rankings were risk adjustment for patients ( 44.7 % ) , content information ( 25.2 % ) , display format ( 18.3 % ) and up date frequency ( 11.8 % ) . One-year up date frequency , risk adjustment , detailed scores of technical quality and interpersonal quality and bar chart display were the most important items noted in our survey . CONCLUSIONS This is the first study to investigate provider 's preferences for a diabetes report card . It enables the policy maker to clearly see the implication of trade-offs between different choices when design ing a report card that doctors will like . Our findings suggest that doctors do not favour the ' less is more ' principle , or the higher frequency of up date s that patients may prefer . Rather , our findings suggest that risk adjustment and more information content are the most important factors for doctors . Future studies should use discrete choice experiment on different aspects of report card design , such as vulnerable patients or health care administrations",
"At present there are no nephrology facilities in Greenl and . Greenl and ic patients with renal failure needing dialysis thus have to travel to Denmark to obtain treatment . For patients in haemodialysis this necessitates a permanent residence in Denmark . Our study was aim ed at examining Greenl and ers ’ preferences for establishing nephrology facilities in Greenl and at Queen Ingrid ’s Hospital in Nuuk , and to estimate the associated change in welfare . Preferences were elicited using a discrete choice experiment ( DCE ) . A r and om sample of 500 individuals of the general population was sent a postal question naire in which they were asked to consider the trade-offs of establishing nephrology facilities in Greenl and as opposed to the current situation . This involved trading off the benefits of having such facilities in their home country against the costs of the intervention . Besides including a payment attribute described in terms of incremental tax payment , the DCE included two interventions attributes related to ( 1 ) the organisation of labour , and ( 2 ) the physical setting s of the patients . Respondents succeeded in answering the DCE despite cultural and linguistic disparity . We found that all the included attributes had a significant effect on respondents ’ choices , and that respondents ’ answers to the DCE were in keeping with their values as stated in the question naire . DCE data was analyzed using a r and om parameter logit model reparametrized in willingness-to-pay space . The results showed that establishing facilities in Greenl and were preferred to the current treatment in Denmark . The welfare estimate from the DCE , at DKK 18.74 million , exceeds the estimated annual costs of establishing treatment facilities for patients with chronic renal failure . Given the estimated confidence interval this result seems robust . Establishing facilities in Greenl and therefore would appear to be welfare-improving , deriving positive net benefits . Despite the relatively narrow policy focus , we believe that our findings provide some insight into individuals ’ preferences for de central ization of public services and on citizens ’ views of ‘ self-governance ’ that go beyond the case of Greenl and . More generally , this paper illustrates how DCE can be applied successfully to developing countries with culturally , demographically , and geographically distinct features",
"RATIONALE , AIMS AND OBJECTIVE To elicit the preferences and trade-offs of UK general practitioners about key features of health information systems , to help inform the design of such systems in future . METHODS A stated choice study to uncover implicit preferences based on a binary choice between scenarios presented in r and om order . PARTICIPANTS were all 303 general practice members of the UK Internet service provider , Medix who were approached by email to participate . The main outcome measure was the number of seconds delay in system response that general practitioners were willing to trade off for each key system feature : the reliability of the system , the sites from which the system could be accessed and which staff are able to view patient data . RESULTS Doctors valued speed of response most in information systems but would be prepared to wait 28 seconds to access a system in exchange for improved reliability from 95 % to 99 % , a further 2 seconds for an improvement to 99.9 % and 27 seconds for access to data from anywhere including their own home compared with one place in a single health care premises . However , they would require a system that was 14 seconds faster to compensate for allowing social care as well as National Health Service staff to read patient data . CONCLUSIONS These results provide important new evidence about which system characteristics doctors value highly , and hence which characteristics design ers need to focus on when large scale health information systems are planned",
"Background Most research ers in health economics cite r and om utility theory ( RUT ) when analysing discrete choice experiments ( DCEs ) . Under RUT , the error term is associated with the analyst ’s inability to properly capture the true choice processes of the respondent as well as the inconsistency or mistakes arising from the respondent themselves . Under such assumptions , it st and s to reason that analysts should explore more complex nonlinear indirect utility functions , than currently used in healthcare , to strive for better estimates of preferences in healthcare . Objective To test whether complex indirect utility functions decrease error variance for models that either implicitly ( i.e. the multinomial logit ( MNL ) model ) or explicitly ( i.e. entropy multinomial logit ( EMNL ) model ) account for error variance in health(care)-related DCEs ; and to determine the impact of complex indirect utility functions on willingness-to-pay ( WTP ) measures . Methods Using data from DCEs aim ed at healthcare-related decisions , we empirically compared ( 1 ) complex and simple indirect utility specifications in terms of goodness of fit , ( 2 ) their impact on WTP measures , including confidence intervals ( CIs ) based on the Delta method , the Krinsky and Robb-procedure , and Bootstrapping , and ( 3 ) MNL and EMNL model results . Results Complex indirect utility functions had a better model fit than simple specifications ( p WTP estimates were quite similar across alternative specifications . The Delta method produced the most narrow CIs . The EMNL model showed that respondents apply simplifying strategies when answering DCE questions . Conclusion Complex indirect utility functions reduce error arisen from research ers , which can have important implication s for measures in healthcare such as the WTP , whereas EMNL provides insights into the behaviour of respondents when answering DCEs . Underst and ing how respondents answer DCE questions may allow research ers to construct DCEs that minimise scale differences , so that the decision error made across respondents is more homogeneous and therefore taken out as additional noise in the data . Hence , better estimates of preferences in healthcare can be provided",
"Despite modern highly efficacious technologies , there is still a lack of consensus on how to optimally treat haemophilia patients with inhibitors . The aim of the study was to evaluate preferences towards the characteristics of different coagulation factor concentrates for haemophilia inhibitors patients , from the perspective of patients or their caregivers , haematologists and pharmacists . A discrete choice study was conducted . Potential products were described with eight selected characteristics : perceived viral safety , risk of anamnestic response , possibility of undergoing major surgery , frequency of infusions in prophylaxis , number of infusions to stop bleeding , time to stop bleeding , time to pain recovery and cost . Participants received 16 pairs of potential products and chose from each pair the option they considered better . Data were analysed with a r and om-effects conditional logistic model . Totally 1614 observations were obtained from 37 patients /caregivers , 39 physicians and 25 pharmacists from Italy . Cost was the most important characteristic to every group . For patients /caregivers , the next most important factors were : risk of anamnestic response , possibility of undergoing major surgery and perceived viral safety . For physicians , the next most important characteristics were : risk of anamnestic response , number of infusions to stop bleeding and possibility of undergoing major surgery . For pharmacists , the next most important factors were : time to stop bleeding , time to pain recovery and possibility of undergoing major surgery . Decisions on treatments must take into account patients clinical needs ; however , preferences can also play an important role in the choice and success of treatments . The results of this study could , therefore , help decision-makers to optimize the overall benefits of treatments",
"Objective . To quantify the relative importance that UK physicians attach to the benefits and risks of current drugs when making treatment decisions for patients with osteoarthritis ( OA ) . Methods . Physicians treating at least 10 patients with OA per month completed an online discrete-choice experiment survey and answered 12 treatment-choice questions comparing medication profiles . Medication profiles were defined by 4 benefits ( reduction in ambulatory pain , resting pain , stiffness , and difficulty doing daily activities ) and 3 treatment-related risks [ bleeding ulcer , stroke , and myocardial infa rct ion ( MI ) ] . Each physician made medication choices for 3 of 9 hypothetical patients ( varied by age , history of MI , hypertension , and history of gastrointestinal bleeding ) . Importance weights were estimated using a r and om-parameters logit model . Treatment-related risks physicians were willing to accept in exchange for various reductions in ambulatory and resting pain also were calculated . Results . The final sample was 475 . A reduction in ambulatory pain from 75 mm to 25 mm ( 1.6 units ) was 1.1 times as important as an increase in MI risk from 0 % to 1.5 % ( 1.5 units ) . The greatest importance was for eliminating a 3 % treatment-related risk of MI or stroke . On average , physicians were willing to accept an increase in bleeding ulcer risk of 0.7 % ( 95 % CI 0.4%–1.7 % ) for a reduction in ambulatory pain of 75 mm to 50 mm . Conclusion . When presented with well-known benefits and risks of OA treatments , physicians placed greater importance on the risks than on the analgesic properties of the drug . This has implication s for the reporting of the results of clinical research to physicians",
"BACKGROUND Dialysis modality preferences of patients with chronic kidney disease ( CKD ) and family caregivers are important , yet rarely quantified . STUDY DESIGN Prospect i ve , unlabeled , discrete-choice experiment with r and om-parameter logit analysis . SETTING & PARTICIPANTS Adults with stages 3 - 5 CKD and caregivers educated about dialysis treatment options from 8 Australian renal clinics . PREDICTORS Preferences for and trade-offs between the dialysis treatment attributes of life expectancy , number of hospital visits per week , ability to travel , hours per treatment , treatment time of day , subsidized transport service , and flexibility of treatment schedule . OUTCOMES & MEASUREMENTS Results presented as ORs for preferring home-based or in-center dialysis to conservative care . RESULTS 105 predialysis patients and 73 family caregivers completed the study . Median patient age was 63 years , and mean estimated glomerular filtration rate was 18.1 ( range , 6 - 34 ) mL/min/1.73 m(2 ) . Median caregiver age was 61 years . Home-based dialysis ( either peritoneal or home hemodialysis ) was chosen by patients in 65 % of choice sets ; in-center dialysis , in 35 % ; and conservative care , in 10 % . For caregivers , this was 72 % , 25 % , and 3 % , respectively . Both patients and caregivers preferred longer rather than shorter hours of dialysis ( ORs of 2.02 [ 95 % CI , 1.51 - 2.70 ] and 2.67 [ 95 % CI , 1.85 - 3.85 ] for patients and caregivers , respectively ) , but were less likely to choose nocturnal than daytime dialysis ( ORs of 0.07 [ 95 % CI , 0.01 - 0.75 ] and 0.03 [ 95 % CI , 0.01 - 0.20 ] ) . Patients were willing to forgo 23 ( 95 % CI , 19 - 27 ) months of life expectancy with home-based dialysis to decrease their travel restrictions . For caregivers , this was 17 ( 95 % CI , 16 - 18 ) patient-months . LIMITATIONS Data were limited to stated preferences rather than actual choice of dialysis modality . CONCLUSIONS Our study suggests that it is rare for caregivers to prefer conservative nondialytic care for family members with CKD . Home-based dialysis modalities that enable patients and their family members to travel with minimal restriction would be strongly aligned with the preferences of both parties",
"OBJECTIVE The objective of the study was to investigate the effect of a priori information on preferences for treatment elicited in a discrete choice experiment . METHODS A convenience sample of 100 subjects was r and omly split into two groups . The groups received minimal or extensive information on the treatment of ankle and foot impairment in stroke . Then , they participated in a discrete choice experiment . Possible treatment was described using eight decision criteria with two to four levels each . Part-worth utility coefficients for the criteria levels , criteria importance and overall treatment preference were estimated . It was tested whether the amount of information that was received influenced the outcome of the discrete choice experiment . RESULTS In the extensively informed group fewer reversals in the expected order of part-worth utilities were found . Criteria importance for four of the eight criteria and criteria importance ranking between the minimally and extensively informed subject groups were significantly different . The difference in part-worth utility of the levels had a minor effect on the predicted utility of the available treatments . CONCLUSION The lower number of level rank reversals in the extensively informed subjects indicates a better underst and ing of outcome desirability and thus a better underst and ing of the decision task . The effect of more extensive information on predicted treatment preference was minimal . PRACTICE IMPLICATION S While interpreting the results of a discrete choice experiment , the effect of prior knowledge on the decision problem has to be taken into account . Although information seems to increase the underst and ing of the decision task , outcomes valuation can also be directed by information and more extensive information increases the cognitive burden which is placed on the subjects . Future research should focus on the exact nature and size of the effects and the results of this study should be clinical ly vali date",
"Little is known about the relative importance of factor VIII ( FVIII ) treatment attributes to haemophilia A patients and their willingness to accept trade-offs among these attributes . To quantify patient and parent preferences for FVIII treatments and compare the relative importance of treatment attributes . Adult patients and parents of children with severe haemophilia A in the US completed a web-enabled , choice-format conjoint survey that presented a series of 12 trade-off questions , each including a pair of hypothetical treatment profiles . Each profile was defined by percent of bleeds stopped with one or two infusions , chance of developing an inhibitor , risk of viral infection , preparation volume , dosage strengths available , and history of supply shortage . Trade-off questions were based on a D-optimal experimental design . Preference weights for attribute levels were estimated using r and om-parameters logit . One hundred and forty seven subjects completed the survey . Over the ranges of attribute levels included in the study , risk of viral infection was the most important attribute . Remaining attributes were ranked in decreasing order of importance as follows : chance of developing an inhibitor , dosage strengths available , percent of bleeds stopped with one or two infusions , history of supply shortage , and preparation volume . Risk of viral infection was 6.0 times as important as percent of bleeds stopped with one or two infusions and 2.7 times as important as the chance of developing an inhibitor . While risk of viral infection was the most important attribute , this research demonstrates that many FVIII treatment attributes are important in the decision-making process",
"OBJECTIVES To examine GPs ' preferences for organisational characteristics in general practice with focus on aspects that can potentially mitigate problems with GP shortages . METHODS A simple r and om sample of 1823 GPs ( corresponding to half of all GPs in Denmark ) was drawn at the beginning of 2010 , and a response rate of 68 % was obtained . A discrete choice experiment ( DCE ) is applied , and attributes included are : practice type ( solo/shared ) , number of GPs in general practice , collaboration with other practice s ( yes/no ) , change in weekly working hours ( administrative versus patient related ) and change in yearly surplus . Multinomial logit analyses ( with and without interaction variables ) are used , and marginal rates of substitution are calculated . RESULTS GPs working in solo practice s have different preferences for the organisational attributes compared to GPs in shared practice s. The compensation needed for GPs to re-organise from solo to shared practice is associated with the size of the practice . GP characteristics such as age , working hours and surplus affect their willingness to undergo organisational changes . CONCLUSIONS Our results are of relevance to decision makers in design ing policies aim ed at influencing GPs ' organisation in order to overcome problems related to shortages",
"Background A new modelling approach for analysing data from discrete-choice experiments ( DCEs ) has been recently developed in transport economics based on the notion of regret minimization-driven choice behaviour . This so-called R and om Regret Minimization ( RRM ) approach forms an alternative to the dominant R and om Utility Maximization ( RUM ) approach . The RRM approach is able to model semi-compensatory choice behaviour and compromise effects , while being as parsimonious and formally tractable as the RUM approach . Objectives Our objectives were to introduce the RRM modelling approach to healthcare-related decisions , and to investigate its usefulness in this domain . Methods Using data from DCEs aim ed at determining valuations of attributes of osteoporosis drug treatments and human papillomavirus ( HPV ) vaccinations , we empirically compared RRM models , RUM models and Hybrid RUM – RRM models in terms of goodness of fit , parameter ratios and predicted choice probabilities . Results In terms of model fit , the RRM model did not outperform the RUM model significantly in the case of the osteoporosis DCE data ( p = 0.21 ) , whereas in the case of the HPV DCE data , the Hybrid RUM – RRM model outperformed the RUM model ( p Differences in predicted choice probabilities between RUM models and ( Hybrid RUM- ) RRM models were small . Derived parameter ratios did not differ significantly between model types , but trade-offs between attributes implied by the two models can vary substantially . Conclusion Differences in model fit between RUM , RRM and Hybrid RUM – RRM were found to be small . Although our study did not show significant differences in parameter ratios , the RRM and Hybrid RUM – RRM models did feature considerable differences in terms of the trade-offs implied by these ratios . In combination , our results suggest that RRM and Hybrid RUM – RRM modelling approach hold the potential of offering new and policy-relevant insights for health research ers and policy makers",
"Background : Prior practical experience in conducting adaptive conjoint analysis ( ACA ) surveys has demonstrated that many subjects have difficulty underst and ing the ‘ importance ’ questions . Objective : To develop a modified version of ACA importance questions . Methods : Modified ACA importance questions composed of two tasks were developed and tested in a pilot study of patients with knee pain . In the first , respondents were presented with the list of attributes and asked to choose which they considered the most important . In the second , they were asked to rate the importance of the remaining attributes relative to the most important one on an 11-point numeric rating scale . Consecutive patients with knee pain , followed at a hospital-based Bone and Joint Clinic , were r and omized to complete the original or modified version of the ACA survey . The two versions were identical except for the importance questions . The ACA survey included six attributes : pain , energy , route of administration , stomach upset , bleeding ulcer and cost . Each attribute contained three levels , all of which had a natural order except for route of administration . As this was a pilot study , we present descriptive statistics only . Results : A total of 49 patients were recruited ; 24 completed the original version and 25 completed the modified version . Subjects felt that bar graphs illustrating the relative importance were more accurate for the modified version of ACA . The proportion of subjects for which the most important attribute chosen on a card-sorting task matched that generated by ACA was greater for the modified than for the original version ( 48 % vs 29 % ) . The proportion of subjects for which the treatment option chosen on a card-sorting task matched that predicted by ACA was also greater for the modified than for the original version ( 80 % vs 75 % ) . Subjects used a greater number of points to rate the importance of attributes on the modified version of ACA ( mean±SD = 3.4±0.9 ) than on the original version ( mean±SD = 2.7±1.0 ) . Conclusions : The modified version of the ACA importance questions appears to perform as well as or better than the original version . Use of a simplified set of ACA importance questions is a reasonable alternative for investigators interested in using ACA as a decision-support tool in clinical practice",
"Study Design . Discrete choice experiment . Objective . To investigate the reduction in the risk of surgery that scoliosis patients would require in order to consider brace treatment as acceptable , and to elicit the trade-offs individuals make between characteristics of brace treatment . Summary of Background Data . The effectiveness of brace treatment in idiopathic scoliosis patients has not been established in r and omized controlled trials ( RCTs ) . Treatment with a brace can be quite bothersome . Patients ' preferences for brace treatment are unknown . Insight into patients ' preferences for ( characteristics of ) brace treatment will be useful for future trials and for the development of braces that may optimize compliance with brace treatment . Methods . A total of 197 patients who had completed treatment ( brace and /or surgery ) for scoliosis were approached for the study , of which 135 gave informed consent . A discrete choice experiment was design ed in which patients had to choose between hypothetical brace treatment profiles that differed in following 4 treatment attributes : effectiveness , visibility , discomfort , and treatment duration . A multinomial logit model was used to analyze the relative importance of these attributes . Subgroup analyses were conducted for brace-only , brace-surgery , and surgery-only patients . Results . The response rate was 86 % ( 116/135 ) . All treatment attributes proved to be important for patients ' choices . All subgroups were prepared to initiate treatment with a Boston brace if the brace would reduce the need for surgery by 53 % . Risk reductions in a range of 32 % to 74 % were required for acceptance of a treatment duration of 3 years . Conclusion . Scoliosis patients stated to be prepared to undergo brace treatment only if it provides sizeable reduction of the risk of surgery . Effectiveness and discomfort in wearing a brace were the most important determinants of the choices . These results are important if RCTs would conclusively establish that bracing is effective , and show directions for the further technical development of braces to increase the compliance with brace treatment",
"Background : Nowadays , an increasing number of discrete-choice experiments ( DCEs ) incorporate cost as an attribute . However , the inclusion of a cost attribute , particularly within collectively funded healthcare systems , can be challenging because health services or goods are generally not traded in a market situation and individuals are not used to paying for a service or a good at the point of consumption . Objective : To examine whether the inclusion of a cost attribute in a DCE results in different preferences regarding a surgical treatment for primary basal cell carcinoma ( BCC ) compared with a DCE without a cost attribute . Methods : A r and omized study was performed in which the impact of a cost attribute on the general public ’s preferences for a surgical treatment ( Mohs micrographic surgery [ MMS ] or st and ard excision [ SE ] ) to remove BCC was examined . This was done by comparing the outcomes of two DCEs , one with a cost attribute ( DCE_cost ) and one without ( DCE_nocost ) . Six attributes ( recurrence , re-excision , travel time , surgical time , waiting time for surgical results , costs ) and their levels were selected , based on results of a clinical trial , a cost-effectiveness study , a review and a focus group of patients who had recently received treatment for BCC . Outcomes of both DCEs were compared in terms of theoretical validity , relative importance of the attributes and the rank order of preferences . Results : A total of 615 respondents ( n = 303 for DCE_nocost ; n = 312 for DCE_cost ) were interviewed by telephone . This gave an overall response rate of 38%.Respondents in DCE_nocost preferred a surgical treatment with a lower probability of recurrence , lower surgery time , lower waiting time and no risk for a re-excision . Respondents in DCE_cost showed the same preferences , but also preferred a treatment with less travel time and lower costs . Overall , respondents in both DCEs showed the same preference for a surgical treatment : MMS was preferred over SE . Conclusion : Results suggest that , in this population , the inclusion of a cost attribute in a DCE leads to the same preference regarding a surgical treatment to remove BCC as a DCE without a cost attribute . However , further research in different setting s is needed to confirm these findings",
"Investigation of the ' rationality ' of responses to discrete choice experiments ( DCEs ) has been a theme of research in health economics . Responses have been deleted from DCEs where they have been deemed by research ers to ( a ) be ' irrational ' , defined by such studies as failing tests for non-satiation , or ( b ) represent lexicographic preferences . This paper outlines a number of reasons why deleting responses from DCEs may be inappropriate after first review ing the theory underpinning rationality , highlighting that the importance placed on rationality depends on the approach to consumer theory to which one ascribes . The aim of this paper is not to suggest that all preferences elicited via DCEs are rational . Instead , it is to suggest a number of reasons why it may not be the case that all preferences labelled as ' irrational ' are indeed so . Hence , deleting responses may result in the removal of valid preferences ; induce sample selection bias ; and reduce the statistical efficiency and power of the estimated choice models . Further , evidence suggests r and om utility theory may be able to cope with such preferences . Finally , we discuss a number of implication s for the design , implementation and interpretation of DCEs and recommend caution regarding the deletion of preferences from stated preference experiments",
"The present study aims to evaluate the impact of cost-effectiveness information on clinical decision making using discrete choice experiment ( DCE ) methodology . Data were collected through a self-completed question naire administered to Italian cardiologists in June 2007 ( n = 129 respondents , 1143 observations ) . The question naire asked clinicians to make choices between paired scenarios , across which three key dimensions were identified and varied : ( 1 ) quality of clinical evidence , ( 2 ) size of health gain ( reduction of relative and absolute risk ) , and ( 3 ) economic impact ( incremental cost-effectiveness ratio ) . A r and om effects probit model was used to estimate clinicians ' preferences for the different dimensions , while the heterogeneity of preferences was tested in a model with interaction terms . Dominance tests were used to assess the consistency of responses . The results indicate that Italian cardiologists regard economic impact ( cost-effectiveness ) as an important factor in their decision making . Economic evidence is valued more highly among clinicians with a higher self-assessed level of knowledge regarding economic evaluation techniques , as well as among younger professionals ( age ) . While relevant study limitations should be acknowledged , our results suggest that DCEs can be used to elicit clinicians ' decision-making criteria and to inform the allocation of re sources for future research in a logical manner . Italian cardiologists appear to take cost-effectiveness information into account when deciding whether to use new treatments",
"OBJECTIVE Recent review s of discrete choice methodology identified method ological issues warranting further exploration , including the issue of \" framing . \" The objective of this study was to conduct a method ological exploration of the effect of attribute framing on marginal rates of substitution ( MRS ) , including willingness to pay ( WTP ) from a discrete choice experiment ( DCE ) , within the context of colorectal cancer screening preferences . METHODS The survey , a fractional factorial design of a two-alternative , unlabeled experiment , was mailed to a sample of 1920 subjects in NSW , Australia . Participants were r and omized to one of four alternative \" frames \" of information . Attributes included : accuracy of the test for finding cancers , accuracy of the test for finding large polyps , how good the test is at saying you do n't have cancer , cost , dietary and medication restrictions and sample collection . A mixed logit model was used to estimate preferences ; MRS between attributes , including WTP , was calculated . RESULTS A total of 1157 surveys from 1920 ( 60.2 % ) were returned . Accuracy of the test for finding cancer was most likely to influence choice of test , followed by accuracy of the test for finding large polyps . Under some circumstances , framing of the attributes ( e.g. , cancers found vs. cancers missed ) influenced the relative importance of attributes . Attribute framing significantly influenced estimates of WTP , and benefit : harm trade-offs that were calculated from MRS . CONCLUSIONS Attribute framing can influence willingness to pay and benefit : harm trade-offs from DCEs . Appropriate design and analysis methods should be explored to further characterize the influence and extent of framing in discrete choice studies",
"OBJECTIVES To identify the principles the public considers important and the trade-offs between different values in health-care re source allocation practice s. METHODS This study approached the issue in both qualitative and quantitative ways . In a qualitative study , two focus groups discussed the issues of re source allocation in health care . To facilitate the discussion , a simple ranking task and a series of pairwise choice practice s were implemented . A discrete choice experiment survey question naire was also administered to a sample of the general population . Attributes and levels were determined through literature review s and the results from the focus group interview . We used a r and om-effect probit model to assess the effects of each attribute . RESULTS Through the focus group interviews , we found strong public support for the principle of equal opportunity . The participants thought that the severity of disease was the most important criterion when setting priorities . The majority supported the idea that the most disadvantaged should have the highest priority even when their health gains are less than those of others . The discrete choice experiment results showed that the severity of disease , health gains , and patients ' socioeconomic status significantly influence their choices , with each parameter having an expected sign . CONCLUSION The results showed that Koreans support not only health maximization but also equal opportunity , fair re source allocation , and e quality",
"BACKGROUND Long-acting insulin treatments with varying clinical benefits are currently available for patients with type 1 diabetes mellitus ( T1DM ) and type 2 diabetes mellitus ( T2DM ) . The current evidence base demonstrates the efficacy of treatments , but it is critical also to underst and patient preferences regarding treatments and how they are determined . OBJECTIVE This study aim ed to measure the willingness to pay ( WTP ) of individuals with diabetes in the United Kingdom for different attributes of long-acting insulin therapy . METHODS A survey based on discrete choice experiment methodology was developed to elicit the preferences and values of adults with T1DM or insulin-dependent T2DM regarding different aspects of their therapy . Participants were presented with a series of 27 paired choices and asked which they preferred . WTP values were calculated for relevant attribute levels . RESULTS A total of 252 participants completed the question naire ( 52 % response rate ) ; 143 had T1DM and 109 had insulin-treated T2DM . The highest WTP values in participants with T1DM were avoiding 2-kg or 4-kg weight gain ( £ 29 and £ 58 , respectively ) , avoiding major difficulties with the injection device ( £ 49 ) , increasing the number of days per week when blood glucose levels are in the target range from 2 to 6 ( £ 40 ) , reducing the number of daily injections from 3 to 1 ( £ 39 ) , and avoiding nighttime hypoglycemia ( £ 33 ) . In participants with T2DM , similar factors had the highest WTP . CONCLUSIONS This is the first study to assess WTP for long-acting insulin therapy and could have implication s for future guidelines on diabetes management , however some limitations , notably in sample selection , could affect generalizability of the results . In both T1DM and T2DM , the highest WTP values were for avoidance of weight gain , and reduction in the number of injections and hypoglycemia"
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BACKGROUND Patients with chronic heart failure ( heart failure ) are at risk of thromboembolic events , including stroke , pulmonary embolism and peripheral arterial embolism , whilst coronary ischaemic events also contribute to the progression of heart failure . Long-term oral anticoagulation is established in certain patient groups , including patients with heart failure and atrial fibrillation , but there is wide variation in the indications and use of oral anticoagulation in the broader heart failure population . OBJECTIVES To determine whether long-term oral anticoagulation reduces total deaths , cardiovascular deaths and major thromboembolic events in patients with heart failure . SEARCH METHODS We up date d the search es in June 2030 in the electronic data bases CENTRAL ( Issue 6 , 2013 ) in The Cochrane Library , MEDLINE ( OVID , 1946 to June week 1 2013 ) and EMBASE ( OVID , 1980 to 2013 week 23 ) . Reference lists of papers and abstract s from national and international cardiovascular meetings were studied to identify unpublished studies . Relevant authors were contacted to obtain further data . No language restrictions were applied . SELECTION CRITERIA R and omised controlled trials ( RCTs ) comparing oral anticoagulants with placebo in adults with heart failure , and with treatment duration at least one month . Non-r and omised studies were also included for assessing side effects . Inclusion decisions were made in duplicate and any disagreement between review authors was resolved by discussion or a third party . DATA COLLECTION AND ANALYSIS Two review authors independently assessed trials for inclusion and assessed the risks and benefits of antithrombotic therapy using relative measures of effects , such as odds ratio , accompanied by the 95 % confidence intervals . MAIN RESULTS Two RCTs were identified . One compared warfarin , aspirin and no antithrombotic therapy and the second compared warfarin with placebo in patients with idiopathic dilated cardiomyopathy . Three small prospect i ve controlled studies of warfarin in heart failure were also identified , but they were over 50 years old with methods not considered reliable by modern st and ards . In both WASH 2004 and HELAS 2006 , there were no significant differences in the incidence of myocardial infa rct ion , non-fatal stroke and death between patients taking oral anticoagulation and those taking placebo . Four retrospective non-r and omised cohort analyses and four observational studies of oral anticoagulation in heart failure included differing population s of heart failure patients and reported contradictory results . AUTHORS ' CONCLUSIONS Based on the two major r and omised trials ( HELAS 2006 ; WASH 2004 ) , there is no convincing evidence that oral anticoagulant therapy modifies mortality or vascular events in patients with heart failure and sinus rhythm . Although oral anticoagulation is indicated in certain groups of patients with heart failure ( for example those with atrial fibrillation ) , the available data does not support the routine use of anticoagulation in heart failure patients who remain in sinus rhythm
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"Background — Chronic heart failure remains a major cause of mortality and morbidity . The role of antithrombotic therapy in patients with chronic heart failure has long been debated . The objective of this study was to determine the optimal antithrombotic agent for heart failure patients with reduced ejection fractions who are in sinus rhythm . Methods and Results — This prospect i ve , r and omized clinical trial of open-label warfarin ( target international normalized ratio of 2.5 to 3.0 ) and double-blind treatment with either aspirin ( 162 mg once daily ) or clopidogrel ( 75 mg once daily ) had a 30-month enrollment period and a minimum of 12 months of treatment . We enrolled 1587 men and women ≥18 years of age with symptomatic heart failure for at least 3 months who were in sinus rhythm and had left ventricular ejection fraction of ≤35 % . The primary outcome was the time to first occurrence of death , nonfatal myocardial infa rct ion , or nonfatal stroke . For the primary composite end point , the hazard ratios were as follows : for warfarin versus aspirin , 0.98 ( 95 % CI , 0.86 to 1.12 ; P=0.77 ) ; for clopidogrel versus aspirin , 1.08 ( 95 % CI , 0.83 to 1.40 ; P=0.57 ) ; and for warfarin versus clopidogrel , 0.89 ( 95 % CI , 0.68 to 1.16 ; P=0.39 ) . Warfarin was associated with fewer nonfatal strokes than aspirin or clopidogrel . Hospitalization for worsening heart failure occurred in 116 ( 22.2 % ) , 97 ( 18.5 % ) , and 89 ( 16.5 % ) patients treated with aspirin , clopidogrel , and warfarin , respectively ( P=0.02 for warfarin versus aspirin ) . Conclusion — The primary outcome measure and the mortality data do not support the primary hypotheses that warfarin is superior to aspirin and that clopidogrel is superior to aspirin ",
"PURPOSE To determine the incidence of major bleeding in out patients treated with warfarin and to identify predictive factors known at the start of therapy . PATIENTS AND METHODS The records of 565 patients starting outpatient therapy with warfarin upon discharge from a university hospital were review ed . Follow-up information was obtained for 562 patients ( 99.5 % ) . Bleeding was classified as major or minor using explicit criteria . The cumulative incidence of bleeding was estimated by means of survival analysis . Independent risk factors for major bleeding were identified using Cox regression analysis in 375 r and omly chosen patients ; they were tested in the remaining 187 patients . RESULTS Major bleeding occurred in 65 patients ( 12 % ) and was fatal in 10 patients ( 2 % ) . The cumulative incidences of major bleeding at one , 12 , and 48 months were 3 % , 11 % , and 22 % , respectively . The monthly risk of major bleeding decreased over time , from 3 % during the first month of outpatient therapy to 0.3 % per month after the first year of therapy . Five independent risk factors for major bleeding -- age 65 years or greater , history of stroke , history of gastrointestinal bleeding , a serious comorbid condition ( recent myocardial infa rct ion , renal insufficiency , or severe anemia ) , atrial fibrillation -- predicted major bleeding in the testing group ; the cumulative incidence of major bleeding at 48 months was 2 % in 57 low-risk patients , 17 % in 110 middle-risk patients , and 63 % in 20 high-risk patients . CONCLUSION These findings provide a quantitative basis for evaluating the risk of major bleeding in individual patients at the start of outpatient therapy with warfarin . Whether the risk of bleeding can be reduced in high-risk patients without reducing the benefit of therapy remains to be determined",
"OBJECTIVES We sought to evaluate the relation between warfarin anticoagulation and survival and morbidity from cardiac disease in patients with left ventricular ( LV ) dysfunction . BACKGROUND Warfarin anticoagulation plays a major role in the management of patients who have had a large myocardial infa rct ion and in those with atrial fibrillation . However , its use in patients with LV systolic dysfunction has been controversial . METHODS We review ed data on warfarin use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction ( SOLVD ) trial and analyzed the relation between warfarin use and all-cause mortality , as well as the combined end point of death or hospital admission for heart failure . We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between warfarin use and selected patient variables in relation to outcome . RESULTS On multivariate analysis , use of warfarin was associated with a significant reduction in all-cause mortality ( adjusted hazard ratio [ HR ] 0.76 , 95 % confidence interval [ CI ] 0.65 to 0.89 , p = 0.0006 ) and in the risk of death or hospital admission for heart failure ( HR 0.82 , 95 % CI 0.72 to 0.93 , p = 0.0002 ) . Risk reduction was observed when each trial or r and omization arm was analyzed separately , as well as in both genders . It was not significantly influenced by the presence of atrial fibrillation , age , ejection fraction , New York Heart Association functional class or etiology . CONCLUSIONS In patients with LV systolic dysfunction , warfarin use is associated with improved survival and reduced morbidity . This association is primarily due to a reduction in cardiac events and does not appear to be limited to any particular subgroup",
"Background Atrial fibrillation in the absence of rheumatic valvular disease is associated with a fivefold to sevenfold increased risk of ischemic stroke . Methods and Main Results . The Stroke Prevention in Atrial Fibrillation Study , a multicenter , r and omized trial , compared 325 mg/day aspirin ( double-blind ) or warfarin with placebo for prevention of ischemic stroke and systemic embolism ( primary events ) , and included 1,330 in patients and out patients with constant or intermittent atrial fibrillation . During a mean follow-up of 1.3 years , the rate of primary events in patients assigned to placebo was 6.3 % per year and was reduced by 42 % in those assigned to aspirin ( 3.6 % per year , p = 0.02 ; 95 % confidence interval , 9–63 % ) . In the subgroup of warfarin-eligible patients ( most less than 76 years old ) , warfarin dose-adjusted to prolong prothrombin time to 1.3-fold to 1.8-fold that of control reduced the risk of primary events by 67 % ( warfarin versus placebo , 2.3 % versus 7.4 % per year , p = 0.01 ; 95 % confidence interval , 27–85 % ) . Primary events or death were reduced 58 % ( p = 0.01 ) by warfarin and 32 % ( p = 0.02 ) by aspirin . The risk of significant bleeding was 1.5 % , 1.4 % , and 1.6%o per year in patients assigned to warfarin , aspirin , and placebo , respectively . Conclusions Aspirin and warfarin are both effective in reducing ischemic stroke and systemic embolism in patients with atrial fibrillation . Because warfarin-eligible patients composed a subset of all aspirin-eligible patients , the magnitude of reduction in events by warfarin versus aspirin can not be compared . Too few events occurred in warfarin-eligible patients to directly assess the relative benefit of aspirin compared with warfarin , and the trial is continuing to address this issue . Patients with nonrheumatic atrial fibrillation who can safely take either aspirin or warfarin should receive prophylactic antithrombotic therapy to reduce the risk of stroke",
"To evaluate the influence of the angiotensin-converting enzyme inhibitor , enalapril ( 2.5 to 40 mg/day ) , on the prognosis of severe congestive heart failure , defined as New York Heart Association functional class IV , a double-blind study was undertaken in which 253 patients were r and omized to receive either placebo ( n = 126 ) or enalapril ( n = 127 ) in addition to conventional treatment , including vasodilators . Follow-up averaged 188 days ( range 1 day to 20 months ) . The reduction in crude mortality within 6 months ( primary objective ) was 40 % in the enalapril-treated group ( from 44 to 26 % , p = 0.002 ) and within 1 year 31 % ( p = 0.001 ) . By the end of the study , 68 subjects in the placebo group and 50 in the enalapril group had died -- a reduction of 27 % ( p = 0.003 ) . The entire reduction in total mortality ( 50 % ) was found in patients dying from progressive heart failure , whereas no difference was seen in the incidence of sudden cardiac death . There was a significant improvement in New York Heart Association classification in the enalapril group , together with a reduction in heart size and a reduced requirement for other heart failure medication . It is concluded that the addition of enalapril to conventional therapy in patients with severe congestive heart failure can reduce mortality and improve symptoms . The effect seems to be due to a reduction in death from progression of heart failure",
"BACKGROUND Heart failure is commonly associated with vascular disease and a high rate of athero-thrombotic events , but the risks and benefits of antithrombotic therapy are unknown . METHODS The current study was an open-label , r and omized , controlled trial comparing no antithrombotic therapy , aspirin ( 300 mg/day ) , and warfarin ( target international normalized ratio 2.5 ) in patients with heart failure and left ventricular systolic dysfunction requiring diuretic therapy . The primary objective was to demonstrate the feasibility and inform the design of a larger outcome study . The primary clinical outcome was death , nonfatal myocardial infa rct ion , or nonfatal stroke . RESULTS Two hundred seventy-nine patients were r and omized and 627 patient-years exposure were accumulated over a mean follow-up time of 27 + /- 1 months . Twenty-six ( 26 % ) , 29 ( 32 % ) , and 23 ( 26 % ) patients r and omized to no antithrombotic treatment , aspirin , and warfarin , respectively , reached the primary outcome ( ns ) . There were trends to a worse outcome among those r and omized to aspirin for a number of secondary outcomes . Significantly ( P = .044 ) more patients r and omized to aspirin were hospitalized for cardiovascular reasons , especially worsening heart failure . CONCLUSIONS The Warfarin/Aspirin Study in Heart failure ( WASH ) provides no evidence that aspirin is effective or safe in patients with heart failure . The benefits of warfarin for patients with heart failure in sinus rhythm have not been established . Antithrombotic therapy in patients with heart failure is not evidence based but commonly contributes to polypharmacy",
"BACKGROUND In patients who have had a myocardial infa rct ion , the long-term risk of stroke and its relation to the extent of left ventricular dysfunction have not been determined . We studied whether a reduced left ventricular ejection fraction is associated with an increased risk of stroke after myocardial infa rct ion and whether other factors such as older age and therapy with anticoagulants , thrombolytic agents , or captopril affect long-term rates of stroke . METHODS We performed an observational analysis of prospect ively collected data on 2231 patients who had left ventricular dysfunction after acute myocardial infa rct ion who were enrolled in the Survival and Ventricular Enlargement trial . The mean follow-up was 42 months . Risk factors for stroke were assessed by both univariate and multivariate Cox proportional-hazards analysis . RESULTS Among these patients , 103 ( 4.6 percent ) had fatal or nonfatal strokes during the study ( rate of stroke per year of follow-up , 1.5 percent ) . The estimated five-year rate of stroke in all the patients was 8.1 percent . As compared with patients without stroke , patients with stroke were older ( mean [ + /-SD ] age , 63+/-9 years vs. 59+/-11 years ; P ejection fraction ( for every decrease of 5 percentage points in the ejection fraction there was an 18 percent increase in the risk of stroke ) , older age , and the absence of aspirin or anticoagulant therapy . Patients with ejection fractions of relative risk of stroke of 1.86 , as compared with patients with ejection fractions of more than 35 percent ( P=0.01 ) . The use of thrombolytic agents and captopril had no significant effect on the risk of stroke . CONCLUSIONS During the five years after myocardial infa rct ion , patients have a substantial risk of stroke . A decreased ejection fraction and older age are both independent predictors of an increased risk of stroke . Anticoagulant therapy appears to have a protective effect against stroke after myocardial infa rct ion",
"Background The incidence of thromboembolism and the benefit of anticoagulation in congestive heart failure are controversial . Methods and Results The data base provided by the Veterans Affairs Vasodilator-Heart Failure Trials ( V-HeFT I and II ) was examined retrospectively to address these issues . In V-HeFT I , 642 men with heart failure were followed an average of 2.28 years , providing 1,464 patient-years of follow-up . In V-HeFT II , 804 men were followed an average of 2.56 years , with 2,061 patient-years of follow-up . Mean left ventricular ejection fraction was 30%o in V-HeFT I and 29 % in V-HeFT II . Functional capacity was at the interface of classes II and III with a peak exercise oxygen consumption of 14.7 mL. kg -1 . min-1 in V-HeFT I and 13.7 mL- kg-1 min-1 in V-HeFT II . Warfarin and antiplatelet agents were administered at the discretion of individual investigators . The incidence of all thromboembolic events during 1,068 patient-years without warfarin in V-HeFIT I was 2.7/100 patient-years and during 1,188 patient-years in V-HeFT II was 2.1/100 patient-years and was not reduced in patients treated with warfarin . Patients experiencing events had a lower peak exercise oxygen consumption ( P mean ejection fraction ( P=0.10 in V-HeFT I and P=0.07 in V-HeFT II ) . Atrial fibrillation was not associated with an increased risk of thromboembolic events . Conclusions The incidence of thromboembolism and stroke in class II or III congestive heart failure is not high and may not be significantly reduced with warfarin treatment . Routine use of anticoagulants in patients with heart failure may not be justified",
"BACKGROUND In patients with congestive heart failure ( CHF ) , clinical trials have demonstrated the benefit of a number of drugs on morbidity and mortality . Nevertheless so far , there is no published controlled study of long-term antithrombotic therapy in patients with CHF . The aim of this work was to identify the relationship between cardiovascular drug use , especially antithrombotic therapy , and survival of CHF patients in current clinical practice , using an observational , population -based data base . METHODS The EPICAL study ( Epidémiologie de l'Insuffisance Cardiaque Avancée en Lorraine ) has identified prospect ively all patients with severe CHF in the community of Lorraine . Inclusion criteria were age 20 - 80 years in 1994 , at least one hospitalisation for cardiac decompensation , NYHA III/IV HF , ventricular ejection fraction or = 60 % and arterial hypotension or peripheral and /or pulmonary oedema . A total of 417 consecutive patients surviving at hospital discharge were included in the data base . The average follow-up period was 5 years . Univariate Cox models were used to test the relationship of baseline biological and clinical factors to survival . Cardiovascular drug prescriptions were tested in a multivariate Cox model adjusted by other known predictive factors . RESULTS Duration of disease > 1 year , renal failure , serum sodium > or = 138 mmol/l , old age , serious comorbidity , previous decompensation , high doses of furosemide and vasodilators use were independently associated with poor prognosis at 1 and 5 years . Oral anticoagulants , aspirin , lipid lowering drugs and beta-blockers use were associated with better survival . There was no interaction between aspirin and angiotensin converting enzyme inhibitor use on survival . CONCLUSION Antithrombotic therapy was associated with a better long-term survival in our study population of severe CHF . These results together with other previously published circumstantial evidence urge for a prospect i ve , controlled and r and omised trial specifically design ed to evaluate optimal oral anticoagulants and aspirin in patients with congestive heart failure",
"BACKGROUND Nonrheumatic atrial fibrillation increases the risk of stroke , presumably from atrial thromboemboli . There is uncertainty about the efficacy and risks of long-term warfarin therapy to prevent stroke . METHODS We conducted an unblinded , r and omized , controlled trial of long-term , low-dose warfarin therapy ( target prothrombin-time ratio , 1.2 to 1.5 ) in patients with nonrheumatic atrial fibrillation . The control group was not given warfarin but could choose to take aspirin . RESULTS A total of 420 patients entered the trial ( 212 in the warfarin group and 208 in the control group ) and were followed for an average of 2.2 years . Prothrombin times in the warfarin group were in the target range 83 percent of the time . Only 10 percent of the patients assigned to receive warfarin discontinued the drug permanently . There were 2 strokes in the warfarin group ( incidence , 0.41 percent per year ) as compared with 13 strokes in the control group ( incidence , 2.98 percent per year ) , for a reduction of 86 percent in the risk of stroke ( warfarin : control incidence ratio = 0.14 ; 95 percent confidence interval , 0.04 to 0.49 ; P = 0.0022 ) . There were 37 deaths altogether . The death rate was markedly lower in the warfarin group than in the control group : 2.25 percent as compared with 5.97 percent per year , for an incidence ratio of 0.38 ( 95 percent confidence interval , 0.17 to 0.82 ; P = 0.005 ) . There was one fatal hemorrhage in each group . The frequency of bleeding events that led to hospitalization or transfusion was essentially the same in both groups . The warfarin group had a higher rate of minor hemorrhage than the control group ( 38 vs. 21 patients ) . CONCLUSIONS Long-term low-dose warfarin therapy is highly effective in preventing stroke in patients with non-rheumatic atrial fibrillation , and can be quite safe with careful monitoring",
" From November , 1985 , to June , 1988 , 1007 out patients with chronic non-rheumatic atrial fibrillation ( AF ) entered a r and omised trial ; 335 received anticoagulation with warfarin openly , and in a double-blind study 336 received aspirin 75 mg once daily and 336 placebo . Each patient was followed up for 2 years or until termination of the trial . The primary endpoint was a thromboembolic complication ( stroke , transient cerebral ischaemic attack , or embolic complications to the viscera and extremities ) . The secondary endpoint was death . The incidence of thromboembolic complications and vascular mortality were significantly lower in the warfarin group than in the aspirin and placebo groups , which did not differ significantly . 5 patients on warfarin had thromboembolic complications compared with 20 patients on aspirin and 21 on placebo . 21 patients on warfarin were withdrawn because of non-fatal bleeding complications compared with 2 on aspirin and none on placebo . Thus , anticoagulation therapy with warfarin can be recommended to prevent thromboembolic complications in patients with chronic non-rheumatic AF",
"BACKGROUND It is not clear if long-term antithrombotic treatment has a beneficial effect on the incidence of thromboembolism in chronic heart failure ( CHF ) . The HELAS study ( Heart failure Long-term Antithrombotic Study ) is a multicentre , r and omised , double-blind , placebo-controlled trial to evaluate antithrombotic treatment in patients with CHF . METHODS 197HF patients ( EF were r and omised to receive either aspirin 325 mg or warfarin . Patients with Dilated Cardiomyopathy ( DCM ) were r and omised to receive either warfarin or placebo . RESULTS Analysis of the data from 312 patient years showed an incidence of 2.2 embolic events per 100 patient years , with no significant difference between groups . The incidence of myocardial infa rct ion , hospitalisation , exacerbation of heart failure , death and haemorrhage were not different between the groups . No peripheral or pulmonary emboli were reported . Echocardiographic follow-up for 2years showed an overall increase in left ventricular ejection fraction from 28.2+/-6 to 30.3+/-7 p warfarin ( EF 26.8+/-5.3 at baseline , 30.7+/-10 at 2 years , p embolic events are rare in heart failure regardless of treatment . ( 2 ) Treatment does not seem to affect outcome"
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41179d76-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND We review ed systematic ally the results of genetic studies investigating associations between putative susceptibility genes for attention-deficit hyperactivity disorder ( ADHD ) and neuropsychological traits relevant for this disorder . METHODS We identified papers for review through the PubMed data base . RESULTS Twenty-nine studies examined 10 genes ( DRD4 , DAT1 , COMT , DBH , MAOA , DRD5 , ADRA2A , GRIN2A , BDNF and TPH2 ) in relation to neuropsychological traits relevant for ADHD . For DRD4 , the continuous performance test ( CPT ) and derived tasks were the most used tests . Association of high reaction time variability with the 7-repeat allele absence appears to be the most consistent result and seems to be specific to ADHD . Speed of processing , set-shifting and cognitive impulsiveness were less frequently investigated but seem to be altered in the 7-repeat allele carriers . No effect of genotype was found on response inhibition ( the stop and go/no-go tasks ) . For DAT1 , 4 studies provide conflicting results in relation to omission and commission errors from CPT and derived tasks . High reaction time variability seems to be the most replicated cognitive marker associated with the 10-repeat homozygosity . The other genes have attracted fewer studies , and the reported findings need to be replicated . LIMITATIONS Although we aim ed to perform a formal meta- analysis , this was not possible because the number of studies using the same neurocognitive endophenotypes was limited . We referred only minimally to the various theoretical frameworks in this field of research ; more detail would have been beyond the scope of our systematic review . Finally , sample sizes in most of the studies we review ed were small . Thus , some negative findings could be attributed to a lack of statistical power , and positive results should be considered preliminary until they are replicated in extended sample s. CONCLUSION Several method ological issues , including measurement errors , developmental changes in cognitive abilities , sex , psychostimulant effects and presence of comorbid conditions , represent confounding factors and may explain conflicting results
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"Predictions concerning development , interrelations , and possible independence of working memory , inhibition , and cognitive flexibility were tested in 325 participants ( roughly 30 per age from 4 to 13 years and young adults ; 50 % female ) . All were tested on the same computerized battery , design ed to manipulate memory and inhibition independently and together , in steady state ( single-task blocks ) and during task-switching , and to be appropriate over the lifespan and for neuroimaging ( fMRI ) . This is one of the first studies , in children or adults , to explore : ( a ) how memory requirements interact with spatial compatibility and ( b ) spatial incompatibility effects both with stimulus-specific rules ( Simon task ) and with higher-level , conceptual rules . Even the youngest children could hold information in mind , inhibit a dominant response , and combine those as long as the inhibition required was steady-state and the rules remained constant . Cognitive flexibility ( switching between rules ) , even with memory dem and s minimized , showed a longer developmental progression , with 13-year-olds still not at adult levels . Effects elicited only in Mixed blocks with adults were found in young children even in single-task blocks ; while young children could exercise inhibition in steady state it exacted a cost not seen in adults , who ( unlike young children ) seemed to re-set their default response when inhibition of the same tendency was required throughout a block . The costs associated with manipulations of inhibition were greater in young children while the costs associated with increasing memory dem and s were greater in adults . Effects seen only in RT in adults were seen primarily in accuracy in young children . Adults slowed down on difficult trials to preserve accuracy ; but the youngest children were impulsive ; their RT remained more constant but at an accuracy cost on difficult trials . Contrary to our predictions of independence between memory and inhibition , when matched for difficulty RT correlations between these were as high as 0.8 , although accuracy correlations were less than half that . Spatial incompatibility effects and global and local switch costs were evident in children and adults , differing only in size . Other effects ( e.g. , asymmetric switch costs and the interaction of switching rules and switching response-sites ) differed fundamentally over age",
"Attention-deficit/hyperactivity disorder ( ADHD ) is the most common behavioral disorder in childhood with substantial heritability . Pharmacological and molecular genetic studies as well as characterization of animal models have implicated serotonergic dysfunction in the pathophysiology of ADHD . Here , we investigated the effect of polymorphic variants in the gene of the tryptophan hydroxylase-2 ( TPH2 ) , the rate-limiting enzyme of serotonin ( 5-HT ) synthesis in the brain , in children and adolescents with ADHD . We analyzed three single nucleotide polymorphisms ( SNPs ) in and downstream of the transcriptional control region of the TPH2 gene in 103 families with 225 affected children . Allelic association in families with more than one affected child was assessed using the pedigree disequilibrium test . Preferential transmissions were detected for the two SNPs in TPH2 's regulatory region ( rs4570625 , P=0.049 ; rs11178997 , P=0.034 ) , but not for the third SNP in intron 2 ( rs4565946 , P=0.3517 ) . Haplotype analysis revealed a strong trend of association between the regulatory region SNPs ( rs4570625 , rs11178997 ) and ADHD ( P=0.064 ) . Our results link potentially functional TPH2 variations to the pathophysiology of ADHD , and further support the relevance of 5-HT in disorders related to altered motor activity and cognitive processes",
"Performance on the covert visuo-spatial attentional functions of orienting and focusing by a group of ADHD children ( n = 20 ) was compared to that of age and sex-matched control children . In Experiment 1 , responses were given to cued targets at valid and invalid locations . In Experiment 2 , responses were given to targets presented in small , medium-sized or large visual field locations . For both experiments , the hypotheses that reaction times of ADHD children would be greater than those of control children and that performance would be asymmetrical , were supported . For Experiment 1 , ADHD children showed bilaterally greater ' benefits ' from having directed attention to the cued location and greater ' costs ' in having to relocate the attentional focus than controls . In Experiment 2 , the hypothesis that the function of focusing attention by ADHD children may show breakdown in the usual pattern of an increase in reaction time with focus area was partly supported by the finding of similar reaction times to targets presented in medium-sized and large regions of the left visual hemifield . These results have been interpreted as reflecting a stronger anchorage of attention by ADHD children upon a cued location and an inability to shift covert attention easily to an alternative location . The breakdown of the focusing function suggests adoption of similar time response sets across focus area size by the more compromised right hemisphere",
"BACKGROUND Active maternal smoking during pregnancy has been associated with a higher risk of behavioural disorders in children , but a few cohort studies measuring smoking data prospect ively have studied its specific effects on the cognitive abilities of pre-schoolers . METHOD A birth cohort was set up in Menorca Isl and in 1997 within the Asthma Multicenter Infants Cohort Study . A total of 420 ( 87 % of those eligible ) children had complete data for final analyses at age 4 years . Interviewer-administered question naires were completed by mothers during the third trimester of pregnancy and then every year up to age 4 years of their child . A st and ardized version of the McCarthy Scales of Children 's Abilities ( MCSA ) was used to evaluate the child 's motor and cognitive capabilities . Multivariable regressions were used with MCSA 's assessed outcomes adjusting for : home location , maternal alcohol consumption , mother 's social class and level of education during pregnancy , parity , marital status , father 's education level , child 's gender , birth weight and height , breastfeeding duration , passive smoking , school season , age during test administration and evaluator ( psychologist ) . RESULTS A high global consistency in maternal smoking habits was found ( total agreement = 88.7 % ) . Maternal social class and education level were inversely associated with maternal smoking behaviour . Maternal smoking during pregnancy ( in cig./day ) was associated with a decrease ( in points ) of children 's global cognitive score [ beta = -0.60 , ( 95 % CI : -1.10 ; -0.09 ) ] ; as well as global cognitive sub- areas like verbal score [ beta = -0.59 , ( 95 % CI : -1.11 ; -0.07 ) ] ; quantitative score [ beta = -0.57 , ( 95 % CI : -1.08 ; -0.06 ) ] ; executive function score [ beta = -0.71 , ( 95 % CI : -1.23 ; -0.20 ) ] ; and working memory score [ beta = -0.46 , ( 95 % CI : -0.92 ; -0.01 ) ] . CONCLUSION Our findings suggest an association with maternal smoking during pregnancy and lowered cognitive development in children at age 4 years",
"Background Current efforts to study the genetics of higher functions have been lacking appropriate phenotypes to describe cognition . One of the problems is that many cognitive concepts for which there is a single word ( e.g. attention ) have been shown to be related to several anatomical networks . Recently we have developed an Attention Network Test ( ANT ) that provides a separate measure for each of three anatomically defined attention networks . In this small scale study , we ran 26 pairs of MZ and DZ twins in an effort to determine if any of these networks show sufficient evidence of heritability to warrant further exploration of their genetic basis . Results The efficiency of the executive attention network , that mediates stimulus and response conflict , shows sufficient heritability to warrant further study . Alerting and overall reaction time show some evidence for heritability and in our study the orienting network shows no evidence of heritability . Conclusions These results suggest that genetic variation contributes to normal individual differences in higher order executive attention involving dopamine rich frontal areas including the anterior cingulate . At least the executive portion of the ANT may serve as a valid endophenotype for larger twin studies and subsequent molecular genetic analysis in normal subject population",
"OBJECTIVE This paper examines whether dopamine transporter gene ( DAT1 ) allele status mediates medication-related change in cognitive and neurophysiological measures among children with attention-deficiency/hyperactivity disorder ( ADHD ) . METHOD A single 10-mg dose of methylpheni date was given in a double-blind , placebo-controlled fashion to children with ADHD who were seen for cognitive testing and EEG recording . Buccal sample s were obtained and genotyped for the DAT1 polymorphism . RESULTS DAT1 allele status was associated with performance on a sustained attention task and medication-related EEG changes . Compared with those with one or more copies of the DAT1 9-repeat allele ( 9R ) , children with two copies of the 10-repeat allele ( 10R ) exhibited poorer performance on the vigilance task . In addition , children with 10R exhibited medication-related EEG changes of increased central and parietal beta power , decreased right frontal theta power , and lower theta/beta ratios ; 9R carriers showed the opposite pattern . CONCLUSIONS The data suggest that the DAT1 polymorphism mediates medication-related changes in cortical activity among children with ADHD",
"Publisher Summary Ultrastructural subcellular studies indicate that most of the dopamine transporter ( DAT ) protein in striatal dopamine axons is distributed at the periphery of synapses and at nonsynaptic membrane sites . The extensive distribution of the DAT protein is likely to greatly restrict the extracellular diffusion of dopamine in this brain region . Several neurochemical observations suggest that extracellular dopamine in the prelimbic division , or prefrontal cortex ( PFC ) , undergoes less regulation by DAT-mediated uptake , compared with the striatum . Relative to total tissue content , extracellular dopamine levels are 20 times higher in the PFC than in the striatum . The electron microscopic results from six rats with the best morphology and most robust staining with the rat antibody were quantified in the experiment demonstrated in this chapter . One to two tissue sections per region per animal were examined , and the surface of the tissue was sample d at r and om until at least 40 DAT-immunoreactive processes were photographed . Processes were then numbered on the micrographs from upper left to lower right , and a r and om number generator was used to select 30 processes per region per animal . The processes were then traced using an image analysis system , which calculated their maximum diameter along the short axis . By electron microscopic examination of the dorsolateral striatum , peroxidase immunoreactivity for DAT was abundantly expressed in axon varicosities , some of which made punctate symmetric synapses on spines or distal dendrites",
"The usual approach for using single base pair polymorphisms ( SNPs ) for the investigation of the genetics of behavioral disorders is to examine a single diagnostic syndrome or personality trait based on variables relating to a cluster of behavioral symptoms . However , since some of these variables may address behaviors that are associated with one allele while others are associated with the other allele , the overall association may be non‐significant and significant sub‐syndromal associations may be missed . Thus , we have reversed the process in a technique we term a “ line item ” approach . As a test of the technique we have examined the association between genotypes of a C‐ > G‐1291 Msp I promotor SNP of the ADRA2A gene and 390 individual symptoms from a structured review of DSM‐IV criteria for twelve different groups of symptoms . We examined 334 individuals consisting of controls and subjects with Tourette syndrome ( TS ) . Based on the mean scores for each genotype , those symptoms that were individually significant at α ≤ 0.05 fell into three major groups by mode of inheritance : allele 1 codominant ( 11 > 12 > 22 ) , allele 2 codominant ( 22 > 12 > 11 ) , and negative heterosis ( 12 number of symptoms that were significant for the twelve symptom clusters was compared by chi‐square analysis . This showed that symptoms were drawn from the diagnostic groups in a significantly non‐r and om fashion . Thus , the allele 1 codominant symptoms came from the anxiety , affective , schizoid , and somatization diagnostic groups ( internalizing symptoms ) ( χ2 = 80.0 , d.f . = 11 , P ≤ 0.0000001 ) , while the allele 2 codominant symptoms came from the ADHD and oppositional defiant/conduct disorder diagnostic groups ( externalizing symptoms ) ( χ2 = 81.0 , d.f . = 11 , P ≤ 0.0000001 ) . The questions that fell in the negative heterosis type of inheritance were not significantly associated with specific diagnostic groups ( P = 0.87 ) . These results showed that the ADRA2A gene was associated with symptoms of autonomic , sympathetic dysfunction from different diagnostic groups . The advantages of the “ line item ” approach include ( a ) the identification of the symptoms associated with each allele , ( b ) the identification of symptom clusters independent of DSM diagnoses , ( c ) the elucidation of heterosis and other mode of inheritance effects , ( d ) the distinction between an association with a primary disorder versus a comorbid disorder , ( e ) the identification of associations with sub‐syndromal symptom clusters that do meet full DSM‐IV criteria , and ( f ) the identification of symptom clusters across data bases . © 2003 Wiley‐Liss ,",
"Many genetic studies have demonstrated an association between the 7‐repeat ( 7r ) allele of a 48‐base pair variable number of t and em repeats ( VNTR ) in exon 3 of the DRD4 gene and the phenotype of attention deficit hyperactivity disorder ( ADHD ) . Previous studies have shown inconsistent associations between the 7r allele and neurocognitive performance in children with ADHD . We investigated the performance of 128 children with and without ADHD on the Fixed and R and om versions of the Sustained Attention to Response Task ( SART ) . We employed time‐series analyses of reaction‐time data to allow a fine‐grained analysis of reaction time variability , a c and i date endophenotype for ADHD . Children were grouped into either the 7r‐present group ( possessing at least one copy of the 7r allele ) or the 7r‐absent group . The ADHD group made significantly more commission errors and was significantly more variable in RT in terms of fast moment‐to‐moment variability than the control group , but no effect of genotype was found on these measures . Children with ADHD without the 7r allele made significantly more omission errors , were significantly more variable in the slow frequency domain and showed less sensitivity to the signal ( d ' ) than those children with ADHD the 7r and control children with or without the 7r . These results highlight the utility of time‐series analyses of reaction time data for delineating the neuropsychological deficits associated with ADHD and the DRD4 VNTR . Absence of the 7‐repeat allele in children with ADHD is associated with a neurocognitive profile of drifting sustained attention that gives rise to variable and inconsistent performance . © 2008 Wiley‐Liss ,",
"ADHD is a childhood-onset behavioural disorder with a heterogeneous profile of neuropsychological impairment . Neuropsychological heterogeneity may , in part , reflect underlying genetic differences . Here we examined sustained attention , response variability and spatial attentional asymmetries in a sample of children and adolescents with ADHD ( n=22 ) in relation to dopamine transporter genotype ( DAT1 ) and also controls ( n=20 ) . Participants performed the sustained attention to response task ( SART ) ( testing sustained attention and response variability ) and the greyscales task ( a perceptual measure of attentional bias ) . The latter has previously been shown to yield a robust leftward attentional asymmetry in healthy subjects . The 10-repeat allele of the DAT1 gene has been associated with ADHD in a number of studies and appears to have biological significance . The ADHD group was sub-divided into those individuals with two copies of the \" high-risk \" 10-repeat allele ( high-risk DAT1 ) versus those with one or no copies of this allele ( low-risk DAT1 ) . The high-risk DAT1 ADHD group displayed greater response variability on the SART than either the low-risk DAT1 group or healthy controls , whereas the latter two groups did not differ . Further , the high-risk DAT1 group showed an attenuated spatial asymmetry , relative to the low-risk DAT1 ADHD group , who showed the typical leftward attentional asymmetry . Our results suggest that the 10-repeat DAT1 allele may mediate neuropsychological impairment in ADHD . The application of molecular genetics may help to define neuropsychological impaired subgroups of ADHD",
"Attention-deficit hyperactivity disorder ( ADHD ) is a heritable disorder , prevalent from childhood through adulthood . Although the noradrenergic ( NA ) system is thought to mediate a portion of the pathophysiology of ADHD , genes in this pathway have not been investigated as frequently as those in the dopaminergic system . Previous association studies of one c and i date gene in the NA system , ADRA2A , showed inconsistent results with regard to an MspI polymorphism . In the current study , two nearby single-nucleotide polymorphisms , which define HhaI and DraI restriction fragment length polymorphisms , were also genotyped and were in significant linkage disequilibrium with the MspI RFLP . Transmission disequilibrium tests ( TDTs ) in a sample of 177 nuclear families showed significant association and linkage of the DraI polymorphism with the ADHD combined subtype ( P=0.03 ) , and the quantitative TDT showed association of this polymorphism with the inattentive ( P=0.003 ) and hyperactive-impulsive ( P=0.015 ) symptom dimensions . The haplotype that contained the less common allele of the DraI polymorphism likewise showed a strong relationship with the inattentive ( P=0.001 ) and hyperactive-impulsive ( P=0.004 ) symptom dimensions . This study supports the hypothesis that an allele of the ADRA2A gene is associated and linked with the ADHD combined subtype and suggests that the DraI polymorphism of ADRA2A is linked to a causative polymorphism",
"We report three related studies of covert visual spatial orienting in child attention deficit hyperactivity disorder ( ADHD ) . In Study 1 , we examined covert visual spatial orienting in ADHD and comparison boys , Study 2 comprised a dose-response study of methylpheni date for the ADHD group , and Study 3 was an investigation of biological and adoptive parents . In contrast with comparison subjects ( n = 17 ) . ADHD boys aged 6 - 12 ( n = 27 ) showed both slower reaction times overall and within-condition ( lateral ) asymmetries in reaction times . Specifically , boys with ADHD reacted more slowly to uncued targets in the left visual field than in the right visual field . Responses to stimuli in the two visual fields were differentially affected by methylpheni date for the ADHD group . Medication equalized visual field responses to the uncued targets , result ing in a significant cue x dose x visual field interaction . Further , medication altered the relative cue responsivity in the two visual fields , result ing in a significant dose x visual field interaction for the Validity Effect . Biological parents of ADHD boys ( n = 16 ) also showed slower reaction times to uncued left visual field targets than to right visual field targets ; in addition they showed slower response to invalidity cued targets in the right visual field . These literal effects were not observed in adoptive parents of ADHD boys ( n = 12 ) or biological parents of comparison boys ( n = 14 ) . Possible abnormal hemispheric asymmetry of attention functions in boys with ADHD and their biological parents is discussed",
"There has been much interest in the genetics of attention deficit hyperactivity disorder and molecular genetic studies are now underway . The success of genetic studies will depend on how well the phenotype is defined . Twin studies using parent and teacher rated question naires or interviews all appear to yield highly heritable measures . Nevertheless , there is evidence to suggest that parent measures are subject to rater bias . Consequently there has been much interest in obtaining more objective measures of related traits such as attention span and impulsiveness using , computerised neuropsychological tasks . However there have been few twin studies examining the genetic contribution to these neuropsychological measures . The present study aims to investigate whether performance on the Matching Familiar Figures Test ( MFFT ) and Continuous Performance Task ( CPT ) is genetically influenced in childhood . 20 monozygotic ( MZ ) and 20 dizygotic ( DZ ) twin pairs were r and omly selected from the Greater Manchester Twin Register . Preliminary data suggest that MZ twins perform more similarly than DZ twins on the MFFT , but not the CPT . Future work needs to examine whether other neuropsychological measures commonly used in research on ADHD are genetically influenced using larger twin sample",
"Tryptophan hydroxylase ( TPH ) , being the rate-limiting enzyme in the bio synthesis of serotonin plays a major role as c and i date gene in several psychiatric disorders . Recently , a second TPH isoform ( TPH2 ) was identified in mice , which was exclusively present in the brain . In a previous post-mortem study of our own group , we could demonstrate that TPH2 is also expressed in the human brain , but not in peripheral tissues . This is the first report of an association study between polymorphisms in the TPH2 gene and major depression ( MD ) . We performed single-nucleotide polymorphism ( SNP ) , haplotype and linkage disequlibrium studies on 300 depressed patients and 265 healthy controls with 10 SNPs in the TPH2 gene . Significant association was detected between one SNP ( P=0.0012 , global P=0.0051 ) and MD . Haplotype analysis produced additional support for association ( P genetic variants of the TPH2 gene in the pathogenesis of MD and might be a hint on the repeatedly discussed duality of the serotonergic system . These results may open up new research strategies for the analysis of the observed disturbances in the serotonergic system in patients suffering from several other psychiatric disorders",
"The symptoms of attention deficit hyperactivity disorder ( ADHD ) can be treated with methylpheni date ( MPH ) , a potent blocker of dopamine transporter ( DAT ) . The homozygosity of the 10-repeat allele at the DAT gene ( DAT1 ) seems to be associated with a poor response to MPH in children with ADHD . In the present study , we investigated the association between DAT density using I-123-N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl)tropane [123I]IPT single photon emission computed tomography ( SPECT ) ] and the homozygosity for 10-repeat allele at DAT1 and response to MPH in Korean children with ADHD . Eleven drug-naive children with ADHD were included in the study and treated with MPH for about 8 weeks . After the genotyping and SPECT were performed , we compared DAT density between ADHD children with and without the homozygosity for 10-repeat allele at DAT1 and investigated the correlation between the homozygosity for 10-repeat allele and response to MPH . ADHD children with 10/10 genotype ( n=7 ) had a significantly greater increase of the DAT density in basal ganglia than the children without 10/10 genotype ( n=4 ) . We found that while only 28.6 % ( 2/7 ) of the subject with 10/10 genotype showed good response to MPH treatment , 100 % ( 4/4 ) of the subjects without 10/10 genotype showed good response to MPH treatment . Our findings support an association between homozygosity for 10-repeat allele at DAT1 and the DAT density assessed in vivo and correlation between the homozygosity for 10-repeat allele and poor response to MPH"
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BACKGROUND Although the regular consumption of green tea or green tea extract has been considered to improve insulin sensitivity , the reported results are inconsistent . Therefore , we conducted a meta- analysis to evaluate the effect of green tea or green tea extract on insulin sensitivity and glycaemic control in population s at risk of type 2 diabetes mellitus ( T2DM ) . METHODS Electronic data bases , including PUBMED , The Cochrane Library , EMBASE , ISI Web of Knowledge , Chinese Biomedical Literature Data base and Chinese Scientific Journals Fulltext Data base , were systematic ally search ed to identify r and omised controlled trials ( RCTs ) up to December 2011 , supplemented by the Clinical trials.gov websites and the reference lists of identified studies . Two review ers independently selected trials , extracted data , and evaluated the method ological qualities and evidence levels . RESULTS Seven RCTs involving 510 participants were identified . There was no statistically significant difference between green tea or green tea extract group and placebo group with regard to fasting plasma glucose [ st and ardised mean difference ( SMD ) 0.04 ; 95 % confidence interval ( CI ) -0.15 to 0.24 ] , fasting serum insulin ( SMD -0.09 ; 95 % CI -0.30 to 0.11 ) , 2-h plasma glucose in the oral glucose tolerance test ( OGTT-2 h ) ( SMD -0.14 ; 95 % CI -0.63 to 0.34 ) , haemoglobin A₁c ( SMD 0.10 ; 95 % CI -0.13 to 0.33 ) and homeostasis model of insulin resistance ( HOMA(IR ) ) index ( SMD -0.06 ; 95 % CI -0.35 to 0.23 ) in participants at risk of T2DM . CONCLUSIONS The consumption of green tea did not decrease the levels of fasting plasma glucose , fasting serum insulin , OGTT-2 h glucose , haemoglobin A₁c and HOMA(IR ) in population s at risk of T2DM . Larger , longer-term and high- quality RCTs are needed to further definitely determine the effect of green tea or green tea extract on insulin sensitivity and glycaemic control in population s at risk of T2DM
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"Background Green tea is one of the most popular beverages worldwide . This review summarizes the beneficial effects of green tea on cancer prevention . Methods Electronic data bases , including PubMed ( 1966–2008 ) , the Cochrane Library ( Issue 1 , 2008 ) and Chinese Biomedical Data base ( 1978–2008 ) with supplement of relevant websites , were search ed . There was no language restriction . The search es ended at March 2008 . We included r and omized and non-r and omized clinical trials , epidemiological studies ( cohort and case-control ) and a meta- analysis . We excluded case series , case reports , in vitro and animal studies . Outcomes were measured with estimation of relative risk , hazard or odd ratios , with 95 % confidence interval . Results Forty-three epidemiological studies , four r and omized trials and one meta- analysis were identified . The overall quality of these studies was evaluated as good or moderate . While some evidence suggests that green tea has beneficial effects on gastrointestinal cancers , the findings are not consistent . Conclusion Green tea may have beneficial effects on cancer prevention . Further studies such as large and long term cohort studies and clinical trials are warranted",
"BACKGROUND Green tea is one of the most popular beverages in the world . It is believed to have beneficial effects in the prevention and treatment of many diseases , one of which is type 2 diabetes . The aim of the study is to examine the effect of a decaffeinated green tea extract ( GTE ) providing a daily dose of 856 mg of epigallocatechin gallate ( EGCG ) on obese individuals with type 2 diabetes . MATERIAL S AND METHODS The clinical trial was a r and omized , double-blind , placebo-controlled clinical trial conducted from December 2007 through November 2008 . The subjects were r and omly assigned to either receive 1,500 mg of a decaffeinated GTE or placebo daily for 16 weeks . Sixty-eight of 80 subjects , ages 20 - 65 years with BMI > 25 kg/m2 and type 2 diabetes for more than one year , completed this study . Homeostasis model assessment for insulin resistance ( HOMA-IR ) was used as the major outcome measurement . At baseline and after 16 weeks of treatment , anthropometric measurements , fasting glucose , hemoglobin A1C percent ( HbA1C ) , hormone peptides , and plasma lipoproteins were measured from both groups . RESULTS No statistically significant differences were detected between the decaffeinated GTE and placebo groups in any measured variable . A statistically significant within-group 0.4-percent reduction in HbA1C ( from 8.4 to 8.0 % ) was observed after GTE treatment compared to baseline . Within-group comparison also revealed that the GTE group had significant reductions in waist circumference ( WC ) , HOMA-IR index , and insulin level , and a significant increase in the level of ghrelin . Within-group comparison of those in the placebo group showed a significant increase in the level of ghrelin . CONCLUSIONS This study found no statistical difference in any measured variable between the decaffeinated GTE and placebo groups ; however , there were some statistically significant within-group changes detected . More research is required to determine whether a decaffeinated GTE st and ardized for EGCG content will provide any clinical benefits in obese individuals with type 2 diabetes . Clinical Trial Registration NO : NCT00567905",
"Objectives : The development of obesity is characterized by an increase in adipose tissue mass and by concomitant and profound changes in almost all organ functions leading to diseases such as hypertension , diabetes mellitus and coronary heart disease . Recent data from human studies indicate that the consumption of green tea and green tea extracts may help reduce body weight , mainly body fat , by increasing postpr and ial thermogenesis and fat oxidation . However , human studies investigating the metabolic effects of the most predominant tea catechin , EGCG , alone are absent . Methods : In a r and omized double blind , placebo-controlled , cross-over pilot study , six overweight men were given 300 mg EGCG/d for 2d . Fasting and postpr and ial changes in energy expenditure ( EE ) and substrate oxidation were assessed . Results : Resting EE did not differ significantly between EGCG and placebo treatments , although during the first postpr and ial monitoring phase , respiratory quotient ( RQ ) values were significantly lower with EGCG compared to the placebo . Conclusions : These findings suggest that EGCG alone has the potential to increase fat oxidation in men and may thereby contribute to the anti-obesity effects of green tea . However , more studies with a greater sample size and a broader range of age and BMI are needed to define the optimum dose",
"BACKGROUND Increasing coffee intake was inversely associated with risk of type 2 diabetes in population s of European descent ; however , data from high-risk Asian population s are lacking as are data on tea intake in general . OBJECTIVE We investigated the prospect i ve associations between intakes of coffee , black tea , and green tea with the risk of type 2 diabetes in Singaporean Chinese men and women . DESIGN We analyzed data from 36 908 female and male participants in the Singapore Chinese Health Study aged 45 - 74 y in 1993 - 1998 who had multiple diet and lifestyle measures assessed and then were followed up between 1999 and 2004 . We used Cox regression models to investigate the association of baseline coffee and tea intakes with incident type 2 diabetes during follow-up , with adjustment for a number of possible confounding or mediating variables . RESULTS In multivariate models participants reporting > or = 4 cups of coffee/d had a 30 % reduction in risk of diabetes [ relative risk ( RR ) : 0.70 ; 95 % CI : 0.53 , 0.93 ] compared with participants who reported nondaily consumption . Participants reporting > or = 1 cup of black tea/d had a suggestive 14 % reduction in risk of diabetes ( RR : 0.86 ; 95 % CI : 0.74 , 1.00 ) compared with participants who reported 0 cups/d , and we observed no association with green tea . CONCLUSION Regular consumption of coffee and potentially black tea , but not green tea , is associated with lower risk of type 2 diabetes in Asian men and women in Singapore",
"Context Caffeine intake from coffee has been associated with a lower incidence of diabetes . Research ers have not studied the relationship of green tea , a popular beverage in Japan , where the incidence of diabetes is increasing rapidly . Contributions The authors estimated the intake of caffeine-containing beverages in a community-based survey in Japan and measured the 5-year incidence of diabetes . Greater intake of green tea or coffee was associated with a reduced incidence of diabetes . The effect of green tea was largely observed in women , was dose-related , and reflected caffeine intake . Implication s Higher intake of caffeine , whether from coffee or green tea , is associated with a lower incidence of diabetes . The Editors The prevalence of type 2 diabetes has increased worldwide , particularly in Asian countries where it was previously low ( 1 ) . In Japan , population -based studies have shown a 2-fold increase in the prevalence of diabetes during the past 2 decades , from 5 % to 10 % to 10 % to 15 % ( 2 ) . Several cohort studies done in Europe and in the United States reported an association between coffee consumption , a major source of caffeine , and reduced risk for diabetes ( 3 - 7 ) . Although these studies did not show any association between consumption of black tea and the risk for diabetes , they did not examine the effect of green or oolong teas , major sources of caffeine in Asian countries . Consumption of green tea is common in Japan ; 80 % of the population drinks green tea , and the average consumption per capita is 2 cups per day ( 8) . We wanted to determine whether there is a relationship between consumption of green tea and the risk for type 2 diabetes and , if so , whether caffeine fully accounts for this relationship . To examine these questions , we analyzed data from a large cohort study of 19487 middle-aged men and women in 25 communities across Japan . We also examined the effect of age , sex , body mass index ( BMI ) , family history , smoking status , alcohol use , magnesium intake , and physical activity on the association between this mode of caffeine consumption and risk for diabetes . Methods The Japan Collaborative Cohort Study for Evaluation of Cancer Risk ( JACC Study ) started between 1988 and 1990 . A total of 110792 individuals ( 46465 men and 64327 women ) who were 40 to 79 years of age and living in 45 communities across Japan participated in municipal health screening examinations and completed self-administered question naires regarding lifestyle and medical history of cardiovascular disease and cancer ( 9 ) . Informed consent was obtained before the completion of the question naire . Participants from 25 of the 45 communities completed 5-year follow-up surveys . Among 35690 participants ( 15177 men and 20513 women ) who were 40 to 65 years of age at baseline without a history of type 2 diabetes , stroke , coronary heart disease , or cancer , 17413 individuals ( 49 % ; 6727 men and 10686 women ) completed the 5-year follow-up question naire and provided valid responses on tea or coffee consumption and history of type 2 diabetes . The data from these 17413 individuals were used for the analyses . The mean age of the nonrespondents was 1 year younger for men ( 52.3 vs. 53.3 years of age ) and did not differ for women ( 53.1 vs. 53.0 years of age ) compared with the respondents . The mean BMI and the prevalence of a BMI of 25.0 kg/m2 or greater did not differ between the respondents and nonrespondents . Mean BMI was 22.7 kg/m2 versus 22.8 kg/m2 for men and 22.8 kg/m2 versus 22.9 kg/m2 for women , respectively ; the prevalence of overweight was 18 % versus 19 % for men and 21 % versus 22 % for women , respectively . The ethical committees at Nagoya University and the University of Tsukuba approved the study . Assessment of Consumption of Tea and Coffee and Caffeine Intake At baseline , consumption of tea and coffee was assessed by using a self-administered dietary question naire . Participants were asked to state their average consumption of green tea , black tea , oolong tea , and coffee during the previous year . They could select any of 4 frequency responses : less than once a week , about 1 to 2 times a week , about 3 to 4 times a week , and almost every day . Participants who selected the response of almost every day were also asked to state their average consumption of these beverages in number of cups per day . We classified the categories of consumption as less than 1 cup per week , 1 to 6 cups per week , 1 to 2 cups per day , 3 to 5 cups per day , and 6 or more cups per day . The highest 2 or 3 consumption categories were combined for coffee , black tea , and oolong tea because of the small number of participants in these categories . The consumption of decaffeinated coffee or tea was not recorded because these products were not commercially available in Japan in the early 1990s . The total intake of caffeine was calculated by adding the caffeine content from each specific beverage ( 1 cup for coffee or tea ) and multiplying it by the participant 's weight proportional to the frequency of caffeine use . We estimated the size of the cup for each beverage from a validation study ( 10 ) and the caffeine content per 100 mL of each beverage from the Japan Food Tables ( 11 ) . The estimated caffeine content was 153 mg per cup ( 170 mL ) of coffee , 30 mg per cup ( 200 mL ) of green tea , 51 mg per cup ( 170 mL ) of black tea , and 38 mg per cup ( 190 mL ) of oolong tea . The mean caffeine intake was 229 mg/d for men and 215 mg/d for women . Relative proportions of caffeine intake by beverage were 46 % from green tea , 44 % to 47 % from coffee , 3 % from black tea , and 4 % to 5 % from oolong tea . For reproducibility , the Spearman correlation coefficients between the 2 question naires , administered 1 year apart for 85 participants ( 8 men and 77 women ) , were 0.79 for green tea , 0.87 for coffee , 0.77 for black tea , and 0.56 for oolong tea ( 10 ) . The validity of the data was confirmed for the 85 participants by comparing the data from the question naire with those from four 3-day dietary records collected approximately 3 to 4 months apart ( 10 ) . The mean frequency of consumption of green tea was 25.4 cups per week according to the question naire and 30.1 cups per week according to four 1-week dietary records ( Spearman correlation coefficient , 0.47 ) . The respective mean frequencies were 8.0 cups and 7.1 cups per week with a correlation coefficient of 0.79 for coffee , 1.4 cups and 1.6 cups per week with a correlation coefficient of 0.70 for black tea , and 1.8 cups and 1.2 cups per week with a correlation coefficient of 0.55 for oolong tea . When we restricted the data to the 77 women , the results were essentially the same . Assessment of Diabetes Cases Participants who reported having diabetes newly diagnosed by physicians on the 5-year follow-up question naire were considered to have incident diabetes . To examine the validity of self-reporting of diabetes , we compared self-report data with laboratory findings and treatment status in a sample of 1230 men and 1837 women . We considered elevated glucose concentrations ( fasting serum glucose concentration 7.8 mmol/L [ 140 mg/dL ] or a r and omly measured concentration of 11.1 mmol/L [ 200 mg/dL ] ) or treatment with oral hypoglycemic agents or insulin to indicate new cases of diabetes . Recent criteria from the American Diabetes Association ( 12 ) were not used because the cases in our study were diagnosed before 1995 . The sensitivity of self-reporting was 70 % for men and 75 % for women ; the specificity was 95 % for men and 98 % for women . Statistical Analysis To examine potential confounding variables reported from previous studies ( 3 - 7 ) , we presented baseline characteristics according to the frequency of consumption for each beverage . Tests for trends were conducted by using the median values of confounding variables in each category of beverage ; the linear regression model was used for continuous variables , and the logistic regression model was used for categorical variables . The odds ratios for incident type 2 diabetes were calculated in each category of beverage consumption and in each quartile of caffeine intake ; less than 1 cup per week or the lowest quartile was used as the reference category . We estimated age , sex , and BMI -adjusted odds ratios and multivariable odds ratios using the logistic regression model , adjusting for age ( in years ) , sex , sex-specific quintiles of BMI ( weight in kilograms divided by the square of height in meters ) , parental history of diabetes ( yes or no ) , smoking status ( never , former , or current [ 1 to 19 , 20 to 29 , or 30 cigarettes/d ] ) , alcohol intake ( never , former , or current [ 1 to 22 , 23 to 45 , 46 to 68 , or 69 g/d ] ) , sex-specific quintiles of magnesium intake , hours of walking ( of participation in sports ( BMI and magnesium intake were used because of different distributions between the sexes . We adjusted for magnesium intake because previous cohort studies indicated an inverse association between magnesium intake and risk for diabetes ( 13 , 14 ) . We conducted a test for trend by treating median values of each category of beverage or caffeine intake as continuous variables . We examined the association between caffeine intake and the risk for diabetes stratified by age group ( 40 to 54 years and 55 to 65 years ) , sex , family history of diabetes ( yes or no ) , current smoking status ( yes or no ) , current alcohol intake ( yes or no ) , magnesium intake ( below and above the sex-specific median ) , BMI ( hours of walking ( hours of participation in sports ( < 5 and 5 h/wk ) . The interactions with these stratified variables were tested by using cross-product terms of caffeine intake and the stratified variables . All analyses were conducted by using the SAS statistical package , version 8.2 ( SAS Institute Inc. , Cary , North Carolina ) . P values for statistical tests were 2-tailed , and 95 % CIs were estimated . Role of",
"Context A recently published study in a Dutch population identified an association between higher coffee consumption and lower risk for type 2 diabetes mellitus but did not distinguish between intake of regular and decaffeinated coffee . Contribution This large epidemiologic study in a U.S. sample confirmed the Dutch study findings . It also found a statistically significant protective association between total caffeine intake and type 2 diabetes mellitus and a modest inverse association with decaffeinated coffee consumption . Implication s Consumption of caffeinated coffee is associated with a reduced risk for type 2 diabetes mellitus . Further studies should explore the long-term effects of caffeine on glucose metabolism . The Editors The prevalence of type 2 diabetes mellitus has increased dramatically in the past decades , and the disease now affects approximately 8 % of U.S. adults ( 1 ) . Diet and lifestyle factors are primary determinants of risk for type 2 diabetes ( 2 ) . In addition to overweight and obesity , other independent behavioral and lifestyle factors include physical inactivity , smoking , and a diet higher in glycemic load and trans fatty acids and lower in fiber and polyunsaturated fatty acids . Coffee consumption may be related to diabetes because short-term metabolic studies have suggested that caffeine adversely affects insulin sensitivity and glucose metabolism ( 3 ) . Coffee consumption is widespread ; more than 50 % of Americans drink coffee , and average per capita intake is about 2 cups per day ( 4 ) . Coffee is the primary source of caffeine intake , providing approximately 210 mg/d per person in the United States . In humans , acute administration of caffeine decreases insulin sensitivity and impairs glucose tolerance ( 3 , 5 - 8 ) . On the other h and , caffeine stimulates thermogenesis and increases energy expenditure ( 9 - 11 ) , which may facilitate weight reduction and maintenance . Because of these complex physiologic effects of caffeine and because tolerance to the humoral and hemodynamic effects of caffeine typically develops with long-term use ( 12 ) , it is difficult to extrapolate findings from short-term metabolic studies to long-term use of coffee and other caffeinated beverages . A recent epidemiologic study has found a statistically significant inverse association between coffee consumption and risk for type 2 diabetes in a sample of Dutch participants ( 13 ) . After adjustment for potential confounders , the relative risk for type 2 diabetes among participants consuming at least 7 cups of coffee per day as compared with those consuming 2 cups or less per day was 0.50 ( 95 % CI , 0.35 to 0.72 ; P regular coffee from decaffeinated coffee and did not evaluate the association with total caffeine intake . In our study , we examined long-term intake of coffee and other caffeinated beverages and decaffeinated coffee in relation to incidence of type 2 diabetes in 2 large prospect i ve cohorts of men and women . In particular , we examined whether the associations were modified by smoking and body mass index . Methods Study Sample The Health Professionals Follow-up Study The Health Professionals Follow-up Study ( HPFS ) was established in 1986 when 51 529 male health professionals , including dentists , optometrists , veterinarians , osteopathic physicians , podiatrists , and pharmacists , who were 40 to 75 years of age returned a mailed question naire providing detailed information about their medical history , lifestyle , and other risk factors ( 14 ) . Information on the cohort is up date d every 2 years to identify newly diagnosed diseases . For our analysis , we excluded men with a previous diagnosis of type 2 diabetes , coronary heart disease , or cancer at baseline . Participants who did not complete more than 70 of 131 food items in the 1986 dietary question naire or had extreme scores for total daily intake of energy ( 4200 kcal ) were excluded . After exclusions , the analysis included 41 934 eligible men who were followed from 1986 to 1998 . The Nurses ' Health Study The Nurses ' Health Study ( NHS ) was established in 1976 when 121 700 female nurses 30 to 55 years of age living in 11 large states completed a mailed question naire providing detailed information about their medical history , lifestyles , and other risk factors ( 15 ) . The information is up date d every 2 years to identify newly diagnosed diseases . In 1980 , a semiquantitative food frequency question naire was added . For our analysis , we excluded women with a previous diagnosis of type 2 diabetes , coronary heart disease , or cancer at baseline . Participants who did not complete more than 10 items on the 1980 dietary question naire or had extreme scores for total daily intake of energy ( 3500 kcal ) were also excluded , leaving 84 276 eligible women who were followed from 1980 to 1998 . Assessment of Coffee and Caffeine Intake Vali date d dietary question naires were sent to the HPFS participants in 1986 , 1990 , and 1994 and to the NHS participants in 1980 , 1984 , 1986 , 1990 , and 1994 . In all the question naires , participants were asked how often on average during the previous year they had consumed coffee and tea . Decaffeinated coffee and different types of caffeinated soft drinks were first assessed in 1986 in the HPFS and in 1984 in the NHS . We assessed the total intake of caffeine by summing the caffeine content for a specific amount of each food during the previous year ( 1 cup for coffee or tea , one 12-ounce bottle or can for carbonated beverages , and 1 ounce for chocolate ) multiplied by a weight proportional to the frequency of its use . The participants could choose from 9 frequency responses ( never , 1 to 3 per month , 1 per week , 2 to 4 per week , 5 to 6 per week , 1 per day , 2 to 3 per day , 4 to 5 per day , and 6 or more per day ) . Using the U.S. Department of Agriculture food composition sources , we estimated that the caffeine content was 137 mg per cup of coffee , 47 mg per cup of tea , 46 mg per bottle or can of cola beverage , and 7 mg per serving of chocolate c and y. In our validation studies , high correlations were recorded for coffee and other caffeinated beverage intake assessed by the food frequency question naire and several 1-week diet records ( coffee , r = 0.78 ; tea , r = 0.93 ; and caffeinated sodas , r = 0.85 ) ( 16 ) . For these analyses , coffee consumption was categorized into 5 groups : never , less than 1 cup per day , 1 to 3 cups per day , 4 to 5 cups per day , and 6 cups or more per day . Caffeine intake was categorized into quintiles . Assessment of Diabetes Cases Participants who reported having diabetes were sent a supplementary mailed question naire that asked about symptoms , diagnostic tests , and treatment . We considered any 1 of the following criteria to represent a new case of diabetes : classic symptoms and elevated glucose levels ( fasting plasma glucose concentration 7.8 mmol/L [ 140 mg/dL ] or r and omly measured concentration 11.1 mmol/L [ 200 mg/dL ] ) ; at least 2 elevated plasma glucose concentrations on different occasions in the absence of symptoms ( plasma glucose level 11.1 mmol/L [ 200 mg/dL ] 2 or more hours after oral glucose tolerance testing ) ; or treatment with oral hypoglycemic agents or insulin . Our criteria for diabetes classification are consistent with those proposed by the National Diabetes Data Group ( 17 ) because most cases were diagnosed before 1997 . The validity of this diagnostic procedure has been verified in a sub sample of this study sample ( 18 ) . The diagnosis of type 2 diabetes was confirmed by medical records in 98 % of the participants . In addition , another sub study assessing the prevalence of undiagnosed diabetes suggested a very low rate of false-negative results ( 19 ) . Statistical Analysis We calculated the follow-up period from the return of the baseline question naires ( in 1986 for men and in 1980 for women ) to the diagnosis of type 2 diabetes , death , or the end of follow-up ( January 1998 for men and June 1998 for women ) , whichever occurred first . Incidence rates for diabetes were calculated by dividing incident cases by person-years of follow-up in each category of coffee intake . Relative risks were calculated as the rate of occurrence of type 2 diabetes in each quintile of caffeine intake divided by the corresponding rate in the lowest quintile , and 95 % CIs were calculated . To inspect potential confounding variables for the analyses , we examined baseline characteristics ( directly st and ardized to the age distribution of each cohort ) according to coffee consumption levels . We used proportional hazards models ( 20 ) to adjust for several risk factors , including age in 5 categories ( or 65 years of age ) ; body mass index ( weight divided by height [ kg/m2 ] ) in 8 categories ( to 28 , 29 to 30 , 31 to 32 , 33 to 34 , 35 to 39 , or 40 kg/m2 ) ; physical activity ( hours of moderate or vigorous exercise in NHS or quintiles of metabolic equivalents in HPFS ) ; family history of diabetes ( yes or no ) ; hormone use ( never , current , or past [ in NHS only ] ) ; smoking status ( never , past , or current smokers [ 1 to 14 , 15 to 24 , or 25 cigarettes per day ] ) ; alcohol consumption ( 0 , 0.1 to 4.9 , 5 to 9.9 , 10 to 14.9 , or 15 g/d ) ; total calorie intake ( continuous ) ; and quintiles of trans fat , glycemic load , and cereal fiber intake . We also adjusted for magnesium intake because our previous analyses have shown an inverse association between dietary magnesium and risk for diabetes ( 21 ) . Information on covariates was up date d periodically during follow-up . We performed a test for trend by treating median values of each category of caffeine and coffee intake as continuous variables . To represent long-term intake of coffee and caffeine and to reduce measurement error , we conducted analyses using cumulative up date d caffeine and coffee intake from all question naires ( 22 ) . For example , in the NHS , diabetes incidence between 1980 and 1984 was related to the coffee intake from the 1980",
"Green tea is rich in polyphenolic antioxidants and has widely reported but largely unsubstantiated health benefits . In the present study , genoprotective effects of two types of green tea were studied both in an in vitro and in a human supplementation trial . For the in vitro study , human lymphocytes were pre-incubated in tea ( 0·005 - 0·1 % , w/v ) , washed and subjected to oxidant challenge induced by H2O2 . In a placebo-controlled , cross-over supplementation study , eighteen healthy volunteers took 2 x 150 ml/d of 1 % ( w/v ) green tea ( ' Longjing ' green tea or ' screw-shaped ' green tea ) or water ( control ) for 4 weeks ( n 6 ) . Subjects took all the three treatments in a r and om order , with 6 weeks ' washout between each treatment . Fasting blood and urine were collected before and after each treatment . The comet assay was used to measure the resistance of lymphocytic DNA to H2O2-induced challenge . Basal oxidation-induced DNA damage was measured using the formamidopyrimidine glycosylase ( Fpg ) enzyme-assisted comet assay . Urine 7,8-dihydro-2-deoxyguanosine ( 8-oxodG , mol/mmol creatinine ) , a biomarker of whole-body oxidative stress , was measured by liquid chromatography with t and em MS . In vitro testing results of tea-treated cells showed increased ( P . In the supplementation trial , a significant ( P increase in resistance was also observed . Furthermore , the FPg comet data showed .20 % decrease in DNA damage with tea supplementation : mean and st and ard deviation changes in % DNA in comet tail in the Fpg-assisted comet assay were : -5·96 ( SD 3·83 ) % after Longjing tea ; -6·22 ( SD 3·34 ) % after screw-shaped tea ; + 0·91 ( SD 5·79 ) % after water ( P No significant changes in urine 8-oxodG were seen . The results indicate that green tea has significant genoprotective effects and provide evidence for green tea as a ' functional food '",
"CONTEXT Only a few studies of coffee consumption and diabetes mellitus ( DM ) have been reported , even though coffee is the most consumed beverage in the world . OBJECTIVE To determine the relationship between coffee consumption and the incidence of type 2 DM among Finnish individuals , who have the highest coffee consumption in the world . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve study from combined surveys conducted in 1982 , 1987 , and 1992 of 6974 Finnish men and 7655 women aged 35 to 64 years without history of stroke , coronary heart disease , or DM at baseline , with 175 682 person-years of follow-up . Coffee consumption and other study parameters were determined at baseline using st and ardized measurements . MAIN OUTCOME MEASURES Hazard ratios ( HRs ) for the incidence of type 2 DM were estimated for different levels of daily coffee consumption . RESULTS During a mean follow-up of 12 years , there were 381 incident cases of type 2 DM . After adjustment for confounding factors ( age , study year , body mass index , systolic blood pressure , education , occupational , commuting and leisure-time physical activity , alcohol and tea consumption , and smoking ) , the HRs of DM associated with the amount of coffee consumed daily ( 0 - 2 , 3 - 4 , 5 - 6 , 7 - 9 , > or = 10 cups ) were 1.00 , 0.71 ( 95 % confidence interval [ CI ] , 0.48 - 1.05 ) , 0.39 ( 95 % CI , 0.25 - 0.60 ) , 0.39 ( 95 % CI , 0.20 - 0.74 ) , and 0.21 ( 95 % CI , 0.06 - 0.69 ) ( P for trend smokers and never smokers ; healthy weight , overweight , and obese participants ; alcohol drinker and nondrinker ; and participants drinking filtered and nonfiltered coffee . CONCLUSION Coffee drinking has a grade d inverse association with the risk of type 2 DM ; however , the reasons for this risk reduction associated with coffee remain unclear",
"Recent evidence suggests that tea from Camellia sinensis ( eg , green , oolong , and black tea ) may have a hypoglycemic effect . We evaluated the ability of an extract of green and black tea to improve glucose control over a 3-month period . A double-blind , placebo-controlled , r and omized multiple-dose ( 0 , 375 , or 750 mg per day for 3 months ) study in adults with type 2 diabetes mellitus not taking insulin was performed . The primary end point was change in glycosylated hemoglobin at 3 months . The 49 subjects who completed this study were predominantly white with an average age of 65 years and a median duration of diabetes of 6 years , and 80 % of them reported using hypoglycemic medication . After 3 months , the mean changes in glycosylated hemoglobin were + 0.4 ( 95 % confidence interval , 0.2 - 0.6 ) , + 0.3 ( 0.1 - 0.5 ) , and + 0.5 ( 0.1 - 0.9 ) in the placebo , 375-mg , and 750-mg arms , respectively . The changes were not significantly different between study arms . We did not find a hypoglycemic effect of extract of green and black tea in adults with type 2 diabetes mellitus",
"Background Results of epidemiological studies have suggested that consumption of green tea could lower the risk of type 2 diabetes . Intervention studies show that green tea may decrease blood glucose levels , and also increase satiety . This study was conducted to examine the postpr and ial effects of green tea on glucose levels , glycemic index , insulin levels and satiety in healthy individuals after the consumption of a meal including green tea . Methods The study was conducted on 14 healthy volunteers , with a crossover design . Participants were r and omized to either 300 ml of green tea or water . This was consumed together with a breakfast consisting of white bread and sliced turkey . Blood sample s were drawn at 0 , 15 , 30 , 45 , 60 , 90 , and 120 minutes . Participants completed several different satiety score scales at the same times . Results Plasma glucose levels were higher 120 min after ingestion of the meal with green tea than after the ingestion of the meal with water . No significant differences were found in serum insulin levels , or the area under the curve for glucose or insulin . Subjects reported significantly higher satiety , having a less strong desire to eat their favorite food and finding it less pleasant to eat another mouthful of the same food after drinking green tea compared to water . Conclusions Green tea showed no glucose or insulin-lowering effect . However , increased satiety and fullness were reported by the participants after the consumption of green tea . Trial registration",
"To study the effects of the intake of green tea and polyphenols , which are a component of green tea , on insulin resistance and systemic inflammation , a r and omized controlled trial was conducted on 66 patients aged 32 - 73 y ( 53 males and 13 females ) with borderline diabetes or diabetes . Subjects in the intervention group were asked to take a packet of green tea extracts/powder containing 544 mg polyphenols ( 456 mg catechins ) daily , which was a dose that could be taken without difficulty , and were asked to divide the green tea extracts/powder in a packet into 3 or 4 fractions dissolved in hot water everyday and to take a fraction after every meal or snack for 2 mo , in addition to daily food intake . The subjects in the control group were simply followed . To calculate the level of green tea polyphenol intake that the subject usually drank at home , the subject was asked to taste 3 teas of different strengths ( 1 , 2 and 3 % ) and the tea that was closest to the one that the subject drank at home , was selected by each subject . After 2 mo , the mean daily polyphenol intake in the intervention group was 747 mg , which was significantly higher than that of 469 mg in the control group . In the intervention group , the body weight , BMI , systolic and diastolic blood pressures , blood glucose level , Hb A1c level , insulin level and HOMA index after taking the supplementation for 2 mo , were lower than the respective value before intervention : however , these parameters in the intervention group at 2 mo did not significantly differ from those in the control group . Within the intervention group , changes in insulin level tended to be associated with changes in polyphenol intake . In addition , changes in BMI were associated with changes in blood glucose level and insulin level . In conclusion , the daily supplementary intake of 500 mg green tea polyphenols did not have clear effects on blood glucose level , Hb A1c level , insulin resistance or inflammation markers . The positive correlation between the level of polyphenol intake and insulin level warrants further studies on the effect of green tea on insulin resistance",
"AIMS To examine the effect of green tea extract ( GTE ) on obese women and to explore the relationship between GTE and obesity-related hormone peptides . METHODS A r and omized , double-blind , placebo-controlled clinical trial was conducted from July 2006 to June 2007 in Taipei Hospital , Taiwan . Seventy-eight of 100 obese women aged between 16 and 60 years with BMI > 27 kg/m(2 ) and who had not received any other weight control maneuvers within the last 3 months completed this study . The subjects were r and omly divided into Groups A and B. Group A ( n=41 ) received GTE while Group B ( n=37 ) took cellulose as a placebo , one capsule ( 400 mg ) three times each day for 12 weeks . The body weight ( BW ) , body mass index ( BMI ) and waist circumflex ( WC ) were measured at the beginning of the study and after 12 weeks of treatment with GTE . The data were compared and expressed as % reduction . RESULTS There was only a 0.3 % reduction in BW ( 0.15 kg ) after 12 weeks of treatment with GTE . There was no statistical difference in % reduction in BW , BMI and WC between the GTE and placebo groups . Within group comparison revealed that the GTE group had significant reduction in LDL-cholesterol and triglyceride , and marked increase in the level of HDL-cholesterol , adiponectin and ghrelin . On the other h and , the placebo group showed significant reduction in triglyceride only , and a marked increase in the level of ghrelin alone . CONCLUSIONS This study showed no statistical difference in % reduction in BW , BMI and WC between the GTE and placebo groups after 12 weeks of treatment . The intake of GTE ( 491 mg catechins containing 302 mg EGCG ) for 12 weeks is considered safe as shown by the results",
"OBJECTIVE Previous studies examining the effect of tea drinking on cardiovascular health have produced mixed results due to their observational nature and qualitatively and quantitatively imprecise definitions of active tea components . The objective of this study was to determine if a st and ardized and defined decaffeinated green tea ( Camellia sinensis ) product lowers blood pressure , serum lipids , oxidative stress , and markers of chronic inflammation . METHODS A r and omized , double-blind , placebo-controlled , parallel study on 111 healthy adult volunteers 21 - 70 y old was performed . We administered a st and ardized capsule of Camellia sinensis compounds ( CSC ) twice a day . Before and after 3 wk , blood pressure , serum lipids , serum amyloid-alpha ( a marker of chronic inflammation ) , and serum malondialdehyde ( a marker of oxidative stress ) were measured . RESULTS After 3 wk , CSC lowered systolic and diastolic blood pressures by 5 and 4 mmHg , respectively . After 3 mo , systolic blood pressure remained significantly lower . CSC lowered serum amyloid-alpha by 42 % and lowered malondialdehyde by 11.9 % . In men , there were 10- and 9-mg/dL reductions in total and low-density lipoprotein ( LDL ) cholesterol , respectively . In all subjects with a baseline LDL cholesterol level > 99 mg/dL , there was 9 mg/dL lowering of total and LDL cholesterol . Adverse effects were mild and few and not different from placebo . CONCLUSION CSC was effective for decreasing , in as quickly as 3 wk , blood pressure , LDL cholesterol , oxidative stress , and a marker of chronic inflammation , all independent cardiovascular risk factors",
"OBJECTIVE The body fat reducing effect and reduction of risks for cardiovascular disease by a green tea extract ( GTE ) high in catechins was investigated in humans with typical lifestyles . RESEARCH METHODS AND PROCEDURES Japanese women and men with visceral fat-type obesity were recruited for the trial . After a 2-week diet run-in period , a 12-week double-blind parallel multicenter trial was performed , in which the subjects ingested green tea containing 583 mg of catechins ( catechin group ) or 96 mg of catechins ( control group ) per day . R and omization was stratified by gender and body mass index at each medical institution . The subjects were instructed to maintain their usual dietary intake and normal physical activity . RESULTS Data were analyzed using per- protocol sample s of 240 subjects ( catechin group ; n = 123 , control group ; n = 117 ) . Decreases in body weight , body mass index , body fat ratio , body fat mass , waist circumference , hip circumference , visceral fat area , and subcutaneous fat area were found to be greater in the catechin group than in the control group . A greater decrease in systolic blood pressure ( SBP ) was found in the catechin group compared with the control group for subjects whose initial SBP was 130 mm Hg or higher . Low-density lipoprotein ( LDL ) cholesterol was also decreased to a greater extent in the catechin group . No adverse effect was found . DISCUSSION The continuous ingestion of a GTE high in catechins led to a reduction in body fat , SBP , and LDL cholesterol , suggesting that the ingestion of such an extract contributes to a decrease in obesity and cardiovascular disease risks"
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41179df8-06ff-11f0-808a-c43d1ab1c353
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UNLABELLED The occlusal surface is the most affected area by dental caries and the sealing of the pits and of the fissures has been found , in time , the preventive method most effective trying to counteract the onset . Currently , the WHO considers it as a primary preventive measure , in other words one of the most effective and least invasive available to ensure the complete protection and the total preservation of the occlusal carious by the phenomenon . PURPOSE THE AIM OF THIS WORK HAS BEEN TO PERFORM A SYSTEMATIC REVIEW OF THE LITERATURE ON CLINICAL TRIALS OF DIFFERENT SEALING MATERIAL S , IN ORDER TO : compare their individual characteristics , highlight the reliability and the long-term efficacy and identify the most significant variables , both technological and clinics , in order to declare whether or not the success of this method prior . MATERIAL S AND METHODS The research has been carried out in the MEDLINE data base by choosing keywords as " sealants " and " follow up " . Only studies published in the last thirteen years have been considered and have been evaluated only types of scientific articles that fall within the definition of Anglo-Saxon " Clinical Trial " and " Controlled Clinical Trial " , excluding all experimental works in vitro , case-reports , meta-analyzes and literature review s. Have been also considered only scientific papers on patients between the ages of 0 and 18 years . RESULTS Out of 29 studies , evaluating a total of 2900 individuals ( aged between 2.5 and 17 years ) , 7411 seals made by using resin-based sealants ( RB Sealants ) , modified glass ionomer sealants ( RMGI ) and compomer sealants have been analyzed . The best retention capacity of the material in time has been obtained from the use of RB Sealants compared to RMGI , demonstrating retention values much lower with partial loss of material at a distance of one year from the clinic . The compomers demonstrate retention values intermediates . The incidence of caries in a year is negligible for all sealants application . CONCLUSIONS In terms of retention , resin-based sealants ( RB Sealants ) are the material s that give more guarantees of success at 12 months , while in the same period there have n't been significant differences in caries prevention of disease among the various classes sealing material s analyzed
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"BACKGROUND Air-abrasion can be used for enamel preparation before fissure sealing as well as acid etching which is the evidence -based method for enamel preparation before sealing . AIM The aim of this study is to evaluate the status of sealed occlusal surfaces of the first permanent molars after one , two , and five years and to compare consequence of using the two different methods for enamel preparation before sealing . MATERIAL S AND METHODS At the baseline of the study 88 children of the age from 6 to 9 with caries-free permanent molars r and omly received 185 sealants after using the air-abrasion system KCP 2000 PLUS ( ADT Inc. ) and 121 sealants using the acid etching method with Vococid ( VoCo ) . Fissurit F ( VoCo ) was used for sealing . The status of occlusal surfaces of molars was scored as caries- free or decayed/restored by visual clinical assessment evaluation after one , two , and five years . RESULTS The sealants retention rate was 97.2 % , 91.9 % , 61.2 % in the air-abrasion group and 96.3 % , 92.6 % , 62.4 % in the acid etching group after one , two , and five years , respectively . The results showed 98.2 % , 98.0 % , 89.8 % caries free occlusal surfaces of molars prepared with air-abrasion method and 100 % , 100 % , 94.6 % caries free occlusal surfaces of molars prepared with acid etching method after one , two , and five years respectively . CONCLUSION The differences between the two methods : air-abrasion and acid etching in terms of sealant retention rate and caries development appeared to be statistically insignificant ( p>0.05 )",
"BACKGROUND Bonding agents could be used as fissure sealants . This study compares the retention three fissure sealants ( Delton , Delton Plus and Concise ) and a filled dentin bonding system ( Optibond Solo ) . METHODS . Fifty-six children aged 7 - 8 years received fissure sealants either in the four permanent first molars , in the four deciduous second molars , or in all eight of these teeth . Every child received a different sealing material in each quadrant on a r and om basis . Clinical evaluation at 12 months was performed by a single blind examiner , and the retention was classified as either a success ( total retention ) or a failure ( partial retention or not present ) . RESULTS There were no statistically significant differences among the four material s in permanent maxillary molars or deciduous molars . In permanent m and ibular molars , Optibond Solo showed a lower percentage of retention ( 40.9 % ) , significantly different ( p=0.002 ) to that of Delton ( 89.5 % ) , Delton Plus ( 87.5 % ) and Concise ( 76.5 % ) . CONCLUSION One bottle dentin bonding system used as a sealant does not improve the retention of conventional fissure sealants . CLINICAL IMPLICATION Because of the scarcity of studies on the use of dental adhesives as sealants , further studies are warranted for the final support of that conclusion",
"To investigate the effectiveness of topical fluorides in preventing fissure caries , we conducted a r and omized controlled trial with parallel groups . In total , 501 children ( 1,539 molars , 3,078 sites ) , mean age 9.1 years , who had at least one sound permanent first molar with deep fissures or fissures with signs of early caries were recruited . They were r and omly allocated among four groups : ( 1 ) resin sealant , single placement ; ( 2 ) 5 % NaF varnish , semi-annual application ; ( 3 ) 38 % silver diamine fluoride ( SDF ) solution , annual application ; and ( 4 ) placebo control . Follow-up examinations were conducted every 6 months by a masked examiner . After 24 months , 485 children ( 97 % ) were examined . Proportions of pit/fissure sites with dentin caries in the sealant , NaF , SDF , and control groups were 1.6 % , 2.4 % , 2.2 % , and 4.6 % , respectively . A multi-level logistic regression analysis accounting for the effects of data clustering and confounding factors showed that fissures in any of the three treatment groups had significantly lower risks of carious cavity development into dentin than did controls ( p placement of resin sealant , semi-annual application of NaF varnish , and annual application of SDF solution are all effective in preventing pit and fissure caries in permanent molars ( Clinical Trials.gov number CT01446107 )",
"Objectives The objective of this one-year clinical study was to investigate the effect of two adhesive systems ( Adper Single Bond , a two-step etch- and -rinse and Clearfil SE Bond , a two-step self-etch system ) on pit- and -fissure sealant retention in newly-erupted teeth . This study compared the success of the sealants in mesial and distopalatal grooves with and without these two adhesive systems . Material and Methods In a clinical trial , 35 children aged 6 - 8 years undergoing sealant placement were recruited . This one-year clinical study scored 70 mesial and 70 distopalatal sealants of newly-erupted permanent maxillary first molar , with a split-mouth design . All children received sealant alone in one permanent maxillary molar tooth . Children were r and omized into two groups . One group received Self-Etch ( SE ) bond plus sealant and the other group received Single Bond plus sealant in another permanent maxillary molar tooth . Clinical evaluation at 3 , 6 and 12 months was performed and the retention was studied in terms of the success and failure . Results The success rate of sealant in the distopalatal groove , using SEB at 3 , 6 and 12 months was 93.3 % ( 95 % CI : 68.0 , 99.8 ) , 73.3 % ( 95 % CI : 44.9 , 92.2 ) and 66.7 % ( 95 % CI : 38.4 , 88.2 ) , respectively . It was greater than that of the distopalatal groove in SB group with a success rate of 62.5 % ( 95 % CI : 35.4 , 84.8 ) , 31.3 % ( 95 % CI : 11.8 , 58.7 ) and 31.3 % ( 95 % CI : 11.8 , 58.7 ) , at the three evaluation periods . The success rate of sealant in the mesial groove using SEB was 86.6 % ( 95 % CI : 59.5 , 98.3 ) , 53.3 % ( 95 % CI : 26.6 , 78.7 ) and 53.3 % ( 95 % CI : 26.6 , 78.7 ) , while this was 100 % ( 95 % CI : 79.4 , 100.0 ) , 81.3 % ( 95 % CI : 54.4 , 96.0 ) and 81.3 % ( 95 % CI : 54.4 , 96.0 ) using SB , at 3 , 6 and 12-month evaluation periods . Conclusions These results support the use of these two bonding agents in pit- and -fissure sealants under both isolated and contaminated conditions . Further , SE bond seemed to be less sensitive to moisture contamination ",
"PURPOSE The aim of this work is to study and compare the retention rate , caries-preventing and antibacterial effects of resin-modified glass ionomer and flowable composite in comparison to conventional fissure sealant . METHODS Forty-five children aged 7 - 10 years with newly erupted lower first permanent molars were r and omly divided into three equal treatment groups . Group I : sealed by a conventional resin sealant ; Group II : sealed by resin modified glass ionomer ( RMGI ) ; and Group III : sealed by flowable composite . Retention and caries status of the sealed teeth were recorded after 1 month , 6 months , year and 2 years . In addition , Streptococcus mutans counts were assessed at baseline , 1 day , 1 month , 6 months , 1 year and 2 years after sealant application . Data were analyzed by Fisher exact , chi-square and ANOVA tests . RESULTS Group III and Group I showed significantly higher retention rates than Group II fissure sealant ( p caries-preventive effects between the tested sealant material s throughout the duration of the study . Streptococcus mutans counts were significantly lower in group II compared to group I or group III up to 6 months of the study ( p Streptococcus mutans counts were not significant ( p>0.05 ) . CONCLUSION This study indicated a lower retention of RMGI compared to flowable composite and resin sealant without significant difference in caries prevention or long-term bacterial inhibition",
"BACKGROUND Long-term retention of pit and fissure sealants is essential for their success . The aim of this study was to compare the retention rates of sealants placed with acid-etching and air abrasion followed by acid etching . METHODS Sixteen subjects aged 16 and 17 years were included in the study . Using a half-mouth design , the authors performed fissure preparation with phosphoric acid gel on r and omly assigned maxillary and m and ibular permanent premolars and molars from one side of the mouth ( Group I ) and performed air abrasion followed by acid etching on the contralateral side of the mouth ( Group II ) . The authors applied sealant material on 162 teeth , and they evaluated the sealants as complete retention , partial loss or total loss at six , 12 and 24 months . RESULTS While fissure sealant retention rates were not significantly different for the two techniques at six months ( P = .97 ) , the retention rates for the teeth in Group II were significantly higher at 12 ( P = .025 ) and 24 months ( P = .002 ) . Molar retention rates were significantly less than those for premolars at each evaluation period ( P sealant retention rates at 12 and 24 months were higher in Group II ( air abrasion followed by acid etching ) . CLINICAL IMPLICATION S As air abrasion followed by acid etching result ed in significantly higher sealant retention rates , this method could be a good choice for fissure preparation before sealant placement for long-term success",
"OBJECTIVE The purpose of the present study was to provide further data for comparison of retention and caries-preventive effect of a resin-based sealant ( Delton , and a glass-ionomer sealant ( Fuji III ) . METHODS The study was conducted in the municipality of Vaerløse located 15 km north of Copenhagen , Denmark in the period 1996 - 2001 . The study comprised 153 children aged 8 - 13 years with a total of 364 site-pairs . Caries was diagnosed both clinical ly and radiographically , and sealant retention was diagnosed clinical ly . Sealants were placed either by one of four dentists , who had the responsibility for the children 's dental care , by a dental hygienist or a dental assistant . Mean follow-up time was 38 - 39 months for sites on first permanent molars and 28 - 29 months for sites on second permanent molars . RESULTS The retention rates were consistently , and considerably lower for Fuji III than for Delton . Relative risks of caries in Delton-sealed teeth over Fuji III-sealed teeth was 0.435 ( 95 % CI 0.150 - 0.846 ) based on the clinical diagnosis , and 0.559 ( 95 % CI 0.342 - 0.905 ) based on the radiographic diagnosis . The ratio of the relative risks ( clinical over radiographic diagnosis ) was close to 1 ( 0.778 ; 95 % CI 0.272 - 1.481 ) . CONCLUSION In the present study , Delton-sealed teeth had a lower risk than Fuji III-sealed teeth of developing caries , independent of the caries diagnostic method used",
"OBJECTIVES Very little independent research has been done on the new self-etching primer/adhesives in dentistry . A recent clinical study compared two sealant application techniques involving self-etching primer adhesives and the traditional phosphoric acid etch . The purpose of this study was to compare these two techniques in an Iowa school-based sealant program . METHODS Twelve-month sealant retention data on 208 students from the Des Moines , Iowa , school-based sealant program were analyzed retrospectively . RESULTS Sealant retention reported at the person level showed that 60 percent of the students who received sealants at the five schools had to be recalled at one year to have one or more surfaces resealed . A logistic regression model at the person level demonstrated that the phosphoric acid technique was six times as likely to have retention of all the sealed tooth surfaces as those sealed with Prompt-L-Pop . CONCLUSIONS In this study , many students had to be recalled to the chair 12 months after sealant application due to incomplete retention . Though sealants were retained in larger numbers with phosphoric acid , overall sealant retention at the tooth level was lower than previously published for clinical studies and school-based programs . Examining retention data at the person level , however , allows program administrators to plan re sources more effectively and reevaluate sealant protocol to ensure as few children return for sealant reapplication",
"This l and mark study of a pit and fissure sealant found 27.6 percent complete retention and 35.4 percent partial retention on permanent first molars . In the matched pair analysis , carious or restored surfaces made up 31.3 percent of the surfaces in the sealed group and 82.8 percent in the unsealed group",
"UNLABELLED This clinical trial evaluated the retention rate of a flowable restorative system ( Bond 1 + Flow-It ! ) used as a pit- and -fissure sealant compared with a conventional filled resin sealant ( Fluroshield ) over a 1-year period . METHOD Using a half-mouth design , 160 sealants ( 80 in primary and 80 in permanent teeth ) were placed on sound first/second primary molars and first permanent molars of 40 children aged between 4 and 7 years . For both primary and permanent dentitions , half the teeth ( n = 40 ) were sealed with Fluroshield and half ( n = 40 ) with Bond 1 + Flow-It ! Teeth were evaluated at baseline , 6- and 12-month intervals . RESULTS For both material s , there was no total loss of sealants placed on either the primary or permanent molars over 1 year . From Fluroshield sealants placed on primary teeth , 33 were completely intact after 6 months and 31 after 1 year . From those placed on permanent molars , no loss of material was observed after 6 months , while partial loss was noticed on 5 % of teeth at 1-year recall . For Flow-It ! resin applied on primary molars , partial loss of material was observed in only 1 sealant after 6 months and in 2 sealants after 1 year . On permanent teeth , 100 % retention rate was observed over a 1-year follow up . There was a statistically significant difference ( P Flow-It ! sealants presented a higher retention rate at both 6-month and 1-year evaluations . Significant differences ( P system yielded optimal retention on both primary and permanent molars . Its retention rate was significantly higher than that of the conventional pit- and -fissure sealant on primary teeth",
"PURPOSE This prospect i ve clinical trial compared the retention rate and caries-preventive efficacy of two types of sealant modalities over a 3-year period . MATERIAL S AND METHODS Using a split-mouth r and omised design , 1280 sealants were r and omly applied on sound permanent second molars of 320 young patients aged between 12 and 16 years . Half of the teeth ( n = 640 ) were sealed with a resin-modified glass ionomer cement ( RMGIC ) ( Vitremer ™ , 3 M ESPE ) and the other half ( n = 640 ) with a conventional light-cure , resin-based fissure sealant ( LCRB ) ( Fluoroshield ® , Dentsply Caulk ) . Teeth were evaluated at baseline , 6- , 12- , 18- , 24- , 30- and 36-month intervals with regard to retention and new caries development . RESULTS On the sealed occlusal surfaces after 3 years , 5.10 % of RMGIC and 91.08 % of LCRB sealants were totally intact and 6.37 % of RMGIC and 7.65 % of LCRB sealants were partially intact . New caries lesions were found in 20.06 % of RMGIC sealed occlusal surfaces , compared to 8.91 % for LCRB sealants . CONCLUSIONS The findings of the present clinical study suggest that RMGIC should be used only as a transitional sealant that can be applied to newly erupting teeth throughout the eruptive process , whereas LCRB sealants are used to successfully prevent occlusal caries lesions once an effective rubber dam can be achieved . It can be concluded that there are differences between the RMGIC and LCRB sealants over a 3-year period in terms of the retention rate and caries-preventive efficacy . RMGIC can serve as a simple and economic sealing solution , however provisional . Due to its poor retention rate , periodic recalls are necessary , even after 6 months , to eventually replace the lost sealant",
"Sealing occlusal pits and fissures with resin-based sealants is a proven method of preventing occlusal caries . Retention of the sealant is very essential for its efficiency . This study evaluated the retention of glass ionomer used as a fissure sealant when compared to a self-cure resin-based sealant . One hundred and seven children between the ages of 6 - 9 years , with all four newly erupted permanent first molars were selected . Two permanent first molars on one side of the mouth were sealed with Delton , a resin-based sealant , and the contralateral two permanent first molars were sealed with Fuji VII glass ionomer cement . Evaluation of sealant retention was performed at regular intervals over 12 months , using Simonsen 's criteria . At the end of the study period , the retention of the resin sealant was seen to be superior to that of the glass ionomer sealant"
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41179e34-06ff-11f0-808a-c43d1ab1c353
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The impact of 25-hydroxyvitamin D ( 25[OH]D ) supplementation on weight change remains controversial . The objective of this study was to summarize the effects of 25[OH]D supplementation ( cholecalciferol or ergocalciferol ) on BMI change through a meta- analysis of published clinical trials . We completed a systematic review of English articles , using MEDLINE ( Ovid , Pubmed ) from January 1 , 1998 through January 1 , 2013 . The articles selected focused on 25[OH]D supplementation and body mass index ( BMI ) in r and omized controlled trials ( RCT ' s ) . The association between 25[OH]D and mean BMI change was estimated utilizing a r and om effects model . A total of 30 studies were review ed and 9 were included in the meta- analysis . Total participants included 1651 adults ( 82.6 % women and mean age 47.9 years ) and mean follow-up ranged between 6 to 196 weeks and mean daily 25[OH]D dose ranged from 200 IU to 1,110 IU . Five of the 9 studies included calcium supplementation in both groups . Average baseline BMI was 30.7 and 30.4 kg/m2 in the intervention and control groups , respectively . Five studies suggested a beneficial effect for 25[OH]D supplementation for BMI change whereas 3 studies showed no effect of 25[OH]D supplementation on BMI change , and one showed a non-perceptible change . Meta- analysis of BMI values at end of trial showed no statistically significant difference in BMI change by use of 25[OH]D supplementation . Based on existing published trials , oral 25[OH]D supplementation does not significantly impact BMI change
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"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",
" The objective of the present trial was to assess the effects of vitamin D supplementation on serum 25-hydroxyvitamin D [ 25(OH)D ] and high-density lipoprotein cholesterol ( HDL-C ) in subjects with high waist circumference . Subjects were r and omly assigned a daily multivitamin and mineral ( MVM ) supplement or a MVM supplement plus vitamin D 1,200 IU/day ( MVM+D ) for 8 weeks . There was a significant difference in mean change for 25(OH)D between the MVM and MVM+D treatment groups ( − 1.2 ± 2.5 nmol/l vs. 11.7 ± 3.0 nmol/l , respectively ; P = 0.003 ) . Vitamin D 1,200 IU/day did not increase 25(OH)D to a desirable level ( ≥ 75 nmol/l ) in 61 % of participants . There were no significant changes in cardiovascular disease risk markers . Thus , vitamin D supplementation with 1,200 IU/day was insufficient to achieve desirable serum 25(OH)D in most participants and did not affect cardiovascular disease risk markers ",
"Background It is undetermined whether calcium supplementation has an effect on obesity or body composition in postmenopausal women . The purpose of the study is to detect the effect of calcium supplementation on indices of obesity and body composition . Methods This is a secondary analysis of data from a population -based , double-blind , placebo-controlled , r and omized trial design ed to determine the effects of calcium and vitamin D on osteoporotic fractures . The cohort included 1179 postmenopausal women who were r and omly assigned into one of three groups : 1 ) supplemental calcium ( 1400 mg/d or 1500 mg/d ) plus vitamin D placebo ( Ca-only group ) ; 2 ) supplemental calcium ( 1400 mg/d or 1500 mg/d ) plus supplemental vitamin D3 ( 1100 IU/d ) ( Ca + D group ) ; or , 3 ) two placebos ( placebo group ) . After applying the exclusion criteria for this analysis , 870 subjects were included in this study . The primary outcomes for the present study were changes in body mass index , trunk fat , trunk lean , and percentage of trunk fat after calcium supplementation . Results Changes in trunk fat , trunk lean , and percentage of trunk fat were significantly different between the calcium intervention groups ( Ca-only group or Ca + D group ) and the placebo group during the trial ( P calcium intervention groups gained less trunk fat and maintained more trunk lean when compared to the placebo group . No significant difference was observed for body mass index between groups . Conclusion Calcium supplementation over four years has a beneficial effect on body composition in postmenopausal women",
"BACKGROUND Weight loss is associated with bone loss , but this has not been examined in overweight premenopausal women . OBJECTIVE The aim of this study was to assess whether overweight premenopausal women lose bone with moderate weight loss at recommended or higher than recommended calcium intakes . DESIGN Overweight premenopausal women [ n = 44 ; x ( + /-SD ) age : 38 + /- 6.4 y ; body mass index ( BMI ): 27.7 + /- 2.1 kg/m(2 ) ] were r and omly assigned to either a normal ( 1 g/d ) or high ( 1.8 g/d ) calcium intake during 6 mo of energy restriction [ weight loss ( WL ) groups ] or were recruited for weight maintenance at 1 g Ca/d intake . Regional bone mineral density and content were measured by dual-energy X-ray absorptiometry , and markers of bone turnover were measured before and after weight loss . True fractional calcium absorption ( TFCA ) was measured at baseline and during caloric restriction by using a dual-stable calcium isotope method . RESULTS The WL groups lost 7.2 + /- 3.3 % of initial body weight . No significant decrease in BMD or rise in bone turnover was observed with weight loss at normal or high calcium intake . The group that consumed high calcium showed a strong relation ( r = 0.71 ) between increased femoral neck bone mineral density and increased serum 25-hydroxyvitamin D. No significant effect of weight loss on TFCA was observed , and the total calcium absorbed was adequate at 238 + /- 81 and 310 + /- 91 mg/d for the normal- and high-calcium WL groups , respectively . CONCLUSION Overweight premenopausal women do not lose bone during weight loss at the recommended calcium intake , which may be explained by sufficient amounts of absorbed calcium",
"BACKGROUND Adequate calcium intake can have a favorable effect on some metabolic variables . OBJECTIVE The objective of the study was to determine the effects of daily calcium intake and of supplementation with calcium and vitamin D ( calcium+D ) during a weight-loss intervention on blood pressures , plasma lipid and lipoprotein concentrations , and glucose and insulin concentrations in low calcium consumers . DESIGN Healthy , overweight or obese women ( n = 63 ) with a daily calcium intake of were r and omly assigned in a double-blind manner to 1 of 2 groups : the group consuming 2 tablets/d of a calcium + vitamin D supplement ( 600 mg elemental calcium and 200 IU vitamin D/tablet ) or the group consuming placebo ; both groups observed a 700 kcal/d energy restriction . These 63 women then completed a 15-wk weight-loss intervention . RESULTS Initial daily calcium intake was significantly correlated with plasma HDL cholesterol ( r = 0.41 , P 2-h postload glycemia ( r = -0.29 , P total : LDL and LDL : HDL ( P LDL cholesterol ( P calcium+D group than in the placebo group . The differences in total : HDL and LDL : HDL were independent of changes in fat mass and in waist circumference . A tendency for more beneficial changes in HDL cholesterol , triacylglycerol , and total cholesterol was also observed in the calcium+D group ( P = 0.08 ) . CONCLUSION Consumption of calcium+D during a weight-loss intervention enhanced the beneficial effect of body weight loss on the lipid and lipoprotein profile in overweight or obese women with usual low daily calcium intake",
"BACKGROUND The role of dairy calcium intake and serum vitamin D concentrations in weight loss is controversial . OBJECTIVE The objective was to assess the association of dairy calcium intake and serum vitamin D with weight loss . DESIGN We analyzed data from participants in the 2-y Dietary Intervention R and omized Controlled Trial ( DIRECT ) [ n = 322 ; mean body mass index ( BMI ; in kg/m² ) : 31 ; mean age : 52 y ] . A representative sample ( n = 126 ) was followed for 6 mo for serum vitamin D changes . RESULTS Baseline serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations decreased significantly across the tertiles of baseline BMI ( 25.6 ± 8.0 , 24.1 ± 8.9 , and 22.9 ± 6.8 ng/mL , respectively ; P for trend = 0.02 ) . Baseline concentrations of vitamin D and dairy calcium intake were not associated with subsequent weight loss . However , in repeated- measures models adjusted for age , sex , baseline BMI , total fat intake , and diet group assignment , higher 6-mo tertile levels of dairy calcium intake ( median for tertiles : 156.5 , 358.0 , and 582.9 mg/d , respectively ) and serum 25(OH)D ( 14.5 , 21.2 , and 30.2 ng/mL , respectively ) were associated with increased weight loss across the 2-y intervention ( -3.3 , -3.5 , and -5.3 kg , respectively , for dairy calcium ; P = 0.043 ; -3.1 , -3.8 , and -5.6 kg , respectively , for vitamin D ; P = 0.013 ) . In a multivariate logistic regression adjusted simultaneously for age , sex , baseline BMI , total fat intake , diet group , vitamin D concentration , and dairy calcium , an increase of 1 SD in dairy calcium intake increased the likelihood of weight loss of > 4.5 kg in the preceding 6 mo [ odds ratio ( OR ) : 1.45 ; P = 0.046 ] . A similar increase was seen for serum 25(OH)D at the 6-mo point ( OR : 1.7 ; P = 0.009 ) . CONCLUSION Our study suggests that both higher dairy calcium intake and increased serum vitamin D are related to greater diet-induced weight loss . This trial was registered at clinical trials.gov as NCT00160108",
"OBJECTIVE Investigate whether cholecalciferol supplementation leads to weight loss in overweight and obese adults . DESIGN R and omized double blind clinical trial with 20,000 IU cholecalciferol twice a week , or 20,000 IU once a week plus placebo , or placebo twice a week , for 12 months . All subjects were given 500 mg calcium supplementation . METHODS Four hundred and forty five healthy , overweight , and obese men and women ( age 21 - 70 years , body mass index ( BMI ) 28.0 - 47.0 kg/m(2 ) ) . Body weight , fatness , and fat distribution parameters were measured by dual-energy X-ray absorptiometry and anthropometry , blood sample s and 24-h urinary sample s were collected . RESULTS At baseline , there were no significant differences between the groups , but there was a significant inverse relation between serum 25-hydroxyvitamin D ( 25(OH)D ) levels and BMI , and a significant positive association between calorie intake and BMI . Three hundred and thirty four subjects completed the study . During the study , there was no significant change in weight , waist-to-hip ratio ( WHR ) or percentage body fat in any of the groups , nor between them . Parathyroid hormone decreased and 25(OH)D increased significantly in both groups receiving cholecalciferol , and serum levels of 25(OH)D stabilized after 3 months . Serum calcium was unchanged in all groups . Urinary calcium excretion increased in all groups , but there was no significant difference between the groups . Weekly dosage of 20,000 - 40,000 IU cholecalciferol for 12 months was associated with a low risk of adverse effects , at least in overweight and obese adults living at latitude 70 degrees N. CONCLUSION Significant weight reduction in overweight and obese subjects is unlikely to occur with cholecalciferol supplementation",
"OBJECTIVE Our objective was to determine the effects of dairy consumption on adiposity and body composition in obese African Americans . RESEARCH METHODS AND PROCEDURES We performed two r and omized trials in obese African-American adults . In the first ( weight maintenance ) , 34 subjects were maintained on a low calcium ( 500 mg/d)/low dairy ( for 24 weeks . In the second trial ( weight loss ) , 29 subjects were similarly r and omized to the low or high dairy diets and placed on a caloric restriction regimen ( -500 kcal/d ) . RESULTS In the first trial , body weight remained stable for both groups throughout the maintenance study . The high dairy diet result ed in decreases in total body fat ( 2.16 kg , p trunk fat ( 1.03 kg , p insulin ( 18.7 pM , p blood pressure ( 6.8 mm Hg systolic , p in lean mass ( 1.08 kg , p weight and fat loss , weight and fat loss on the high dairy diet were approximately 2-fold higher ( p of lean body mass was markedly reduced ( p adiposity and improved metabolic profiles in obese African Americans without energy restriction or weight loss and augmented weight and fat loss secondary to energy restriction",
"Hypovitaminosis D is common in Asian Indians . Physicians often prescribe 1500 mug ( 60 000 IU ) cholecalciferol per week for 8 weeks for vitamin D deficiency in India . Its efficacy to increase serum 25-hydroxy vitamin D ( 25(OH)D ) over short ( 2 months ) and long ( 1 year ) term is not known . We supplemented a group of twenty-eight apparently healthy Asian Indians detected to have low serum 25(OH)D ( mean 13.5 ( sd 3.0 ) nmol/l ) on screening during January-March 2005 . Serum parathyroid hormone ( PTH ) level was supranormal in 30 % of them . Oral supplementation included 1500 mug cholecalciferol per week and 1 g elemental Ca daily for 8 weeks . Serum 25(OH)D , total Ca , inorganic P and intact ( i ) PTH were reassessed in twenty-three subjects ( twelve females and eleven males ) who had follow up at both 8 weeks and 1 year . At 8 weeks the mean 25(OH)D levels increased to 82.4 ( sd 20.7 ) nmol/l and serum PTH normalized in all . Twenty-two of the twenty-three subjects had 25(OH)D levels>49.9 nmol/l . At 1 year , though the mean 25(OH)D level of 24.7 ( sd 10.9 ) nmol/l was significantly higher than the baseline , all subjects were 25(OH)D deficient . Five subjects with supranormal iPTH at baseline showed recurrence of biochemical hyperparathyroidism . Thus , with 8 weeks of cholecalciferol supplementation in Asian Indians with chronic hypovitaminosis D , mean serum 25(OH)D levels would be normalized and serum PTH value would be reduced to half . However , such quick supplementation would not maintain their 25(OH)D levels in the sufficient range for 1 year . For sustained improvement in 25(OH)D levels vitamin D supplementation has to be ongoing after the initial cholecalciferol loading",
"Background : Vitamin D insufficiency is prevalent in the northeast United States . Since vitamin D insufficiency is readily amenable to supplementation , it is important to underst and what factors are associated with serum 25 hydroxy vitamin D ( 25(OH)D ) response to vitamin D supplementation . Objective : In this study we examined the association of serum 25(OH)D response to vitamin D supplementation with body size in a population of elderly subjects . Methods : 257 healthy , ambulatory men and women 65 years of age or older were r and omly assigned to treatment with either 700 IU/day ( 17.5 μg/d ) of supplemental vitamin D3 and 500 mg/day ( 12.5 mmol/d ) of supplemental calcium , or to placebo . Results : In multivariate regression analyses , after adjusting for baseline 25(OH)D , season , and sex , we found change in 25(OH)D to be inversely associated with baseline BMI ( p = 0.01 ) in subjects treated with supplements for one year . Change in 25(OH)D was also negatively associated with other baseline anthropometric measurements in these subjects . Conclusion : Our study implies that body size should be taken into account when estimating the amount of vitamin D intake needed to raise 25(OH)D to the desired level",
"BACKGROUND Several studies suggest that calcium and vitamin D ( CaD ) may play a role in the regulation of abdominal fat mass . OBJECTIVE This study investigated the effect of CaD-supplemented orange juice ( OJ ) on weight loss and reduction of visceral adipose tissue ( VAT ) in overweight and obese adults ( mean ± SD age : 40.0 ± 12.9 y ) . DESIGN Two parallel , double-blind , placebo-controlled trials were conducted with either regular or reduced-energy ( lite ) orange juice . For each 16-wk trial , 171 participants were r and omly assigned to 1 of 2 groups . The treatment groups consumed three 240-mL glasses of OJ ( regular or lite ) fortified with 350 mg Ca and 100 IU vitamin D per serving , and the control groups consumed either unfortified regular or lite OJ . Computed tomography scans of VAT and subcutaneous adipose tissue were performed by imaging a single cut at the lumbar 4 level . RESULTS After 16 wk , the average weight loss ( ∼2.45 kg ) did not differ significantly between groups . In the regular OJ trial , the reduction of VAT was significantly greater ( P = 0.024 ) in the CaD group ( -12.7 ± 25.0 cm(2 ) ) than in the control group ( -1.3 ± 13.6 cm(2 ) ) . In the lite OJ trial , the reduction of VAT was significantly greater ( P = 0.039 ) in the CaD group ( -13.1 ± 18.4 cm(2 ) ) than in the control group ( -6.4 ± 17.5 cm(2 ) ) after control for baseline VAT . The effect of calcium and vitamin D on VAT remained highly significant when the results of the 2 trials were combined ( P = 0.007 ) . CONCLUSIONS The findings suggest that calcium and /or vitamin D supplementation contributes to a beneficial reduction of VAT . This trial is registered at clinical trial.gov as NCT00386672 , NCT01363115",
"Dairy products provide Ca and protein which may facilitate appetite control . Conversely , weight loss is known to increase the motivation to eat . This r and omised controlled trial verified the influence of milk supplementation on appetite markers during weight loss . Low Ca consumer women participated in a 6-month energy-restricted programme ( -2508 kJ/d or -600 kcal/d ) and received either a milk supplementation ( 1000 mg Ca/d ) or an isoenergetic placebo ( n 13 and 12 , respectively ) . Fasting appetite sensations were assessed by visual analogue scales . Anthropometric parameters and fasting plasma concentrations of glucose , insulin , leptin , ghrelin and cortisol were measured as well . Both groups showed a significant weight loss ( P with milk supplementation induced a smaller increase in desire to eat and hunger ( P decrease in fullness ( -17·1 v. -8·8 ; -2·7 v. 3·3 mm , P changes in ghrelin concentration predicted those in desire to eat ( r 0·56 , P 0·01 ) , hunger ( r 0·45 , P ) and fullness ( r -0·40 , P the change in ghrelin concentration in response to the intervention . These results show that milk supplementation attenuates the orexigenic effect of body weight loss",
"Data suggest that a diet deficient in calcium is associated with higher body weight and that augmenting calcium intake may reduce weight and fat gain or enhance loss . Our aim was to determine whether calcium supplementation during a weight loss intervention affects body fat or weight loss . Data were combined from three separate 25-wk r and omized , double blind , placebo-controlled trials of 1000 mg/d calcium supplementation in 100 premenopausal and postmenopausal women . The primary outcome measures were change in body weight and fat mass adjusted for baseline values . There were no significant differences in body weight or fat mass change between the placebo and the calcium-supplemented groups in the pooled analysis ( adjusted mean + /- SE ; body weight , placebo -6.2 + /- 0.7 vs. Ca -7.0 + /- 0.7 kg ; fat mass , placebo -4.5 + /- 0.6 vs. Ca -5.5 + /- 0.6 kg ) , and no significant interactions of calcium supplementation with menopausal/diet status . Analysis as separate trials also found no significant differences between the placebo and the calcium groups . Calcium supplementation did not significantly affect amount of weight or fat lost by women counseled to follow a moderately restricted diet for 25 wk . Nevertheless , the magnitude and direction of the differences for group means are consistent with a hypothesized small effect",
"This r and omized , double-blind , placebo-controlled study was conducted to compare the effect of a 15-week weight-reducing programme ( -2900 kJ/d ) coupled with a calcium plus vitamin D ( calcium+D ) supplementation ( 600 mg elemental calcium and 5 microg vitamin D , consumed twice a day ) or with a placebo , on body fat and on spontaneous energy/macronutrient intake . Sixty-three overweight or obese women ( mean age 43 years , mean BMI 32 kg/m2 ) reporting a daily calcium intake . Anthropometric variables , resting energy expenditure and spontaneous energy intake were measured before and after the 15-week programme . The calcium+D supplementation induced no statistically significant increase in fat mass loss in response to the programme . However , when analyses were limited to very low-calcium consumers only ( initial calcium intake calcium+D , n 6 for placebo ) , a significant decrease in body weight and fat mass ( P spontaneous dietary lipid intake ( P calcium+D but not in the placebo group . In very low-calcium consumers , change in fat mass was positively correlated with change in lipid intake . During the weight-reducing programme , a calcium+D supplementation was necessary in female overweight/obese very low-calcium consumers to reach significant fat mass loss that seemed to be partly explained by a decrease in lipid intake . We propose that this change in lipid intake could be influenced by a calcium-specific appetite control",
"There is increasing epidemiological evidence linking sub-optimal vitamin D status with overweight and obesity . Although increasing BMI and adiposity have also been negatively associated with the change in vitamin D status following supplementation , results have been equivocal . The aim of this r and omised , placebo-controlled study was to investigate the associations between anthropometric measures of adiposity and the wintertime serum 25-hydroxycholecalciferol ( 25(OH)D ) response to 15 μg cholecalciferol per d in healthy young and older Irish adults . A total of 110 young adults ( 20 - 40 years ) and 102 older adults ( ≥ 64 years ) completed the 22-week intervention with > 85 % compliance . The change in 25(OH)D from baseline was calculated . Anthropometric measures of adiposity taken at baseline included height , weight and waist circumference ( WC ) , along with skinfold thickness measurements to estimate fat mass ( FM ) . FM was subsequently expressed as FM ( kg ) , FM ( % ) , FM index ( FMI ( FM kg/height m2 ) ) and as a percentage ratio to fat-free mass ( FFM ) . In older adults , vitamin D status was inversely associated with BMI ( kg/m2 ) , WC ( cm ) , FM ( kg and % ) , FMI ( kg/m2 ) and FM : FFM ( % ) at baseline ( r - 0·33 , - 0·36 , - 0·33 , - 0·30 , - 0·33 and - 0·27 , respectively , all P values BMI in older adults was also negatively associated with the change in 25(OH)D following supplementation ( β - 1·27 , CI - 2·37 , - 0·16 , P = 0·026 ) ; however , no such associations were apparent in younger adults . Results suggest that adiposity may need to be taken into account when determining an adequate wintertime dietary vitamin D intake for healthy older adults residing at higher latitudes",
"OBJECTIVES The objective of the present study was to examine the cross-sectional relation between serum 25-hydroxyvitamin D [ 25-(OH ) D ] levels and depression in overweight and obese subjects and to assess the effect of vitamin D supplementation on depressive symptoms . DESIGN Cross-sectional study and r and omized double blind controlled trial of 20,000 or 40,000 IU vitamin D per week versus placebo for 1 year . SETTING A total of 441 subjects ( body mass index 28 - 47 kg m(-2 ) , 159 men and 282 women , aged 21 - 70 years ) recruited by advertisements or from the out-patient clinic at the University Hospital of North Norway . MAIN OUTCOME MEASURES Beck Depression Inventory ( BDI ) score with subscales 1 - 13 and 14 - 21 . RESULTS Subjects with serum 25(OH)D levels depressive traits ) than those with serum 25(OH)D levels > or = 40 nmol L(-1 ) on the BDI total [ 6.0 ( 0 - 23 ) versus 4.5 ( 0 - 28 ) ( median and range ) ] and the BDI subscale 1 - 13 [ 2.0 ( 0 - 15 ) versus 1.0 ( 0 - 29.5 ) ] ( P vitamin D , but not in the placebo group , there was a significant improvement in BDI scores after 1 year . There was a significant decrease in serum parathyroid hormone in the two vitamin D groups without a concomitant increase in serum calcium . CONCLUSIONS It appears to be a relation between serum levels of 25(OH)D and symptoms of depression . Supplementation with high doses of vitamin D seems to ameliorate these symptoms indicating a possible causal relationship",
"The loss of weight was analysed in a group of sixty overweight/obese women of childbearing age ( 20 - 35 years ) according to their initial vitamin D status . Subjects were r and omly assigned to one of two slightly hypocaloric diets : Diet V , in which the consumption of vegetables was increased , or Diet C , in which the relative consumption of cereals ( especially breakfast cereals ) was increased . Dietetic , anthropometric and biochemical data were collected at the start of the study and again at 2 weeks after dividing the women into groups depending on their having an initial serum 25-hydroxyvitamin D ( 25(OH)D ) concentration of or=50 nmol/l ( HD ) . Dietary intervention led to a reduction in energy intake , body weight and BMI in all groups . The HD women showed greater body fat losses during the study than the LD women ( 1.7 ( SD 1.8 ) kg compared to 0.5 ( SD 0.8 ) kg ) . A better vitamin D status therefore aided the loss of body fat over the experimental period ( OR 0.462 ; CI 0.271 , 0.785 ; P hypocaloric diets and lose more body fat ; this was especially clear among the C subjects who had a greater vitamin D supply during the experimental period",
"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 AIMS Recent studies suggest that calcium metabolism and perhaps other components of dairy products may contribute to shifting the energy balance and thus play a role in weight regulation . We compared the effects of cows ' milk , calcium fortified soy milk and calcium supplement on weight and body fat reduction in premenopausal overweight and obese women . METHODS AND RESULTS In this clinical trial , 100 healthy overweight or obese premenopausal women were r and omized to one of the following dietary regimens for 8 weeks : ( 1 ) a control diet providing a 500kcal/day deficit , with 500 - 600mg/day dietary calcium ; ( 2 ) a calcium-supplemented diet identical to the control diet with 800mg/day of calcium as calcium carbonate ; ( 3 ) a milk diet providing a 500kcal/day deficit and containing three servings of low-fat milk ; ( 4 ) a soy milk diet providing a 500kcal/day deficit and containing three servings of calcium fortified soy milk . At baseline and after 8 weeks , weight , waist circumference , and hip circumference were measured . Three 24-h dietary records and physical activity records were also taken . Comparing the mean differences in weight , waist circumference , body mass index ( BMI ) and waist-to-hip ratio ( WHR ) using repeated measure of variance analysis showed that changes in waist circumference and WHR were significant among the four groups ( p=0.029 and p=0.015 , respectively ) . After adjustment for baseline values , changes in weight and BMI were also significant ( p=0.017 and p=0.019 , respectively ) . Weight reductions in high milk , soy milk , calcium supplement and control groups were 4.43±1.93(kg ) , 3.46±1.28(kg ) , 3.89±2.40(kg ) and 2.87±1.55(kg ) , respectively . The greatest changes were seen in the high dairy group in all variables . CONCLUSION Increasing low fat milk consumption significantly reduces the general and central obesity beyond a low calorie diet",
"UNLABELLED Overweight postmenopausal women may be more susceptible to bone loss with weight reduction than previously studied obese women . The influence of energy restriction and Ca intake on BMD was assessed in 66 individuals . Weight reduction result ed in bone loss at several sites in women consuming 1 g Ca/day and was mitigated with higher calcium intake at 1.7 g/day . INTRODUCTION Bone loss is associated with weight loss in obese postmenopausal women and can be prevented with calcium ( Ca ) supplementation . However , because bone loss caused by weight loss may be greater in overweight than obese women , it is not clear whether Ca supplementation is also beneficial in overweight women . MATERIAL S AND METHODS We assessed the influence of caloric restriction at two levels of Ca intake on BMD and BMC in 66 overweight postmenopausal women ( age , 61 + /- 6 years ; body mass index , 27.0 + /- 1.8 kg/m2 ) . Subjects completed either a 6-month energy-restricted diet ( WL , n = 47 ) and lost 9.3 + /- 3.9 % weight or maintained weight ( WM ; 1 g Ca/day , n = 19 ) . Participants in the WL group were r and omly assigned to either normal ( 1 g/day ; WL NL-Ca ) or high ( 1.7 g/day ; WL Hi-Ca ) Ca intake . Regional BMD and BMC were measured at baseline and after 6 months . RESULTS During normal Ca intake , trochanter BMD and BMC and total spine BMD were decreased more in WL than WM women ( p trochanter BMD ( -4.2 + /- 4.1 % ) and BMC ( -4.8 + /- 7.1 % ) than the WL Hi-Ca group ( -1.4 + /- 5.6 % and -1.1 + /- 8.1 % , respectively ; p BMD or BMC at the femoral neck in any group . Weight loss correlated with trochanter BMD loss ( r = 0.687 , p bone loss occurred at some sites because of weight loss . Calcium intake of 1.7 g/day will minimize bone loss during weight loss in postmenopausal overweight women",
"Background : Dairy products not only reduce the risk of hypertension and cardiovascular diseases but may play a role in the treatment of obesity . As there is some evidence that calcium ( Ca ) and vitamin D may play a role in effective weight management , we decided to evaluate the influence of Ca and vitamin D supplementation on weight and fat loss in obese women . Material and Methods : Forty obese women were enrolled in this study . Subjects were divided into 2 groups comparable with body mass index ( BMI ) and age . Group 1 was provided with calcium carbonate and 1-(OH)-vitamin D supplementation . Group 2 was provided with only a diet . Subjects participated in a 3-month weight reduction therapy ( balanced diet , modification of life style , and regular physical exercise ) . Blood sample s ( serum concentration of Ca , phosphorus ( P ) , parathormone ( PTH ) , 25-(OH)-D3 ) and clinical characteristics ( weight , height , BMI , body composition ) were taken at baseline and after the 3-month program . Results : No significant differences of body weight , body fat content , serum parathormone , 25-(OH)-D3 concentration , and plasma total Ca and P concentration were observed between analyzed groups both before and after the treatment . Additionally , we did not observe any significant influence of Ca and vitamin D supplementation on weight and fat loss . Conclusion : Ca plus vitamin D supplementation during a 3-month low caloric diet has no additional effect on weight and fat loss in obese women",
"A significant relationship between body weight ( BW ) and bone mass ( BM ) has been established previously . A diet-induced weight loss is accompanied by a significant decrease in bone mineral density ( BMD ) and total body bone mineral ( TBBM ) , but the underlying mechanisms are not clarified . Sixty-two obese women were included in the study . Dual-energy X-ray absorptiometry ( DXA ) and measurements of a series of calcium-regulating hormones and biochemical markers of bone turnover were performed at baseline and after 1 month and 3 months on a low calorie diet . Thirty of the women were r and omized to a daily supplement of 1 g of calcium . After an additional 3 months without dietary prescriptions or calcium supplements , a subgroup of 48 subjects ( 24 from each group ) were scanned again using DXA . There was a significant decrease in TBBM after 1 month and 3 months . A similar pattern was observed in the bone mineral content ( BMC ) of the lumbar spine in the patients who did not receive a calcium supplement , whereas no changes occurred in the supplemented group . The initial calcium supplementation seemed to protect against bone loss in the lumbar spine but not in the TBBM . In the nonsupplemented group , a statistically significant inverse correlation was found between the calcium/creatinine ratio in the morning urine and the changes in BMC of the lumbar spine . Such a relationship was not seen in the calcium-supplemented group . In the nonsupplemented group , no significant biochemical changes were observed , whereas a significant decrease in serum parathyroid hormone ( PTH ) was seen in the calcium-supplemented group . This might explain some of the protective effects of calcium supplementation on trabecular bone mass . We conclude that a diet-induced weight loss is accompanied by a generalized bone loss , which probably is explained mainly by a reduced mechanical strain on the skeleton . This loss can be partly inhibited by a high calcium intake . Therefore , a calcium supplementation should be recommended during weight loss , even if the diet contains the officially recommended amounts of calcium",
"Experimental and epidemiological studies suggest that calcium intake is inversely related to weight gain . Calcium of dairy origin has been shown to be more effective in promoting weight loss . However , clinical studies yielded controversial results concerning the role of calcium intake in weight change . The aim of this study was to ascertain whether the addition of calcium can affect the outcome of 3-week weight management ( WM ) with a hypocaloric diet characterized by a decreased calcium intake . Overweight/ obese women ( n=67 ; BMI 32.2+/-4.1 kg/m(2 ) ; age 49.1+/-12.1 years ) underwent a 4-week comprehensive WM program . WM included a 7 MJ/day diet result ing in a stable weight during the first week and a 4.5 MJ/day diet with mean daily calcium intake 350 mg during the second to fourth week . Participants were divided into three age- and BMI -matched groups who received placebo or calcium ( 500 mg/day ) . Calcium was administered either as carbonate or calcium of dairy origin ( Lactoval ) . There was no significant difference in weight loss in response to WM between the placebo-treated and calcium-treated groups . However , addition of calcium to the diet result ed in a lower hunger score in the Eating Inventory as well as a decrease in plasma resistin levels . Body composition measured by bioimpedance demonstrated that added calcium leads to preservation of fat-free mass . Nevertheless , a greater loss of fat-free mass in the placebo group might be partly due to a greater loss of water",
"BACKGROUND In light of the current obesity epidemic , treatment models are needed that can prevent weight gain or provide weight loss . We examined the long-term effects of a supervised program of moderate-intensity exercise on body weight and composition in previously sedentary , overweight and moderately obese men and women . We hypothesized that a 16-month program of verified exercise would prevent weight gain or provide weight loss in the exercise group compared with controls . METHODS This was a r and omized controlled efficacy trial . Participants were recruited from 2 midwestern universities and their surrounding communities . One hundred thirty-one participants were r and omized to exercise or control groups , and 74 completed the intervention and all laboratory testing . Exercise was supervised , and the level of energy expenditure of exercise was measured . Controls remained sedentary . All participants maintained ad libitum diets . RESULTS Exercise prevented weight gain in women and produced weight loss in men . Men in the exercise group had significant mean + /- SD decreases in weight ( 5.2 + /- 4.7 kg ) , body mass index ( calculated as weight in kilograms divided by the square of height in meters ) ( 1.6 + /- 1.4 ) , and fat mass ( 4.9 + /- 4.4 kg ) compared with controls . Women in the exercise group maintained baseline weight , body mass index , and fat mass , and controls showed significant mean + /- SD increases in body mass index ( 1.1 + /- 2.0 ) , weight ( 2.9 + /- 5.5 kg ) , and fat mass ( 2.1 + /- 4.8 kg ) at 16 months . No significant changes occurred in fat-free mass in either men or women ; however , both had significantly reduced visceral fat . CONCLUSIONS Moderate-intensity exercise sustained for 16 months is effective for weight management in young adults ",
"OBJECTIVE The purpose of this study was to investigate the impact of dietary calcium or dairy product intake on total energy expenditure ( TEE ) , fat oxidation , and thermic effect of a meal ( TEM ) during a weight loss trial . METHODS AND PROCEDURES The intervention included a prescribed 500-kcal deficit diet in a r and omized placebo-controlled calcium or dairy product intervention employing twenty-four 18 to 31-year-old ( 22.2+/-3.1 years , mean + /- s.d . ) overweight women ( 75.5+/-9.6 kg ) . TEM and fat oxidation were measured using respiratory gas exchange after a meal challenge , and TEE was measured by doubly labeled water . Fat mass ( FM ) and lean mass ( fat-free mass ( FFM ) ) were measured by dual-energy X-ray absorptiometry . Subjects were r and omized into one of these three intervention groups : ( i ) placebo ( mg/day calcium supplement ; ( iii ) three servings of dairy products/day to achieve an additional 900 mg/day . RESULTS There were no group effects observed in change in TEE ; however , a group effect was observed for fat oxidation after adjusting for FFM ( P=0.02 ) . The treatment effect was due to an increase in fat oxidation in the calcium-supplemented group of 1.5+/-0.6 g/h , P=0.02 . Baseline 25-hydroxyvitamin D ( 25OHD ) was positively correlated with TEM ( R=0.31 , P=0.004 ) , and trended toward a correlation with fat oxidation ( P=0.06 ) , independent of group assignment . Finally , the change in log parathyroid hormone ( PTH ) was positively correlated with the change in trunk FM ( R=0.27 , P=0.03 ) . DISCUSSION These results support that calcium intake increases fat oxidation , but does not change TEE and that adequate vitamin D status may enhance TEM and fat oxidation",
"BACKGROUND Obesity in the United States has increased significantly during the past several decades . The role of calcium in the maintenance of a healthy body weight remains controversial . METHODS A r and omized , double-blinded , placebo-controlled trial was performed with 36 282 postmenopausal women , aged 50 to 79 years , who were already enrolled in the dietary modification and /or hormone therapy arms of the Women 's Health Initiative clinical trial . Women were r and omized at their first or second annual visit to receive a dose of 1000 mg of elemental calcium plus 400 IU of cholecalciferol ( vitamin D ) or placebo daily . Change in body weight was ascertained annually for an average of 7 years . RESULTS Women receiving calcium plus cholecalciferol supplements vs women receiving placebo had a minimal but consistent favorable difference in weight change ( mean difference , -0.13 kg ; 95 % confidence interval , -0.21 to -0.05 ; P = .001 ) . After 3 years of follow-up , women with daily calcium intakes less than 1200 mg at baseline who were r and omized to supplements were 11 % less likely to experience small weight gains ( 1 - 3 kg ) and 11 % less likely to gain more moderate amounts of weight ( > 3 kg ) ( P for interaction for baseline calcium intake = .008 ) . CONCLUSION Calcium plus cholecalciferol supplementation has a small effect on the prevention of weight gain , which was observed primarily in women who reported inadequate calcium intakes . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000611",
"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 )",
"Purpose The serum 25-hydroxyvitamin D ( 25(OH)D ) levels are lower in obese than lean subjects . The present study examines the cross-sectional and longitudinal relations between body mass index ( BMI ) and serum 25(OH)D , and the serum 25(OH)D response to vitamin D supplementation in relation to BMI . Methods The Tromsø study is a longitudinal population -based multi purpose study . The fourth survey was conducted in 1994 and the sixth in 2008 . The intervention study was a 1-year placebo-controlled r and omized intervention trial , where the results from the 93 subjects given 40,000 IU per week are presented . Results A total of 10,229 subjects were included in the 2008 cross-sectional study . There was a significant negative association between serum 25(OH)D levels and BMI which was also present during the winter months . Serum 25(OH)D levels varied through seasons , but not BMI . In the longitudinal study from 1994 to 2008 which included 2,656 subjects , change in BMI was a significant negative predictor of change in 25(OH)D. In the intervention study , there was a significant and negative correlation between BMI and serum 25(OH)D both at baseline and at the end of the study . The increase in serum 25(OH)D after 1 year was significantly and inversely related to baseline BMI . Conclusions We have confirmed the strong association between serum 25(OH)D and BMI . The very obese need higher vitamin D doses than lean subjects to achieve the same serum 25(OH)D levels",
"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"
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41179e70-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND Rheumatoid arthritis ( RA ) is a chronic , debilitating disease with a significant impact on workplace productivity . AIM To perform a systematic review of studies of the relationship between RA and reduced workplace productivity . METHODS Screening of 307 titles identified in bibliographic data base search es result ed in 38 articles subject to systematic review . Productivity loss was expressed by three different measures : work disability , work loss ( synonymous with absenteeism or short-term sick leave ) and work limitation ( reduction in productivity while present at work ) . RESULTS A median of 66 % ( range 36 - 84 % ) of employed RA subjects experienced work loss due to RA in the previous 12 months , for a median duration of 39 days ( range 7 - 84 days ) . The times from RA diagnosis until a 50 % probability of being work disabled varied from 4.5 to 22 years . In inception cohort studies , the baseline variables consistently predictive of subsequent work disability were a physically dem and ing work type , more severe RA and older age . CONCLUSIONS RA-related work-disability rates were similar in the USA and European countries . An apparent decrease in the prevalence of RA-related work disability since the 1970s may be related to a decrease in physically dem and ing work rather than to epidemiologic changes in RA . The majority of the literature addresses permanent disability and temporary work loss ; none of the studies review ed reported the effect of RA on presenteeism , i.e. work limitation from the employer perspective , and there are few published studies of the effectiveness of disease-modifying anti-rheumatic drugs in reducing work-related productivity loss
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"OBJECTIVE To investigate 1 ) the magnitude of indirect costs , 2 ) changes in cost components , and 3 ) correlations between changes in cost and social , clinical , and occupational variables within the first 3 years of rheumatoid arthritis ( RA ) . METHODS We evaluated the indirect costs per person-year in 133 consecutive gainfully employed out- patients with early RA , in a prospect i ve multicenter followup study . Costs due to RA-related sick leave , work disability , and other work loss were assessed using the human capital approach . Variables associated with reduction in lost productivity were tested by multivariate logistic regression analysis . RESULTS Mean + /- SEM annual indirect costs were $ 11,750 + /- 1,120 per person . During the 3-year period of observation , a marked reduction in the costs associated with sick leave was seen , which exceeded the increase in costs due to work disability and other work loss . This phenomenon result ed in an overall reduction in indirect costs of 21 % . The final logistic regression model of reduced loss of productivity included 3 variables : no problems with st and ing ( odds ratio [ OR ] 7.1 ) , no problems with working speed ( OR 4.1 ) , and no problems with outdoor work ( OR 3.1 ) . CONCLUSION High indirect costs in early RA were demonstrated . An overall decrease of costs can be seen in the first 3 years , due to the reduction in sick leave . Since the absence of problems due to strenuous working conditions was found to be associated with a reduction in indirect costs , it is assumed that early intensified vocational rehabilitation , apart from controlling disease activity by adequate treatment , might help to reduce indirect costs",
"OBJECTIVE To assess separate and combined effects of work factors and behavioural coping in relation to withdrawal from the labour force among patients with rheumatoid arthritis ( RA ) . METHODS A cross sectional study was conducted in a Dutch nationwide r and om sample of 720 patients with RA . Information about work factors and behavioural coping was collected by a self-administered postal question naire . A broad variety of work factors and coping styles were evaluated separately and in combination using multivariate logistic regression analyses , controlling for sociodemographic and disease related variables . Attributable and preventable fractions were calculated from the combined analyses to assess the relative importance of the contributing factors . RESULTS Additional job training , equal career opportunities , letting the disease influence the choice of the current job position , and informing colleagues about having the disease were negatively associated with withdrawal from the labour force . The most relevant factor in terms of decreasing the risk was adjusting job dem and s which accounted for 63 % of the patients still in the labour force . Decreasing activities and diverting attention in order to cope with pain , and pacing in order to cope with limitations were the coping styles which were positively associated with withdrawal from the labour force . The most relevant factor in terms of increasing the risk of withdrawal was pacing which accounted for 67 % of the withdrawals . CONCLUSION Work factors are potentially important modifiable risk factors for withdrawal from the labour force in patients with RA . Behavioural coping is also relevant",
"OBJECTIVE To explore baseline risk factors for productivity loss and work disability over 5 years in patients with early , active RA . PATIENTS AND METHODS In the FIN-RACo trial , 195 patients with recent onset RA were r and omised to receive either a combination of DMARDs with prednisolone or a single DMARD for 2 years . At baseline , 162 patients were working or available for work . After 5 years ' follow up , data on sick leave and retirement were obtained from social insurance registers or case records . The cumulative duration of sick leaves and RA related disability pensions was counted for each patient . To analyse predictors of productivity loss , the patients were divided into four groups according to duration of work disability per patient year . RESULTS Patient 's and physician 's global assessment of RA severity > or = 50 and HAQ score > or = 1.0 were risk factors for extension of productivity loss ( OR ( 95 % ( CI ) 1.77 ( 1.00 to 3.16 ) , 1.85 ( 1.03 to 3.32 ) , and 1.78 ( 1.01 to 3.14 ) , respectively ) . Additional risk factors were low education level ( 2.40 ( 1.18 to 4.88 ) ) and older age ( 1.03 ( 1.00 to 1.06 ) ) ; combination treatment was a protective factor ( 0.59 ( 0.35 to 0.99 ) ) . CONCLUSION At baseline , the risk of future productivity loss is best predicted by education level , age , global assessment s of RA severity , and HAQ score",
"Learning Objectives Recall the overall magnitude of lsot productive time ( LPT ) and its dollar cost as found in the American Productivity Audit , and the respective contributions of absenteeism and decreased producitivity at work . Be aware of how LPT varies with a number of demographic and workrelated factors . Compare the factors predisposing to LPT for personal and family-related reasons . The American Productivity Audit ( APA ) is a telephone survey of a r and om sample of 28,902 U.S. workers design ed to quantify the impact of health conditions on work . Lost productive time ( LPT ) was measured for personal and family health reasons and expressed in hours and dollars . Health-related LPT cost employers $ 225.8 billion/year ( $ 1685/employee per year ) ; 71 % is explained by reduced performance at work . Personal health LPT was 30 % higher in females and twice as high in smokers ( ≥1 pack/day ) versus nonsmokers . Workers in high-dem and , low-control jobs had the lowest average LPT/week versus the highest LPT for those in low-dem and , high-control jobs . Family health-related work absence accounted for 6 % of all health-related LPT . Health-related LPT costs are substantial but largely invisible to employers . Costs vary significantly by worker characteristics , suggesting that intervention needs vary by specific subgroups",
"OBJECTIVE To evaluate the efficacy and safety of repeated administration of infliximab plus methotrexate ( MTX ) over a 2-year period in patients with rheumatoid arthritis ( RA ) who previously experienced an incomplete response to MTX . METHODS Four hundred twenty-eight patients were r and omly assigned to receive MTX plus placebo or infliximab at a dose of 3 or 10 mg/kg plus MTX for 54 weeks , with an additional year of followup . The protocol was later amended to allow for continued treatment during the second year . Of 259 patients who entered the second year of treatment , 216 continued to receive infliximab plus MTX for 102 weeks . Ninety-four of these 259 patients experienced a gap in therapy of > 8 weeks before continuing therapy . Infusions were administered at weeks 0 , 2 , and 6 , followed by treatment every 4 weeks or every 8 weeks ( alternating with placebo infusions in the interim 4-week visits ) at a dose of 3 or 10 mg/kg for a total of 102 weeks ( including the gap in therapy ) . For safety and efficacy assessment s , data on the patients who were r and omized to receive treatment , irrespective of whether treatment was administered for 102 weeks , were evaluated using all actual observations available . The efficacy measures included the Health Assessment Question naire ( HAQ ) ( physical function ) , Short Form 36 health survey ( SF-36 ) ( health-related quality of life ) , total radiographic scores ( structural damage ) , and the American College of Rheumatology 20 % improvement criteria ( ACR20 ) ( signs and symptoms ) . RESULTS The infliximab plus MTX regimens result ed in significantly greater improvement in HAQ scores ( P SF-36 physical component summary scores ( P MTX-only group . There also was stability in the SF-36 mental component summary score among patients who received the infliximab plus MTX regimens . Median changes from baseline to week 102 in the total radiographic score were 4.25 for patients who received the MTX-only regimen and 0.50 for patients who received the infliximab plus MTX regimen . The proportion of patients achieving an ACR20 response at week 102 varied from 40 % to 48 % for the infliximab plus MTX groups compared with 16 % for the MTX-only group . CONCLUSION Throughout 102 weeks of therapy , infliximab plus MTX provided significant , clinical ly relevant improvement in physical function and quality of life , accompanied by inhibition of progressive joint damage and sustained improvement in the signs and symptoms of RA among patients who previously had an incomplete response to MTX alone",
"This paper traces the work history of patients with rheumatoid arthritis ( RA ) from the year of diagnosis to 1985 . The paper also describes the risk factors for work loss among patients with RA . It uses data from a panel of 698 RA patients , observed for 4 years , from the practice s of a r and om sample of northern California rheumatologists . Of these 698 , 353 had worked for pay at some point in their lives . Three hundred six of the 353 had worked when diagnosed as having RA . Of these 306 , 157 ( 51 % ) were no longer working in 1985 . Forty-seven individuals started working after the onset of illness , but of these , approximately one-third had stopped working by 1985 . In all , 50 % of RA patients with some work experience stopped working within a decade of diagnosis , 60 % within 15 years , and 90 % within 30 years . We found that the probability of work loss is lessened among persons in jobs that have few physical requirements , among those with high levels of discretion over the pace and activities of work , and among those who were able to stay on the job held when the diagnosis was made . The probability of work loss is increased among service workers . The findings of this longitudinal study , showing that work characteristics profoundly alter the probability of work loss among persons with RA , are consistent with the findings of our earlier cross-sectional studies of work outcome and RA",
"OBJECTIVE Work disability is a common outcome of rheumatoid arthritis ( RA ) . Yet there have been no longitudinal , longterm , prospect i ve studies of work disability in this illness . This 18 year longitudinal study investigates the rate of work disability , its concomitants , and its predictors , using a large series of clinical , laboratory , and self-report measures . METHODS In 1974 , a computerized data base was developed for the contemporaneous entry of all patient visits . Data included clinical , laboratory , and self-report information . Patients were also assessed by mailed question naires at 6 month intervals . In 1994 , patients with RA were interviewed in detail about lifetime work status and work disability . RESULTS Work disability was estimated to occur in 25 % at 6.4 years and 50 % at 20.9 years after disease onset , and most disability occurred late in the course of disease . Work disability was predicted by almost every demographic and clinical variable . Education level , body mass index ( BMI ) , erythrocyte sedimentation rate , rheumatoid factor , pain , Health Assessment Question naire ( HAQ ) disability , and physical dem and s of the job were independently associated with disability . Over the course of their illness , the work disabled had a 35 % reduction in family income , and had more abnormal scores for joint counts , grip strength , sedimentation rate , pain , global severity , HAQ disability , and anxiety and depression . Except for BMI , the results were essentially similar in a subset of 156 patients seen first with a disease duration of less than one year . CONCLUSION Work disability can be predicted by patient and work characteristics present at the first clinic visit , but it is persistent abnormalities of sedimentation rate , HAQ disability , and pain , which may be detected in longitudinal followup , that best predict work disability after work and demographic characteristics are accounted for",
"Objective : To develop a systematic set of German cost data in rheumatoid arthritis ( RA ) based solely on valid healthcare payer ’s cost data sources . Methods : Retrospectively one year cost data of 338 patients with RA were generated and analysed . The cost data were derived from a major statutory health insurance plan ( “ Allgemeine Ortskrankenkasse Niedersachsen ” ) and the regional physicians ’ association ( “ Kassenärztliche Vereinigung Niedersachsen ” ) . The recently published matrix of cost domains in RA was applied to structure the analysis . Descriptive statistics were used to analyse the data . Results : The total direct costs for the 338 patients during one year ( third quarter 2000 to second quarter 2001 ) were € 3815 per patient-year . RA related direct costs were € 2312 per patient-year . Outpatient costs accounted for 73.7 % , inpatient costs for 24.0 % , and other disease related costs for 2.3 % of RA related direct costs . Out patients cost drivers were RA related drugs ( € 1019 per patient-year ) , physician visits ( € 323 per patient-year ) , diagnostic and therapeutic procedures and tests ( € 185 per patient-year ) , and devices and aids ( € 168 per patient-year ) . 98 patients were retired prematurely owing to RA related work disability and incurred costs of € 8358 per retired patient-year . 96 patients were gainfully employed and incurred sick leave costs of € 2835 per employed patient-year . Conclusion : Micro-costing based on healthcare payer ’s data provides a relatively conservative albeit highly accurate estimate of costs in RA . Both RA related and non-RA related costs must be taken into account . In gainfully employed patients and in patients who receive RA related retirement payments productivity costs exceed direct costs",
"OBJECTIVE To evaluate the development of h and icap in patients with rheumatoid arthritis ( RA ) followed 8 years from onset . METHODS The study group consisted of 106 patients participating in a prospect i ve early RA study . The mean duration of joint symptoms at inclusion was one year . The patients were assessed at least once annually . Disability was measured with the Health Assessment Question naire ( HAQ ) and emotional distress with a self-administered test ( Symptom Checklist ) . Work status and different social measures were registered . A structured interview regarding work capacity , leisure time , and social activities was performed about 8 years after disease onset . RESULTS Compared to study start , disease activity had decreased , emotional distress was unchanged , disability had increased somewhat , and radiographic changes had increased markedly . The prevalence of work disability at the end of the study was 37 % . The majority of patients that eventually got disability pension had stopped working the first year after onset . Seventy-eight percent of the patients who continued to work had to adjust their work conditions to stay employed . The 3 most important predictors for work disability were higher HAQ at study start , lower educational level , and older age . Three-quarters of the patients had to alter leisure time activities and half of them were not satisfied with their recreation . Many patients experienced difficulties in their roles as spouse and parent . Higher levels of emotional distress were associated with these h and icaps . CONCLUSION In this cohort of patients with RA we found a high frequency of different types of h and icaps at an early stage . Slightly more than 1/3 were work disabled . The majority had stopped working during the first year . Patients perceived h and icaps in terms of changed leisure time activities , and difficulties performing different social roles were frequent . Patients with these h and icaps felt more emotional distress",
"In a prospect i ve study of recent arthritis , 103 patients had rheumatoid arthritis ( RA ) , 63 seronegative oligoarthritis ( SO ) , 67 reactive arthritis ( REA ) , 20 ankylosing spondylitis ( AS ) , and 13 psoriatic arthritis ( PA ) . At the 8-year check-up , 36 % of patients with RA were at work , compared with 69 % in PA ( p less than 0.002 ) , and 85 - 90 % in AS , SO , and REA ( p less than 0.001 ) . Correspondingly 43 % of the RA patients were disabled by arthritis , compared with 23 % in PA ( NS ) , 15 % in AS ( p less than 0.005 ) , none in SO , and 4 % in REA ( p less than 0.001 ) . No significant differences in work capacity were noted between patients with PA , AS , SO or REA . In RA , the educational background s of patients unable to work ( 44 patients ) and able to work ( 37 patients ) did not differ from each other or from the overall population of Finl and , but a significantly ( p less than 0.01 ) smaller number of patients with arduous work were able to continue at work . The mean age of 49 years for RA patients unable to work differed highly significantly ( p less than 0.001 ) from the 35 years of RA patients at work . However , the weightiest cause of limited work capacity was severity of disease",
"OBJECTIVE To evaluate labor force characteristics among patients with rheumatoid arthritis ( RA ) in Lithuania . To assess if Lithuania 's transition from a state-planned to a free-market economy after 1990 changed the employment perspectives of patients with RA . METHODS RA patients , age 16 - 65 years ( n = 238 ) , were r and omly selected from the RA register in Vilnius . They completed questions about sociodemographics , working status , and disease characteristics , they underwent a clinical examination , and they completed the modified Health Assessment Question naire and the Short Form 36 . RESULTS Age- and sex-adjusted employment was 24.2 % lower and work disability 51.7 % higher in patients compared with the general population in Lithuania . After 10 years of disease , 48 % of the patients had withdrawn from the labor force . In those with a paid job , the average sick leave in the past year was 31.9 days compared with the national average of 10.8 days . Although disease activity was not significantly different in employed compared with work-disabled patients , physical function and perceived quality of life ( except general health ) were worse among patients with work disability . The change in economic organization in 1990 was noted to increase the risk for work withdrawal by a factor of 2.75 ( 95 % confidence interval 1.68 - 4.53 ) . CONCLUSION In Lithuania , the impact of RA on work disability is important . Although work disability in Lithuanian patients with RA seems more pronounced compared with reports from Western societies , variables associated with work disability are comparable . The transition to a market-orientated economy in 1990 increased the risk of becoming work disabled",
"OBJECTIVE To describe employment status of patients with early rheumatoid arthritis ( RA ) 10 years after diagnosis ; and to identify predictive and associative factors related to permanent work disability . METHODS The study population consisted of 82 patients with early RA who were gainfully employed at onset of RA . Patients were prospect ively followed for an average of 10 years and were treated according to the \" sawtooth \" strategy . RESULTS After a time since diagnosis of 2 and an average of 9.9 years , respectively , 19/82 ( 19 % ) and 36/82 ( 44 % ) cases have been retired merely or partly due to RA . Further , at the latest checkup 42/82 ( 51 % ) patients were still gainfully employed , while the prevalence of patients working full time under the common retirement age of 65 yrs was 58 % ( 42/72 ) . Cox regression analysis revealed that physically heavy work at baseline was the strongest independent predictive factor for permanent work disability . Ten years after disease onset , however , work disabled patients had more severe disease than those who continued in work . CONCLUSION Our study confirms that the working capacity of patients with RA is in danger from the very start . Despite early and active therapy with disease modifying antirheumatic drugs , at 10 years the cumulative work disability prevalence was 44 %",
"Objectives : To assess the occurrence and prognostic factors for the ability to maintain paid work in patients with rheumatoid arthritis ( RA ) . Setting : Inception cohort of patients with RA recruited from rheumatology departments in nine NHS Hospital Trusts in Engl and . Patients : All consecutive patients with RA of less than two years ' duration , before any second line ( disease modifying ) drug treatment , and followed up for five years . Methods : Clinical , laboratory , and radiological assessment s , and all treatments were recorded prospect ively using a st and ardised format at presentation and yearly . Outcome measures : Changes in , and loss of paid work by five years ' follow up . Results : 732 patients completed the five year follow up . 353/721 ( 49 % ) were gainfully employed at the onset of RA , 211 ( 60 % ) were still working at five years , 104 ( 29 % ) stopped because of the disease , and 31 ( 9 % ) retired for reasons other than RA . Work disability at five years was more likely in manual workers ( odds ratio ( OR ) 2.3 , 95 % confidence interval ( CI ) 1.4 to 3.8 ) and worse baseline Health Assessment Question naire ( HAQ>1.5 , OR 2.26 , 95 % CI 1.38 to 3.7 ) . In combination with other baseline variables ( erythrocyte sedimentation rate , sex , age of onset , and radiological erosions ) , employment outcome was predicted in 78 % using multivariate analysis . Conclusions : Nearly half of the patients with RA were in paid employment at onset , work disability was an adverse outcome for a third of these patients by five years , and manual work and high baseline HAQ were important predictors for this . These details are likely to be useful to clinicians , health professionals , and patients in order to plan medical , orthopaedic , and remedial treatments in early RA . Future disease modifying treatments could be compared with this cohort of patients who were treated with conventional second line drugs",
"CONTEXT Common pain conditions appear to have an adverse effect on work , but no comprehensive estimates exist on the amount of productive time lost in the US workforce due to pain . OBJECTIVE To measure lost productive time ( absence and reduced performance due to common pain conditions ) during a 2-week period . DESIGN AND SETTING Cross-sectional study using survey data from the American Productivity Audit ( a telephone survey that uses the Work and Health Interview ) of working adults between August 1 , 2001 , and July 30 , 2002 . PARTICIPANTS R and om sample of 28 902 working adults in the United States . MAIN OUTCOME MEASURES Lost productive time due to common pain conditions ( arthritis , back , headache , and other musculoskeletal ) expressed in hours per worker per week and calculated in US dollars . RESULTS Thirteen percent of the total workforce experienced a loss in productive time during a 2-week period due to a common pain condition . Headache was the most common ( 5.4 % ) pain condition result ing in lost productive time . It was followed by back pain ( 3.2 % ) , arthritis pain ( 2.0 % ) , and other musculoskeletal pain ( 2.0 % ) . Workers who experienced lost productive time from a pain condition lost a mean ( SE ) of 4.6 ( 0.09 ) h/wk . Workers who had a headache had a mean ( SE ) loss in productive time of 3.5 ( 0.1 ) h/wk . Workers who reported arthritis or back pain had mean ( SE ) lost productive times of 5.2 ( 0.25 ) h/wk . Other common pain conditions result ed in a mean ( SE ) loss in productive time of 5.5 ( 0.22 ) h/wk . Lost productive time from common pain conditions among active workers costs an estimated 61.2 billion dollars per year . The majority ( 76.6 % ) of the lost productive time was explained by reduced performance while at work and not work absence . CONCLUSIONS Pain is an inordinately common and disabling condition in the US workforce . Most of the pain-related lost productive time occurs while employees are at work and is in the form of reduced performance",
"OBJECTIVES To assess work history and labour force participation among patients with rheumatoid arthritis ( RA ) in the Netherl and s. METHODS A r and om sample of 1056 patients with RA aged 16–59 years from 17 rheumatology practice s in the Netherl and s was examined . Data on disease status and outcome were obtained by a question naire including st and ardised instruments , such as the Rapid Assessment of Disease Activity in Rheumatology ( RADAR ) and R AND -36 question naires . Labour force participation was defined as having a paid job . RESULTS Of the study group with a mean disease duration of 12 years , 35.7 % held a paid job ( men 56.7 % ; women 27.7 % ) . When st and ardised for age , sex , and educational level , the labour force participation of patients with RA was 61.2 % compared with 65.5 % for the general population , which was not statistically significant . Disease duration of six years and more was negatively associated with labour force participation . CONCLUSIONS After controlling for the confounding effects of age , sex , and education , the labour force participation of patients with RA in the Netherl and s is only slightly lower than that of the general population",
"OBJECTIVE To assess the association between use of etanercept and employment outcomes among patients with rheumatoid arthritis ( RA ) . METHODS In 1999 , 497 RA patients of working ages ( 18 - 64 years ) reported their employment status in the year of diagnosis and as of the study year , in structured telephone interviews . Of these , 238 had been in clinical trials of etanercept and were currently taking that medication , while 259 were members of an observational study and were not taking etanercept . We used regression techniques to estimate whether employment outcomes in 1999 ( employed versus not and , among the employed , hours of work per week , weeks of work per year , and hours of work per year ) among the 379 of the 497 patients who were employed at the time of diagnosis were associated with etanercept use , with and without adjustment for demographic characteristics , RA status , overall health status , and the nature of the job held at the time of diagnosis . RESULTS At the time of diagnosis , 75 % of RA patients from the observational study who did not take etanercept and 77 % of those who did take the medication were employed . By 1999 , among those employed at diagnosis , 55 % of the former group and 71 % of the latter were employed ( difference 16 percentage points ) . After adjustment for demographics , overall health status , duration of RA , RA status , and occupation and industry , the difference widened to 20 percentage points . Among all who were employed at the time of diagnosis , those from the etanercept clinical trials worked an average of 5.4 more hours per week in 1999 ; after adjustment , the etanercept group worked 7.4 more hours per week . CONCLUSION Among all persons who were employed at the time of RA diagnosis , having been in the etanercept clinical trials was associated with higher employment rates in 1999 and a greater number of hours per week of work in that year , suggesting that a r and omized trial to establish the relationship between treatment and employment outcomes is now warranted",
"OBJECTIVE Physically dem and ing occupations have been associated with becoming a disability pensioner with rheumatoid arthritis ( DPRA ) , but not with the disease of RA . The association with becoming DPRA probably reflects that patients with RA have difficulties in maintaining employment in a physically dem and ing occupation . However , the attitudes of the employers concerning employment of persons with RA might vary . For example , the patient 's age may influence the strength of the association between a physically dem and ing occupation and becoming DPRA . We assessed whether the association between the predictors and becoming DPRA was stronger for the youngest or the oldest age group . METHODS The study was prospect i ve with data on persons in Norway 30 - 56 years old either in the census of 1970 or 1980 . All new cases of DPRA during the 2 followup periods 1971 - 80 and 1981 - 90 were identified and analyzed by logistic regression . RESULTS For women the predictors employment , low level of education , and period ( 1981 - 90 compared to 1971 - 80 ) were more strongly associated with becoming DPRA for the youngest compared to the oldest persons , while manual work and part time work were not predictors of becoming DPRA . For men , all the predictors in the study were more strongly associated with becoming DPRA for the youngest compared to the oldest age group . CONCLUSION The higher risk of becoming DPRA was associated with most predictors for persons aged 30 - 39 years than the group aged 50 - 56 years . Our results appear to indicate that the consequences of having RA in the labor market are greater for the youngest age group",
"Aim : Work disability is a frequent and serious outcome of rheumatoid arthritis ( RA ) , accounting for the greatest indirect costs of this condition . A longitudinal , long-term prospect i ve study was conducted on a large cohort of RA patients ( pts ) to investigate the rate/risk of work disability and the factors that may be considered concomitant with and therefore predictors of work disability , using a broad series of clinical , laboratory and self-reported measures in all pts and in a subgroup of early RA pts . Methods : RA pt data from 1974 were recorded in a data base at the Wichita Arthritis Center in which demographic , clinical , and pt self-reported variables were registered at every pt visit . In 1994 , 823 RA pts were examined and interviewed about their employment and work history . The pts were asked for occupation data the start and stop date s of each job , the specific job title , the reason for which the job was stopped ; demographic variables ( sex , age , ethnic origin , education level , number of children , smoking history , total income , and current marital status ) ; and clinical data [ tender joint count , grip strength , health assessment question naire ( HAQ ) , pain on a visual analogic scale ( VAS ) , VAS global severity , AIMS anxiety and depression , co-morbid conditions , body mass index ( BMI ) , and rheumatoid factor ( RF ) ] . Values used in the prediction of work disability were those detected at the first visit , 2-year average values , and average values over the length of the study . Average variables were considered as full predictors when work disability could not be considered to have caused the predictor value . The primary analyses were Kaplan-Meier survival statistics and Cox regression . Proportional hazard assumptions were verified . Results : 79 out of the 823 RA pts ( 9.6 % ) never worked for a salary . All the males and 87.3 % of the females had been employed with a salary . 509 pts were employed at the time they had RA : the following statistical analyses were limited to these subjects . Work discontinuation was reported by 37.7 % . The median survival time or time to work disability was 20.9 years , but the 25 % survival time was 6.4 years . Out of 456 pts working at the first visit , 23 % were work disabled in the first 5 years ( 8.6 in the first 2.5 years ) , 19.4 % in the next 5 years and 57.6 % beginning after 10 years of follow-up . The 25 % survival time ( time to work disability ) was 10.05 years . Fewer years of formal education , a high BMI ( showing a late e ffect on wo rk disab i l i t y ) , VAS pain score s , high HAQ scores , high RF and erythrocyte sedimentation rate ( ESR ) values , and high physical dem and s of the job were the covariates independently associated with work disability . Over the course of the illness , the work disabled patients had a 35 % reduction in family income , and more abnormal scores for the joint count , grip strength , ESR , depression and anxiety . The results , except for BMI , were essentially similar in a subset of 156 pts in whom RA duration was less than one year . Conclusions : Work disability in RA pts was frequent and could be predicted by almost all of the demographic and clinical variables and by the physical characteristics of the work process present at the first visit . The best predicting factors were a persistent elevation of ESR , pain , and disability according to HAQ detected in longitudinal follow-up . Thus , the optimal management of RA pts may differ based on their clinical , demographic , and work variables . The physician should try to treat the clinical variables medically and to m o d u l ate the demographic and wo rk va ri ables by active interaction with the patient , calling in other specialists ( e.g. , psychiatrists or psychiatrics ) where necessary",
"The effect of early vs delayed initiation of slow acting antirheumatic drug ( SAARD ) therapy on the ability to maintain regular work , was evaluated in 83 patients with early rheumatoid arthritis ( RA ) in a placebo controlled , double blind 24-month study . The estimated probability to maintain working ability was higher in the early treatment group , especially during the second study year . Predicting factors were age , type of work , degree of disability and number of swollen joints . Despite the difficulties in interpreting the results due to the complexity of the underlying socioeconomical and labor market situation , the study supports early treatment in RA with regard to the maintenance of normal life",
"Interleukin-1 receptor antagonist ( IL-1Ra ) is a member of the IL-1 gene family , which blocks IL-1-mediated signal transduction . In rheumatoid arthritis ( RA ) , recombinant human IL-1Ra ( anakinra ) has been evaluated in 5 r and omized , placebo-controlled clinical trials . In the European monotherapy study , 43 % of patients receiving 150 mg/day anakinra achieved a 20 % response according to the American College of Rheumatology criteria ( ACR 20 ) , compared to 27 % in the placebo group . In the methotrexate combination therapy study , 42 % of the patients receiving 1 mg/kg/day anakinra achieved an ACR20 response , 24 % an ACR50 response , and 10 % an ACR70 response . In each study , clinical ly meaningful improvements in the Health Assessment Question naire scores were observed . The Economic Re source Survey was employed in the European monotherapy study to evaluate patient and caregiver days of missed work or domestic activity in successive 4-week periods . There were rapid gains in the number of days at work or domestic activity in the treated patients , and the increases in productivity were dose-related . The mean change in the total modified Sharp score of patients who completed treatment with anakinra was significantly less than in the patients who received placebo . Anakinra , a new biologic approach to the treatment of RA , results in significant improvements in the signs and symptoms , has beneficial effects on functional status , and on the rate of progressive structural joint damage"
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Increasing epidemiological studies suggest that there is an association between vitamin D deficiency and risk of type 2 diabetes mellitus ( T2DM ) . Therefore , r and omized clinical trials ( RCTs ) have been performed to observe the effect of vitamin D supplementation on preventing T2DM , decreasing fasting plasma glucose ( FPG ) and improving insulin resistance to confirm the association between vitamin D and T2DM . However , the results of RCTs on controlling FPG level , improving insulin resistance and preventing T2DM in non-diabetics are inconsistent . In the present study , a systematic meta- analysis considering individual variation and intervention strategy was conducted to establish an objective and definitive conclusion . The results suggested that vitamin D supplementation had no significant effect on controlling FPG level , improving insulin resistance or preventing T2DM in non-diabetics in a pooled meta- analysis of 23 articles ( containing 28 RCTs ) . However , stratified analysis indicated that supplementation of vitamin D had differential effects on FPG control , insulin sensitivity improvement and T2DM prevention in individuals with different baseline states : FPG was decreased for those with BMI ; insulin resistance was improved for those with 25(OH)D ≥30 ng/ml ( P=0.021 ) ; and risk of T2DM was lower for pre-diabetic individuals ( P=0.047 ) or for those with 25≤ BMI effect on T2DM prevention was improved when the supplement dose was > 2,000 IU/day ( P=0.047 ) and with intervention without calcium ( P=0.047 ) . Thus , further trials should focus on individual baselines and the supplementation strategy of vitamin D in the prevention of T2DM
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"OBJECTIVE In observational studies , low serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations have been associated with insulin resistance and other risk factors for cardiovascular disease . RESEARCH DESIGN AND METHODS We present 1-year data from an ongoing 5-year trial in 511 individuals with impaired fasting glucose ( IFG ) and /or impaired glucose tolerance ( IGT ) r and omly assigned to 20,000 IU/week vitamin D3 or placebo . An oral glucose tolerance test was performed at baseline and after 1 year . RESULTS Mean baseline serum 25(OH)D was 59.9 nmol/L and 61.1 nmol/L in the vitamin D and placebo groups , respectively , and increased by 45.8 nmol/L and 3.4 nmol/L , respectively . With adjustment for baseline concentrations , no differences in measures of glucose metabolism , insulin secretion or sensitivity , blood pressure , or hs-CRP were found after 1 year . There was a slight , but significant decrease in total and LDL cholesterol in the vitamin D group compared with the placebo group , but as there was also a decrease in HDL cholesterol , the change in the total/HDL cholesterol ratio did not differ significantly . Only analyzing subjects with 25(OH)D vitamin D supplementation does not improve glycemic indices , blood pressure , or lipid status in subjects with IFG and /or IGT ",
"OBJECTIVE Low vitamin D levels predict the development of diabetes . This double-blind , r and omized , control study in subjects with prediabetes and hypovitaminosis D evaluated whether high doses of vitamin D for 1 year affected insulin secretion , insulin sensitivity , and the development of diabetes . RESEARCH DESIGN AND METHODS A total of 1,551 subjects ≥40 years of age not known to have diabetes were screened with A1C levels . Subjects with A1C levels of 5.8–6.9 % underwent an oral glucose tolerance test ( OGTT ) . Subjects with prediabetes and 25-OH vitamin D ( 25-OHD ) levels were r and omized to receive weekly placebo ( n = 53 ) or vitamin D ( n = 56 ) with doses based on body weight and baseline 25-OHD levels . OGTTs were performed 3 , 6 , 9 , and 12 months later . Insulin secretion and sensitivity were measured , and the proportion of subjects developing diabetes was assessed . RESULTS 25-OHD levels rapidly rose from 22 to nearly 70 ng/mL after vitamin D supplementation with a mean weekly dose of 88,865 IU . There were no differences between the placebo and vitamin D groups regarding fasting plasma glucose , 2-h glucose , or insulin secretion and sensitivity or in the percent developing diabetes or returning to normal glucose tolerance . No subjects experienced increased serum or urinary calcium levels . At 12 months , A1C levels were significantly slightly less ( 0.2 % ) in the vitamin D group . CONCLUSIONS In individuals with prediabetes and hypovitaminosis D , doses of vitamin D supplementation design ed to raise serum 25-OHD levels into the upper-normal range for 1 year had no effect on insulin secretion , insulin sensitivity , or the development of diabetes compared with placebo administration",
"CONTEXT Observational studies show an association between low vitamin D status assessed by circulating 25-hydroxyvitamin D and cardiovascular events and mortality . Data from r and omized controlled trials are limited . OBJECTIVE The aim of this study was to test whether daily doses of vitamin D(3 ) at 400 or 1000 IU/d for 1 yr affected conventional markers of cardiovascular disease ( CVD ) risk . DESIGN We conducted a parallel-group , double-blind , placebo-controlled r and omized controlled trial . R and omization was computer generated . Participants and study investigators were blinded to intervention groupings throughout the trial . SETTING The study was conducted at the Clinical Research Facility , University of Aberdeen , United Kingdom . PARTICIPANTS A total of 305 healthy postmenopausal women aged 60 - 70 yr were recruited for the study . INTERVENTION Each woman received a daily capsule of 400 or 1000 IU vitamin D(3 ) or placebo r and omly allocated . MAIN OUTCOME MEASURES Primary outcomes were serum lipid profile [ total , high-density lipoprotein , and low-density lipoprotein cholesterol ; triglycerides ; and apolipoproteins A-1 and B100 ] , insulin resistance ( homeostatic model assessment ) , inflammatory biomarkers ( high-sensitivity C-reactive protein , IL-6 , soluble intracellular adhesion molecule-1 ) , and blood pressure . RESULTS A total of 265 ( 87 % ) participants completed all study visits . Small differences between groups for serum apolipoprotein B100 change [ repeated measures ANOVA , P=0.04 ; mean ( sd ) , -1.0 ( 10.0 ) mg/dl ( 400 IU ) ; -1.0 ( 10.0 ) mg/dl ( 1000 IU ) ; and + 0.02 ( 10.0 ) mg/dl ( placebo ) ] were not considered clinical ly significant . Other systemic markers for CVD risk remained unchanged . There was significant seasonal variation in systolic and diastolic blood pressure independent of vitamin D dose ( P ( sd ) reduction in systolic blood pressure from winter to summer was -6.6 ( 10.8 ) mm Hg . CONCLUSIONS Improving vitamin D status through dietary supplementation is unlikely to reduce CVD risk factors . Confounding of seasonality should be recognized and addressed in future studies of vitamin",
"BACKGROUND Adequate calcium intake can have a favorable effect on some metabolic variables . OBJECTIVE The objective of the study was to determine the effects of daily calcium intake and of supplementation with calcium and vitamin D ( calcium+D ) during a weight-loss intervention on blood pressures , plasma lipid and lipoprotein concentrations , and glucose and insulin concentrations in low calcium consumers . DESIGN Healthy , overweight or obese women ( n = 63 ) with a daily calcium intake of were r and omly assigned in a double-blind manner to 1 of 2 groups : the group consuming 2 tablets/d of a calcium + vitamin D supplement ( 600 mg elemental calcium and 200 IU vitamin D/tablet ) or the group consuming placebo ; both groups observed a 700 kcal/d energy restriction . These 63 women then completed a 15-wk weight-loss intervention . RESULTS Initial daily calcium intake was significantly correlated with plasma HDL cholesterol ( r = 0.41 , P 2-h postload glycemia ( r = -0.29 , P total : LDL and LDL : HDL ( P LDL cholesterol ( P calcium+D group than in the placebo group . The differences in total : HDL and LDL : HDL were independent of changes in fat mass and in waist circumference . A tendency for more beneficial changes in HDL cholesterol , triacylglycerol , and total cholesterol was also observed in the calcium+D group ( P = 0.08 ) . CONCLUSION Consumption of calcium+D during a weight-loss intervention enhanced the beneficial effect of body weight loss on the lipid and lipoprotein profile in overweight or obese women with usual low daily calcium intake",
"Higher circulating 25-hydroxyvitamin D ( 25[OH]D ) concentration has been linked to a lower prevalence of insulin resistance and type 2 diabetes mellitus . However , r and omized controlled trials have not clarified the effect of vitamin D supplementation on insulin resistance in healthy adults . The objective of this study was to assess the effect of vitamin D supplementation for 1 year on insulin resistance ; the study was a secondary analysis of a clinical trial . We hypothesized that increased 25(OH)D concentration after vitamin D supplementation for 1 year would significantly improve insulin resistance . Ninety-six healthy adults participated in this study , of whom 81 completed the study . The participants r and omly received daily either 420 IU vitamin D3 or placebo in a double-blind manner for 1 year . The levels of fasting insulin , glucose , and other parameters were assessed at baseline and after 1 year of intervention . Homeostasis model assessment of insulin resistance index was calculated from insulin and glucose levels . Visceral fat area and physical activity were also investigated . Serum 25(OH)D and 1,25-dihydroxyvitamin D concentrations were significantly increased by approximately 29.5 nmol/L and 7.0 pg/mL , respectively , after 1-year vitamin D supplementation . After vitamin D supplementation , fasting glucose levels and values of homeostasis model assessment of insulin resistance index significantly decreased from 88.3 to 85.3 mg/dL ( P vitamin D supplementation for 1 year effectively improves fasting glucose level and insulin resistance in healthy Japanese adults",
"BACKGROUND Obese adolescents are at a greater risk of vitamin D deficiency because vitamin D is thought to be sequestered by excess adipose tissue . Poor vitamin D status has been associated with a higher prevalence of the metabolic syndrome , type 2 diabetes , or both in adults and adolescents . OBJECTIVE The objective was to determine in obese adolescents the efficacy and safety of 4000 IU vitamin D3/d and whether subsequent increased circulating concentrations of 25-hydroxyvitamin D [ 25(OH)D ] are associated with improved markers of insulin sensitivity and resistance and reduced inflammation . DESIGN Obese adolescent patients [ n = 35 ; mean ± SD age : 14.1 ± 2.8 y ; BMI ( in kg/m(2 ) ) : 39.8 ± 6.1 ; 25(OH)D : 19.6 ± 7.1 ng/mL ] were recruited from the University of Missouri Adolescent Diabetes and Obesity Clinic and were r and omly assigned to receive either vitamin D3 ( 4000 IU/d ) or placebo as part of their st and ard care . Anthropometric measurements , inflammatory markers ( IL-6 , TNF-α , C-reactive protein ) , adipokines ( leptin , adiponectin ) , fasting glucose , fasting insulin , and HOMA-IR values were measured at baseline and at 2 follow-up visits ( 3 and 6 mo ) . RESULTS After 6 mo , there were no significant differences in BMI , serum inflammatory markers , or plasma glucose concentrations between groups . Participants supplemented with vitamin D3 had increases in serum 25(OH)D concentrations ( 19.5 compared with 2.8 ng/mL for placebo ; P 0.001 ) , fasting insulin ( -6.5 compared with + 1.2 μU/mL for placebo ; P = 0.026 ) , HOMA-IR ( -1.363 compared with + 0.27 for placebo ; P = 0.033 ) , and leptin-to-adiponectin ratio ( -1.41 compared with + 0.10 for placebo ; P = 0.045 ) . Inflammatory markers remained unchanged . CONCLUSION The correction of poor vitamin D status through dietary supplementation may be an effective addition to the st and ard treatment of obesity and its associated insulin resistance . This trial was registered at clinical trials.gov as NCT00994396",
"CONTEXT Vitamin D deficiency is associated with insulin resistance and risk of future diabetes . OBJECTIVE The objective of the study was to test whether supplementation with vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes mellitus ( T2DM ) . DESIGN This was a r and omized controlled trial performed in 2008 through 2015 . SETTING The study was conducted at the clinical research unit at a teaching hospital . PATIENTS Five hundred eleven subjects ( mean age 62 y , 314 males ) with prediabetes diagnosed with an oral glucose tolerance test as part of the Tromsø Study 2007–2008 were included . A total of 256 were r and omized to vitamin D and 255 to placebo . Twenty-nine subjects in the vitamin D and 24 in the placebo group withdrew because of adverse events . INTERVENTIONS Interventions included vitamin D ( cholecalciferol ) 20 000 IU/wk vs placebo for 5 years . Annual oral glucose tolerance tests were performed . MAIN OUTCOME MEASURE Progression to T2DM was the main outcome measure . Secondary outcomes were change in glucose levels , insulin resistance , serum lipids , and blood pressure . RESULTS The mean baseline serum 25-hydroxyvitamin D level was 60 nmol/L ( 24 ng/mL ) . One hundred three in the vitamin D and 112 in the placebo group developed T2DM ( hazard risk 0.90 ; 95 % confidence interval 0.69–1.18 , Cox regression , P = .45 , intention to treat analysis ) . No consistent significant effects on the other outcomes were seen . Subgroup analyses in subjects with low baseline 25-hydroxyvitamin D yielded similar results . No serious side effects related to the intervention were recorded . CONCLUSIONS In subjects without vitamin D deficiency , vitamin D supplementation is unlikely to prevent progression from prediabetes to diabetes . Very large studies with inclusion of vitamin D-deficient subjects will probably be needed to show such a putative effect . This study tested if supplementation with vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes ( T2DM )",
"Background : Whether Vitamin D supplementation in prediabetes subjects prevents the development of diabetes is a matter of debate , and the results are inconsistent . This open-label , r and omized study in subjects with prediabetes evaluated the effect of 12 months of Vitamin D supplementation on glycemic parameters and progression of prediabetes to diabetes in an ethnically homogeneous Kashmiri population . Material s and Methods : A total of 147 subjects were diagnosed as prediabetes out of which 137 subjects were r and omized to receive in addition to st and ard lifestyle measures , either Vitamin D 60,000 IU weekly for 4 weeks and then 60,000 IU monthly ( n = 69 ) or no Vitamin D ( n = 68 ) . Fasting plasma glucose ( FPG ) , 2-h plasma glucose and A1C levels were estimated at 0 , 6 and 12 months . Changes in FPG , 2-h plasma glucose , A1C level and the proportion of subjects developing diabetes were assessed among 129 subjects . Results : At 12 months , A1C levels were significantly lesser ( 5.7 % ± 0.4 % ) in the Vitamin D supplemented group when compared with non-Vitamin D supplemented ( 6.0 % ± 0.3 % ) . Similarly , FPG ( 97 ± 7 ) and 2-h plasma glucose ( 132 ± 16 ) were significantly less in Vitamin D supplemented group as compared with non-Vitamin D supplemented group ( FPG = 116 ± 6 and 2-h plasma glucose = 157 ± 25 ) at 12 months . Nine out of 65 in non-Vitamin D supplemented and seven out of 64 in the Vitamin D supplemented group developed diabetes . Conclusions : Vitamin D supplementation in prediabetes subjects significantly lowered FPG , 2-h plasma glucose and A1C levels ",
"Objective : Considering the physiologic roles of vitamin D on insulin regulation , the effects of vitamin D treatment on insulin sensitivity and resistance indexes and beta cell function in pre-diabetic vitamin D deficient patients were investigated . Methods : In a r and omized open clinical trial , 61 pre-diabetic vitamin D deficient patients who were the first degree relatives of type 2 diabetic patients , were enrolled and r and omized into three groups ( A , B and C ) . Group A ( n = 21 ) were treated with intramuscular injection of 300,000 units of vitamin D at the beginning of the study and one month later . In group B ( n = 20 ) , injection of vitamin D plus 500 mg/d calcium and in group C ( n = 20 ) , just calcium was administered for two months . At baseline and two months later , oral glucose tolerance test was done . Homeostasis Model of Assessment -Insulin Resistance ( HOMA-IR ) , insulin resistance index , Homeostasis Model of Assessment -B ( HOMA-B ) which is a beta cell function index , and Matsuda index , an insulin sensitivity index , were calculated and compared before and after intervention and between three groups . Findings : In vitamin D treated groups ( A + B ) , the mean ( SD ) of HOMA-IR increased from 2.46 ( 1.36 ) to 3.1 ( 2.3 ) ( P = 0.02 ) , and Matsuda index decreased from 11 ( 3 ) to 9.0 ( 2.3 ) ( P = 0.001 ) . Conclusion : Injection of vitamin D increased insulin resistance and decreased insulin sensitivity indexes",
"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",
"OBJECTIVE Vitamin D deficiency is associated with an unfavorable metabolic profile in observational studies . The intention was to compare insulin sensitivity ( the primary end point ) and secretion and lipids in subjects with low and high serum 25(OH)D ( 25-hydroxyvitamin D ) levels and to assess the effect of vitamin D supplementation on the same outcomes among the participants with low serum 25(OH)D levels . RESEARCH DESIGN AND METHODS Participants were recruited from a population -based study ( the Tromsø Study ) based on their serum 25(OH)D measurements . A 3-h hyperglycemic clamp was performed , and the participants with low serum 25(OH)D levels were thereafter r and omized to receive capsules of 20,000 IU vitamin D3 or identical-looking placebo twice weekly for 6 months . A final hyperglycemic clamp was then performed . RESULTS The 52 participants with high serum 25(OH)D levels ( 85.6 ± 13.5 nmol/L [ mean ± SD ] ) had significantly higher insulin sensitivity index ( ISI ) and lower HbA1c and triglycerides ( TGs ) than the 108 participants with low serum 25(OH)D ( 40.3 ± 12.8 nmol/L ) , but the differences in ISI and TGs were not significant after adjustments . After supplementation , serum 25(OH)D was 142.7 ± 25.7 and 42.9 ± 17.3 nmol/L in 49 of 51 completing participants r and omized to vitamin D and 45 of 53 r and omized to placebo , respectively . At the end of the study , there were no statistically significant differences in the outcome variables between the two groups . CONCLUSIONS Vitamin D supplementation to apparently healthy subjects with insufficient serum 25(OH)D levels does not improve insulin sensitivity or secretion or serum lipid profile ",
"AIMS Vitamin D deficiency may increase the risk for type 2 diabetes . African Americans tend to have poor vitamin D status and increased risk of diabetes , but effects of vitamin D supplementation on components of diabetes risk have not been tested in this group . This study was conducted to determine whether vitamin D supplementation improves insulin secretion , insulin sensitivity and glycaemia in African Americans with prediabetes or early diabetes . METHODS In this r and omized , placebo-controlled trial , we examined the effect of 4000 IU/day vitamin D(3 , ) on glycaemia and contributing measures including insulin secretion , insulin sensitivity and the disposition index over 12 weeks in 89 overweight or obese African Americans with prediabetes or early diabetes . Outcome measures were derived from oral glucose tolerance testing . RESULTS Mean plasma 25-hydroxyvitamin D was about 40 nmol/l in the placebo and vitamin D groups at baseline and increased to 81 nmol/l with supplementation . Insulin sensitivity decreased by 4 % in the vitamin D group compared with a 12 % increase in the placebo group ( p = 0.034 ) . Insulin secretion increased by 12 % in the vitamin D group compared with a 2 % increase in the placebo group ( p = 0.024 ) , but changes in the disposition index were similar across groups . There was no effect of supplementation on post-load glucose or other measures of glycaemia . CONCLUSIONS Supplementation with 4000 IU/day vitamin D(3 ) successfully corrected vitamin D insufficiency and had divergent effects on insulin secretion and sensitivity with no overall effect on disposition index or glycaemia . In this study , vitamin D supplementation for 3 months did not change the pathophysiology of prediabetes in overweight and obese African Americans",
"AIMS Low serum 25-hydroxyvitamin-D ( 25(OH)D ) concentrations are associated with insulin resistance , β-cell dysfunction and type 2 diabetes . We conducted a 24-week double-blind , r and omized , placebo-controlled trial to examine the effect of 28 000 IU of vitamin D3 once weekly on plasma glucose after a 2 hour-75 g oral glucose tolerance test ( 2hrPC glucose ) , insulin sensitivity and β-cell function . STUDY DESIGN AND METHODS A total of 71 participants with serum 25(OH)D ≤65 nmol/L , impaired fasting glucose and elevated glycated hemoglobin were r and omly assigned to receive 28 000 IU of vitamin D3 ( VitD ; n = 35 ) or placebo ( n = 36 ) in cheese once weekly for 24 weeks . The primary outcome was the change in 2hPC glucose . Secondary outcomes were fasting glucose , fasting and postpr and ial insulin , indices of insulin sensitivity and β-cell function , glycated hemoglobin and lipid profile . Participants underwent an oral glucose tolerance test to determine 2hPC glucose . RESULTS Mean baseline serum 25(OH)D was 48.1 and 47.6 nmol/L in the VitD and placebo groups , respectively . Serum 25(OH)D significantly increased to 98.7 nmol/L ( 51 nmol/L increase ; P in fasting ( P = .42 ) or 2hPC glucose ( P = .55 ) or other indices of glucose metabolism , including β-cell function and insulin sensitivity , were observed between groups . A subgroup analysis of individuals with 25(OH)D nmol/L and prediabetes did not change these results . The VitD group exhibited a significant reduction in LDL cholesterol ( -0.27 vs 0.01 mmol/L , P = .03 ) . CONCLUSION Weekly doses of vitamin D3 in individuals with suboptimal vitamin D levels who were at risk for type 2 diabetes did not improve oral glucose tolerance or markers of glycaemic status ",
"AIMS Vitamin D deficiency is considered as a risk factor in cardiometabolic disorders , including cardiovascular diseases , hypertension and Type 2 diabetes mellitus . We have investigated the effect of vitamin D3 supplementation on glucose homeostasis in healthy overweight and obese women . METHODS In a double-blind r and omized placebo-controlled clinical trial , 77 healthy overweight or obese women ( mean age 38 ± 8 years ; BMI 29.9 ± 4.2 kg/m(2 ) ) were r and omly assigned to the vitamin D3 group ( 25 μg/day as cholecalciferol tablets ) or the placebo group . Selected anthropometric indices , glucose , insulin , HbA(1c ) and homeostasis model assessment of insulin resistance at baseline and after 12 weeks were measured . Dietary intakes using 24-h food recall and food frequency question naires were assessed . Physical activity was assessed by the International Physical Activity Question naire . Adjusted mean differences were calculated using analysis of covariance . Correlation coefficients were calculated by Pearson 's analysis . RESULTS Mean fasting blood glucose concentrations declined in the vitamin D3 and placebo groups ( -0.28 ± 0.4 vs. -0.65 ± 0.4 mmol/l , P the mean percentage of HbA(1c ) was decreased ( -13 ± 18 vs. -19 ± 17 mmol/l , P = 0.06 ) in both groups , respectively . Mean 25-hydroxyvitamin D concentrations increased in the vitamin D3 and placebo groups ( 38.2 ± 32 vs. 4.6 ± 14 nmol/l , P correlation between HbA(1c ) and 25-hydroxyvitamin D concentrations ( r = -0.271 ; P = 0.018 ) . CONCLUSIONS The results indicate that the vitamin D3 supplement of 25 μg/day had no beneficial effect on glycaemic indices in healthy overweight or obese women",
"BACKGROUND Low serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations have been associated with insulin resistance , the metabolic syndrome , and type 2 diabetes . Because many non-Western immigrants in the Netherl and s are vitamin D deficient , obese , and at high risk of diabetes , vitamin D supplementation may contribute to prevent diabetes and insulin resistance . OBJECTIVE We examined the effect of vitamin D supplementation on insulin sensitivity and β cell function in overweight , vitamin D-deficient , non-Western immigrants at high risk of diabetes . DESIGN The study was a 16-wk , r and omized , placebo-controlled trial . A total of 130 non-Western immigrants with prediabetes ( fasting glucose concentration > 5.5 mmol/L or r and om glucose concentration from 7.8 to 11.1 mmol/L ) and vitamin D deficiency ( serum 25[OH]D concentration were r and omly assigned after stratification by sex to receive either cholecalciferol ( 1200 IU/d ) or a placebo for 16 wk . All participants received 500 mg Ca/d as calcium carbonate . The primary outcome was the difference in the area under the curve of insulin and glucose after a 75-g oral-glucose-tolerance test after 4 mo of treatment . Secondary outcomes were insulin-sensitivity variables , β cell-function variables , and metabolic syndrome . RESULTS Mean serum 25(OH)D concentrations increased significantly in the vitamin D compared with placebo groups . After 4 mo of therapy , the mean between-group difference was 38 nmol/L ( 95 % CI : 32.1 , 43.9 nmol/L ; P effect on insulin sensitivity and β cell function . In a post hoc analysis , when patients with diabetes at baseline were excluded , a significant increase in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L ( P = 0.040 ) . CONCLUSIONS Vitamin D supplementation in non-Western vitamin D-deficient immigrants with prediabetes did not improve insulin sensitivity or β cell function or change the incidence of metabolic syndrome . However , after the exclusion of diabetic subjects , an improvement in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L. This trial was registered at trialregister.nl as NTR1827",
"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 )",
"BACKGROUND A suboptimal vitamin D and calcium status has been associated with higher risk of type 2 diabetes in observational studies , but evidence from trials is lacking . OBJECTIVE We determined whether vitamin D supplementation , with or without calcium , improved glucose homeostasis in adults at high risk of diabetes . DESIGN Ninety-two adults were r and omly assigned in a 2-by-2 factorial- design , double-masked , placebo-controlled trial to receive either cholecalciferol ( 2000 IU once daily ) or calcium carbonate ( 400 mg twice daily ) for 16 wk . The primary outcome was the change in pancreatic β cell function as measured by the disposition index after an intravenous-glucose-tolerance test . Other outcomes were acute insulin response , insulin sensitivity , and measures of glycemia . RESULTS Participants had a mean age of 57 y , a body mass index ( BMI ; in kg/m(2 ) ) of 32 , and glycated hemoglobin ( Hb A(1c ) ) of 5.9 % . There was no significant vitamin D × calcium interaction on any outcomes . The disposition index increased in the vitamin D group and decreased in the no-vitamin D group ( adjusted mean change ± SE : 300 ± 130 compared with -126 ± 127 , respectively ; P = 0.011 ) , which was explained by an improvement in insulin secretion ( 62 ± 39 compared with -36 ± 37 mU · L(-1 ) · min , respectively ; P = 0.046 ) . Hb A(1c ) increased less , but nonsignificantly , in the vitamin D group than in the no-vitamin D group ( 0.06 ± 0.03 % compared with 0.14 ± 0.03 % , respectively ; P = 0.081 ) . There was no significant difference in any outcomes with calcium compared with no calcium . CONCLUSION In adults at risk of type 2 diabetes , short-term supplementation with cholecalciferol improved β cell function and had a marginal effect on attenuating the rise in Hb A(1c ) . This trial was registered at clinical trials.gov as NCT00436475",
"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"
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BACKGROUND Allergies and food reactions are common and may be associated with foods including adapted cow 's milk formulas . Formulas containing hydrolysed proteins have been used to treat infants with allergy or food intolerance , and have been advocated for prevention of allergy and food intolerance in infants . OBJECTIVES To determine whether use of hydrolysed formulas for infant feeding prevents allergy and food intolerance . If hydrolysed formulas are effective , to determine what type of hydrolysed formula is most effective including extensively and partially hydrolysed formulas . To determine which infants benefit including infants at low or high risk of allergy and infants receiving early , short term or prolonged formula feeding . SEARCH STRATEGY The st and ard search strategy of the Cochrane Neonatal Review Group was used including search es of the Cochrane Controlled Trials Register ( 2003 , Issue 1 ) , MEDLINE ( 1966 - January 2003 ) , EMBASE ( 1980 - January 2003 ) and CINAHL ( 1982 - January 2003 ) and previous review s including cross references . SELECTION CRITERIA R and omised and quasi-r and omised trials that compare the use of a hydrolysed infant formula to human milk or cow 's milk formula . Trials with > 80 % follow up of participants were eligible for inclusion . DATA COLLECTION AND ANALYSIS Eligibility of studies for inclusion , method ological quality and data extraction were assessed independently by each review er . Primary outcomes included clinical allergy , specific allergies and food intolerance . Meta- analysis was conducted using a fixed effects model . MAIN RESULTS Eighteen trials met criteria for inclusion . No eligible trials compared prolonged hydrolysed formula to human milk feeding . Two trials compared early , short term hydrolysed formula to human milk feeding and reported no significant difference in infant allergy or childhood cow 's milk allergy ( CMA ) . Two trials compared early , short term hydrolysed formula to cow 's milk formula feeding with no significant benefits reported . One large quasi-r and om study reported a reduction in infant CMA of borderline significance in low risk infants ( RR 0.62 , 95 % CI 0.38 , 1.00).Seven studies compared prolonged feeding of hydrolysed formula to cow 's milk formula without using co- interventions for allergy prevention . Meta- analysis of 4 studies ( 386 infants ) found a significant reduction in allergy incidence in infancy ( typical RR 0.63 , 95 % CI 0.47 , 0.85 ; RD -0.15 , 95 % CI -0.25 , -0.06 ) . One study reported a significant reduction in allergy incidence in childhood ( RR 0.54 , 95 % CI 0.36 , 0.81 ) . Significant reductions were found in asthma prevalence in childhood , eczema incidence in infancy and prevalence in childhood , food allergy prevalence in childhood , and CMA incidence in infancy . All studies enrolled infants at high risk of allergy . Only three trials comparing prolonged hydrolysed formula feeding to cow 's milk formula feeding were considered of good methodology . Only one of these trials demonstrated a benefit into childhood ( 5 years of age ) . No eligible trials examined the effects of prolonged hydrolysed formula feeding on allergy beyond early childhood . Costs were not reported . Three trials compared prolonged feeding with an extensive to a partially hydrolysed formula and reported no significant difference in allergy incidence in infancy . REVIEW ER 'S CONCLUSIONS There is no evidence to support feeding with a hydrolysed formula for the prevention of allergy in preference to exclusive breast feeding . In high risk infants who are unable to be completely breast fed , there is evidence that prolonged feeding with a hydrolysed compared to a cow 's milk formula reduces infant and childhood allergy and infant CMA . Further trials are required to determine if significant clinical benefits persist beyond 5 years of age and if there is any additional benefit from use of an extensive compared to a partially hydrolysed formula . Incremental costs of formula and the effect on compliance should be measured
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"Vomiting , large gastric residuals and abdominal distension are common in very immature infants on formula feeding . The present trial investigated whether a protein hydrolysate formula reduces the gastrointestinal transit time in preterm infants . Fifteen preterm infants ( median gestational age 29 ( 24–32 ) wk , birthweight 1241 ( 660–1900 ) g , postnatal age 18 ( 5–54 ) d ) on full enteral feeds ( > 150 ml/kg*d ) were enrolled . It was hypothesized that the gastrointestinal transit time is at least 2 h shorter when protein hydrolysate formula is fed compared with st and ard preterm formula . In a r and omized cross‐over design study , each formula was fed for 5 d. On days 4 and 9 the gastrointestinal transit time was estimated using carmine red . The protein hydrolysate formula had a markedly shorter gastrointestinal transit time ( 9.8 h ) than the st and ard formula ( 19 h ) ( p= 0.0022 , two‐sided Mann‐Whitney U test )",
"AIMS Different protein sources could determine differences in the maturation of the exocrine pancreas in humans during the first months after birth ; however , no studies have been carried out in man to evaluate the effect of a hydrolyzed protein diet on exopancreatic function . Our aim was therefore to determine the effect of two different milk formulas on pancreatic secretion in patients with cow 's milk protein allergy ( CMPA ) . METHODS We selected 12 infants ( median age , 3.0 months ) , fed for 6 weeks with a hydrolyzed casein-based formula , and 14 infants ( median age , 3.0 months ) who received a soy-protein based formula over the same period . As controls , two groups of age-matched infants with no gastrointestinal disease and receiving a free diet were studied . In the patients with CMPA a secretin-cerulein test was performed at the commencement of the diet and after 6 weeks ; in the controls the same test was performed only once . Enzyme concentrations and outputs of trypsin , chymotrypsin , lipase , and phospholipase were assayed . RESULTS No significant difference was observed between the two groups of patients with CMPA for any of the enzymes studied , either at base line or after 6 weeks of diet . No difference was recorded between CMPA patients and age-matched controls on a free diet either . In both CMPA groups there was a significant increase over basal values in trypsin , chymotrypsin , and lipase concentrations after 6 weeks . Furthermore , there was a significant positive correlation between the age of the patients and enzyme concentrations . Mean daily weight gain was 27.4 + /- 3.9 g with hydrolyzed casein and 27.2 + /- 3.5 g in soyfed patients . CONCLUSIONS It is suggested that the diets with different protein content used in subjects with CMPA did not determine any difference in the stimulation of proteolytic and lipolytic pancreatic enzymes",
"OBJECTIVE To determine the effect of brief early exposure to cows ’ milk on atopy in the first 2 years of life . DESIGN Double blind , placebo controlled , r and omised feeding intervention trial ( Bokaal study ) . SETTING Dutch midwifery practice s. PARTICIPANTS 1533 breast fed neonates . INTERVENTION Exposure to cows ’ milk protein ( n = 758 ) or a protein free placebo ( n = 775 ) during the first 3 days of life . MAIN OUTCOME MEASURES Clinical atopic disease and any positive radioallergosorbent ( RAST ) tests at 1 year of age . RESULTS Atopic disease in the first year was found in 10.0 % ( cows ’ milk)v 9.3 % ( placebo ) of the children , with a relative risk of 1.07 ; in the second year , atopic disease was found in 9.6 % v 10.2 % , respectively , with a relative risk of 0.94 . Per protocol analysis showed similar results . Any RAST positive test was found in 9.4 % ( cows ’ milk)v 7.9 % ( placebo ) of children , with a relative risk of 1.19 . Stratified analysis for high family risk of allergy showed a doubled incidence of atopic disease but no effect from the intervention . CONCLUSION Early and brief exposure to cows ’ milk in breast fed children does not increase the risk of atopic disease in the first 2 years",
" A group of 130 healthy term infants were r and omly assigned at birth to one of three feeding regimens for the first 3 days of life : human milk ( HM ) , cow-milk formula ( CMF ) , or a casein hydrolysate formula ( CHF ) . The formula-fed infants received no human milk during the study days . After day 3 , all infants were exclusively breast-fed . Blood sample s were taken at 4 days and at 2 and 4 months of age during outpatient visits . Macromolecular absorption was analyzed 60 min after a feed of human milk by measuring the serum α-lactalbumin ( S-αLA ) concentrations by a competitive radioimmunoassay . Total serum IgE ( S-lgE ) was assayed by radioimmu-noassay . The median S-IgE value was significantly lower at 2 months of age in the CHF group than in the HM group . The values remained significantly lower , even at 4 months of age , in the CHF group than in either the HM or the CMF group . The median S-αLA concentration at 2 months of age was significantly higher in the CHF group than in either the HM group or the CMF group . No significant differences could be found between the CMF and HM groups at any time . One infant in the HM group and one infant in the CMF group developed infantile colic . Two infants in the CHF group developed symptoms of cow-milk allergy . All other infants were healthy at 4 months of age",
"OBJECTIVE --To study the effect of early diet on the development of allergic reactions in infants born preterm . DESIGN --Two r and omised prospect i ve trails . In trail A infants were r and omly allocated banked donor milk or preterm formula as their sole diet or ( separately r and omised ) as a supplement to their mother 's expressed breast milk . In trial B infants were allocated term or preterm formula . A blind follow up examination was done 18 months after the expected date of birth . SETTING --Neonatal units of hospitals in Cambridge , Ipswich , King 's Lynn , Norwich , and Sheffield . Outpatient follow up . PARTICIPANTS --777 Infants with a birth weight less than 1850 g born during 1982 to 1984 . MAIN OUTCOME MEASURES --Development of eczema , allergic reactions to food or drugs , and asthma or wheezing by nine and 18 months after term . Whenever possible the observations were confirmed by rechallenge or clinical examination . RESULTS --At 18 months after term there was no difference in the incidence of allergic reactions between dietary groups in either trial . In the subgroup of infants with a family history of atopy , however , those in trial A who received preterm formula rather than human milk had a significantly greater risk of developing one or more allergic reactions ( notably eczema ) by 18 months ( odds ratio 3.6 ; 95 % confidence interval 1.4 to 9.1 ) . CONCLUSIONS --Feeding neonates on formulas based on cows ' milk , including those with a high protein content , did not increase the overall risk of allergy . Nevertheless , in the subgroup with a family history of atopy early exposure to cows ' milk increased the risk of a wide range of allergic reactions , especially eczema",
"A total of 105 “ high‐risk ” infants born in 1988 were studied prospect ively from birth to 18 months of age . The infants were recommended breastfeeding and /or hypoallergenic formula ( Nutramigen or Profylac ) combined with avoidance of solid foods during the first 6 months of life . All mothers had unrestricted diet . Avoidance of daily exposure to tobacco smoke , furred pets and dust‐collecting material s in the bedroom were advised . This prevention group was compared with a control group consisting of 54 identically defined “ high‐risk ” infants born in 1985 in the same area . All infants had either severe single atopic predisposition combined with cord blood IgE ≥ 0.5 KU/1 or biparental atopic predisposition . The control group had unrestricted diet and was not advised about environmental factors . Apart from the prevention programme and year of birth the prevention group and the control group were comparable . The parents were highly motivated and compliance was good . The rate of participation was 97 % , and 85 % followed the dietary measures strictly . The cumulative prevalence of atopic symptoms was significantly lower at 18 months in the prevention group ( 32 % ) , as compared with the control group ( 74 % ) ( p prevalence of recurrent wheezing ( 13 % , versus 37 % ; p ) , atopic dermatitis ( 14 % versus 31 % ; p ) , vomiting/diarrhoea ( 5 % versus 20 % ; p and infantile colic ( 9 % versus 24 % ; p The cumulative prevalence of food allergy was significantly lower in the prevention group ( 6 % versus 17 % ; p groups daily exposure to tobacco smoke increased the risk of recurrent wheezing significantly ( p with breastmilk and /or hypoallergenic formula combined with avoidance of solid foods until the age of 6 months appeared to reduce the cumulative prevalence of atopic symptoms during the first 18 months of life",
"Abstract Objectives : To investigate the association between the duration of exclusive breast feeding and the development of asthma related outcomes in children at age 6 years . Design : Prospect i ve cohort study . Setting : Western Australia . Subjects : 2187 children ascertained through antenatal clinics at the major tertiary obstetric hospital in Perth and followed to age 6 years . Main outcome measures : Unconditional logistic regression to model the association between duration of exclusive breast feeding and outcomes related to asthma or atopy at 6 years of age , allowing for several important confounders : sex , gestational age , smoking in the household , and early childcare . Results : After adjustment for confounders , the introduction of milk other than breast milk before 4 months of age was a significant risk factor for all asthma and atopy related outcomes in children aged 6 years : asthma diagnosed by a doctor ( odds ratio 1.25 , 95 % confidence interval 1.02 to 1.52 ) ; wheeze three or more times since 1 year of age ( 1.41 , 1.14 to 1.76 ) ; wheeze in the past year ( 1.31 , 1.05 to 1.64 ) ; sleep disturbance due to wheeze within the past year ( 1.42 , 1.07 to 1.89 ) ; age when doctor diagnosed asthma ( hazard ratio 1.22 , 1.03 to 1.43 ) ; age at first wheeze ( 1.36 , 1.17 to 1.59 ) ; and positive skin prick test reaction to at least one common aeroallergen ( 1.30 , 1.04 to 1.61 ) . Conclusion : A significant reduction in the risk of childhood asthma at age 6 years occurs if exclusive breast feeding is continued for at least the 4 months after birth . These findings are important for our underst and ing of the cause of childhood asthma and suggest that public health interventions to optimise breast feeding may help to reduce the community burden of childhood asthma and its associated traits . Key messages Asthma is the leading cause of admission to hospital in Australian children and its prevalence is increasing Whether breast feeding protects against asthma or atopy , or both , is controversial Asthma is a complex disease , and the relative risks between breast feeding and asthma or atopy are unlikely to be large ; this suggests the need for investigation in a large prospect i ve birth cohort with timely assessment of atopic outcomes and all relevant exposures Exclusive breast feeding for at least 4 months is associated with a significant reduction in the risk of asthma and atopy at age 6 years and with a significant delay in the age at onset of wheezing and asthma being diagnosed by a doctor Public health interventions to promote an increased duration of exclusive breast feeding may help to reduce the morbidity and prevalence of childhood asthma and",
"A total of 1167 infants were followed for 1 year in a population -based prospect i ve study to assess the effect of environmental factors on the development of allergic disorders . Some of these environmental factors are interdependent . Mothers who formula fed their infants smoked more often ( p less than 0.001 ) and tended to belong to lower social classes ( p less than 0.01 ) . Logistic regression analysis was performed to adjust for these confounding variables . Maternal smoking adversely affected the prevalence of asthma ( p = 0.003 ) defined as three or more separate episodes of wheezing and total allergy ( p = 0.02 ) . Infants in lower socioeconomic groups developed asthma significantly more often ( p = 0.03 ) than infants born in higher socioeconomic groups . There was a nonsignificant trend for infants born in summer to develop asthma more than infants born in winter ( p = 0.08 ) . No effect of these factors was observed on eczema , food intolerance , or on the subgroup of infants with definite allergy ( clinical disorder with positive skin prick test [ SPT ] ) . Exposure to animal d and er did not influence the prevalence of clinical disorder , but positive SPT reaction to cat d and er was more prevalent in infants who were exposed to cats and /or dogs ( p = 0.04 ) . Positive SPT to house dust mite occurred significantly more often in infants who were formula fed ( p = 0.05 ) . The environmental factors had a profound effect on the prevalence of asthma but not on other allergic disorders",
"OBJECTIVES To determine the prevalence of soy allergy in IgE-associated cow 's milk allergy ( CMA ) . STUDY DESIGN Children were evaluated for soy allergy by double-blind , placebo-controlled food challenge , open challenge , or convincing previous history of an anaphylactic reaction to soy . Children tolerant to soy at entry received soy formula and were followed up for 1 year . RESULTS Of this IgE-associated CMA cohort ( ages 3 to 41 months ) , 14 % ( 95 % CI = 7 . 7%-22.7 % ) were determined to have soy allergy , 12 definitely at entry and 1 possibly after 1 year of soy ingestion . The latter child experienced severe failure to thrive at enrollment and exhibited improved growth while receiving soy during follow-up but was diagnosed with eosinophilic esophagitis at study completion . Improved growth ( P soy formula ( 579 31 mL/d ) during the year of follow-up . CONCLUSIONS Soy allergy occurs in only a small minority of young children with IgE-associated CMA . As such , soy formula may provide a safe and growth-promoting alternative for the majority of children with IgE-associated CMA shown to be soy tolerant at the time of introduction of soy formula",
"Abstract Objective : To describe the incidence and prognosis of wheezing illness from birth to age 33 and the relation of incidence to perinatal , medical , social , environmental , and lifestyle factors . Design : Prospect i ve longitudinal study . Setting : Engl and , Scotl and , and Wales . Subjects : 18 559 people born on 3 - 9 March 1958 . 5801 ( 31 % ) contributed information at ages 7 , 11 , 16 , 23 , and 33 years . Attrition bias was evaluated using information on 14 571 ( 79 % ) subjects . Main outcome measure : History of asthma , wheezy bronchitis , or wheezing obtained from interview with subjects ' parents at ages 7 , 11 , and 16 and reported at interview by subjects at ages 23 and 33 . Results : The cumulative incidence of wheezing illness was 18 % by age 7 , 24 % by age 16 , and 43 % by age 33 . Incidence during childhood was strongly and independently associated with pneumonia , hay fever , and eczema . There were weaker independent associations with male sex , third trimester antepartum haemorrhage , whooping cough , recurrent abdominal pain , and migraine . Incidence from age 17 to 33 was associated strongly with active cigarette smoking and a history of hay fever . There were weaker independent associations with female sex , maternal albuminuria during pregnancy , and histories of eczema and migraine . Maternal smoking during pregnancy was weakly and inconsistently related to childhood wheezing but was a stronger and significant independent predictor of incidence after age 16 . Among 880 subjects who developed asthma or wheezy bronchitis from birth to age 7 , 50 % had attacks in the previous year at age 7 ; 18 % at 11 , 10 % at 16 , 10 % at 23 , and 27 % at 33 . Relapse at 33 after prolonged remission of childhood wheezing was more common among current smokers and atopic subjects . Conclusion : Atopy and active cigarette smoking are major influences on the incidence and recurrence of wheezing during adulthood . Key messages Incidence of wheezing illness at all ages was strongly and consistently related to a history of hay fever or eczema ( atopy ) . Associations with maternal smoking during pregnancy , abdominal pain , and migraine were largely confined to those without atopy Active smoking was a powerful and potentially avoidable risk factor for wheeze starting in adult life among both atopic and non-atopic subjects A quarter of the children with a history of asthma or wheezy bronchitis by age 7 reported wheeze in the past year at age 33 Recurrence of wheezing after prolonged remis- sion during late adolescence was strongly associ- ated with atopy and cigarette smoking",
"In a double blind study , 40 infants with cows ' milk intolerance of various causes were r and omised to receive a nutritionally complete formula in which nitrogen was supplied either as whey hydrolysate or amino acids . The median age of infants was 10 weeks ( range 36 weeks ' gestation to 108 weeks ' postnatal age ) . After a median follow up period of 25 weeks there was no significant difference in dietary intake between the formulas . Twenty four weeks after entry , weight and weight for length improved equally on both formulas . Plasma albumin improved significantly on the hydrolysed whey formula but not in the amino acid group . Both milks were palatable and normal intakes of formula were maintained . Biochemical and haematological indices remained within normal limits . There was no difference in stool frequency and vomiting between the two formulas . Two infants developed a probable allergic colitis while receiving hydrolysed whey . Amino acid formula may have a role in the management of atopic infants with severe cows ' milk intolerance who have already reacted to whey or casein hydrolysate formula",
"Several different protein hydrolysate-based infant formulas have been promoted as hypoallergenic and considered suitable for the dietary management of cow 's milk allergy ( CMA ) . Accepting that none of the hydrolysate-based products is completely safe , the American Academy of Pediatrics ( AAP ) recommends that these formulas should be tested in a double-blind placebo-controlled setting and tolerated by at least 90 % of children with proven CMA . In principle , this recommendation is also endorsed by the European Society of Paediatric Gastroenterology and Nutrition ( ESPGAN ) and the European Society of Paediatric Allergy and Clinical Immunology ( ESPACI ) . In this two-center study , 32 children with proven CMA were tested with the extensive hydrolysate whey formula Nutrilon Pepti , for comparison with Profylac ( extensive ) and Nan HA ( partial ) whey hydrolysate products . Skin-prick tests ( SPTs ) were , respectively , positive to the three hydrolysate formulas in 19 % , 15 % , and 32 % of children . After oral challenge it was concluded that 97 % ( 95 % CI : 85 - 100 % ) of the children tolerated Nutrilon Pepti , 94 % ( 95 % CI : 75 - 100 % ) tolerated Profylac , and 64 % ( 95 % CI : 37 - 81 % ) tolerated Nan HA . This study demonstrates that the extensive hydrolysates Nutrilon Pepti and Profylac are well tolerated in a population of children with proven CMA and that both products can be considered safe for their intended use . This study confirms that a very small number of children react even to extensively hydrolyzed formulas . SPT prior to oral exposure to the hydrolysate-based formulas can indicate whether a child is at risk of showing reactions to the product . Introduction of new products to these children should be carried out under a doctor 's supervision . However , the majority of the SPT-positive children did tolerate the two extensively hydrolyzed whey-based formulas tested",
"BACKGROUND Many infants with cow 's milk protein intolerance have adverse reactions to soy , casein and whey hydrolysate formula and to other foods . The recent development of Neocate , a hypoallergenic , nutritionally complete infant formula composed of individual amino acids and other nutrients , has enabled these infants to be stabilized . OBJECTIVE We observed the effect of food challenges in infants with reported hypersensitivity to hypoallergenic formulas . METHODS Eighteen infants ( median age , 7 1/2 months ) were given Neocate formula for 2 months and then underwent a 7-day double-blind placebo-controlled challenge with the formula previously best tolerated . RESULTS In 12 of the 18 infants irritability , vomiting , diarrhea , and /or eczema flares developed during the formula challenge . In two patients symptoms developed immediately , but in the remainder adverse reactions evolved within 7 days ( range , 4 to 7 days ) . Adverse reactions were to soy formula ( six patients ) , whey hydrolysate ( two ) , and casein hydrolysate ( four ) . When infants were 12 months of age , parents reported adverse reactions after the ingestion of other low allergen foods ( median , six ; from a panel of 10 such foods ) . CONCLUSION A group of infants with late-onset adverse reactions to soy , extensively hydrolyzed casein , and whey formulas and to other foods has been identified . Neocate formula proved to be an effective substitute formula for these patients",
"BACKGROUND Early feeding with cow 's milk ( CM ) may increase the risk of cow 's milk allergy ( CMA ) . OBJECTIVE We sought to examine prospect ively whether supplementary feeding of CM at the maternity hospital would increase the risk when compared with feeding with pasteurized human milk or hydrolyzed formula . METHODS We studied 6209 unselected healthy , full-term infants , of whom 5385 ( 87 % ) required supplementary milk while in the hospital . The infants were r and omly assigned to receive CM formula ( 1789 infants ) , pasteurized human milk ( 1859 infants ) , or whey hydrolysate formula ( 1737 infants ) . The comparison group ( 824 infants ) was composed of infants who were exclusively breast-fed . The infants were followed for 18 to 34 months for symptoms suggestive of CMA . The primary endpoint was a challenge-proven adverse reaction to CM after a successful CM elimination diet . RESULTS The cumulative incidence of CMA in the infants fed CM was 2.4 % compared with 1.7 % in the pasteurized human milk group ( odds ratio [ OR ] , 0.70 ; 95 % confidence interval [ CI ] , 0 . 44 - 1.12 ) and 1.5 % in the whey hydrolysate group ( OR , 0.61 ; 95 % CI , 0 . 38 - 1.00 ) . In the comparison group , CMA developed in 2.1 % of the infants . Among the infants who required supplementary feeding at hospital , both exposure to CM while in the hospital ( OR , 1.54 ; 95 % CI , 1.04 - 2.30 ; P = .03 ) and obvious parental atopy ( OR , 2.32 ; 95 % CI , 1.53 - 3.52 ; P CMA . CONCLUSIONS Our data indicate that feeding of CM at maternity hospitals increases the risk of CMA when compared with feeding of other supplements , but exclusive breast-feeding does not eliminate the risk",
"This prospect i ve , long-term study assessed the effects of a protein hydrolysate formula on allergy prevention in infants with a family history of allergy . Infants were r and omly assigned to receive either the hydrolysate formula ( n = 92 ) or an adapted cow milk formula ( n = 85 ) alone or with breast-feeding for 4 months . The groups did not differ in family allergy history scores or cord blood IgE levels . After 4 months , total IgE levels and allergic reactions did not differ significantly between groups , although the hydrolysate group had a lower prevalence of eczema . At 12 months of age , neither IgE levels nor allergic reactions were significantly different . At 2 years of age , however , 18 allergic reactions had occurred in the hydrolysate group and 31 had occurred in the control group ; the differences were significant for eczema ( p asthma . At 4 years of age , allergic signs were found in 11 children in the hydrolysate group and in 17 children in the control group ; the difference was significant only for eczema ( p protein hydrolysate formula to infants at risk for allergies had a long-term preventive effect on the prevalence of eczema but not of asthma",
"In a prospect i ve study of a 1-year birth cohort of 158 high-risk infants the effect of feeding breastmilk , a casein hydrolysate ( Nutramigen ) or a new ultrafiltrated whey hydrolysate ( Profylac ) on the development of cow milk protein allergy/intolerance ( CMPA/CMPI ) was assessed and compared . All the infants had biparental or severe single atopic predisposition , the latter combined with cord blood IgE > or = 0.5 kU/L. At birth all infants were r and omized to Nutramigen or Profylac , which was used when breastfeeding was insufficient or not possible during the first 6 months of life . During the same period this regimen was combined with avoidance of solid foods and cow milk protein . All mothers had unrestricted diets and were encouraged to do breastfeeding only . Moreover , avoidance of daily exposure to tobacco smoking , furred pets and dust-collecting material s in the bedroom was advised . The infants were followed prospect ively from birth to 18 months of age . All possible atopic symptoms were registered and controlled elimination/challenge studies were performed when symptoms suggested CMPA/CMPI . A total of 154 ( 97 % ) were followed up and 141 followed the diet strictly . Eighty-eight ( 62 % ) of the infants were breastfed for at least 6 months , 20 ( 14 % ) were breastfed exclusively , 59 and 62 had varying amounts of Nutramigen or Profylac respectively . CMPA/CMPI was diagnosed in 1/20 , 1/59 and 3/62 in the breastfed , the Nutramigen and Profylac groups respectively , but 1 of the latter also had Nutramigen . None of the infants showed reactions against Nutramigen or Profylac . In 4 infants symptoms were provoked by breastmilk when the mother ingested cow milk and in 1 only by cow milk . ( ABSTRACT TRUNCATED AT 250 WORDS",
"BACKGROUND Allergy is a common cause of illness . The effect of feeding different infant formulas on the incidence of atopic disease and food allergy was assessed in a prospect i ve r and omized double-blind study of high-risk infants with a family history of atopy . METHODS 216 high-risk infants whose mothers had elected not to breast-feed were r and omized to receive exclusively a partial whey hydrolysate formula or a conventional cow 's milk formula or a soy formula until 6 months of age . Seventy-two high risk infants breast-fed for > or = 4 months were also studied . RESULTS Follow-up until 5 years of age showed a significant lowering in the cumulative incidence of atopic disease in the breast-fed ( odds ratio 0.422 [ 0.200 - 0.891 ] ) and the whey hydrolysate ( odds ratio 0.322 [ 0.159 - 0.653 ) groups , compared with the conventional cow 's milk group . Soy formula was not effective ( odds ratio 0.759 [ 0.384 - 1.501 ] ) . The occurrence of both eczema and asthma was lowest in the breast-fed and whey hydrolysate groups and was comparable in the cow 's milk and soy groups . Similar significant differences were noted in the 18 - 60 month period prevalence of eczema and asthma . Eczema was less severe in the whey hydrolysate group compared with the other groups . Double-blind placebo-controlled food challenges showed a lower prevalence of food allergy in the whey hydrolysate group compared with the other formula groups . CONCLUSIONS Exclusive breast-feeding or feeding with a partial whey hydrolysate formula is associated with lower incidence of atopic disease and food allergy . This is a cost-effective approach to the prevention of allergic disease in children",
"STUDY OBJECTIVES To examine the prevalence of asthma and hay fever , and the incidence and temporal relationships of asthma , hay fever , and chronic bronchitis among adult twins during a 15-year period . DESIGN Prospect i ve cohort study . PARTICIPANTS A population of 11,540 Finnish adult men and women , initially 18 to 45 years of age , who returned a health question naire in 1975 , 1981 , and 1990 as part of the Finnish Twin Cohort study . METHODS Age-st and ardized prevalences and cumulative incidences among individuals were calculated for asthma , hay fever , and chronic bronchitis . The incidence of asthma among subjects with and without hay fever or chronic bronchitis was analyzed in the entire cohort as well as in twin pairs discordant for incident asthma . RESULTS The prevalence of asthma increased slightly from 1975 ( 2.0 % in men and 2.2 % in women ) to 1990 ( 2.9 % in men and 3.1 % in women ) . The prevalence of hay fever showed a larger increase in men and women ( from 6.8 % and 9.8 % to 11.8 % and 15.3 % , respectively ) . Compared with figures for 1976 to 1981 , no significant increase in asthma incidence occurred from 1982 to 1990 , whereas the incidence of hay fever was lower during the latter period among men ( incidence rate ratio , 0.7 ; 95 % confidence interval , 0.6 to 0.9 ) as was the incidence of chronic bronchitis among women ( incidence rate ratio , 0.7 ; 95 % confidence interval , 0.6 to 0.9 ) . Hay fever and chronic bronchitis were usually diagnosed before asthma . Both diseases increased the risk of asthma significantly on the basis of analyses of all individuals and of discordant twin pairs . CONCLUSIONS The pattern of increase in asthma and hay fever prevalence with time was similar , and hay fever was a strong predictor of asthma . These diseases showed no significant increase in incidence",
"Abstract . One hundred and twenty‐one women with history of a previous child with atopic disease were r and omly allocated during the next pregnancy to antigen avoidance or control groups . Dietary advice consisted of almost complete exclusion of milk and dairy products , egg , fish , beef and peanut throughout pregnancy and lactation . A total of 109 completed the study . Maternal antigen avoidance was associated with reduced occurrence of atopic eczema and the skin involvement was less extensive and milder . The beneficial effect was observed mainly in the breast‐fed group . Among the fifty‐five who completed the trial of antigen avoidance , seventeen infants developed atopic eczema , five out of thirty‐five who were breast‐fed and twelve out of twenty who were formula‐fed . Among the offspring of fifty‐four control mothers given no dietary restriction , eczema was observed in twenty‐four infants , eleven out of thirty‐six breast‐fed and thirteen of eighteen formula‐fed . Avoidance of common dietary allergens during pregnancy and lactation enhanced the preventive beneficial effect of exclusive breast feeding on the incidence of atopic eczema among infants at high risk",
"A large multicentre study on the short and long term clinical and developmental outcome of infants r and omised to different diets is being undertaken . This report represents an interim analysis of the early postnatal growth performance of an unselected population of 194 preterm infants ( gestation , mean ( SD ) 31 . 0 ( 2 . 9 ) weeks ; birthweight , mean ( SD ) 1364 ( 294 ) g ) , both ill and well , examined in two ( of four ) parallel trials . One trial compared banked breast milk with a new preterm formula ( primary trial ) ; the other compared these diets as supplements to maternal milk ( supplement trial ) . A major dietary effect on the number of days taken to regain birthweight and subsequent gains in weight , length , and head circumference was observed in the primary trial . Infants fed banked breast milk and weighing less than 1200 g at birth took a calculated additional three weeks to reach 2000 g compared with those fed on the preterm formula . A significant influence of diet on body proportions was seen in the relation between body weight , head circumference , and length . Similar though smaller differences in growth patterns were seen in the supplement trial . By the time they reach 2000 g , infants of birthweights 1200 to 1849 g fed on banked breast milk and infants below 1200 g fed on either banked breast milk or maternal milk supplemented ( as necessary ) with banked breast milk , fulfilled stringent criteria for failure to thrive ( weight less than 2 SD below the mean for age ) . Only infants fed the preterm formula as their sole diet had maintained their birth centile by discharge from hospital . The misleading nature of comparisons between extrauterine and intrauterine steady state weight gains is emphasised",
"The determinants of wheezing and allergy were investigated in 453 children with a family history of allergic disease . A r and omised controlled trial examined the effects of withholding cows ' milk protein during the first three months of life and replacing cows ' milk with soya milk . The children were followed up to the age of 7 years . Withholding cows ' milk did not reduce the incidence of allergy or wheezing . Children who had ever been breast fed had a lower incidence of wheeze than those who had not ( 59 % and 74 % respectively ) . The effect persisted to age 7 years in the non-atopics only , the risk of wheeze being halved in the breast fed children after allowing for employment status , sex passive smoking , and overcrowding . Allergic disease was not associated with exposure to tobacco smoke , house dust mite antigen , or cats . Breast feeding may confer long term protection against respiratory infection",
"Early feeding with cows ' milk ( CM ) may cause cows ' milk allergy ( CMA ) . Breast milk contains many immune factors which compensate for the undeveloped defence mechanisms of the gut of the newborn infant . We studied the effect of supplementary CM feeding at the maternity hospital on the subsequent incidence of CMA , the effects of formula and breast feeding on the subsequent immunologic types of CMA , and the importance of immune factors present in colostrum in the immune responses of infants with CMA . In a cohort of 6209 infants , 824 were exclusively breast-fed and 87 % required supplementary milk while in the maternity hospital : 1789 received CM formula , 1859 pasteurized human milk , and 1737 whey hydrolysate formula . The cumulative incidence of CMA , verified by a CM elimination-challenge test , was 2.4 % in the CM , 1.7 % in the pasteurized human milk and 1.5 % in the whey hydrolysate group . Among these infants , exposure to CM at hospital and a positive atopic heredity increased the risk of CMA . Of the exclusively breast-fed infants , 2.1 % had CMA . Risk factors for the development of IgE-mediated CMA were : exposure to CM at hospital , breast-feeding during the first 8 weeks at home either exclusively or combined with infrequent exposure to small amounts of CM and long breast-feeding . The content of transforming growth factor-beta1 ( TGF-beta1 ) in colostrum from mothers of infants with IgE-mediated CMA was lower than from mothers of infants with non-IgE-mediated CMA . In infants with CMA , TGF-beta1 in colostrum negatively correlated with the result of skin prick test and the stimulation of peripheral blood mononuclear cells to CM , but positively with infants ' IgA and IgG antibodies to CM proteins . Feeding of CM formula at maternity hospital increases the risk of CMA , but exclusive breast-feeding does not eliminate the risk . Prolonged breast-feeding exclusively or combined with infrequent exposure to small amounts of CM during the first 8 weeks induces the development of IgE-mediated CMA . Colostral TGF-beta1 may inhibit IgE- and cell mediated reactions and promote IgG-IgA antibody production to CM in infants prone to developing CMA",
"The allergy preventive effect of extensively ( N ) and partially ( PH ) hydrolysed cows ’ milk formulas compared with a regular formula ( RM ) was assessed in 155 infants with a family history of allergy . No cows ’ milk was given during the first nine months of life and no egg and fish up to 12 months of age . Breast feeding mothers avoided the same foods . At weaning the infants were r and omised to one of the formula groups . The cumulative incidence of atopic symptoms at 18 months was 51 , 64 , and 84 % in the N , PH , and RM groups , respectively . From 6 to 18 months there were significantly less cumulative atopic symptoms in the N group compared with the RM group , and significantly less than the PH group up to 6 ( N = 25 % ; PH = 46 % ) and 9 months ( N = 34 % , PH = 58 % ) . At 9 months significantly fewer infants in the N group ( 10 % ) than in the PH group ( 33 % ) had a positive skin prick test to eggs . The findings support an allergy preventive effect of an extensively hydrolysed formula , but not of a partially hydrolysed formula , during the first 18 months of life of high risk infants",
"BACKGROUND One hundred twenty children , identified before birth as being at high risk for atopy , were prenatally assigned to prophylactic or control groups . METHODS The infants in the prophylactic group either received breast milk from mothers on an exclusion diet or an extensively hydrolyzed formula . Their bedrooms and living rooms were treated repeatedly with an acaricide , and they used polyvinyl-covered mattresses with vented head areas . The infants in the control group were fed conventionally , and no environmental control was recommended . RESULTS A significant advantage , first demonstrated at 1 year of age , persists for children in the prophylactic group . They have less of any allergy or eczema , but the reduced prevalence of asthma is no longer significant . Only three children in the prophylactic group had positive skin prick test results compared with 16 in the control group , suggesting a significant reduction in sensitization . CONCLUSION A dual approach to allergen avoidance , focusing on foods and aeroallergens , appears to be beneficial in selected high-risk infants . Avoidance of potent allergens in early life increases the threshold for sensitization in these high-risk infants . Whether sensitization has been avoided or merely deferred has yet to be proved",
"ABSTRACT A prospect i ve case‐control study is presented to assess an allergy prevention programme in children up to 36 months of age . Infants born at three maternity hospitals were followed from birth : 279 infants with high atopic risk ( intervention group ) were compared with 80 infants with similar atopic risk but no intervention ( non‐intervention group ) . The intervention programme included dietary measures ( exclusive and prolonged milk feeding diet followed by a hypoantigenic weaning diet ) and environmental measures ( avoidance of parental smoking in the presence of the babies , day care > 2 years of life ) . Mothers in this group who had insufficient breast milk were r and omly assigned to one of two coded formulas : either a hydrolysed milk formula ( Nidina HA , Nestlé ) or a conventional adapted formula ( Nan , Nestlé ) . Other environmental measures remained the same as for the breastfeeding mothers . The non‐intervention group were either breastfed or received the usual Italian milk feeding and weaning diet , without environmental advice . The main outcome measures were anthropometric measurements and allergic disease manifestations . Normal anthropometric data were observed both in the intervention group and in the nonintervention group . The incidence of allergic manifestations was much lower in the intervention group than in the nonintervention group at 1 year ( 11.5 versus 54.4 % , respectively ) and at 2 years ( 14.9 versus 65.6 % ) and 3 years ( 20.6 versus 74.1 % ) . Atopic dermatitis and recurrent wheezing were found in both the intervention group and the non‐intervention group from birth up to the second year of life , while urticaria and gastrointestinal disorders were only present in the non‐intervention group in the first year of life . Conjunctivitis and rhinitis were present after the second year in both the intervention group and the non‐intervention group . Relapse of the same allergic symptom was less in the intervention group ( 13.0 % ) than in the non‐intervention group ( 36.9 % ) . In comparison to the non‐intervention group , there were fewer intervention group cases with two or more different allergic symptoms ( 8.7 versus 32.6 % ) , and they were more likely to avoid steroid treatment ( 0 versus 10.8 % ) and hospital admission ( 0 versus 6.5 % ) . Babies in the non‐intervention group fed with adapted formula were more likely to develop allergies than breastfed babies in the same group . In the intervention group the breastfed infants had the lowest incidence of allergic symptoms , followed by the infants fed the hydrolysed formula ( ns ) . Infants in the intervention group fed the adapted formula had significantly more allergies than the breastfed and hydrolysed milk fed infants , although less than their counterparts in the non‐intervention group . Of the affected subjects in the intervention group , 80.4 % were RAST and /or Prick positive to food or inhalant allergens . Total serum IgE values detected at birth in the intervention group were not predictive , but at 1 and 2 years of age , IgE values more than 2 SD above the mean in asymptomatic babies were found to predictive for later allergy . In breastfed babies the total IgE level at 1 and 2 years of age was lower than in the other two feeding groups . Of the various factors tested in the non‐intervention group , the following were the most important in the pathogenesis of allergic symptoms : ( i ) formula implementation begun in the first week of life ; ( ii ) early weaning ( ; ( iii ) feeding beef ( ; ( iv ) early introduction of cow 's milk ( parental smoking in the presence of the babies and early day care admission ( ( exclusive breastfeeding and /or hydrolysed milk feeding , delayed and selective introduction of solid foods , and environmental advice ) were effective at the third year of follow‐up , greatly reducing allergic manifestations in high atopic risk babies in comparison with those not receiving these interventions",
"Aims : To determine the effect of brief early exposure to cows ' milk on the expression of atopy during the first five years of life . Methods : Follow up analysis of a double blind , placebo controlled , r and omised feeding intervention trial ( BOKAAL study ) . Subjects were 1108 children from 1533 initially r and omised breast fed neonates in the Netherl and s. Atopic disease and prevalence of allergic symptoms at age 1 , 2 , and 5 , and specific IgE at age 1 and 5 were determined . Results : Atopic disease in the first year was found in 10.0 % ( cows ' milk ) versus 9.3 % ( placebo ) of the children , with a relative risk ( RR ) of 1.07 . No differences were found in the second year either . At age 5 , atopic disease was found in 26.3 % ( cows ' milk ) versus 25.0 % ( placebo ) , RR 1.05 . There was no difference in the prevalence of allergic symptoms . Specific IgE to cows ' milk ( RAST positive 2 + or more ) was 5.8 % ( cows ' milk ) versus 4.1 % ( placebo ) at age 1 ( RR 1.43 ) , and 5.3 % versus 3.0 % at age 5 ( RR 1.77 ) . There was no difference in sensitisation to other common allergens between the two groups . Conclusion : Early , brief exposure to cows ' milk in breast fed children is not associated with atopic disease or allergic symptoms up to age 5",
"BACKGROUND The natural history of allergic disease and its potential for prevention merit close examination because of the explosive worldwide increase in the prevalence and morbidity of atopic disorders . This study examines the development of atopy at age 7 years in 165 children in a high-risk cohort , previously reported from birth to age 4 years . METHODS In this prospect i ve , r and omized , controlled study of food allergen avoidance in infancy , the prophylactic-treated group consisted of infants whose mothers avoided cow 's milk , egg , and peanut during the last trimester of pregnancy and lactation and who , themselves , avoided cow 's milk until age 1 year ( casein hydrolysate supplementation before age 1 ) , egg until age 2 years , and peanut and fish until age 3 years . The control group consisted of maternal/infant pairs who followed st and ard feeding practice s. RESULTS Despite a significant reduction in food allergy and milk sensitization before age 2 years , none of the following differed between the groups at age 7 years : food allergy , atopic dermatitis , allergic rhinitis , asthma , any atopic disease , lung function , food or aeroallergen sensitization , serum IgE level , or presence of nasal eosinophils or nasal basophilic cells . Children with food allergy by 4 years evidence d higher 7-year ( current ) prevalences of allergic rhinitis and asthma ( p Atopic diseases/parameters at age 7 years were shown , by multivariate analysis ( p ( elevated serum IgE level ; egg , cow 's milk , and peanut sensitization ; and nasal eosinophils and nasal basophilic cells ) . CONCLUSIONS These findings help to : ( 1 ) eluci date the natural history of atopic disease in high-risk children ; ( 2 ) document the progression of allergy from atopic dermatitis , food allergy , and food sensitization to respiratory allergy and aeroallergen sensitization despite food allergy prevention in infancy ; ( 3 ) identify allergy predictive markers ; and ( 4 ) exp and our appreciation of the interactions of genetic and environmental factors in the development of atopy",
"BACKGROUND Hydrolysates are used in the treatment and prevention of cows milk protein allergy . Hydrolysis might alter the plasma level of amino acids . METHODS Forty-five infants were included in a double-blind prospect i ve study and were r and omized in two groups : one receiving a whey predominant formula ( n = 20 ) and the second group receiving a whey hydrolysate formula ( n = 25 ) . Weight and length gain was evaluated up to the age of 13 weeks , when blood was sample d for determination of fasting plasma amino acids . RESULTS Four infants of the hydrolysate group dropped out because refusal to ingest the formula . Weight and length gain at 13 weeks of age were extremely comparable . Significant differences in plasma concentrations were observed for a number of nonessential and essential amino acids ( p = .035 to .0001 ) . Threonine and lysine were both higher in the hydrolysate group , and aspartic acid , cystine , methionine , tyrosine , phenylalanine , histidine , and arginine were lower in the hydrolysate group . CONCLUSIONS These differences in plasma amino acid levels have to be regarded with care because all concentrations were within normal ranges , with the exception of threonine . Weight and length gain of the hydrolysate and the whey predominant formula were identical",
"Summary Aim of the study . An allergen-reduced dietary intervention programme with strict dietary requirements was implemented over the first four months of life in an unselected population -based infant cohort and compared to a non-intervention cohort ( the ZUFF study ) . Recommendations for the dietary programme in the intervention cohort were extended , but not strictly implemented , until the end of month six . The intervention was based on breastfeeding , a moderate whey hydrolysate formula ( pHF ) , and delayed introduction of weaning foods with a high allergenicity . This study was a prospect i ve , controlled , and unblinded study , the first to assess the effects of an allergen-reduced , pHF-based early nutritional programme in a broad unselected infant population . Because overall healthy development of the infant is a major objective of any nutritional programme , the study evaluated the effects of the dietary intervention on infant growth and general health status rather than specific allergic manifestations . Part I of this paper gave results for nutritional behaviour only , and Part II gives results for growth and general health status during the intervention period through the sixth month of life . Methods . Assignment of study infants was to demographically comparable intervention ( Z ) or control ( FF ) cohorts according to place of birth . In the intervention cohort ( Z=564 ) , the recommended dietary regimen was breastfeeding and – if exclusive breastfeeding was not possible – supplementation with a moderately hydrolysed , allergen-reduced infant formula ( pHF ) . Weaning foods were delayed until four months of age or later in case of weaning foods with high allergenicity . In the control cohort ( FF=566 ) , there was no specific intervention . Imbalances between cohorts in confounding ( adjuvant ) factors that could influence health related outcomes were integrated as covariates into the logistic regression of the main analyses . Growth parameters included weight , length , head circumference , BMI , and Z scores ( SDS ) . General health status was assessed by clinical ly significant findings in gastrointestinal , respiratory , or skin symptoms . Results . Growth at 6 weeks and at 3 and 6 months was similar for Z and FF . Significantly fewer Z than FF infants had clinical ly noteworthy health findings at 3 months ( Z=27 % versus FF=37 % , odds ratio=0.63 , CI=0.48–0.82 ) and 6 months ( Z=33 % versus FF=49 % , odds ratio=0.51 , CI=0.40–0.66 ) . This corresponds to a 30 % reduction in overall health concerns at 6 months for the intervention cohort . At 3 and 6 months , differences between cohorts in most measures of general health status were strongly influenced by a lower incidence of skin symptoms in the Z cohort . Within FF , there were fewer exclusively breastfed ( eBF ) infants with health problems at 3 months compared with those who were partially ( pBF ) or non-breastfed ( nBF ) ( eBF=31 % , pBF=40 % , nBF=39 % , p number of infants with health concerns was similar for exclusively breastfed infants and for those in whom mother 's milk was supplemented or replaced by pHF ( eBF=29 % , pBF=25 % , nBF=26 % , ns ) . In a sub analysis of overall health findings in infants without a family risk of allergies , there were again significantly fewer Z than FF infants with any health or any skin problem . Conclusion .An allergen-reduced dietary recommendation that includes a moderate whey hydrolysate infant formula ( pHF ) has no negative effects on growth parameters up to 6 months of life in an infant population unselected for atopic risk . The dietary intervention produced improvements in general health status when compared with a control cohort that received infant formula with unhydrolysed proteins ( IF ) , and high allergenic weaning foods at an earlier age . The difference between cohorts was principally due to fewer adverse skin findings . In infants following our allergen-reduced feeding recommendation , 3-month general health status was comparable between those who were exclusively breastfed and those in whom breastfeeding was supplemented or replaced by pHF . Our results demonstrate that a pHF feeding recommendation during the first 4 to 6 months of life – when exclusive breestfeeding is not possible – is a safe and feasible regimen not only in high-allergic risk population s but in general unselected infant population . The general use of pHF formula in non- or partly breastfed infants could therefore be considered an important contribution to optimised infant nutrition",
"There is much evidence that the development of allergic disorders may be related to early exposure of allergens , including those in breastmilk . We have tried to find out whether avoidance of food and inhaled allergens in infancy protects against the development of allergic disorders in high-risk infants . In a prenatally r and omised , controlled study 120 infants with family history of atopy and high ( greater than 0.5 kU/l ) cord-blood concentrations of total IgE were allocated r and omly to prophylactic and control groups . In the prophylactic group ( n = 58 ) , lactating mothers avoided allergenic foods ( milk , egg , fish , and nuts ) and avoided feeding their infants these foods and soya , wheat , and orange up to the age of 12 months ; the infants ' bedrooms and living rooms were treated with an acaricidal powder and foam every 3 months , and concentrations of Dermatophagoides pteronyssinus antigen(Der p l ) in dust sample s were measured by enzyme-linked immunosorbent assay . In the control group ( n = 62 ) , the diet of mothers and infants was unrestricted ; no acaricidal treatment was done and Der p l concentrations were measured at birth and at 9 months . A paediatric allergy specialist unaware of group assignment examined the infants for allergic disorders at 10 - 12 months . Odds ratios were calculated by logistic regression analysis for various factors with control for other confounding variables . At 12 months , allergic disorders had developed in 25 ( 40 % ) control infants and in 8 ( 13 % ) of the prophylactic group ( odds ratio 6.34 , 95 % confidence intervals 2.0 - 20.1 ) . The prevalences at 12 months of asthma ( 4.13 , 1.1 - 15.5 ) and eczema ( 3.6 , 1.0 - 12.5 ) were also significantly greater in the control group . Parental smoking was a significant risk factor for total allergy at 12 months whether only one parent smoked ( 3.97 , 1.2 - 13.6 ) or both parents smoked ( 4.72 , 1.2 - 18.2 )",
"BACKGROUND The relationship between infant feeding and childhood asthma is controversial . This study tested the hypothesis that the relation between breast feeding and childhood asthma is altered by the presence of maternal asthma . METHODS Healthy non-selected newborn infants ( n=1246 ) were enrolled at birth . Asthma was defined as a physician diagnosis of asthma plus asthma symptoms reported on ⩾2 question naires at 6 , 9 , 11 or 13 years . Recurrent wheeze ( ⩾4 episodes in the past year ) was reported by question naire at seven ages in the first 13 years of life . Duration of exclusive breast feeding was based on prospect i ve physician reports or parental question naires completed at 18 months . Atopy was assessed by skin test responses at the age of 6 years . RESULTS The relationship between breast feeding , asthma , and wheeze differed with the presence or absence of maternal asthma and atopy in the child . After adjusting for confounders , children with asthmatic mothers were significantly more likely to have asthma if they had been exclusively breast fed ( OR 8.7 , 95 % CI 3.4 to 22.2 ) . This relationship was only evident for atopic children and persisted after adjusting for confounders . In contrast , the relation between recurrent wheeze and breast feeding was age dependent . In the first 2 years of life exclusive breast feeding was associated with significantly lower rates of recurrent wheeze ( OR 0.45 , 95 % CI 0.2 to 0.9 ) , regardless of the presence or absence of maternal asthma or atopy in the child . Beginning at the age of 6 years , exclusive breast feeding was unrelated to prevalence of recurrent wheeze , except for children with asthmatic mothers in whom it was associated with a higher odds ratio for wheeze ( OR 5.7 , 95 % CI 2.3 to 14.1 ) , especially if the child was atopic . CONCLUSION The relationship between breast feeding and asthma or recurrent wheeze varies with the age of the child and the presence or absence of maternal asthma and atopy in the child . While associated with protection against recurrent wheeze early in life , breast feeding is associated with an increased risk of asthma and recurrent wheeze beginning at the age of 6 years , but only for atopic children with asthmatic mothers",
"Background : Chronic diarrhea is the most common gastrointestinal symptom of intolerance of cow 's milk among children . On the basis of a prior open study , we hypothesized that intolerance of cow 's milk can also cause severe perianal lesions with pain on defecation and consequent constipation in young children . Methods : We performed a double-blind , crossover study comparing cow 's milk with soy milk in 65 children ( age range , 11 to 72 months ) with chronic constipation ( defined as having one bowel movement every 3 to 15 days ) . All had been referred to a pediatric gastroenterology clinic and had previously been treated with laxatives without success ; 49 had anal fissures and perianal erythoma or edema . After 15 days of observation , the patients received cow 's milk or soy milk for 2 weeks . After a one week washout period , the feedings were reversed . A response was defined as eight or more bowel movements during a treatment period . Results : Forty-four of the 65 children ( 68 percent ) had a response while receiving soy milk . Anal fissures and pain with defecation resolved . None of the children who received cow 's milk had a response . In all 44 children with a response , the response was confirmed with a double blind challenge with cow 's milk . Children with a response had a higher frequency of coexistent rhinitis , dermatitis , or bronchospasm than those with no response ( 11 of 44 children vs. 1 of 21 , P = 0.05 ) ; they were also more likely to have anal fissures and erythema or edema at base line ( 40 of 44 vs. 9 of 21 , P inflammation of the rectal mucosa on biopsy ( 26 of 44 vs. 5 of 21 , P = 0.008 ) , and signs of hypersensitivity , such as specific IgE antibodies to cow's-milk antigens ( 31 of 44 vs. 4 of 21 , p In young children , chronic constipation can be a manifestation of intolerance of cow 's milk",
"Background Because infant formulas containing hydrolyzed cow milk protein are used to reduce feeding intolerance and to improve gastric emptying , the effect on gastrointestinal motility of a hydrolysate formula was compared with that of a st and ard preterm formula . Methods Thirty-six preterm newborns with a gestational age of 32.2 ± 2.3 weeks were assigned r and omly to st and ard formula or hydrolyzed formula . Cutaneous electrogastrography and ultrasound examination of gastric emptying were performed simultaneously to evaluate gastrointestinal motility before and after the test meal . All recording sessions were performed 1 week after infants had reached full enteral feeding . Results No significant difference in gastrointestinal symptoms was noted in the newborns fed the different formulas . In particular , regurgitation and vomiting were observed in 78 % versus 64 % of preterm newborns after st and ard and hydrolyzed formula , respectively ( Fisher exact test , not significant ) . No differences were found in terms of gastric electrical activity and gastric emptying time between the two groups . Conclusions It seems unnecessary to use hydrolysate formulas to improve motility in preterm infants ",
"BACKGROUND The importance of the inflammatory response in allergic disease has warranted investigation of two of the more integral cells in the pathogenesis of allergic rhinitis , namely , nasal basophilic cells ( NBCs ) and nasal eosinophils ( NEs ) . In the present study the natural history of NBCs and NEs was studied from birth through 4 years of age in infants of atopic parents to better underst and their relationship to the development of various atopic disorders . METHODS During a prospect i ve , r and omized , controlled trial of the effect of maternal and infant food avoidance on the development of atopic disorders in 288 infants of atopic parents , NBCs and NEs were determined semiquantitatively on Wright-Geimsa stained nasal mucosal scrapings and related to each other and to various atopic parameters . RESULTS In these infants who are at high risk NBCs developed in both those becoming atopic and those remaining nonatopic , but they occurred with increased frequency and quantity in those children in whom most allergic disorders and food or inhalant sensitization developed . NEs , rare at 4 months in all infants , increased in atopic children from 1 to 4 years , and remained infrequent and nominal in nonatopic children . Levels of NBCs and NEs ( 1 ) correlated with each other strongly , directly , and with increasing magnitude in children from ages 4 months to 4 years and ( 2 ) correlated with log serum IgE levels weakly and moderately in children from ages 2 to 4 years . Stepwise linear regression analyses revealed that allergic rhinitis accounted for most of the variance seen in the level of NBCs and NEs during early childhood , reaching 50 % by age 4 years . Asthma , atopic dermatitis , food allergy , food and inhalant sensitization , serum IgE level , and IgG beta-lactoglobulin level accounted for a small proportion of the variance in NBCs and NEs from ages 4 months to 4 years . CONCLUSIONS These findings help to eluci date the natural history of NBCs and NEs in infants at risk for atopic disorders and document the temporal association of these cells with the development of atopic disease , principally allergic rhinitis",
"BACKGROUND The prevalence of asthma has increased in developed countries in the past 2 decades . The effectiveness of intervention measures on the primary prevention of asthma has not been well studied . OBJECTIVE To assess the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants ( in this study , infants are defined as persons from birth to the age of 1 year ) . DESIGN Prospect i ve , prenatally r and omized , controlled study with follow-up through the age of 1 year . SETTING University hospital-based setting s at 2 Canadian centers : Vancouver , British Columbia , and Winnipeg , Manitoba . PARTICIPANTS A total of 545 high-risk infants ( at least 1 first-degree relative with asthma or 2 first-degree relatives with other IgE-mediated allergic diseases ) identified before birth . INTERVENTIONS Avoidance of house dust mite and pet allergens and environmental tobacco smoke , encouragement of breastfeeding , and supplementation with a partially hydrolyzed formula . MAIN OUTCOME MEASURES Probable or possible asthma , rhinitis without apparent colds , and a prick skin test result positive for common inhalant allergens . RESULTS Thirty-eight ( 15.1 % ) of the 251 infants available for assessment in the intervention group and 49 ( 20.2 % ) of the 242 infants available for assessment in the control group fulfilled the criteria for possible or probable asthma ( adjusted relative risk , 0.66 ; 90 % confidence interval , 0.44 - 0.98 ) . Also , 16.7 % of the infants in the intervention group and 27.3 % of the infants in the control group developed rhinitis without colds ( adjusted relative risk , 0.51 ; 90 % confidence interval , 0.35 - 0.74 ) . The incidence of positive skin test results to 1 or more inhalant allergens was similar in both groups ( 4.4 % in the intervention group and 4.6 % in the control group ) . CONCLUSIONS Our multifaceted intervention program result ed in a modest but significant ( P= .04 ) reduction in the risk of possible or probable asthma and rhinitis without apparent colds at the age of 12 months in high-risk infants . In the absence of a vali date d definition of asthma at the age of 12 months , follow-up studies are needed to determine the effectiveness of the intervention program in the primary prevention of asthma in high-risk infants",
"The aim of this study was to compare the allergy-preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas , in infants with a high risk for development of allergic disease . High-risk infants from four Danish centres were included in the period from June 1994 to July 1995 . Five-hundred and ninety-five high-risk infants were identified . High-risk infants were defined as having biparental atopy , or a single atopic first-degree relative combined with cord blood immunoglobulin E ( IgE ) > or = 0.3 kU/l . At birth all infants were r and omized to one of three different blinded formulas . All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast-feed exclusively . If breast-feeding was insufficient , one of the three formulas , according to r and omization , was given during the first 4 months . It was recommended not to introduce cow 's milk , cow 's milk products . and solid foods until the age of 4 months . After the age of 4 months a normal unrestricted diet and conventional cow 's milk-based formula were given when needed . All infants were followed-up prospect ively with interview and physical examination at the age of 6 , 12 , and 18 months , and if any possible atopic symptoms were reported . If food allergy was suspected , controlled elimination/challenge procedures were performed in a hospital setting . Of 550 infants included in the study , 514 were seen at all visits and 36 were excluded owing to noncompliance . Of 478 infants who completed the study , 232 were exclusively breast-fed , 79 received an extensively hydrolyzed casein formula ( Nutramigen ) , 82 an extensively hydrolyzed whey formula ( Profylac ) , and 85 a partially hydrolyzed whey formula ( Nan HA ) , during the first 4 months of life . These four groups were identical in regard to atopic predisposition , cord blood IgE , birthplace , and gender . Exclusively breast-fed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes , whereas the three formula groups were identical concerning environmental factors . The frequency of breast-feeding was high ; only eight ( 2 % ) children were not breast-fed at all . The three formula groups were identical in regard to duration of breast-feeding and age at introduction of formula and solid foods . No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms . The cumulative incidence of parental-reported cow 's milk allergy was significantly higher in children fed partially hydrolyzed formula ( Nan HA ) compared with extensively hydrolyzed formula ( Nutramigen or Profylac ) at 12 and 18 months ( NanHA , 7.1 % ; Nutramigen , 2.5 % ; Profylac , 0 % ; p=0.033 ) . The cumulative incidence of confirmed cow 's milk allergy was 1.3 % ( three of 232 ) in exclusively breast-fed infants , 0.6 % ( one of 161 ) in infants fed extensively hydrolyzed formula ( Nutramigen or Profylac ) , and 4.7%(four of 85 ) in infants fed partially hydrolyzed formula ( Nan HA ) . Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow 's milk allergy , 0.6 % vs. 4.7 % ( p=0.05 ) , but because of the small number of cases the results should be interpreted with caution . Compared with other similar studies the frequency ofatopic symptoms was low , even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 4 months",
"BACKGROUND Distressed behavior is common in infants and is often attributed to gastroesophageal reflux ( GER ) or food protein intolerance . OBJECTIVE To examine the effect of a hypoallergenic amino acid-based infant formula ( AAF ) on distressed behavior and GER symptoms in infants who failed to respond to extensively hydrolyzed formula and antireflux medications . STUDY DESIGN Nineteen distressed infants ( 9 boys and 10 girls ; median age , 5.0 months ) with presumed GER underwent gastroscopy ( n = 17 ) and esophageal 24-hour pH monitoring ( n = 14 ) . Double-blind placebo-controlled ( DBPC ) formula challenges of AAF versus previously besttolerated formula were conducted . RESULTS Nine infants had histologic evidence of esophagitis , and 9 had inflammatory changes in the stomach and /or duodenum . Symptoms remitted in all infants within 2 weeks of the start of feeding with AAF . On DBPC challenge after a median period of 3 months of receiving AAF , 12 infants were intolerant to active formula ( distress score , 287 vs 580 min/wk , P = . 01 ; symptom score , 23.1 vs 36.1 , P = .03 ) . Seven infants did not relapse and were considered tolerant ( distress score , 470 vs 581 , P = .77 ; symptom score , 29.5 vs 20.2 ; P = .89 ) . CONCLUSION Treatment with AAF may reduce distressed behavior and symptoms of GER in infants with food protein intolerance",
"Serum levels of IgE , IgE antibodies to egg white ( EW ) and cow 's milk ( CM ) , IgG , and IgA antibodies to ovalbumin ( OA ) and beta-lactoglobulin ( BLG ) were measured in a group of 115 infants with a family history of atopy/allergy at birth and at 3 , 6 , 9 , 12 , and 18 months of age . The mothers of 65 infants avoided eggs , CM , and fish during the first 3 months of lactation ( maternal antigen avoidance diet , D group ) , whereas the remaining 50 mothers had no diet restrictions ( no maternal antigen avoidance diet , ND group ) . CM was introduced after 6 months of age and EW after 9 months . The only statistically significant difference between the D and ND group infants was a lower rate of specimens with IgE antibodies to EW and /or CM in the infants at 3 months of age ( p = 0.008 ) . IgE antibodies to EW and /or CM appeared in 62 infants during the study period and often during complete breast-feeding . In 40 of the infants , IgE antibodies appeared before the introduction of EW and CM into the diet . The IgE concentrations of the D and the ND group infants were similar . Cord-blood IgE was a poor predictor of atopy/allergy ; for example , only seven of 103 infants with double heredity for atopy/allergy had values above the 90th percentile of our normal reference . The concentrations of IgG antibodies to OA and BLG were similar in the two groups . The levels decreased significantly ( p less than 0.001 ) from birth to 6 months of age , indicating a passive placental transfer . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Forty-five healthy infants were included in a double-blind r and omized prospect i ve study comparing the nutritional value of two formulas . One group received a whey-predominant formula ( n = 20 ) ; the other group received a whey hydrolysate formula ( n = 25 ) . Four infants of the whey hydrolysate group were dropped because they refused the formula . Although the mean daily volume intake was smaller with the whey hydrolysate formula compared with the whey-predominant formula ( p weight gain in the two groups after 13 weeks was identical ( 27.2 g/day in both groups ; the mean difference in weight gain between the groups after 13 weeks was only 8 g ) . Length gain at 13 weeks was 10.4 cm in the whey-predominant formula group and 10.8 cm in the whey hydrolysate formula group ( p = NS ) . After 13 weeks , blood was sample d for hemoglobin , hematocrit , red blood cell count , white blood cell count , lymphocytes , glycemia , proteins , albumin , prealbumin , calcium , phosphorus , urea , creatinine , iron , iron-binding capacity , zinc , and vitamins A and E. Except for the iron-binding capacity , zinc , urea ( in plasma as well as in urine ) ( all three were higher in the whey hydrolysate group ) , no significant differences were found . According to these results , exclusive feeding of the whey hydrolysate formula from birth to 3 months of age to healthy infants appears to result in an adequate nutritional status , as assessed at 3 months of age",
"Background Decreased nitrogen levels , calcium intestinal absorption rates , and plasma amino acid imbalances were reported for preterm infants who were fed partially hydrolyzed preterm formulas . In this pilot study , we evaluated a new formula with modified nitrogen and calcium sources . Methods During their second week of life , 16 preterm infants were r and omly assigned to one of two groups : 9 were fed the new partially hydrolyzed formula and 7 were fed a conventional formula . Nutrient balance was performed at the end of the first month of life . Amino acid concentrations and anthropometric parameters were measured at theoretical term . Results Birth weight and gestational age ( mean ± SD ) were similar in the two groups ( 28.9 ± 7.0 weeks and 1183 ± 242 g vs. 27.7 ± 1.0 weeks and 1139 ± 162 g ) . Median nitrogen absorption rates ( 85 % vs. 89%;P = 0.03 ) and biological values ( 59 % vs. 69%;P = 0.13 ) were lower for infants who were fed the new formula than for those fed the conventional formula . After correction for difference in nitrogen intake , there was no significant difference in nitrogen retained between the two groups ( P = 0.11 ) . Plasma amino acid concentrations were also similar in the two groups . Median calcium absorption tended to be higher in the new-formula group than in the conventional-formula group ( 54 % vs. 45 % , P = 0.19 ) . At theoretical term , infants fed the conventional formula were heavier than infants fed the new formula ( 3559 ± 362 g vs. 3193 ± 384 g , P = 0.04 ) . Conclusions Because nitrogen content is 10 % higher in hydrolyzed-protein formula than in entire-protein formula , appropriate nitrogen retention , plasma amino acid profile , and mineral use can be achieved with the new partially hydrolyzed formula . Further studies with larger groups are needed to evaluate the effect on growth",
"The effect of withholding cows ' milk was examined in 487 infants at high risk of allergic disease . Before birth they were r and omly allocated either to a control group , most of whom received cows ' milk preparations , or to an intervention group , who were offered a soya based substitute . Eczema and wheezing occurred to a similar extent in the two groups during the first year of life , although napkin rash , diarrhoea , and oral thrush were commoner in the intervention group , especially during the first three months . Breast feeding for any length of time was associated with a reduced incidence of wheezing and diarrhoea",
"BACKGROUND Cow 's milk allergy ( CMA ) is a common disease of infancy and childhood . An appropriate cow 's milk ( CM ) substitute is necessary for feeding babies with CMA . CM substitutes are soy formulas and casein- or whey-based extensively hydrolyzed formulas . In several countries , including Italy , goat 's milk ( GM ) formulas are available , and some physicians recommend them for feeding babies with CMA . OBJECTIVE We sought to investigate , in vitro and in vivo , the allergenicity of GM in 26 children with proven IgE-mediated CMA . METHODS All the children underwent skin tests with CM and GM ; detection of specific serum IgE to CM and GM ; and double-blind , placebo-controlled , oral food challenges ( DBPCOFCs ) with fresh CM , GM , and , as placebo , a soy formula ( Isomil , Abbott , Italy ) . CAP inhibition and immunoblotting inhibition assays were also carried out in 1 of 26 and 4 of 26 children with positive RAST results to both CM and GM , respectively . RESULTS All the children had positive skin test responses and CAP results to both CM and GM , all had positive DBPCOFC results to CM , and 24 of 26 had positive DBPCOFCs to GM . In CAP inhibition tests , preincubation of serum with CM or GM strongly inhibited IgE either to CM or to GM . In immunoblotting inhibition assays , preincubation with CM completely extinguished reactivity to GM , whereas GM partially inhibited reactivity to CM . CONCLUSIONS These data strongly indicate that GM is not an appropriate CM substitute for children with IgE-mediated CMA . A warning on the lack of safety of GM for children with CMA should be on the label of GM formulas to prevent severe allergic reactions in babies with CMA",
" This study examined 120 infants , aged 3–12 weeks , with severe colics and compared the results of a specific hypoallergenic diet ( group A ) with those of pharmacological treatment ( group B ) . Non‐breastfed group A infants received soy milk and if unresponsive , hydrolyzed milk formulas ; mothers of breast‐fed infants received a diet without cow 's milk , eggs or fish . Breast‐fed and non‐breast‐fed group B infants received dicyclomine hydrochloride 3 mg/kg/day . Results , based on quantitative measurements of crying . indicated that in breast‐fed infants there was no significant improvement between group A ( 62.5 % ) and group B ( 66.6 % ) infants . Among formula‐fed infants , comparison of positive results using soy milk ( 65.9 % ) with positive results using dicyclomine ( 53.3 % ) was not significant ; positive results using soy milk and hydrolyzed milk formulas in non‐responders to soy milk , provided an improvement in 95.4 % of cases . Pharmacological treatment provided an improvement in 53.3 % ) of cases . The diffcrence was significant ( p<0.01 )",
"Ninety-one high atopy-risk infants were prospect ively followed up to 18 months of age with regard to the development of allergic/atopic manifestations and sensitization . They were r and omized into one of two feeding groups , i.e. , a hydrolyzed , ultrafiltered cow 's milk whey formula , Profylac ( n = 32 ) , or an ordinary cow 's milk formula ( n = 39 ) , for 12 months , started after exclusive breast-feeding for 0 - 9 ( median 6.0 ) months . Lactating mothers avoided milk , egg , and fish , as did the infants up to 12 months of age . Twenty of the 91 infants were breast-fed exclusively for more than 9 months and regarded as a control group . All infants were followed-up by question naires , physical examinations , skin prick tests , and determination of serum total IgE and cow ' milk-specific IgE. The frequency of allergic/atopic disease was similar in the three groups . However , all three infants who developed cow 's milk allergy with skin symptoms belonged to the cow 's milk formula group . The skin prick test with whey hydrolysate was negative in all , while with cow 's milk it was positive in eight infants . Growth was similar in the three groups . The study comprises too few infants to allow us to make statistically based statements . However , the difficulties encountered and the limited effects obtained by the use of whey hydrolysate at weaning at about 6 months of age made us conclude that we can spare high atopy-risk families this extra burden",
"Incidence and clinical manifestation of cow 's milk protein intolerance ( CMPI ) were studied in 1158 unselected newborn infants followed prospect ively from birth to 1 year of age . No food changes were required in 914 infants who were used as healthy controls . When CMPI was suspected ( 211 infants ) , diagnostic dietary interventions according to a st and ard protocol were performed . After exclusion of lactose intolerance , two positive cow 's milk elimination/challenge tests were considered diagnostic of CMPI . Two hundred and eleven symptomatic infants were examined for possible CMPI . A large group of 80 infants improved on a lactose reduced formula . In 87/211 infants CMPI was excluded ( sick controls ) . Finally CMPI was proven in 26 infants . The calculated incidence rate for CMPI was 2.8 % . The principal symptoms in infants with CMPI were gastrointestinal , dermatological and respiratory in 50 % , 31 % and 19 % respectively . A positive family history for atopy ( first or second degree relatives ) was more frequent in either CMPI infants ( 65 % ) , or sick controls ( 63 % ) when compared to either healthy controls ( 35 % ) or infants improving on a low lactose formula ( 51 % ) . Differences between patients with CMPI and sick controls were only found for the presence of atopy in at least 2 first degree relatives [ ( 5/26 in CMPI infants and 4/87 in sick controls ( P multiorgan involvement [ 10/26 infants with CMPI as opposed to 12/87 in the sick control group ( P<0.02 ) ] . These statistical differences are too weak to be of clinical value",
"Weight-gain in 35 slightly undernourished Australian Aboriginal infants was studied in hospital ( 49 admissions ) during a blind controlled trial of a pre-hydrolysed low-lactose milk preparation and reconstituted full-cream milk powder . Infants fed the lactose hydrolysed milk gained 70 % more weight than those receiving normal milk . Better weight-gains were achieved in those on the lactose hydrolysed milk irrespective of percentage st and ard weight for age , the presence of diarrhoea on admission to the trial , and stool sugar concentrations . The use of low-lactose milk should be considered in nutritional aid programmes for undernourished children throughout the world",
"The effect of different feeding regimens , notably the use of hydrolysed cow 's milk formulas , on the development of allergic reactions and the development of cow 's milk protein-IgG antibodies is still disputed . We prospect ively compared the development of allergic manifestations and cow 's milk protein-IgG antibodies in a total of 702 infants who were divided into six groups:1.exclusively breast milk for at least 4 weeks (n=206).2.Breast milk plus initial partially hydrolysed formula (n=104).3.Breast milk plus extensively hydrolysed formula (n=50).4.Breast milk plus initial conventional cow 's milk formula (n=73).5.Conventional cow 's milk with or without breast milk throughout (n=187).6.Extensively hydrolysed cow 's milk formula for 2 months , followed by conventional cow 's milk (n=82).Cow 's milk protein antibodies were determined by an indirect immuno-fluorescent test . Antibody titres rose slowly in groups 1 , 3 and 6 . Children in group 5 showed two high peaks . There were no significant differences in the frequency and type of allergic manifestations between the groups . Introduction of cow 's milk formula during the first trimenon result ed in elevated antibody titres in all breast fed infants compared with introduction at a later date . Conclusion : In contrast to a previous study from the same laboratory , there is no diagnostic significance of cow 's milk protein-IgG antibodies for allergic manifestations . The occurrence of these antibodies is a physiological phenomenon : the shorter the breast feeding period and the earlier cow 's milk formula is introduced , the higher the antibody levels",
"Background : In patients with cow 's milk protein intolerance ( CMPI ) , delayed clinical reactions to cow 's milk ( CM ) ingestion may be misdiagnosed if the clinical symptoms are not “ classical ” and there is a long time lapse between ingestion of CM and the clinical reaction . The aim was to evaluate the clinical outcome of CMPI in a cohort of CM‐intolerant children , with particular attention to the occurrence of clinical manifestations beyond 72 h after CM challenge ",
"The aim of the study was to compare , during the first month of life , growth parameters , biochemical indices of protein metabolism and plasma amino acid concentrations in newborn infants fed either human milk ( n = 23 ) , three different whey hydrolysate formulae ( WHF 1 , n = 13 ; WHF 2 , n = 10 ; WHF 3 , n = 13 ) , a soy-collagen hydrolysate formula ( SCHF n = 18 ) or a whey-casein hydrolysate formula ( WCHF , n = 20 ) . Growth parameters and the various protein concentrations determined in the infants fed WHF 1 and WHF 2 were similar to the values observed with human milk . With WHF 3 , growth in weight , length and head circumference and serum total protein concentrations were reduced significantly whereas blood urea nitrogen was increased . With SCHF , growth in weight and length as well as serum total protein and transferrin concentration were decreased significantly , whereas serum IgG concentration was increased . With WCHF growth in length and serum transferrin concentration were decreased compared to the human milk group . In the various groups , the plasma amino acid pattern reflected the amino acid content of the formula . Whey hydrolysate formula induced mainly an increase in threonine and a decrease in tyrosine concentrations . Soy-collagen hydrolysate formula led to an increase of non-essential amino acids , such as glycine and hydroxyproline , and a decrease in plasma lysine and cystine . Whey-casein hydrolysate formula induced a plasma amino acid pattern close to the profile observed with human milk . Nevertheless , the plasma concentrations of most of the various amino acids were higher . ( ABSTRACT TRUNCATED AT 250 WORDS",
"BACKGROUND The potential of extensively or partially hydrolyzed formulas to reduce the risks for allergies is controversial . OBJECTIVE We sought to assess the preventive effect of differently hydrolyzed formulas compared with cow 's milk formula ( CMF ) in high-risk infants . METHODS Between 1995 and 1998 , 2252 infants with a hereditary risk for atopy were enrolled in the German Infant Nutritional Intervention Study and r and omly assigned at birth to one of 4 blinded formulas : CMF , partially hydrolyzed whey formula , extensively hydrolyzed whey formula , and extensively hydrolyzed casein formula ( eHF-C ) . The primary end point at 1 year of age was the presence of allergic manifestation , which was defined as atopic dermatitis ( AD ) , gastrointestinal manifestation of food allergy , allergic urticaria , or a combination of these factors . RESULTS At 12 months per protocol , analysis was performed on 945 infants exposed to study formula : 304 ( 13.5 % ) infants had left the study , 138 ( 6.1 % ) infants were excluded because of noncompliance , and 865 infants were exclusively breast-fed the first 4 months of life . The incidence of allergic manifestation was significantly reduced by using eHF-C compared with CMF ( 9 % vs 16 % ; adjusted OR , 0.51 ; 95 % CI , 0.28 - 0.92 ) , and the incidence of AD was significantly reduced by using eHF-C ( OR , 0.42 ; 95 % CI , 0.22 - 0.79 ) and partially hydrolyzed whey formula ( OR , 0.56 ; 95 % CI , 0.32 - 0.99 ) . Family history of AD was a significant risk factor and modified the preventive effect of the hydrolysates . CONCLUSIONS Prevention of allergic diseases in the first year of life is feasible by means of dietary intervention but influenced by family history of AD . The preventive effect of each hydrolyzed formula needs to be clinical ly evaluated",
"A cohort of 1749 newborns from the municipality of Odense born during 1985 in the University Hospital of Odense were followed prospect ively for the development of cow 's milk allergy (CMA)/cow 's milk protein intolerance ( CMI ) during their first year . The diagnosis of CMA/CMI was based on elimination/open milk challenge procedures according to generally accepted criteria . Thirty nine infants ( 2.2 % ) developed CMA/CMI . Infants with CMA/CMI were fed cow 's milk formula daily during the first month of life significantly more often than infants in the study population ( p less than .001 ) . All 39 infants with CMA/CMI had ingested cow 's milk formula ( 40 - 830 mL ) neonatally , whereas none of the 210 neonates without supplements of cow 's milk formula developed CMA/CMI ( p less than .05 ) . Based on a positive skin-prick test ( 2 + or more ) and /or specific serum IgE antibody to cow 's milk ( AL-RAST class 2 or more ) 16 infants were classified as having CMA . In infants solely breast-fed for greater than 1 month CMA was as frequent ( 1 % [ 14/1414 ] as in cow 's milk formula fed infant ( 0.6 % [ 2/335 ] ) . In infants with CMI , a significant majority ( 3.9 % [ 13/335 ] versus 0.7 % [ 10/1414 ] , p less than .001 ) had been cow 's milk formula fed during the first month . These data indicate an association between early cow 's milk formula feeding and development of reproducible adverse reactions to cow 's milk protein . Early neonatal intake of cow 's milk protein is probably a condition of sensitization and later adverse reactions to cow 's milk protein",
"OBJECTIVE To determine the effect of a partially hydrolysed formula on genetically predisposed children , with respect to the development of atopic clinical manifestations and in vitro testing of serum IgE levels ( total and milk-specific ) . METHODS One hundred and ten infants were r and omly assigned to receive either partially hydrolysed formula or st and ard infant formula , and were prospect ively monitored from birth for clinical atopic symptoms and serum IgE levels . RESULTS Eczema occurred less frequently in infants receiving partially hydrolysed formula . This was significant ( P wheezing occurred less frequently in infants receiving partially hydrolysed formula , compared to those receiving st and ard infant formula , the difference did not reach statistical significance ( P > 0.05 ) . CONCLUSIONS Exclusive feeding of hypoallergenic milk formula in the first 4 months of life has a protective effect in terms of the development of atopic dermatitis in the first 2 years of life , compared to feeding with cow 's milk formula",
"Type 1 diabetes is considered to be a T-cell-mediated autoimmune disease in which insulin-producing beta-cells are destroyed . Immunity to insulin has been suggested to be one of the primary autoimmune mechanisms leading to islet cell destruction . We have previously shown that the first immunization to insulin occurs by exposure to bovine insulin ( BI ) in cow 's milk ( CM ) formula . In this study , we analyzed the development of insulin-specific T-cell responses by proliferation test , emergence of insulin-binding antibodies by enzyme immunoassay , and insulin autoantibodies by radioimmunoassay in relation to CM exposure and family history of type 1 diabetes in infants with a first-degree relative with type 1 diabetes and increased genetic risk for the disease . The infants were r and omized to receive either an adapted CM-based formula or a hydrolyzed casein (HC)-based formula after breast-feeding for the first 6 - 8 months of life . At the age of 3 months , both cellular and humoral responses to BI were higher in infants exposed to CM formula than in infants fully breast-fed ( P = 0.015 and P = 0.007 ) . IgG antibodies to BI were higher in infants who received CM formula than in infants who received HC formula at 3 months of age ( P = 0.01 ) , but no difference in T-cell responses was seen between the groups . T-cell responses to BI at 9 months of age ( P = 0.05 ) and to human insulin at 12 ( P = 0.014 ) and 24 months of age ( P = 0.009 ) as well as IgG antibodies to BI at 24 months of age ( P = 0.05 ) were lower in children with a diabetic mother than in children with a diabetic father or a sibling , suggesting possible tolerization to insulin by maternal insulin therapy . The priming of insulin-specific humoral and T-cell immunity occurs in early infancy by dietary insulin , and this phenomenon is influenced by maternal type 1 diabetes",
"BACKGROUND Reported prevalence rates of asthma vary within and between countries around the world . These differences suggest environmental factors in addition to genetic factors in the cause of the disease and may provide clues for preventive strategies . We examined the variability of asthma-related symptoms and medication use among adults in 6 sites across Canada ( Vancouver , Winnipeg , Hamilton , Montreal , Halifax and Prince Edward Isl and ) and compared our findings with those from sites that had participated in a recent European survey . METHODS We used the same sampling strategy and st and ardized question naire as those used in the European Community Respiratory Health Survey ( ECRHS ) . The 6 Canadian sites were selected to represent different environments with respect to climate , air pollution and occupational exposure . Community-based sample s of 3000 to 4000 people aged 20 - 44 years were r and omly selected in each site . Subjects were asked to complete the question naire by mail between March 1993 and November 1994 . Prevalence rates ( and 95 % confidence intervals [ CIs ] ) of asthma symptoms , self-reported asthma attacks and use of asthma medication were compared across the Canadian sites and with sites that had participated in the ECRHS . RESULTS The overall response rate of those selected to receive the question naire was 86.5 % ( range 74.5%-92.8 % ) . The prevalence rates of most asthma symptoms varied significantly among the Canadian sites . For instance , 21.9 % ( Montreal ) to 30.4 % ( Halifax ) of the men and 24.0 % ( Vancouver ) to 35.2 % ( Halifax ) of the women reported wheezing in the year before the survey . Depending on the site , 4.4 % to 6.3 % of the men and 5.2 % to 9.5 % of the women reported an asthma attack in the last year , and 4.0 % to 6.1 % of the men and 4.9 % to 9.7 % of the women were currently using asthma medication . Prevalence rates of symptoms , asthma attacks and medication use did not change with age , but they were higher among women than among men . Compared with the results from the ECRHS sites , those from the Canadian sites were among the highest . INTERPRETATION Significant variation in the prevalence of asthma symptoms , asthma attacks and use of asthma medication between Canadian sites and international sites suggests environmental influences . Different combinations of factors in different sites may be responsible for the high prevalence rates and should be the subject of further research to guide clinical management and public health intervention ",
"One hundred and sixty‐two women with respiratory allergy to animal d and ers and /or pollens were r and omly allocated to a diet consisting of either a very low ingestion of hens ' egg and cows ' milk or a daily ingestion of one hens ' egg and about 11 of cows ' milk during the last 3 months of pregnancy . One hundred and sixty‐three infants were followed prospect ively up to 18 months of age when the cumulated incidence of atopic disease in each child was evaluated blindly . No significant differences in the distribution of atopic disease were found among the infants in relation to the maternal diet during late pregnancy . The numbers of skin‐prick tests positive to ovalbumin , ovomucoid , β‐lactoglobulin and cows ' milk were likewise not influenced by differences in the maternal diet during late pregnancy . Genetic factors rather than maternal diet during the perinatal period probably have a greater effect on the incidence of atopic diseases during early infancy",
"The effect of genetic and environmental factors on the prevalence of allergic disorders in early childhood was determined in a prospect i ve follow‐up study . Information was available on 1174 children at the age of 2 years . Two‐hundred and seventy‐five were considered to have an allergic disorder . The prevalence varied from 3.2 % for rhinitis to 10.9 % , for asthma . At 2 years 60 children reacted positively on skin‐prick test ( SPT ) . Multivariate logistic regression analysis was used to obtain adjusted odds ratios ( 95 % confidence interval ) for each factor . For asthma , positive family history , male sex , low birth‐weight , maternal smoking and season of birth were significant risk factors . For eczema , positive family history was the only significant risk factor . For rhinitis , lower socio‐economic group and autumn birth were significant . Maie sex and low birth‐weight were significant for skin test positivity . Positive family history and low birth‐weight were significant risk factors for any allergy . Low birth‐weight was also a significant risk for skin test reactivity to house dust mite . Genetic and environmental factors have a profound effect on the development of allergic disorders in the first two years of life",
"BACKGROUND To improve the nutritional management of pre-term infants , a new individualized human milk fortification system based on presupplementation milk protein analyses was evaluated . METHODS In an open , prospect i ve , r and omized multicenter study , 32 healthy preterm infants ( birth weights , 920 - 1750 g ) were enrolled at a mean of 21 days of age ( range , 9 - 36 days ) when tolerating exclusive enteral feedings of 150 ml/kg per day . All infants were fed human milk and were r and omly allocated to fortification with a bovine whey protein fortifier ( n = 16 ) or ultrafiltrated human milk protein ( n = 16 ) . All human milk was analyzed for protein content before fortification with the goal of a daily protein intake of 3.5 g/kg . During the study period ( mean , 24 days ) daily aliquots of the fortified milk were obtained for subsequent analyses of the protein content . RESULTS Both fortifiers were well tolerated , and growth gain in weight , length , and head circumference , as well as final prepr and ial concentrations of serum urea , transthyretin , transferrin , and albumin were similar in both groups . The ultimate estimated protein intake was equivalent in both groups ( mean 3.1+/-0.1 g/kg per day ) . Serum amino acid profiles were similar in both feeding groups , except for threonine ( significantly higher in the bovine fortifier group ) and proline and ornithine ( significantly higher in the human milk protein group ) . CONCLUSIONS Protein analyses of the milk before individual fortification provides a new tool for an individualized feeding system of the preterm infant . The bovine whey protein fortifier attained biochemical and growth results similar to those found in infants fed human milk protein exclusively with the corresponding protein intakes",
"It has been reported that the feeding of cow 's milk may enhance the development of atopy in predisposed infants . A prospect i ve study following children from birth through 15 years of age in a private pediatric practice was design ed to determine if the food ingested during the first months of life is related to the development of atopy in the offspring of allergic families . Each of 328 children with a positive family history of allergy was assigned to one of three groups . according to the feeding preference of the parents : 48 were fed breast milk ; 79 , soy-based formula ; and 201 , cow 's milk formula . All groups had egg , citrus , tomato , and wheat restrictions as well as inhalant allergen avoidance . These were compared to a control group of 580 children with no family history of allergy . Breast fed infants were found to have approximately one-half the incidence of atopy of cow 's milk or soy formula fed infants from atopic families when followed for up to 15 years . Soy feeding produced no advantage over cow 's milk in the prophylaxis of allergic disease . There was a threefold increase in clinical ly apparent atopic disease in offspring of allergic families when compared to controls but only a two-fold increase if the infant was breast fed . These results support the hypothesis that breast feeding and delay of exposure to known allergens may reduce the frequency of clinical allergic disease in the offspring of allergic families",
"OBJECTIVE To determine the antigenicity , nutritional adequacy , and growth-promoting efficacy of protein hydrolysate or amino acid-derived formulas in infants with cow milk allergy . STUDY DESIGN Several protein hydrolysate or amino acid-derived formulas were grade d for beta-lactoglobulin content and skin reactivity in 74 atopic children with cow milk allergy proved by a double-blind , placebo-controlled challenge . A r and omized , prospect i ve follow-up study of 9 months included 22 infants with a mean age of 6 months ( 95 % confidence interval , 4 to 7 ) , who were fed an extensively hydrolyzed whey formula ( group We ) , and 23 infants with a mean age of 17 ( 95 % confidence interval , 4 to 7 ) months , who were given an amino acid-derived formula ( group AA ) . RESULTS Both formulas were clinical ly and biochemically tolerated . The mean concentration of essential amino acids in plasma was lower in group We but higher in group AA compared with values for breast-fed control infants ( p = 0.001 ) . There was a different trend between the groups in weight ( p = 0.09 ) and length ( p = 0.006 ) . Growth was promoted in group AA during the follow-up ; it was constant during the first months , followed by a gradual decline in rate in group We . In both groups , atopic eczema improved significantly and progressively , and a downward trend was found in serum total and milk-specific IgE concentrations , proving the efficacy of both formulas . CONCLUSIONS Extensively hydrolyzed formulas are safe and effective for most infants ; an amino acid-derived formula may be preferable for infants with multiple food allergies , especially for the maintenance of normal growth",
"A prospect i ve r and omized study of growth and digestive tolerance in a cohort of 60 healthy infants with no history for allergic disease is reported . A milk-based formula and a formula of identical composition whose proteins had undergone hydrolysis were fed successively to the study infants according to a crossover design , for eight weeks . Intake , weight gain and length gain were comparable and satisfactory with both diets . With the hydrolyzed protein formula , stools were greener in color and significantly more numerous , although both parameters remained within normal limits . The most noteworthy result was the significantly greater rate of regurgitations in the group given the hydrolyzed protein formula , i.e. , 26 % versus 8 % in the group fed a conventional modified milk formula . These results show that use of partial protein hydrolysate formulas is associated with minor digestive adverse effects",
"At the age of 5 years , the prevalence of atopic manifestations was analysed in 58 formula-fed “ at risk ” infants because of a history of atopic disease in at least two first degree relatives . Infants were r and omly assigned to receive either a partial whey-hydrolysate formula ( n : 28 ) or a regular cow 's milk formula ( n : 30 ) during the first 6 months of life ; thereafter , feeding was unrestricted . Only non-breastfed infants were included . The groups did not differ in risk factors or in known confounding factors possibly influencing the incidence of manifestations suggestive of atopic disease . At 6 months , the prevalence of cow 's milk protein ( CMP ) sensitivity was significantly decreased in the hydrolysate group ( 7 % versus 43%;P : 0.002 ) . At the age of 12 ( 21 % versus 53%;P : 0.029 ) , 36 ( 25 % versus 57%;P : 0.018 ) and 60 months ( 29 % versus 60%;P : 0.016 ) there was still a significant difference in the number of atopic manifestations , if calculated cumulatively . There was no difference between the groups if only the new cases after the age of 6 months were considered . Eczema was less frequent in the whey-hydrolysate group , but only during the 1st year of life , suggesting a decreased prevalence of CMP sensitivity . During the first 6 months , diarrhoea of non-infectious origin occurred in 8/30 infants ( 27 % ) of the adapted formula group , and in no infant in the hydrolysate group . “ Colic as single manifestation ” was considered of “ allergic ” origin in 1/28 infants in the hydrolysate group , and in 4/30 infants in the adapted formula group . If gastro-intestinal symptoms such as “ diarrhoea and colic as single manifestation ” are not considered , the number of infants with CMP sensitivity remains only significant for the first 6 months ( P : 0.004 ) . At 12 , 36 and 60 months , differences are not significant ( 0.106 , 0.116 and 0.07 , respectively ) . The results of this study support the hypothesis that allergy prevention is antigen specific . Conclusion If mother 's milk is not available and other studies confirm these results , there might be an indication for partial hydrolysates in infants with a family history of atopy , since these formulae reduce the incidence of CMP sensitivity",
"Five children aged 12‐40 months with IgE‐mediated adverse reactions to cow milk ( immediate onset clinical pattern of cow milk allergy ) were orally challenged double‐blind in r and om order with three different milk preparations processed from the same batch of milk 1 ) raw untreated cow milk , 2 ) pasteurized cow milk , 3 ) homogenized and pasteurized cow milk , and 4 ) Nutramigen ® (a commercial hypoallergenic infant formula based on hydrolysed casein ) as placebo . Skin prick tests with the same preparations were also performed . On oral challenge the three different processed milk types provoked significant and similar allergic reactions in each child , and no adverse reactions followed the challenge with placebo ( Nutramigen ) . Skin prick test with the same milk products were positive in all children and comparable to the results with an extract of purified raw cow milk protein ( Soluprickreg ; ) , whereas Nutramigen did not elicit any skin reactions . A tendency towards a lower threshold of reaction and larger skin reactions induced by the processed milk preparations might indicate an increased ability of pasteurized and homogenized/pasteurized milk to evoke allergic reactions in patients allergic to milk",
"The addition of different organic substrates to st and ard glucose oral rehydration solution ( G‐ORS ) has been shown to improve the intestinal absorption of sodium and water , and thereby decrease stool losses . Therefore , we evaluated , in infants with acute diarrhoea , the safety and efficacy of three oral rehydration solutions ( ORS ) which had the same concentrations of electrolytes ( with sodium 60 mmol/l ) but different substrates of proteins and carbohydrates . One solution ( LAD‐ORS ) contained hydrolyzed lactalbumin ( LAD ) with maltodextrin and sucrose , a second ( MS‐ORS ) was identical but without LAD and a third ( G‐ORS ) was st and ard glucose ORS . The three solutions were compared in a double‐blind , r and omized trial in 74 hospitalized well‐nourished children in Panama and the United States . All three oral rehydration solutions were equally efficacious and safe in these children , 54 % of whom were infected with rotavirus . There was no suggestion that hydrolyzed lactalbumin or maltodextrin provided any advantage over glucose‐ORS in terms of stool output or in duration of diarrhoea . We conclude that all three solutions are efficacious in the therapy of acute diarrhoea in infants",
"Oral administration of foreign proteins , e.g. cow 's milk ( CM ) proteins , stimulates the immune system and induces humoral and cellular immune response against these antigens in infants . Up-regulation of adhesion molecules is known to be associated with activation of the immune system . The purpose of the study was to examine whether orally administered CM proteins induce elevation in soluble adhesion molecules , i.e. intercellular adhesion molecule-1 ( ICAM-1 ) and L-selectin , in infants . In a double-blind trial , 10 infants received CM-based formula and 10 infants casein hydrolysate formula until the age of 9 mo . The infants of mothers with insulin-dependent diabetes mellitus ( IDDM ) were recruited into a pilot study of a trial for primary prevention of IDDM by elimination of CM proteins from the diet during early infancy . A cord blood sample and peripheral blood sample s were taken at the ages of 3 , 6 , 9 , and 12 mo of age . The levels of soluble ICAM-1 and L-selectin were measured by ELISA . The levels of soluble ICAM-1 were higher at the ages of 3 , 6 , 9 , and 12 mo in infants who received CM-based formula than in infants who received hydrolyzed formula ( p = 0.05 ) . Instead , no difference was found in the the levels of soluble L-selectin . The levels of soluble ICAM-1 and L-selectin were higher in all infants when compared with the levels reported in adults or to the levels seen in cord blood . Orally fed CM proteins induce an elevation in soluble ICAM-1 in infants . This may reflect the generation of an immune response against these proteins , because ICAM-1 has an important costimulatory role in lymphocyte activation",
"Cow 's milk allergy/intolerance is treated by complete avoidance of cow 's milk proteins . Because cow 's milk is an important food for infants , its avoidance may lead to an increased risk of growth impairment . Whilst there is evidence for the beneficial effects of extensively hydrolyzed cow 's milk formulate ( eHF ) in infants with cow 's milk allergy/intolerance , little is known about the effects of amino-acid-based formulae ( AA ) in such infants . We therefore performed a prospect i ve , controlled , multi-center trial to study the efficacy of AA in comparison with eHF , on the growth and clinical symptoms of 73 infants ( median age 5.7 months ) with cow 's milk allergy/intolerance and atopic dermatitis . Cow 's milk allergy/intolerance was proven in all infants by double-blind , placebo-controlled food-challenge . We observed a significant improvement in the SCORAD index in both groups , from a mean of 24.6 , at entry , to a mean of 10.7 ( p length st and ard deviation score ( p weight-for-length values were stable in both groups . The energy intake during the study was similar in both groups . Both an AA and eHF result ed in a significant clinical improvement in infants with an early onset of symptoms of cow 's milk allergy/intolerance . Feeding an AA result ed in improved growth compared with feeding eHF , despite similar dietary intakes , and may therefore be considered as a beneficial alternative in infants with severe cow 's milk allergy intolerance",
"OBJECTIVE To determine the effectiveness of whey hydrolysate formula in the treatment of infantile colic in a primary care setting in the Netherl and s. STUDY DESIGN R and omized , double-blind , parallel trial with a 1-week qualification period and a 1-week intervention period . Participants . Forty-three healthy , thriving , formula-fed infants , 3 hours per day on at least 3 days per week . Infants were r and omized to whey hydrolysate formula ( n = 23 ) or st and ard formula ( n = 20 ) . MAIN OUTCOME MEASURE Difference in duration of crying ( minutes per day ) between qualification week and intervention week . RESULTS Analysis according to the intention to treat principle showed a difference in the decrease of crying duration of 63 minutes per day [ 95 % confidence interval : 1 - 127 minutes per day ] in favor of the whey hydrolysate formula . Five infants did not complete the trial . The scope of the study was not sufficient to expect significant differences in the subgroup analyses . CONCLUSIONS An extensively hydrolyzed whey formula is effective in reducing the duration of crying in a primary care setting",
"BACKGROUND Development of humoral and cellular immune responses to orally administered antigens in human beings is poorly understood , although antigen administration has been suggested as a treatment for hypersensitivity disorders and autoimmune diseases . OBJECTIVE The purpose of the study was to investigate the development of systemic immune response in infants fed with formula containing whole cow 's milk proteins or hydrolyzed formula containing casein peptides . METHODS In a double-blind trial , 10 infants received cow 's milk-based formula , and 10 infants received a casein hydrolysate formula until the age of 9 months . Blood sample s were taken at the ages of 6 , 9 , and 12 months . Cellular responses were assessed by proliferation assay of peripheral blood mononuclear cells to cow 's milk proteins ( beta-lactoglobulin , bovine serum albumin , and alpha-casein ) . Humoral responses to the same proteins were measured by ELISA for IgG antibodies . RESULTS Feeding infants with cow 's milk-based formula induced systemic humoral and cellular responses to cow 's milk proteins . T-cell response later declined , supporting the concept of oral tolerization . Exposure to cow 's milk proteins after the age of 9 months result ed in depressed cellular and humoral responsiveness to these proteins . CONCLUSION Our results support the view that induction of oral tolerance in human beings is an age-dependent phenomenon",
"OBJECTIVE To determine the hypoallergenicity and efficacy of a pediatric amino acid-based formula ( AAF ) , EleCare , for children with cow 's milk allergy ( CMA ) and multiple food allergies ( MFA ) . STUDY DESIGN Hypoallergenicity was determined by performing blinded oral food challenges in 31 consecutive children with documented CMA . Growth , tolerance , and biochemical response were evaluated during a nonr and omized feeding study with each child serving as his or her own control . RESULTS Thirty-one children ( median age , 23.3 months ; range , 6 months to 17.5 years ) were recruited ; 29 had MFA , 17 had acute reactions and cow 's milk-specific IgE antibody , and 14 had allergic eosinophilic gastroenteritis . At study entry , 23 were receiving another AAF ; 13 had not tolerated extensively hydrolyzed formula . Eighteen subjects with allergic eosinophilic gastroenteritis and /or MFA were followed up while receiving AAF for a median of 21 months ( range , 7 to 40 months ) , with biochemical analysis performed at 4 months . No statistically significant differences were observed in the change in weight or height National Center for Health Statistics z scores from entry ; the percent of expected growth exceeded 90 % . There was a small decline in percent eosinophils and increase in hemoglobin , hematocrit , and serum ferritin level ( P plasma leucine and valine levels ( P AAF was hypoallergenic and effective in maintaining normal growth for children with CMA and MFA",
"Whey hydrolysate formulas are a recent and important innovation in infant feeding . This study compared clinical tolerance and acceptability of a whey hydrolysate formula ( WH ) with those of a whey-predominant formula ( WF ) in 45 infants . Four infants ( 16 % ) who refused to drink WH formula were eliminated from the study . Mean volume intake was significantly lower for WH ( 120 mL/kg/day ) than for WF ( 147 mL/kg/day ; P mean caloric intake was also significantly different : 80 kcal/kg/day ( WF ) vs 97 kcal/kg/day ( WF ; P weight gain from birth to 13 weeks of age was nearly identical in both groups ( 171 % for WH vs 178 % for WF ) . No significant differences were noted in duration of feeding , number of pauses during feeding , number of stools per day , or number of regurgitations per day . The lower rate of caloric intake and the dropout rate of 16 % for WH raise questions about the use of WH formula in normal infants , as has become the case in some Western European regions",
"The purpose of this study was to determine whether a new casein hydrolysate infant formula , Alimentum , could be administered safely to children with cow milk hypersensitivity . The formula was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and with a sensitive enzyme-linked inhibition immunoassay , and it was judged to be safe for clinical trials in children allergic to cow milk . Twenty-five such children underwent double-blind placebo-controlled oral food challenges with 10 gm of powdered cow milk and casein hydrolysate formula . All children were highly atopic and had positive skin prick reactions to cow milk . No patient reacted to placebo during a double-blind , placebo-controlled food challenge . Two patients lost their allergy to cow milk and did not react during the challenge ; the remaining patients reacted with a variety of cutaneous , respiratory , and gastrointestinal symptoms within 15 to 90 minutes of challenge . All children tolerated the blinded challenge to the casein hydrolysate and were fed the hydrolysate openly without difficulty . We conclude that this casein hydrolysate is generally safe to feed to children with immediate hypersensitivity to cow milk . We recommend that all infant formulas promoted as \" hypoallergenic \" be tested in milk-allergic patients to assess their allergenic potential , in addition to st and ard nutritional evaluation and animal testing for antigenicity",
"Summary Background : The best nutritional option for newborn infants is mother 's milk . However , some newborn babies may not be exlusively breastfed during the first months of life , potentially leading to reduced overall health status and the early onset of allergic diseases in some infants . Considerable research has been devoted to the development and assessment of infant nutrition programmes , particularly to the prevention of allergies in high-risk infants . However , equal numbers of infants with and without an elevated familial risk of allergies will eventually develop allergic diseases . Therefore , optimizing nutritional programmes for the early infant population as a whole is an important – but as yet insufficiently studied – area of investigation . Moreover , although safe and effective nutrition must primarily support healthy development of the infant , few studies have evaluated the overall health benefits of nutritional interventions , but have focussed on specific allergic manifestations . In animal models , an allergen-reduced moderate whey hydrolysate formula ( pHF , Nestlé Beba HA ) induces the development of oral tolerance towards cow 's milk proteins , without inducing sensitization . In infants with a high risk for allergies , pHF formulae reduce the early onset of allergic disease during the first 5 years of life by approximately 50 % compared with a dietary regimen of unaltered proteins . At present , very little is known about the overall health benefits of such a dietary intervention on the unselected infant population as a whole . Aim of the study : The aim of our prospect i ve , controlled study was to investigate the overall health benefits of an allergen-reduced nutritional programme in a newborn infant population unselected for atopic risk factors . The population in our study was a comparable as possible to the general population of healthy newborn infants . Our study included exclusive breastfeeding , use of a moderate whey hydrolysate formula ( pHF , Nestlé Beba HA ) if infant formula was needed , and delayed introduction of low-allergenic weaning foods . The study included assessment s of compliance with the dietary programme , and evaluated nutritional habits , growth , and overall health status for 24 months . The health evaluation included allergic manifestations but die – by purpose – not define or evaluate them specifically . Part I of this paper gives results for nutritional habits during the first 6 months of life , Part II gives results for growth and general health status for the same time period , Part III will present feeding habits during the second half of the first year of life , and Part IV will present results to 24 months of age . The complete study report is published as a supplement to this journal . Methods : Nuritional assignment was to demographically comparable intervention ( Z ) or control ( FF ) cohorts according to the infant 's place of birth . In the intervention cohort ( Z , n=564 ) , the recommended dietary regimen was breastfeeding and /or the pHF formula , with no weaning food before 4 months of age . In the control cohort ( FF , n=566 ) , there was no intervention . Longitudinal diet groups , defined for 4 months , excluding dropouts and noncompliants , were exclusive breastfeeding ( eBF , Z , n=201 , FF , n=162 ) , partial breastfeeding ( pBF , Z , n=222 , FF , n=311 ) , or non-breastfeeding ( nBF , Z , n=42 , FF , n=62 ) . Imbalances between groups and cohorts in confounding factors that could influence health-related symptoms were integrated as covariates into the main analyses using logistic regression . Nutritional surveillance was carried out using continuous prospect i ve monitoring . Results : The overall rate of breastfeeding , irrespective of partial or excluive breastfeeding or the additional use of weaning foods , was similar in both cohorts at 4 and 6 months . However , from ages 3 to 6 month , significantly more Z than FF infants were excluively breastfed ( p different kinds of weaning foods compared with FF ( 2 versus 10 ; p Six-month rates of dropout were very low in both groups ( Z=4.3 % , FF=1.8 % ) and compliance with the programme was excellent over the strict intervention period of 4 months ( Z=86.9 % ) until the sixth month . Conclusions : A dietary recommendation that promotes breastfeeding , includes a moderate whey hydrolysate formula ( Nestlé Beba HA ) , and delays the introduction of highly allergenic weaning foods ( an allergen-reduced dietary regimen ) significantly increases breastfeeding and delays weaning in a normal infant population without any compliance problem to the moderate hydroysate formula that is quite often seen in the eHF . The regimen was followed closely , with a high degree of compliance and a low dropout rate compared with previous allergy-prevention studies . Compliance with the dietary regimen was excellent over the 4 months of intervention and throughout the following 2 months",
"20 out of 36 children ( aged two to eight years ) with atopic eczema completed a twelve-week , double-blind , controlled , crossover trial of an egg and cows ' milk exclusion diet . During the first and third four-week periods , patients on an egg and cows ' milk exclusion diet received a soya-based milk substitute ( trial period ) or an egg and cows ' milk preparation ( control period ) . Response was assessed in terms of eczema activity , number of areas affected , pruritus , sleeplessness , and antihistamine usage while on the two diets . During the middle period patients resumed their normal diet to minimise any carry-over effect . 14 patients responded more favourably to the antigen-avoidance diet than to the control diet , whereas only 1 responded more favourably to the control diet than the trial diet . Patients experienced more benefit during the first diet period than the second , whatever the nature of the diet . There was no correlation between a positive prick test to egg and cows ' milk antigen and response to the trial diet",
" Infants ( n = 18 ) with intolerance to extensively hydrolyzed formulas and soy who responded to an L-amino acid-based elemental formula ( AAF ) were studied until 3 years of age . By 2 years of age most tolerated non-formula foods , and by 3 years only 3 required AAF . Growth normalized during AAF feeding in 4 infants with failure to thrive",
"Clinical experience ( \" the dangerous bottle \" ) and experimental evidence indicate that the early life of an infant is particularly important for the development of the immune responses to food antigens . However , the clinical and immunologic consequences of a brief exposure to , or avoidance of , food antigens during the neonatal period in human infants are poorly understood and documented . We present the preliminary results of a prospect i ve controlled study of 256 normal breast-fed infants r and omly assigned to receive ( blind ) either an adapted formula ( Nidina ) or a partially hydrolyzed formula ( Nidal HA ) as a supplement to breast-feeding for a few days when necessary , and to be examined at days 5 , 90 , 150 , and 365 . The results indicated that ( 1 ) the prevalence of clinical symptoms and of total and specific IgE responses was not statistically different in the two groups of infants and ( 2 ) infants fed a hydrolyzed formula had median titers of specific IgG lower than those fed an adapted formula ; the difference was significant for alpha-lactalbumin at day 90 ( p immune responses of breast-fed infants to food antigens thus appear to be modulated by early , short-term exposure to them",
"Background : Hydrolyzed milk formulas are recommended to feed infants at high risk of atopy if breast‐feeding is not possible . We studied the specific cellular and humoral immune response to cow 's milk proteins and occurrence of atopic dermatitis under different feeding regimens : two hydrolyzed infant milk formulas ( partially [ pHF ] and extensively hydrolyzed [ eHF ] ) and under exclusive breast‐feeding ( BF )",
"BACKGROUND Plasma amino acid concentrations were measured in preterm infants who were fed either a new hydrolyzed cow 's milk protein formula or a st and ard preterm infant formula . It was hypothesized that feeding with the hydrolysate results in prepr and ial amino acid concentrations that are significantly different from the concentrations found when feeding with the st and ard formula . METHODS Fifteen preterm infants , median gestational age , 29 weeks ( range , 24 - 32 weeks ) ; birth weight , 1241 g ( range , 660 - 1900 g ) ; and postnatal age , 18 days ( range , 7 - 54 days ) receiving full enteral feedings ( > 150 ml/kg x day ) , were enrolled . The intervention was r and omized allocation to the formula with hydrolyzed or natural cow 's milk protein ( the whey/casein ratio was 60:40 in both formulas ) . In a crossover design , each formula was fed for 5 days , and plasma amino acids were analyzed on day 4 or 5 of each 5-day period . RESULTS In spite of the 12 % higher amino acid intake with hydrolysate formula , the median individual plasma amino acid concentrations were virtually identical with both formulas , and they were within the 10th and the 90th percentile of the reference of levels in the umbilical cord artery after elective cesarean delivery or of breast-fed newborn infants . The median concentrations of lysine and aspartic acid were higher with hydrolyzed formula feeding ( p single amino acid concentrations were out of the reference values . CONCLUSION Virtually identical plasma amino acid concentration patterns were measured with the new hydrolyzed preterm infant formula and the st and ard preterm infant formula , but longitudinal studies are required before the studied protein hydrolysate can be recommended for preterm feeding in general",
"BACKGROUND The role of exposure to dietary antigens through maternal milk is intriguing , because it may result either in immunization or in tolerance . Exposure to cow 's milk proteins results in antibody formation against bovine insulin in infants at risk for type 1 diabetes . OBJECTIVE To study the appearance of IgG antibodies to bovine and human insulin in infants with an atopic family history whose mothers followed a cow 's milk-free diet during the first 3 months of lactation . METHODS In a prospect i ve cohort study on prevention of food allergies , 123 infants were exclusively breast-fed or received supplementation with a hydrolyzed casein-based formula ( Nutramigen ) until the age of 6 months . The mothers either avoided cow 's milk during the first 3 months of lactation ( diet group ) or had an unrestricted diet ( nondiet group ) . The levels of IgG antibodies to bovine and human insulin were determined by enzyme immunoassay at 3 , 6 , 12 , and 18 months and at 4 years . In addition , cord blood was obtained at birth and a maternal sample at delivery . RESULTS At 3 months , IgG antibodies to bovine insulin were low in both dietary groups ( median levels 0.150 and 0 . 114 optical density units in the diet and nondiet groups ) . After exposure to dietary insulin , IgG antibodies to bovine insulin increased in both groups , reaching a peak at 12 months in the nondiet group and at 18 months in the diet group . At 18 months , IgG antibodies to bovine insulin were lower in infants in the nondiet group than in infants in the diet group ( 0.287 vs 0.500 , P antibodies no longer differed between the groups . CONCLUSION The exposure to cow 's milk proteins through breast milk during the first 3 months of life result ed in decreased levels of antibodies to dietary bovine insulin at 18 months of age , suggesting a role for breast milk antigens in early tolerance induction",
"Formulas containing proteins with reduced potential to sensitize might be effective in reducing the risk of atopic disease , but such products should be nutritionally adequate . We design ed a r and omized , double-blind study to evaluate nutritional adequacy and sensitization potential of a formula containing partially hydrolyzed whey-predominant milk proteins . Subjects were term infants enrolled at birth . Infants in group A were fed human milk , and group B received the partially hydrolyzed formula ; group C , fed a formula containing intact whey-predominant milk proteins , served as control subjects . We recorded anthropometric measurements and symptoms of formula intolerance at monthly intervals for 4 months in 205 infants . Milk IgE and IgG antibodies were measured until 8 months of age in 63 infants . Daily weight gain was not significantly different among the groups . Gastrointestinal symptoms attributed to feeding intolerance were also comparable . Increases in serum IgG antibodies were significantly greater in group C throughout the study . There were no significant differences in IgE antibodies . Thus a formula containing partially hydrolyzed whey-predominant milk protein promoted adequate growth and induced a lesser priming effect for IgG antibody response than did an intact whey-predominant formula",
" A group of 129 infants were r and omly assigned at birth to one of three feeding regimens : human milk ( HM ) , cow 's milk formula ( CMF ) or a casein hydrolysate formula ( CHF ) during the first 3 days of life . Blood sample s were taken on at 4 days and at 2 , 4 , 8 , 12 and 24 months of age . Macromolecular absorption was analysed by measuring the serum concentration of human α‐lactalbumin ( S‐α‐LA ) with a competitive radioimmunoassay ( RIA ) . Total serum IgE was measured by RIA . A family history of allergy correlated to the proportion of infants with allergic symptoms both at 24 and 36 months of age ( p= 0.03 and p= 0.04 respectively ) . In none of the three groups did correlation exist between the duration of breastfeeding and serum α‐LA , serum IgE , family history of allergy , frequency of allergic symptoms and proportion of infants with infections ",
"Allergic reactions were investigated in 777 preterm infants who were r and omly assigned to early diet and followed up to 18 months post term . Wheezing or asthma was common ( incidence 23 % ) ; it was associated with neonatal ventilation , maternal smoking , and a family history of atopy and was unexpectedly reduced in babies born by caesarean section . Even in non-ventilated infants , the incidence of subsequent wheezing was 18 % , rising to an estimated 44 % ( using logistic regression ) when the foregoing risk factors ( excluding ventilation ) were present . Eczema occurred in 151 infants ( 19 % ) and was strongly associated with multiple pregnancy ( 30 % incidence in twins or triplets ) . Reactions to cows ' milk ( incidence : 4.4 % from detailed history ; 0.8 % confirmed by challenge ) , other foods ( 10 % ) , and drugs ( 5 % ) were within the range reported in full term infants . Milk and food reactions were associated with multiple pregnancy ( 19 % ) and a family history of atopy . Reactions to drugs were least likely to occur in infants who had been ventilated and were on multiple medications in the neonatal period , suggesting that drug tolerance may have developed . We speculate that preterm infants may be a high risk group for asthma and eczema , which could imply an association between atopy and prematurity",
"BACKGROUND The effect of diet change in 38 bottle-fed and 77 breast-fed \" colicky \" infants , referred from community-based pediatric facilities was studied over a 1-week period in a double-blind ( within each feeding mode ) , r and omized , placebo-controlled trial . METHODS Bottle-fed infants were assigned to either casein hydrolysate or cow 's milk formula . All mothers of breast-fed infants were started on an artificial color-free , preservative-free , additive-free diet and also r and omized to an active low allergen diet ( milk- , egg- , wheat- , nut-free ) or a control diet . RESULTS The response to diet was assessed on day 1 and day 8 with the use of a previously vali date d infant distress chart on which parents recorded distress levels . If successful outcome was defined as a reduction in distress of 25 % or more , after adjusting for age and feeding mode , infants on active diet had a significantly higher rate of improvement than those on the control diet ( odds ratio , 2.32 ; 95 % confidence interval , 1.07 - 5.0 ; p = 0.03 ) . Analysis of the day 8 to day 1 distress ratio , again adjusted for age and feeding mode , showed that infants on the active diet had distress reduced by 39 % ( 95 % confidence interval , 26 - 50 ) compared with 16 % ( 95 % confidence interval , 0 - 30 ) for those on the control diet ( p = 0.012 ) . CONCLUSION The results suggest a period of dietary modification with a low allergen diet and appropriate nutritional support should be considered in healthy infants with colic",
"The effect of maternal and infant avoidance of allergenic foods on food allergy was examined in a prenatally r and omized , controlled trial of infants of atopic parents . The diet of the prophylactic-treated group ( N = 103 ) included ( 1 ) maternal avoidance of cow 's milk , egg , and peanut during the third trimester of pregnancy and lactation and ( 2 ) infant use of casein hydrolysate ( Nutramigen ) for supplementation or weaning , and avoidance of solid foods for 6 months ; cow 's milk , corn , soy , citrus , and wheat , for 12 months ; and egg , peanut , and fish , for 24 months . In the control group ( N = 185 ) , mothers had unrestricted diets , and infants followed American Academy of Pediatrics feeding guidelines . The cumulative prevalence of atopy was lower at 12 months in the prophylactic-treated ( 16.2 % ) compared to the control ( 27.1 % ) group ( p = 0.039 ) , result ing from reduced food-associated atopic dermatitis , urticaria and /or gastrointestinal disease by 12 months ( 5.1 % versus 16.4 % ; p = 0.007 ) , and any positive food skin test by 24 months ( 16.5 % versus 29.4 % ; p = 0.019 ) , caused primarily by fewer positive milk skin tests ( 1 % versus 12.4 % ; p = 0.001 ) . The prevalences of allergic rhinitis , asthma , and inhalant skin tests were unaffected . Serum IgE levels in the prophylactic-treated group were marginally lower only at 4 months . Thus , reduced exposure of infants to allergenic foods appeared to reduce food sensitization and allergy primarily during the first year of life",
"BACKGROUND Early exposure to dust mite allergens may be critical for primary sensitization . Reducing exposure may offer a realistic chance for primary prevention of sensitization and asthma , but it is essential to implement measures that can achieve and maintain the low-allergen environment . OBJECTIVE Our purpose was to assess the effectiveness of mite allergen avoidance measures in achieving and maintaining a low-allergen environment during pregnancy and in the first year of life . METHODS The Manchester Asthma and Allergy Study is a prospect i ve , prenatally r and omized study that follows the development of asthma and atopy in a cohort of infants at high risk ( both parents atopic ) who are r and omly allocated to full mite allergen avoidance or to a normal regimen . Avoidance measures comprise ( 1 ) mite-proof covers ( mattress , pillow , and quilt ) for parental bed , ( 2 ) high-filtration vacuum cleaner , ( 3 ) vinyl flooring in infant 's bedroom , ( 4 ) new crib and portable crib mattresses encased in mite-proof material , ( 5 ) benzyl benzoate ( Acarosan ) applied on carpets and soft furniture , ( 6 ) bed linens washed in hot water weekly , and ( 7 ) washable soft toys . Dust sample s from the parental bed , bedroom floor , living room floor , infant 's mattress , and nursery floor were collected between the 10th and 14th weeks of pregnancy , immediately after birth , and then at age 6 months and 1 year , and Der p 1 levels were determined by mAb-based ELISA . RESULTS Recovered Der p 1 from maternal mattress was reduced by 97 . 25 % ( 95 % confidence interval [ CI ] 95.25%-98.41 % ) during the second and third trimesters of pregnancy , with the effect persisting for 6 months ( 98 % reduction , 95 % CI 97.25%-99.1 % ) and 12 months ( 97.6 % reduction , 95 % CI 95.7%-98.6 % ) after the birth ( active vs control , P Total Der p 1 from bedroom floor in the active group was reduced by 53.7 % ( 95 % CI 25.7%-71.2 % ) in sample s collected within 4 weeks of the child 's birth , with the percentage reduction being 62 . 8 % ( 95 % CI 39.3%-77.2 % ) at 6 months and 26.5 % ( 95 % CI -24 % to 57.1 % ) at 1 year ( active compared vs control , P Der p 1 levels in crib mattress and nursery floor in the active group were extremely low ( crib mattresses geometric mean [ 95 % CI ] 2.3 ng [ 1.6 - 3.4 ] at birth , 6.8 ng [ 4.5 - 10 ] at age 6 months , and 15.6 ng [ 9.8 - 24.8 ] at age 1 year [ active vs control , P = .001 ] ; nursery 1 ng [ 0.9 - 1.1 ] at birth , 1.7 ng [ 1.2 - 2.5 ] at age 6 months , and 2 ng [ 1.3 - 3.5 ] at age 1 year [ active vs control , P total amount of allergen recovered at age 1 year was 29-fold ( 95 % CI 15.1- to 56.7-fold ) higher in the control group than in the active group . CONCLUSIONS The avoidance measures used in this study achieved and maintained a low mite allergen environment during pregnancy and in the first year of life in homes of infants at risk of atopy",
"Latent systemic anaphylactic sensitisation to cows ' milk was assessed in 61 preterm infants who were r and omly assigned to receive either a special formula for preterm infants based on cows ' milk or banked breast milk or one or other of these as a supplement to maternal milk . A single sample of venous blood was taken near to the time of discharge from the neonatal intensive care unit , and the histamine release by blood basophils in response to in vitro challenge with cows ' milk and anti-IgE was measured . Compared with the blood from infants fed on human milk , that from infants fed on preterm formula showed a significant increase in histamine release to challenge with cows ' milk , the response being greater in blood from infants of lower birth weight and gestational age . A smaller but significant increase in blood histamine release with anti-IgE challenge was observed in the group fed on preterm formula . Infants of low birth weight fed on preterm formula based on cows ' milk may develop latent systemic sensitisation more rapidly than infants born at term . The clinical importance of this requires further investigation",
"BACKGROUND Asthma places huge dem and s on health-care services , and its prevalence is increasing . Reduction of exposure to environmental allergens could offer a realistic chance for primary prevention . Our aim was to ascertain whether or not living in a low-allergen environment reduces the risk of asthma and atopic diseases in infants . METHODS We assigned infants to four risk groups according to parental atopic status . We enrolled 291 high-risk couples ( both parents atopic , no pets ) into a prospect i ve , prenatally r and omised , cohort study , and allocated them to environmental manipulation , in which measures to reduce prenatal and postnatal allergen exposure were undertaken ( active HRA ) ( n=145 ) or no intervention ( control HRC ) ( n=146 ) . Two further prospect i ve groups were studied : 161 high-risk infants with pets in the home ( HRP group ) and 168 low-risk infants , whose parents were both non-atopic ( LR group ) . The main outcome measures were signs and symptoms of atopic disease at 1 year of age . FINDINGS 103 families dropped out or were lost to follow up . At age 1 year we followed-up 133 HRA , 118 HRC , 140 HRP , and 126 LR infants . Children in the HRA group were less likely to have respiratory symptoms during the first year of life than those in the HRC group . The most pronounced differences were in the relative risks for severe wheeze with shortness of breath ( relative risk 0.44 [ 95 % CI 0.20 - 1.00 ] ) , prescribed medication for the treatment of wheezy attacks ( 0.58 [ 0.36 - 0.95 ] ) , and wheezing after vigorous playing , crying , or exertion ( 0.18 [ 0.04 - 0.79 ] ) . Probability of respiratory symptoms in HRC and HRP infants was similar , whereas it was much lower in the LR than in the HRC group . Cat ownership was significantly associated with sensitisation to cats ( 24.6 [ 3.04 - 199.05 ] ; p=0.003 ) . INTERPRETATION Environmental manipulation reduces some respiratory symptoms in the first year of life in high-risk infants . Further follow up is needed , however , to ascertain whether living in a low-allergen environment reduces allergy and asthma in later life",
"We prospect ively studied the incidence of atopic disease in healthy term infants with a birth weight between ‐1 and ‐2 SD who were fed a cow milk formula during the first few days of life . A total of 216 infants were r and omized to receive either early feeding with formula before normal breastfeeding was started ( n= 112 ) or “ normal feeding ” with breastmilk ( n= 104 ) . Symptoms of allergy developed in 18%% of the infants before 18 months of age in the formula fed group , as compared to 33 % in the breastfed group ( P infants with a history of allergy in two family members . Thus , 11 % of the formula‐fed infants developed allergy symptoms , as compared to 61 % of the control infants ( P with a cow milk formula , before the introduction of breastmilk , may reduce the incidence of allergy symptoms before 18 months of age in infants with a family history of allergy",
"STUDY OBJECTIVE : To identify environmental determinants of six symptoms associated with allergic disease in infancy . DESIGN : Infants were participants in a prospect i ve r and omised controlled trial of feeding practice s in families with a history of atopy . SETTING : Infants were recruited in two maternity hospitals in S Wales and followed up in the community for 1 year . PARTICIPANTS : Mothers of 519 infants agreed to participate , but 36 were excluded ( mainly for moving home or failing to attend for follow-up ) , leaving 483 in the study ( 253 male , 230 female ) . Infants were followed up and examined for evidence of allergic disease at 3 , 6 , and 12 months . MEASUREMENTS AND MAIN RESULTS : At each examination , mothers were question ed about episodes of illness in the infant , and the data presented relate to ( reported and observed ) eczema and nasal discharge , and ( reported ) wheeze , prolonged colds , diarrhoea and vomiting . Mothers kept a diary with details of feeding for the first 6 months . All homes were visited by a nurse who took sample s of dust for dust mite antigen analysis . Extensive socio-demographic data were collected . None of the factors studied showed a convincing relationship with eczema . In a multiple logistic regression analysis breast feeding appeared to protect against wheeze , nasal discharge , colds , vomiting and diarrhoea . Having more siblings increased the likelihood of prolonged colds , and ( together with overcrowding ) of wheeze and nasal discharge . Maternal smoking and low social class were associated with wheeze , and house dust antigen with prolonged colds . Respiratory symptoms were associated with some aspects of housing but these could not be distinguished clearly from other social factors . Babies born in Autumn were at increased risk of wheeze , vomiting and diarrhoea . CONCLUSIONS : Environmental factors play an important part in determining risk of symptoms in potentially atopic babies . These factors are in principle open to manipulation",
"OBJECTIVES We conducted a prospect i ve , r and omized study to evaluate the cumulative incidence of allergy or other adverse reactions to soy formula and to extensively hydrolyzed formula up to the age of 2 years in infants with confirmed cow 's milk allergy . STUDY DESIGN Infants ( n = 170 ) with documented cow 's milk allergy were r and omly assigned to receive either a soy formula or an extensively hydrolyzed formula . If it was suspected that the formula caused symptoms , a double-blind , placebo-controlled challenge ( DBPCFC ) with the formula was performed . The children were followed to the age of 2 years , and soy-specific immunoglobulin E antibodies were measured at the time of diagnosis and at the ages of 1 and 2 years . RESULTS An adverse reaction to the formula was confirmed by challenge in 8 patients ( 10 % ; 95 % confidence interval , 4.4%-18.8 % ) r and omly assigned to soy formula and in 2 patients ( 2.2 % ; 95 % confidence interval , 0.3 % to 7.8 % ) r and omly assigned to extensively hydrolyzed formula . Adverse reactions to soy were similar in IgE-associated and non-IgE-associated cow 's milk allergy ( 11 % and 9 % , respectively ) . IgE to soy was detected in only 2 infants with an adverse reaction to soy . Adverse reactions to soy formula were more common in younger ( Soy formula was well tolerated by most infants with IgE-associated and non-IgE-associated cow 's milk allergy . Development of IgE-associated allergy to soy was rare . Soy formula can be recommended as a first-choice alternative for infants > or=6 months of age with cow 's milk allergy",
"BACKGROUND Distinct wheezing disorders co-exist in young ( preschool ) children , some of which ( early transient wheeze and viral wheeze ) are thought to be unrelated to atopy . Investigation of changes in prevalence of wheezing disorders in preschool children could provide important clues about underlying mechanisms responsible for increasing prevalence of asthma in schoolchildren . METHODS Repeated population surveys of the prevalence of respiratory symptoms were done by parent-completed postal question naires in r and om sample s of 1650 ( 1990 ) and 2600 ( 1998 ) caucasian children aged 1 - 5 years living in the county of Leicestershire , UK . FINDINGS The response rates were 86 % ( 1422 of 1650 ) in 1990 and 84 % ( 2127 of 2522 ) in 1998 . Between 1990 and 1998 , there was a significant increase in the prevalance of reported wheeze ever ( 16 % to 29 % , p current wheeze ( 12 % to 26 % , p diagnosis of asthma ( 11 % to 19 % , p treatment for wheeze ( 15 % to 26 % , p admission for wheeze or other chest trouble ( 6 % to 10 % , p transient early wheezers ( 3 % to 5 % ) , persistent wheezers ( 5 % to 13 % ) , and late-onset wheezers ( 6 % to 8 % ) , and in all severity groups . The increase could not be accounted for by putative household risk factors because these declined between the 2 years . INTERPRETATION The fact that all preschool wheezing disorders increased ( including viral wheeze ) makes it probable that factors unrelated to atopy are implicated in the changing epidemiology of wheeze in childhood",
"The ingestion of food antigens usually results in the induction of oral tolerance , but the clinical and immunologic consequences of brief exposure to cow 's milk proteins during the neonatal period are not well-documented . The aim of this work was to study immunoglobulin (Ig)E and IgG responses to cow 's milk proteins and ovalbumin after exposure during the first three days of life in infants who were otherwise exclusively breast-fed . A group of 129 infants was r and omly assigned at birth to one of three feeding regimens : human milk ( HM ) , cow 's milk formula ( CMF ) , or a casein hydrolysate formula ( CHF ) , during the first three days of life . They were then all exclusively breast-fed for a varying period of time and followed for two years . Serum IgG and IgE antibodies to cow 's milk proteins and ovalbumin ( OVA ) were analyzed in blood sample s obtained at birth , at 4 days and at 2 , 4 , 8 , 12 and 24 months of age . The levels of IgG antibodies to beta-lactoglobulin ( IgG-BLG ) and bovine serum albumin ( IgG-BSA ) were higher in the CMF and the HM groups than in the CHF group for up to two years . This was particularly obvious for IgG-BLG in infants who started weaning before two months . The levels of IgG antibodies to casein ( IgG-CAS ) were higher in the CMF group , as compared with the CHF group at 8 and 12 months . The levels of IgG antibodies to OVA were similar in all three feeding groups . The levels of IgE antibodies to CAS or OVA were similar in the three feeding groups . Exposure to cow 's milk during the first three days of life stimulated IgG antibody production to cow 's milk proteins and this was still obvious at 2 years of age , while feeding with a casein hydrolysate during the first three days of life was associated with low levels of IgG antibodies to cow 's milk proteins",
"Retraction On 28 October 2015 , The BMJ retracted this article , published in 1989 : Ch and ra RK , Puri S , Hamed A. Influence of maternal diet during lactation and use of formula feeds on development of atopic eczema in high risk infants . BMJ 1989;299:228–30 . The BMJ has retracted the article after receiving a copy of an inquiry into the research of R K Ch and ra , which was conducted by the Memorial University of Newfoundl and and completed in August 1995 . The university did not publish the inquiry report at the time . Nor did it notify the editors of journals that had published articles by Ch and ra that were considered in the report . The BMJ obtained a copy of the report when it came into the public domain as a result of Ch and ra taking and losing a legal action against the Canadian Broadcasting Corporation ( CBC ) , which aired television programmes about Ch and ra in 2006 . The inquiring committee experienced great difficulty with its work , but its final conclusion was that “ scientific misconduct has been committed by Dr Ch and ra . ” It looked at three studies and found that : “ absolutely no raw data ( or files ) of any kind were exhibited ” “ the Committee can not identify anyone who did the recruiting , can not identify anyone who did or remembers a significant amount of work ” “ the coauathors had little or very likely nothing to do with the work ” “ it is unbelievable that there are essentially no hospital records to support the study in question ” “ the committee can not accept that the Carnation study was done anywhere near to completeness or with the accuracy reported in the Annals of Allergy and Journal of Clinical Nutrition , For that matter , the same can probably be said for the Mead Johnson work published in the British Medical Journal . ” When asked by The BMJ in 2015 why it had not published the report in 1995 , Memorial University of Newfoundl and said that the report “ was the product of a flawed investigation process and could not be relied upon . ” In the CBC programmes , however , a university spokesman said that the university had not acted on the report because of legal threats from Ch and ra . The university further told The BMJ : “ In the spirit of being helpful , we acknowledge that over the years serious questions have been raised about the 1989 publication , leading to much controversy . If [ The ] BMJ decides to retract the paper on the basis of evidence apart from the findings of the 1995 report , then we would underst and your decision in this regard . ” The BMJ is retracting the paper because of the 1995 report , and because of the convincing evidence given in the CBC television programmes and the court case that the work of R K Ch and ra is not to be trusted . For more information , see The BMJ 's feature article(1 ) and editorial,(2 ) published on 28 October 2015"
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OBJECTIVE Lateral wedge insoles are intended to reduce biomechanical risk factors of medial knee osteoarthritis ( OA ) progression , such as increased knee joint load ; however , there has been no definitive consensus on this topic . The aim of this systematic review and meta- analysis was to establish the within-subject effects of lateral wedge insoles on knee joint load in people with medial knee OA during walking . METHODS Six data bases were search ed from inception until February 13 , 2015 . Included studies reported on the immediate biomechanical effects of lateral wedge insoles during walking in people with medial knee OA . Primary outcomes of interest relating to the biomechanical risk of disease progression were the first and second peak external knee adduction moment ( EKAM ) and knee adduction angular impulse ( KAAI ) . Eligible studies were pooled using r and om-effects meta- analysis . RESULTS Eighteen studies were included with a total of 534 participants . Lateral wedge insoles result ed in a small but statistically significant reduction in the first peak EKAM ( st and ardized mean difference [ SMD ] -0.19 ; 95 % confidence interval [ 95 % CI ] -0.23 , -0.15 ) and second peak EKAM ( SMD -0.25 ; 95 % CI -0.32 , -0.19 ) with a low level of heterogeneity ( I(2 ) = 5 % and 30 % , respectively ) . There was a favorable but small reduction in the KAAI with lateral wedge insoles ( SMD -0.14 ; 95 % CI -0.21 , -0.07 , I(2 ) = 31 % ) . Risk of method ologic bias scores ( quality index ) ranged from 8 to 13 out of 16 . CONCLUSION Lateral wedge insoles cause small reductions in the EKAM and KAAI during walking in people with medial knee OA . Current evidence demonstrates that lateral wedge insoles appear ineffective at attenuating structural changes in people with medial knee OA as a whole and may be better suited to targeted use in biomechanical phenotypes associated with larger reductions in knee load
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"OBJECTIVE To test the hypothesis that a custom-fit valgus knee brace and custom-made lateral wedge foot orthotic will have greatest effects on decreasing the external knee adduction moment during gait when used concurrently . DESIGN Proof-of-concept , single test session , crossover trial . SETTING Biomechanics laboratory within a tertiary care center . PARTICIPANTS Patients ( n=16 ) with varus alignment and knee osteoarthritis ( OA ) primarily affecting the medial compartment of the tibiofemoral joint ( varus gonarthrosis ) . INTERVENTIONS Custom-fit valgus knee brace and custom-made full-length lateral wedge foot orthotic . Amounts of valgus angulation and wedge height were tailored to each patient to ensure comfort . MAIN OUTCOME MEASURES The external knee adduction moment ( % body weight [BW]*height [ Ht ] ) , frontal plane lever arm ( cm ) , and ground reaction force ( N/kg ) , determined from 3-dimensional gait analysis completed under 4 r and omized conditions : ( 1 ) control ( no knee brace , no foot orthotic ) , ( 2 ) knee brace , ( 3 ) foot orthotic , and ( 4 ) knee brace and foot orthotic . RESULTS The reduction in knee adduction moment was greatest when concurrently using the knee brace and foot orthotic ( effect sizes ranged from 0.3 to 0.4 ) . The mean decrease in first peak knee adduction moment compared with control was .36 % BW*Ht ( 95 % confidence interval [ CI ] , -.66 to -.07 ) . This was accompanied by a mean decrease in frontal plane lever arm of .59 cm ( 95 % CI , -.94 to -.25 ) . CONCLUSIONS These findings suggest that using a custom-fit knee brace and custom-made foot orthotic concurrently can produce a greater overall reduction in the knee adduction moment , through combined effects in decreasing the frontal plane lever arm ",
"We examined if a subject-specific amount of lateral wedge added to a foot orthosis could alter knee mechanics to potentially reduce the progression of knee osteoarthritis in patients with medial knee osteoarthritis . Twenty individuals with medial knee osteoarthritis ( > /=2 Kellgren Lawrence grade ) were prescribed a custom laterally wedged foot orthotic device . The prescribed wedge amount was the minimal wedge amount that provided the maximum amount of pain reduction during a lateral step-down test . Following an accommodation period , all subjects returned to the laboratory for a gait analysis . Knee mechanics were collected as the subjects walked at an intentional walking speed . Walking in the laterally wedged orthotic device significantly reduced the peak adduction moment during early stance ( p knee adduction excursion from heel strike to peak adduction ( p peak adduction moment during propulsion or peak adduction during stance were observed between the orthotic conditions . A subject-specific laterally wedged orthotic device was able to reduce the peak knee adduction moment during early stance , which is thought to be associated with the progression of knee osteoarthritis . Previous studies on this device have reported issues associated with foot discomfort when using wedge amounts > 7 degrees ; however , no such issues were reported in this study . Therefore , providing a custom laterally wedged orthotic device may potentially increase compliance while still potentially reducing disease progression",
"Objective This study aim ed to determine whether the effect of laterally wedged insoles on the adduction moment in knee osteoarthritis ( OA ) declined after one month of wear , and whether higher reported use of insoles was associated with a reduced effect on the adduction moment at one month . Methods Twenty people with medial compartment OA underwent gait analysis in their own shoes wearing i ) no insoles and ; ii ) insoles wedged laterally 5 ° in r and om order . Testing occurred at baseline and after one month of use of the insoles . Participants recorded daily use of insoles in a log-book . Outcomes were the first and second peak external knee adduction moment and the adduction angular impulse , compared across conditions and time with repeated measures general linear models . Correlations were obtained between total insole use and change in gait parameters with used insoles at one month , and change scores were compared between high and low users of insoles using general linear models . Results There was a significant main effect for condition , whereby insoles significantly reduced the adduction moment ( all p total insole use and change in gait parameters with used insoles at one month , nor was there a difference in effectiveness of insoles between high and low users of the insoles at this time . Conclusion Effects of laterally wedged insoles on the adduction moment do not appear to decline after one month of continuous use , suggesting that significant wedge degradation does not occur over the short-term",
"Background The results of conservative treatment of knee osteoarthritis ( OA ) are generally evaluated in epidemiological studies with clinical outcome measures as primary outcomes . Biomechanical evaluation of orthoses shows that there are potentially beneficial biomechanical changes to joint loading ; however , evaluation in relation to clinical outcome measures in longitudinal studies is needed . Questions / purpose sWe asked ( 1 ) is there an immediate effect on gait in patients using a laterally wedged insole or valgus knee brace ; ( 2 ) is there a late ( 6 weeks ) effect ; and ( 3 ) is there a difference between subgroups within each group with respect to patient compliance , body mass index , and OA status ? Methods This was a secondary analysis of data from a previous r and omized controlled trial of patients with early medial knee OA . A total of 91 patients were enrolled in that trial , and 73 ( 80 % ) completed it after 6 months . Of the enrolled patients , 80 ( 88 % ) met prespecified inclusion criteria for analysis in the present study . The patients were r and omized to an insole or brace . Gait was analyzed with and without wearing the orthosis ( insole or brace ) at baseline and after 6 weeks . Measurements were taken of the knee adduction moment , ground reaction force , moment arm , walking speed , and toe-out angle . Data were analyzed with regression analyses based on an intention-to-treat principle . Results A mean reduction of 4 % ( ± 10 ) ( 95 % confidence interval [ CI ] , −0.147 to −0.03 , p = 0.003 ) of the peak knee adduction moment and 4 % ( ± 13 ) ( 95 % CI , −0.009 to −0.001 , p = 0.01 ) of the moment arm at baseline was observed in the insole group when walking with an insole was compared with walking without an insole . A mean reduction of 1 % ( ± 10 ) ( 95 % CI , −0.002 to −0.001 , p = 0.001 ) of the peak knee adduction moment and no reduction of the moment arm were measured after 6 weeks . No reduction of knee adduction moment , moment arm , or ground reaction force was seen in the brace group at baseline and after 6 weeks . Subgroup analysis showed no differences in biomechanical effect for obesity , stage of OA , and whether patients showed a clinical response to the treatment . Conclusions Laterally wedged insoles unload the medial compartment only at baseline in patients with varus alignment and by an amount that might not be clinical ly important . No biomechanical alteration was seen after 6 weeks of wearing the insole . Valgus brace therapy did not result in any biomechanical alteration . Taken together , this study does not show a clinical ly relevant biomechanical effect of insole and brace therapy in patients with varus medial knee OA.Level of Evidence Level I , therapeutic study . See Instructions for Authors for a complete description of levels of evidence",
"OBJECTIVE To evaluate the effects of a modified shoe that incorporates both lateral wedging and a variable-stiffness sole on knee joint loading in 3 population s : individuals with symptomatic and radiographic knee osteoarthritis ( OA ) , asymptomatic overweight individuals , and asymptomatic healthy weight individuals . METHODS Ninety participants ( 30 per group ) underwent a 3-dimensional gait analysis across 3 test conditions : modified shoes , st and ard control shoes , and barefoot . For each condition , the first peak knee adduction moment ( KAM ) and knee flexion moment ( KFM ) ( both expressed as Nm/[body weight × height]% ) as well as the KAM impulse ( expressed as Nm.s/[body weight × height]% ) were determined . RESULTS The modified shoes significantly reduced the peak KAM as compared to the control shoes in both the OA ( P = 0.002 ) and the overweight ( P = 0.03 ) groups . In the OA group , there was no significant difference in peak KAM when walking in the modified shoe as compared to walking barefoot . In the overweight and the healthy weight groups , the peak KAM when walking in the modified shoe was significantly higher than that when walking barefoot ( P the KAM impulse was significantly reduced when walking in the modified shoe as compared to the control shoe ( P in the KFM between walking conditions for any group . CONCLUSION The findings illustrate that a shoe incorporating both a lateral wedge and a variable-stiffness sole can significantly reduce medial knee joint load . Further research examining the effects of these shoes on pain , function , and structural changes in the joint is warranted",
"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",
"OBJECTIVE To assess immediate effects of laterally wedged insoles on walking pain , external knee adduction moment , and static alignment , and whether these immediate effects together with age , body mass index , and disease severity predict clinical outcome after 3 months of wearing insoles in medial knee osteoarthritis . METHODS Forty volunteers ( mean age 64.7 years , 16 men ) were tested in r and om order with and without a pair of 5 degrees full-length lateral wedges . Immediate changes in static alignment were measured via radiographic mechanical axis and changes in adduction moment via 3-dimensional gait analysis . After 3 months of treatment with insoles , changes in pain and physical functioning were assessed via the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and patient-perceived global change scores . RESULTS Reductions in the adduction moment occurred with insoles ( first peak mean [ 95 % confidence intervals ( 95 % CI ) ] -0.22 [ -0.28 , -0.15 ] Nm/body weight x height % ) , accompanied by a reduction in walking pain of approximately 24 % ( mean [ 95 % CI ] -1.0 [ -4.0 , 2.0 ] ) . Insoles had no mean effect on static alignment . Mean improvement in WOMAC pain ( P = 0.004 ) and physical functioning ( mean [ 95 % CI ] -6 [ -11 , -1 ] ) was observed at 3 months , with 25 ( 69 % ) and 26 ( 72 % ) of 36 individuals reporting global improvement in pain and functioning , respectively . Regression analyses demonstrated that disease severity , baseline functioning , and magnitude of immediate change in walking pain and the first peak adduction moment with insoles were predictive of clinical outcome at 3 months . CONCLUSION Lateral wedges immediately reduced knee adduction moment and walking pain but had no effect on static alignment . Although some parameters predicted clinical outcome , these explained only one-third of the variance , suggesting that other unknown factors are also important",
"OBJECTIVE Gait biomechanics ( knee adduction moment , center of pressure ) and static alignment were investigated to determine the mechanical effect of foot orthoses in people with medial compartment knee osteoarthritis . DESIGN Repeated measures design in which subjects were exposed to three conditions ( normal footwear , heel wedge and orthosis ) in r and om order . BACKGROUND The knee adduction moment is an indirect measure of medial compartment loading . It was hypothesized that the use of a 5 degrees valgus wedge and 5 degrees valgus modified orthosis would shift the center of pressure laterally during walking , thereby decreasing the adduction moment arm and the adduction moment . METHODS Peak knee adduction moment and center of pressure excursion were obtained in nine subjects with medial compartment knee OA during level walking using an optoelectric system and force plate . Static radiographs were taken in 12 subjects using precision radiographs . RESULTS There was no difference between conditions in static alignment , the peak adduction moment or excursion of the center of pressure in the medial-lateral direction . No relationship was found between the adduction moment and center of pressure excursion in the medial-lateral plane . The displacement of the center of pressure in the anterior-posterior direction , measured relative to the laboratory coordinate system , was decreased with the orthosis compared to the control condition ( P=0.036 ) and this measure was correlated with the adduction moment ( r=0.45 , P=0.019 ) . CONCLUSIONS The proposed mechanism was not supported by the findings . The reduction in the center of pressure excursion in the anterior-posterior direction suggests that foot positioning was altered , possibly to a toe-out position , while subjects wore the orthoses . Based on the current findings , we hypothesize that toe-out positioning may reduce medial joint load . RELEVANCE Knee Osteoarthritis is the most common cause of chronic disability amongst seniors . Developing inexpensive , non-invasive treatment strategies for this large population has potential to impact health care costs , quality of life and clinical outcomes"
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41179f74-06ff-11f0-808a-c43d1ab1c353
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Abstract Objective : To review contemporary knowledge concerning the innovative trends and perspectives in the treatment of erectile dysfunction ( ED ) . Methods : Medline was review ed for English- language journal articles between January 2000 and March 2016 , using the terms ‘ erectile dysfunction treatments ’ , ‘ new trends ’ and ‘ perspectives ’ . In all , 114 original articles and 16 review articles were found to be relevant . Of the 76 cited papers that met the inclusion criteria , 51 papers had level of evidence of 1a–2b , whilst 25 had level of evidence of 3–4 . Criteria included all pertinent review articles , r and omised controlled trials with tight method ological design , cohort studies , and retrospective analyses . We also manually review ed references from selected articles . Results : Several interesting studies have addressed novel phosphodiesterase type 5 inhibitors ( PDE5Is ) , orodispersible tablets , their recent chronic use , and combination with other agents . A few controlled studies have addressed herbal medicine as a sole or additional treatment for ED . Experimental studies and exciting review papers have addressed stem cells as novel players in the field of ED treatment . Other recent articles have revised the current status of low-intensity extracorporeal shockwave therapy in the field of ED . A few articles without long-term data have addressed new technologies that included : external penile support devices , penile vibrators , tissue engineering , nanotechnology , and endovascular tools for ED treatment . Conclusions : The current treatment of ED is still far from ideal . We expect to see new drugs and technologies that may revolutionise ED treatment , especially in complex cases
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"Background To explore the impact of patient-characteristics and relevant comorbidities on treatment continuation rates , effectiveness , and satisfaction in patients with erectile dysfunction ( ED ) who started or switched to tadalafil 5 mg once daily ( TAD-OaD ) at baseline . Methods In the E DATE observational study , phosphodiesterase-type-5 (PDE5)-inhibitor pretreated or naïve ED patients who started or switched to TAD-OaD were prospect ively followed for 6 months . Time to discontinuation of TAD-OaD was estimated using the Kaplan-Meier product-limit method at Months 2 , 4 , and 6 in subgroups stratified by age ( 18 − 65 years and > 65 years ) , PDE5-inhibitor pretreatment , ED-severity ( mild , moderate , severe ) , and presence or absence of relevant comorbidities ( BPH , diabetes , CVD , hypertension , dyslipidemia ) . LSmean change from baseline in International Index of Erectile Function ( IIEF ) and Erectile Dysfunction Inventory of Treatment Satisfaction ( EDITS ) scores and associated 95 % CIs were assessed using a mixed-model for repeated measures . Visit , ED etiology , and subgroups were included as fixed-effects . Results Overall , 778 patients received prescriptions for initiating or switching to TAD-OaD at baseline . At Month 2 , > 90 % of patients remained on TAD-OaD , except those aged > 65 years ( 86.7 % ) and patients with severe ED ( 89.0 % ) . More than 80 % of patients in all subgroups , except those aged > 65 years ( 75.0 % ) , continued TAD-OaD at Month 6 . There was a significant LSmean negative effect on IIEF- EF domain-score improvement for BPH ( LSmean effect [ 95 % CI ] : −2.77 [ −4.98 , −0.55 ] , p = 0.014 ) , previous PDE5-inhibitor treatment ( −2.13 [ −3.33,-0.94 ] , p The LSmean effect on change in IIEF-EF was significantly positive for diabetes ( 2.28 [ 0.64,3.92 ] , p = 0.007 ) , most likely because those with diabetes had more severe ED at baseline . For all other parameters , no statistically significant LSmean effects in IIEF-EF changes were observed . No comorbidity or baseline-characteristic except age ( 18 − 65 years vs > 65 years : 11.25 [ 2.96,19.54 ] , p = 0.008 ) affected changes in EDITS . Conclusions Under routine clinical conditions , treatment continuation rate or satisfaction does not seem to be significantly affected by the presence of comorbidities in men who choose ED-treatment with TAD-OaD. The magnitude of treatment effectiveness was affected by certain baseline characteristics and comorbid conditions . Trial Registration The study ( H6D-EW-LVIU ) is registered in the German VfA Registry of Non-Interventional Studies ( Verb and Forschender Arzneimittelhersteller ) since 06 December 2011 ; available at : http://www.vfa.de/de/arzneimittel-forschung/ date nbanken-zu-arzneimitteln/nisdb/nis-details/_741",
"OBJECTIVE To evaluate the efficacy and safety of combination therapy of sildenafil plus vacuum erection devices in men with type 2 diabetes mellitus with moderate to severe erectile dysfunction who are dissatisfied with the results of using sildenafil alone . METHODS The study included 66 diabetes mellitus patients presenting erectile dysfunction for at least 6 months and dissatisfied with the use of 100 mg sildenafil monotherapy . The patients were r and omized in two groups . Those in group A ( n = 33 ) were instructed to use a vacuum erection device only , whereas those in group B ( n = 33 ) were treated with combination therapy , including sildenafil 100 mg and a vacuum erection device . Erectile function was evaluated subjectively using the International Index of Erectile Function , Sexual Encounter Profile question naire questions 2 and 3 at visit 1 ( baseline ; study entry ) , visit 2 ( 4 weeks after baseline ) , and visit 3 ( 12 weeks after baseline ; study end ) . RESULTS There were no significant differences in average patient age , duration of diabetes , duration of erectile dysfunction , baseline International Index of Erectile Function scores , hypertension , blood testosterone , smoking and alcohol consumption between two groups . Mean International Index of Erectile Function scores were significantly higher for group B at the 1-month ( 14.86 ± 2.17 vs 12.41 ± 2.63 ; P better successful penetration ( 73.3 % vs 46.6 % ) and successful intercourse ( 70 % vs 46.6 % ) at 3 months compared with group A. CONCLUSION Combined use of sildenafil and vacuum erection device therapy significantly enhances erectile function , and it is well tolerated by diabetes mellitus patients not responding to first-line sildenafil alone",
"INTRODUCTION The role of testosterone in erectile dysfunction ( ED ) is increasingly recognized . It is suggested that assessment of testosterone deficiency in men with ED and symptoms of hypogonadism , prior to first-line treatment , may be a useful tool for improving therapy . AIM In this prospect i ve , observational , and longitudinal study , we investigated the effects of vardenafil treatment as adjunctive therapy to testosterone undecanoate in hypogonadal ED patients who failed to respond to testosterone treatment alone . METHODS One hundred twenty-nine testosterone deficient ( serum total testosterone ≤ 3.4 ng/mL ) patients aged 56 ± 3.9 years received intramuscular injections of long-acting parenteral testosterone undecanoate at 3-month intervals for 8 months mean follow-up . MAIN OUTCOME MEASURES Scores on the International Index of Erectile Function Question naire-five items ( IIEF-5 ) and partner survey scores were compared at baseline and posttreatment with testosterone therapy alone or in combination with vardenafil . Patient baseline demographics and concomitant disease were correlated with patients ' IIEF-5 scores . RESULTS Seventy one ( 58.2 % ) responded well to monotherapy within 3 months . Nonresponders had lower testosterone levels and higher rates of concomitant diseases and smoking . Thirty-four of the 51 nonresponders accepted the addition of 20 mg vardenafil on dem and . Efficacy assessment s were measured by the IIEF-erectile function domain ( IIEF-EF , questions 1 - 5 plus 15 , 30 points ) and partner self- design ed survey at baseline after 4 - 6 weeks and at study end point . Thirty out of 34 patients responded well to this combination . IIEF-EF Sexual Health Inventory for Men score improved from 12 to 24 ( P and partner survey showed significantly higher satisfaction ( P reported spontaneous or nocturnal and morning erections or tumescence . No changes in adverse effects were recorded . CONCLUSIONS These data suggest that combination therapy of testosterone and vardenafil is safe and effective in treating hypogonadal ED patients who failed to respond to testosterone monotherapy",
"Our previous study showed that vacuum erectile device ( VED ) therapy has improved erectile function in rats with bilateral cavernous nerve crush ( BCNC ) injuries . This study was design ed to explore the mechanism of VED in penile rehabilitation by analyzing cavernous oxygen saturation ( SO2 ) and to examine the effect of VED therapy on preventing penile shrinkage after BCNC . Thirty adult Sprague-Dawley rats were r and omly assigned into three groups : group 1 , sham surgery ; group 2 , BCNC ; and group 3 , BCNC+VED . Penile length and diameter were measured on a weekly basis . After 4 weeks of therapy , the penile blood was extracted by three methods for blood gas analysis ( BGA ) : method 1 , cavernous blood was aspirated at the flaccid state ; method 2 , cavernous blood was aspirated at the traction state ; and method 3 , cavernous blood was aspirated immediately after applying VED . SO2 values were tested by the blood gas analyzer . The results showed that VED therapy is effective in preventing penile shrinkage induced by BCNC ( Penile shortening : BCNC group 1.9±1.1 mm ; VED group 0.3±1.0 mm ; P : BCNC group 0.28±0.14 mm ; VED group 0.04±0.14 mm ; P were increased by VED application ( 88.25%±4.94 % ) compared to the flaccid ( 76.53%±4.16 % ) or traction groups ( 78.93%±2.56 % ) ( P The calculated blood constructs in the corpus cavernosum right after VED application were 62 % arterial and 38 % venous blood . These findings suggest that VED therapy can effectively preserve penile size in rats with BCNC injury . The beneficial effect of VED therapy is related to antihypoxia by increasing cavernous blood SO2 ",
"INTRODUCTION Stem cell therapy is thought to improve wound healing and promote vasculogenesis and has also been investigated as a treatment for patients with erectile dysfunction ( ED ) , which is usually caused by a microvascular disease such as diabetes mellitus or hypertension . OBJECTIVE To determine the feasibility and effects of using placental matrix-derived mesenchymal stem cells ( PM-MSCs ) in the treatment of patients with ED . METHODS Participants were recruited from a private practice urology in Coral Springs , Florida . Each patient received an injection of PM-MSCs and was followed up with at 6 weeks , 3 months , and 6 months to assess peak systolic velocity ( PSV ) , end diastolic velocity , stretched penile length , penile width , and erectile function status based on the International Index of Erectile Function question naire . RESULTS Eight patients were injected with PM-MSCs . At the 6-week follow-up , PSV ranged from 25.5 cm/s to 56.5 cm/s ; at 3 months , PSV ranged from 32.5 cm/s to 66.7 cm/s . Using unpaired t tests , the increase in PSV was statistically significant ( P PSV ranged from 50.7 cm/s to 73.9 cm/s ( P Changes in measured end diastolic velocity , stretched penile length , penile width , and International Index of Erectile Function scores were not statistically significant . At the 6-week follow-up , 2 patients for whom previous oral therapies failed had the ability to sustain erections on their own . At the 3-month follow-up , 1 additional patient was able to achieve erections on his own . CONCLUSION To our knowledge , this is one of the first human studies to report on the feasibility of using stem cell therapy to treat patients with ED . The results indicate that this treatment may be beneficial , and further investigations with larger sample sizes should be conducted . ( Clinical Trials.gov number NCT02398370 )",
"To investigate the therapeutic effect of different doses of low energy shock wave therapy ( LESWT ) on the erectile dysfunction ( ED ) in streptozotocin ( STZ ) induced diabetic rats . SD rats ( n = 75 ) were r and omly divided into 5 groups ( normal control , diabetic control , 3 different dose LESWT treated diabetic groups ) . Diabetic rats were induced by intra-peritoneal injection of STZ ( 60 mg/kg ) and rats with fasting blood glucose ≥ 300 mg/dL were selected as diabetic models . Twelve weeks later , different doses of LESWT ( 100 , 200 and 300 shocks each time ) treatment on penises were used to treat ED ( 7.33 MPa , 2 shocks/s ) three times a week for two weeks . The erectile function was evaluated by intracavernous pressure ( ICP ) after 1 week washout period . Then the penises were harvested for histological study . The results showed LESWT could significantly improve the erectile function of diabetic rats , increase smooth muscle and endothelial contents , up-regulate the expression of α-SMA , vWF , nNOS and VEGF , and down- regulate the expression of RAGE in corpus cavernosum . The therapeutic effect might relate to treatment dose positively , and the maximal therapeutic effect was noted in the LESWT300 group . Consequently , 300 shocks each time might be the ideal LESWT dose for diabetic ED treatment",
"AIMS This was the first observational study evaluating treatment continuation , effectiveness and tolerability of tadalafil 5 mg once daily ( TAD-OaD ) in patients who chose and paid for treatment of erectile dysfunction ( ED ) in routine clinical practice . METHODS Men ≥ 18 years with ED , treated previously with phosphodiesterase type 5 (PDE5)-inhibitor on-dem and ( PRN ) or treatment-naïve , were enrolled at 59 sites . For patients prescribed TAD-OaD at baseline ( T1 ) , change in erectile function ( IIEF-EF and GAQ ) was documented after 1 - 3 ( T2 ) and 4 - 6 ( T3 ) months . The primary outcome was the probability to switch/discontinue from TAD-OaD , estimated by Kaplan-Meier ( KM ) product-limit method . Changes in IIEF-EF were evaluated using a mixed model for repeated measures adjusting for patient baseline characteristics . RESULTS Of 975 men enrolled ( median age 56.8 years , 33.7 % with previous PDE5-inhibitor use ) , 778 were prescribed TAD-OaD , 135 TAD-PRN and 62 sildenafil or vardenafil PRN . During the 6-month longitudinal observation , 107 patients ( 13.8 % of 778 ) switched or discontinued TAD-OaD-treatment . KM-rates ( 95%CI ) for continuing TAD-OaD at 2 , 4 and 6 months were 94.0 % ( 92.3 , 95.7 ) , 88.3 % ( 85.9 , 90.6 ) and 86.3 % ( 83.7 , 88.9 ) , respectively . The 25th percentile of time to switch/discontinuation of TAD-OaD was estimated as 31.1 weeks ( lower 95%CI 30.3 weeks ) . At T3 , IIEF-EF scores had increased by 7.1 ( LSmean ; 95%CI 5.8 , 8.5 ) points ; 91.3 % of patients reported improved erections . The most frequently reported AE was headache ( 10 patients ; 1.3 % ) ; no new/unexpected safety signals were observed . CONCLUSION Under routine conditions , and when patients were involved in treatment decision-making , more than 86 % of men starting/switching to tadalafil once daily ( OaD ) at baseline continued tadalafil OaD treatment for ≥ 6 months",
"INTRODUCTION Peyronie 's disease ( PD ) has frequently been associated with erectile dysfunction ( ED ) and may further compromise coitus . AIM To investigate the efficacy of intratunical injection of genetically modified rat adipose tissue-derived stem cells ( ADSCs ) expressing human interferon α-2b ( ADSCs-IFN ) in decreasing fibrosis and restoring erectile function in a rat model of tunica albugineal fibrosis ( TAF ) . METHODS A total of 36 Sprague-Dawley rats ( 12 weeks old ; 300 - 350 g ) were r and omly divided in six equal groups : ( i ) sham group ( 50 μL saline-injected into the tunica albuginea [ TA ] ) ; ( ii ) TAF group ( transforming growth factor [TGF]-β1 [ 0.5 μg/50 μL ] injected into the TA ) ; ( iii ) TGF-β1 plus 5 × 10(5 ) control ADSCs injected same day ; ( iv ) TGF-β1 plus 5 × 10(5 ) ADSCs-IFN injected same day ; ( v ) TGF-β1 plus 5 × 10(5 ) control ADSCs injected after 30 days ; and ( vi ) TGF-β1 plus 5 × 10(5 ) ADSCs-IFN injected after 30 days . Rat allogeneic ADSCs were harvested from inguinal fat tissue . MAIN OUTCOME MEASURES Forty-five days following the TGF-β1 injection , erectile function was assessed , and penile tissues were harvested for further evaluations . RESULTS In the same-day injection groups , intratunical injection of ADSCs and ADSC-IFN improved erectile response observed upon stimulation of cavernous nerve compared with TAF group . Intratunical ADSC-IFN injection at day 30 improved erectile responses 3.1 , 1.8 , and 1.3 fold at voltages of 2.5 , 5.0 , and 7.0 , respectively , when compared with TAF group . Furthermore , at voltages of 2.5 and 5.0 , treatment on day 30 with ADSCs-IFN improved erectile responses 1.6- and 1.3-fold over treatment with ADSCs alone . Local injection of ADSCs or ADSCs-IFN reduced Peyronie's-like manifestations , and these effects might be associated with a decrease in the expression of tissue inhibitors of metalloproteinases . CONCLUSION This study documents that transplantation of genetically modified ADSCs , with or without human IFN α-2b , attenuated Peyronie's-like changes and enhanced erectile function in a rat model of TAF",
"PURPOSE We investigated the clinical and physiological effect of low intensity extracorporeal shock wave therapy on men with organic erectile dysfunction who are phosphodiesterase type 5 inhibitor responders . MATERIAL S AND METHODS After a 1-month phosphodiesterase type 5 inhibitor washout period , 67 men were r and omized in a 2:1 ratio to receive 12 sessions of low intensity extracorporeal shock wave therapy or sham therapy . Erectile function and penile hemodynamics were assessed before the first treatment ( visit 1 ) and 1 month after the final treatment ( followup 1 ) using vali date d sexual function question naires and venoocclusive strain gauge plethysmography . RESULTS Clinical ly we found a significantly greater increase in the International Index of Erectile Function-Erectile Function domain score from visit 1 to followup 1 in the treated group than in the sham treated group ( mean ± SEM 6.7 ± 0.9 vs 3.0 ± 1.4 , p = 0.0322 ) . There were 19 men in the treated group who were initially unable to achieve erections hard enough for penetration ( Erection Hardness Score 2 or less ) who were able to achieve erections sufficiently firm for penetration ( Erection Hardness Score 3 or greater ) after low intensity extracorporeal shock wave therapy , compared to none in the sham group . Physiologically penile hemodynamics significantly improved in the treated group but not in the sham group ( maximal post-ischemic penile blood flow 8.2 vs 0.1 ml per minute per dl , p discomfort or reported any adverse effects from the treatment . CONCLUSIONS This is the first r and omized , double-blind , sham controlled study to our knowledge that shows that low intensity extracorporeal shock wave therapy has a positive short-term clinical and physiological effect on the erectile function of men who respond to oral phosphodiesterase type 5 inhibitor therapy . The feasibility and tolerability of this treatment , coupled with its potential rehabilitative characteristics , make it an attractive new therapeutic option for men with erectile dysfunction",
"OBJECTIVE To investigate combined therapeutic efficacy of human adipose-derived stem cells ( h-ADSCs ) application on injured cavernous nerve and low-energy shockwave therapy ( SWT ) on the corpus cavernosum in a rat model of post-prostatectomy erectile dysfunction . MATERIAL S AND METHODS Rats were r and omly divided into 5 groups : control , bilateral cavernous nerve injury ( BCNI ) , adipose-derived stem cell ( ADSC ) ( BCNI group with h-ADSCs on the cavernous nerve ) , SWT ( BCNI group with low-energy SWT on the corpus cavernosum ) , and ADSC/SWT ( BCNI group with a combination of h-ADSCs and low-energy SWT ) . After 4 weeks , erectile function was assessed using intracavernosal pressure . The cavernous nerves and penile tissue were evaluated through immunostaining , Western blotting , and a cyclic guanosine monophosphate assay . RESULTS ADSC/SWT significantly improved intracavernosal pressure compared to the other experimental group . ADSC had significantly increased β-III tubulin expression of the cavernous nerve , and SWT had a markedly enhanced vascular endothelial growth factor expression in corpus cavernosum . The ADSC/SWT group had a significantly increased in alpha smooth muscle actin content ( P ( P ( P , and cyclic guanosine monophosphate level ( P reduces the apoptotic index in the corpus cavernosum . CONCLUSION In this study , h-ADSCs showed an effect on the recovery of injured cavernous nerve and low-energy SWT improved angiogenesis in the corpus cavernosum . The h-ADSCs combined with low-energy SWT showed beneficial effect on the recovery of erectile function in a rat model of postprostatectomy erectile dysfunction",
"Introduction . Low-energy shockwave therapy ( LESWT ) has been shown to improve erectile function in patients suffering from diabetes mellitus (DM)-associated erectile dysfunction ( ED ) . However , the underlying mechanism remains unknown . Aim . The aim of this study is to investigate whether LESWT can ameliorate DM-associated ED in a rat model and examine the associated changes in the erectile tissues . Methods . Newborn male rats were intraperitoneally injected with 5-ethynyl-2-deoxyuridine ( EdU ; 50 mg/kg ) for the purpose of tracking endogenous mesenchymal stem cells ( MSCs ) . Eight weeks later , eight of these rats were r and omly chosen to serve as normal control ( N group ) . The remaining rats were injected intraperitoneally with 60 mg/kg of streptozotocin ( STZ ) to induce DM . Eight of these rats were r and omly chosen to serve as DM control ( DM group ) , whereas another eight rats were subject to shockwave ( SW ) treatment ( DM+SW group ) . Each rat in the DM+SW group received 300 shocks at energy level of 0.1 mJ/mm(2 ) and frequency of 120/minute . This procedure was repeated three times a week for 2 weeks . Another 2 weeks later , all 24 rats were evaluated for erectile function by intracavernous pressure ( ICP ) measurement . Afterward , their penile tissues were examined by histology . Main Outcome Measures . Erectile function was measured by ICP . Neuronal nitric oxide synthase (nNOS)-positive nerves and the endothelium were examined by immunofluorescence staining . Smooth muscle and MSCs were examined by phalloidin and EdU staining , respectively . Results . STZ treatment caused a significant decrease in erectile function and in the number of nNOS-positive nerves and in endothelial and smooth muscle contents . These DM-associated deficits were all partially but significantly reversed by LESWT . MSCs ( EdU-positive cells ) were significantly more numerous in DM+SW than in DM rats . Conclusion . LESWT can partially ameliorate DM-associated ED by promoting regeneration of nNOS-positive nerves , endothelium , and smooth muscle in the penis . These beneficial effects appear to be mediated by recruitment of endogenous MSCs . Qiu X , Lin G , Xin Z , Ferretti L , Zhang H , Lue TF , and Lin C-S. Effects of low-energy shockwave therapy on the erectile function and tissue of a diabetic rat model . J Sex Med 2013;10:738 - 746",
"OBJECTIVES To evaluate the impact of endovascular embolisation therapy in men with erectile impotence due to veno-occlusive dysfunction . METHODS We retrospectively evaluated 29 patients with a history of erectile impotence due to veno-oclusive dysfunction confirmed by pharmacocavernosometry and cavernosography . All underwent endovascular embolisation therapy over transfemoral approach . After positioning the catheter system at the target level heights , embolisation with N-butyl-2-cyanoacrylate ( Histoacryl ( ® ) ) was performed . Technical and clinical success as well as major and minor complications were evaluated . RESULTS All procedures were performed without any major or minor events . Complication rate was 0 % . Technical success was achieved in 27/29 ( 93.1 % ) . Two patients failed for anatomical reasons . Overall clinical success was achieved in 24/27 ( 88.8 % ) patients with recovering from E1 ( poor tumescense/no rigidity ) to E4 ( good tumescence/intermediate rigidity ) in 11/27 ( 40.7 % ) , E1 to E5 in 8/27 ( tumescence/normal rigidity ) ( 29.6 % ) and E1 to E3 ( good tumescence/poor rigidity ) in 5/27 ( 18.5 % ) respectively . 3/27 ( 11.1 % ) received no change in ED severity score . CONCLUSION Endovascular embolisation therapy for veno-occlusive dysfunction in erectile impotence is a safe and effective therapeutic option with low complication rate and highly technical and clinical success rates",
"PURPOSE Recently intracavernous injection of stem cells has garnered great interest as a potential treatment of erectile dysfunction . However , most stem cells are washed out immediately after intracavernous injection . The goal of this study was to investigate using NanoShuttle ™ magnetic nanoparticles to maintain stem cells in the corpus cavernosum after intracavernous injection , thereby improving stem cell therapy of erectile dysfunction in an animal model . MATERIAL S AND METHODS Adipose derived stem cells were magnetized with NanoShuttle magnetic nanoparticles to create Nano-adipose derived stem cells . A total of 24 rats underwent bilateral cavernous nerve crush and were r and omly assigned to 3 groups , including adipose derived stem cells , Nano-adipose derived stem cells and Nano-adipose derived stem cells plus magnet . Cells were tracked at days 1 , 3 , 5 and 9 after intracavernous injection . Another 40 rats with bilateral cavernous nerve crush were r and omly assigned to 4 groups , including bilateral cavernous nerve crush , bilateral cavernous nerve crush plus adipose derived stem cell intracavernous injection , bilateral cavernous nerve crush plus Nano-adipose derived stem cell intracavernous injection and bilateral cavernous nerve crush plus Nano-adipose derived stem cell intracavernous injection plus magnet . Functional testing and histological analysis were performed 4 weeks after intracavernous injection . RESULTS In the in vitro study 1 ) NanoShuttle magnetic nanoparticles were successfully bound to adipose derived stem cells and 2 ) Nano-adipose derived stem cells migrated toward the magnet . In the in vivo study 1 ) cell tracking showed that Nano-adipose derived stem cells were successfully retained in the corpus cavernosum using the magnet for up to 3 days while most adipose derived stem cells were washed out in other groups by day 1 after intracavernous injection , and 2 ) intracavernous pressure/mean arterial pressure , and αSMA ( α-smooth muscle actin ) and PECAM-1 ( platelet endothelial cell adhesion molecule 1 ) expression in the Nano-adipose derived stem cell group was significantly higher than in the other groups . CONCLUSIONS Magnetization of adipose derived stem cells with NanoShuttle magnetic nanoparticles kept adipose derived stem cells in the corpus cavernosum and improved adipose derived stem cell therapy of erectile dysfunction in an animal model",
"AIMS Despite effective control of blood glucose levels in diabetic patients , complaints of diabetes-associated erectile dysfunction ( ED ) persist . Resveratrol has been indicated to possess anti-diabetic effects and therapeutic potential for ED . This study was conducted to observe the effect of resveratrol alone or in combination with sildenafil on ED in streptozotocin (STZ)-induced diabetic rats . MAIN METHOD Among 58 adult male STZ-induced ( 60 mg/kg ) diabetic Sprague-Dawley rats , 48 STZ-induced diabetic rats were r and omized equally to four groups : untreated diabetic rats , resveratrol ( 25mg/kg ) , sildenafil ( 5mg/kg ) or resveratrol ( 25mg/kg ) plus sildenafil ( 5mg/kg ) through oral gavage for 8 weeks . Additionally , 12 age-matched rats were chosen as controls . Intracavernous pressure ( ICP ) and mean arterial blood pressure ( MAP ) were used to measure erectile function . The cavernous level of cyclic guanosine monophosphate ( cGMP ) , protein and mRNA of endothelial NO synthase ( eNOS ) , neuronal NOS ( nNOS ) , and phosphodiesterase-5 ( PDE5 ) was measured . KEY FINDINGS Treatment with either resveratrol or sildenafil improved ICP/MAP compared to the untreated diabetic rats ( P increased nNOS and eNOS expression , inhibited PDE5 expression , and increased the cavernous cGMP level compared to the untreated diabetic rats . Resveratrol significantly decreased superoxide anion and ROS production . Two-way ANOVA indicated that resveratrol in combination with sildenafil therapy had a significant synergistic effect in improving ICP/MAP and cavernous cGMP levels . SIGNIFICANCE Resveratrol improves diabetes-associated ED in rats . Combination therapies with resveratrol and sildenafil have a synergistic effect in improving ED . The mechanisms might be attributed to its anti-oxidative properties and NO-cGMP signaling pathway upregulation",
"This double-blind , placebo-controlled study assessed the efficacy of 3 weeks of impulse magnetic-field therapy for erectile dysfunction ( ED ) . Twenty volunteers who suffered from ED or orgasmic disturbances were r and omly assigned to either active treatment or placebo ( n = 10 each ) . Efficacy was assessed in terms of intensity and duration of erection , general well-being , sexual activity , and warm sensation in the genital area . In the active-treatment group , all efficacy endpoints were significantly improved at study end ( P=.01 ) , with 80 % reporting increases in intensity and duration of erection , frequency of genital warmth , and general wellbeing . The remaining 20 % , who experienced minor improvements , were found to have an influenza-like infection after the study that may have influenced their results . Only 30 % of the placebo group noted some improvement in their sexual activity ; 70 % had no change . No side effects were reported",
"OBJECTIVES This study sought to evaluate the safety and feasibility of zotarolimus-eluting stent implantation in focal atherosclerotic lesions of the internal pudendal arteries among men with erectile dysfunction ( ED ) and a suboptimal response to phosphodiesterase-5 inhibitors . BACKGROUND ED , a common condition , is often mediated by atherosclerosis . Current treatment options are limited . METHODS Male subjects with atherosclerotic ED and a suboptimal response to phosphodiesterase-5 inhibitors were enrolled in this prospect i ve , multicenter , single-armed safety and feasibility trial . A novel combination of clinical , duplex ultrasound , and invasive angiographic factors were used to determine eligibility for stent therapy . The primary safety endpoint was any major adverse event 30 days after the procedure . The primary feasibility end point was improvement in the International Index of Erectile Function ( Erectile Dysfunction Domain ) score ≥ 4 points in ≥ 50 % of subjects at 3 months . We report 6-month follow-up results , including duplex ultrasound and angiography . RESULTS Forty-five lesions were treated with stents in 30 subjects . Procedural success was 100 % with no major adverse events through follow-up . The primary feasibility endpoint at 6 months was achieved by 59.3 % of intention-to-treat subjects ( 95 % confidence interval : 38.8 % to 77.6 % ) and 69.6 % of per- protocol subjects ( 95 % confidence interval : 47.1 % to 86.8 % ) . Duplex ultrasound peak systolic velocity of the cavernosal arteries increased from baseline by 14.4 ± 10.7 cm/s at 30 days and 22.5 ± 23.7 cm/s at 6 months . Angiographic binary restenosis ( ≥ 50 % lumen diameter stenosis ) was reported in 11 ( 34.4 % ) of 32 lesions . CONCLUSIONS Among patients with ED and limited response with pharmacologic therapy , percutaneous stent revascularization of the internal pudendal artery is feasible and is associated with clinical ly meaningful improvement in both subjective and objective measures of erectile function ",
"Abstract Objective : Phosphodiesterase type-5 inhibitors ( PDE5Is ) are first-line therapies for erectile dysfunction ( ED ) . Sildenafil ( SIL ) and vardenafil ( VAR ) are approved for as-needed ( PRN ) dosing ; tadalafil ( TAD ) is approved for both PRN and once-a-day ( OaD ) dosing for ED . Recent evidence suggests that TAD-OaD may be effective as therapy in men with an incomplete response to PRN-PDE5I therapy . This study evaluated whether TAD-OaD provides similar efficacy in men with ED who had previously demonstrated a partial response to PRN-PDE5I therapy . Research design and methods : In this r and omized , double-blind , placebo-controlled trial , men with a ≥3 month ED history received SIL 100 mg , TAD 20 mg , or VAR 20 mg during a 4 week open-label lead-in period . Those with International Index of Erectile Function – Erectile Function ( IIEF-EF ) domain scores TAD 2.5 mg up-titrated to 5 mg , TAD 5 mg , or placebo ( PBO ) OaD for 12 weeks . Main outcome measures obtained from patients treated with TAD-OaD were compared to PBO-treated patients . Additionally , results of treatment with TAD-OaD were compared to results obtained from 4 week PRN-PDE5I therapy to determine whether OaD and PRN regimens provided comparable efficacy . Clinical trial registration : NCT01130532 . Main outcome measures : International Index of Erectile Function ( IIEF ) domain scores ; Sexual Encounter Profile ( SEP ) questions 2–5 . Results : Endpoint data was obtained from 590 men ( 391 TAD ; 199 PBO ) . Results for all IIEF and SEP measures were significantly better for TAD-OaD ( p TAD 2.5 mg and TAD 5 mg OaD therapy were safe and generally well tolerated . Conclusion : Tadalafil once daily is a viable alternative to as-needed PDE5I therapy in men with ED . Key limitations include the lack of a PRN PDE5I study group during the double-blind period , and that many more patients took tadalafil than sildenafil or vardenafil during the PRN period",
"CONTEXT Sildenafil increases insulin sensitivity in mice . In humans , phosphodiesterase 5 inhibition improves disposition index , but the mechanism of this effect has not been eluci date d and may depend on duration . In addition , increasing cyclic GMP without increasing nitric oxide could have beneficial effects on fibrinolytic balance . OBJECTIVE The objective was to test the hypothesis that chronic phosphodiesterase 5 inhibition with sildenafil improves insulin sensitivity and secretion without diminishing fibrinolytic function . DESIGN This was a r and omized , double-blind , placebo-controlled study . SETTING This trial was conducted at V and erbilt Clinical Research Center . PARTICIPANTS Participants included overweight individuals with prediabetes . INTERVENTIONS Subjects were r and omized to treatment with sildenafil 25 mg three times a day or matching placebo for 3 months . Subjects underwent a hyperglycemic clamp prior to and at the end of treatment . MAIN OUTCOME MEASURES The primary outcomes of the study were insulin sensitivity and glucose-stimulated insulin secretion . RESULT Twenty-one subjects completed each treatment arm . After 3 months , the insulin sensitivity index was significantly greater in the sildenafil group compared to the placebo group by 1.84 mg/kg/min per μU/mL*100 ( 95 % confidence interval , 0.01 to 3.67 mg/kg/min per μU/mL*100 ; P = .049 ) , after adjusting for baseline insulin sensitivity index and body mass index . In contrast , there was no effect of 3-month treatment with sildenafil on acute- or late-phase glucose-stimulated insulin secretion ( P > .30 ) . Sildenafil decreased plasminogen activator inhibitor-1 ( P = .01 ) , without altering tissue-plasminogen activator . In contrast to placebo , sildenafil also decreased the urine albumin-to-creatinine ratio from 12.67 ± 14.67 to 6.84 ± 4.86 μg/mg Cr . This effect persisted 3 months after sildenafil discontinuation . CONCLUSIONS Three-month phosphodiesterase 5 inhibition enhances insulin sensitivity and improves markers of endothelial function "
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MDMA ( " ecstasy " ) is widely used as a recreational drug , although there has been some debate about its neurotoxic effects in humans . However , most studies have investigated subjects with heavy use patterns , and the effects of transient MDMA use are unclear . In this review , we therefore focus on subjects with moderate use patterns , in order to assess the evidence for harmful effects . We search ed for studies applying neuroimaging techniques in man . Studies were included if they provided at least one group with an average of All studies published before July 2015 were included . Of the 250 studies identified in the data base search , 19 were included . There is no convincing evidence that moderate MDMA use is associated with structural or functional brain alterations in neuroimaging measures . The lack of significant results was associated with high method ological heterogeneity in terms of dosages and co-consumption of other drugs , low quality of studies and small sample sizes
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"Rationale Although 3,4-methylenedioxymethamphetamine ( MDMA ; Ecstasy ) has been reported to cause fatal hyperthermia , few studies of the effects of MDMA on core body temperature in humans have been conducted demonstrating increased body temperature . In rats , MDMA causes hyperthermia at warm ambient temperatures but hypothermia at cold ones . Objectives In this study , the physiological and subjective effects of MDMA in humans were determined at cold ( 18 ° C ) and warm ( 30 ° C ) ambient temperatures in a temperature and humidity-controlled laboratory . Methods Ten healthy volunteers who were recreational users of MDMA were recruited . Four laboratory sessions were conducted in a 2 × 2 design [ i.e. , two sessions at 30 ° C and two at 18 ° C , two during MDMA ( 2 mg/kg , p.o . ) and two during placebo , in double-blind fashion ] . Core body temperature ( ingested radiotelemetry pill ) , skin temperature ( four weighted sites ) , heart rate , blood pressure , metabolic rate ( indirect calorimetry ) , shivering ( electromyogram levels ) , and sweat rate ( capacitance hygrometry ) were measured as well as subjective effects for several time periods following capsule ingestion . Results MDMA produced significant elevations in core body temperature and metabolic rate in both warm and cold conditions . MDMA also produced significant elevations in blood pressure and heart rate and significantly increased several ratings of subjective effects similar to those previously reported . There were no differences related to ambient temperature for any of the subjective effects , except that ratings of cold and warm were appropriate to the ambient temperature and were not influenced by MDMA . Conclusions Unlike findings in rats , MDMA increased core body temperature regardless of ambient temperature in humans . These increases appeared related to increases in metabolic rate , which were substantial . These findings warrant further investigations on the role of MDMA and other stimulants in altering metabolism and thermogenesis",
"Rationale Recreational use of ecstasy ( 3,4-methylenedioxymethamphetamine [ MDMA ] ) has been associated with memory impairments . Functional neuroimaging studies with cross-sectional design s reported altered memory-related hippocampal functioning in ecstasy-polydrug users . However , differences might be pre-existing or related to the concomitant use of amphetamine . Objective To prospect ively investigate the specific effects of ecstasy on memory-related hippocampal functioning . Methods We used an associative memory task and functional magnetic resonance imaging ( fMRI ) in 40 ecstasy and /or amphetamine users at baseline ( t1 ) and after 12 months ( t2 ) . At t1 , all subjects had very limited amphetamine and /or ecstasy experience ( less than 5 units lifetime dose ) . Based on the reported drug use at t2 , subjects with continued ecstasy and /or amphetamine use ( n = 17 ) were compared to subjects who stopped use after t1 ( n = 12 ) . Results Analysis of repeated measures revealed that encoding-related activity in the left parahippocampal gyrus changed differentially between the groups . Activity in this region increased in abstinent subjects from t1 to t2 , however , decreased in subjects with continued use . Decreases within the left parahippocampal gyrus were associated with the use of ecstasy , but not amphetamine , during the follow-up period . However , there were no significant differences in memory performance . Conclusions The current findings suggest specific effects of ecstasy use on memory-related hippocampal functioning . However , alternative explanations such as (sub-)acute cannabis effects are conceivable",
"Drug addiction is a chronic , relapsing brain disorder . The identification of biomarkers that render individuals vulnerable for the transition from occasional drug use to addiction is of key importance to develop early intervention strategies . The aim of the present study was to prospect ively assess brain structural markers for escalating drug use in two independent sample s of occasional amphetamine-type stimulant users . At baseline occasional users of amphetamine and 3,4-methylenedioxymethamphetamine ( cumulative lifetime use ≤10 units ) underwent structural brain imaging and were followed up at 12 months and 24 months ( Study 1 , n = 38 ; Study 2 , n = 28 ) . Structural vulnerability markers for escalating amphetamine-type drug use were examined by comparing baseline grey matter volumes of participants who increased use with those who maintained or reduced use during the follow-up period . Participants in both sample s who subsequently increased amphetamine-type drugs use displayed smaller medial prefrontal cortex volumes and , additionally , in the basolateral amygdala ( Study 1 ) and dorsal striatum ( Study 2 ) . In both sample s the baseline volumes were significantly negatively correlated with stimulant use during the subsequent 12 and 24 months . Additional multiple regression analyses on the pooled data sets revealed some evidence of a compound-specific association between the baseline volume of the left basolateral amygdala and the subsequent use of amphetamine . These findings indicate that smaller brain volumes in fronto-striato-limbic regions implicated in impulsivity and decision-making might render an individual vulnerable for the transition from occasional to escalating amphetamine-type stimulant use",
"Previous studies have suggested toxic effects of recreational ecstasy use on the serotonin system of the brain . However , it can not be excluded that observed differences between users and non-users are the cause rather than the consequence of ecstasy use . As part of the Netherl and s XTC Toxicity ( NeXT ) study , we prospect ively assessed sustained effects of ecstasy use on the brain in novel ecstasy users using repeated measurements with a combination of different neuroimaging parameters of neurotoxicity . At baseline , 188 ecstasy-naive volunteers with high probability of first ecstasy use were examined . After a mean period of 17 months follow-up , neuroimaging was repeated in 59 incident ecstasy users and 56 matched persistent ecstasy-naives and their outcomes were compared . Neuroimaging included [(123)I]beta-carbomethoxy-3beta-(4-iodophenyl)tropane ( CIT ) SPECT to measure serotonin transporter densities as indicators of serotonergic function ; (1)H-MR spectroscopy ( (1)H-MRS ) to measure brain metabolites as indicators of neuronal damage ; diffusion tensor imaging ( DTI ) to measure the apparent diffusion coefficient and fractional anisotropy ( FA ) of the diffusional motion of water molecules in the brain as indicators of axonal integrity ; and perfusion weighted imaging ( PWI ) to measure regional relative cerebral blood volume ( rrCBV ) which indicates brain perfusion . With this approach , both structural ( (1)H-MRS and DTI ) and functional ( [(123)I]beta-CIT SPECT and PWI ) aspects of neurotoxicity were combined . Compared to persistent ecstasy-naives , novel low-dose ecstasy users ( mean 6.0 , median 2.0 tablets ) showed decreased rrCBV in the globus pallidus and putamen ; decreased FA in thalamus and frontoparietal white matter ; increased FA in globus pallidus ; and increased apparent diffusion coefficient in the thalamus . No changes in serotonin transporter densities and brain metabolites were observed . These findings suggest sustained effects of ecstasy on brain microvasculature , white matter maturation and possibly axonal damage due to low dosages of ecstasy . Although we do not know yet whether these effects are reversible or not , we can not exclude that ecstasy even in low doses is neurotoxic to the brain",
"Rationale Neurotoxic effects of 3,4-methylenedioxymethamphetamine ( MDMA , “ ecstasy ” ) on the serotonin ( 5-HT ) system have been described in animals and humans , but little is known about long-term effects of ecstasy use on mood . Objectives To investigate short-term and long-term effects of ecstasy use on mood and its association with 5-HT neurotoxicity , dose , and gender in humans . Methods Fifteen moderate ecstasy users , 23 heavy ecstasy users , 16 former heavy ecstasy users and 15 drug-using , but ecstasy-naive controls were included . Mood was assessed using the Composite International Diagnostic Interview ( CIDI ) and the Beck Depression Inventory ( BDI ) . Outcomes were correlated with 5-HT transporter ( SERT ) density , assessed with [123I]β-CIT single photon emission computed tomography ( SPECT ) . Results The prevalence of mood disorders assessed by CIDI did not differ between all groups . The overall test for differences in BDI scores between groups was near significance ( P=0.056 ) , with BDI scores higher in former heavy ecstasy users than in ecstasy-naive controls ( P=0.045 ) . BDI scores were correlated with the total number of ecstasy tablets used ( r=0.310 ; P=0.021 ) . No associations between CIDI or BDI outcomes and SERT density or gender were observed . Conclusions These results suggest that ecstasy use is not associated with clinical depression ( CIDI ) . However , the number of ecstasy tablets taken lifetime was associated with higher BDI scores for depressive mood , and this relationship seemed to persist after ecstasy use had stopped . We did not find that depressed mood in ecstasy users was associated with decrease in SERT density . Prospect i ve studies are needed to establish the causal relationship between ecstasy use and depressed mood",
"OBJECTIVE To determine incidence and patterns of natural course of ecstasy/stimulant/hallucinogen ( ESH ) use and disorders as well as cohort effects in a community sample of adolescents and young adults . METHOD Cumulative incidence and patterns of ecstasy use and disorders were examined in a prospect i ve longitudinal design ( mean follow-up period=42 months ) in a representative sample ( N=2446 ) aged 14 - 24 years at the outset of the study . Patterns of DSM-IV defined ESH use , abuse and dependence were assessed with the Munich Composite International Diagnostic Interview ( M-CIDI ) . RESULTS ( 1 ) Cumulative lifetime incidence for use of ESH at second follow-up : 9.1 % , 1.0 % for abuse , 0.6 % for dependence ; ( 2 ) men used and abused ESH more often than women ; ( 3 ) the younger birth cohort ( 1977 - 81 ) tended to start earlier with substance (ab)use compared to the older birth cohort ( 1970 - 77 ) ; ( 4 ) use of ESH was associated with increasing rates of concomitant use of other licit and illicit drugs ; ( 5 ) the majority of the lifetime ESH users without disorder had stopped to use these substances and not consumed them during the 12 months preceding the second follow-up ; ( 6 ) those who had stopped to take ecstasy and related drugs at follow-up also took other illicit drugs less often than those who continued to consume ESH . CONCLUSIONS Use of design er drugs is widespread in our sample , but the probability of developing use disorders is fairly low ( 1.6 % ) . The majority of the ESH users stopped their use spontaneously in their twenties ( 80 % of the prior users without disorder , 67 % of the prior abusers ) , but 50 % of those that once had fulfilled DSM-IV criteria of dependence continued to use these substances",
"Case reports indicate that psychiatrists administered ±3,4-methylenedioxymethamphetamine ( MDMA ) as a catalyst to psychotherapy before recreational use of MDMA as ‘ Ecstasy ’ result ed in its criminalization in 1985 . Over two decades later , this study is the first completed clinical trial evaluating MDMA as a therapeutic adjunct . Twenty patients with chronic posttraumatic stress disorder , refractory to both psychotherapy and psychopharmacology , were r and omly assigned to psychotherapy with concomitant active drug ( n = 12 ) or inactive placebo ( n = 8) administered during two 8-h experimental psychotherapy sessions . Both groups received preparatory and follow-up non-drug psychotherapy . The primary outcome measure was the Clinician-Administered PTSD Scale , administered at baseline , 4 days after each experimental session , and 2 months after the second session . Neurocognitive testing , blood pressure , and temperature monitoring were performed . After 2-month follow-up , placebo subjects were offered the option to re-enroll in the experimental procedure with open-label MDMA . Decrease in Clinician-Administered PTSD Scale scores from baseline was significantly greater for the group that received MDMA than for the placebo group at all three time points after baseline . The rate of clinical response was 10/12 ( 83 % ) in the active treatment group versus 2/8 ( 25 % ) in the placebo group . There were no drug-related serious adverse events , adverse neurocognitive effects or clinical ly significant blood pressure increases . MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm , and it may be useful in patients refractory to other treatments",
"It is debated whether ecstasy use has neurotoxic effects on the human brain and what the effects are of a low dose of ecstasy use . We prospect ively studied sustained effects ( > 2 weeks abstinence ) of a low dose of ecstasy on the brain in ecstasy-naive volunteers using a combination of advanced MR techniques and self-report question naires on psychopathology as part of the NeXT ( Netherl and s XTC Toxicity ) study . Outcomes of proton magnetic resonance spectroscopy ( 1H-MRS ) , diffusion tensor imaging ( DTI ) , perfusion-weighted imaging ( PWI ) , and question naires on depression , impulsivity , and sensation seeking were compared in 30 subjects ( 12 M , 21.8±3.1 years ) in two sessions before and after first ecstasy use ( 1.8±1.3 tablets ) . Interval between baseline and follow-up was on average 8.1±6.5 months and time between last ecstasy use and follow-up was 7.7±4.4 weeks . Using 1H-MRS , no significant changes were observed in metabolite concentrations of N-acetylaspartate ( NAA ) , choline ( Cho ) , myo-inositol ( mI ) , and creatine ( Cr ) , nor in ratios of NAA , Cho , and mI relative to Cr . However , ecstasy use was followed by a sustained 0.9 % increase in fractional anisotropy ( FA ) in frontoparietal white matter , a 3.4 % decrease in apparent diffusion ( ADC ) in the thalamus and a sustained decrease in relative regional cerebral blood volume ( rrCBV ) in the thalamus ( −6.2 % ) , dorsolateral frontal cortex ( −4.0 % ) , and superior parietal cortex ( −3.0 % ) ( all significant at p rrCBV decrease in the dorsolateral frontal cortex remained significant . We also observed increased impulsivity ( + 3.7 % on the Barratt Impulsiveness Scale ) and decreased depression ( −28.0 % on the Beck Depression Inventory ) in novel ecstasy users , although effect sizes were limited and clinical relevance question able . As no indications were found for structural neuronal damage with the currently used techniques , our data do not support the concern that incidental ecstasy use leads to extensive axonal damage . However , sustained decreases in rrCBV and ADC values may indicate that even low ecstasy doses can induce prolonged vasoconstriction in some brain areas , although it is not known whether this effect is permanent . Additional studies are needed to replicate these findings",
"Previous research has shown drug-free Ecstasy users to demonstrate selective cognitive impairment However , there seems to be a degree of individual variation in the occurrence of such deficits . The present study aim ed to assess whether these cognitive deficits are related to an awareness of problematic Ecstasy use , or to past drug dosage . Twenty regular Ecstasy users who reported experiencing Ecstasy-related problems were compared with 20 Ecstasy users who had not reported any previous problems . The two groups displayed similar past histories in relation to a range of illicit drugs , and were divided into low , medium and high users . The controls comprised 20 illicit recreational drug users who had never taken Ecstasy . Executive task measures comprised the Tower of London ( TOL ) , the Wisconsin Card Sorting Task ( WCST ) and spatial working memory . Immediate and delayed word recall , matched verbal recognition and recall and simple reaction time were also included . Both Ecstasy groups performed significantly worse than controls on two executive measures : TOL planning time and spatial working memory score . There were no differences in cognitive impairment between the Ecstasy users who complained of problems and those who did not . In both groups , decrement on executive tasks was demonstrated as a function of previous drug dose . The study confirms that heavy Ecstasy polydrug use may culminate in selective executive deficits . It also demonstrates that two differently self-perceived Ecstasy groups showed similar cognitive impairment , despite only one group complaining of problems . Because all Ecstasy participants also consumed a range of other illicit drugs , the results are reflective of Ecstasy polydrug use in individuals who use Ecstasy as a drug of preference",
"This paper describes the objectives and methods of The Netherl and s XTC Toxicity ( NeXT ) study focussing on the causality , course , and clinical relevance of ecstasy neurotoxicity . Previous studies suggest that ecstasy ( 3,4 methylene-dioxymethamphetamine , MDMA , XTC ) is toxic toward brain serotonin axons , but most of these studies have serious method ological limitations . The current study is a combination of different approaches with three sub studies : ( 1 ) a crosssectional sub study among heavy ecstasy users and controls with variation in drug use , which will provide information about potential neurotoxic consequences of ecstasy in relation to other drugs ; ( 2 ) a prospect i ve cohort sub study in ecstasy-naive subjects with high risk for future ecstasy use , which will provide information on the causality and short-term course of ecstasy use and potential neurotoxicity , and ( 3 ) a retrospective cohort sub study in lifetime ecstasy users and matched controls of an existing epidemiological sample that will provide information on long-term course and outcome of ecstasy use in the general population . Neurotoxicity is studied using ( a ) different imaging techniques ( beta-CIT SPECT , 1H-MR spectroscopy , diffusion tensor imaging , perfusion weighted imaging and functional magnetic resonance imaging ) , and ( b ) neuropsychological and psychiatric assessment s of memory , depression , and personality . The combined results will lead to conclusions that can be used in prevention messages , clinical decision making , and the development of an (inter)national ecstasy policy",
"Abstract . Rationale : 3,4-Methylenedioxymethamphetamine ( MDMA ) mainly releases serotonin ( 5-HT ) and is contained in the recreational drug Ecstasy . 5-HT is known to play an important role in mood and anxiety disorders , for which there is a female preponderance . To date , there are no systematic data on gender differences in the subjective effects of MDMA . Objectives : The present work analyzed the pooled data from three controlled studies on the psychological and physiological effects of MDMA in healthy volunteers with no or minimal MDMA experience . A particular focus of the analyses were possible gender differences . Methods : A total of 74 subjects ( 54 male , 20 female ) participated in all three studies . MDMA in oral doses ranging from 70–150 mg ( 1.35–1.8 mg/kg ) was administered under double-blind placebo-controlled conditions . Subjective peak changes were assessed by st and ardized psychometric rating scales . Physiological measures were blood pressure , heart rate , and peripheral body temperature . Adverse drug effects were assessed during the experimental session and after 24 h. Results : Psychoactive effects of MDMA were more intense in women than in men . Women especially had higher scores for MDMA-induced perceptual changes , thought disturbances , and fear of loss of body control . The dose of MDMA positively correlated with the intensity of perceptual changes in women . Acute adverse effects and sequelae were also more frequent in female than in male subjects . In contrast , men showed higher increases in blood pressure than woman . Conclusions : The fact that equal doses of MDMA per kilogram body weight produce stronger responses in women compared to men is consistent with an increased susceptibility of women to the 5-HT-releasing effects of MDMA . Our results also indicate that increasing doses of MDMA produce more hallucinogen-like perceptual alterations , particularly in women",
"Poor cognitive performance in ecstasy ( 3,4-methylenedioxymethamphetamine ; MDMA ) users has been related to the well-recognized neurotoxic effects of the drug upon central serotonergic and possibly also dopaminergic systems . However , concomitant use of other drugs has been a critical confound in most investigations . In this study we used an n-back task and fMRI to investigate working memory performance and related cerebral activation in eight , currently abstinent pure MDMA users and two matched groups of polyvalent MDMA users and non-users . Pure MDMA users presented lower activations than controls and /or polyvalent users , most notably in inferior temporal regions , the angular gyrus and the striate cortex , whereas polyvalent users did not differ from controls . Our results suggest that altered brain activation patterns during cognitive processing in ecstasy users may be mainly associated with prior MDMA use . Concomitant use of other drugs may modify this effect",
"Rationale Heavy ecstasy use in humans has been associated with cognitive impairments and changes in cognitive brain function supposedly due to damage to the serotonin system . There is concern that even a single dose of 3,4-methylenedioxymethamphetamine may be neurotoxic , but very little is known about the consequences of a low dose of ecstasy for cognitive brain function . Objectives The objective of the study was to assess the effects of a low dose of ecstasy on human cognitive brain function using functional magnetic resonance imaging ( fMRI ) . Material s and method We prospect ively studied , as part of the NeXT ( Netherl and s XTC toxicity ) study , sustained effects of a low dose of ecstasy on brain function in 25 subjects before and after their first episode of ecstasy use ( mean 2.0 ± 1.4 ecstasy pills , on average 11.1 ± 12.9 weeks since last ecstasy use ) , compared to 24 persistent ecstasy-naive controls , also measured twice and matched with the novice users on age , gender , IQ , and cannabis use . Cognitive brain function was measured in the domains of working memory , selective attention , and associative memory using fMRI . Results No significant effects were found of a low dose of ecstasy on working memory , selective attention , or associative memory neither at the behavioral level nor at the neurophysiological level . Conclusions This study yielded no firm evidence for sustained effects of a low dose of ecstasy on human cognitive brain function . The present findings are relevant for the development of prevention and harm reduction strategies . Furthermore , the study is relevant to the discussion concerning potential therapeutic use of ecstasy",
"The popular recreational drug ecstasy ( 3,4-methylenedioxymethamphetamine = MDMA and related congeners ) is neurotoxic upon central serotonergic systems in animal studies . So far , the most convincing evidence for neurotoxicity-related functional deficits in humans derives from neurocognitive studies demonstrating dose-related long-term learning and memory problems in ecstasy users . In our study we used functional magnetic resonance imaging ( fMRI ) and a working memory task to investigate cerebral activation in eleven heavy , but currently abstinent MDMA users and two equally sized groups of moderate users and non-users . There were no significant group differences in working memory performance and no differences in cortical activation patterns for a conservative level of significance . However , for a more liberal statistical criterion , both user groups showed stronger activations than controls in right parietal cortex . Furthermore , heavy users had a weaker blood oxygenation level-dependent ( BOLD ) response than moderate users and controls in frontal and temporal areas . Our results may indicate subtle altered brain functioning associated with prior MDMA use , although alternative interpretations of these group differences must be considered",
"BACKGROUND After no research in humans for > 40 years , there is renewed interest in using lysergic acid diethylamide ( LSD ) in clinical psychiatric research and practice . There are no modern studies on the subjective and autonomic effects of LSD , and its endocrine effects are unknown . In animals , LSD disrupts prepulse inhibition ( PPI ) of the acoustic startle response , and patients with schizophrenia exhibit similar impairments in PPI . However , no data are available on the effects of LSD on PPI in humans . METHODS In a double-blind , r and omized , placebo-controlled , crossover study , LSD ( 200 μg ) and placebo were administered to 16 healthy subjects ( 8 women , 8 men ) . Outcome measures included psychometric scales ; investigator ratings ; PPI of the acoustic startle response ; and autonomic , endocrine , and adverse effects . RESULTS Administration of LSD to healthy subjects produced pronounced alterations in waking consciousness that lasted 12 hours . The predominant effects induced by LSD included visual hallucinations , audiovisual synesthesia , and positively experienced derealization and depersonalization phenomena . Subjective well-being , happiness , closeness to others , openness , and trust were increased by LSD . Compared with placebo , LSD decreased PPI . LSD significantly increased blood pressure , heart rate , body temperature , pupil size , plasma cortisol , prolactin , oxytocin , and epinephrine . Adverse effects produced by LSD completely subsided within 72 hours . No severe acute adverse effects were observed . CONCLUSIONS In addition to marked hallucinogenic effects , LSD exerts methylenedioxymethamphetamine-like empathogenic mood effects that may be useful in psychotherapy . LSD altered sensorimotor gating in a human model of psychosis , supporting the use of LSD in translational psychiatric research . In a controlled clinical setting , LSD can be used safely , but it produces significant sympathomimetic stimulation",
"Psychiatrists and psychotherapists in the US ( 1970s to 1985 ) and Switzerl and ( 1988–1993 ) used MDMA legally as a prescription drug , to enhance the effectiveness of psychotherapy . Early reports suggest that it is useful in treating trauma-related disorders . Recently , the first completed pilot study of MDMA-assisted psychotherapy for PTSD yielded encouraging results . Design ed to test the safety and efficacy of MDMA-assisted psychotherapy in patients with treatment-resistant PTSD ; our r and omized , double-blind , active-placebo controlled trial enrolled 12 patients for treatment with either low-dose ( 25 mg , plus 12.5 mg supplemental dose ) or full-dose MDMA ( 125 mg , plus 62.5 mg supplemental dose ) . MDMA was administered during three experimental sessions , interspersed with weekly non-drug-based psychotherapy sessions . Outcome measures used were the Clinician-Administered PTSD Scale ( CAPS ) and the Posttraumatic Diagnostic Scale ( PDS ) . Patients were assessed at baseline , three weeks after the second and third MDMA session ( end of treatment ) , and at the 2-month and 1-year follow-ups . We found that MDMA-assisted psychotherapy can be safely administered in a clinical setting . No drug-related serious adverse events occurred . We did not see statistically significant reductions in CAPS scores ( p = 0.066 ) , although there was clinical ly and statistically significant self-reported ( PDS ) improvement ( p = 0.014 ) . CAPS scores improved further at the 1-year follow-up . In addition , three MDMA sessions were more effective than two ( p = 0.016 )"
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BACKGROUND Aspirin is the most widely studied and prescribed antiplatelet agent for preventing serious vascular events , reducing the odds of such events among high vascular risk patients by about a quarter . Thienopyridine derivatives inhibit platelet activation by a different mechanism and so may be more effective . OBJECTIVES To determine the effectiveness and safety of thienopyridine derivatives ( ticlopidine and clopidogrel ) versus aspirin for preventing serious vascular events ( stroke , myocardial infa rct ion ( MI ) or vascular death ) in patients at high risk , and specifically in patients with a previous TIA or ischaemic stroke . SEARCH STRATEGY We search ed the trials registers of the Stroke , Heart and Peripheral Vascular Diseases Cochrane Review Groups ( last search ed July 2008 ) , the Cochrane Central Register of Controlled Trials ( CENTRAL ) ( The Cochrane Library Issue 3 , 2008 ) , MEDLINE ( 1966 to August 2008 ) and EMBASE ( 1980 to August 2008 ) . We also search ed reference lists of relevant papers , and contacted other research ers and the pharmaceutical company Sanofi-BMS ( December 2008 ) . SELECTION CRITERIA All unconfounded , double blind , r and omised trials directly comparing a thienopyridine derivative with aspirin in high vascular risk patients . DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed trial quality . We sought additional data from the principal investigators of the largest trials . MAIN RESULTS We included 10 trials involving 26,865 high vascular risk patients . The trials were generally of high quality . Aspirin was compared with ticlopidine in nine trials ( 7633 patients ) and with clopidogrel in one trial ( 19,185 patients ) . Compared with aspirin , allocation to a thienopyridine produced a modest , just statistically significant , reduction in the odds of a serious vascular event ( 11.6 % versus 12.5 % ; odds ratio ( OR ) 0.92 , 95 % confidence interval ( CI ) 0.85 to 0.99 ) , corresponding to the avoidance of 10 ( 95 % CI 0 to 20 ) serious vascular events per 1000 patients treated for about two years . However , the wide confidence interval includes the possibility of negligible additional benefit . Compared with aspirin , thienopyridines significantly reduced gastrointestinal adverse effects . However , thienopyridines increased the odds of skin rash and diarrhoea , ticlopidine more than clopidogrel . Allocation to ticlopidine , but not clopidogrel , significantly increased the odds of neutropenia . In patients with TIA/ischaemic stroke , the results were similar to those for all patients combined . AUTHORS ' CONCLUSIONS The thienopyridine derivatives are at least as effective as aspirin in preventing serious vascular events in patients at high risk , and possibly somewhat more so . However , the size of any additional benefit is uncertain and could be negligible . Clopidogrel has a more favourable adverse effects profile than ticlopidine and so is the thienopyridine of choice . It should be used as an alternative to aspirin in patients genuinely intolerant of or allergic to aspirin
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"BACKGROUND Patients with transient ischaemic attack ( TIA ) or minor stroke are at high immediate risk of stroke . The optimum early treatment options for these patients are not known . METHODS Within 24 h of symptom onset , we r and omly assigned , in a factorial design , 392 patients with TIA or minor stroke to clopidogrel ( 300 mg loading dose then 75 mg daily ; 198 patients ) or placebo ( 194 patients ) , and simvastatin ( 40 mg daily ; 199 patients ) or placebo ( 193 patients ) . All patients were also given aspirin and were followed for 90 days . Descriptive analyses were done by intention to treat . The primary outcome was total stroke ( ischaemic and haemorrhagic ) within 90 days . Safety outcomes included haemorrhage related to clopidogrel and myositis related to simvastatin . This study is registered as an International St and ard R and omised Controlled Trial ( number 35624812 ) and with Clinical Trials.gov ( NCT00109382 ) . FINDINGS The median time to stroke outcome was 1 day ( range 0 - 62 days ) . The trial was stopped early due to a failure to recruit patients at the prespecified minimum enrolment rate because of increased use of statins . 14 ( 7.1 % ) patients on clopidogrel had a stroke within 90 days compared with 21 ( 10.8 % ) patients on placebo ( risk ratio 0.7 [ 95 % CI 0.3 - 1.2 ] ; absolute risk reduction -3.8 % [ 95 % CI -9.4 to 1.9 ] ; p=0.19 ) . 21 ( 10.6 % ) patients on simvastatin had a stroke within 90 days compared with 14 ( 7.3 % ) patients on placebo ( risk ratio 1.3 [ 0.7 - 2.4 ] ; absolute risk increase 3.3 % [ -2.3 to 8.9 ] ; p=0.25 ) . The interaction between clopidogrel and simvastatin was not significant ( p=0.64 ) . Two patients on clopidogrel had intracranial haemorrhage compared with none on placebo ( absolute risk increase 1.0 % [ -0.4 to 2.4 ] ; p=0.5 ) . There was no difference between groups for the simvastatin safety outcomes . INTERPRETATION Immediately after TIA or minor stroke , patients are at high risk of stroke , which might be reduced by using clopidogrel in addition to aspirin . The haemorrhagic risks of the combination of aspirin and clopidogrel do not seem to offset this potential benefit . We were unable to provide evidence of benefit of simvastatin in this setting . This aggressive prevention approach merits further study",
"We investigated the effects of aspirin ( 300 mg/d ) , ticlopidine ( 500 mg/d ) and their low‐dose combination ( aspirin 100 mg/d plus ticlopidine 250 mg/d ) on the platelet aggregability using the Wu and Hoak method . Each treatment group consisted of 25 patients with acute ischemic stroke . Platelet aggregation ratios ( PAR ) were measured on the 1st ( before treatment ) , 10th and 90th days in the treatment groups and compared with those of 25 control cases . On the first day , comparison of PAR in each treatment group with the control was significant , while the differences between treatment groups were not significant . On the 90th day , differences of PAR between aspirin and control were significant , but differences between the other treatment groups and the control group were not significant , indicating a lower anti‐aggregant efficacy of aspirin",
"BACKGROUND Concurrent therapy with a proton-pump inhibitor is a st and ard treatment for patients receiving aspirin who are at risk for ulcer . Current U.S. guidelines also recommend clopidrogel for patients who have major gastrointestinal intolerance of aspirin . We compared clopidogrel with aspirin plus esomeprazole for the prevention of recurrent bleeding from ulcers in high-risk patients . METHODS We studied patients who took aspirin to prevent vascular diseases and who presented with ulcer bleeding . After the ulcers had healed , we r and omly assigned patients who were negative for Helicobacter pylori to receive either 75 mg of clopidogrel daily plus esomeprazole placebo twice daily or 80 mg of aspirin daily plus 20 mg of esomeprazole twice daily for 12 months . The end point was recurrent ulcer bleeding . RESULTS We enrolled 320 patients ( 161 patients assigned to receive clopidogrel and 159 to receive aspirin plus esomeprazole ) . Recurrent ulcer bleeding occurred in 13 patients receiving clopidogrel and 1 receiving aspirin plus esomeprazole . The cumulative incidence of recurrent bleeding during the 12-month period was 8.6 percent ( 95 percent confidence interval , 4.1 to 13.1 percent ) among patients who received clopidogrel and 0.7 percent ( 95 percent confidence interval , 0 to 2.0 percent ) among those who received aspirin plus esomeprazole ( difference , 7.9 percentage points ; 95 percent confidence interval for the difference , 3.4 to 12.4 ; P=0.001 ) . CONCLUSIONS Among patients with a history of aspirin-induced ulcer bleeding whose ulcers had healed before they received the study treatment , aspirin plus esomeprazole was superior to clopidogrel in the prevention of recurrent ulcer bleeding . Our finding does not support the current recommendation that patients with major gastrointestinal intolerance of aspirin be given clopidogrel",
"Background — Chronic heart failure remains a major cause of mortality and morbidity . The role of antithrombotic therapy in patients with chronic heart failure has long been debated . The objective of this study was to determine the optimal antithrombotic agent for heart failure patients with reduced ejection fractions who are in sinus rhythm . Methods and Results — This prospect i ve , r and omized clinical trial of open-label warfarin ( target international normalized ratio of 2.5 to 3.0 ) and double-blind treatment with either aspirin ( 162 mg once daily ) or clopidogrel ( 75 mg once daily ) had a 30-month enrollment period and a minimum of 12 months of treatment . We enrolled 1587 men and women ≥18 years of age with symptomatic heart failure for at least 3 months who were in sinus rhythm and had left ventricular ejection fraction of ≤35 % . The primary outcome was the time to first occurrence of death , nonfatal myocardial infa rct ion , or nonfatal stroke . For the primary composite end point , the hazard ratios were as follows : for warfarin versus aspirin , 0.98 ( 95 % CI , 0.86 to 1.12 ; P=0.77 ) ; for clopidogrel versus aspirin , 1.08 ( 95 % CI , 0.83 to 1.40 ; P=0.57 ) ; and for warfarin versus clopidogrel , 0.89 ( 95 % CI , 0.68 to 1.16 ; P=0.39 ) . Warfarin was associated with fewer nonfatal strokes than aspirin or clopidogrel . Hospitalization for worsening heart failure occurred in 116 ( 22.2 % ) , 97 ( 18.5 % ) , and 89 ( 16.5 % ) patients treated with aspirin , clopidogrel , and warfarin , respectively ( P=0.02 for warfarin versus aspirin ) . Conclusion — The primary outcome measure and the mortality data do not support the primary hypotheses that warfarin is superior to aspirin and that clopidogrel is superior to aspirin ",
"OBJECTIVES We studied the modifier effect of platelet antigen polymorphism ( PlA2 ) on platelet inhibition by acetylsalicylic acid ( ASA , i.e. , aspirin ) , clopidogrel , or their combination in patients with coronary heart disease . BACKGROUND Clopidogrel , when administered with ASA , was shown to significantly improve the outcome of patients with acute coronary syndromes compared with patients receiving only ASA . We have shown previously that the effect of ASA on platelets is modified by the glycoprotein IIIa single nucleotide polymorphism PlA2 . Hence , an important pharmacogenetic question remains whether the antiplatelet effect of clopidogrel is uniform for all patients or , like acetylsalicylic acid , more selective . METHODS Thirty PlA1/A1 and 30 PlA1/A2 patients were assigned r and omly to ASA 325 mg/day , clopidogrel 75 mg/day , or both . After 10 days , platelet function was studied . RESULTS Clopidogrel provided stronger platelet inhibition than ASA with adenosine diphosphate as the agonist , and combination therapy result ed in greater inhibition than either inhibitor used alone ( p ASA result ed in greater inhibition compared with clopidogrel with epinephrine ( p platelets from PlA1/A2 donors were markedly and significantly less inhibited by ASA ( p = 0.005 ) . In contrast , with clopidogrel , no significant difference could be detected between inhibition of Pl(A1/A1 ) and Pl(A1/A2 ) platelets . CONCLUSIONS The combination of ASA and clopidogrel appears superior to either agent alone in inhibiting platelet function . Pl(A2 ) functions as an important modifier for platelet responsiveness to ASA but not to clopidogrel . These findings could have significant impact on the future design of pharmacogenetic antithrombotic strategies for patients with coronary heart disease",
"OBJECTIVES The aim of the present study was to compare clopidogrel and ticlopidine after coronary stenting with regard to cardiovascular death during long-term follow-up . BACKGROUND R and omized trials comparing clopidogrel and ticlopidine with a restricted use of intravenous glycoprotein IIb/IIIa inhibition have reported a trend toward a higher incidence of thrombotic stent occlusion with clopidogrel at 30 days . METHODS After successful coronary stent implantation , 700 patients with 899 lesions were r and omly assigned to receive a four-week course of either 500 mg ticlopidine ( n = 345 ) or 75 mg clopidogrel ( n = 355 ) in addition to 100 mg aspirin . Cardiovascular death was the primary end point and was recorded during a median follow-up period of 28 months . RESULTS Cardiovascular death occurred in eight patients with ticlopidine versus 26 patients with clopidogrel ( hazard ratio with ticlopidine compared with clopidogrel , 0.30 ; 95 % confidence interval [ CI ] , 0.14 to 0.66 ; p = 0.003 ) . After adjustment for co-variables , ticlopidine reduced the risk of cardiovascular death by 63 % compared with clopidogrel . The combined end point of cardiovascular death or nonfatal myocardial infa rct ion was present in 19 patients assigned ticlopidine , compared with 40 patients assigned clopidogrel ( hazard ratio , 0.45 ; p = 0.005 ) . The hazard ratio for all-cause mortality with ticlopidine as compared with clopidogrel was 0.30 ( 95 % CI , 0.14 to 0.64 ; p = 0.002 ) . CONCLUSIONS After the placement of coronary artery stents in unselected patients , ticlopidine was associated with a significantly lower mortality than clopidogrel . This raises concern about the current practice of substituting clopidogrel for ticlopidine after stenting and highlights the need for further long-term studies",
"This study aim ed to compare the effects of clopidogrel , acetylsalicylic acid ( ASA ) , and the combination of both substances on platelet aggregation and expression of platelet membrane glycoproteins in patients with chronic coronary artery disease . We investigated platelet activation by flow cytometry and by platelet aggregation and disaggregation in 60 patients r and omly assigned to 3 treatment groups : ASA , clopidogrel , combination of clopidogrel and ASA , treated for 14 days . Adenosine diphosphate (ADP)–induced expression of P-selectin and of PAC-1 was significantly reduced after 2 wk of clopidogrel but not of ASA treatment . Treatment with clopidogrel reduced the ADP-induced platelet aggregation . The combination of clopidogrel and ASA did not increase the inhibition of platelet activation compared with clopidogrel alone . A significant increase in platelet disaggregation was observed with clopidogrel alone and was more pronounced with the combination of clopidogrel and ASA . ADP-induced platelet degranulation , activation of GPIIb/IIIa receptor , and aggregation in vivo are effectively inhibited by clopidogrel . The significantly increased disaggregation under clopidogrel and ASA suggests that the combined therapy may be superior to the monotherapy in patients with coronary artery disease and a high risk for vascular events",
"Background — Evidence for efficacy of dual antiplatelet therapy in stroke is limited . Symptomatic carotid stenosis patients are at high risk of early recurrent stroke . In this group , asymptomatic microembolic signals ( MES ) , detected by transcranial Doppler ultrasound ( TCD ) , are markers of future stroke and transient ischemic attack ( TIA ) risk . They offer a surrogate marker to evaluate antiplatelet therapy , but no multicenter study has evaluated the feasibility of this approach . Methods and Results —Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis ( CARESS ) is a r and omized , double-blind study in subjects with recently symptomatic ≥50 % carotid stenosis . Patients were screened with TCD , and if MES were detected , they were r and omized to clopidogrel and aspirin or aspirin monotherapy . Repeated TCD recordings were made on days 2 and 7 . MES were detected in 110 of 230 patients by online analysis at baseline , of whom 107 were r and omized . Intention-to-treat analysis revealed a significant reduction in the primary end point : 43.8 % of dual-therapy patients were MES positive on day 7 , as compared with 72.7 % of monotherapy patients ( relative risk reduction 39.8 % ; 95 % CI , 13.8 to 58.0 ; P=0.0046 ) . The secondary end point of MES frequency per hour was reduced ( compared with baseline ) by 61.4 % ( 95 % CI , 31.6 to 78.2 ; P=0.0013 ) in the dual-therapy group at day 7 and by 61.6 % ( 95 % CI , 34.9 to 77.4 ; P=0.0005 ) on day 2 . There were 4 recurrent strokes and 7 TIAs in the monotherapy group versus no stroke and 4 TIAs in the dual-therapy group that were treatment emergent and ipsilateral to the qualifying carotid stenosis ; 2 additional ipsilateral TIAs occurred before treatment started . MES frequency was greater in the 17 patients with recurrent ipsilateral events compared with the 90 without ( mean±SD : 24.4±27.7 versus 8.9±11.5 per hour ; P=0.0003 ) . Conclusions —In patients with recently symptomatic carotid stenosis , combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing asymptomatic embolization . Doppler MES detection is a feasible method to evaluate the efficacy of antiplatelet therapy in multicenter studies",
"BACKGROUND Clopidogrel was superior to aspirin in patients with previous manifestations of atherothrombotic disease in the CAPRIE study and its benefit was amplified in some high-risk subgroups of patients . We aim ed to assess whether addition of aspirin to clopidogrel could have a greater benefit than clopidogrel alone in prevention of vascular events with potentially higher bleeding risk . METHODS We did a r and omised , double-blind , placebo-controlled trial to compare aspirin ( 75 mg/day ) with placebo in 7599 high-risk patients with recent ischaemic stroke or transient ischaemic attack and at least one additional vascular risk factor who were already receiving clopidogrel 75 mg/day . Duration of treatment and follow-up was 18 months . The primary endpoint was a composite of ischaemic stroke , myocardial infa rct ion , vascular death , or rehospitalisation for acute ischaemia ( including rehospitalisation for transient ischaemic attack , angina pectoris , or worsening of peripheral arterial disease ) . Analysis was by intention to treat , using logrank test and a Cox 's proportional-hazards model . FINDINGS 596 ( 15.7 % ) patients reached the primary endpoint in the group receiving aspirin and clopidogrel compared with 636 ( 16.7 % ) in the clopidogrel alone group ( relative risk reduction 6.4 % , [ 95 % CI -4.6 to 16.3 ] ; absolute risk reduction 1 % [ -0.6 to 2.7 ] ) . Life-threatening bleedings were higher in the group receiving aspirin and clopidogrel versus clopidogrel alone ( 96 [ 2.6 % ] vs 49 [ 1.3 % ] ; absolute risk increase 1.3 % [ 95 % CI 0.6 to 1.9 ] ) . Major bleedings were also increased in the group receiving aspirin and clopidogrel but no difference was recorded in mortality . INTERPRETATION Adding aspirin to clopidogrel in high-risk patients with recent ischaemic stroke or transient ischaemic attack is associated with a non-significant difference in reducing major vascular events . However , the risk of life-threatening or major bleeding is increased by the addition of aspirin",
"Two treatments , based on either ticlopidine or indobufen at their optimal individual daily dose ( median dose : 250 and 200 mg/day , respectively ) , were compared in an open r and omized multicenter trial in patients at risk of cerebral ischemia ( men and women , aged 39 to 80 years , who had experienced in the month before entry into the study transient ischemic attack or amaurosis fugax or minor stroke ) . The total number of patients screened was 4033 ; 1632 were enrolled , 821 r and omized to ticlopidine , 811 to indobufen . The overall frequency of the composite primary end-point ( stroke , myocardial infa rct ion , and death from any cause ) was 4.4 % . The ticlopidine-based regimen proved significantly better than the indobufen one in preventing the composite of fatal and non fatal events ( 49.6 % relative risk reduction ) , or death alone ( 54.4 % relative risk reduction ) . The two groups had similar percentages of adverse events ( 5.5 % and 6.4 % for ticlopidine and indobufen group , respectively ) with withdrawals because of adverse events in 3.4 % and 2.5 % ; gastrointestinal disorders and bleeding were more frequent in the indobufen group , whereas rash and abnormal liver function were more frequent in the ticlopidine one",
"BACKGROUND Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of vascular events after ischaemic stroke of presumed arterial origin are inconsistent . Our aim was to resolve this uncertainty . METHODS We did a r and omised controlled trial in which we assigned patients to aspirin ( 30 - 325 mg daily ) with ( n=1363 ) or without ( n=1376 ) dipyridamole ( 200 mg twice daily ) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin . Our primary outcome event was the composite of death from all vascular causes , non-fatal stroke , non-fatal myocardial infa rct ion , or major bleeding complication , whichever happened first . Treatment was open , but auditing of outcome events was blinded . Primary analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial ( number IS RCT N73824458 ) and with ( NCT00161070 ) . FINDINGS Mean follow-up was 3.5 years ( SD 2.0 ) . Median aspirin dose was 75 mg in both treatment groups ( range 30 - 325 ) ; extended-release dipyridamole was used by 83 % ( n=1131 ) of patients on the combination regimen . Primary outcome events arose in 173 ( 13 % ) patients on aspirin and dipyridamole and in 216 ( 16 % ) on aspirin alone ( hazard ratio 0.80 , 95 % CI 0.66 - 0.98 ; absolute risk reduction 1.0 % per year , 95 % CI 0.1 - 1.8 ) . Addition of the ESPRIT data to the meta- analysis of previous trials result ed in an overall risk ratio for the composite of vascular death , stroke , or myocardial infa rct ion of 0.82 ( 95 % CI 0.74 - 0.91 ) . Patients on aspirin and dipyridamole discontinued trial medication more often than those on aspirin alone ( 470 vs 184 ) , mainly because of headache . INTERPRETATION The ESPRIT results , combined with the results of previous trials , provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin",
"In 1988 , we undertook a r and omized , placebo-controlled , double-blind trial to investigate the safety and efficacy of low-dose acetylsalicylic acid ( ASA ) , modified-release dipyridamole , and the two agents in combination for secondary prevention of ischemic stroke . Patients with prior stroke or transient ischemic attack ( TIA ) were r and omized to treatment with ASA alone ( 50 mg daily ) , modified-release dipyridamole alone ( 400 mg daily ) , the two agents in a combined formulation , or placebo . Primary endpoints were stroke , death , and stroke or death together . TIA and other vascular events were secondary endpoints . Patients were followed on treatment for two years . Data from 6,602 patients were analysed . Factorial analysis demonstrated a highly significant effect for ASA and for dipyridamole in reducing the risk of stroke ( p stroke or death combined ( p stroke risk in comparison to placebo was reduced by 18 % with ASA alone ( p = 0.013 ) ; 16 % with dipyridamole alone ( p = 0.039 ) ; and 37 % with combination therapy ( p Risk of stroke or death was reduced by 13 % with ASA alone ( p = 0.016 ) ; 15 % with dipyridamole alone ( p = 0.015 ) ; and 24 % with the combination ( p death rate alone . Factorial analysis also demonstrated a highly significant effect of ASA ( p dipyridamole ( p risk reduction for the combination was 36 % ( p placebo . Headache was the most common adverse event , occurring more frequently in dipyridamole-treated patients . All-site bleeding and gastrointestinal bleeding were significantly more common in patients who received ASA in comparison to placebo or dipyridamole . We conclude that ( 1 ) ASA 25 mg twice daily and dipyridamole , in a modified-release form , at a dose of 200 mg twice daily have each been shown to be equally effective for the secondary prevention of ischemic stroke and TIA ; ( 2 ) when co-prescribed the protective effects are additive , the combination being significantly more effective than either agent prescribed singly ; ( 3 ) low-dose ASA does not eliminate the propensity for induced bleeding",
"BACKGROUND Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention . METHODS To compare prasugrel , a new thienopyridine , with clopidogrel , we r and omly assigned 13,608 patients with moderate-to-high-risk acute coronary syndromes with scheduled percutaneous coronary intervention to receive prasugrel ( a 60-mg loading dose and a 10-mg daily maintenance dose ) or clopidogrel ( a 300-mg loading dose and a 75-mg daily maintenance dose ) , for 6 to 15 months . The primary efficacy end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . The key safety end point was major bleeding . RESULTS The primary efficacy end point occurred in 12.1 % of patients receiving clopidogrel and 9.9 % of patients receiving prasugrel ( hazard ratio for prasugrel vs. clopidogrel , 0.81 ; 95 % confidence interval [ CI ] , 0.73 to 0.90 ; P rates of myocardial infa rct ion ( 9.7 % for clopidogrel vs. 7.4 % for prasugrel ; P urgent target-vessel revascularization ( 3.7 % vs. 2.5 % ; P stent thrombosis ( 2.4 % vs. 1.1 % ; P Major bleeding was observed in 2.4 % of patients receiving prasugrel and in 1.8 % of patients receiving clopidogrel ( hazard ratio , 1.32 ; 95 % CI , 1.03 to 1.68 ; P=0.03 ) . Also greater in the prasugrel group was the rate of life-threatening bleeding ( 1.4 % vs. 0.9 % ; P=0.01 ) , including nonfatal bleeding ( 1.1 % vs. 0.9 % ; hazard ratio , 1.25 ; P=0.23 ) and fatal bleeding ( 0.4 % vs. 0.1 % ; P=0.002 ) . CONCLUSIONS In patients with acute coronary syndromes with scheduled percutaneous coronary intervention , prasugrel therapy was associated with significantly reduced rates of ischemic events , including stent thrombosis , but with an increased risk of major bleeding , including fatal bleeding . Overall mortality did not differ significantly between treatment groups . ( Clinical Trials.gov number , NCT00097591 [ Clinical Trials.gov ] .",
"BACKGROUND This study was performed to analyze the influence of either aspirin , ticlopidine , or their combination on platelet activation and aggregation parameters after stent implantation . METHODS AND RESULTS Sixty-one patients with successful implantation of a single Palmaz-Schatz stent in a native coronary artery were r and omly assigned to either group A ( aspirin 300 mg/d+ticlopidine 2X250 mg/d ) , group B ( ticlopidine 2X250 mg/d ) , or group C ( aspirin 300 mg/d ) . Platelet activation was evaluated on days 1 , 7 , and 14 by flow cytometry measurement of expression of CD62p ( p-selectin ) and the binding of fibrinogen to the platelet surface glycoprotein IIb/IIIa receptor . Platelet aggregation was induced by addition of ADP or collagen . Differences between treatment groups were compared by ANOVA . Between days 1 and 14 , we observed a significant decrease in collagen-induced platelet aggregation in group A ( 62.2+/-2.5 % versus 36.9+/-3.1 % ) , whereas an increase was seen in group B ( 58.3+/-2.5 % versus 67.7+/-3.2 % ) and no change was seen in group C ( P ADP-induced aggregation declined significantly in group A ( 74.7+/-1.4 % versus 55.3+/-2.6 % ) , whereas a delayed reduction was seen in group B ( 72.0+/-3.0 % versus 52.6+/-4.2 % ) and no change was seen in group C ( P=.0017 ) . The CD62p expression declined significantly in groups A ( 68.2+/-2.7 % versus 41.3+/-2.7 % ) and B ( 64.8+/-2.9 % versus 39.3+/-3.5 % ) but not in group C ( P fibrinogen binding decreased significantly in group A ( 61.0+/-4.3 % versus 36.3+/-4.2 % ) and with delay in group B ( 58.3+/-2.2 % versus 39.4+/-3.0 % ) , whereas no alterations were seen in group C ( P=.012 ) . CONCLUSIONS Our results demonstrate synergistic and accelerated platelet inhibitory effects of ticlopidine plus aspirin in patients after stent implantation compared with a monotherapy with either ticlopidine or aspirin alone",
"No direct comparisons of the effects of ticlopidine and aspirin on platelet aggregability , clotting parameters , and blood count are available in a cross-over study design in humans . We investigated 45 patients with cerebrovascular disease . Twenty-one patients received 300 mg aspirin once daily for 2 weeks and then for 2 more weeks received 250 mg ticlopidine twice daily . In 24 other patients , the scheme was reversed . ADP-induced aggregability was lower during ticlopidine treatment ; epinephrine- and collagen-induced aggregabilities were lower with aspirin treatment . Platelet counts were higher during ticlopidine than during aspirin treatment ( 199.6/ nl with aspirin , 213.0/nl with ticlop dine , p = 0.008 ) , probably reflecting less platelet activation and degradation and a longer platelet survival time induced by ticlopidine treatment",
"A r and omized , double-blind multicenter trial-the Clopidogrel and Aspirin : Determination of the Effects on Thrombogenicity ( CADET ) trial-was carried out to compare the effects of clopidogrel vs. aspirin on thrombotic variables and C-reactive protein ( CRP ) , over a 6-month period of treatment , in patients with an acute myocardial infa rct ion within the previous 3 - 7 days , who were not scheduled for major surgery including coronary artery bypass grafting . Patients ( n = 184 ) were r and omly allocated to aspirin ( 75 mg day(-1 ) ) or clopidogrel ( 75 mg day(-1 ) ) . Blood sample s were taken at baseline and then at clinic visits at 1 , 3 and 6 months . By 1 month , clottable and immunonephelometric fibrinogen , D-dimer , von Willebr and factor , factor VIII and CRP were significantly ( P plasminogen activator antigen in the aspirin group only . At 6 months , there were no differences between treatment groups ( P > 0.05 ) for any of the variables , whether or not potential confounding variables were adjusted for . Similarly , there were no differences between treatments in the difference between baseline and final values for any of the variables . Aspirin and clopidogrel were thus found to have similar effects on thrombotic variables and CRP in this patient population",
"ADP-induced platelet aggregation was studied in 28 patients with myocardial infa rct ion r and omized , at admission , into three groups . Conventional therapy with heparin and antianginal drugs was combined with aspirin ( 250 mg/day , n = 9 ) , tiklid ( 500 mg/day , n = 9 ) , tiklid ( 500 mg/day ) + aspirin ( 250 mg/day , n = 10 ) in group 1 , 2 and 3 , respectively . Tiklid diminished platelet aggregation more effectively than aspirin on the disease day 7 and 21 . Tiklid + aspirin combination suppresses platelet aggregation more than monotherapy with either of the drugs , provides insignificant attenuation of postinfa rct ion angina but is associated with a high risk of hemorrhagic complications",
"To prevent recurrence of cerebral infa rct ion ( CI ) , the efficacy of antiplatelet therapy , when used in combination with a calcium antagonist , was examined . The study subjects were 57 chronic CI patients ( 40 men , 17 women ; mean age , 68.5 years ) who experienced either CI or its recurrence more than 3 months before the start of the study . They were r and omly allocated into one of the following four groups for the 8-week study ; group A -- ticlopidine hydrochloride 200 mg once daily and nicardipine hydrochloride 20 mg three times daily ( TID ) ; group B -- ticlopidine hydrochloride 200 mg once daily ; group C -- aspirin 81 mg once daily and nicardipine hydrochloride 20 mg TID ; or group D -- aspirin 81 mg once daily . Platelet aggregation was measured before treatment and 4 and 8 weeks after the initiation of each therapy by using adenosine diphosphate ( ADP ) ( 2 microM and 0.5 microM ) and collagen ( 2 micrograms/mL ) , and evaluated in terms of percent maximum platelet aggregation . Results showed significant suppression of 2.0 microM ADP platelet aggregation in groups A , B , and C. At 0.5-microM ADP , only groups A and B showed significant platelet aggregation suppression . All groups showed significant suppression of collagen platelet aggregation . In comparing single therapy with combination therapy , groups A and B were not significantly different from one another after 4 or 8 weeks in 2-microM ADP or collagen platelet aggregation suppression . In contrast , group C had significantly greater suppression of both 2-microM ADP and collagen aggregations compared with group D. In conclusion , nicardipine hydrochloride administration with aspirin may be a useful alternative therapy for the prevention of CI recurrence",
"Aspirin and ticlopidine are two commonly used drugs in the prevention of cerebral embolic ischemic events . No direct comparisons in a cross-over design of the effects of ticlopidine and aspirin on asymptomatic circulating cerebral microemboli are available . We investigated 53 patients with cerebrovascular disease . Twenty-six patients were dosed for 2 weeks , 300 mg aspirin once daily and then for 2 weeks , 250 mg ticlopidine twice daily . In 27 other patients the scheme was reversed . Transcranial Doppler monitoring ( both middle cerebral arteries simultaneously for 1 h were performed at the end of the two weeks . The signal was recorded on digitalised audio tapes and analyzed blinded off-line . The number of embolic signals per hour and vessel was 15.7 under aspirin and 11.7 under ticlopidine ( difference not significant ) . The correlation between the number of emboli under the two medications was high . The highest number of embolic signals was found in high grade carotid stenosis . In patients with a low number of embolic signals , reproducibility was low . A minimum of 7 embolic signals in one treatment group is required for further therapeutic drug trials to allow reasonable comparisons . This study may help to plan further therapeutic trials using emboli detection",
"Angiotensin-converting enzyme ( ACE ) inhibitors are effective drugs that have been shown to lower morbidity and mortality in patients with heart failure who have left ventricular systolic dysfunction . 1–3 Patients with congestive heart failure ( CHF ) often have indications for using both ACE inhibitors and antiplatelet agents . Various clinical trials have suggested that an adverse interaction exists from the combined use of aspirin and an ACE inhibitor in patients with CHF , but few studies have measured this effect directly . 3–12 The most compelling evidence of a potential adverse interaction between ACE inhibitors and aspirin stems from the Studies Of Left Ventricular Dysfunction ( SOLVD ) 1,10 and Cooperative New Sc and inavian Enalapril Survival Study II ( CONSENSUS II ) 11 trials . In SOLVD , although enalapril and aspirin when used alone were associated with lower mortality rates , retrospective analysis revealed that the addition of enalapril did not reduce mortality in patients already taking aspirin , and conversely , neither did the addition of aspirin in patients receiving enalapril . In a post hoc analysis of CONSENSUS II , aspirin and enalapril , when utilized alone , were associated with lower mortality rates . However , the relative risk of death at the end of the study was 1.23 ( 95 % confi dence interval [ CI ] 0.99 to 1.53 ) for patients taking aspirin and enalapril , and 0.86 ( 95 % CI 0.63 to 1.16 ) for patients taking enalapril without aspirin ( p 0.047 ) . Guazzi et al , 7 in a small prospect i ve study , measured maximal exercise oxygen uptake ( VO2max ) in patients with CHF , and demonstrated an adverse effect when ACE inhibitors were combined with aspirin , but not with ACE inhibitors alone . Therefore , we hypothesized that exercise duration and VO2max would not be attenuated by clopidogrel compared with aspirin in patients with CHF who are taking ACE inhibitors . This study was approved by the institutional review board and all participants gave written consent before starting the study . We consecutively enrolled 18 patients with chronic stable CHF at our institution . Patient selection was made through chart review and phone interview of those patients who were likely to meet entry criteria . Inclusion criteria included patients between ages 19 and 80 years who were in stable New York Heart Association class II or III CHF due to ischemic or idiopathic dilated cardiomyopathy , with a documented left ventricular ejection fraction of 40 % within the past year . Patients had to be in sinus rhythm and on maintainance moderate-to-high dose ACE inhibitor therapy for 3 months . Exclusion criteria included a history of chronic lung disease , severe valvular heart disease , moderate-to-severe pulmonary hypertension , or a myocardial infa rct ion or cerebrovascular accident within the preceding 3 months . Patients with chronic stable angina or any other vascular , musculoskeletal , or metabolic condition precluding exercise testing were also excluded . Antiplatelet therapy other than aspirin or clopidogrel within 4 weeks of the study or warfarin anticoagulation was not allowed . Exercise testing was performed using",
"BACKGROUND Clopidogrel is a new antiplatelet agent that offers increased protection over aspirin in preventing vascular ischaemic events in patients with symptomatic atherosclerosis . In a large , r and omized , international study of clopidogrel and aspirin ( n = 19,185 patients ) clopidogrel was associated with a lower incidence of gastrointestinal adverse events , including gastrointestinal haemorrhage and hospitalizations because of gastrointestinal haemorrhage . The aim of the study was to determine whether macroscopic differences in the gastric mucosa between aspirin- and clopidogrel-treated subjects could be detected by gastroscopy after short-term treatment . METHODS Thirty-six healthy volunteers were r and omized in a double-blind , double-dummy , parallel design , to 75 mg/day of clopidogrel or 325 mg/day of aspirin for 8 days . Gastroscopy was performed at base line before administration of study drug and directly after treatment completion . Gastroduodenal effects were measured in accordance with a modified Lanza scale . RESULTS At base line no difference between the groups was detected ( median Lanza score , 0.0 in both groups ) . At the end of treatment the aspirin group showed a median score of 7.5 , and the clopidogrel group showed an unchanged median score of 0.0 ( P adverse events versus 8 individuals and 13 adverse events for clopidogrel , with approximately half of the adverse events being gastrointestinal in each group . No serious adverse events were reported . CONCLUSION In contrast to aspirin , short-term treatment with clopidogrel does not induce macroscopic changes in the gastroduodenal mucosa . The study results show that in patients without gastroduodenal disease clopidogrel , but not aspirin , does not induce any gastroscopically evident erosions during short-term treatment",
"Background —Aspirin is widely used as an antiplatelet drug in patients with coronary heart disease . Despite documented clinical benefit , many patients on aspirin still experience severe cardiovascular events . Several laboratory reports have shown lack of platelet inhibition in 5–40 % of aspirin‐treated patients , and the term aspirin resistance has been introduced . The clinical relevance of these laboratory findings is , however , still unknown . New antiplatelet drugs have been developed , and the adenosin diphosphate ( ADP ) receptor inhibitor clopidogrel has at least the same efficacy as aspirin with an acceptable safety profile . Laboratory methods for determination of platelet reactivity and treatment efficacy have been complicated and time consuming . New method ologies , like the PFA‐100 ® system , have made such analyses more suitable for clinical use . Design —In the ASCET study , 1000 patients with documented coronary heart disease will be r and omized to either continued treatment with aspirin 160 mg/d or change to clopidogrel 75 mg/d after initial determination of their platelet reactivity while on aspirin treatment . Clinical endpoints will be recorded for at least 2 years and related to the initial aspirin response",
"This r and omized , double-blind study on 79 patients reported the efficacy of ticlopidine – pentoxifylline combination in the treatment of atherosclerosis and the prevention of cerebrovascular accidents . Comparisons were made with aspirin – dipyridamole – buflomedil and buflomedil – placebo combinations as controls . Global symptoms , sensorimotor disorders and vertigo were improved in all treatment groups , although improvement tended to be more pronounced with ticlopidine – pentoxifylline . None of the groups showed any change in stenosis or vessel wall rigidity although ticlopidine – pentoxifylline reduced flow irregularity . This combination therapy also normalized the direction of flow in the ophthalmic artery in 46.2 % of patients with retro grade flow prior to treatment , compared with 30.0 % following aspirin – dipyridamole – buflomedil and 28.6 % following buflomedil – placebo administration . Significantly fewer cerebrovascular accidents occurred after treatment with ticlopidine – pentoxifylline . In conclusion , ticlopidine – pentoxifylline showed good therapeutic efficacy against atherosclerosis and a preventative effect against new cerebrovascular accidents . This therapy was well tolerated",
"BACKGROUND Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events . METHODS We r and omly assigned 15,603 patients with either clinical ly evident cardiovascular disease or multiple risk factors to receive clopidogrel ( 75 mg per day ) plus low-dose aspirin ( 75 to 162 mg per day ) or placebo plus low-dose aspirin and followed them for a median of 28 months . The primary efficacy end point was a composite of myocardial infa rct ion , stroke , or death from cardiovascular causes . RESULTS The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin ( relative risk , 0.93 ; 95 percent confidence interval , 0.83 to 1.05 ; P=0.22 ) . The respective rate of the principal secondary efficacy end point , which included hospitalizations for ischemic events , was 16.7 percent and 17.9 percent ( relative risk , 0.92 ; 95 percent confidence interval , 0.86 to 0.995 ; P=0.04 ) , and the rate of severe bleeding was 1.7 percent and 1.3 percent ( relative risk , 1.25 ; 95 percent confidence interval , 0.97 to 1.61 percent ; P=0.09 ) . The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo ( relative risk , 1.2 ; 95 percent confidence interval , 0.91 to 1.59 ; P=0.20 ) and the rate of death from cardiovascular causes also was higher with clopidogrel ( 3.9 percent vs. 2.2 percent , P=0.01 ) . In the subgroup with clinical ly evident atherothrombosis , the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo ( relative risk , 0.88 ; 95 percent confidence interval , 0.77 to 0.998 ; P=0.046 ) . CONCLUSIONS In this trial , there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors . Overall , clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infa rct ion , stroke , or death from cardiovascular causes . ( Clinical Trials.gov number , NCT00050817 . )",
"OBJECTIVES We sought to compare the efficacy of aspirin and ticlopidine in survivors of acute myocardial infa rct ion ( AMI ) treated with thrombolysis . BACKGROUND The role of ticlopidine in secondary prevention after AMI has not yet been explored . METHODS Of 4,696 patients with AMI treated with thrombolysis who were screened , 261 died in the hospital ( 5.6 % ) and 1,470 were enrolled in this r and omized , double-blind , multicenter trial and allocated to treatment with either aspirin ( 160 mg/day ) or ticlopidine ( 500 mg/day ) . The most frequent reasons for exclusion were refusal to give informed consent , planned myocardial revascularization , risk of noncompliance with study procedures , need for anticoagulant therapy and contraindications to the study treatments . The primary end point was the first occurrence of any of the following events during the six-month follow-up : fatal and nonfatal AMI , fatal and nonfatal stroke , angina with objective evidence of myocardial ischemia , vascular death or death due to any other cause . RESULTS The primary end point was recorded in 59 ( 8.0 % ) of the 736 aspirin-treated and 59 ( 8.0 % ) of the 734 ticlopidine-treated patients ( p = 0.966 ) . Vascular death was the first event in five patients taking aspirin and in six patients taking ticlopidine ( 0.7 % vs. 0.8 % ; p = NS ) ; nonfatal AMI in 18 and 8 ( 2.4 % vs. 1.1 % ; p = 0.049 ) ; nonfatal stroke in 3 and 4 ( 0.4 % vs. 0.5 % ; p = NS ) ; and angina in 33 and 40 ( 4.5 % vs. 5.4 % ; p = NS ) , respectively . The frequency of adverse reactions was not significantly different between the two groups . CONCLUSIONS No difference was found between the ticlopidine and aspirin groups in the rate of the primary combined end point of death , recurrent AMI , stroke and angina",
"BACKGROUND AND AIMS OF THE STUDY This study investigated the efficacy of postoperative ticlopidine as antiplatelet therapy in patients shortly after heart valve repair or replacement . METHODS Between 1990 and 1995 , 235 consecutive patients underwent either valve repair ( n = 67 ) or replacement with a bioprosthesis ( n = 168 ) . The bioprostheses used were Carpentier-Edwards porcine or pericardial ( n = 158 ) valves , Prima stentless valves ( n = 3 ) and cryopreserved homografts ( n = 7 ) . Types of repair were aortic ( one ) , mitral annuloplasty with Carpentier ring ( 65 ) and tricuspid repair ( one ) . Mean patient age was 67 ( range : 16 to 83 ) years for valve replacement and 57 ( range : 32 to 74 ) years for repair ( p Atrial fibrillation occurred in 34 % of patients . The hospital mortality rate was 11 % ( 26 patients ) . Of the 209 survivors , 137 were assigned to antiplatelet treatment with ticlopidine for the first three months of follow up . The other 72 received either oral anticoagulation ( coumadin ; n = 40 ) , aspirin ( n = 14 ) or no medication ( n = 18 ) . In 15 patients , ticlopidine treatment was interrupted due to diarrhea ( 13 cases ) , mild allergic reaction ( one ) or anemia ( one ) . The mean follow up was 3.2 years ( range : 1 month to 6 years ) ; cumulative follow up was 684 patient-years ( pt-yr ) and was complete in 96 % of cases . RESULTS There were two episodes of thromboembolism in the ticlopidine group at 1 month and 6 months respectively , with a linearized incidence of 0.5 % pt-yr . In the coumadin group there were four episodes of thromboembolism , three within the first three months of follow up . The linearized incidence was 3 % pt-yr ( p hemorrhage in the ticlopidine group in the first three months of follow up and one in the coumadin group . The linearized incidence was 0.75 % pt-yr . CONCLUSIONS Following heart valve repair or replacement with a bioprosthesis , the first three months is a high-risk period for thromboembolism . Ticlopidine seems to prevent this complication better than conventional therapy with oral anticoagulants . Nevertheless , hemorrhage continues to be a problem with ticlopidine therapy",
"BACKGROUND Recurrent stroke is a frequent , disabling event after ischemic stroke . This study compared the efficacy and safety of two antiplatelet regimens -- aspirin plus extended-release dipyridamole ( ASA-ERDP ) versus clopidogrel . METHODS In this double-blind , 2-by-2 factorial trial , we r and omly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily . The primary outcome was first recurrence of stroke . The secondary outcome was a composite of stroke , myocardial infa rct ion , or death from vascular causes . Sequential statistical testing of noninferiority ( margin of 1.075 ) , followed by superiority testing , was planned . RESULTS A total of 20,332 patients were followed for a mean of 2.5 years . Recurrent stroke occurred in 916 patients ( 9.0 % ) receiving ASA-ERDP and in 898 patients ( 8.8 % ) receiving clopidogrel ( hazard ratio , 1.01 ; 95 % confidence interval [ CI ] , 0.92 to 1.11 ) . The secondary outcome occurred in 1333 patients ( 13.1 % ) in each group ( hazard ratio for ASA-ERDP , 0.99 ; 95 % CI , 0.92 to 1.07 ) . There were more major hemorrhagic events among ASA-ERDP recipients ( 419 [ 4.1 % ] ) than among clopidogrel recipients ( 365 [ 3.6 % ] ) ( hazard ratio , 1.15 ; 95 % CI , 1.00 to 1.32 ) , including intracranial hemorrhage ( hazard ratio , 1.42 ; 95 % CI , 1.11 to 1.83 ) . The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups ( 1194 ASA-ERDP recipients [ 11.7 % ] , vs. 1156 clopidogrel recipients [ 11.4 % ] ; hazard ratio , 1.03 ; 95 % CI , 0.95 to 1.11 ) . CONCLUSIONS The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel . There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke . ( Clinical Trials.gov number , NCT00153062 .",
"AIM To evaluate effects of tiklid and aspirin on hemostasis , antithrombogenic activity of vascular wall in patients with unstable angina ( UA ) . MATERIAL AND METHODS An open r and omized trial enrolled 30 UA patients given tiklid ( n = 16 ) or aspirin ( n = 14 ) . Hemostasis , platelet aggregation , antithrombogenic activity of the vascular wall were examined on the treatment day 1 and 20 . The response was assessed by the number of anginal attacks , dose of nitroglycerine , data of Holter monitoring . RESULTS Tiklid was more effective than aspirin in UA patients as it by the treatment day 20 lowered platelet aggregation more , higher elevated anticoagulation potential of the blood and vessels , and stronger activated fibrinolytic hemostasis . CONCLUSION Compared to aspirin , tiklid is more potent antiaggregant , has greater effect on antithrombogenic properties of the vascular wall",
"Peripheral arterial disease ( PAD ) is associated with platelet hyperactivity . Aspirin and clopidogrel , two platelet inhibitors , act by different mechanisms . Aspirin inhibits thromboxane A2 synthesis and clopidogrel acts on the P2Y12 platelet ADP receptor . We evaluated the effect of clopidogrel ( 75 mg/day ) , aspirin ( 75 mg/day ) and then both drugs on several platelet function indices in patients with PAD ( n = 20 ) . There was a significant ( P = 0.0001 ) decrease in ADP-induced aggregation , after clopidogrel but not after taking aspirin . Clopidogrel plus aspirin significantly decreased spontaneous platelet aggregation ( SPA ) ( P = 0.01 to P = 0.002 ) but SPA was not significantly altered by either aspirin or clopidogrel monotherapy . Similarly , monotherapy did not inhibit serotonin (5HT)-induced aggregation but there was a significant inhibition ( P = 0.03 to P therapy . ADP ( 0.8 μM)-induced platelet shape change ( PSC ) was significantly inhibited by clopidogrel ( P = 0.004 ) or aspirin ( P = 0.01 ) . This was also true for 5HT-induced PSC ( clopidogrel , P = 0.01 ; aspirin , P = 0.03 ) . Soluble P-selectin decreased significantly ( from 32 ± 24 to 25 ± 17 ng/ml , P = 0.04 ) with combination therapy . Plasma platelet-derived growth factor and intraplatelet 5HT levels were not altered by combination therapy . In PAD , clopidogrel is a more potent inhibitor of ADP-induced platelet activation than aspirin ; combination therapy is more effective than clopidogrel or aspirin monotherapy . These potentially clinical ly relevant findings should be evaluated in appropriately design ed trials"
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BACKGROUND Although the detrimental effects of severe iodine deficiency are well recognised , the benefits of correcting mild-to-moderate iodine deficiency are uncertain . OBJECTIVES We undertook a systematic review of the impact of iodine supplementation in population s with mild-to-moderate iodine deficiency . METHODS We search ed Medline and the Cochrane library for relevant articles published between January 1966 and April 2013 , which investigated the effect of iodine supplementation on maternal and newborn thyroid function , infant neurodevelopment and cognitive performance in school-age children . The quality of studies was grade d and eligible trials were evaluated in the meta- analysis . RESULTS Nine r and omised controlled trials ( RCTs ) and eight observational studies met the inclusion criteria . Controlled trials on infant neurodevelopment were lacking ; gestational iodine supplementation reduced maternal thyroid volume and serum thyroglobulin and in some studies prevented a rise in serum thyroid-stimulating hormone . None of the intervention trials recorded an excess frequency of thyroid dysfunction in contrast to observational studies . A pooled analysis of two RCTs which measured cognitive function in school-age children showed modest benefits of iodine supplementation on perceptual reasoning ( st and ardised mean difference ( SMD ) 0.55 ; 95 % CI 0.05 , 1.04 ; P=0.03 ) and global cognitive index ( SMD 0.27 ; 95 % CI 0.10 , 0.44 ; P=0.002 ) with significant heterogeneity between studies . CONCLUSION Iodine supplementation improves some maternal thyroid indices and may benefit aspects of cognitive function in school-age children , even in marginally iodine-deficient areas . Further large prospect i ve controlled studies are urgently required to clarify these findings and quantify the risk/ benefits of iodine supplementation in regions previously believed to be iodine sufficient such as the UK
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"Micronutrient status is of fundamental importance both upon conception and throughout pregnancy . There is an abundance of literature investigating nutrient intakes during individual trimesters of pregnancy but few studies have investigated baseline intakes of nutrients throughout gestation as a continuum . The current investigation set out to measure habitual micronutrient intakes at weeks 13 , 25 , 35 of pregnancy and 6 weeks postpartum using a prospect i ve background information question naire , 4 - 7-day weighed food diary and postnatal question naire . Seventy-two primiparous , Caucasian Londoners were recruited at the study start with 42 completing the first , second , third trimester and postpartum study stages respectively . Study findings indicated that sodium intakes were significantly higher than UK guidelines throughout and after pregnancy ( P Intakes of folate , iron , vitamin D , potassium , iodine and selenium were lower than UK recommendations during and after pregnancy , but to varying levels of statistical significance ( P UK recommendations for folate ( 300 microg day(-1 ) ) through dietary sources . Similarly , only a small percentage of women met dietary guidelines for iron ( 19 - 28 % ) . The findings from the current study indicate that public health interventions may be required to help expectant mothers achieve an optimal diet , particularly after birth when dietary recommendations increase for some micronutrients",
"BACKGROUND An adequate iodine supply in utero and shortly after birth is known to be crucial to an individual 's physical and mental development . The question of whether iodine supplementation later in life can exert a favorable influence on the mental performance of iodine-deficient population s was addressed in various studies , but with contradictory results . OBJECTIVE The aim of this study was to examine the effect of an improvement in iodine status on mental and psychomotor performance of schoolchildren ( 7 - 11 y ) who were moderately to severely iodine deficient . DESIGN The study , which was originally planned as a double-blind , r and omized , placebo-controlled intervention , was carried out in an iodine-deficient population of schoolchildren ( n = 196 ) in northern Benin . As the population began to have access to iodized salt during the 1-y intervention period , the study population was split post hoc-on the basis of urinary iodine concentrations-into a group with improved iodine status and a group with unchanged iodine status . Changes in mental and psychomotor performance over the intervention period were compared . RESULTS Children with increased urinary iodine concentrations had a significantly greater increase in performance on the combination of mental tests than did the group with no change in urinary iodine concentrations . CONCLUSIONS An improvement in iodine status , rather than iodine status itself , determined mental performance in this population , which was initially iodine deficient . These findings suggest a \" catch-up \" effect in terms of mental performance",
"BACKGROUND Iodine is required for the production of thyroid hormones , which are necessary for normal brain development and cognition . Although several r and omized trials examined the effect of iodine supplementation on cognitive performance in schoolchildren , the results were equivocal . OBJECTIVE We aim ed to ascertain whether providing iodized oil to iodine-deficient children would affect their cognitive and motor performance . DESIGN In a double-blind intervention trial , 10 - 12-y-old children ( n = 310 ) in primary schools in rural southeastern Albania were r and omly assigned to receive 400 mg I ( as oral iodized oil ) or placebo . We measured urinary iodine ( UI ) , thyroid-stimulating hormone ( TSH ) , and total thyroxine ( TT4 ) concentrations and thyroid gl and volume ( by ultrasound ) . The children were given a battery of 7 cognitive and motor tests , which included measures of information processing , working memory , visual problem solving , visual search , and fine motor skills . Thyroid ultrasound and the biochemical and psychological tests were repeated after 24 wk . RESULTS At baseline , the children 's median UI concentration was 43 microg/L ; 87 % were goitrous , and nearly one-third had low concentrations of circulating TT4 . Treatment with iodine markedly improved iodine and thyroid status : at 24 wk , median UI in the treated group was 172 microg/L , mean TT4 was approximately 40 % higher , and the prevalence of hypothyroxinemia was placebo , iodine treatment significantly improved performance on 4 of 7 tests : rapid target marking , symbol search , rapid object naming , and Raven 's Coloured Progressive Matrices ( P Information processing , fine motor skills , and visual problem solving are improved by iodine repletion in moderately iodine-deficient schoolchildren",
"Mild iodine deficiency during pregnancy can have significant effects on fetal development and future cognitive function . The purpose of this study was to characterise the iodine status of South Australian women during pregnancy and relate it to the use of iodine-containing multivitamins . The impact of fortification of bread with iodized salt was also assessed . Women ( n = 196 ) were recruited prospect ively at the beginning of pregnancy and urine collected at 12 , 18 , 30 , 36 weeks gestation and 6 months postpartum . The use of a multivitamin supplement was recorded at each visit . Spot urinary iodine concentrations ( UIC ) were assessed . Median UICs were within the mildly deficient range in women not taking supplements ( taking iodine-containing multivitamins UICs were within WHO recommendations ( 150–249 μg/L ) for sufficiency and showed an increasing trend through gestation . The fortification of bread with iodized salt increased the median UIC from 68 μg/L to 84 μg/L ( p = .011 ) which was still in the deficient range . Pregnant women in this region of Australia were unlikely to reach recommended iodine levels without an iodine supplement , even after the m and atory iodine supplementation of bread was instituted in October 2009",
"BACKGROUND The effects of severe iodine deficiency during critical periods of brain development are well documented . There is little known about the consequences of milder forms of iodine deficiency on neurodevelopment . OBJECTIVE The objective was to determine whether supplementing mildly iodine-deficient children with iodine improves cognition . DESIGN A r and omized , placebo-controlled , double-blind trial was conducted in 184 children aged 10 - 13 y in Dunedin , New Zeal and . Children were r and omly assigned to receive a daily tablet containing either 150 microg I or placebo for 28 wk . Biochemical , anthropometric , and dietary data were collected from each child at baseline and after 28 wk . Cognitive performance was assessed through 4 subtests from the Wechsler Intelligence Scale for Children . RESULTS At baseline , children were mildly iodine deficient [ median urinary iodine concentration ( UIC ) : 63 microg/L ; thyroglobulin concentration : 16.4 microg/L ] . After 28 wk , iodine status improved in the supplemented group ( UIC : 145 microg/L ; thyroglobulin : 8.5 microg/L ) , whereas the placebo group remained iodine deficient ( UIC : 81 microg/L ; thyroglobulin : 11.6 microg/L ) . Iodine supplementation significantly improved scores for 2 of the 4 cognitive subtests [ picture concepts ( P = 0.023 ) and matrix reasoning ( P = 0.040 ) ] but not for letter-number sequencing ( P = 0.480 ) or symbol search ( P = 0.608 ) . The overall cognitive score of the iodine-supplemented group was 0.19 SDs higher than that of the placebo group ( P = 0.011 ) . CONCLUSIONS Iodine supplementation improved perceptual reasoning in mildly iodine-deficient children and suggests that mild iodine deficiency could prevent children from attaining their full intellectual potential . The trial was registered with the Australia New Zeal and Clinical Trials Register as ACTRN12608000222347",
"Maternal hypothyroidism and hypothyroxenemia due to iodine deficiency have been shown to affect development of the newborn negatively . Maternal iodine supplementation may therefore improve cognitive performance of the offspring , even in areas of mild-to-moderate iodine deficiency ( ID ) . Several iodine supplementation studies have been performed in mildly ID pregnant women in Europe . These studies have shown that iodine supplementation increases maternal urinary iodine ( UI ) excretion and reduces thyroid volume , as well as prevents increases in infant thyroid volume and thyroglobuline . However , r and omized controlled studies with long-term outcomes are lacking . Therefore , two trials were started in 2008 in areas of low iodine status ; one in Bangalore , India ( n=325 ) , and another in Bangkok , Thail and ( n=514 ) . Pregnant women were recruited to either receive a daily dose of 200 μg I ( as KI ) or an identical placebo throughout pregnancy . Both trials are ongoing , and women are followed up during pregnancy and at delivery . UI , thyroid hormones , and thyroid size are measured . Birth outcomes are recorded , such as gestational age at delivery , height , weight , and APGAR scores , and cord blood and heel stick blood ( ) is collected from the child . Child development is assessed at 6 weeks of age using the Neonatal Behavioral Assessment Scale ( NBAS ) , and at 12 and 24 months of age using the Bayley Scales of Infant Development . The outcomes of these trials will contribute importantly to the evidence base for iodine supplementation of pregnant women living in areas of mild iodine deficiency",
" In moderately iodine-deficient , pregnant , thyroid peroxidase antibody (TPO-Ab)-positive women the role of iodine supplementation in the development of postpartum thyroid dysfunction ( PPTD ) was studied in a placebo-controlled , r and omized , double blind trial . Screening for TPO-Ab was performed in early pregnancy in a population of healthy pregnant Danish women with no previous diagnosed thyroid disease ( prevalence , 117 of 1,284 ; 9.1 % ) . The participants were r and omized , stratified according to TPO-Ab level , to three groups . All participants received a daily vitamin and mineral tablet with 150 microg iodine or no iodine . The + /+ group received iodine during pregnancy and the postpartum period , the + /- group received iodine during pregnancy only , and the -/- group received no iodine supplementation . A total of 66 TPO-Ab positive women were followed , and in the postpartum period sera were collected at 8-week interval for biochemical evaluation of thyroid function and antibody level . Compliance was evaluated by 24-h urinary iodine measurements . PPTD developed in 55 % of the participants . In 67 % of the cases abnormal TSH was accompanied by abnormalities in thyroid hormones , whereas 33 % had abnormal serum TSH only . There was no statistically significant difference in the frequency of PPTD in the three groups : + /+ group , 59 % ( 95 % confidence interval , 36 - 79 % ) ; + /- group , 60 % ( 36 - 81 % ) ; and -/- group , 46 % ( 26 - 67 % ) . There were also no differences in the severity of the PPTD , as evaluated by duration and grade of deviation of TSH and thyroid hormones from normality . The occurrence , severity , and type of PPTD predominantly depended on the TPO-Ab level : TPO-Ab below 200 U/L at screening , 35 % developed PPTD ; TPO-Ab of 200 - 900 U/L , 54 % ; and TPO-Ab above 900 U/L , 75 % developed PPTD . Women with low levels of antibodies predominantly remained euthyroid or had hyperthyroidism only , whereas women with high antibody levels had hyperthyroidism followed by hypothyroidism or hypothyroidism only . We conclude that iodine supplementation ( 150 microg ) during pregnancy and the postpartum period to TPO-Ab-positive women living in an area with mild to moderate iodine deficiency did not induce or worsen PPTD . The study confirmed that screening for TPO-Ab in early pregnancy can predict women at high risk for development of PPTD",
" One hundred and eighty euthyroid pregnant women were selected at the end of the first trimester of gestation on the basis of biochemical criteria of excessive thyroid stimulation , defined as supranormal serum thyroglobulin ( TG > 20 micrograms/L ) associated with a low normal free T4 index ( 25 x 10(-3 ) ) . Women were r and omized in a double blind protocol into three groups and treated until term with a placebo , 100 micrograms potassium iodide (KI)/day , or 100 micrograms iodide plus 100 micrograms L-T4/day . Parameters of thyroid function , urinary iodine excretion , and thyroid volume were monitored sequentially . Neonatal thyroid parameters , including thyroid volume by echography , were also assessed in the newborns from mothers of the three groups . In women receiving a placebo , the indices of excessive thyroid stimulation worsened as gestation progressed , with low free T4 levels , markedly increased serum TG and T3/T4 ratio . Serum TSH doubled , on the average , and was supranormal in 20 % of the cases at term . Urinary iodine excretion levels were low , around 30 micrograms/L at term . The thyroid volume increased , on the average , by 30 % , and 16 % of the women developed a goiter , confirming the goitrogenic stimulus associated with pregnancy . Moreover , the newborns of these mothers had significantly larger thyroid volumes at birth as well as elevated serum TG levels . In both groups of women receiving an active treatment , the alterations in thyroid function associated with pregnancy were markedly improved . The increase in serum TSH was almost suppressed , serum TG decreased significantly , and changes in thyroid volume were minimized ( group receiving KI ) or almost suppressed ( group receiving KI combined with L-T4 ) . Moreover , in the newborns of the mothers in the two groups receiving an active treatment , serum TG was significantly lower , and thyroid volume at birth was normal . The effects of therapy were clearly more rapid and more marked in the group receiving a combination of T4 and KI than in the women receiving KI alone . The differences could be partly attributed to the slightly higher amount of iodine received by women in the combined treatment . However , the main benefits of the combined treatment were almost certainly attributable to the hormonal effects of the addition of L-T4 . Furthermore , the study demonstrated that the administration of T4 did not hamper the beneficial effect of iodine supplementation . In conclusion , the present work emphasizes the potential risk of goitrogenic stimulation in both mother and newborn in the presence of mild iodine deficiency . ( ABSTRACT TRUNCATED AT 400 WORDS",
"The benefits of iodine supplements during pregnancy remain controversial in areas with a mild-to-moderate iodine deficiency . The aim of the present study was to determine the effect of improving iodine intakes , with iodised salt ( IS ) or iodine supplements , in pregnant Spanish women . A total of 131 pregnant women in their first trimester were r and omly assigned to three groups : ( 1 ) IS in cooking and at the table , ( 2 ) 200 μg potassium iodide (KI)/d or ( 3 ) 300 μg KI/d . No differences were found in thyroid-stimulating hormone ( TSH ) , free thyroxine ( FT4 ) , free triiodothyronine ( FT3 ) or thyroid volume ( TV ) between the three groups . Regardless of the group in which women were included , those who had been taking IS for at least 1 year before becoming pregnant had a significantly lower TV in the third trimester ( P= 0.01 ) and a significantly higher urinary iodine in the first ( 173.7 ( sd 81.8 ) v. 113.8 ( sd 79.6 ) μg/l , P= 0.001 ) and third trimesters ( 206.3 ( sd 91.2 ) v. 160.4 ( sd 87.7 ) μg/l , P= 0.03 ) . Also , no differences were seen in TSH , FT4 or FT3 . Children 's neurological development was not significantly associated with the consumption of IS for at least 1 year before becoming pregnant and no differences were found according to the treatment group . In conclusion , in pregnant women with insufficient iodine intake , the intake of IS before becoming pregnant was associated with a better maternal thyroid function . The form of iodide intake was not associated with maternal thyroid function or children 's neurological development",
"CONTEXT Mild to moderate iodine deficiency during pregnancy can cause transient maternal hypothyroidism and impaired mental development of the progeny . These unfavorable effects are preventable by iodine supplementation . In Europe , however , less than 50 % pregnant women receive iodine-containing supplements , thus representing dietary iodized salt the only carrier of iodine for most women in this life stage . OBJECTIVE / DESIGN This longitudinal study is aim ed to investigate the effects of long-term iodized salt consumption on maternal thyroid function during gestation . PARTICIPANTS / OUTCOME MEASURES : We prospect ively evaluated thyroid function in 100 consecutive thyroperoxidase antibody-negative pregnant women from a mildly iodine-deficient area . Sixty-two women who had regularly used iodized salt for at least 2 yr prior to becoming pregnant and 38 who commenced iodized salt consumption upon becoming pregnant were classified as long-term ( LT ) and short-term ( ST ) iodine supplemented , respectively . RESULTS Long-term iodized salt consumption result ed in a very low prevalence of maternal thyroid failure ( MTF ) in LT women . Conversely , short-term iodine prophylaxis does not seem to protect against the risk of MTF , the prevalence of which was almost 6-fold higher in ST than LT women ( 36.8 % vs. 6.4 % ; chi(2 ) 14.7 , P relative risk reduction amounted to 82.5 % , this measure indicating the extent to which long-term iodine prophylaxis using iodized salt would reduce the risk of MTF in ST women . CONCLUSIONS Prolonged iodized salt significantly improves maternal thyroid economy and reduces the risk of maternal thyroid insufficiency during gestation , probably because of a nearly restoring intrathyroidal iodine stores",
"OBJECTIVE A prospect i ve r and omized trial was performed to assess the usefulness of iodine supplementation in the prevention of goiter in pregnant women living in marginally iodine-deficient areas . DESIGN Eighty-six pregnant women were recruited and r and omized in two groups and treated daily for up to six months after delivery with 200 microg iodide ( group A ) or 50 microg iodide ( group B ) . Sixty-seven women ( 32 in group A and 35 in group B ) completed the study . METHODS Thyroid volume ( TV ) , thyroid functional parameters and urinary iodine concentration were determined in all subjects at booking , at the 18th-26th , and the 29th-33rd week of gestation , and at the 3rd and 6th month after delivery . RESULTS A slight but not significant increase in TV during gestation was observed only in group B. After delivery a progressive decrease in TV was documented in both groups , the final TV being significantly reduced with respect to the initial volume in group A. No significant changes in serum free thyroid hormones and TSH concentrations were found during gestation in either group . Postpartum thyroiditis was observed in 5 women ( 2 in group A , 3 in group B ) . No side effects were seen . CONCLUSION The present data indicate that in marginally iodine-deficient areas , the administration of iodide is recommended in pregnancy and lactation . In the conditions of the present trial a dose of 50 microg iodide/day is a safe and effective measure in preventing an increase in TV during pregnancy but a dose of 200 microg iodide/day appeared to be more effective without inducing side effects and without enhancing the frequency of post-partum thyroiditis",
"CONTEXT The definition of what constitutes a normal TSH during pregnancy is in flux . Recent studies suggested that the first trimester upper limit of normal for TSH should be 2.5 mIU/liter . OBJECTIVE The objective of the study was to evaluate the pregnancy loss and preterm delivery rate in first-trimester thyroid peroxidase antibody-negative women with TSH values between 2.5 and 5.0 mIU/liter . DESIGN The present study is a component of a recently published large-scale prospect i ve trial that evaluated the impact of levothyroxine treatment on maternal and neonatal complications in thyroid peroxidase-positive women with TSH levels above 2.5 mIU/liter . The present study evaluated 4123 thyroid peroxidase antibody-negative women with TSH levels at or below 5.0 mIU/liter . Women were divided into two groups based on their initial TSH : group A , TSH level below 2.5 mIU/liter , excluding hyperthyroid women defined as an undetectable TSH with an elevated free T(4 ) , and group B , TSH level between 2.5 and 5.0 mIU/liter . SETTING The study was conducted at two ambulatory clinics of community hospitals in southern Italy . PATIENTS A total of 4123 women were evaluated . INTERVENTION There was no intervention . MAIN OUTCOME MEASURES The incidence of pregnancy loss and preterm delivery in group A as compared with group B was measured . RESULTS The rate of pregnancy loss was significantly higher in group B as compared with group A ( 6.1 vs. 3.6 % respectively , P = 0.006 ) . There was no difference in the rate of preterm delivery between the two groups . CONCLUSIONS The increased incidence of pregnancy loss in pregnant women with TSH levels between 2.5 and 5.0 mIU/liter provides strong physiological evidence to support redefining the TSH upper limit of normal in the first trimester to 2.5 mIU/liter",
"During pregnancy complex changes of maternal thyroid function occur and they are influenced by the maternal iodine supply . It has been demonstrated that with decreasing iodine supply maternal goiter and hypothyroxinemia as well as fetal and neonatal hypothyroidism become more prevalent . Therefore iodine supplementation during pregnancy is now strongly recommended also in areas of moderate iodine deficiency . To monitor the success of iodine supplementation and its theoretical risk of increasing the frequency of thyroid autoantibodies , we have investigated the thyroid volume , thyroid function , urinary iodine excretion and antibodies to thyroid peroxidase at 10 - 12 weeks of gestation and postpartum in 38 mothers receiving 300 micrograms potassium iodide/day and in 70 mothers without iodine supplementation . In all of their newborns thyroid volume was determined by ultrasound . The thyrotropin ( TSH ) levels and antibodies to thyroid peroxidase ( TPO-ab ) in the neonates were measured in dried blood spots on filter paper from their newborn screening . Urinary iodine excretion was increased significantly after iodine supplementation in mothers ( p hypo- or hyperthyroidism was observed in the mothers or newborns . Interestingly , no difference of maternal thyroid volumes was observed between the two groups after pregnancy , but the volumes of the thyroid gl and s in newborns of mothers who received iodine were significantly ( p frequency of TPO-ab in either group after pregnancy . In four mothers transplacental passage of these antibodies was documented by positive measurement in the blood sample of the newborn . This study documents that iodine supplementation during pregnancy in an area of moderate iodine deficiency results in a lower size of neonatal thyroid volume and that this supplementation was not accompanied by an increase in the frequency of TPO-ab",
"Iodine deficiency has re-emerged in many parts of the world including the UK , Australia and New Zeal and ( NZ ) . In 2009 , the NZ government introduced the m and atory fortification of bread with iodised salt as a strategy to improve iodine intakes . The aim of the present study was to assess the impact of fortification on the iodine status of NZ schoolchildren . A school-based cluster survey was used to r and omly select schools from two NZ cities . Children aged 8 - 10 years were administered a general question naire , and asked to provide a casual urine and finger-prick blood sample . The median urinary iodine concentration ( UIC ) of the children ( n 147 ) was 113 μg/l , which falls between 100 and 199 μg/l indicating adequate iodine status ; 12 % of children had a UIC The median serum thyroxine concentration was 115 nmol/l . The median serum thyroglobulin ( Tg ) concentration was 10.8 μg/l and falls in the 10.0 - 19.9 μg/l range indicative of mild iodine deficiency , suggesting that these children still had enlarged thyroid gl and s. When compared with the median UIC of 68 μg/l reported in the 2002 NZ Children 's Nutrition Survey , the UIC of children in the present study had increased , which is probably caused by the addition of iodised salt to bread . However , the elevated concentration of Tg in these children suggests that the increase in UIC is not sufficient to ensure that thyroid volume has normalised . The fortification of other staple foods , in addition to bread , should be considered to ensure good iodine status in NZ children",
"OBJECTIVE To study the evolution of thyroid autoimmunity , in relation to the change in goitre prevalence , during 3 Years of iodine prophylaxis in Sri Lanka . METHODS Two groups of Sri Lankan schoolgirls between the ages of 10.8 and 17.5 Years were studied in 1998 ( 401 girls ) and 2001 ( 282 girls ) . A prospect i ve study was performed in 42 schoolgirls who were thyroid autoantibody (Ab)-positive ( + ve ) in 1998 . Anthropometric measures , urinary iodine excretion ( UIE ) , thyroid Volume , free thyroxine , free tri-iodothyronine , TSH , and thyroglobulin ( Tg ) and thyroid peroxidase ( TPO ) Ab were evaluated in all 683 girls . RESULTS Goitre prevalence was significantly lower in 2001 compared with 1998 related to age ( 2.9 % compared with 20.2 % ) and body surface area ( 11.6 % compared with 40.8 % ) , although UIE was unchanged . Prevalence of thyroid Ab in 2001 was also lower ( 23.4 % compared with 49.9 % ) ; among those with the Ab , 34.8 % had TgAb alone and 46.9 % had a combination of TgAb+TPOAb , compared with 82.0 % TgAb alone in 1998 . In 2001 , sub clinical hypothyroidism was more frequent in Ab+ve ( 6.3 % ) than Ab-negative girls ( 1.0 % ) . A cohort of 42 Ab+ve schoolgirls in 1998 ( 34 with TgAb alone , eight with TgAb+TPOAb ) were evaluated again in 2001 . Only 10 of them ( 23.8 % ) remained Ab+ve ( mostly TPOAb+/-TgAb ) in 2001 . CONCLUSIONS This study demonstrates that : ( 1 ) in 2001 , goitre prevalence and thyroid autoimmunity rates were significantly lower than in 1998 ; ( 2 ) the pattern of thyroid Ab was different in the two surveys ; ( 3 ) in 2001 alone , the occurrence of hypothyroidism was correlated with the presence of thyroid autoimmunity . These results indicate an evolution of thyroid autoimmune markers during the course of iodine prophylaxis , which has not been described before",
"Thyroid gl and size was ultrasonographically determined in 35 pregnant women who live in an area with moderate iodine deficiency . Iodide salt was administered to group A ( n = 17 ) , whereas group B ( n = 18 ) was used as a control . Each group was tested for thyroid-stimulating hormone serum levels , iodine excretion , and thyroid volume . In both groups thyroid-stimulating hormone levels were similar and did not change throughout pregnancy . The iodine excretion at the third trimester in the treated group was significantly ( p less than 0.01 ) higher than that of group B ( 100.0 + /- 39.0 versus 50.0 + /- 37.0 micrograms iodine per 24 hours , respectively ) . Initially , thyroid volume did not differ between the two groups . At the end of pregnancy , no difference was found in thyroid size in group A , whereas in the untreated women it increased significantly ( p less than 0.0001 ) with a mean increase of 1.6 + /- 0.6 ml ( 16.2 % + /- 6.0 % ) . These results show that the increased thyroid size in the control group was mainly a result of relative iodine deficiency and that iodoprophylaxis should be warranted even in areas with moderate iodine deficiency to prevent the increase in thyroid size and , probably , to avoid the risk of maternal and fetal hypothyroidism",
"Knowledge of the effect of differences in iodine intake levels on public health in areas with no endemic goiter is limited . Groups at risk when iodine intake is relatively low are pregnant and lactating women and their newborns . A prospect i ve r and omized study was performed to evaluate the effect of iodine supplementation in an area where the median daily iodine excretion in urine is around 50 micrograms . Fifty-four normal pregnant women were r and omized to be controls or to receive 200 micrograms iodine/day from weeks 17 - 18 of pregnancy until 12 months after delivery . In the control group , serum TSH , serum thyroglobulin ( Tg ) , and thyroid size showed significant increases during pregnancy . These variations were ameliorated by iodine supplementation . Iodine did not induce significant variations in serum T4 , T3 , or free T4 . Cord blood Tg was much lower when the mother had received iodine , whereas TSH , T4 , T3 , and free T4 levels were unaltered . The results suggest that a relatively low iodine intake during pregnancy leads to thyroidal stress , with increases in Tg release and thyroid size . However , the thyroid gl and is able to adapt and keep thyroid hormones in the mother and the child normal , at least under normal circumstances , as evaluated in the present study . It is not known whether this stress is sufficient to be of importance for late development of autonomous thyroid growth and function",
"To assess the prevalence of thyroid disorders in a region with mild iodine deficiency , this study was undertaken in a r and omized sample of pregnant women during different gestational periods . Evaluations were performed in 215 women : thyroid ultrasound scanning , thyroid stimulating hormone ( TSH ) , free thyroxine ( T4 ) and thyroid peroxidase ( TPO ) antibodies . At the time of participation in the study , some women ( 90/215 ) had been receiving 150–200 µg iodine . Hypothyroidism was found in four women ( 1.86 % ) . Positive TPO antibodies were seen in 34 of 215 women ( 15.8 % ) , and TPO antibody level over 150 mU/l was found in 9.8 % ( 21/215 ) . There was no significant difference between TSH levels in women with positive or negative TPO antibodies . There were no differences in TSH level between the women receiving and those not receiving iodine prophylaxis . The prevalence of goiter in 211 euthyroid women was found to be 24.2 % ( 51/211 ) . In the group with iodine prophylaxis , thyroid volume was found to be significantly lower ( t = 2.5 ; p = 0.02 ) than in women who had not received it , or had started it during the second trimester . By comparison of history data on the prevalence of aborted pregnancy between the group with positive ( 26.5 % ; 9/34 ) and the group with negative TPO antibodies ( 14.3 % ; 26/181 ) , no significant differences were found . We conclude that , in mild iodine deficiency , pregnancy is related to a high risk of goiter , which can be prevented by iodine prophylaxis . TPO antibody carrier status in pregnant women is probably not associated with a significant risk of thyroid dysfunction or spontaneous abortion"
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BACKGROUND While hypertension is a leading risk factor for an initial stroke , the role of blood pressure lowering to prevent subsequent stroke is less clear . The results of recent large clinical trials investigating effects of antihypertensive agents in patients with a history of stroke have not shown a significant benefit ; findings that are at odds with previous data . Our meta- analysis systematic ally evaluates the available , relevant trials to examine the role of antihypertensive drugs in preventing recurrent stroke . METHODS MEDLINE , CENTRAL , and Clinical Trials.gov were systematic ally search ed and bibliographies from key reports were examined . All r and omized , placebo-controlled trials that tested blood pressure lowering agents in patients with stroke or transient ischemic attack were identified . The results from these trials were combined and meta-analyses were performed . RESULTS Ten studies were found to contain relevant endpoints and presented data allowing meta- analysis . Agents that lowered blood pressure reduced recurrent stroke ( OR 0.71 , 95 % CI 0.59 - 0.86 , P = 0.0004 ) and cardiovascular events ( OR 0.69 , 95 % CI 0.57 - 0.85 , P = 0.0004 ) in patients with a previous stroke or TIA . These agents did not affect the rate of myocardial infa rct ion ( OR 0.86 , 95 % CI 0.73 - 1.01 , P = 0.07 ) or all-cause mortality ( OR 0.95 , 95 % CI 0.83 - 1.07 , P = 0.39 ) in this patient population . CONCLUSION Despite recent large trials showing no significant effect , in patients that have experienced a TIA or stroke , blood pressure lowering agents reduced the occurrence of subsequent stroke and cardiovascular events . The rate of myocardial infa rct ion and all-cause mortality was unchanged
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"Background and Purpose — The Acute C and esartan Cilexetil Therapy in Stroke Survivors ( ACCESS ) study was design ed to assess the safety of modest blood pressure reduction by c and esartan cilexetil in the early treatment of stroke . The study was also design ed to provide an estimate of the number of cases required to perform a larger phase III efficacy study . Methods — Five hundred patients were recruited in a prospect i ve , double-blind , placebo-controlled , r and omized , multicenter phase II study . Results — This safety trial was stopped prematurely when 342 patients ( 339 valid ) had been r and omized because of an imbalance in end points . Demographic data , cardiovascular risk factors , and blood pressure on admission , on study onset , and within the whole study period were not significantly different between the 2 groups . However , the cumulative 12-month mortality and the number of vascular events differed significantly in favor of the c and esartan cilexetil group ( odds ratio , 0.475 ; 95 % CI , 0.252 to 0.895 ) . There were no significant differences in concomitant medication and in number or type of side effects . Conclusions — Although the mechanisms by which angiotensin type 1 ( AT1 ) receptor blockade affects cardiovascular morbidity and mortality are still unresolved , the present study shows that early neurohumoral inhibition has similar beneficial effects in cerebral and in myocardial ischemia . The fact that no cardiovascular or cerebrovascular event occurred as a result of hypotension is of significant clinical importance . When there is need for or no contraindication against early antihypertensive therapy , c and esartan cilexetil is a safe therapeutic option according to the ACCESS results",
" Two hundred and sixty-four patients were included in an open , r and omized , multicenter trial , with the aim of determining whether nicardipine can be useful in the prevention of cerebral infa rct ion . The patients had experienced one or more transient ischemic attacks , reversible ischemic neurologic defect , or stroke with minor permanent neurological deficit in the 12 months before enrolling in the study . Each patient was r and omly assigned to received 250 mg of aspirin once daily plus 20 mg of nicardipine thrice daily ( n = 170 ) or 250 mg of aspirin once daily ( n = 94 ) for 12 months . During the 12-month treatment period , 12 % of the aspirin-plus-nicardipine group and 19 % of the aspirin-only group experienced an ischemic cerebrovascular event ; at six months , the cumulative incidence of events was significantly lower in the aspirin-plus-nicardipine group than in the aspirin-only group . One patient in each group died of a recurrent stroke . Aspirin-related side effects were dyspepsia ( reported by four patients ) , heartburn ( by seven ) , nausea and vomiting ( by four ) , and melena ( by five ) ; nicardipine-related side effects were transient hypotension ( by two ) , headache ( by four ) , ankle edema ( by three ) , and constipation ( by four ) . Results indicate that the addition of nicardipine to antiplatelet treatment may safely prevent the recurrence of ischemic cerebrovascular events",
"Background and Purpose — In hypertensive stroke patients , for the same level of blood pressure control , eprosartan will be more effective than nitrendipine in reducing cerebrovascular and cardiovascular morbidity and mortality . Methods — A total of 1405 well-defined , high-risk hypertensives with cerebral event during the last 24 months ( proven by cerebral computed tomography scan or nuclear magnetic resonance ) were r and omized to eprosartan or nitrendipine ( mean follow-up 2.5 years ) . Primary end point was the composite of total mortality and all cardiovascular and cerebrovascular events , including all recurrent events . Results — R and omization was successful without significant differences in the baseline characteristics . Blood pressure was reduced to a comparable extent without any significant differences between the 2 groups during the whole study period ( 150.7/84 mm Hg and 152.0/87.2 mm Hg with eprosartan and nitrendipine therapy to 137.5/80.8 mm Hg and 136.0/80.2 mm Hg , respectively , confirmed by ambulatory blood pressure monitoring ) . Moreover , already after 3 months , normotensive mean values were achieved , and 75.5 % reached values eprosartan regimen and 77.7 % with the nitrendipine regimen . During follow-up , in total , 461 primary events occurred : 206 eprosartan and 255 nitrendipine ( incidence density ratio [ IDR ] , 0.79 ; 95 % CI , 0.66 to 0.96 ; P=0.014 ) . Cardiovascular events were : 77 eprosartan and 101 nitrendipine ( IDR , 0.75 ; 95 % CI , 0.55 to 1.02 ; P=0.06 ) ; cerebrovascular events : 102 eprosartan and 134 nitrendipine ( IDR , 0.75 ; 95 % CI , 0.58 to 0.97 ; P=0.03 ) . Conclusions — The Morbidity and Mortality After Stroke , Eprosartan Compared With Nitrendipine for Secondary Prevention ( MOSES ) study was the first to compare an angiotensin II type 1 receptor antagonist with a calcium antagonist in secondary stroke prevention . In these high-risk hypertensive stroke patients , an early normotensive and comparable blood pressure was achieved . The combined primary end point was significantly lower in the eprosartan group",
"Abstract Objective : To determine the effect of the angiotensin converting enzyme inhibitor ramipril on the secondary prevention of stroke . Design : R and omised controlled trial with 2 × 2 factorial design . Setting : 267 hospitals in 19 countries . Participants : 9297 patients with vascular disease or diabetes plus an additional risk factor , followed for 4.5 years as part of the HOPE study . Outcome measures : Stroke ( confirmed by computed tomography or magnetic resonance imaging when available ) , transient ischaemic attack , and cognitive function . Blood pressure was recorded at entry to the study , after 2 years , and at the end of the study . Results : Reduction in blood pressure was modest ( 3.8 mm Hg systolic and 2.8 mm Hg diastolic ) . The relative risk of any stroke was reduced by 32 % ( 156 v 226 ) in the ramipril group compared with the placebo group , and the relative risk of fatal stroke was reduced by 61 % ( 17 v 44 ) . Benefits were consistent across baseline blood pressures , drugs used , and subgroups defined by the presence or absence of previous stroke , coronary artery disease , peripheral arterial disease , diabetes , or hypertension . Significantly fewer patients on ramipril had cognitive or functional impairment . Conclusion : Ramipril reduces the incidence of stroke in patients at high risk , despite a modest reduction in blood pressure . What is already known on this topic Treatment with aspirin and lowering blood pressure reduce the incidence of stroke What this study adds Ramipril , an angiotensin converting enzyme inhibitor , reduces strokes in patients at high risk whose blood pressure is not elevated , despite only a modest lowering of blood pressure The benefits are observed even when patients receive aspirin and other blood pressure lowering",
"BACKGROUND Blood pressure is a determinant of the risk of stroke among both hypertensive and non-hypertensive individuals with cerebrovascular disease . However , there is uncertainty about the efficacy and safety of blood-pressure-lowering treatments for many such patients . The perindopril protection against recurrent stroke study ( PROGRESS ) was design ed to determine the effects of a blood-pressure-lowering regimen in hypertensive and non-hypertensive patients with a history of stroke or transient ischaemic attack . METHODS 6105 individuals from 172 centres in Asia , Australasia , and Europe were r and omly assigned active treatment ( n=3051 ) or placebo ( n=3054 ) . Active treatment comprised a flexible regimen based on the angiotensin- converting-enzyme inhibitor perindopril ( 4 mg daily ) , with the addition of the diuretic indapamide at the discretion of treating physicians . The primary outcome was total stroke ( fatal or non-fatal ) . Analysis was by intention to treat . FINDINGS Over 4 years of follow up , active treatment reduced blood pressure by 9/4 mm Hg . 307 ( 10 % ) individuals assigned active treatment suffered a stroke , compared with 420 ( 14 % ) assigned placebo ( relative risk reduction 28 % [ 95 % CI 17 - 38 ] , p risk of total major vascular events ( 26 % [ 16 - 34 ] ) . There were similar reductions in the risk of stroke in hypertensive and non-hypertensive subgroups ( all p perindopril plus indapamide reduced blood pressure by 12/5 mm Hg and stroke risk by 43 % ( 30 - 54 ) . Single-drug therapy reduced blood pressure by 5/3 mm Hg and produced no discernable reduction in the risk of stroke . INTERPRETATION This blood-pressure-lowering regimen reduced the risk of stroke among both hypertensive and non-hypertensive individuals with a history of stroke or transient ischaemic attack . Combination therapy with perindopril and indapamide produced larger blood pressure reductions and larger risk reductions than did single drug therapy with perindopril alone . Treatment with these two agents should now be considered routinely for patients with a history of stroke or transient ischaemic attack , irrespective of their blood pressure",
"Background In the Valsartan Antihypertensive Long-term Use Evaluation ( VALUE ) trial the primary outcome ( cardiac morbidity and mortality ) did not differ between valsartan and amlodipine-based treatment groups , although systolic blood pressure ( SBP ) and diastolic blood pressure reductions were significantly more pronounced with amlodipine . Stroke incidence was non-significantly , and myocardial infa rct ion was significantly lower in the amlodipine-based regimen , whereas cardiac failure was non-significantly lower on valsartan . Objectives The study protocol specified additional analyses of the primary endpoint according to : sex ; age ; race ; geographical region ; smoking status ; type 2 diabetes ; total cholesterol ; left ventricular hypertrophy ; proteinuria ; serum creatinine ; a history of coronary heart disease ; a history of stroke or transient ischemic attack ; and a history of peripheral artery disease . Additional subgroups were isolated systolic hypertension and classes of antihypertensive agents used immediately before r and omization . Methods The 15 245 hypertensive patients participating in VALUE were divided into subgroups according to baseline characteristics . Treatment by subgroup interaction analyses were carried out by a Cox proportional hazard model . Within each subgroup , treatment effects were assessed by hazard ratios and 95 % confidence intervals . Results For cardiac mortality and morbidity , the only significant subgroup by treatment interaction was of sex ( P = 0.016 ) , with the hazard ratio indicating a relative excess of cardiac events with valsartan treatment in women but not in men , but SBP differences in favour of amlodipine were distinctly greater in women . No other subgroup showed a significant difference in the composite cardiac outcome between valsartan and amlodipine-based treatments . For secondary endpoints , a sex-related significant interaction was found for heart failure ( P heart failure with valsartan . Conclusion As in the whole VALUE cohort , in no subgroup of patients were there differences in the incidence of the composite cardiac endpoint with valsartan and amlodipine-based treatments , despite a greater blood pressure decrease in the amlodipine group . The only exception was sex , in which the amlodipine-based regimen was more effective than valsartan in women , but not in men , whereas the valsartan regimen was more effective in preventing cardiac failure in men than in women",
"BACKGROUND Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke . In addition , inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events , including stroke . However , the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established . We evaluated the effects of therapy with an angiotensin-receptor blocker , telmisartan , initiated early after a stroke . METHODS In a multicenter trial involving 20,332 patients who recently had an ischemic stroke , we r and omly assigned 10,146 to receive telmisartan ( 80 mg daily ) and 10,186 to receive placebo . The primary outcome was recurrent stroke . Secondary outcomes were major cardiovascular events ( death from cardiovascular causes , recurrent stroke , myocardial infa rct ion , or new or worsening heart failure ) and new-onset diabetes . RESULTS The median interval from stroke to r and omization was 15 days . During a mean follow-up of 2.5 years , the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group . A total of 880 patients ( 8.7 % ) in the telmisartan group and 934 patients ( 9.2 % ) in the placebo group had a subsequent stroke ( hazard ratio in the telmisartan group , 0.95 ; 95 % confidence interval [ CI ] , 0.86 to 1.04 ; P=0.23 ) . Major cardiovascular events occurred in 1367 patients ( 13.5 % ) in the telmisartan group and 1463 patients ( 14.4 % ) in the placebo group ( hazard ratio , 0.94 ; 95 % CI , 0.87 to 1.01 ; P=0.11 ) . New-onset diabetes occurred in 1.7 % of the telmisartan group and 2.1 % of the placebo group ( hazard ratio , 0.82 ; 95 % CI , 0.65 to 1.04 ; P=0.10 ) . CONCLUSIONS Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke , major cardiovascular events , or diabetes . ( Clinical Trials.gov number , NCT00153062 .",
"BACKGROUND Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction , whether or not they have heart failure . We assessed the role of an angiotensin-converting-enzyme inhibitor , ramipril , in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure . METHODS A total of 9297 high-risk patients ( 55 years of age or older ) who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were r and omly assigned to receive ramipril ( 10 mg once per day orally ) or matching placebo for a mean of five years . The primary outcome was a composite of myocardial infa rct ion , stroke , or death from cardiovascular causes . The trial was a two-by-two factorial study evaluating both ramipril and vitamin E. The effects of vitamin E are reported in a companion paper . RESULTS A total of 651 patients who were assigned to receive ramipril ( 14.0 percent ) reached the primary end point , as compared with 826 patients who were assigned to receive placebo ( 17.8 percent ) ( relative risk , 0.78 ; 95 percent confidence interval , 0.70 to 0.86 ; P rates of death from cardiovascular causes ( 6.1 percent , as compared with 8.1 percent in the placebo group ; relative risk , 0.74 ; P myocardial infa rct ion ( 9.9 percent vs. 12.3 percent ; relative risk , 0.80 ; P stroke ( 3.4 percent vs. 4.9 percent ; relative risk , 0.68 ; P death from any cause ( 10.4 percent vs. 12.2 percent ; relative risk , 0.84 ; P=0.005 ) , revascularization procedures ( 16.3 percent vs. 18.8 percent ; relative risk , 0.85 ; P cardiac arrest ( 0.8 percent vs. 1.3 percent ; relative risk , 0.62 ; P=0.02 ) , [ corrected ] heart failure ( 9.1 percent vs. 11.6 percent ; relative risk , 0.77 ; P complications related to diabetes ( 6.4 percent vs. 7.6 percent ; relative risk , 0.84 ; P=0.03 ) . CONCLUSIONS Ramipril significantly reduces the rates of death , myocardial infa rct ion , and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure",
"Blood pressure and clinical status of 1,736 patients with cerebrovascular disease were observed during 12 months of treatment with nicardipine . The most common diagnoses were chronic cerebral ischemia ( 53.2 % ) , transient ischemic attacks ( TIA ; 25.1 % ) , and cerebral infa rct ( 8.7 % ) ; 50.1 % of patients were classed as hypertensive [ systolic blood pressure ( SBP ) ≥ 160 mm Hg or diastolic blood pressure ( DBP ) ≥ 90 mm Hg ] . Most patients ( 91.2 % ) received a daily dose of 60 mg nicardipine . Additional treatments included diuretics ( 37 % ) , β-blockers ( 11.5 % ) , other antihypertensive drugs ( 15.8 % ) , platelet antiaggregants ( 25.1 % ) , and cardiotonic drugs ( 15.1 % ) . A total of 282 patients ( 16.2 % ) were lost to follow-up , 21 ( 1.2 % ) patients withdrew due to side effects , 32 ( 1.8 % ) died , and 9 ( 0.5 % ) patients had treatment interrupted due to concomitant illness . In the hypertensive subgroup , blood pressure ( SBP/ DBP ) was reduced from a mean baseline value of 175 ± 22/97 ± 14 mm Hg to 152 ± 17/85 ± 11 mm Hg at 3 months and 149 ± 23/81 ± 11 mm Hg after 12 months of treatment . The incidence of TIA or stroke among these patients was reduced from 29 cases ( 3.5 % ) during the first 3 months to 11 cases ( 1.54 % ) during months 4–12 ( p normotensive patients there were 18 ( 2.15 % ) cases during months 1–3 and 13 ( 1.55 % ) cases during months 4–12 ( difference not significant ) . In the 280 patients treated with nicardipine alone , the most frequent side effects during the first month were facial flushing ( 6.8 % ) , gastrointestinal problems ( 5 % ) , dizziness ( 3.2 % ) , headache ( 3.2 % ) , drowsiness ( 3.2 % ) , and hypotension ( 1.1 % ) . Most of these side effects were transient . These results demonstrate that nicardipine lowered blood pressure over the 12 months of observation . This may have contributed to the reduction in the incidence of TIA or stroke among hypertensive patients during months 4–12",
"Post-stroke Antihypertensive Treatment Study ( PATS ) was a r and omized , double-blind and placebo-controlled trial , which aim ed at determining whether antihypertensive treatment could reduce the risk of fatal and nonfatal stroke incidence in patients with a history of stroke or transient ischemic attack ( TIA ) . 5,665 patients were r and omized by a sealed envelope system . Systolic blood pressure ( SBP ) ranged from 80 to 280 mm Hg and diastolic ( DBP ) from 50 to 150 mmHg . The average SBP was 154 mmHg and average DBP 93 mmHg . The mean age was 60 years . Among the patients , women accounted for 28 % . In 71 % the latest stroke was ischemic . Average follow-up approximated to 2 years . The three-year average SBP was 149 mmHg for the placebo group and 144 mmHg for the indapamide treatment group , and the three-year DBP was 89 mmHg and 87 mmHg respectively . The three-year first incidence of fatal and nonfatal stroke was 12.3 per 100 patients placebo treatment and 9.4 per 100 with indapamide . The relative risk by proportional hazards regression analysis was 0.71 ( P = 0.0009 ) . For deaths from all causes , the relative risk was 0.91 . ( P > 0.05 ) . The findings of this trial indicate that in patients with a history of stroke or TIA , blood pressure reduction of 5/2 mmHg with 2.5 mg indapamide reduced the first incidence of fatal and nonfatal stroke by 29 % , with three-year absolute benefit of 29 events per 1000 participants",
"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",
"BACKGROUND Angiotensin-converting-enzyme ( ACE ) inhibitors are effective in reducing the risk of heart failure , myocardial infa rct ion , and death from cardiovascular causes in patients with left ventricular systolic dysfunction or heart failure . ACE inhibitors have also been shown to reduce atherosclerotic complications in patients who have vascular disease without heart failure . METHODS In the Prevention of Events with Angiotensin Converting Enzyme Inhibition ( PEACE ) Trial , we tested the hypothesis that patients with stable coronary artery disease and normal or slightly reduced left ventricular function derive therapeutic benefit from the addition of ACE inhibitors to modern conventional therapy . The trial was a double-blind , placebo-controlled study in which 8290 patients were r and omly assigned to receive either tr and olapril at a target dose of 4 mg per day ( 4158 patients ) or matching placebo ( 4132 patients ) . RESULTS The mean ( + /-SD ) age of the patients was 64+/-8 years , the mean blood pressure 133+/-17/78+/-10 mm Hg , and the mean left ventricular ejection fraction 58+/-9 percent . The patients received intensive treatment , with 72 percent having previously undergone coronary revascularization and 70 percent receiving lipid-lowering drugs . The incidence of the primary end point -- death from cardiovascular causes , myocardial infa rct ion , or coronary revascularization -- was 21.9 percent in the tr and olapril group , as compared with 22.5 percent in the placebo group ( hazard ratio in the tr and olapril group , 0.96 ; 95 percent confidence interval , 0.88 to 1.06 ; P=0.43 ) over a median follow-up period of 4.8 years . CONCLUSIONS In patients with stable coronary heart disease and preserved left ventricular function who are receiving \" current st and ard \" therapy and in whom the rate of cardiovascular events is lower than in previous trials of ACE inhibitors in patients with vascular disease , there is no evidence that the addition of an ACE inhibitor provides further benefit in terms of death from cardiovascular causes , myocardial infa rct ion , or coronary revascularization",
"There is widespread clinical uncertainty about lowering blood pressure in patients with ischaemic cerebrovascular disease . This often manifests as comparatively high thresholds for starting treatment and modest targets in reducing blood pressure . Concern has arisen partly from reports of a J shaped association between blood pressure and recurrent stroke in these patients .1 This relation may , however , be because severe strokes are associated both with a fall in blood pressure2 and independently with a relatively high risk of stroke recurrence , rather than from any adverse effects of low blood pressure itself . If this were true , then people with a history of minor cerebrovascular disease would have direct and continuous relations between usual blood pressure and risk of stroke , as observed in people without cerebrovascular disease.3 Data from",
"Background and Purpose : & bgr;‐Blockers prevent vascular events in patients after myocardial infa rct ion and lower blood pressure , the main risk factor for stroke . Hence , we assessed the effects of atenolol on the occurrence of death from vascular causes , stroke , or myocardial infa rct ion and on blood pressure in patients after a transient ischemic attack or nondisabling ischemic stroke . Methods : In a double‐blind , placebo‐controlled r and omized clinical trial we studied the occurrence of the outcome event death from vascular causes , nonfatal stroke , or nonfatal myocardial infa rct ion and the outcome event fatal or nonfatal stroke as well as blood pressure on follow‐up . A total of 1,473 aspirin‐treated patients with transient ischemic attack or nondisabling ischemic stroke were r and omized to 50 mg atenolol daily or placebo . The mean follow‐up was 2.6 years . Results : Patients on atenolol had a risk of 97/732 ( 13.3 % ) for the combined outcome event versus a risk of 95/741 ( 12.8 % ) for those on placebo ( adjusted hazard ratio , 1.00 ; 95 % confidence interval , 0.76‐1.33 ) . The adjusted hazard ratio for fatal or nonfatal stroke was 0.82 ( 95 % confidence interval , 0.57‐1.19 ) . More patients on & bgr;‐blocker ( 153 ) reported adverse effects than on placebo ( 103 ) . At the first follow‐up visit after r and omization ( median at 4 months ) systolic blood pressure in the atenolol group had dropped by 8.0 mm Hg compared with 2.2 mm Hg in the placebo group ( difference , 5.8 mm Hg ; 95 % confidence interval , 2.9‐8.6 mm Hg ) . For diastolic blood pressure this difference was 2.9 mm Hg ( 95 % confidence interval , 1.5‐4.4 mm Hg ) . Conclusions : Our data neither confirm nor rule out that atenolol prevents important vascular events in patients after transient ischemic attack or nondisabling ischemic stroke , given the modest effect on blood pressure , the restrictions in patient selection , and the limited number of patient‐years . ( Stroke 1993;24:543‐548",
"The Study on COgnition and Prognosis in the Elderly ( SCOPE ) assessed the effect of c and esartan on cardiovascular outcomes in elderly patients with mild to moderate hypertension . Patients were r and omized to c and esartan 8–16 mg daily ( n = 2477 ) or placebo ( n = 2460 ) . Due to extensive add‐on therapy , blood pressure reduction was only about 3/2 mmHg greater in the c and esartan group than in the control group . Nevertheless , non‐fatal stroke was reduced by 28 % ( p = 0.04 ) in the c and esartan group compared to the control group , and there was a non‐significant 11 % reduction in major cardiovascular events ( p = 0.19 ) . This report provides results in pre‐specified subgroups of patients ( age , gender , diabetes , history of stroke , smoking and cardiovascular risk at r and omization ) . Reductions in major cardiovascular events and stroke with c and esartan‐based therapy were indicated in all subgroups . A significant interaction between treatment and subgroups was found for one pair of subgroups only ; the reduction in major cardiovascular events with c and esartan was greater in patients with a previous stroke ( 64 % reduction , p = 0.004 ) than in those without ( 5 % reduction , p>0.20 ) . In conclusion , this analysis indicates consistent favourable effects of c and esartan‐based therapy on major cardiovascular events and stroke across the different subgroups of patients . However , the benefit was particularly pronounced in patients who entered the study with a previous stroke"
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INTRODUCTION AND OBJECTIVES Zinc deficiency has been associated with poor prognosis in chronic liver disease . This systematic review and meta- analysis aim ed to evaluate the role of zinc supplementation in the management of chronic liver diseases . MATERIAL S AND METHODS We search ed MEDLINE , LILACS , EMBASE , and Cochrane CENTRAL data bases from inception to August 2018 . We included r and omized controlled trials evaluating adult patients with chronic liver disease of any etiology receiving zinc supplementation . Studies with other design s or evaluating chronic conditions other than liver disease were excluded . Two review ers independently screened and extracted data from eligible studies . Study quality was assessed using the Cochrane Collaboration 's tool for assessing risk of bias in r and omized studies . RESULTS Of 1315 studies screened , 13 were included . Six assessed chronic hepatitis C treatment , with a relative risk of 0.83 indicating no protective effect of zinc supplementation on the improvement of sustained virological response . Three evaluated response to hepatic encephalopathy treatment , with a relative risk of 0.66 indicating a favorable effect of zinc supplementation on clinical improvement of this condition . Of four studies evaluating the management of cirrhosis , two analyzed the effect of zinc supplementation on serum albumin levels , with no statistical difference between zinc and placebo groups . CONCLUSIONS Clinical trials assessing zinc supplementation in liver diseases do not show benefits in terms of clinical improvement or disease halting . There are possible benefits of zinc supplementation on hepatic encephalopathy , however , this is based on limited evidence . This research question is still open for evaluation in larger , well- design ed , clinical trials
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"OBJECTIVES The effect of long-term oral zinc supplementation , in addition to st and ard therapy ( protein-restricted diet and lactulose ) on recurrent hepatic encephalopathy , was assessed in a double-blind study . METHODS Ninety cirrhotic patients with stable recurrent hepatic encephalopathy , after following a one month period of st and ard therapy , were r and omized to receive oral zinc acetate supplementation ( 600 mg/day ) in addition to st and ard therapy or to continue only st and ard therapy ( a diet containing 0.8 g/kg/day of protein and 90 g/day of lactulose ) for six months . Psychometric tests , NCT ( number correction test ) and PSE ( portal-systemic encephalopathy ) Index , were used to evaluate the degree of hepatic encephalopathy , both at the beginning and the end of each treatment period . RESULTS Oral zinc supplementation in addition to st and ard therapy was able to normalize serum zinc levels . The patients who never showed clinical signs of hepatic encephalopathy during the trial were 88.6 % in zinc-group and 86 % in only st and ard therapy group . Psychometric tests , NCT and PSE Index , were statistically better than basal values either in zinc-group or in only st and ard therapy group . CONCLUSIONS Final values of psychometric tests were better in zinc-group than only st and ard therapy group but the differences were not statistically significant",
"We administered zinc supplementation therapy over three years to patients with chronic hepatitis C and reported and that the aspartate aminotransferase ( AST ) and alanine aminotaransferase ( ALT ) levels decreased , and platelet counts increased , significantly in the group with increased serum zinc concentrations . We are continuing this treatment to clarify the long-term consequences and report here the changes in serum zinc concentrations over seven years and compare the cumulative incidence of hepatocellular carcinoma ( HCC ) . We administered polaprezinc to 32 patients , r and omly selected for zinc therapy ( treatment group ) , while another 30 formed the control group . We measured the serum zinc and albumin concentrations and conducted a prospect i ve study to determine long-term outcomes . The changes and rates of change of serum zinc concentrations after seven years were 76.7 ± 18.2 µg/dl and + 0.302 ± 0.30 % in the treatment group and 56.7 ± 12.4 µg/dl and + 0.033 ± 0.21 % in the control group and had increased significantly ( p = 0.0002 , p = 0.0036 ) . Progression of liver disease seemed to vary , depending on serum albumin concentrations . In the group with baseline serum albumin concentrations of 4.0 g/dl or more , the change and rate of change of serum zinc concentrations increased significantly , and the cumulative incidence of HCC tended to decrease , in the treated group . According to multivariate analysis , the factors that contribute to a reduction in the incidence of HCC are zinc therapy ( risk ratio : 0.113 , 95 % CI : 0.015–0.870 , p = 0.0362 ) , and platelet counts ( 0.766 , 0.594–0.989 , 0.0409 ) . Zinc supplementation therapy seems to improve liver pathology and reduce the incidence of HCC",
"OBJECTIVE To our knowledge , no r and omized study has shown whether zinc replacement therapy is effective for hyperammonemia in liver cirrhosis ; therefore , we performed a double-blind , placebo-controlled trial to examine efficacy and safety of the zinc replacement therapy . METHODS Patients with liver cirrhosis and hyperammonemia ( at or above the institutional reference value ) and hypozincemia ( ≤65 μg/dL ) were enrolled in the outpatient units of the participating institutions and were r and omly divided to receive placebo ( P group ) or zinc acetate preparation at a dose of 3 capsules/d for a total zinc content of 150 mg/d ( Z group ) by the envelope method . Of the 18 enrolled patients , 6 dropped out ; thus , the analyses included 12 patients ( 5 in the P group and 7 in the Z group ) . Variations in blood concentrations of zinc and ammonia as well as liver function test results were compared . RESULTS Blood zinc levels significantly increased in the Z group ( P = 0.0037 ; Friedman test ) but not the P group . Blood ammonia levels significantly decreased in the Z group ( P = 0.0114 ; Friedman test ) but not the P group . The percent change in blood ammonia level also revealed significant reduction at the eighth week in the Z group ( P = 0.0188 : Mann-Whitney test ) . No serious adverse events attributable to the zinc preparation were noted . CONCLUSION Although this study is preliminary and includes a small sample , it is , to our knowledge , the first r and omized controlled trial to show that zinc supplementation for 3 mo seems effective and safe for treating hyperammonemia in liver cirrhosis . Studies with a larger sample size are needed to confirm our findings",
"BACKGROUND The present study aim ed to evaluate the effects of low dose zinc ( Zn ) supplementation on biochemical markers and underlying disease status in non-alcoholic cirrhotic patients . METHODS We enrolled 60 cirrhotic patients in a double-blind , placebo-controlled , r and omized clinical trial . All patients in the interventional group ( n = 30 ) received long-term , low dose Zn supplementation ( 50 mg elemental Zn sulfate daily ) . The control group ( n = 30 ) received placebo ( starch ) . Child-Pugh scores and biochemical markers were assessed for both interventional and control groups at the first day and the end of the 90th day of the interventional period . A per- protocol analysis was performed after excluding all participants who did not receive or complete the r and omized intervention . The mean differences of quantitative variables between and within groups were evaluated by independent sample s t-test and paired- sample s t-test , respectively . SPSS version 13.00 was used for statistical analysis . RESULTS In the initial evaluation , 16 ( 53.30 % ) patients from the interventional group had a Child-Pugh score of 5 - 8 and 14 ( 46 . 70 % ) had a score of 9 - 12 . In the control group 18 ( 60.00 % ) had a Child-Pugh score of 5 - 8 and 12 ( 40.00 % ) scored 9 - 12 . After three months the mean Child-Pugh score in the interventional group showed a significant improvement ( from 6.56 ± 0.21 to 5.72 ± 0.22 , P = 0.001 ) whereas in the control group despite no significant decline , the mean Child-Pugh score increased slightly ( from 6.25 ± 0.27 to 6.67 ± 0.31 , P = 0.14 ) . Zn supplementation significantly decreased copper ( Cu ; P = 0.01 ) and creatinine ( Cr ; P non-alcoholic cirrhotic patients . Zn supplementation produces metabolic effects and trends towards improvements in liver function , hepatic encephalopathy , and nutritional status . Registration ID in I RCT : I RCT 201106122017N4",
"We have evaluated the efficacy of interferon-α ( IFN-α ) plus zinc therapy in hepatitis C patients with genotype 1b , poor responders for IFN alone . Ten patients were injected with 10 MU of IFN-α every day for 4 wk , followed by three times a week for 20 wk ( control group ) . Nine patients took 300 mg of zinc sulfate a day orally during IFN-α therapy ( zinc sulfate group ) , and 15 patients took IFN-α and 150 mg of polaprezinc ( polaprezinc group).On the d 8 of IFN therapy , circadian zinc levels in serum elevated significantly in the polaprezinc group compared to the zinc sulfate group or control group . Serum ALT levels normalized in 73.3 % of the polaprezinc group , 55.6 % of the zinc sulfate group , and 40.0 % of the control group at 6 mo after the end of IFN therapy . Sustained eradication for the hepatitis C virus RNA judged at the end of the 6-mo follow-up period was higher in the polaprezinc group than in the zinc sulfate group ( 53.3 % vs 11.1 % , p ) . No clinical side effects of zinc were observed at the dose used . The data suggest that polaprezinc is expected to increase the therapeutic response of IFN-α for chronic hepatitis C with genotype 1b",
"We evaluated the synergistic effect of zinc supplementation on the response to interferon ( IFN ) therapy in patients with intractable chronic hepatitis C in a pilot study using natural IFN-alpha with or without zinc . No clinical differences were observed between patients treated with IFN alone ( n=40 ) and IFN with polaprezinc ( IFN + Zn , n=35 ) . All patients were positive for HCV genotype Ib and had more than 105 copies of the virus/mL serum . Ten million units of natural IFN-alpha was administered daily for 4 weeks followed by the same dose every other day for 20 weeks . In the IFN + Zn group , patients received an additional dose of 150 mg/day polaprezinc orally throughout the 24-week IFN course . No additional side-effects of polaprezinc were noted but four out of 40 IFN alone treatment and three out of 35 IFN + Zn group withdrew because of side-effects . Complete response ( CR ) was defined as negative HCV RNA in the serum on PCR and normal aminotransferase level 6 months after therapy . Incomplete response ( IR ) was normal liver enzyme and positive serum HCV RNA . Both of them were evaluated at the 6 months after the completion of the treatment . Patients with higher levels of serum HCV ( more than 5 x 105 copies/mL ) had little response in both treatment groups . Patients with moderate amount of HCV ( 105 to 4.99 x 105/mL ) showed high response rates in combination group ( CR : 11/27 , 40.7 % ; CR + IR 15/27 , 64.3 % ) , better than IFN alone ( CR : 2/15 , 18.2 % ; CR + IR : 2/15 , 18.2 % ) . Serum zinc levels were higher in patients with IFN + Zn group than in the IFN group . Our results indicate that zinc supplementation enhances the response to interferon therapy in patients with intractable chronic hepatitis",
"Background : Minimal hepatic encephalopathy ( MHE ) has a far-reaching impact on quality and function ability in daily life and may progress to overt hepatic encephalopathy . There is a synergistic effect between systemic oxidative stress and ammonia that is implicated in the pathogenesis of hepatic encephalopathy . The aim of this study is to investigate the effectiveness of oral supplementation of antioxidants and zinc gluconate on MHE versus lactulose . Methods : Our study included 58 patients with cirrhosis diagnosed as having MHE by neuropsychometric tests , including number connection test part A ( NCT-A ) , digit symbol test ( DST ) and block design tests ( BDTs ) . Patients were r and omized to receive 175 mg zinc gluconate , 50,000 IU vitamin A , 500 mg vitamin C and 100 mg vitamin E once daily plus lactulose , dose 30–60 ml/day for 3 months [ group A ( n = 31 ) ] or initiated and maintained on lactulose dose 30–60 ml/day for 3 months [ group B ( n = 27 ) ] . Neuropsychometric tests and laboratory investigations were repeated after 3 months of therapy . Results : Compared with the baseline neuropsychometric tests , a significant improvement was reported in patients with MHE after 3 months of antioxidant and zinc therapy ( group A ) versus patients with lactulose therapy ( group B ) ( NCT-A , p . Antioxidant and zinc supplementation significantly decreased arterial ammonia level , alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) ( p improved Child – Pugh score in MHE after 3 months of therapy ( p= 0.024 ) . Conclusion : Antioxidant and zinc supplementation can improve MHE in patients with liver cirrhosis",
"OBJECTIVES To evaluate the effects of zinc supplementation on serum zinc and copper levels , and the severity of adverse reactions and virologic responses in chronic hepatitis C patients undergoing interferon (IFN)/ribavirin therapy . DESIGN AND METHODS Forty subjects were r and omly assigned to receive IFN-alpha-2a/ribavirin with or without zinc gluconate for 24 weeks , then a period of 6 months for follow-up . Twenty healthy controls were also enrolled in the study . Blood sample s were collected at different time points during therapy and at 6 months after the completion of therapy and were analyzed for zinc and copper levels . The adverse reactions and the virologic responses were also examined accordingly . RESULTS Serum zinc levels were significantly lower in chronic hepatitis C patients than in healthy controls and further depressed by IFN/ribavirin treatment . However , serum zinc levels in patients were remediable by zinc supplements . No apparent difference was seen in virologic responses between subjects with or without zinc supplements , but certain adverse side effects associated with the zinc therapy were significantly decreased . CONCLUSIONS Zinc supplementation may be a complementary therapy in chronic hepatitis C patients to increase the tolerance to IFN-alpha-2a and ribavirin",
"22 cirrhotic patients with chronic encephalopathy were given oral zinc supplementation or placebo in a double-blind r and omised trial . In the group which received zinc acetate 600 mg a day for 7 days , serum zinc had been restored to normal by day 8 . On day 8 hepatic encephalopathy , as assessed by a trailmaking test , was improved in the supplemented group but not in the placebo group . There was also a significant increase in blood urea nitrogen in the supplemented group . Short-term oral zinc supplementation probably improved hepatic encephalopathy by correcting the zinc deficiency that compromises conversion of ammonia to urea . The duration of this improvement requires further investigation",
"AIM To study the therapeutic effect of interferon ( IFN ) and ribavirin with zinc supplement on patients with chronic hepatitis C viral ( HCV ) infection . METHODS A total of 102 patients confirmed histologically to have chronic HCV infection with genotype 1b and more than 100 KIU/mL of HCV were r and omly assigned to each arm of the study and each received 10 million units of pegylated interferon ( IFN-alpha-2b ) daily for 4 wk followed by the same dose every other day for 20 wk plus ribavirin ( 600 or 800 mg/d depending on body weight ) , with or without polaprezinc ( 150 mg/d ) orally for 24 wk . The primary endpoint was sustained virological response ( SVR ) defined as negative HCV-RNA in the serum 6 mo after treatment . RESULTS There were no differences in the clinical background between the two groups except for more females in the dual therapy group than in the other group ( P SVR was observed in 33.3 % of the triple therapy group and 33.3 % of the dual therapy group . The side effects were almost the same in both groups except for gastrointestinal symptoms , which were less in the triple therapy group ( P=0.019 ) . CONCLUSION Considered together , triple therapy of zinc plus IFN and ribavirin for HCV infection patients with genotype 1b and high viral load is not better than dual therapy except for lower incidence of gastrointestinal side effects",
"INTRODUCTION Zinc deficiency has been reported in patients with both hepatitis C and beta thalassemia major . Zinc supplementation in addition to antiviral therapy of chronic hepatitis C has been accompanied by some success in patients with chronic hepatitis C. OBJECTIVE The aim of the present pilot study is to determine the effect of 30 mg elemental zinc on biochemical and virological response in a population of patients with chronic hepatitis C with beta thalassemia major . MATERIAL S AND METHODS A prospect i ve , double blind , placebo controlled trial included 40 patients being treated with Pegylated interferon Alfa ( Peg IFN-α ) and ribavirin . Biochemical and virological parameters and plasma zinc levels were determined before starting treatment . Patients were r and omly selected to receive either zinc or a placebo in addition to Peg IFN-α and ribavirin for a period of one year . AST , ALT , sustained viral response ( SVR ) , and zinc levels were measured after treatment . Of the original 40 eligible patients , eight withdrawn from the study and 32 patients completed the study ; 16 in the zinc group and 16 in the placebo group . Analysis of the data shows that there is no difference between the two groups in AST , ALT , SVR or zinc level following one year of treatment ( p=0.224 , p=0.616 , p=0.670 , p=0.999 , respectively ) . CONCLUSION The results of this study indicate that using 30 mg/day elemental zinc did not significantly improve the outcome of treatment in thalassemia patients with chronic hepatitis C. In future studies , we recommend trying higher doses zinc in patients with hepatitis C who had beta thalassemia major",
"We investigated the effects of zinc supplementation on clinical observations in chronic hepatitis C patients receiving pegylated interferon ( PEG-IFN ) alpha-2b plus ribavirin combination therapy . Patients were r and omly allocated to receive 150 mg polaprezinc ( zinc group , n=11 ) or no supplement ( control group , n=12 ) daily in addition to PEG-IFN alpha-2b plus ribavirin therapy and 300 mg vitamin E and 600 mg vitamin C supplementation daily for 48 wk . Among the patients who continued treatment , the serum alanine aminotransferase ( ALT ) level at 12 wk in the zinc group was significantly lower than that in the control group . All patients in the zinc group ( 9/9 ) and 67 % ( 8/12 ) of the control patients at 24 wk , and all patients in the zinc group ( 7/7 ) and 60 % ( 6/10 ) of the control patients at 48 wk showed a decrease in serum ALT levels to within the normal range ( 7 - 44 U/L ) . HCV RNA disappeared in all patients ( 7/7 ) in the zinc group and in 8 of 10 control patients at 48 wk . Polaprezinc supplementation decreased plasma thiobarbituric acid reactive substances and prevented the decrease of polyunsaturated fatty acids of erythrocyte membrane phospholipids . No significant differences were observed in the dosage of medicines or other clinical data during the treatment . These observations indicate that polaprezinc supplementation may have induced some antioxidative functions in the liver which result ed in reduced hepatocyte injury during PEG-IFN alpha-2b plus ribavirin therapy",
"A double-blind clinical trial with zinc sulfate , 0.2 g three times daily , and a placebo was performed in 30 patients with biopsy-proven alcoholic liver cirrhosis . The disease was in a stable phase , and none of the patients showed evidence of a decompensated liver function . Parameters of liver function , taste acuity , dark adaptation and of zinc and vitamin A metabolism were followed for six weeks . In the zinc-treated group of 16 patients , serum zinc rose from a normal mean value of 13.3 to 17.4 mumol/l , whereas the mean serum vitamin A level remained practically unaltered within the normal range , 1.89 at the entry and 1.83 mumol/l at the end of the study . Plasma prothrombin and serum alkaline phosphatase levels of the zinc group increased and serum bilirubin and serum carotene decreased significantly . The dark adaptation did not change , but the taste function was significantly improved during zinc treatment . The results indicate that zinc supplementation causes alleviation of certain abnormalities of cirrhotics , which deserves further attention"
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Childhood obesity rates have risen dramatically over the past few decades . Although obesity has been linked to poorer neurocognitive functioning in adults , much less is known about this relationship in children and adolescents . Therefore , we conducted a systematic review to examine the relationship between obesity and obesity-related behaviors with neurocognitive functioning in youth . We review ed articles from 1976 to 2013 using PsycInfo , PubMed , Medline and Google Scholar . Search terms included cognitive function , neurocognitive function/performance , executive function , impulsivity , self-regulation , effortful control , cognitive control , inhibition , delayed gratification , memory , attention , language , motor , visuo-spatial , academic achievement , obesity , overweight , body mass index , waist-hip ratio , adiposity and body fat . Articles were excluded if participants had health problems known to affect cognitive functioning , the study used imaging as the only outcome measure , they were non-peer- review ed dissertations , theses , review papers , commentaries , or they were non-English articles . Sixty-seven studies met inclusion criteria for this review . Overall , we found data that support a negative relationship between obesity and various aspects of neurocognitive functioning , such as executive functioning , attention , visuo-spatial performance , and motor skill . The existing literature is mixed on the effects among obesity , general cognitive functioning , language , learning , memory , and academic achievement . Executive dysfunction is associated with obesity-related behaviors , such as increased intake , disinhibited eating , and less physical activity . Physical activity is positively linked with motor skill . More longitudinal research is needed to determine the directionality of such relationships , to point towards crucial intervention time periods in the development of children , and to inform effective treatment programs
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"Objective : To examine the link between childhood overweight status and elementary school outcomes . Design : Prospect i ve study design : multivariate regression models examining the association between changes in overweight status and school outcomes between kindergarten entry and end of third grade , after controlling for various child , family and school characteristics . Subjects : Nationally representative sample of US children who entered kindergarten in 1998 , with longitudinal data on body mass index ( BMI ) and school outcomes at kindergarten entry and end of third grade . Measurements : Wide range of elementary school outcomes collected in each wave including academic achievement ( math and reading st and ardized test scores ) ; teacher reported internalizing and externalizing behavior problems ( BP ) , social skills ( self-control , interpersonal skills ) and approaches to learning ; school absences ; and grade repetition . Measurements of height and weight in each wave were used to compute BMI and indicators of overweight status based on CDC growth charts . A rich set of control variables capturing child , family , and school characteristics . Results : Moving from not-overweight to overweight between kindergarten entry and end of third grade was significantly associated ( P reductions in test scores , and teacher ratings of social-behavioral outcomes and approaches to learning among girls . However , this link was mostly absent among boys , with two exceptions – boys who became overweight had significantly fewer externalizing BPs ( P absences from school compared to boys who remained normal weight . Being always-overweight was associated with more internalizing BP among girls but fewer externalizing BPs among boys . Conclusion : Change in overweight status during the first 4 years in school is a significant risk factor for adverse school outcomes among girls but not boys . Girls who become overweight during the early school years and those who start school being overweight and remain that way may need to be monitored carefully",
"Inhibitory control and performance monitoring are critical executive functions of the human brain . Lesion and imaging studies have shown that the inferior frontal cortex plays an important role in inhibition of inappropriate response . In contrast , specific brain areas involved in error processing and their relation to those implicated in inhibitory control processes are unknown . In this study , we used a r and om effects model to investigate error‐related brain activity associated with failure to inhibit response during a Go/NoGo task . Error‐related brain activation was observed in the rostral aspect of the right anterior cingulate ( BA 24/32 ) and adjoining medial prefrontal cortex , the left and right insular cortex and adjoining frontal operculum ( BA 47 ) and left precuneus/posterior cingulate ( BA 7/31/29 ) . Brain activation related to response inhibition and competition was observed bilaterally in the dorsolateral prefrontal cortex ( BA 9/46 ) , pars triangularis region of the inferior frontal cortex ( BA 45/47 ) , premotor cortex ( BA 6 ) , inferior parietal lobule ( BA 39 ) , lingual gyrus and the cau date , as well as in the right dorsal anterior cingulate cortex ( BA 24 ) . These findings provide evidence for a distributed error processing system in the human brain that overlaps partially , but not completely , with brain regions involved in response inhibition and competition . In particular , the rostal anterior cingulate and posterior cingulate/precuneus as well as the left and right anterior insular cortex were activated only during error processing , but not during response competition , inhibition , selection , or execution . Our results also suggest that the brain regions involved in the error processing system overlap with brain areas implicated in the formulation and execution of articulatory plans . Hum . Brain Mapping 12:131–143 , 2001 . © 2001 Wiley‐Liss ,",
"OBJECTIVES To determine if limited ability to delay gratification ( ATDG ) at age 4 years is independently associated with an increased risk of being overweight at age 11 years and to assess confounding or moderation by child body mass index z score at 4 years , self-reported maternal expectation of child ATDG for food , and maternal weight status . DESIGN Longitudinal prospect i ve study . SETTING Ten US sites . PARTICIPANTS Participants in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development . Main Exposure Ability to delay gratification at 4 years , measured as pass or fail on a vali date d task . OUTCOME MEASURES Overweight at 11 years , defined as a body mass index greater than or equal to the 85th percentile based on measured weight and height . RESULTS Of 805 children , 47 % failed the ATDG task . Using multiple logistic regression , children who failed the ATDG task were more likely to be overweight at 11 years ( relative risk , 1.29 ; 95 % confidence interval , 1.06 - 1.58 ) , independent of income to needs ratio . Body mass index z score at 4 years and maternal expectation of child ATDG for food did not alter the association , but maternal weight status reduced the association significantly . CONCLUSIONS Children with limited ATDG at age 4 years were more likely to be overweight at age 11 years , but the association was at least partially explained by maternal weight status . Further underst and ing of the association between the child 's ATDG and maternal and child weight status may lead to more effective obesity intervention and prevention programs",
"The purpose of this study was to investigate the associations between obesity and motor coordination ability in Taiwanese children with and without developmental coordination disorder ( DCD ) . 2029 children ( 1078 boys , 951 girls ) aged nine to ten years were chosen r and omly from 14 elementary schools across Taiwan . We used bioelectrical impedance analysis to measure percentage of body fat ( PBF ) and the Movement Assessment Battery for Children test ( MABC test ) to evaluate the motor coordination ability . Using cut-off points based on PBF from past studies , boys and girls were divided into obese , overweight and normal-weight groups , respectively . In boys , total impairment scores and scores on balance subtest in the MABC were significantly higher in the obese and overweight groups when compared against the normal-weight group . Girls in the obese and the overweight groups had higher balance impairment scores than those of the normal-weight group . Among boys , the prevalence of obesity was highest in the DCD group , when compared to the borderline DCD and TD boys . A higher percentage of DCD girls were overweight and obese than TD girls . Obesity may be associated with poor motor coordination ability among boys and girls , and particularly in relation to balance ability . Children with DCD may have a higher risk to be overweight or obese in Taiwan",
"We report 10-year treatment outcomes for obese children in 4 r and omized treatment studies . At 10 years , 34 % decreased percentage overweight by 20 % or more , and 30 % were not obese . Significant effects were observed when parents and children were targeted and reinforced for weight loss in comparison with nontargeted controls and for children given lifestyle or aerobic exercise in comparison with a calisthenics control . Thirty-four percent of the variance in change in percentage overweight was predicted from sex , baseline percentage overweight , self-monitoring weight , meals eaten at home , and family and friends ' support for eating and exercise . Results show long-term changes in children depend on the treatment , and evidence converges on the importance of the family and other sources of support for eating and activity change",
"Obese ( n = 20 ) and normal weight ( n = 20 ) children ( 8 - 11 years ) were compared using the delay of gratification paradigm . All children were asked to choose between an immediate reward or a larger delayed ( one day ) reward . Half the children were offered an edible incentive and half a non-edible incentive . Results showed that the obese choose immediate rewards more often than normals only when the incentive was edible . This suggests that deficits in delay of gratification shown by obese children are not generalized dispositions but are specific to food . A second aspect of the study examined preference for food vs non-food items and activities . Normals showed a much stronger preference for non-food items , nutritious foods and non-food related activities than the obese . This suggests that the deficits in delay of gratification shown by the obese children for food related items may be due to the stronger incentive value of these items for them",
"Exergames are videogames that require gross motor activity , thereby combining gaming with physical activity . This study examined the role of competitive versus cooperative exergame play on short-term changes in executive function skills , following a 10-week exergame training intervention . Fifty-four low-income overweight and obese African American adolescents were r and omly assigned to a competitive exergame condition , a cooperative exergame condition , or a no-play control group . Youths in the competitive exergame condition improved in executive function skills more than did those in the cooperative exergame condition and the no-play control group . Weight loss during the intervention was also significantly positively correlated with improved executive function skills . The findings link competitive exergame play to beneficial cognitive outcomes for at-risk ethnic minority adolescents",
"Background Over the last decades , a decline in motor skills and in physical activity and an increase in obesity has been observed in children . However , there is a lack of data in young children . We tested if differences in motor skills and in physical activity according to weight or gender were already present in 2- to 4-year-old children . Methods Fifty-eight child care centers in the French part of Switzerl and were r and omly selected for the Youp'là bouge study . Motor skills were assessed by an obstacle course including 5 motor skills , derived from the Zurich Neuromotor Assessment test . Physical activity was measured with accelerometers ( GT1 M , Actigraph , Florida , USA ) using age-adapted cut-offs . Weight status was assessed using the International Obesity Task Force criteria ( healthy weight vs overweight ) for body mass index ( BMI ) . Results Of the 529 children ( 49 % girls , 3.4 ± 0.6 years , BMI 16.2 ± 1.2 kg/m2 ) , 13 % were overweight . There were no significant weight status-related differences in the single skills of the obstacle course , but there was a trend ( p = 0.059 ) for a lower performance of overweight children in the overall motor skills score . No significant weight status-related differences in child care-based physical activity were observed . No gender-related differences were found in the overall motor skills score , but boys performed better than girls in 2 of the 5 motor skills ( p ≤ 0.04 ) . Total physical activity as well as time spent in moderate-vigorous and in vigorous activity during child care were 12 - 25 % higher and sedentary activity 5 % lower in boys compared to girls ( all p in global motor skills . However , in accordance to data in older children , child care-based physical activity was higher in boys compared to girls . These results are important to consider when establishing physical activity recommendations or targeting health promotion interventions in young children",
"OBJECTIVE This present study examined time spent in the target heart zone ( THZ ) and its relationship to tasks requiring variable amounts of executive control function in prepubescent children participating in a 9-month r and omized controlled physical activity program . METHODS A sample of 59 participants performed the Stroop Color-Word Test and the Comprehensive Trail Making Test cognitive assessment s. Heart rate data were collected during participation in the physical activity program using E600 heart rate monitors ( Polar , Finl and ) . RESULTS There was a significant difference , F(1 , 58)=7.44 , p relative VO2max , but not absolute ( p=.69 ) or percent VO2max ( p=.73 ) . Regression analysis identified KBIT , age , and mean time above the THZ as significant predictors of performance in the Stroop Color-Word condition , F(1 , 56)=5.21 , p=.02 . KBIT and mean time above the THZ were significant predictors for Trails B , F(1 , 56)=7.60 . CONCLUSIONS These results suggest that heart rate , as a measure of physical activity intensity , should be closely monitored during research that is intended to make inferences about its effects on cognitive performance as participation in vigorous activities may have specific benefits over lower intensities among prepubescent children",
"OBJECTIVE Deficits in executive functioning , including working memory ( WM ) deficits , have been suggested to be important in attention-deficit/hyperactivity disorder ( ADHD ) . During 2002 to 2003 , the authors conducted a multicenter , r and omized , controlled , double-blind trial to investigate the effect of improving WM by computerized , systematic practice of WM tasks . METHOD Included in the trial were 53 children with ADHD ( 9 girls ; 15 of 53 inattentive subtype ) , aged 7 to 12 years , without stimulant medication . The compliance criterion ( > 20 days of training ) was met by 44 subjects , 42 of whom were also evaluated at follow-up 3 months later . Participants were r and omly assigned to use either the treatment computer program for training WM or a comparison program . The main outcome measure was the span-board task , a visuospatial WM task that was not part of the training program . RESULTS For the span-board task , there was a significant treatment effect both post-intervention and at follow-up . In addition , there were significant effects for secondary outcome tasks measuring verbal WM , response inhibition , and complex reasoning . Parent ratings showed significant reduction in symptoms of inattention and hyperactivity/impulsivity , both post-intervention and at follow-up . CONCLUSIONS This study shows that WM can be improved by training in children with ADHD . This training also improved response inhibition and reasoning and result ed in a reduction of the parent-rated inattentive symptoms of ADHD",
"Objective To assess whether a physical activity intervention reduces body mass index in young children . Design Cluster r and omised controlled single blinded trial over 12 months . Setting Thirty six nurseries in Glasgow , Scotl and . Participants 545 children in their preschool year , mean age 4.2 years ( SD 0.2 ) at baseline . Intervention Enhanced physical activity programme in nursery ( three 30 minute sessions a week over 24 weeks ) plus home based health education aim ed at increasing physical activity through play and reducing sedentary behaviour . Main outcome measure Body mass index , expressed as a st and ard deviation score relative to UK 1990 reference data . Secondary measures were objective ly measured physical activity and sedentary behaviour ; fundamental movement skills ; and evaluation of the process . Results Group allocation had no significant effect on the primary outcome measure at six and 12 months or on measures of physical activity and sedentary behaviour by accelerometry . Children in the intervention group had significantly higher performance in movement skills tests than control children at six month follow-up ( P=0.0027 ; 95 % confidence interval 0.3 to 1.3 ) after adjustment for sex and baseline performance . Conclusions Physical activity can significantly improve motor skills but did not reduce body mass index in young children in this trial . Trial registration Current Controlled Trials IS RCT N36363490",
"OBJECTIVE This experiment tested the hypothesis that exercise would improve executive function . DESIGN Sedentary , overweight 7- to 11-year-old children ( N = 171 , 56 % girls , 61 % Black , M ± SD age = 9.3 ± 1.0 years , body mass index [ BMI ] = 26 ± 4.6 kg/m² , BMI z-score = 2.1 ± 0.4 ) were r and omized to 13 ± 1.6 weeks of an exercise program ( 20 or 40 min/day ) , or a control condition . MAIN OUTCOME MEASURES Blinded , st and ardized psychological evaluations ( Cognitive Assessment System and Woodcock-Johnson Tests of Achievement III ) assessed cognition and academic achievement . Functional MRI measured brain activity during executive function tasks . RESULTS Intent to treat analysis revealed dose-response benefits of exercise on executive function and mathematics achievement . Preliminary evidence of increased bilateral prefrontal cortex activity and reduced bilateral posterior parietal cortex activity attributable to exercise was also observed . CONCLUSION Consistent with results obtained in older adults , a specific improvement on executive function and brain activation changes attributable to exercise were observed . The cognitive and achievement results add evidence of dose-response and extend experimental evidence into childhood . This study provides information on an educational outcome . Besides its importance for maintaining weight and reducing health risks during a childhood obesity epidemic , physical activity may prove to be a simple , important method of enhancing aspects of children 's mental functioning that are central to cognitive development . This information may persuade educators to implement vigorous physical activity ",
"OBJECTIVE To examine the extent to which self-regulatory capacities , measured behaviorally at ages 3 and 5 years , were linked to rapid weight gain in children from age 3 to 12 years . Self-regulation failure , or the inability to control an impulse or behavior , has been implicated as a mechanism in the development of overweight . DESIGN Prospect i ve longitudinal cohort study . SETTING Home and laboratory-based setting s in 10 sites across the United States . PARTICIPANTS Data were drawn from 1061 children as part of the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development . Main Exposure Self-regulatory capacity was measured in 2 behavioral protocol s ; children participated in a self-control procedure at age 3 years and a delay of gratification procedure at age 5 years . MAIN OUTCOME MEASURES Age- and sex-specific body mass index ( BMI ) z scores were calculated based on measured BMI at 6 points . RESULTS Mixed-modeling analyses were used to examine differences in the rate of weight gain over time based on the extent to which children exhibited the ability to self-regulate in the behavioral procedures . Compared with children who showed high self-regulation in both behavioral protocol s at ages 3 and 5 years , children who exhibited a compromised ability to self-regulate had the highest BMI z scores at each point and the most rapid gains in BMI z scores over the 9-year period . Effects of pubertal status were also noted for girls . CONCLUSION Self-regulation failure in early childhood may predispose children to excessive weight gain through early adolescence",
"For obese children behavioral treatment results in only small changes in relative weight and frequent relapse . The current study investigated the effects of an Executive Functioning ( EF ) training with game-elements on weight loss maintenance in obese children , over and above the care as usual in an inpatient treatment program . Forty-four children ( aged 8 - 14 years ) who were in the final months of a 10-months inpatient treatment program in a medical paediatric centre were r and omized to either the 6 week EF-training condition or to a care as usual only control group . The EF-training consisted of a 25-session training of inhibition and working memory . Treatment outcomes were child performances on cognitive tasks of inhibition and working memory and childcare worker ratings on EF-symptoms as well as weight loss maintenance after leaving the clinic . Children in the EF-training condition showed significantly more improvement than the children in the care as usual only group on the working memory task as well as on the childcare worker reports of working memory and meta-cognition . They were also more capable to maintain their weight loss until 8 weeks post-training . This study shows promising evidence for the efficacy of an EF-training as weight stabilization intervention in obese children",
"BACKGROUND This study examined associations of fitness and fatness with cognitive processes , academic achievement , and behavior , independent of demographic factors , at the baseline of an exercise trial . METHODS Overweight , sedentary but otherwise healthy 7 - 11 year olds ( N=170 ) participated in a study of health , cognition and achievement in the Augusta , GA area from 2003 - 2006 . Children underwent evaluations of fatness and fitness , psychological assessment s of cognition and academic achievement , and behavior ratings by parents and teachers . Partial correlations examined associations of fitness and fatness with cognitive and achievement scores and behavior ratings , controlling for demographic factors . RESULTS Fitness was associated with better cognition , achievement and behavior , and fatness with worse scores . Specifically , executive function , mathematics and reading achievement , and parent ratings of child behavior were related to fitness and fatness . Teacher ratings were related to fitness . CONCLUSION These results extend prior studies by providing reliable , st and ardized measures of cognitive processes , achievement , and behavior in relation to detailed measures of fitness and fatness . However , cross-sectional associations do not necessarily indicate that improving one factor , such as fatness or fitness , will result in improvements in factors that were associated with it . Thus , r and omized clinical trials are necessary to determine the effects of interventions",
"OBJECTIVE Differences in fundamental movement skills and self-perceptions of physical ability and physical appearance of overweight and non-overweight children were investigated . METHOD Overweight ( n = 89 , mean age = 8.75 ± 1.4 years , BMI z-score = 2.22 , SD = 0.46 , 46 % male ) and non-overweight ( n = 27 , mean age = 8.25 ± 1.5 years , BMI z-score = 0.03 , SD = 0.73 , 62.1 % male ) participants enrolled in the KOALA ( Kinder Overweight Activity Lifestyle Actions ) project were included . The overall objective of the KOALA project was to determine in a r and omized controlled trial the effect of a Triple P ( Positive Parenting Program ) , and a family ' Eat Well Be Active ' Scouts Camp program on BMI in overweight children . Baseline between-group differences on measures of fundamental movement skills and self-concept perceptions were analyzed using independent sample s t-tests . Relationships between BMI and these variables were investigated with multiple linear regression . RESULTS Overweight children had lower scores on Bruninks-Oseretsky Test of Motor Performance-2 subtests ( Bilateral Coordination , Upper Limb Coordination , Strength , Balance , and Running Speed and Agility ) , and Physical abilities self-concept than non-overweight children . CONCLUSIONS Children who were overweight had significant fundamental movement skill difficulties , as well as having poorer Physical abilities self-concept perceptions compared to non-overweight children . The association between increasing BMI and poor performance of gross motor tasks has potential implication s for physical activity participation . Future research is needed to determine if fundamental movement skill difficulties and low physical ability self-concept are predisposing factors for children who are overweight or associated outcomes",
"Objective : The success of treatment for pediatric obesity is variable and often unsatisfactory . This study eluci date s the influence of inattention and hyperactivity/impulsivity on short- and long-term weight loss and maintenance after outpatient treatment . Methods : We included 8- to 16-year-old overweight and obese participants treated in 17 multidisciplinary outpatient treatment centers in a nationwide observational study . All treatment centers that reported long-term ( 1-year ) follow-up weight data of at least 60 % of the participants were included . At the beginning and end of treatment and at 1 year follow-up weight and height were measured at the center . Inattention and hyperactivity/impulsivity were assessed with the hyperactivity/inattention subscale ( HI ) of the parent-rated Strengths and Difficulty Question naire ( SDQ ) . General linear models were used with the st and ard deviation scores of the BMI ( BMI -SDS ) as dependent variable and HI scores as main independent variable adjusting for age , sex , baseline BMI -SDS , and center . Results : 394 participants were included ( 57 % female , age : 11.7± 2.0 years , baseline BMI -SDS 2.32 ±.46 kg/m2 ) . HI scores were significantly associated with short- and long-term BMI -SDS ( p higher baseline HI scores predicting less weight loss . Conclusions : Our results indicate that inattention and hyperactivity/impulsivity are linearly associated with reduced short- and long-term weight loss . Implication s for treatment are discussed",
"The aim of this study was to explore the effects of a multidisciplinary behavioral intervention including cognitive behavioral therapy , structured physical activity , and dietary counseling on impulsive personality and cognitive skills and subsequent BMI loss in excess weight adolescents . Forty-two adolescents with excess weight ( 14 males and 28 females , range 12–17 years ) , as defined by the International Obesity Task Force Criteria , participated in our study . We used a longitudinal observational design with two assessment s : before and after treatment . We collected baseline measures of impulsive personality ( UPPS-P scale ) , cognitive performance ( letter number sequencing , Stroop and Iowa gambling task ) , and biometric parameters . After 12 weeks of intervention , parallel measures were used to determine whether treatment-induced changes in impulsivity and cognition predicted changes in BMI . BMI showed a statistically significant reduction after treatment [ from mean ( SD ) 29.36 ( 4.51 ) to 27.31 ( 4.41 ) , Cohen ’s d=0.5 ] . Greater reductions in negative urgency ( negative-emotion-driven impulsivity ) and greater improvement in cognitive inhibitory control skills were associated with greater reductions in BMI . Because the design was correlational and lacked a control group , future studies should clarify whether these associations reflect a causal effect or just overlapping improvements associated with a third variable ( e.g. increases in attention procurement or motivation )",
"The global epidemic of obesity and physical inactivity may have detrimental implication s for young people ’s cognitive function and academic achievement . This prospect i ve study investigated whether childhood motor function predicts later academic achievement via physical activity , fitness , and obesity . The study sample included 8,061 children from the Northern Finl and Birth Cohort 1986 , which contains data about parent-reported motor function at age 8 y and self-reported physical activity , predicted cardiorespiratory fitness ( cycle ergometer test ) , obesity ( body weight and height ) , and academic achievement ( grade s ) at age 16 y. Structural equation models with unst and ardized ( B ) and st and ardized ( β ) coefficients were used to test whether , and to what extent , physical activity , cardiorespiratory fitness , and obesity at age 16 mediated the association between childhood motor function and adolescents ’ academic achievement . Physical activity was associated with a higher grade -point average , and obesity was associated with a lower grade -point average in adolescence . Furthermore , compromised motor function in childhood had a negative indirect effect on adolescents ’ academic achievement via physical inactivity ( B = –0.023 , 95 % confidence interval = –0.031 , –0.015 ) and obesity ( B = –0.025 , 95 % confidence interval = –0.039 , –0.011 ) , but not via cardiorespiratory fitness . These results suggest that physical activity and obesity may mediate the association between childhood motor function and adolescents ’ academic achievement . Compromised motor function in childhood may represent an important factor driving the effects of obesity and physical inactivity on academic underachievement"
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There is a need for easily accessible tuberculosis unit cost data , as well as an underst and ing of the variability of methods used and reporting st and ards of that data . The aim of this systematic review was to descriptively review papers reporting tuberculosis unit costs from a healthcare provider perspective looking at method ological variation ; to assess quality using a study quality rating system and machine learning to investigate the indicators of reporting quality ; and to identify the data gaps to inform st and ardised tuberculosis unit cost collection and consistent principles for reporting going forward . We search ed grey and published literature in five sources and eight data bases , respectively , using search terms linked to cost , tuberculosis and tuberculosis health services including tuberculosis treatment and prevention . For inclusion , the papers needed to contain empirical unit cost estimates for tuberculosis interventions from low- and middle-income countries , with reference years between 1990 and 2018 . A total of 21,691 papers were found and screened in a phased manner . Data were extracted from the eligible papers into a detailed Microsoft Excel tool , extensively cleaned and analysed with R software ( R Project , Vienna , Austria ) using the user interface of RStudio . A study quality rating was applied to the review ed papers based on the inclusion or omission of a selection of variables and their relative importance . Following this , machine learning using a recursive partitioning method was utilised to construct a classification tree to assess the reporting quality . This systematic review included 103 provider perspective papers with 627 unit costs ( costs not presented here ) for tuberculosis interventions among a total of 140 variables . The interventions covered were active , passive and intensified case finding ; tuberculosis treatment ; above-service costs ; and tuberculosis prevention . Passive case finding is the detection of tuberculosis cases where individuals self-identify at health facilities ; active case finding is detection of cases of those not in health facilities , such as through outreach ; and intensified case finding is detection of cases in high-risk population s. There was heterogeneity in some of the reported methods used such cost allocation , amortisation and the use of top-down , bottom-up or mixed approaches to the costing . Uncertainty checking through sensitivity analysis was only reported on by half of the papers ( 54 % ) , while purposive and convenience sampling was reported by 72 % of papers . Machine learning indicated that reporting on ‘ Intervention ’ ( in particular ) , ‘ Urbanicity ’ and ‘ Site Sampling ’ , were the most likely indicators of quality of reporting . The largest data gap identified was for tuberculosis vaccination cost data , the Bacillus Calmette – Guérin ( BCG ) vaccine in particular . There is a gap in available unit costs for 12 of 30 high tuberculosis burden countries , as well as for the interventions of above-service costs , tuberculosis prevention , and active and intensified case finding . Variability in the methods and reporting used makes comparison difficult and makes it hard for decision makers to know which unit costs they can trust . The study quality rating system used in this review as well as the classification tree enable focus on specific reporting aspects that should improve variability and increase confidence in unit costs . Research ers should endeavour to be explicit and transparent in how they cost interventions following the principles as laid out in the Global Health Cost Consortium ’s Reference Case for Estimating the Costs of Global Health Services and Interventions , which in turn will lead to repeatability , comparability and enhanced learning from others
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"Objective : In Botswana , a 36-month course of isoniazid treatment of latent tuberculosis ( TB ) infection [ isoniazid preventive therapy ( IPT ) ] was superior to 6-month IPT in reducing TB and death in persons living with HIV ( PLHIV ) , having positive tuberculin skin tests ( TSTs ) but not in those with negative TST . We examined the cost-effectiveness of IPT in Botswana , where antiretroviral therapy ( ART ) is widely available . Design : Using a decision-analytic model , we determined the incremental cost-effectiveness of strategies for reducing TB and death in 10,000 PLHIV over 36 months . Methods : IPT for 6 months and provision of ART if CD4 + lymphocyte count Botswana policy ) was compared with 6 alternative strategies that varied the use of IPT , TST , and ART for CD4 + count thresholds , including CD4 + IPT of 36 months for TST-positive PLHIV with ART for CD4 + TB cases for an additional cost of $ 1612 per case averted and result ed in 80 fewer deaths for an additional $ 2418 per death averted compared with provision of 6-month IPT to TST-positive PLHIV who received ART for CD4 + lower incremental effectiveness at higher cost . These findings remained consistent in sensitivity analyses . Conclusions : A strategy of treating PLHIV who have positive TST with 36-month IPT is more cost effective for reducing both TB and death compared with providing IPT without a TST , providing only 6-month IPT , or exp and ing ART eligibility without IPT",
"Background Identifying new approaches to tuberculosis treatment that are effective and put less dem and to meagre health re sources is important . One such approach is community based direct observed treatment ( DOT ) . The purpose of the study was to determine the cost and cost effectiveness of health facility and community based directly observed treatment of tuberculosis in an urban setting in Tanzania . Methods Two alternative strategies were compared : health facility based directly observed treatment by health personnel and community based directly observed treatment by treatment supervisors . Costs were analysed from the perspective of health services , patients and community in the year 2002 in US $ using st and ard methods . Treatment outcomes were obtained from a r and omised-controlled trial which was conducted alongside the cost study . Smear positive , smear negative and extra-pulmonary TB patients were included . Cost-effectiveness was calculated as the cost per patient successfully treated . Results The total cost of treating a patient with conventional health facility based DOT and community based DOT were $ 145 and $ 94 respectively . Community based DOT reduced cost by 35 % . Cost fell by 27 % for health services and 72 % for patients . When smear positive and smear negative patients were considered separately , community DOT was associated with 45 % and 19 % reduction of the costs respectively . Patients used about $ 43 to follow their medication to health facility which is equivalent to their monthly income . Indirect costs were as important as direct costs , contributing to about 49 % of the total patient 's cost . The main reason for reduced cost was fewer number of visits to the TB clinic . Community based DOT was more cost-effective at $ 128 per patient successfully treated compared to $ 203 for a patient successfully treated with health facility based DOT . Conclusion Community based DOT presents an economically attractive option to complement health facility based DOT . This is particularly important in setting s where TB clinics are working beyond capacity under limited re sources",
"Early , efficient and inexpensive methods for the detection of pulmonary tuberculosis are urgently needed for effective patient management as well as to interrupt transmission . These methods to detect M. tuberculosis in a timely and affordable way are not yet widely available in re source -limited setting s. In a developing-country setting , we prospect ively evaluated two methods for culturing and detecting M. tuberculosis in sputum . Sputum sample s were cultured in liquid assay ( micro broth culture ) in microplate wells and growth was detected by microscopic observation , or in Löwenstein – Jensen ( LJ ) solid media where growth was detected by visual inspection for colonies . Sputum sample s were collected from 321 tuberculosis ( TB ) suspects attending Bug and o Medical Centre , in Mwanza , Tanzania , and were cultured in parallel . Pulmonary tuberculosis cases were diagnosed using the American Thoracic Society diagnostic st and ards . There were a total of 200 ( 62.3 % ) pulmonary tuberculosis cases . Liquid assay with microscopic detection detected a significantly higher proportion of cases than LJ solid culture : 89.0 % ( 95 % confidence interval [ CI ] , 84.7 % to 93.3 % ) versus 77.0 % ( 95 % CI , 71.2 % to 82.8 % ) ( p = 0.0007 ) . The median turn around time to diagnose tuberculosis was significantly shorter for micro broth culture than for the LJ solid culture , 9 days ( interquartile range [ IQR ] 7–13 ) , versus 21 days ( IQR 14–28 ) ( p The cost for micro broth culture ( labor inclusive ) in our study was US $ 4.56 per sample , versus US $ 11.35 per sample for the LJ solid culture . The liquid assay ( micro broth culture ) is an early , feasible , and inexpensive method for detection of pulmonary tuberculosis in re source limited setting",
"Summary Background In 2010 a new diagnostic test for tuberculosis , Xpert MTB/RIF , received a conditional programmatic recommendation from WHO . Several model-based economic evaluations predicted that Xpert would be cost-effective across sub-Saharan Africa . We investigated the cost-effectiveness of Xpert in the real world during national roll-out in South Africa . Methods For this real-world cost analysis and economic evaluation , we applied extensive primary cost and patient event data from the XTEND study , a pragmatic trial examining Xpert introduction for people investigated for tuberculosis in 40 primary health facilities ( 20 clusters ) in South Africa enrolled between June 8 , and Nov 16 , 2012 , to estimate the costs and cost per disability-adjusted life-year averted of introducing Xpert as the initial diagnostic test for tuberculosis , compared with sputum smear microscopy ( the st and ard of care ) . Findings The mean total cost per study participant for tuberculosis investigation and treatment was US$ 312·58 ( 95 % CI 252·46–372·70 ) in the Xpert group and $ 298·58 ( 246·35–350·82 ) in the microscopy group . The mean health service ( provider ) cost per study participant was $ 168·79 ( 149·16–188·42 ) for the Xpert group and $ 160·46 ( 143·24–177·68 ) for the microscopy group of the study . Considering uncertainty in both cost and effect using a wide range of willingness to pay thresholds , we found less than 3 % probability that Xpert introduction improved the cost-effectiveness of tuberculosis diagnostics . Interpretation After analysing extensive primary data collection during roll-out , we found that Xpert introduction in South Africa was cost-neutral , but found no evidence that Xpert improved the cost-effectiveness of tuberculosis diagnosis . Our study highlights the importance of considering implementation constraints , when predicting and evaluating the cost-effectiveness of new tuberculosis diagnostics in South Africa . Funding Bill & Melinda Gates Foundation",
"Objective : Initiation of antiretroviral therapy ( ART ) during tuberculosis ( TB ) treatment improves survival in TB-HIV coinfected patients . In patients with CD4 + counts , there is a substantial clinical and survival benefit of early ART initiation . The purpose of this study was to assess the costs and cost-effectiveness of starting ART at various time points during TB treatment in patients with CD4 + counts ≥50 cells per cubic millimeter . Methods : In the SAPiT trial , 642 HIV-TB coinfected patients were r and omized to 3 arms : receiving ART within 4 weeks of starting TB treatment ( early treatment arm ; Arm-1 ) , after the intensive phase of TB treatment ( late treatment arm ; Arm-2 ) , or after completing TB treatment ( sequential arm ; Arm-3 ) . Direct health care costs were measured from a provider perspective using a micro-costing approach . The incremental cost per death averted was calculated using the trial outcomes . Results : For patients with CD4 + count ≥50 cells per cubic millimeter , median monthly variable costs per patient were US $ 116 , US $ 113 , and US $ 102 in Arm-1 , Arm-2 and Arm-3 , respectively . There were 12 deaths in 177 patients in Arm-1 , 8 deaths in 180 patients in the Arm-2 , and 19 deaths in 172 patients in Arm-3 . Although the costs were lower in Arm-3 , it had a substantially higher mortality rate . The incremental cost per death averted associated with moving from Arm-3 to Arm-2 was US $ 4199 . There was no difference in mortality between Arm-1 and Arm-2 , but Arm-1 was slightly more expensive . Conclusions : Initiation of ART after the completion of the intensive phase of TB treatment is cost-effective for patients with CD4 + counts ≥50 cells per cubic millimeter",
"In many high-risk population s , access to tuberculosis ( TB ) diagnosis and treatment is limited and pockets of high prevalence persist . We estimated the cost-effectiveness of an extensive active case finding program in areas of Cambodia where TB notifications and household poverty rates are highest and access to care is restricted . Thirty operational health districts with high TB incidence and household poverty were r and omized into intervention and control groups . In intervention operational health districts , all household and symptomatic neighborhood contacts of registered TB patients of the past two years were encouraged to attend screening at mobile centers . In control districts , routine passive case finding activities continued . The program screened more than 35,000 household and neighborhood contacts and identified 810 bacteriologically confirmed cases . The cost-effectiveness analysis estimated that in these cases the reduction in mortality from 14 % to 2 % would result in a cost per daily adjusted life year averted of $ 330 , suggesting that active case finding was highly cost-effective",
"This study determined the costs associated with tuberculosis ( TB ) diagnosis and treatment for the public health services and patients in Sana'a , Yemen . Data were collected prospect ively from 320 pulmonary and extrapulmonary TB patients ( 160 each ) who were followed until completion of treatment . Direct medical and nonmedical costs and indirect costs were calculated . The proportionate cost to the patients for pulmonary TB and extrapulmonary TB was 76.1 % arid 89.4 % respectively of the total for treatment . The mean cost to patients for pulmonary and extrapulmonary TB treatment was US$ 108.4 and US$ 328.0 respectively . The mean cost per patient to the health services for pulmonary and extrapulmonary TB treatment was US$ 34.0 and US$ 38.8 respectively . For pulmonary and extrapulmonary TB , drug treatment represented 59.3 % and 77.9 % respectively of the total cost to the health services . The greatest proportionate cost to patients for pulmonary TB treatment was time away from work ( 67.5 % of the total cost ) , and for extrapulmonary TB was laboratory and X-ray costs ( 55.5 % ) followed by transportation ( 28.6 % )",
"BACKGROUND Resistance to commonly used antituberculosis drugs is emerging worldwide . Conventional drug-susceptibility testing ( DST ) methods are slow and dem and ing . Alternative , rapid DST methods would permit the early detection of drug resistance and , in turn , arrest tuberculosis transmission . METHODS A cost-effectiveness analysis of 5 DST methods was performed in the context of a clinical trial that compared rapid with conventional DST methods . The methods under investigation were direct phage-replication assay ( FASTPlaque-Response ; Biotech ) , direct amplification and reverse hybridization of the rpoB gene ( INNO-LiPA ; Innogenetics ) , indirect colorimetric minimum inhibitory concentration assay ( MTT ; ICN Biomedicals ) , and direct proportion method on Löwenstein-Jensen medium . These were compared with the widely used indirect proportion method on Löwenstein-Jensen medium . RESULTS All alternative DST methods were found to be cost-effective , compared with other health care interventions . DST methods also generate substantial cost savings in setting s of high prevalence of multidrug-resistant tuberculosis . Excluding the effects of transmission , the direct proportion method on Löwenstein-Jensen medium was the most cost-effective alternative DST method for patient groups with prevalences of multidrug-resistant tuberculosis of 2 % , 5 % , 20 % , and 50 % ( cost in US$ 2004 , $ 94 , $ 36 , $ 8 , and $ 2 per disability-adjusted life year , respectively ) . CONCLUSION Alternative , rapid methods for DST are cost-effective and should be considered for use by national tuberculosis programs in middle-income countries",
"Introduction Since the endorsement of GeneXpert MTB/RIF by the WHO , many countries have embarked on implementing this technology . Objective : We outline the cost of installing GeneXpert in district hospitals in Abuja , Nigeria . Methods We prospect ively documented costs related to the installation of GeneXpert at five sites . Costs were collected from receipts received from suppliers and normalized to USD 2012 values . Results Costs were often identified after initiating installation for many reasons . Installation varied widely between sites with sufficient space and power supply ; sites with insufficient space or power supply and costs not directly associated with site installation . The basic cost for installation was USD 2,621.98 per machine . Sites that required additional space cost close to USD 7,000.00 . Conclusion Space and power requirements have a significant effect on installation costs . Countries need to carefully consider the placement of Xpert machines based on the quality and size of the available infrastructure",
"Background Shortened treatment regimens for tuberculosis are under development to improve treatment outcomes and reduce costs . We estimated potential savings from a societal perspective in Brazil following the introduction of a hypothetical four-month regimen for tuberculosis treatment . Methods Data were gathered in ten r and omly selected health facilities in Rio de Janeiro . Health service costs were estimated using an ingredient approach . Patient costs were estimated from a question naire administered to 126 patients . Costs per visits and per case treated were analysed according to the type of therapy : self-administered treatment ( SAT ) , community- and facility-directly observed treatment ( community-DOT , facility-DOT ) . Results During the last 2 months of treatment , the largest savings could be expected for community-DOT ; on average USD 17,351 - 18,203 and USD 43,660 - 45,856 ( bottom-up and top-down estimates ) per clinic . Savings to patients could also be expected as the median ( interquartile range ) patient-related costs during the two last months were USD 108 ( 13–291 ) , USD 93 ( 36–239 ) and USD 11 ( 7–126 ) , respectively for SAT , facility-DOT and community-DOT . Conclusion Introducing a four-month regimen may result in significant cost savings for both the health service and patients , especially the poorest . In particular , a community-DOT strategy , including treatment at home , could maximise health services savings while limiting patient costs . Our cost estimates are likely to be conservative because a 4-month regimen could hypothetically increase the proportion of patients cured by reducing the number of patients defaulting and we did not include the possible cost benefits from the subsequent prevention of costs due to downstream transmission averted and rapid clinical improvement with less side effects in the last two months",
"SETTING In 2007 , the World Health Organization recommended introducing rapid Mycobacterium tuberculosis culture into the diagnostic algorithm of smear-negative pulmonary tuberculosis ( TB ) . OBJECTIVE To assess the cost-effectiveness of introducing a rapid non-commercial culture method ( thin-layer agar ) , together with Löwenstein-Jensen culture to diagnose smear-negative TB at a district hospital in Kenya . DESIGN Outcomes ( number of true TB cases treated ) were obtained from a prospect i ve study evaluating the effectiveness of a clinical and radiological algorithm ( conventional ) against the alternative algorithm ( conventional plus M. tuberculosis culture ) in 380 smear-negative TB suspects . The costs of implementing each algorithm were calculated using a ' micro-costing ' or ' ingredient-based ' method . We then compared the cost and effectiveness of conventional vs. culture-based algorithms and estimated the incremental cost-effectiveness ratio . RESULTS The costs of conventional and culture-based algorithms per smear-negative TB suspect were respectively € 39.5 and € 144 . The costs per confirmed and treated TB case were respectively € 452 and € 913 . The culture-based algorithm led to diagnosis and treatment of 27 more cases for an additional cost of € 1477 per case . CONCLUSION Despite the increase in patients started on treatment thanks to culture , the relatively high cost of a culture-based algorithm will make it difficult for re source -limited countries to afford",
"by HEWs in the health posts and general health workers at health facility were compared along a community-r and omized trial . Costs were analysed from societal perspective in 2007 in US $ using st and ard methods . We prospect ively enrolled smear positive patients , and calculated cost-effectiveness as the cost per patient successfully treated . The total cost for each successfully treated smear-positive patient was higher in health facility ( $ 158.9 ) compared with community ( $ 61.7 ) . Community-based treatment reduced the total , patient and caregiver cost by 61.2 % , 68.1 % and 79.8 % , respectively . Involving HEWs added a total cost of $ 8.80 ( 14.3 % of total cost ) on health service per patient treated in the community . Conclusions / Significance Community-based treatment by HEWs costs only 39 % of what treatment by general health workers costs for similar outcomes . Involving HEWs in TB treatment is a cost effective treatment alternative to the health service , to the patients and the family . There is an economic and public health reason to consider involving HEWs in TB treatment in Ethiopia . However , community-based treatment requires initial investment to start its implementation , training and supervision . Trial Registration Clinical Trials.gov",
"OBJECTIVE To estimate the incremental cost-effectiveness of tuberculosis ( TB ) screening and isoniazid preventive therapy ( IPT ) among human immunodeficiency virus ( HIV ) infected adults in Rio de Janeiro , Brazil . DESIGN We used decision analysis , populated by data from a cluster-r and omized trial , to project the costs ( in 2010 USD ) and effectiveness ( in disability-adjusted life years [ DALYs ] averted ) of training health care workers to implement the tuberculin skin test ( TST ) , followed by IPT for TST-positive patients with no evidence of active TB . This intervention was compared to a baseline of usual care . We used time horizons of 1 year for the intervention and 20 years for disease outcomes , with all future DALYs and medical costs discounted at 3 % per year . RESULTS Providing this intervention to 100 people would avert 1.14 discounted DALYs ( 1.57 undiscounted DALYs ) . The median estimated incremental cost-effectiveness ratio was $ 2273 ( IQR $ 1779-$3135 ) per DALY averted , less than Brazil 's 2010 per capita gross domestic product ( GDP ) of $ 11,700 . Results were most sensitive to the cost of providing the training . CONCLUSION Training health care workers to screen HIV-infected adults with TST and provide IPT to those with latent tuberculous infection can be considered cost-effective relative to the Brazilian GDP per capita",
"This paper explores the measurement of hospital costs and efficiency in a context where data is scarce , incomplete or of poor quality . It argues that there is scope for using tracers to examine and compare hospital cost structures and relative efficiency in such context s. Two high-burden diseases , malaria and pulmonary tuberculosis , are used as tracers to calculate the average costs of inpatient care at selected tertiary hospitals . This study shows that it is feasible to prospect ively collect cost data for specific diseases and explore in detail both patient cost distribution and susceptible areas for efficiency improvement . The present study found that the critical source of efficiency variation in public hospitals in Zimbabwe lies in the way hospital beds are used",
"OBJECTIVE To compare the cost of managing HIV-positive and HIV-negative tuberculosis ( TB ) patients in Sudan . METHODS A prospect i ve cohort of 1797 consecutive TB patients referred to the chest clinics within the general health services from March 1998 to March 2000 were included in this study . Patients were tested blindly for HIV ; 1724 were HIV-negative and 73 were HIV-positive . FINDINGS The total cost associated with management of tuberculosis was significantly higher for HIV-positive , as compared with HIV-negative TB patients ( 105.08 US dollars versus 73.92 , p=0.003 ) . This difference was due mainly to greater costs for hospitalization of those HIV-positive , as compared with those HIV-negative ( 190.80 versus 141.00 , p=0.001 ) . The differences in cost for diagnostic tests , for drugs , for management of adverse reactions and for intercurrent symptoms were not significant ( p>0.05 ) between HIV-positive TB patients and HIV-negative TB patients . Side effects of treatment were slightly more common among persons without HIV infection than among HIV-positive patients ( 14 and 9.6 % , respectively ) . The total cost of management of HIV-positive patients in this series of patients was 6 % of all costs for TB case management and the marginal cost attributable to HIV-positivity was 0.9 % of the total cost . CONCLUSION The management of the HIV-positive TB case was more costly than that of the HIV-negative case in this stage of the HIV/AIDS epidemic in Sudan",
"BACKGROUND Sputum obtained either under instruction from a health-care worker or through induction can improve case detection of active tuberculosis . However , the best initial sputum sampling strategy for adults with suspected smear-negative or sputum-scarce tuberculosis in primary care is unclear . We compared these two methods of sample acquisition in such patients . METHODS In this r and omised controlled trial , we enrolled adults ( age ≥18 years ) with sputum-scarce or smear-negative suspected tuberculosis from three primary care clinics in Cape Town , South Africa . Patients were r and omly assigned ( 1:1 ) to receive either health-care worker instruction or induction to obtain sputum sample s. Neither patients nor investigators were masked to allocation . The primary outcome was the proportion of patients who had started treatment after 8 weeks in a modified intention-to-treat population . Secondary outcomes were proportions starting treatment within different time periods , proportion of patients producing sputum for diagnosis , adverse effects , sputum sample s ' quality , and case detection by diagnostic method . This study is registered with Clinical Trials.gov , number NCT01545661 . FINDINGS We enrolled 481 patients , of whom 213 were assigned to health-care worker instruction versus 268 assigned to induction . The proportion of patients who started treatment in the 8 weeks after enrolment did not differ significantly between groups ( 53/213 [ 25 % ] vs 73/268 [ 27 % ] ; OR 0·88 , 95 % CI 0·57 - 1·36 ; p=0·56 ) . A higher proportion of instructed versus induced patients initiated empiric treatment based on clinical and radiography findings ( 32/53 [ 60 % ] vs 28/73 [ 38 % ] ; p=0·015 ) . An adequate sputum sample ≥1 mL was acquired in a lower proportion of instructed versus induced patients ( 164/213 [ 77 % ] vs 238/268 [ 89 % ] ; p ) , and culture-based diagnostic yield was lower in instructed versus induced patients ( 24/213 [ 11 % ] vs 51/268 [ 19 % ] ; p=0·020 ) . However , same-day tuberculosis case detection was similar in both groups using either smear microscopy ( 13/213 [ 6 % ] vs 22/268 [ 8 % ] ; p=0·38 ) or Xpert-MTB/RIF assay ( 13/89 [ 15 % ] vs 20/138 [ 14 % ] ; p=0·98 ) . No serious adverse events occurred in either group ; side-effects related to sample acquisition were reported in 32 of 268 ( 12 % ) patients who had sputum induction and none who had instruction . Cost per procedure was lower for instructed than for induced patients ( US$ 2·14 vs US$ 7·88 ) . INTERPRETATION Although induction provides an adequate sample and a bacteriological diagnosis more frequently than instruction by a health-care worker , it is more costly , does not result in a higher proportion of same-day diagnoses , and -because of widespread empiric treatment-may not result in more patients starting treatment . Thus , health-care worker instruction might be the preferred strategy for initial collection of sputum sample s in adults with suspected sputum-scarce or smear-negative tuberculosis in a high burden primary care setting . FUNDING South African National Research Foundation , European Commission , National Institutes of Health , European and Developing Countries Clinical Trials Partnership , Discovery Foundation",
"SETTING South Africa reports more cases of tuberculosis ( TB ) than any other country , but an up-to- date , precise estimate of the costs associated with diagnosing , treating and preventing TB at the in-patient level is not available . OBJECTIVE To determine the costs associated with TB management among in- patients and to study the use of personal protective equipment ( PPE ) at a central academic hospital in Cape Town . DESIGN Retrospective and partly prospect i ve cost analysis of TB cases diagnosed between May 2008 and October 2009 . RESULTS The average daily in-patient costs were US$ 238 ; the average length of stay was 9.7 days . Mean laboratory and medication costs per stay were respectively US$ 26.82 and US$ 8.68 . PPE use per day cost US$ 0.99 . The average total TB management costs were US$ 2373 per patient . PPE was not always properly used . DISCUSSION The costs of in-patient TB management are high compared to community-based treatment ; the main reason for the high costs is the high number of in-patient days . An efficiency assessment is needed to reduce costs . Cost reduction per TB case prevented was approximately US$ 2373 per case . PPE use accounted for the lowest costs . Training is needed to improve PPE use",
"OBJECTIVE To evaluate the cost-effectiveness of an educational outreach intervention to improve primary respiratory care by South African nurses . METHODS Cost-effectiveness analysis alongside a pragmatic cluster r and omised controlled trial , with individual patient data . The intervention , the Practical Approach to Lung Health in South Africa ( PALSA ) , comprised educational outreach based on syndromic clinical practice guidelines for tuberculosis , asthma , chronic obstructive pulmonary disease , pneumonia and other respiratory diseases . The study included 1999 patients aged 15 or over with cough or difficult breathing , attending 40 primary care clinics staffed by nurses in the Free State province . They were interviewed at first presentation , and 1856 ( 93 % ) were interviewed 3 months later . RESULTS The intervention increased the tuberculosis case detection rate by 2.2 % and increased the proportion of patients appropriately managed ( that is , diagnosed with tuberculosis or prescribed an inhaled corticosteroid for asthma or referred with indicators of severe disease ) by 10 % . It costs the health service $ 68 more for each extra patient diagnosed with tuberculosis and $ 15 more for every extra patient appropriately managed . Analyses were most sensitive to assumptions about how long training was effective for and to inclusion of household and tuberculosis treatment costs . CONCLUSION This educational outreach method was more effective and more costly than usual training in improving tuberculosis , asthma and urgent respiratory care . The extra cost of increasing tuberculosis case detection was comparable to current costs of passive case detection . The syndromic approach increased cost-effectiveness by also improving care of other conditions . This educational intervention was sustainable , reaching thous and s of health workers and hundreds of clinics since the trial",
"OBJECTIVE To compare the cost of facility-based MDR TB care ( F ) to home-based care ( H ) from the perspective of the Nigerian national health system . METHODS We assessed the expected costs of the two MDR TB treatment approaches using a decision-analytic model with a follow-up of 6 months . MDR TB treatment outcomes were obtained from a systematic review of r and omised clinical trials . The outcomes of interest included treatment success , treatment failure , treatment default and mortality and did not vary significantly between the two alternatives . Treatment costs included the cost of the following : drug therapy ( F , H ) , hospital stay ( F ) , nurse care ( F , H ) , physician care ( F ) , nursing facility ( F ) and transport to the healthcare provider ( H ) . Finally , we estimated the potential cost savings associated with home-based treatment for all patients starting MDR TB treatment in Nigeria . RESULTS The average expected total treatment cost for a Nigerian patient treated for MDR TB was estimated at US2095 for facility - based care and 1535 for home-based care , a potential saving of 25 % . One of the major drivers of this difference is significantly more intensive , and therefore more costly , nursing care in hospitals . In 2013 , a total of 426 patients were initiated on facility-based MDR TB treatment in Nigeria . Thus , the potential savings through home-based care are US$ 223 204 per year . CONCLUSION In Nigeria , treatment of MDR TB using home-based care is expected to result in similar patient outcomes at markedly reduced public health costs as facility-based care",
"BACKGROUND Directly observed treatment short-course ( DOTS ) strategy is an effective mode of treating TB . We aim ed to study the cost effectiveness and patients ' satisfaction with home based direct observation of treatment ( DOT ) , an innovative approach to community-based DOT ( CBDOT ) and hospital based DOT ( HBDOT ) . METHODS A r and omized controlled trial involving 150 newly diagnosed pulmonary TB patients in four TB clinics in Ile Ife , Nigeria , was done . They were r and omly assigned to receive treatment with anti TB drugs for the intensive phase administered at home by a TB worker ( CBDOT ) or at the hospital ( HBDOT ) . Outcome measures were treatment completion/default rates , cost effectiveness and patients ' satisfaction with care using a 13 item patients satisfaction question naire ( PS-13 ) at 2 months . This trial was registered with pactr.org : number PACTR 201503001058381 . RESULTS At the end of intensive phase , 15/75 ( 20 % ) and 2/75 ( 3 % ) of patients in the HBDOT and CBDOT , respectively had defaulted from treatment , p= 0.01 . Of those with pretreatment positive sputum smear , 97 % ( 68/70 ) on CBDOT and 54/67 ( 81 % ) on HBDOT were sputum negative for AFB at the end of 2 months of treatment , p=0.01 . The CBDOT method was associated with a higher patient satisfaction score compared with HBDOT ( OR 3.1 ; 95 % CI 1.25 - 7.70 ) , p=0.001.The total cost for patients was higher in HBDOT ( US$ 159.38 ) compared with the CBDOT ( US$ 89.52 ) . The incremental cost effectiveness ratio was US$ 410 per patient who completed the intensive phase treatment with CBDOT . CONCLUSIONS CBDOT is a cost effective approach associated with better compliance to treatment and better patient satisfaction compared to HBDOT"
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4117a24e-06ff-11f0-808a-c43d1ab1c353
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Background A feature of stroke is that it recurs ( 25 % within five-years ) . Risk factors for stroke and recurrent stroke include smoking , alcohol consumption , poor diet , and physical inactivity . Aim To evaluate the effectiveness of secondary prevention lifestyle interventions design ed to change lifestyle behavior following stroke . This short paper presents a summary of the systematic review process and findings . Methods Ten major data bases were search ed using subject headings and key words . Papers were screened using review -specific criteria . Critical appraisal and data extraction were conducted independently by two review ers . Data were pooled in statistical meta- analysis ; where this was not possible findings were presented in narrative form . Results Three studies involving 581 participants were review ed . Two models of intervention delivery were reported : shared care and nurse-led . Interventions were delivered to groups or in one-to-one consultations . Metaanalyses of the pooled lifestyle data favored the interventions ( 2P = 0.02 ) . In terms of physiological outcomes , while overall treatment effect was not significant , pooled results did approach statistical significance ( 2P = 0.08 ) , however the test of heterogeneity was significant , suggesting differences in the variables that were pooled . Pooled secondary outcomes , including perceived health status and stroke knowledge , favored the interventions ( 2P # Stroke secondary prevention lifestyle interventions are effective in terms of effecting positive change in lifestyle behaviors and secondary outcomes , and appear promising in relation to physiological outcomes . There was insufficient evidence to determine the effect of intervention on incidence of stroke recurrence
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"Background and Purpose — Reduction in the risk of stroke and increase in the speed of hospital presentation after the onset of stroke both depend on the level of knowledge of stroke in the general population . The aim of the present study was to assess baseline knowledge regarding stroke risk factors , symptoms , treatment , and information re sources . Methods — A community-based telephone interview survey was conducted in the Newcastle urban area in Australia . A total of 1278 potential participants between the ages of 18 to 80 were selected at r and om from an electronic telephone directory . A trained telephone interviewer conducted a telephone survey using the Computer-Assisted Telephone Interviewing ( CATI ) program . Results — A total of 822 participants completed the telephone interview . Six hundred three participants ( 73.4 % ) correctly identified the brain as the affected organ in stroke . The most common risk factors for stroke identified by respondents were smoking ( identified by 324 [ 39.4 % ] ) and stress ( identified by 277 [ 33.7 % ] ) . The most common warning sign of stroke described by respondents was “ blurred and double vision or loss of vision in an eye , ” listed by 198 ( 24.1 % ) . A total of 626 ( 76.2 % ) respondents correctly listed ≥1 established stroke risk factor , but only 409 ( 49.8 % ) respondents correctly listed ≥1 warning sign . Conclusions — The level of knowledge in the community of established stroke risk factors , warning signs , and treatment as indicated by this survey suggests that a community-based education program to increase public knowledge of stroke may contribute to reducing the risk of stroke and to increasing the speed of hospital presentation after the onset of stroke",
"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",
"Background and Purpose — The Stroke PROTECT ( Preventing Recurrence Of Thromboembolic Events through Coordinated Treatment ) program systematic ally implements , at the time of acute transient ischemic attack ( TIA ) or ischemic stroke admission , 8 medication/behavioral secondary prevention measures known to improve outcome in patients with cerebrovascular disease . The objective of this study was to determine if the high utilization rates previously demonstrated at hospital discharge were maintained at 90 days after discharge . Methods — Data were prospect ively collected on consecutively encountered ischemic stroke and TIA patients admitted to a university hospital stroke service beginning September 1 , 2002 . PROTECT interventions were initiated before hospital discharge in all PROTECT – target ( underlying stroke mechanism large vessel atherosclerosis or small vessel disease ) and PROTECT – ACS ( At-risk for Coronary Sequelae ) patients . Adherence to program goals was assessed 3 months after discharge . Results — During the period from September 2002 to August 2003 , 144 individuals met criteria for PROTECT intervention . Of the 130 patients ( 90 % ) with available day 90 follow-up data , mean age was 72 ( range , 37 to 95 ) , and 63 % were male . Adherence rates in patients without specific contraindications were 100 % for antithrombotics , 99 % for statins , 92 % for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers , and 80 % for thiazides . Awareness of the importance of calling 911 in response to stroke was 87 % . Adherence to diet and exercise guidelines were 78 % and 70 % , respectively . Of the 24 smokers , tobacco cessation was maintained in 20 ( 83 % ) . Conclusions — High rates of adherence to PROTECT therapies were maintained at 90 days after hospital discharge",
"Smoking cessation treatment is now integrated into many health-care systems and a major research effort is under way to improve current success rates . Until now results from r and omized clinical trials have been reported in many different ways , leading to problems of interpretation . We propose six st and ard criteria comprising the ' Russell St and ard ' ( RS ) . These criteria are applicable to trials of cessation aids where participants have a defined target quit date and there is face-to-face contact with research ers or clinic staff , as follows . ( 1 ) Follow-up for 6 months ( RS6 ) or 12 months ( RS12 ) from the target quit date or the end of a predefined ' grace period ' ; ( 2 ) self-report of smoking abstinence over the whole follow-up period allowing up to five cigarettes in total ; ( 3 ) biochemical verification of abstinence at least at the 6-month or 12-month follow-up point ; ( 4 ) use of an ' intention-to-treat ' approach in which data from all r and omized smokers are included in the analysis unless they have died or moved to an untraceable address ( participants who are included in the analysis are counted as smokers if their smoking status at the final follow-up can not be determined ) ; ( 5 ) following-up ' protocol violators ' and using their true smoking status in the analysis ; and ( 6 ) collecting follow-up data blind to smokers ' allocation to trial group . We believe that these criteria provide the best compromise between practicability and surrogacy for long-term cessation and will enable meaningful comparison between studies . There may be good reasons why other outcome criteria would also be reported , and studies that involve interventions with special groups or where there is no design ated target quit date or face to face contact would need to adapt these criteria accordingly",
"Nir Z , Zolotogorsky Z , Sugarman H : Structured nursing intervention versus routine rehabilitation after stroke . Am J Phys Med Rehabil 2004;83:522–529 . Objective : The goal of this study was to examine the effect of a structured , comprehensive nursing intervention on the course of rehabilitation over the first 6 mos after a first-ever stroke . Design : Intervention ( experimental ) study . The participants were 155 elderly stroke survivors who were admitted to a geriatric rehabilitation department . Stratified r and om sampling generated intervention and control groups . The intervention was design ed to work together with the routine rehabilitation program and consisted of 12 consecutive weekly meetings . The control group received only the routine rehabilitation program . Study variables were measured at entry to study and after 3- and 6-mo intervals . Results : Although there were no significant differences between the two groups at entry to study , at 3 and 6 mos after stroke , the intervention group showed better scores than the control group in functional status ( FIM ™ instrument ) , depression ( Geriatric Depression Scale ) , self-perceived health , self-esteem , and dietary adherence . Conclusion : The nursing intervention had both short- and long-term effects on functional , psychological , and emotional variables . Serious consideration should be given to implementing comprehensive nursing interventions during rehabilitation tailored to meet the specific needs of stroke survivors and their caregivers",
"Background and Purpose — Few reliable estimates of the long-term functional outcome after stroke are available . This population -based study aim ed to describe disability , dependency , and related independent prognostic factors at 5 years after a first-ever stroke in patients in Perth , Western Australia . Methods — All individuals with a suspected acute stroke who were resident in a geographically defined region ( population , 138 708 ) of Perth , Western Australia , were registered prospect ively and assessed according to st and ardized diagnostic criteria over a period of 18 months in 1989 to 1990 . Patients were followed up prospect ively at 4 and 12 months and 5 years after the index event . Results — There were 370 cases of first-ever stroke , and 277 patients survived to 30 days . Of these early survivors , 152 ( 55 % ) were alive at 5 years , and among those who were neither institutionalized ( n=146 ) nor disabled ( n=129 ) at the time of their stroke , 21 ( 14 % ) were institutionalized in a nursing home , and 47 ( 36 % ) were disabled . The most important predictors of death or disability at 5 years were increasing age , baseline disability defined by a Barthel Index score of moderate hemiparesis ( OR , 2.7 ; 95 % CI , 1.1 to 6.2 ) , severe hemiparesis ( OR , 4.5 ; 95 % CI , 1.1 to 19 ) , and recurrent stroke ( OR , 9.4 ; 95 % CI , 3.0 to 30 ) . A low level of activity before the stroke was a significant predictor of institutionalization , and subsequent recurrent stroke was a consistent , independent predictor of institutionalization , disability , and death or institutionalization , increasing the odds of each of these 3 adverse outcomes by 5- to 15-fold . Conclusions — Among 30-day survivors of first-ever stroke , about half survive 5 years ; of survivors , one third remain disabled , and 1 in 7 are in permanent institutional care . The major modifiable predictors of poor long-term outcome are a low level of activity before the stroke and subsequent recurrent stroke . Efforts to increase physical activity among the elderly and to prevent recurrent stroke in survivors of a first stroke are likely to reduce the long-term burden of cerebrovascular disease ",
"Background and Purpose — Increased knowledge of stroke risk factors in the general population may lead to improved prevention of stroke . The objective of the present study was to assess knowledge of stroke risk factors and to determine factors associated with knowledge . Methods — In a population -based survey , we sent a question naire to r and omly selected residents in Berlin who were ≥50 years of age enquiring about knowledge of stroke risk factors . Knowledge was assessed in an open-ended question . In addition , we enquired about the source of participants ' information . Sociodemographic factors , including age , sex , educational level , and nationality , were also assessed . Results — A total of 28 090 of 75 720 residents ( response rate , 37 % ) responded to the question naire . Of all respondents , 68 % were able to name ≥1 correct stroke risk factor , and 13 % named 4 correct risk factors . The majority of respondents named mass media as source of information ( 82 % ) , followed by family/friends ( 45 % ) and by general physicians ( 20 % ) . In multivariable analysis , increased knowledge of stroke risk factors was significantly associated with younger age , a higher educational level , not living alone , a German nationality , and having received any information about stroke during the last year . However , characteristics of respondents using the respective sources of information varied significantly . Conclusions — Mass media was most frequently named as a source of information about stroke risk factors . Source of information used varied according to population characteristics . Health education programs should take this into account and be adapted accordingly",
"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",
"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"
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4117a28a-06ff-11f0-808a-c43d1ab1c353
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Background Metal-on-metal hip resurfacing was developed for younger , active patients as an alternative to THA , but it remains controversial . Study heterogeneity , inconsistent outcome definitions , and unst and ardized outcome measures challenge our ability to compare arthroplasty outcomes studies . Questions / purpose sWe asked how early revisions or reoperations ( within 5 years of surgery ) and overall revisions , adverse events , and postoperative component malalignment compare among studies of metal-on-metal hip resurfacing with THA among patients with hip osteoarthritis . Secondarily , we compared the revision frequency identified in the systematic review with revisions reported in four major joint replacement registries . Methods We conducted a systematic review of English language studies published after 1996 . Adverse events of interest included rates of early failure , time to revision , revision , reoperation , dislocation , infection/sepsis , femoral neck fracture , mortality , and postoperative component alignment . Revision rates were compared with those from four national joint replacement registries . Results were reported as adverse event rates per 1000 person-years stratified by device market status ( in use and discontinued ) . Comparisons between event rates of metal-on-metal hip resurfacing and THA are made using a quasilikelihood generalized linear model . We identified 7421 abstract s , screened and review ed 384 full-text articles , and included 236 . The most common study design s were prospect i ve cohort studies ( 46.6 % ; n = 110 ) and retrospective studies ( 36 % ; n = 85 ) . Few r and omized controlled trials were included ( 7.2 % ; n = 17 ) . Results The average time to revision was 3.0 years for metal-on-metal hip resurfacing ( 95 % CI , 2.95–3.1 ) versus 7.8 for THA ( 95 % CI , 7.2–8.3 ) . For all devices , revisions and reoperations were more frequent with metal-on-metal hip resurfacing than THA based on point estimates and CIs : 10.7 ( 95 % CI , 10.1–11.3 ) versus 7.1 ( 95 % CI , 6.7–7.6 ; p = 0.068 ) , and 7.9 ( 95 % CI , 5.4–11.3 ) versus 1.8 ( 95 % CI , 1.3–2.2 ; p = 0.084 ) per 1000 person-years , respectively . This difference was consistent with three of four national joint replacement registries , but overall national joint replacement registries revision rates were lower than those reported in the literature . Dislocations were more frequent with THA than metal-on-metal hip resurfacing : 4.4 ( 95 % CI , 4.2–4.6 ) versus 0.9 ( 95 % CI , 0.6–1.2 ; p = 0.008 ) per 1000 person-years , respectively . Adverse event rates change when discontinued devices were included . Conclusions Revisions and reoperations are more frequent and occur earlier with metal-on-metal hip resurfacing , except when discontinued devices are removed from the analyses . Results from the literature may be misleading without consistent definitions , st and ardized outcome metrics , and accounting for device market status . This is important when clinicians are assessing and communicating patient risk and when selecting which device is most appropriate for individual patients
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" The first 100 consecutive primary hip arthroplasties with the Arthopor 2 acetabular component ( Joint Medical Products , Stamford , CT ) with supplemental screw fixation performed by the senior author were prospect ively studied . The mean patient age was 57 years . Seventy-seven cemented and 23 cementless stems were placed , with 32-mm femoral heads used in most of the patients . Eighty-six hips were review ed at 7 - 8.8 years ( mean , 7.8 years ) . The mean Harris hip score at final follow-up evaluation was 94 points . No cups have been revised , although 2 cups in patients with radiation osteonecrosis were loose radiographically . One patient underwent revision of a severely worn liner . Despite a relatively high mean linear wear rate of 0.27 mm/y ( range , 0.13 - 0.57 mm/y ) , no radiographic evidence of pelvic osteolysis was seen . The Arthopor 2 cup performed well with respect to pelvic osteolysis , despite the presence of substantial polyethylene debris . The relatively high polyethylene wear rate is attributed in part to the younger patient population and the use of 32-mm femoral heads paired with thin polyethylene liners",
"The purpose of this study was to evaluate the clinical outcomes and possible causes of early failure in a multicenter trial of metal-on-metal hip resurfacing . Two hundred patients were prospect ively enrolled and followed for an average of 31.2 months ( range , 12 - 54 months ) . Of 200 patients , 14 ( 7.0 % ) required revision surgery at a mean time of 19.5 months ( range , 3 - 47 months ) . Patients with failures were significantly younger and heavier than the nonfailures , and all were male . Patients who were revised did not differ from those who were not revised in terms of radiographic outcomes , but they did report lower functional outcome scores at all preoperative and postoperative testing intervals . Most failures ( 10/14 ) were related to early acetabular loosening . The learning curve was likely a factor in these cup failures . This report highlights the importance of patient selection and surgical technique in hip resurfacing arthroplasty . It is anticipated that further surgical experience will lead to a reduction in this high early failure rate",
" We describe the experience with the first consecutive 230 Birmingham hip resurfacings at our centre . At a mean follow-up of three years ( 25 to 52 months ) survivorship was 99.14 % with revision in one patient for a loose acetabular component and one death from unrelated causes . One patient developed a fracture of the femoral neck at six weeks which united unremarkably after a period of non-weight-bearing . The Harris hip score improved from a mean of 62.54 ( 8 to 92 ) to 97.74 ( 61 to 100 ) . The mean flexion improved from 91.52 degrees ( 25 to 140 ) to 110.41 degrees ( 80 to 145 ) . Most patients ( 97 % ) considered the outcome to be good or excellent . Our preliminary experience with this implant is encouraging and the results are superior to the earlier generation of resurfacings for the same length of follow-up",
"A comparison of pertinent preoperative and postoperative data relative to total hip resurfacing versus total hip arthroplasty ( THA ) would assist in evaluating current perceptions in outcome . We compared 50 consecutive metal-metal resurfacing replacements in 50 patients with 44 consecutive conventional total hip arthroplasties in 35 patients , who were implanted during the same time period , by the same surgeon , and followed prospect ively for 2 to 4 years . The patients undergoing hip resurfacing were 62 % male , 9 years younger , and 3.2 inches taller , with a lower mean body mass index and American Society of Anesthesiologists ( ASA ) grade than patients undergoing total hip arthroplasty . Preoperatively , patients undergoing resurfacing had a lower Harris hip score ( 46 vs 52 points ) , more pain , higher UCLA ( University of California at Los Angeles ) activity scores ( 4.2 vs 3.6 ) , and better range of motion . Surgical time for resurfacing was 18 % longer , but there was less total blood loss and fewer transfusions . Postoperatively , there was no difference in Harris hip score ( 97 vs 96 ) . Patients undergoing resurfacing had higher function , Short Form-12 physical activity scores , and UCLA activity scores , but also a higher incidence of slight or mild pain . There were no differences in postoperative range of motion or dislocation ( one each ) . The preoperative characteristics and general health status of the average patient undergoing resurfacing are more favorable than that of the average patient undergoing conventional total hip arthroplasty . Caution should be applied in attributing differences in outcomes directly to the arthroplasty technology",
"Background To investigate prospect ively the patient-relevant outcome 7 years after total hip replacement ( THR ) for osteoarthritis ( OA ) . Methods 219 consecutive patients ( 120 women ) with primary OA , mean age 71 ( range 50 - 92 ) were assigned for THR . They were examined preoperatively , at 3 , 6 , 12 months , and at 4 , 5 and 7 years postoperatively with the self-administered question naires SF-36 and WOMAC . Supplementary questions regarding postoperative complications , general co-morbidity , social circumstances and patient satisfaction were asked at the three last follow-ups . A reference group , 117 subjects ( 67 women ) , mean age 72 ( range 52 - 92 ) without hip complaints were recruited from the community and investigated at the same times . Results 151/170 ( 89 % ) of the patients and 65/74 ( 88 % ) of the reference group participated at the 7 year follow-up . The best postoperative result was reported one year postoperatively . At the 7 year follow up there was a significant difference between the patients and controls in SF-36 physical function ( PF ) and role physical ( RP ) but not of WOMAC function . There was no difference in frequency of co-morbid conditions between those operated and the reference group , but those operated were in greater need of walking aid ( 46 % vs. 8 % p regional and widespread pain ( 68 % vs. 53 % p health-related quality of life as a reference group of a similar age and sex structure 7 years after THR except for general physical function where the patients score worse",
"OBJECTIVE To evaluate the effect of obesity on the incidence of main complications ( infection , dislocation , and revision ) , functional outcome , and patient satisfaction 5 years after primary total hip arthroplasty ( THA ) , and to determine whether results differ between obese women and men . METHODS We conducted a hospital-based prospect i ve cohort study including patients who underwent primary THA ( 2,495 hips ) between 1996 and 2005 . We used rates and rate ratios to compare the incidence of main complications in obese and nonobese patients , and we stratified the data for sex . Functional outcome was measured using the Harris Hip Score and Western Ontario and McMaster Universities Osteoarthritis Index . RESULTS The adjusted incidence rate ratio for infection ( obese versus nonobese ) was 4.4 ( 95 % confidence interval [ 95 % CI ] 1.8 , 10.8 ) . Obesity substantially increased the infection rate in women ( incidence rate ratio comparing obese with nonobese women 16.1 ; 95 % CI 3.4 , 75.7 ) , whereas obesity appeared to have no effect in men ( incidence rate ratio 1.0 ; 95 % CI 0.2 , 5.3 ) . The adjusted incidence rate ratio for dislocation ( obese versus nonobese ) was 2.4 ( 95 % CI 1.4 , 4.2 ) , with a higher rate increase in obese women . A total of 817 patients had a 5-year clinical followup visit . Functional outcome and satisfaction were slightly lower in obese women partly due to higher complication rates . No difference was seen in men . CONCLUSION Primary THA is a successful intervention in obese patients , but physician and patient must be aware of increased complications , particularly in women",
"We report an independent prospect i ve review of the first 230 Birmingham hip resurfacings in 212 patients at a mean follow-up of five years ( 4 to 6 ) . Two patients , one with a loose acetabular component and the other with suspected avascular necrosis of the femoral head , underwent revision . There were two deaths from unrelated causes and one patient was lost to follow-up . The survivorship with the worst-case scenario was 97.8 % ( 95 % confidence interval 95.8 to 99.5 ) . The mean Harris hip score improved significantly ( paired t-test , p mean flexion improved from 91.5 degrees ( 25 degrees to 140 degrees ) to 110.4 degrees ( 80 degrees to 145 degrees ) at a mean of three years with no further improvement at five years ( 111.2 degrees ; 70 degrees to 160 degrees ) . On radiological review at five years , one patient had a progressive lucent line around the acetabular component and six had progressive lucent lines around the femoral component . A total of 18 femoral components ( 8 % ) had migrated into varus and those with lucent lines present migrated a mean of 3.8 degrees ( 1.02 degrees to 6.54 degrees ) more than the rest . Superolateral notching of the femoral neck and reactive sclerosis at the tip of the peg of the femoral component were associated with the presence of lucent lines ( chi-squared test , p Birmingham hip resurfacing continue to be satisfactory at a mean follow-up of five years",
"Objectives : To investigate prospect ively long term patient relevant outcomes after unilateral total hip replacement ( THR ) for osteoarthritis ( OA ) . To identify non-responders to this intervention and patient related predictors of unsatisfactory outcome . Methods : A case-control study comparing health related quality of life of 219 patients ( mean age 71 ) after THR with that of a matched reference group of 117 subjects without hip complaints recruited from the community . Patients and reference group answered SF-36 and WOMAC question naires preoperatively , at 3 , 6 , 12 months , and at 3.6 years ( range 26–65 months ) postoperatively . Supplementary questions were asked at the final follow up . Results : 198/211 ( 94 % ) of the patients and 83/109 ( 76 % ) of the reference group participated at the final follow up . At follow up , the only difference between the two groups in the SF-36 was physical function , where patients scored worse . Patients also reported worse WOMAC function . 31 % of the patients had improved by at final follow up , compared with preoperatively . More pain preoperatively and higher age and postoperative low back pain predicted a worse outcome in WOMAC function . Conclusion : 3.6 years after THR for OA , health related quality of life was similar for patients and reference group except for function , where patients had worse function . Higher age and more pain preoperatively predicted a poor outcome . Patients with hip OA with musculoskeletal comorbidities , such as low back pain and OA of the non-operated hip , have less long term functional improvement after THR",
"Objective To investigate differences in pre- and postoperative patient-relevant outcome between hybrid total hip replacement ( THR ) and cemented THR in patients with primary osteoarthritis ( OA ) . Methods 245 consecutive patients were included in the study . 68 of the patients ( mean age 62 ) were operated on with hybrid THR and 177 ( mean age 74 ) were operated on with cemented THR . All patients were investigated preoperatively and 0.5 , 1 and 3.6 years postoperatively with two self-administered question naires , SF-36 and WOMAC ( Western Ontario and MacMaster Universities Osteoarthritis Index , LK 3.0 ) . Results Preoperatively , there was a difference in the SF-36 subscales RP ( role physical ) and GH ( general health ) where the patients with the hybrid THR attained better scores . At 3.6-years the patients with the hybrid THR reached better scores in all SF-36 subscales except BP ( bodily pain ) and GH . Further , they had better scores in WOMAC function . However , after adjusting for age , sex , follow-up time and baseline values there were no differences in outcome between the two different surgical techniques . Conclusion This medium term ( 3–5 years ) , controlled , open cohort study , using patient-relevant outcome measures , did not reveal any differences between hybrid THR and cemented THR for OA at 3.6 years after surgery . Since the study had 75–94 % power to detect the clinical ly significant score difference of 10 points , we suggest that any difference in outcome between these two methods is small and may require a large-scale , blinded , r and omized trial to show",
"Background Even though there are multiple studies documenting the outcome of the Charnley low-friction arthroplasty as well as abundant studies on uncemented arthroplasties , there is a dearth of comparative studies of the uncemented acetabular component and a cemented component . In this study we aim ed to document the long-term clinical and radiographic outcome as well as component survival in a r and omized controlled trial . Material s and methods Two hundred fifteen patients ( 240 hips ) were r and omly allocated to receive a cemented Charnley cup or uncemented Duraloc 1200 cup . All patients received cemented Charnley stems and were evaluated clinical ly and radiographically after 6 months , and 2 , 5 , and 10 years . Results Harris Hip Scores improved from 48.3 [ 95 % confidence interval ( CI ) 45.0–51.6 ] to 90.2 [ 95 % CI 87.9–92.6 ] in the Charnley group and from 49.3 [ 95 % CI 86.9–91.3 ] in the Duraloc group at 6 months . After 10 years , the Charnley group ’s Harris Hip Score was 89.8 [ 95 % confidence interval ( CI ) 87.0–92.6 ] , and the Duraloc group ’s score was 87.3 ( 95 % CI 84.1–90.6 ) . In the radiographic analysis after 10 years , there was no statistical difference in the prevalence of radiographic signs of loosening . Nine cups were revised in the Charnley group , and five cups were removed in the Duraloc group . The difference was not statistically significant . There was no statistical difference between the cups when aseptic loosening was the end-point , nor in survival analyses . Conclusions There is no statistically significant difference in clinical or radiological outcome between the Charnley cup and the Duraloc after 10 years , and no difference in implant survival after 12–14 years . The uncemented Duraloc cup is as good as the cemented Charnley cup after 10 years",
"Objective . To present the results of a prospect i ve analysis of proximal femoral bone mineral density changes around a hydroxyapatite-coated total hip joint replacement . Methods . 14 patients with osteoarthritis of the hip were enrolled in the study and treated with an uncemented ABG prosthesis . Dual energy X-ray absorptiometry scanning was performed in 9 patients preoperatively , and at 3 , 6 , 12 , and 24 months postoperatively . An orthopaedic software program was used to determine the bone mineral density in the proximal femur , expressed as a percentage of the preoperative value . Results . The values of Gruen zones 1 to 6 averaged between 96.0 % and 113.8 % of the preoperative value by 24 months ( overall average , 104.1 % ) . In zone 7 , however , there was a gradual decline in bone mineral density to an average of 72.1 % of the preoperative value by 24 months . This represented ongoing loss of bone from the calcar ; although this may not pose a problem to the prosthetic 's short-term stability , it may render potential revision surgery more difficult . Conclusion . The initial outcome of uncemented total hip replacement appears to be promising . There was excellent maintenance of bone around the femoral component in all regions other than the calcar and lesser trochanter . Further scans are required to see if these trends continue in the long term",
"OBJECTIVE To determine the prevalence of heterotopic bone formation in cemented versus noncemented total hip joint replacement . DESIGN A prospect i ve r and omized controlled trial . Follow-up ranged from 2 to 6 years ( mean 4 years ) . SETTING A university hospital . PATIENTS Two hundred and twenty-six patients who had primary or secondary osteoarthrosis of the hip were stratified according to type of fixation , surgeon and age . Patients were r and omized within strata : 112 received noncemented total hip prostheses and 114 received cemented prostheses . The 2 groups were similar with respect to age and sex . INTERVENTION Primary total hip arthroplasty . A cemented ( methylmethacrylate ) or noncemented prosthesis was inserted by a lateral surgical approach . MAIN OUTCOME MEASURE The Brooker classification was used to grade heterotopic bone formation from postoperative radiographs . RESULTS Overall , 148 ( 66 % ) hips had no heterotopic ossification , 56 ( 25 % ) were Brooker class I , 14 ( 6 % ) were class II , 8 ( 3 % ) were class III and none were class IV . In the noncemented group of patients , 76 ( 68 % ) hips had no heterotopic ossification , 25 ( 22 % ) were Brooker class I , 7 ( 6 % ) were class II , 4 ( 4 % ) were class III and none were class IV . In the cemented group of patients , 72 ( 63 % ) hips had no heterotopic ossification , 31 ( 27 % ) hips were Brooker class I , 7 ( 6 % ) were class II , 4 ( 4 % ) were class III and none were class IV . CONCLUSION There was no significant difference in the prevalence of heterotopic ossification between cemented and noncemented total hip replacements in patients with osteoarthrosis",
"We evaluated the clinical and radiographic outcomes of 100 consecutive primary total hip arthroplasties in which a proximally coated anatomically design ed femoral component was fixed without cement for the treatment of primary osteoarthritis . The minimum duration of follow-up was six years ( average , 7.1 years ) . The eighty-eight patients who had the arthroplasties were followed prospect ively with a st and ard clinical evaluation that involved use of the Harris hip score and a radiographic evaluation based on the criteria of the Hip Society . Bone ingrowth was evaluated with the method of Engh et al. The average age of the patients at the time of the operation was 62.6 years ( range , thirty-nine to eighty-four years ) . Fifty-one patients were men and thirty-seven were women . The average preoperative Harris hip score was 48 points , with an average pain score of 15 points and an average function score of 26 points . Nonmechanical complications that necessitated a revision operation included one deep hematogenous infection , one late periprosthetic fracture , and a 0.5-inch ( 1.27-centimeter ) limb-length discrepancy . At the time of the most recent follow-up , the average Harris hip score was 96 points , with an average pain score of 42 points and an average function score of 45 points . The prevalence of pain in the anterior part of the thigh was 5 percent ( five hips ) . One patient had a revision of the femoral component because of aseptic loosening , and one had a revision of the acetabular component because of recurrent dislocations . Radiographic assessment revealed consistent evidence of proximal bone ingrowth . No complete radiolucent line was identified , except around the stem that had loosened . Twenty-seven femoral components were associated with slight pedestal formation . No osteolytic lesion of the femur was identified . Nonprogressive pelvic osteolysis was identified in four hips , but none of the lesions were more than two millimeters in diameter . None of the acetabular components migrated , and no radiolucent line of more than two millimeters in thickness was seen around any acetabular cup . The data from this study , in which the minimum duration of follow-up was six years , indicate that the anatomically design ed prosthesis can provide good results , with low prevalences of pain in the thigh and loosening of the component , in younger , active patients",
"Two series of 100 consecutive primary total hip arthroplasties , each using a single design of noncemented or cemented femoral component ( all 28 mm heads ) , were compared . One cemented and two noncemented stems underwent revision for aseptic loosening . Of unrevised hips , outcome data statistically favored cemented , rather than noncemented , stems . The data for cemented and noncemented stems , respectively , were : An excellent to good result in 97 % versus 88 % ; thigh pain in 3 % versus 40 % ; subsidence in 0 % versus 22 % ; and endosteal cavitation in 6 % versus 12 % . For patients with 25 unrevised matched pairs , selected by gender , age , diagnosis , and weight , outcome data also statistically favored cemented over noncemented stems , respectively : an excellent or good result in 25 versus 20 hips ; thigh pain in two versus eight hips ; and subsidence in none versus six hips . Midterm followup data for these concurrent total hip arthroplasty series of a mid1980s design revealed prevalence of mechanical failure of 1 % for cemented stems and 4 % for noncemented stems . Corroborating matched pair comparison neutralized selection bias as a causative factor for these differences . These data indicate contemporary cemented femoral stem fixation is superior to second generation noncemented femoral stem fixation . Controlled comparative studies at midterm to long term followup , such as in this report , are needed to define outcome and indications for current third generation noncemented stem fixation",
"The purpose of this study was to evaluate the mid- to long-term survivorship of Bimetric cementless total hip replacement and assess how it is affected by the acetabular design . This was a retrospective analysis of 127 Bimetric cementless total hip replacements in 110 patients with a follow-up of 7–18 years . A single design stem and three different cementless metal-backed acetabular design s were used . Patients were assessed clinical ly using the Harris hip score and radiologically by independent review of current hip radiographs . There was only one case of aseptic loosening of the femoral stem . The earliest acetabular design showed a high failure rate whilst the latter two design s showed a 96 % survivorship at a mean of 9.5 years . We conclude that a combination of the bimetric stem with either of the latter acetabular cup design s has a good mid- to long-term performance . Résumél’étude de l’évaluation à moyen ou à long terme de la survie d’une prothèse sans cimentde type Bimétric . il s’agit d’une étude prospect i ve de 127 prothèses totales de hanche chez110 patients avec un suivi moyen de 7 à 18 ans . Un seul dessin de tige fémorale et troisdessins différents de cupule métal back sans ciment ont été utilisés . Les patients ont étéévalués sur le plan clinique ( score de Harris ) et sur le plan radiologique . Un seul cas de descellement aseptique de tige fémorale a été retrouvé . Sur les troismodèles de cupule , le premier modèle montre un taux d’échec très important alors que les deuxderniers modèles ont un taux de survie de 96 % à 9,5 ans de recul . En conclusion , nous pouvons affirmer que la combinaison d’une tige de type bimétric associéeaux modèles acétabulaires les plus tardifs ont permis un bon résultat moyen à long terme",
"We prospect ively examined the functional and radiographic outcomes of a serial cohort of 104 Birmingham Hip Resurfacings in an independent centre . Final follow-up was to a mean of 61 months , and six cases were lost to follow-up . Excellent results were obtained in 91 % , but obese patients had significantly ( p . Whilst there were no cases of neck fracture neck narrowing of up to 20 mm was noted . Radiolucent lines were present in a single zone in 9.4 % ( 9/96 ) acetabular and 3.1 % ( 3/96 ) femoral components . However , no components were definitely loose and there were no revisions for any reason during the period of the study . This independent series confirms that the Birmingham Hip Resurfacing gives excellent early clinical results and little early evidence of radiographic failure . The high rate of neck narrowing gives us cause for concern and we would recommend regular radiographic follow-up",
"We performed a prospect i ve study in 108 consecutive patients ( 116 hips ) who were followed for a minimum of 10 years ( 10 - 12 years ) after primary total hip arthroplasty using an uncemented porous-coated anatomic ( PCA ) hip prosthesis . The average age of the patients at operation was 48.4 years ( range , 19 - 85 years ) , and the diagnosis was avascular necrosis of the femoral head in 46 hips , neglected femoral neck fracture in 27 , osteoarthrosis secondary to childhood pyogenic arthritis in 24 , childhood tuberculous arthritis in 5 , and miscellaneous in 14 . The average preoperative Harris Hip Score was 55 points , which improved to 87 points at 11 years . Seventy-five hips ( 65 % ) were excellent , 11 ( 9 % ) were good , and 30 ( 39 % ) were poor . The overall rate of revision was 15 % ( 17 of 116 hips ) . The rate of revision of the femoral component was 11 % ( 13 of 116 hips ) , and the rate of revision of the acetabular component was 15 % ( 17 of 116 hips ) . The prevalence of thigh pain was 28 % at 11 years . The increase in the incidence of aseptic loosening of the femoral component was found to explain the high incidence of severe thigh pain at 11 years ' follow-up . At 11 years , there was femoral osteolysis in 69 hips ( 59 % ) and acetabular osteolysis in 65 hips ( 56 % ) . At 6 years , 20 hips ( 17 % ) showed definite wear of the polyethylene liner . At 11 years , 81 hips ( 70 % ) showed definite wear of the polyethylene liner . Because the complication rate of the PCA hip prosthesis with respect to loosening , osteolysis , and excessive wear in the polyethylene liner is high , we ab and oned the use of this implant",
" One hundred and eighty-four patients who had been managed , between 1984 and 1985 , with a total of 204 consecutive primary total hip arthroplasties with insertion of a Harris-Galante type-I acetabular component without cement were prospect ively studied . There were eighty-two men ( 45 per cent ) and 102 women ( 55 per cent ) . The mean age at the time of the operation was fifty-two years ( range , twenty to eighty-four years ) . One hundred and fifty-seven patients ( 173 hips ) were available for clinical review at a mean of 104 months ( range , seventy-eight to 126 months ) . At this time , the mean preoperative Harris hip score of 52 points ( range , 12 to 79 points ) had improved to a mean of 90 points ( range , 44 to 100 points ) . Two patients ( two hips ) had had an exchange of an excessively worn polyethylene liner . One patient ( one hip ) had had débridement and grafting of an area of massive retroacetabular osteolysis . Two stable acetabular components ( 1 per cent ) had been revised at the time of femoral revision . None of the cups had been revised because of aseptic loosening . Radiographic examination of 150 patients ( 165 hips ) at a mean of 104 months ( range , seventy-eight to 126 months ) revealed that 156 cups ( 95 per cent ) were stable . Eight cups ( 5 per cent ) were considered to be possibly unstable , with a radiolucent line between the prosthesis and the bone that was one millimeter wide or less in at least four of five zones ; two of the eight had a complete radiolucent line in all zones . One component , which had been implanted with a bulk allograft from a femoral head , migrated more than two millimeters in the first two years and then stabilized without complication . Osteolysis was seen in seven acetabula ( 4 per cent ) and was limited to the periphery of the cup in six . Survivorship analysis at ten years revealed that the acetabular component had a 99 per cent chance of survival ( 95 per cent confidence interval , 0.98 to 1.0 ) with revision or aseptic loosening as the end point and a 97 per cent chance of survival ( 95 per cent confidence interval , 0.95 to 1.0 ) with revision , aseptic loosening , or reoperation because of a problem related to the acetabular component as the end point",
" Two hundred consecutive primary total hip arthroplasties ( 196 patients ) carried out between January 1994 and May 1995 using the Elite Plus cemented femoral components ( DePuy International , Leeds , UK ) were enrolled in a prospect i ve study . Fifteen patients were lost to follow-up . The patients were evaluated clinical ly using the Harris Hip Score ( HHS ) and radiographically . The mean HHS was raised from 39.3 preoperatively to 89.6 at 5 years . Radiologically the mean femoral subsidence was 1.40 mm at 5 years . The mean annual rate of re-operation was 0.2 % . There were no revisions for aseptic loosening . In the present series , the Elite Plus hip arthroplasty has produced clinical and radiological results , which are comparable with the Charnley hip at five years",
"There is no published literature to support mid to long term results of hip resurfacing ( HR ) arthroplasty in patients over the age of 70 years . The purpose of our study was to evaluate the function HR in this age group ( 70 or older at the time of surgery ) at medium to long term follow-up . Between July 1997 and November 2002 , the Oswestry Outcome Centre independently and prospect ively collected data on 5000 Birmingham Hip Resurfacings ( BHRs ) . 106 had been implanted in elderly patients who were 70 years of age or older . The post-operative Harris and Merle D'Aubigné and Postel ( MDP ) hip scores and causes for revision were used to ascertain function and implant survival . Hip scores for the older BHR patients were compared with those from younger patients . The average age at surgery of the elderly BHR cohort was 73.2 years ( range , 70.0 to 87.9 years ) with a mean follow-up of 7.1 years ( range , 0.5 to 10.9 years ) . Four patients had a femoral neck fracture and required conversion to a conventional total hip replacement . There were no patients lost to follow-up and no dislocations in this series . The median Harris hip score ( HHS ) was significantly better in the younger BHR group compared with the elderly BHR group , ( 96 vs. 94 p=0.008 ) . There was no significant difference in recovery rates after surgery . There was a significantly higher rate of revision in women than men among the elderly patients ( male= 1 of 65 ( 1.5 % ) ; women = 3 of 19 ( 15.8 % ) , p=0.03 ) . At latest follow-up the elderly patients continued to function well when compared with the younger BHR patients . There was a high mid to long term success rate after HR in patients who were 70 years of age or older , without the failure burden possibly anticipated . Elderly patients had a poorer functional outcome , but a difference in HHS of two points may be of only minor clinical significance",
"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 Hip replacement as a routine procedure was introduced in Lithuania in 1991 . At Klaipeda Hospital , one of the 2 hospitals at which this was begun , the arthroplasties were followed prospect ively from the start . This study concerns the 10-year results from a country with no previous experience of hip replacement . The results are compared with those from a hospital with considerable experience of total hip replacement . Methods We compared the revision rate for the first 658 primary ScanHip arthroplasties inserted at Klaipeda to that for the first 939 ScanHip primary arthroplasties inserted at Lund University Hospital , Sweden . Only patients with osteoarthritis were included , and the endpoint was revision for aseptic loosening with exchange of one or both components . Results We found that patients operated at Klaipeda Hospital had a significantly higher risk of revision ( 12 % ) than those operated in Lund ( 6 % ) . Interpretation Although we could not identify any specific reason for the Swedish results being better than the Lithuanian results , it is probable that previous surgical inexperience of hip replacement in Lithuania played a role . We believe that the findings will stimulate surgeons in Lithuania to analyze their failures and improve the results",
"Some authors suggest the use of larger ( 36 and 40 mm ) femoral heads against highly cross-linked polyethylene acetabular liners will reduce the prevalence of early dislocation after primary total hip arthroplasty ( THA ) . We prospect ively followed 61 consecutive patients at high risk for dislocation to determine the prevalence of early dislocation after primary THA with 36 and 40 mm femoral heads . We established specific indications for the use of these larger heads in primary arthroplasty . There were 65 hips in 61 patients with a minimum followup of 1 year ( mean 2 years , range 1 - 4 years ) . There were 55 36 mm heads and 10 40 mm heads . All arthroplasties were performed by the posterior approach with capsular repair . The prevalence of early dislocation was 4.6 % ( 3 of 65 ) . There was one patient with an anterior dislocation and two with posterior dislocation . No patient underwent reoperation for dislocation . There was no dislocation in the 10 hips that had a 40 mm head . We identified no complications related to the larger femoral heads . The use of larger femoral heads did not notably reduce the prevalence of early dislocation after primary THA in high risk patients compared to historical controls . Therapeutic study : Level IV , case series . See Guidelines for Authors for a complete description of levels of evidence",
"Background Total hip arthroplasty ( THA ) has been associated with high survival rates , but debate remains concerning the best fixation mode of THA . Questions / purpose sWe conducted a r and omized controlled trial ( RCT ) with 250 patients with a mean age of 64 years between October 1987 and January 1992 to compare the results of cementless and cemented fixation . Patients and Methods Patients were evaluated for revision of either of the components . One hundred twenty-seven patients had died ( 51 % ) and 12 ( 4.8 % ) were lost to followup . The minimum 17-year followup data ( mean , 20 years ; range , 17–21 years ) for 52 patients of the cementless group and 41 patients of the cemented group were available for evaluation . Results Kaplan-Meier survivorship analysis at 20 years revealed lower survival rates of cemented compared with cementless THA . The cementless tapered stem was associated with a survivorship of 99 % . Age younger than 65 years and male gender were predictors of revision surgery . Conclusions The efficacy of future RCTs can be enhanced by r and omizing patients in specific patient cohorts stratified to age and gender in multicenter RCTs . Including only younger patients might improve the efficacy of a future RCT with smaller sample sizes being required . A minimum 10-year followup should be anticipated , but this can be expected to be longer if the difference in level of quality between the compared implants is smaller . Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence",
"BACKGROUND The purpose of the present study was to determine cobalt and chromium ion levels in the blood and urine of patients in whom a modern-generation metal-on-metal hip resurfacing device had been implanted . METHODS A total of ninety-seven patients with a Conserve Plus metal-on-metal hip resurfacing implant were followed prospect ively for two years . Cobalt and chromium levels in erythrocytes , serum , and urine were measured preoperatively as well as three , six , twelve , and twenty-four months postoperatively . RESULTS The median serum cobalt and chromium ion levels were 1.04 μg/L ( range , 0.31 to 7.42 μg/L ) and 2.00 μg/L ( range , 0.28 to 10.49 μg/L ) , respectively , at one year after surgery and 1.08 μg/L ( range , 0.44 to 7.13 μg/L ) and 1.64 μg/L ( range , 0.47 to 10.95 μg/L ) , respectively , at two years after surgery . The corresponding mean levels ( and st and ard deviations ) of serum cobalt and chromium were 1.68 ± 1.66 μg/L and 2.70 ± 2.22 μg/L , respectively , at one year after surgery and 1.79 ± 1.66 μg/L and 2.70 ± 2.37 μg/L , respectively , at two years after surgery . CONCLUSIONS These levels compare favorably with other published ion results for metal-on-metal hip resurfacing and replacement implants . No pseudotumors or other adverse soft-tissue reactions were encountered in our study population . Further research is needed to determine the clinical importance of increased cobalt and chromium ion levels in serum and urine following metal-on-metal hip resurfacing ",
"BACKGROUND The use of cementless , proximally porous-coated femoral stems for total hip arthroplasty has increased in popularity . The purpose of the present report was to examine the five to ten-year results associated with the use of a so-called second-generation circumferentially proximally porous-coated titanium-alloy stem . METHODS Between 1991 and 1994 , 123 Harris-Galante Multilock femoral stems were implanted in 101 patients . The average age of the patients at the time of surgery was 53.8 years . The patients were followed prospect ively and were reevaluated at a minimum of five years postoperatively . No patient was lost to follow-up . Twenty-five patients ( thirty hips ) were interviewed by telephone , and four patients ( five hips ) died during the study period because of problems that were unrelated to the operation . The remaining seventy-two patients ( eighty-eight hips ) had a minimum of five years of clinical and radiographic follow-up . RESULTS The average duration of follow-up was seventy-eight months . At the time of the most recent follow-up , the average Harris Hip Score was 95 points . Eighty-seven ( 99 % ) of eighty-eight stems were biologically stable , with eighty-four hips ( 95 % ) having osseous ingrowth and three hips ( 3 % ) having stable fibrous fixation . One stem was revised because of loosening . Thirty-three hips ( 38 % ) had minimal proximal osteolysis , and no hip had diaphyseal osteolysis . Seventy-two hips ( 82 % ) had some degree of stress-shielding in the proximal metaphysis , but only two hips had cortical resorption . None of these patients required additional surgery , and all reported a satisfactory outcome . CONCLUSIONS Given the young age and high activity level of these patients , this stem fared well : the levels of patient function and satisfaction were high , the rates of loosening and revision were very low , and distal osteolysis did not occur . Osseous fixation occurred reliably . Proximal stress-shielding was seen but did not seem to be clinical ly important",
"This study review s the early clinical experience with the Birmingham Hip resurfacing system ( Smith & Nephew , Memphis , Tenn ) in the United States since its approval by the FDA . A total of 230 patients were followed for a mean of 16 months ( range , 6 months ) . There was a significant improvement in the mean preoperative Oxford hip score at the latest follow-up ( 44 points [ range , 30 - 58 points ] to 17 points [ range , 12 - 28 points ] ) . The most commonly used femoral component was 50 mm , and the mean duration of the procedures was 95 minutes ( range , 65 - 180 min ) . there were 3 revisions ( 1.3 % ) . Early results are favorable . As with any device , there is a continuing need for longterm monitoring and large-scale epidemiologic surveillance",
"Background : This study was design ed to compare the fixation of a Mallory-Head total hip prosthesis with and without cement . Methods : Two hundred and fifty patients with osteoarthritis of the hip were r and omized to receive a Mallory-Head total hip prosthesis design ed for insertion with cement or the same prosthesis design ed for insertion without cement . Neither the patient nor the outcomes assessor was aware of the type of prosthesis . Outcomes were assessed with respect to mortality , revision arthroplasty , health-related quality of life ( evaluated with the Harris hip score , Merle d'Aubigné and Postel hip score , McMaster-Toronto Arthritis Patient Preference Disability Question naire ( MACTAR ) , Western Ontario and McMaster University Osteoarthritis Index ( WOMAC ) , and the time trade-off technique ) , and the six-minute-walk test . Patients were seen at three , six , and twelve months and yearly thereafter . Results : The prosthesis was inserted with cement in 124 patients and without cement in 126 patients . The mean age of the patients was sixty-four years , 48 % were female , and the mean duration of follow-up was 6.3 years . There were thirteen revisions in the group that had fixation with cement and six in the group that had fixation without cement ( p = 0.11 ) , and more femoral components were revised in the group that had fixation with cement ( twelve versus one ; p = 0.002 ) . All health-related quality -of-life measures improved postoperatively in both groups . Conclusions : In this r and omized trial , the group that had the cemented Mallory-Head hip prostheses required more revisions of the femoral component than did the group with the cementless Mallory-Head prostheses , which was perhaps related to the titanium-alloy femoral stem . Our findings are specific to the implants evaluated in this study",
" In a matched-pair study of primary total hip arthroplasty , 45 all-polyethylene cemented acetabular components were compared with 45 cementless , hemispheric , titanium acetabular components . At 9 to 12 years , 1 of the cemented acetabular components was revised for aseptic loosening , and 14 ( 31 % ) were radiographically loose . Nine ( 20 % ) cemented acetabular components had pelvic osteolysis . In the cementless acetabular component group , 2 well-fixed components were revised . No components were radiographically loose , and 3 ( 7 % ) had pelvic osteolysis . Thirty-eight ( 97 % ) of the patients in each group were satisfied with the surgery . The clinical results of the cemented and cementless components were excellent . The cementless components had less loosening ( P < .001 ) than the cemented components",
"The Anatomique Benoist Girard ( ABG ) I total hip arthroplasty has been widely used in Europe since 1989 . Two recent midterm reports have shown high rates of component failure secondary to polyethylene wear . To further investigate this issue , our study prospect ively follows 157 consecutive primary total hip arthroplasties using the ABG I prosthesis at an average follow-up of 10 years . Clinical outcomes have been excellent , although the incidence of thigh pain was 7.2 % . Radiographic evaluation of the cup showed eccentric polyethylene wear in 93.6 % of the patients . The average polyethylene linear wear was 2.40 mm , whereas the average annual wear rate was 0.25 mm/y . There were 7 hips ( 5.6 % ) with severe periacetabular osteolysis . Nine revisions were performed for loosening or wear . The overall component survival rate was 92.6 % . The overall survival rate was 92.6 % ( confidence interval , 78.55 - 96.47 ) for the acetabular component and 96.3 % ( confidence interval , 85.67 - 100 ) for the femoral component . Although the clinical and radiographic results of the ABG I total hip arthroplasty in this series have been acceptable , high rates of polyethylene wear , most likely related to sterilization by gamma-irradiation in air , have been the limiting factor in the long-term success of this design",
"Background : Second-generation cementless femoral components were design ed to provide more reliable ingrowth and to limit distal osteolysis by incorporating circumferential proximal ingrowth surfaces . We examined the eight to eleven-year results of total hip arthroplasty with a cementless , anatomically design ed femoral component and a cementless hemispheric acetabular component . Methods : Ninety-two consecutive primary total hip arthroplasties with implantation of a femoral component with a circumferential proximal porous coating ( Anatomic Hip ) and a cementless hemispheric porous-coated acetabular component ( Harris-Galante II ) were performed in eighty-five patients . These patients were prospect ively followed clinical ly and radiographically . Six patients ( seven hips ) died and five patients ( seven hips ) were lost to follow-up , leaving seventy-four patients ( seventy-eight hips ) who had been followed for a mean of ten years ( range , eight to eleven years ) . The mean age at the time of the arthroplasty was fifty-two years . Results : The mean preoperative Harris hip score of 51 points improved to 94 points at the time of final follow-up ; 86 % of the hips had a good or excellent result . Thigh pain was reported as mild to severe after seven hip arthroplasties . No femoral component was revised for any reason , and none were loose radiographically at the time of the last follow-up . Two hips underwent acetabular revision ( one because of dislocation and one because of loosening ) . Kaplan-Meier survivorship analysis was performed with revision or loosening of any component as the end point . The ten-year survival rate was 96.4 % ± 2.1 % for the total hip prosthesis , 100 % for the femoral component , and 96.4 % ± 2.1 % for the acetabular component . Radiolucencies adjacent to the nonporous portion of the femoral component were seen in sixty-eight ( 93 % ) of the -seventy-three hips with complete radiographic follow-up . Femoral osteolysis proximal to the lesser trochanter was noted in four hips ( 5 % ) . No osteolysis was identified distal to the lesser trochanter . Periacetabular osteolysis was identified in twelve hips ( 16 % ) . Five patients underwent exchange of the acetabular liner because of polyethylene wear . Conclusions : This second-generation cementless , anatomically design ed femoral component provided excellent clinical and radiographic results with a 100 % survival rate at ten years . The circumferential porous coating of this implant improved ingrowth and prevented distal osteolysis at a mean of ten years after the arthroplasty",
"We conducted a prospect i ve study of the clinical and radiographic variables related to the survival of 114 cementless resurfacing double-cup hip replacements ( RHR ) with a mean follow-up of 9 ( range : 1 - -16 ) years . Three patients died , and 22 were unavailable for the final review in 2003 . Sixty-one RHRs had to be revised to a total hip replacement . Failure analysis of these revised RHRs showed femoral head and neck resorption under the prosthesis in 33 , acetabular protrusion in seven , both femoral and acetabular resorption in 14 and a femoral-neck fracture in three . One hip had dislocated , and there were three hips with unexplained pain . The Kaplan-Meier 5-year mean survival was 92 % , the 10-year survival was 47 % ( 95 % CI 37 - -57 % ) and the 15-year survival was 30 % ( 95 % CI 20 - -40 % ) . Pre-operative joint destruction ( grade 1 ) , a high degree of radiological osteoporosis , a body mass index > 25 and prosthesis mismatch were significantly related to failure of the RHR . We believe that in young , non-obese patients with pre-operative radiological central destruction but without severe proximal femoral osteoporosis , a resurfacing arthroplasty may have some value . Our failures were mainly due to femoral resorption under the prosthetic femoral component",
"Abstract Metal-on-metal total hip resurfacing arthroplasty has had excellent reported results at early to midterm followup , and some studies suggest that outcomes are comparable to conventional THA . We compared the clinical and radiographic outcomes of two closely matched groups of 54 patients who underwent resurfacing and conventional THA , respectively . Each group consisted of 36 men and 18 women who had a mean age of 52 years and a mean body mass index of 29 kg/m2 . At a minimum followup of 24 months ( mean , 40 months ; range , 24–60 months ) , the mean Harris hip scores increased similarly in both groups ( from 52 to 90 points and from 50 to 91 points for the resurfacing and conventional groups , respectively ) . Radiographic outcomes , revision rates , complications , pain scores , and satisfaction ratings of the two groups were similar . The patients who underwent resurfacing had higher postoperative weighted activity scores than the patients who underwent conventional THA , although they had higher preoperative weighted activity scores as well . The early outcomes of resurfacing are comparable to those of conventional THA . Level of Evidence : Level III , therapeutic study . See the Guidelines for Authors for a complete description of levels of evidence"
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OBJECTIVE The aim of this study was to perform a systematic review and meta- analysis on insulin resistance in adult patients with type 1 diabetes mellitus compared to healthy controls , assessed by hyperinsulinemic euglycemic clamp studies . DESIGN AND METHODS We conducted a systematic search of publications using PubMed , EMBASE , Web of Science and COCHRANE Library . Hyperinsulinemic euglycemic clamp studies comparing adult patients with type 1 diabetes mellitus to healthy controls were eligible . Primary outcome measures were pooled mean differences of insulin sensitivity of endogenous glucose production ( EGP ) , of glucose uptake and of lipolysis . We estimated mean ( st and ardized ) differences and 95 % CIs using r and om effects meta- analysis . RESULTS We included 38 publications in this meta- analysis . The weighed mean differences in EGP during hyperinsulinemia between patients and controls was 0.88 ( 95 % CI : 0.47 , 1.29 ) in the basal state and 0.52 ( 95 % CI : 0.09 , 0.95 ) in insulin stimulated conditions , indicating decreased hepatic insulin sensitivity in patients . Insulin sensitivity of glucose uptake was either reported as M value ( M ) , glucose infusion rate ( GIR ) , glucose disposal rate ( GDR ) or metabolic clearance rate ( MCR ) . Weighed mean differences were similar for M -3.98 ( 95 % CI : -4.68 , -3.29 ) and GIR -4.61 ( 95 % CI : -5.86 , -3.53 ) . Weighed mean difference for GDR was -2.43 ( 95 % CI : -3.03 , -1.83 ) and -3.29 ( 95 % CI : -5.37 , -1.22 ) for MCR , indicating decreased peripheral insulin sensitivity in patients . Insulin mediated inhibition of lipolysis was decreased in patients , reflected by increased non-esterified fatty acid levels . CONCLUSIONS Insulin resistance is a prominent feature of patients with type 1 diabetes mellitus and involves hepatic , peripheral and adipose tissues
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"OBJECTIVE To determine the independent risk factors for coronary artery disease ( CAD ) in type 1 diabetes by type of CAD at first presentation . RESEARCH DESIGN AND METHODS This is a historical prospect i ve cohort study of 603 patients with type 1 diabetes diagnosed before 18 years of age between 1950 and 1980 . The mean age and duration of diabetes at baseline were 28 ( range 8 - 47 ) and 19 years ( 7 - 37 ) , respectively , and patients were followed for 10 years . Patients with prevalent CAD were excluded from the study . Electrocardiogram ( ECG ) ischemia was defined by Minnesota Code ( MC ) 1.3 , 4.1 - 3 , 5.1 - 3 , or 7.1 ; angina was determined by Pittsburgh Epidemiology of Diabetes Complications ( EDC ) study physician diagnosis ; and hard CAD was determined by angiographic stenosis > or = 50 % , revascularization procedure , Q waves ( MC 1.1 - 1.2 ) , nonfatal myocardial infa rct ion ( MI ) , or CAD death . RESULTS A total of 108 incident CAD events occurred during the 10-year follow-up : 17 cases of ECG ischemia , 49 cases of angina , and 42 cases of hard CAD ( 5 CAD deaths , 25 nonfatal MI or major Q waves , and 12 revascularization or > or = 50 % stenosis ) . Blood pressure , lipid levels , inflammatory markers , renal disease , and peripheral vascular disease showed a positive gradient across the groups of no CAD , angina , and hard CAD ( P estimated glucose disposal rate ( eGDR ) and physical activity showed inverse associations ( P angina ( P = 0.016 ) , whereas HbA(1 ) showed no association with subsequent CAD . CONCLUSIONS These data suggest that although the st and ard CAD risk factors are still operative in type 1 diabetes , greater glycemia does not seem to predict future CAD events . In addition , depressive symptomatology predicts angina and insulin resistance ( eGDR ) predicts hard CAD end points",
"Insulin resistance is a key pathogenic factor of type 2 diabetes ( T2DM ) ; in contrast , in type 1 diabetes ( T1DM ) it is considered a secondary alteration . Increased intramyocellular lipid ( IMCL ) content accumulation and reduced plasma adiponectin were suggested to be pathogenic events of insulin resistance in T2DM . This study was design ed to assess whether IMCL content and plasma adiponectin were also associated with the severity of insulin resistance in T1DM . We studied 18 patients with T1DM , 7 older and overweight/obese patients with T2DM , and 15 nondiabetic , insulin-resistant offspring of T2DM parents ( OFF ) and 15 healthy individuals ( NOR ) as appropriate control groups matched for anthropometric features with T1DM patients by means of the euglycemic hyperinsulinemic clamp combined with the infusion of [6,6 - 2H2]glucose and 1H magnetic resonance spectroscopy of the calf muscles . T1DM and T2DM patients showed reduced insulin-stimulated glucose metabolic clearance rate ( MCR : 5.1 + /- 0.6 and 3.2 + /- 0.8 ml x kg(-1 ) min(-1 ) ) similar to OFF ( 5.3 + /- 0.4 ml x kg(-1 ) x min(-1 ) ) compared with NOR ( 8.5 + /- 0.5 ml x kg(-1 ) min(-1 ) , P Soleus IMCL content was increased in T1DM ( 112 + /- 15 AU ) , T2DM ( 108 + /- 10 AU ) and OFF ( 82 + /- 13 AU ) compared with NOR ( 52 + /- 7 AU , P MCR ( R2 = 0.27 , P IMCL content and Hb A1c was found only in T1DM ( R2 = 0.57 , P Fasting plasma adiponectin was reduced in T2DM ( 7 + /- 1 microg/ml , P = 0.01 ) and OFF ( 11 + /- 1 microg/ml , P = 0.03 ) but not in T1DM ( 25 + /- 6 microg/ml ) , whose plasma level was increased with respect to both OFF ( P = 0.03 ) and NOR ( 16 + /- 2 microg/ml , P = 0.05 ) . In conclusion , in T1DM , T2DM , and OFF , IMCL content was associated with insulin resistance , demonstrating that IMCL accretion is a marker of insulin resistance common to both primary genetically determined and secondary metabolic ( chronic hyperglycemia ) alterations . The increased adiponectin levels in insulin-resistant patients with T1DM , in contrast to the reduced levels found in patients with T2DM and in OFF , demonstrated that the relationship of adiponectin to insulin resistance in humans is still unclear",
"AIMS To quantify and compare associations between femoral-gluteal adiposity and insulin sensitivity in adults with Type 1 diabetes mellitus with adults with normal glucose tolerance . METHODS Individuals with Type 1 diabetes ( n = 28 ) were recruited from the Pittsburgh Epidemiology of Diabetes Complication study , a 24-year prospect i ve study of childhood-onset diabetes , and compared cross-sectionally with individuals with normal glucose tolerance ( n = 56 ) of similar age , sex and BMI . Insulin sensitivity was defined as whole-body glucose disposal measured by hyperinsulinaemic-euglycaemic clamps . Adiposity was quantified by dual energy X-ray absorptiometry . RESULTS Individuals with Type 1 diabetes exhibited lower insulin sensitivity ( 5.8 vs. 8.2 mg min(-1 ) kg fat-free mass(-1 ) , P total fat mass ( 20.1 vs. 29.0 kg , P leg fat mass ( 36.0 vs.37.7 % , P = 0.03 ) , but similar proportional trunk fat ( % trunk fat mass ) compared with individuals with normal glucose tolerance . Overall , results from linear regression demonstrated that higher % leg fat mass ( P % trunk fat mass ( P insulin sensitivity after adjustments for age , sex , height , total fat mass ( kg ) and diabetes status . Higher % leg fat mass was independently associated with higher insulin sensitivity in individuals with normal glucose tolerance ( P insulin sensitivity is a prominent feature of Type 1 diabetes and is associated with total and abdominal adiposity . Compared with adults with normal glucose tolerance , leg fat mass does not show any positive association with insulin sensitivity in Type 1 diabetes",
"OBJECTIVE To determine the incidence of retinopathy and the relative importance of its risk factors in type 1 diabetes . RESEARCH DESIGN AND METHODS This is a 7.3-year follow-up of 764 of 1,215 ( 63 % ) people with type 1 diabetes across Europe , aged 15 - 60 years at baseline with no retinopathy ( the EURODIAB Prospect i ve Complications Study ) . Retinal photographs were taken at baseline and follow-up and risk factors were assessed to a st and ard protocol . RESULTS Retinopathy incidence was 56 % ( 429/764 , 95 % CI 52 - 59 % ) . Key risk factors included diabetes duration and glycemic control . We found no evidence of a threshold effect for HbA1c on retinopathy incidence . Univariate associations were observed between incidence and albumin excretion rate , cholesterol , triglyceride , fibrinogen , von Willebr and factor , gamma-glutamyltransferase , waist-to-hip ratio , and insulin dose . No associations were observed for blood pressure , cardiovascular disease , or smoking . Independent risk factors , as assessed by st and ardized regression effects , were HbA1C ( 1.93 , P = 0.0001 ) , duration ( 1.32 , P = 0.008 ) , waist-to-hip ratio ( 1.32 , P = 0.01 ) , and fasting triglyceride ( 1.24 , P = 0.04 ) . CONCLUSIONS Retinopathy incidence in type 1 diabetes remains high . Key risk factors include diabetes duration and glycemic control , with no evidence of a threshold for the latter . Other independent risk factors , such as waist-to-hip ratio and triglyceride levels , both markers of insulin resistance , were strongly related to incidence",
"Background Hypertensive patients frequently show resistance to insulin-stimulated glucose uptake and hyperinsulinemia . Diuretics and β-adrenoceptor blocking agents have been found to decrease insulin sensitivity , whereas α1-blockers and angiotensin converting enzyme inhibitors seem to improve it . Objective To compare the effects of a 3 months ' antihypertensive treatment with carvedilol , a non-selective β-adrenoceptor blocker with α1-blocking properties , with the β1-selective receptor blocker metoprolol on insulin sensitivity in non-diabetic hypertensive patients . Design A multicenter double-blind r and omized study . Subjects and methods Seventy-two non-diabetic hypertensive patients were r and omly assigned to treatment with either carvedilol or metoprolol . An isoglycemic , hyperinsulinemic glucose clamp was conducted before and after 12 weeks of treatment ; the metabolic clearance rate for glucose was taken as an indicator of insulin sensitivity . Results The two groups did not differ in age , sex , body mass index , blood pressure or lipids , and treatment effectively lowered blood pressure . In both groups , insulin sensitivity was impaired at baseline . After metoprolol treatment , insulin sensitivity further decreased significantly by about 14 % , whereas it increased after carvedilol . There was also a decrease in high-density lipoprotein and an increase in triglycerides levels in patients in the metoprolol-treated group , whereas these parameters remained unchanged in patients in the carvedilol-treated group . Conclusion This study confirms previous findings of a reduction in insulin sensitivity after chronic metoprolol treatment . Carvedilol treatment , however , result ed in a slight increase in insulin resistance and a better lipid profile . We thus demonstrate that a β-blocker with α1-blocking properties has favorable effects on glucose metabolism , suggesting a potentially important role of peripheral blood flow in regulating glucose uptake . These findings imply that β-blocker treatment , when combined with α1-blocking activity has advantageous effects on insulin sensitivity and lipids and could therefore be suitable for patients with the metabolic syndrome",
"OBJECTIVE in type 2 diabetic patients and their first-degree relatives , insulin resistance ( IR ) is associated with impairment of insulin-stimulated myocellular glucose-6-phosphate ( g6p ) and unidirectional flux through ATP synthase ( fATP ) , suggesting the presence of inherited abnormal mitochondrial oxidative fitness . We hypothesized that patients with long-st and ing type 1 diabetes may also exhibit insulin resistance as well as lower fATP . DESIGN this single-centre trial was registered at Clinical Trials.gov ( NCT00481598 ) . SUBJECTS we included eight nonobese type 1 diabetic patients ( mean diabetes duration : 17 years ) with near-target glycaemic control [ haemoglobin A1c ( HbA1c ) : 6.8 ± 0.4 % ] during treatment with continuous subcutaneous insulin infusion pumps and eight healthy volunteers ( HbA1c : 5.4 ± 0.2 % ) of comparable age , body mass and level of physical activity . OUTCOME MEASURES myocellular fATP , g6p and intramyocellular lipid content ( IMCL ) were measured with ( 1 ) H/(31 ) P magnetic resonance spectroscopy during fasting and hyperinsulinaemic-euglycaemic clamp tests . RESULTS fasting fATP , g6p and IMCL did not differ between groups . During stimulation by insulin , type 1 diabetic patients exhibited approximately 50 % ( P lower whole-body glucose disposal along with approximately 42 % ( P = 0.003 ) lower intramyocellular g6p and approximately25 % ( P = 0.024 ) lower fATP . Insulin-stimulated fATP correlated positively with whole-body insulin sensitivity ( R = 0.706 , P = 0.002 ) and negatively with HbA1c ( R = -0.675 , P = 0.004 ) . CONCLUSIONS despite documented near-target glycaemic control for 1 year , nonobese patients with long-st and ing type 1 diabetes can exhibit insulin resistance . This associates with lower insulin-stimulated flux through muscular ATP synthase which could result from glucose toxicity",
"To examine the natural course of insulin action in Type I diabetes , we followed 15 patients prospect ively for one year after the diagnosis of diabetes and also performed a cross-sectional study of 53 additional patients who had had diabetes for 2 to 32 years . Two weeks after diagnosis , the rate of glucose uptake during hyperinsulinemia , a measure of insulin action , was 32 percent lower in the patients with diabetes than in 30 matched normal subjects ( P less than 0.01 ) , but it rose to normal during the subsequent three months . At three months after diagnosis , 9 of 21 patients ( 43 percent ) were in clinical remission and did not require insulin therapy . In these patients , insulin action was 40 percent greater ( P less than 0.002 ) than in the patients who continued to need insulin treatment . Fasting plasma C-peptide levels were slightly but not significantly higher in the patients who had a remission than in the other patients . In patients who had had diabetes for one year or more , insulin action was also reduced by an average of 40 percent ( although there was considerable variation between patients ) , and it was inversely related to glycemic control and relative body weight . Thus , in patients with newly diagnosed Type I diabetes , a transient normalization of insulin action may occur after an initial reduction , along with a partial recovery of endogenous insulin secretion , and these events may contribute to the development of a clinical remission ( \" honeymoon \" period ) . A majority of patients with diabetes of long duration are characterized by varying degrees of insulin resistance"
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The effects of pycnogenol on plasma lipids are controversial . A systematic review and meta- analysis of clinical trials were conducted to obtain a conclusive result in humans . PubMed , Scopus , and Google Scholar were systematic ally search ed until March 2018 , to explore the clinical trials that examined the effect of pycnogenol supplementation on lipid parameters among adult human . Method ological quality of the eligible studies was evaluated using the Cochrane Collaboration 's tool . To estimate the effect size , changes in blood lipids were implemented . Results were pooled using a r and om effects model . Potential sources of heterogeneity were explored by subgroup analysis . A systematic review and meta- analysis of 14 clinical trials with 1,065 participants suggested a significant increase in plasma concentration of high density lipoprotein cholesterol ( HDL-C ; 3.27 mg/dL ; 95 % CI [ 0.19 , 6.36 ] ; p = 0.038 ) . In contrast , plasma levels of total cholesterol ( TC ; -4.45 mg/dL , 95 % CI [ -11.24 , 2.34 ] ; p = 0.199 ) , triacylglycerol ( TAG ; -3.64 mg/dL ; 95 % CI [ -17.89 , 10.61 ] ; p = 0.616 ) , and low density lipoprotein cholesterol ( LDL-C ; -3.61 mg/dl ; 95 % CI [ -8.76 , 1.55 ] ; p = 0.171 ) were not altered . Adjustment for confounding variables was poor in included studies . Also , these studies did not assess dietary lipid intake . The results indicate that pycnogenol supplementation improves levels of HDL-C ; however , the changes in TC , TAG , and LDL-C were not clinical ly relevant . Since there are few phytochemicals that have a significant increasing effect on HDL-C levels , pycnogenol may have important role in prevention of cardiovascular diseases
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"Association between white rice intake and risk factors of cardiovascular diseases remained uncertain . Most of the previous published studies have been done in western countries with different lifestyles , and scant data are available from the Middle East region , including Iran . This cross-sectional study was conducted in the structure of Isfahan Healthy Heart Program ( IHHP ) to assess the association between white rice consumption and risk factors of cardiovascular diseases . In the present study , 3,006 men were included from three counties of Isfahan , Najafabad , and Arak by multistage cluster r and om-sampling method . Dietary intake was assessed with a 49-item food frequency question naire ( FFQ ) . Laboratory assessment was done in a st and ardized central laboratory . Outcome variables were fasting blood glucose , serum lipid levels , and anthropometric variables . Socioeconomic and demographic data , physical activity , and body mass index ( BMI ) were considered covariates and were adjusted in analysis . In this study , Student 's t-test , chi-square test , and logistic regression were used for statistical analyses . Means of BMI among those subjects who consumed white rice less than 7 times per week and people who consumed 7 - 14 times per week were almost similar—24.8±4.3 vs 24.5±4.7 kg/m2 . There was no significant association between white rice consumption and risk factors of cardiovascular diseases , such as fasting blood sugar and serum lipid profiles . Although whole grain consumption has undeniable effect on preventing cardiovascular disease risk , white rice consumption was not associated with cardiovascular risks among Iranian men in the present study . Further prospect i ve studies with a semi-quantitative FFQ or dietary record question naire , representing type and portion-size of rice intake as well as cooking methods and other foods consumed with rice that affect glycaemic index ( GI ) of rice , are required to support our finding and to illustrate the probable mechanism",
"BACKGROUND Cardiovascular diseases ( CVD ) are a set of metabolic disorders affecting heart and blood vessels . Green tea and sour tea ( Hibiscus sabdariffa L. ) have attracted significant attention recently due to their high popularity , nutrient profile and therapeutic effects . The aim of the present study was to compare the effects of green tea and sour tea supplementation on blood pressure and lipid profile in healthy adult men . METHODS This r and omized , double-blind , placebo-controlled trial included 54 healthy adult men . The participants were r and omly assigned to two intervention groups receiving 450 mg green tea or sour tea and one placebo group which consumed 450 mg placebo ( maltodextrin ) for 6 weeks . Blood pressure , lipid profile , dietary intake and physical activity were measured pre- and post-intervention and compared . RESULTS After 6 weeks of intervention , sour tea supplementation led to a significant decrease in systolic blood pressure ( SBP ) compared with the placebo group . However , we faild to find any significant difference in SBP between green tea and control groups . Also , no significant changes were observed in diastolic blood pressure ( DBP ) and lipid profile between the three groups . In comparison with baseline , there was a significant increase in the mean level of serum high-density lipoprotein cholesterol ( HDL-C ) in green tea and sour tea groups . Also , the interventions result ed in significant decrease in the mean levels of serum total cholesterol ( TC ) and low-density lipoprotein cholesterol ( LDL-C ) and DBP in the sour tea group compared with the pre-intervention value . CONCLUSION On the basis of our findings , sour tea supplementation led to decreased SBP in healthy men compared with the placebo , but there was no significant difference between their effects on DBP and lipid profile",
" Pycnogenol ® ( PYC ) , an extract of French maritime pine bark ( Pinus pinaster ) , is a potent antioxidant with potential health benefits . Its bioavailabilty has previously been shown by urinary excretion studies of constituents and metabolites of PYC . The aim of this study was to test the effect of PYC supplementation on measures of oxidative stress and the lipid profile in humans . Twenty-five healthy subjects received PYC ( 150 mg/d ) for 6 wk . Fasting blood was collected at baseline , after 3 and 6 wk of supplementation , and again after a 4-wk washout period . After 6 wk of supplementation with PYC , a significant increase in plasma polyphenol levels was detectable , which was reversed after the 4-wk washout phase . The antioxidant effect of PYC was demonstrated by a significant increase in oxygen radical absorbance capacity ( ORAC ) in plasma throughout the supplementation period ( P The ORAC value returned to baseline after the 4-wk washout period . Moreover , in addition to its antioxidant effects , PYC significantly reduced LDL-cholesterol levels and increased HDL-cholesterol levels in plasma of two-thirds of the subjects . While the LDL changes reversed during washout , the HDL increase did not . There was no significant difference in LDL oxidizability or plasma lipid peroxides following PYC supplementation . Hence , following oral supplementation in humans , PYC significantly increases antioxidant capacity of plasma , as determined by ORAC , and exerts favorable effects on the lipid profile",
"BACKGROUND Orange juice-a rich source of vitamin C , folate , and flavonoids such as hesperidin-induces hypocholesterolemic responses in animals . OBJECTIVE We determined whether orange juice beneficially altered blood lipids in subjects with moderate hypercholesterolemia . DESIGN The sample consisted of 16 healthy men and 9 healthy women with elevated plasma total and LDL-cholesterol and normal plasma triacylglycerol concentrations . Participants incorporated 1 , 2 , or 3 cups ( 250 mL each ) of orange juice sequentially into their diets , each dose over a period of 4 wk . This was followed by a 5-wk washout period . Plasma lipid , folate , homocyst(e)ine , and vitamin C ( a compliance marker ) concentrations were measured at baseline , after each treatment , and after the washout period . RESULTS Consumption of 750 mL but not of 250 or 500 mL orange juice daily increased HDL-cholesterol concentrations by 21 % ( P : triacylglycerol concentrations by 30 % ( from 1.56 + /- 0.72 to 2.03 + /- 0.91 mmol/L ; P : folate concentrations by 18 % ( P : LDL-HDL cholesterol ratio by 16 % ( P : homocyst(e)ine concentrations . Plasma vitamin C concentrations increased significantly during each dietary period ( 2.1 , 3.1 , and 3.8 times , respectively ) . CONCLUSIONS Orange juice ( 750 mL/d ) improved blood lipid profiles in hypercholesterolemic subjects , confirming recommendations to consume > /=5 - 10 servings of fruit and vegetables daily",
"BACKGROUND Although modifiable cardiovascular disease risk factors are common , some patients eschew conventional drug treatments in favor of natural alternatives . Pine bark extract , a dietary supplement source of antioxidant oligomeric proanthocyanidin complexes , has multiple putative cardiovascular benefits . Studies published to date about the supplement have notable method ological limitations . METHODS We r and omized 130 individuals with increased cardiovascular disease risk to take 200 mg of a water-based extract of pine bark ( n = 64 ; Toyo-FVG , Toyo Bio-Pharma , Torrance , California ; Shinyaku Co , Ltd , Saga , Japan ; also marketed as Flavagenol in Japan ) or placebo ( n = 66 ) once per day . Blood pressure , our primary outcome , and other cardiovascular disease risk factors were measured at baseline and at 6 and 12 weeks . Statistical analyses were conducted using regression models . RESULTS Baseline characteristics did not differ between the study groups . Over the 12-week intervention , the sum of systolic and diastolic blood pressures decreased by 1.0 mm Hg ( 95 % confidence interval , -4.2 to 2.1 mm Hg ) in the pine bark extract-treated group and by 1.9 mm Hg ( -5.5 to 1.7 mm Hg ) in the placebo group ( P = .87 ) . Other outcomes were likewise not significantly different , including body mass index , lipid panel measures , liver transaminase test results , lipoprotein cholesterol particle size , and levels of insulin , lipoprotein(a ) , fasting glucose , and high-sensitivity C-reactive protein . There were no subgroups for whom intake of pine bark extract affected cardiovascular disease risk factors . CONCLUSIONS This pine bark extract ( at a dosage of 200 mg/d ) was safe but was not associated with improvement in cardiovascular disease risk factors . Although variations among participants , dosages , and chemical preparations could contribute to different findings compared with past studies , our results are consistent with a general failure of antioxidants to demonstrate cardiovascular benefits . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00425945",
"The aim of this study was to compare the efficacy of Venostasin ( horse chestnut seed extract ) and Pycnogenol ( French maritime pine bark extract ) in the treatment of chronic venous insufficiency ( CVI ) . In an open , controlled comparative study 40 patients with diagnosed CVI were treated either with 600 mg chestnut seed extract per day or 360 mg Pycnogenol per day over a period of 4 weeks . The following parameters were investigated before the start of treatment and after 2 and 4 weeks of treatment : circumference of the lower legs and rating of subjective symptoms ( scores ) of pain , cramps , night-time swelling , feeling of \" heaviness \" , and reddening of the skin . In addition , blood levels of cholesterol LDL and HDL were determined before and at the end of treatment . Pycnogenol significantly reduced the circumference of the lower limbs and significantly improved subjective symptoms . Furthermore , Pycnogenol significantly decreased cholesterol and LDL values in the blood , whereas HDL remained unaffected . Venostasin only moderately but not significantly , reduced the circumference of the lower limbs and marginally improved symptoms . Venostasin had no influence on the determined lipid values . Both medications were equally well tolerated . In conclusion , Pycnogenol was found to be more efficacious than Venostasin for the treatment of CVI",
"AIMS Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine . Pycnogenol is a proprietary bark extract of the French maritime pine tree ( Pinus pinaster ssp . atlantica ) that exerts antioxidative , anti-inflammatory , and anti-platelet effects . However , the effects of Pycnogenol on endothelial dysfunction , a precursor of atherosclerosis and cardiovascular events , remain still elusive . METHODS AND RESULTS Twenty-three patients with coronary artery disease ( CAD ) completed this r and omized , double-blind , placebo-controlled cross-over study . Patients received Pycnogenol ( 200 mg/day ) for 8 weeks followed by placebo or vice versa on top of st and ard cardiovascular therapy . Between the two treatment periods , a 2-week washout period was scheduled . At baseline and after each treatment period , endothelial function , non-invasively assessed by flow-mediated dilatation ( FMD ) of the brachial artery using high-resolution ultrasound , biomarkers of oxidative stress and inflammation , platelet adhesion , and 24 h blood pressure monitoring were evaluated . In CAD patients , Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 ( P observed with placebo ( 5.4 ± 2.4 to 4.7 ± 2.0 ; P = 0.051 ) . This difference between study groups was significant [ estimated treatment effect 2.75 ; 95 % confidence interval ( CI ) : 1.75 , 3.75 , P 0.0001 ] . 15-F(2t)-Isoprostane , an index of oxidative stress , significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment , while no change was observed in the placebo group ( mean difference 0.06 pg/mL with an associated 95 % CI ( 0.01 , 0.11 ) , P = 0.012 ] . Inflammation markers , platelet adhesion , and blood pressure did not change after treatment with Pycnogenol or placebo . CONCLUSION This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress",
"The aim of this study was to investigate the clinical efficacy of oral Pycnogenol ® ( Horphag Research Ltd , United Kingdom ) in patients with diabetic microangiopathy . Patients without a history of diabetic ulcerations were treated with Pycnogenol . Patients received oral Pycnogenol ( 50 mg capsules , 3 times daily for a total of 150 mg daily for 4 weeks ) . A group of 30 patients was included ( severe microangiopathy ) ; 30 comparable patients were observed as controls ( no treatment during the observation period ) . All patients ( age , 59 years ; range , 55 - 68 years ; male : female = 18:12 ) included in the treatment group completed the 4-week study . Also , all controls completed the follow-up period . There were no drop-outs . All included subjects had signs and symptoms of diabetic microangiopathy . The duration of diabetes — from the first signs/symptoms — was on average 7.5 years ( SD = 3 ) . After 4 weeks , microcirculatory and clinical evaluations showed a progressive decrease in skin flux at rest in the foot ( indicating an improvement in the level of microangiopathy ) , a significant decrease in capillary filtration , and a significant improvement in the venoarteriolar response in all treated subjects . There were no visible effects in controls except a slight reduction in skin flux at rest in the foot . Treatment was well tolerated in both groups . In conclusion , this study confirms the clinical efficacy of Pycnogenol in patients with diabetic microangiopathy . The study indicates the clinical role of Pycnogenol in the management , treatment , and control of this common clinical problem . The treatment may be also useful to prevent diabetic ulcerations by controlling the level of microangiopathy",
"Patients with type 2 diabetes are at considerable risk of excessive morbidity and mortality from cardiovascular disease ( CVD ) . We investigated the clinical effectiveness of Pycnogenol , a flavonoid-rich dietary supplement , in reducing antihypertensive medication use and CVD risk factors in subjects with type 2 diabetes . Forty-eight individuals were enrolled in a r and omized , double-blind , placebo-controlled trial with parallel-group design . Patients were diagnosed with both type 2 diabetes and mild to moderate hypertension and were undergoing treatment with angiotensin-converting enzyme ( ACE ) inhibitors . Subjects were r and omly assigned to receive either Pycnogenol pill ( 125 mg daily ) or matched placebo for 12 weeks . According to the values of blood pressure ( BP ) measured at 2-week intervals , the pretrial ACE inhibitor dosage was left unchanged , reduced by 50 % , or brought back to the pretrial dosage until a stable BP was obtained . Fasting plasma glucose , low-density lipoprotein ( LDL ) cholesterol , glycosylated hemoglobin ( HbA1c ) , serum endothelin-1 , and urinary albumin were evaluated monthly . Pycnogenol treatment achieved BP control in 58.3 % of subjects at the end of the 12 weeks with 50 % reduction in individual pretrial dose of ACE-inhibitors ( P Plasma endothelin-1 decreased by 3.9 pg/mL in Pycnogenol-treated group vs 0.5 pg/mL increase in control group ( P Mean HbA1c dropped by 0.8 % in Pycnogenol-treated group ( P Fasting plasma glucose declined by 23.7 mg/dL in Pycnogenol-treated group vs 5.7 mg/dL in control group ( P Low-density lipoprotein cholesterol improved significantly in Pycnogenol-treated group , declining by 12.7 mg/dL ( P urinary albumin level was observed at week 8 compared with the control group ( P Pycnogenol result ed in improved diabetes control , lowered CVD risk factors , and reduced antihypertensive medicine use vs controls",
" Pycnogenol ® , an extract of bark from the French maritime pine , Pinus pinaster Ait . , consists of a concentrate of water-soluble polyphenols . Pycnogenol ® contains the bioflavonoids catechin and taxifolin as well as phenolcarbonic acids . Antioxidants , such as bioflavonoids , enhance endothelial nitric oxide ( NO ) synthase expression and subsequent NO release from endothelial cells . The purpose of this study was to determine Pycnogenol ® 's effects on endothelium-dependent vasodilation in humans . This was a double-blind , r and omized , placebo and active drug study . We evaluated forearm blood flow ( FBF ) responses to acetylcholine ( ACh ) , an endothelium-dependent vasodilator , and to sodium nitroprusside ( SNP ) , an endothelium-independent vasodilator , in healthy young men before and after 2 weeks of daily oral administration of Pycnogenol ® ( 180 mg/day ) ( n=8 ) or placebo ( n=8 ) . FBF was measured by using strain-gauge plethysmography . Neither the placebo nor Pycnogenol ® altered forearm or systemic hemodynamics . Pycnogenol ® , but not placebo , augmented FBF response to ACh , from 13.1±7.0 to 18.5±4.0 mL/min per 100 mL tissue ( p was similar before and after 2 weeks of treatment in the control and Pycnogenol ® groups . The administration of NG-monomethyl-L-arginine , an NO synthase inhibitor , completely abolished Pycnogenol ® -induced augmentation of the FBF response to ACh . These findings suggest that Pycnogenol ® augments endothelium-dependent vasodilation by increasing in NO production . Pycnogenol ® would be useful for treating various diseases whose pathogeneses involve endothelial dysfunction",
"A placebo-controlled , double-blind , parallel group study was performed with 58 patients to investigate effects of French maritime pine bark extract , Pycnogenol , on patients with hypertension . Supplementation of the patients with 100 mg Pycnogenol over a period of 12 weeks helped to reduce the dose of the calcium antagonist nifedipine in a statistically significant manner . The intake of Pycnogenol decreased endothelin-1 concentrations significantly compared to placebo while concentrations of 6-keto prostagl and in F1a in plasma were significantly higher compared to placebo . Values for nitric oxide ( NO ) in plasma increased in both groups , but the differences were not significant . Angiotensin II concentrations in plasma were lowered in the placebo group to a larger extent than in the Pycnogenol group . Heart rate , electrolytes and blood urea nitrogen were not changed during treatment in both groups of patients . Unwanted effects observed in both groups were of mild and transient nature , such as gastrointestinal problems , vertigo , headache and nausea . Differences in rate of side effects were not statistically significant between the two groups . Study results support a supplementation with Pycnogenol for mildly hypertensive patients",
"BACKGROUND The aim of the study was the evaluation of the efficacy of Pycnogenol ® in peri-menopausal women in controlling homocysteine and C-reactive protein ( CRP ) levels , borderline cardiovascular risk factors , oxidative stress ( OS ) and symptoms associated to menopausal transition ( MT ) . METHODS Pycnogenol ® , 100mg/day , was used as a supplement for 8 weeks by a group of 35 women . A comparable group of 35 women with identical cardiovascular risk factors was included as the control group . All women were instructed to participate in a best management plan of menopause . RESULTS The two groups were comparable . All women completed the eight weeks study . Only minor deviations from the best management plan were observed . At inclusion , both groups were similar in respect to risk factors . Supplementation with Pycnogenol ® decreased the slightly elevated cholesterol and triglycerides after 8 weeks ( P the fasting glucose levels were normalized ( P borderline increased blood pressure was reduced to normal values at 8 weeks ( P ) . Plasma free radicals dropped significantly by 22 % ( P decreased sharply by 43 % and 60 % , respectively ( P menopausal symptoms , scored by The Menopausal Symptoms Question naire 34 , improved significantly following supplementation with Pycnogenol ® . The supplementation was well tolerated . CONCLUSIONS The supplementation with Pycnogenol ® improved the quality of life of perimenopausal women and normalized a series of cardiovascular risk factors , especially factors connected to cardiovascular events , as homocysteine and CRP",
"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",
"This study evaluated the effects of Pycnogenol as an adjunct to angiotensin-converting enzyme (ACE)-inhibitor ramipril treatment of hypertensive patients presenting with early signs of renal function problems . One group of 26 patients was medicated with 10 mg ramipril per day only ; a second group of 29 patients took Pycnogenol in addition to the ACE inhibitor over a period of 6 months . At trial end , a lowered systolic and diastolic blood pressure was found in both groups , with a significant further reduction of diastolic pressure in the group given Pycnogenol in addition to ramipril . The major aim of this study was the investigation of kidney-protective effects of Pycnogenol . Urinary albumin decreased from 87 ± 23 to 64 ± 16 mg/d with ramipril only . Additional Pycnogenol lowered albumin significantly better from 91 ± 25 to 39 ± 13 mg/day ( P groups , serum creatinine was lowered ; however , only in the combination treatment group did the effect reached statistical significance . In both groups , CRP levels decreased from 2.1 to 1.8 with ramipril and from 2.2 to 1.1 with the ramipril — Pycnogenol combination ; the latter reached statistical significance . Kidney cortical flow velocity was investigated by Doppler color duplex ultrasonography . Both systolic and diastolic flow velocities increased significantly after 6 months medication with ramipril . The addition of Pycnogenol to the regimen statistically significantly further enhanced kidney cortical flow velocities , by 8 % for diastolic flow and 12 % for systolic flow , relative to values found for the group taking ramipril only . The protective effects of Pycnogenol for initial kidney damage found in this study warrant further research with a larger number of patients and over a longer period of time",
"The study examines the effects of the antioxidant flavonoid Pycnogenol on a range of cognitive and biochemical measures in healthy elderly individuals . The study used a double-blind , placebo-controlled , matched-pair design , with 101 elderly participants ( 60—85 years ) consuming a daily dose of 150 mg of Pycnogenol for a three-month treatment period . Participants were assessed at baseline , then at 1 , 2 , and 3 months of the treatment . The control ( placebo ) and Pycnogenol groups were matched by age , sex , body mass index , micronutrient intake , and intelligence . The cognitive tasks comprised measures of attention , working memory , episodic memory , and psychomotor performance . The biological measures comprised levels of clinical hepatic enzymes , serum lipid profile , human growth hormone , and lipid peroxidation products . Statistically significant interactions were found for memory-based cognitive variables and lipid peroxidation products , with the Pycnogenol group displaying improved working memory and decreased concentrations of F2-isoprostanes relative to the control group",
"BACKGROUND Oligopinۚ ( OP ) is a quantified extract from French Maritime Pine bark ( FMPB ) with low molecular weight procyanidins . The cardioprotective effects of OP need to be tested in human clinical intervention trials with an appropriate design . PURPOSE The aim of the present study was to assess the effect of subchronic consumption of OP on cardiovascular disease risk factors such as lipid profile , systolic blood pressure ( BP ) and oxidized-Low Density Lipoprotein ( ox-LDL ) in stage-1-hypertensive subjects . METHODS Between February 14 and May 31 , 2014 , eligible subjects were recruited from the outpatient clinics of Hospital Universitari Sant Joan ( Reus , Spain ) . A total of 24 participants ( mean age ± DS ; 57.36 ± 11.25 ; 17 men ) with stage-1-hypertension who were not receiving BP-lowering medication and LDL cholesterol were r and omized in a double-blind , placebo-controlled , crossover study . The subjects received 2 capsules/day with 75 mg of OP or placebo for 5-weeks . RESULTS At 5-weeks , compared to the placebo , OP raised High Density Lipoprotein-cholesterol ( HDL-c ) by 14.06 % ( p = 0.012 ) and apolipoprotein A-1 by 8.12 % ( p = 0.038 ) and reduced the ratio of apolipoprotein B-100/A-1 by 10.26 % ( p = 0.046 ) . Moreover , at 5-weeks , compared to the baseline , OP reduced the systolic BP by 6.36 mmHg ( p = 0.014 ) , and decreased ox-LDL concentrations by 31.72 U/l ( p = 0.015 ) . CONCLUSION At 5-weeks , the consumption of 150 mg/day of OP improve lipid cardiovascular profile and represents one of the scarce ways to increase HDL-c in stage-1-hypertensive subjects . TRIAL REGISTRATION Clinical Trials.gov : NCT02063477"
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BACKGROUND There are studies that show preliminary evidence of the benefits of physical exercise for people with Attention Deficit Hyperactivity Disorder ( ADHD ) . The objective of the research being reported here was to carry out a systematic review of articles relating to the effects that exercise sessions have on children and adolescents with this pathology . METHOD The total sample of studies considered was 1,723 , of which only 11 met the eligibility criteria . RESULTS The research included in this review showed that children with ADHD undertaking exercise experienced improvements in their characteristic symptoms , mainly attention deficit and hyperactivity , in comparison to other sedentary tasks such as watching a video . Five minutes of jumping or thirty minutes on a treadmill or static bicycle were enough to produce appreciable improvements in inhibitory control or in cognitive and executive functions . Benefits following exercise were also seen in other aspects such as reaction times and preparation for response , motor skills or brain activity . CONCLUSION The findings make us optimistic that in the future physical exercise may become an alternative , or at least an effective complement , to the pharmacological treatments currently used for this pathology
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"CONTEXT Data from a previous prospect i ve study of lobar volumes in children with attention-deficit/hyperactivity disorder ( ADHD ) are reexamined using a measure of cortical thickness . OBJECTIVE To determine whether regional differences in cortical thickness or cortical changes across time characterize ADHD and predict or reflect its clinical outcome . DESIGN , SETTING , AND PARTICIPANTS Longitudinal study of 163 children with ADHD ( mean age at entry , 8.9 years ) and 166 controls recruited mainly from a local community in Maryl and . Participants were assessed with magnetic resonance imaging . Ninety-seven patients with ADHD ( 60 % ) had 2 or more images and baseline and follow-up clinical evaluations ( mean follow-up , 5.7 years ) . MAIN OUTCOME MEASURES Cortical thickness across the cerebrum . Patients with ADHD were divided into better and worse outcome groups on the basis of a mean split in scores on the Children 's Global Assessment Scale and persistence/remission of DSM-IV-defined ADHD . RESULTS Children with ADHD had global thinning of the cortex ( mean reduction , -0.09 mm ; P=.02 ) , most prominently in the medial and superior prefrontal and pre central regions . Children with worse clinical outcome had a thinner left medial prefrontal cortex at baseline than the better outcome group ( -0.38 mm ; P=.003 ) and controls ( -0.25 mm ; P=.002 ) . Cortical thickness developmental trajectories did not differ significantly between the ADHD and control groups throughout except in the right parietal cortex , where trajectories converged . This normalization of cortical thickness occurred only in the better outcome group . CONCLUSIONS Children with ADHD show relative cortical thinning in regions important for attentional control . Children with a worse outcome have \" fixed \" thinning of the left medial prefrontal cortex , which may compromise the anterior attentional network and encumber clinical improvement . Right parietal cortex thickness normalization in patients with a better outcome may represent compensatory cortical change",
"Attention Deficit Hyperactivity Disorder ( ADHD ) mainly affects the academic performance of children and adolescents . In addition to bringing physical and mental health benefits , physical activity has been used to prevent and improve ADHD comorbidities ; however , its effectiveness has not been quantified . In this study , the effect of physical activity on children 's attention was measured using a computer game . Intense physical activity was promoted by a relay race , which requires a 5-min run without a rest interval . The proposed physical stimulus was performed with 28 volunteers : 14 with ADHD ( GE-EF ) and 14 without ADHD symptoms ( GC-EF ) . After 5 min of rest , these volunteers accessed the computer game to accomplish the tasks in the shortest time possible . The computer game was also accessed by another 28 volunteers : 14 with ADHD ( GE ) and 14 without these symptoms ( GC ) . The response time to solve the tasks that require attention was recorded . The results of the four groups were analyzed using D'Agostino statistical tests of normality , Kruskal-Wallis analyses of variance and post-hoc Dunn tests . The groups of volunteers with ADHD who performed exercise ( GE-EF ) showed improved performance for the tasks that require attention with a difference of 30.52 % compared with the volunteers with ADHD who did not perform the exercise ( GE ) . The ( GE-EF ) group showed similar performance ( 2.5 % difference ) with the volunteers in the ( GC ) group who have no ADHD symptoms and did not exercise . This study shows that intense exercise can improve the attention of children with ADHD and may help their school performance",
"This individual differences study examined the separability of three often postulated executive functions-mental set shifting ( \" Shifting \" ) , information updating and monitoring ( \" Updating \" ) , and inhibition of prepotent responses (\"Inhibition\")- and their roles in complex \" frontal lobe \" or \" executive \" tasks . One hundred thirty-seven college students performed a set of relatively simple experimental tasks that are considered to predominantly tap each target executive function as well as a set of frequently used executive tasks : the Wisconsin Card Sorting Test ( WCST ) , Tower of Hanoi ( TOH ) , r and om number generation ( RNG ) , operation span , and dual tasking . Confirmatory factor analysis indicated that the three target executive functions are moderately correlated with one another , but are clearly separable . Moreover , structural equation modeling suggested that the three functions contribute differentially to performance on complex executive tasks . Specifically , WCST performance was related most strongly to Shifting , TOH to Inhibition , RNG to Inhibition and Updating , and operation span to Updating . Dual task performance was not related to any of the three target functions . These results suggest that it is important to recognize both the unity and diversity of executive functions and that latent variable analysis is a useful approach to study ing the organization and roles of executive functions",
"Objective : In the general population , attention is reliably enhanced after exposure to certain physical environments , particularly natural environments . This study examined the impacts of environments on attention in children with ADHD . Method : In this within subjects design , each participant experienced each of three treatments ( environments ) in single blind controlled trials . Seventeen children 7 to12 years old professionally diagnosed with ADHD experienced each of three environments — a city park and two other well-kept urban setting s — via individually guided 20-minute walks . Environments were experienced 1 week apart , with r and omized assignment to treatment order . After each walk , concentration was measured using Digit Span Backwards . Results : Children with ADHD concentrated better after the walk in the park than after the downtown walk ( p = .0229 ) or the neighborhood walk ( p = .0072 ) . Effect sizes were substantial ( Cohen 's d = .52 and .77 , respectively ) and comparable to those reported for recent formulations of methylpheni date . Conclusion : Twenty minutes in a park setting was sufficient to elevate attention performance relative to the same amount of time in other setting s. These findings indicate that environments can enhance attention not only in the general population but also in ADHD population s. “ Doses of nature ” might serve as a safe , inexpensive , widely accessible new tool in the tool kit for managing ADHD symptoms . ( J. of Att . Dis . 2009 ; 12(5 ) 402 - 409",
"A few studies have recently reported that higher cardiorespiratory fitness is associated with higher volumes of subcortical brain structures in children . It is , however , unknown how different fitness measures relate to shapes of subcortical brain nuclei . We aim ed to examine the association of the main health-related physical fitness components with shapes of subcortical brain structures in a sample of forty-four Spanish children aged 9·7 ( sd 0·2 ) years from the NUtraceuticals for a HEALthier life project . Cardiorespiratory fitness , muscular strength and speed agility were assessed using valid and reliable tests ( ALPHA-fitness test battery ) . Shape of the subcortical brain structures was assessed by MRI , and its relationship with fitness was examined after controlling for a set of potential confounders using a partial correlation permutation approach . Our results showed that all physical fitness components studied were significantly related to the shapes of subcortical brain nuclei . These associations were both positive and negative , indicating that a higher level of fitness in childhood is related to both expansions and contractions in certain regions of the accumbens , amygdala , cau date , hippocampus , pallidum , putamen and thalamus . Cardiorespiratory fitness was mainly associated with expansions , whereas h and grip was mostly associated with contractions in the structures studied . Future r and omised-controlled trials will confirm or contrast our findings , demonstrating whether changes in fitness modify the shapes of brain structures and the extent to which those changes influence cognitive function ",
"PURPOSE As adjuvant therapy for enhancing the effects of stimulants and thereby minimizing medication doses , we hypothesized that aerobic exercise might be an effective adjunctive therapy for enhancing the effects of methylpheni date on the clinical symptoms , cognitive function , and brain activity of adolescents with attention deficit hyperactivity disorder ( ADHD ) . METHODS Thirty-five adolescents with ADHD were r and omly assigned to one of two groups in a 1/1 ratio ; methylpheni date treatment + 6-wk exercise ( sports-ADHD ) or methylpheni date treatment + 6-wk education ( edu-ADHD ) . At baseline and after 6 wk of treatment , symptoms of ADHD , cognitive function , and brain activity were evaluated using the Dupaul attention deficit hyperactivity disorder rating scale -- Korean version ( K-ARS ) , the Wisconsin Card Sorting Test , and 3-T functional magnetic resonance imaging , respectively . RESULTS The K-ARS total score and perseverative errors in the sports-ADHD group decreased compared with those in the edu-ADHD group . After the 6-wk treatment period , the mean β value of the right frontal lobe in the sports-ADHD group increased compared with that in the edu-ADHD group . The mean β value of the right temporal lobe in the sports-ADHD group decreased . However , the mean β value of the right temporal lobe in the edu-ADHD group did not change . The change in activity within the right prefrontal cortex in all adolescents with ADHD was negatively correlated with the change in K-ARS scores and perseverative errors . CONCLUSIONS The current results indicate that aerobic exercise increased the effectiveness of methylpheni date on clinical symptoms , perseverative errors , and brain activity within the right frontal and temporal cortices in response to the Wisconsin card sorting test stimulation",
"Objective : To examine the role of physical activity in determining the affect and executive functioning of children with symptoms of ADHD . Method : In Study 1 , the association between physical activity and affect in the daily lives of children with varying degrees of hyperactivity was examined . In Study 2 , children with ADHD were r and omly assigned a physical activity or a sedentary task before working on a task requiring executive control . Results : Lack of physical activity was shown to relate to depressed affect , more strongly in participants with severe hyperactivity symptoms ( Study 1 ) . The physically active participants showed improved executive functioning after only 5 min of vigorous activity ; the sedentary control participants showed no improvement ( Study 2 ) . Conclusion : These results indicate that interventions to increase the level of physical activity in children with and without ADHD might improve affect and executive functioning",
"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",
"PURPOSE The effects of exercise on children with attention-deficit hyperactivity disorder ( ADHD ) were evaluated by study ing the rate of spontaneous eye blinks , the acoustic startle eye blink response ( ASER ) , and motor impersistence among 8- to 12-yr-old children ( 10 boys and 8 girls ) meeting DSM-III-R criteria for ADHD . METHODS Children ceased methylpheni date medication 24 h before and during each of three daily conditions separated by 24 - 48 h. After a maximal treadmill walking test to determine cardiorespiratory fitness ( VO(2peak ) ) , each child was r and omly assigned to counterbalanced conditions of treadmill walking at an intensity of 65 - 75 % VO(2peak ) or quiet rest . Responses were compared with a group of control participants ( 11 boys and 14 girls ) equated with the ADHD group on several key variables . RESULTS Boys with ADHD had increased spontaneous blink rate , decreased ASER latency , and decreased motor impersistence after maximal exercise . Girls with ADHD had increased ASER amplitude and decreased ASER latency after submaximal exercise . CONCLUSIONS The findings suggest an interaction between sex and exercise intensity that is not explained by physical fitness , activity history , or selected personality attributes . The clinical meaning of the eye blink results is not clear , as improvements in motor impersistence occurred only for boys after maximal exercise . Nonetheless , these preliminary findings are sufficiently positive to encourage additional study to determine whether a session of vigorous exercise has efficacy as a dopaminergic adjuvant in the management of behavioral features of ADHD",
"The revised new forest parenting programme ( NFPP ) is an 8-week psychological intervention design ed to treat ADHD in preschool children by targeting , amongst other things , both underlying impairments in self-regulation and the quality of mother – child interactions . Forty-one children were r and omized to either the revised NFPP or treatment as usual conditions . Outcomes were ADHD and ODD symptoms measured using question naires and direct observation , mothers ’ mental health and the quality of mother – child interactions . Effects of the revised NFPP on ADHD symptoms were large ( effect size > 1 ) and significant and effects persisted for 9 weeks post-intervention . Effects on ODD symptoms were less marked . There were no improvements in maternal mental health or parenting behavior during mother – child interaction although there was a drop in mothers ’ negative and an increase in their positive comments during a 5-min speech sample . The small-scale trial , although limited in power and generalizability , provides support for the efficacy of the revised NFPP . The findings need to be replicated in a larger more diverse sample",
"BACKGROUND Evaluation of broad-spectrum micronutrient ( vitamins and minerals ) treatment for childhood ADHD has been limited to open-label studies that highlight beneficial effects across many aspects of psychological functioning . METHOD This is the first fully blinded r and omized controlled trial of medication-free children ( n = 93 ) with ADHD ( 7 - 12 years ) assigned to either micronutrients ( n = 47 ) or placebo ( n = 46 ) in a 1:1 ratio , for 10 weeks . All children received st and ardized ADHD assessment s. Data were collected from clinicians , parents , participants and teachers across a range of measures assessing ADHD symptoms , general functioning and impairment , mood , aggression and emotional regulation . RESULTS Intent-to-treat analyses showed significant between-group differences favouring micronutrient treatment on the Clinical Global Impression-Improvement ( ES = 0.46 ) , with 47 % of those on micronutrients identified as ' much ' to ' very much ' improved versus 28 % on placebo . No group differences were identified on clinician , parent and teacher ratings of overall ADHD symptoms ( ES ranged 0.03 - 0.17 ) . However , according to clinicians , 32 % of those on micronutrients versus 9 % of those on placebo showed a clinical ly meaningful improvement on inattentive ( OR = 4.9 ; 95 % CI : 1.5 - 16.3 ) , but no group differences on improvement in hyperactive-impulsive symptoms ( OR = 1.0 ; 95 % CI : 0.4 - 2.5 ) . Based on clinician , parent and teacher report , those on micronutrients showed greater improvements in emotional regulation , aggression and general functioning compared to placebo ( ES ranged 0.35 - 0.66 ) . There were two dropouts per group , no group differences in adverse events and no serious adverse events identified . Blinding was successful with guessing no better than chance . CONCLUSIONS Micronutrients improved overall function , reduced impairment and improved inattention , emotional regulation and aggression , but not hyperactive/impulsive symptoms , in this sample of children with ADHD . Although direct benefit for core ADHD symptoms was modest , with mixed findings across raters , the low rate of adverse effects and the benefits reported across multiple areas of functioning indicate micronutrients may be a favourable option for some children , particularly those with both ADHD and emotional dysregulation . Trial registered with the Australian New Zeal and Clinical Trials Registry ACTRN12613000896774",
"Acute physical activity of moderate to vigorous intensity has been shown to improve cognitive functions in children . However , the empirical evidence associated with Attention Deficit Hyperactivity Disorder ( ADHD ) in children is still limited , in particular regarding which specific cognitive functions benefit . This study investigated the effects of an acute bout of physical activity on multiple aspects of executive functions ( inhibition , switching , and visual working memory ) in children with ADHD . Forty-six children ( 8–12 years old ; 82.6 % boys ) were r and omly assigned to either 15 minutes of acute exergaming ( physical activity of moderate intensity ) or to a control condition ( sedentary ) . Executive function performance in inhibition , switching and visual working memory were assessed before and after each condition , using a modified version of both the Flanker and the Color Span Backwards Task . The results revealed that participants in the exergaming group performed significantly faster than those in the control group in terms of both inhibition and switching , but there was no significant difference in the accuracy of the two tasks nor in visual working memory performance . These findings suggest that acute physical activity utilizing exergaming has the potential to improve specific aspects of executive functions ( reaction times in inhibition and switching ) in children with ADHD",
"The greater coronary heart disease morbidity of sedentary as opposed to physically active workers was demonstrated many years ago by J N Morris and his colleagues in a comparison of London bus drivers and conductors . These two groups of transport workers belonged to the same social class and had similar lifestyles . They differed principally in the amount of physical activity in which they engaged when at work . The drivers were confined to a small enclosed driving compartment which rendered them almost completely immobile , whilst the conductors were continuously active , especially as they constantly had to run up and down the stairs of the doubledecker London buses . During the five-year follow-up the drivers had a CHD incidence almost double that of the conductors . The differences between the two groups became greater as their members grew older ( Table IX.1 ) . ' The finding of this untoward accompaniment of physical inactivity has been confirmed by the results of the Framingham study 2 and a 27 cohort based rigorous meta- analysis reported by Jesse Berlin and Graham Colditz . These authors found a relative risk of death from coronary heart disease of 1.9 ( CL 1.6 - 2.2 ) for sedentary as opposed to high physical activity groups , and the benefits were shown to be greater in the studies that the authors judged to be method ologically stronger.3 Conversely , in the Whitehall study of British civil servants leisure-time physical activity has been found to have cardiovascular health benefits similar to those apparently conferred on the London bus conductors by their workaday exertions . Vigorous weekend exercise apparently protected the middle-aged men from fatal heart attacks and non-fatal first episodes of coronary heart disease.4 It is probable that a r and omized and controlled prospect i ve study of the cardiovascular consequences of prolonged inactivity will never be undertaken . It would be both unethical and impractical to enforce a long-term sedentary lifestyle on a control group . However , the physiological means by which regular exercise has cardioprotective effects are now well defined . Animal studies have shown that the coronary arterial capacity becomes greater relative to the cardiac muscle mass and an increase in coronary artery diameter has been demonstrated angiographically . Capillary growth is induced and increase in coronary blood flow in response to"
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4117a384-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND Silver diamine fluoride ( SDF ) solution gains increasing popularity in arresting dentine caries in clinical practice . The aim of this systematic review was to summarize the findings from laboratory studies on the influence of SDF application on the bond strength of dentine to various adhesives and to glass ionomer cements ( GICs ) . METHODS Two independent review ers conducted a literature search in the data bases Medline , Ovid , PubMed and Web of Science until 15th August 2019 using the search keywords [ ' bond strength ' ] AND [ ' silver diamine fluoride ' OR ' silver diammine fluoride ' OR ' SDF ' OR ' silver fluoride ' OR ' diamine silver fluoride ' ] . Articles investigating the effect of SDF application on the bond strength of dentine to various adhesives and to GICs were included in this review . Information on how SDF application influenced the bond strength was extracted from the included articles . Besides , related information , e.g. test method of bond strength , concentration and br and of SDF , type of adhesive system and GIC , testing dental substrate , protocol of specimen preparation , and failure mode was also review ed . RESULTS A total of 13 articles were included in this review , with 8 and 6 studies investigating the effect of SDF application on the bond strength of dentine to various adhesives and to GICs , respectively . Sound dentine as well as demineralized dentine created by chemical methods , e.g. immersing in a demineralizing solution , was commonly adopted as the testing dental substrate . The microtensile bond strength ( mTBS ) test was the predominant method employed . However , the bond strength values had large variations among studies , ranging from bond strength to different adhesives , 4 studies indicated that SDF application followed by rinsing with water had no significant influence . However , another 4 studies reported reduced bond strength after SDF application . Regarding the bond strength to GICs , 4 studies concluded that SDF application had no adverse impact on the bond strength . CONCLUSIONS No solid conclusion can be drawn on the effect of SDF application on the bond strength of dentine to adhesives and to GICs due to the high degree of variation of the included studies
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"OBJECTIVE To compare the effectiveness of annual topical application of silver diamine fluoride ( SDF ) solution , semi-annual topical application of SDF solution , and annual application of a flowable high fluoride-releasing glass ionomer in arresting active dentine caries in primary teeth . METHODS A total of 212 children , aged 3 - 4 years , were r and omly allocated to one of three groups for treatment of carious dentine cavities in their primary teeth : Gp1-annual application of SDF , Gp2-semi-annual application of SDF , and Gp3-annual application of glass ionomer . Follow-up examinations were carried out every six months to assess whether the treated caries lesions had become arrested . RESULTS After 24 months , 181 ( 85 % ) children remained in the study . The caries arrest rates were 79 % , 91 % and 82 % for Gp1 , Gp2 and Gp3 , respectively ( p=0.007 ) . In the logistic regression model using GEE to adjust for clustering effect , higher caries arrest rates were found in lesions treated in Gp2 ( OR=2.98 , p=0.007 ) , those in anterior teeth ( OR=5.55 , p SDF solution or high fluoride-releasing glass ionomer can arrest active dentine caries . Increasing the frequency of application to every 6 months can increase the caries arrest rate of SDF application . CLINICAL SIGNIFICANCE Arrest of active dentine caries in primary teeth by topical application of SDF solution can be enhanced by increasing the frequency of application from annually to every 6 months , whereas annual paint-on of a flowable glass ionomer can also arrest active dentine caries and may provide a more aesthetic outcome",
"OBJECTIVE To compare the effectiveness of three applications of silver diammine fluoride ( SDF ) solution at yearly interval and three applications of SDF solution or sodium fluoride ( NaF ) varnish at weekly interval at baseline in arresting active caries in the primary teeth of preschool children . METHODS Children aged 3 - 4 years ( n = 371 ) who had at least one active caries lesion ( ICDAS codes 3 - 6 ) in their primary teeth were r and omly allocated into three groups : Group 1 - annual application of 30 % SDF solution ; Group 2 - three applications of 30 % SDF at weekly intervals ; and Group 3 - three applications of 5 % NaF varnish at weekly intervals . Follow-up examinations were performed every 6 mo nths by the same masked examiner . RESULTS After 30 months , 309 ( 83 % ) children with 1877 caries lesions remained in the study . For cavitated lesions ( ICDAS code 5 or 6 ) , the caries arrest rate of Group 1 ( 48 % ) was significantly higher than those of Group 2 ( 33 % ) and Group 3 ( 34 % ) , ( p multi-level survival analysis showed that the arrest times of cavitated lesions in both SDF groups ( Groups 1 and 2 ) were significantly shorter than that of the NaF varnish group . For moderate caries lesions without visible dentine ( ICDAS code 3 or 4 ) , the caries arrest rates were 45 % , 44 % and 51 % in Groups 1 , 2 and 3 , respectively ( p > 0.05 ) . Presence of plaque on caries lesion , tooth type and tooth surface type had an influence on caries arrest . CONCLUSION Over a 30-month period , annual applications of SDF solution is more effective than three weekly applications of NaF varnish or SDF solution at baseline in arresting active cavitated dentine caries lesions in primary teeth . CLINICAL SIGNIFICANCE As annual application of SDF solution was found to be more effective than 3 weekly applications of NaF varnish or SDF solution at baseline in arresting active cavitated dentine caries lesions , the former application protocol is preferred for young children who are available for regular caries arrest treatment",
"This r and omized clinical trial aim ed to compare the adverse effects and parental satisfaction following the different regimes of silver diamine fluoride ( SDF ) treatment among preschool children . A total of 888 preschool children who had active dentin caries received different SDF application regimes : group 1 , 12 % SDF applied annually ; group 2 , 12 % SDF applied semiannually ; group 3 , 38 % SDF applied annually ; and group 4 , 38 % SDF applied semiannually . Information on adverse effects — including tooth or gum pain , gum swelling , gum bleaching , and systemic toxicity — was collected through a parent-reported question naire within 1 wk after every SDF or placebo application . Information of parental satisfaction on children ’s dental appearance was collected at baseline and 30-mo examination . At the 30 mo , 799 children ( 90 % ) remained in the study . No acute systemic illness or major adverse effect was reported . No differences of all minor adverse effects among the 4 groups were found ( P > 0.05 ) . Overall , prevalence of tooth and gum pain as perceived by patients and reported by parents was 6.6 % , while gum swelling and gum bleaching were 2.8 % and 4.7 % , respectively . Blackening of carious lesions was common among all groups , with 36.7 % , 49.5 % , 65.6 % and 76.3 % in groups 1 to 4 , respectively ( χ2 test , P proportion of parents who were satisfied with their children ’s dental appearance in groups 1 to 4 was as follows : 67.6 % , 61.5 % , 70.8 % , and 62.3 % , respectively ( χ2 test , P > 0.05 ) . Based on parental reporting , SDF does not cause acute systemic illness . Tooth or gum pain , gum swelling , and gum bleaching were uncommon and not significantly different among the study groups . Parental satisfaction with children ’s dental appearance was similar among all groups . The use of SDF following the study protocol for caries arrest is safe for preschool children . Collecting information on parental satisfaction and adverse effects is beneficial for dental professionals when deciding to adopt SDF treatment for preschool children ( Clinical Trials.gov NCT02385474 )",
"OBJECTIVES This ex vivo study compared the physico-chemical structural differences between primary carious teeth biannually treated with silver diamine fluoride ( SDF ) and carious teeth without such treatment . METHOD Twelve carious primary upper- central incisors were collected from 6-year-old children . Six teeth had arrested caries after 24-month biannual SDF applications and 6 had active caries when there was no topical fluoride treatment . The mineral density , elemental contents , surface morphology , and crystal characteristics were assessed by micro-computed tomography ( micro-CT ) , energy-dispersive X-ray spectrometry ( EDX ) , scanning electron microscopy ( SEM ) , and transmission electron microscopy ( TEM ) . RESULTS Micro-CT examination revealed a superficial opaque b and approximately 150μm on the arrested cavitated dentinal lesion . This b and was limited in the active carious lesion . EDX examination detected a higher intensity of calcium and phosphate of 150μm in the surface zone than in the inner zone , but this zone was restricted in the active cavitated dentinal lesion . SEM examination indicated that the collagens were protected from being exposed in the arrested cavitated dentinal lesion , but were exposed in the active cavitated dentinal lesion . TEM examination suggested that remineralised hydroxyapatites were well aligned in the arrested cavitated dentinal lesion , while those in the active cavitated dentinal lesion indicated a r and om apatite arrangement . CONCLUSIONS A highly remineralised zone rich in calcium and phosphate was found on the arrested cavitated dentinal lesion of primary teeth with an SDF application . The collagens were protected from being exposed in the arrested cavitated dentinal lesion . CLINICAL SIGNIFICANCE Clinical SDF application positively influences dentine remineralisation ",
"Arresting Caries Treatment ( ACT ) has been proposed to manage untreated dental caries in children . This prospect i ve r and omized clinical trial investigated the caries-arresting effectiveness of a single spot application of : ( 1 ) 38 % silver diamine fluoride ( SDF ) with tannic acid as a reducing agent ; ( 2 ) 38 % SDF alone ; ( 3 ) 12 % SDF alone ; and ( 4 ) no SDF application in primary teeth of 976 Nepalese schoolchildren . The a priori None hypothesis was that the different treatments have no effect in arresting active cavitated caries . Only the single application of 38 % SDF with or without tannic acid was effective in arresting caries after 6 months ( 4.5 and 4.2 mean number of arrested surfaces ; p Tannic acid conferred no additional benefit . ACT with 38 % SDF provides an alternative when restorative treatment for primary teeth is not an option",
"PURPOSE The purpose of this study was to investigate the effect of silver diamine fluoride ( SDF ) on the microtensile bonding strength of resin composite to the dentin of primary molars . METHODS Twelve primary molars were r and omly assigned to either the control or the SDF groups , and microtensile bonding strength ( mTBS ) was measured . The surface morphology was evaluated by visual inspection and scanning electron microscopy ( SEM ) imaging . RESULTS The mean±(SD ) value of mTBS in the control and SDF group was 162.09±81.08 and 139.85±88.53 , respectively ( P=0.402 ) . SEM images showed that , in the control group , the majority of the fractures occurred at the adhesive-dentin conjunction , while in the SDF group failure mostly occurred within the adhesives . CONCLUSIONS Pretreating dentin with 38 percent silver diamine fluoride does not affect the bonding strength of composite resin to dentin . The fracture patterns observed suggest that bonding strength might be stronger between the adhesive and the SDF-applied dentin . Our data suggest that SDF can be used as a dentin pretreatment prior to resin restoration potentially contributing to secondary caries prevention in primary teeth",
"OBJECTIVES This study measured the microhardness of arrested dentinal caries on primary teeth receiving regular fluoride applications after 30 months . METHODS Caries on primary upper anterior teeth of preschool children were r and omly assigned to receive 38 % silver diamine fluoride every 12 months or 5 % sodium fluoride varnish every 3 months . Lesions that were hard on probing were considered arrested . At 30 months , very mobile teeth were extracted , sectioned , and polished and they underwent Knoop hardness number ( KHN ) measurements at sites below the surface at the center of the carious lesion every 25 microm toward the pulp . Three sets of measurements were made on parallel tracks approximately 150 - 200 microm apart , and the median KHN at each depth were analyzed . RESULTS Five arrested and five soft carious lesions were examined . Within the outer 25 - 200 microm , the median KHN of arrested carious lesions ( range , 20 - 46 or 196 - 451 MPa ) were greater than those of soft carious lesions ( range , 5 - 20 , or 49 - 196 MPa ) . The difference between them , however , was not statistically significant . At a distance of 225 microm or more from the surface of the lesion , the median KHN of both groups were between 20 and 30 ( 196 - 294 MPa ) . CONCLUSIONS The outermost dentinal surface of carious lesions that had been arrested by topical fluoride application was harder than that of active carious lesions . At a distance of 225 microm or more from the lesion surface , the microhardness of both arrested and soft dentinal caries was similar",
"Untreated dental caries in Chinese pre-school children is common . This prospect i ve controlled clinical trial investigated the effectiveness of topical fluoride applications in arresting dentin caries . Three hundred seventy-five children , aged 3 - 5 years , with carious upper anterior teeth were divided into five groups . Children in the first and second groups received annual applications of silver diamine fluoride solution ( 44,800 ppm F ) . Sodium fluoride varnish ( 22,600 ppm F ) was applied every three months to the lesions of children in the third and fourth groups . For children in the first and third groups , soft carious tissues were removed prior to fluoride application . The fifth group was the control . Three hundred eight children were followed for 30 months . The respective mean numbers of arrested carious tooth surfaces in the five groups were 2.5 , 2.8 , 1.5 , 1.5 , and 1.3 ( p Silver diamine fluoride was found to be effective in arresting dentin caries in primary anterior teeth in pre-school children",
"OBJECTIVES To investigate the effectiveness of silver diammine fluoride ( SDF ) solution application in arresting dental root caries and to assess the color of arrested caries lesions . METHODS This study was conducted in elderly centers in Hong Kong . A total of 83 elders with 157 root surfaces with active caries lesion were r and omly allocated into 3 groups : Gp1 ( placebo control)-annual application of soda water ; Gp2-annual application of SDF solution ; Gp3-annual application of SDF solution immediately followed by potassium iodide ( KI ) solution . Color of the arrested root caries lesion was assessed with reference to PANTONE color plates and classified into one of the followings : yellow ( 7401U ) ; light brown ( 1245U ) ; dark brown ( 4635U ) ; and black ( Black U ) . Status of root surfaces was assessed every 6 months by the same independent examiner . RESULTS After 30 months , 100 ( 64 % ) of the included root caries lesions were review ed . The arrest rates of root caries were 45 % , 90 % , and 93 % in Gp1 ( control ) , Gp2 ( SDF ) and Gp3 ( SDF/KI ) , respectively ( χ(2 ) test , p the active root caries changed to arrested ( p proportions of root caries being arrested in the SDF and SDF/KI groups were not significantly different ( p>0.05 ) . The distributions of arrested caries lesions by color were not significantly different between the SDF and SDF/KI groups ( χ(2 ) test , p>0.05 ) . CONCLUSIONS Application of SDF solution , with or without application of KI afterwards , is effective in arresting root caries among elders in a water fluori date d area . In the long term , blackening of arrested root caries is not reduced by immediate application of KI after the application of SDF . CLINICAL SIGNIFICANCE In a water fluori date d area , annual application of SDF solution or SDF/KI solution can arrest dental root caries in elders . In the long term , application of KI does not reduce the blackening of arrested caries lesions caused by SDF",
"The aim of this in vitro study was to investigate the effect of the cariostatic and preventive agent silver diamine fluoride ( SDF ) on the microtensile bond strength of resin composite to dentin . Forty-two caries-free , extracted molars were flattened occlusally and apically using a diamond saw , and the exposed occlusal dentin was polished with a series of silicon carbide papers , all under water irrigation . The teeth were then r and omly divided into six groups of seven teeth each that were treated as follows : 1 ) Peak SE self-etch bonding agent ; 2 ) 12 % SDF + Peak SE ; 3 ) 38 % SDF + Peak SE ; 4 ) Peak LC etch- and -rinse bonding agent ; 5 ) 12 % SDF + Peak LC ; and 6 ) 38 % SDF + Peak LC . Four-millimeter buildups of Amelogen Plus were incrementally placed on all teeth ; after a 24-hour storage period in distilled water , the specimens were sectioned perpendicular to the adhesive interface to produce beams of cross-sectional surface area measuring approximately 1 mm(2 ) . The beams were placed on a microtensile testing machine , which utilized a single-speed pump motor and force gauge at 20 kgf × 0.01 second to record maximum tensile force before failure occurred . Two-way analysis of variance and post hoc Tukey tests were performed to compare the effects of the SDF on microtensile bond strength , with statistical significance set at α = 0.05 . None of the experimental groups treated with different concentrations of SDF showed a significant difference in bond strength compared to the control groups , and there was no significant difference in bond strength between self-etch and etch- and -rinse groups . However , the effect of SDF on self-etch bonded teeth compared to etch- and -rinse bonded teeth was statistically significant ( p=0.0363 ) , specifically at the 12 % concentration . SDF does not adversely affect the bond strength of resin composite to noncarious dentin",
"OBJECTIVES To verify the influence of cutting speed during microtensile specimen preparation , on bond strength values and on the sample microscopic integrity of a single-bottle adhesive system to enamel and dentin . METHODS Thirty sound human third molars were restored with light-cured Excite and Tetric Ceram according to manufacturers ' instructions , being half in ground enamel [ E ] , and half in flat dentin [ D ] . After 24 h storage in distilled water at 37 degrees C , the restored teeth were sectioned in x and y-axes under different cutting speed : 100 , 200 or 400 RPM , obtaining stick shaped specimens with cross-sectional area of 1.0 mm(2 ) . Five specimens from each experimental group were r and omly selected before being loaded for SEM analysis , while the remaining sample s were subjected to the microtensile bond strength test . Because the variance of dentin specimens was significantly higher than the variance of enamel sample s , analysis of the influence of the cutting speed was performed separately , by substrate . RESULTS The mean values in MPa were calculated including/excluding premature failures : E1 : 24.67/27.31(a ) ; E2 : 24.03/25.81(a ) ; E4 : 19.06/21.52(b ) ; D1 : 35.80/36.33(A ) ; D2 : 35.84/36.65(A ) ; D4 : 37.78/38.50(A ) . In the SEM analysis , better integrity of the dentin specimens was observed when compared to the enamel sample s , for which the integrity was greater in the lower cutting speed groups . SIGNIFICANCE It can be concluded that the cutting speed is an important factor that should be considered , mainly when enamel is involved , since it may affect the bond strength results and the integrity of the specimens",
"This 30-mo r and omized clinical trial compared the effectiveness of 2 concentrations ( 12 % or 38 % ) of silver diamine fluoride ( SDF ) and 2 periodicity of application ( once or twice a year ) in arresting cavitated dentin caries in primary teeth . Children aged 3 to 4 y who had at least 1 active cavitated caries lesion were enrolled and r and omly allocated into 4 groups for intervention . Group 1 had 12 % SDF applied annually ( every 12 mo ) , group 2 had 12 % SDF applied semiannually ( every 6 mo ) , group 3 had 38 % SDF applied annually , and group 4 had 38 % SDF applied semiannually . Clinical examinations were performed semiannually in kindergarten by a single examiner to investigate whether the SDF-treated caries became arrested . A total of 888 children with 4,220 decayed tooth surfaces received SDF application at baseline , and 799 ( 90.0 % ) children with 3,790 surfaces ( 89.8 % ) were evaluated at the 30-mo examination . The caries arrest rates were 55.2 % , 58.6 % , 66.9 % , and 75.7 % for groups 1 , 2 , 3 , and 4 , respectively ( P SDF had a higher chance of becoming arrested than those treated with 12 % SDF ( odds ratio [ OR ] , 1.98 ; 95 % confidence interval [ CI ] , 1.51–2.60 , P interaction between frequency of SDF application and visible plaque index ( VPI ) score was significant ( P = 0.017 ) . Among those children who received annual SDF application , children with a higher VPI score had a lower chance to have their caries become arrested ( OR , 0.59 , 95 % CI , 0.49–0.72 ) . In conclusion , SDF at a concentration of 38 % is more effective than that of 12 % in arresting active caries in primary teeth . For children with poor oral hygiene , caries arrest rate of SDF treatment can be increased by increasing the frequency of application from annually to semiannually ( Clinical Trials.gov NCT02385474 )",
"Purpose : The study objectives were to investigate the effect of silver diamine fluoride ( SDF ) on the microtensile bond strength between glass ionomer cement and carious primary dentin and evaluate the mode of restoration failure . Methods : Forty carious primary molars were sectioned in half through the middle of the carious lesion and r and omly allocated to test and control groups . The test specimens were treated with 38 percent SDF , and the control , deionized water . The sample s were stored in artificial saliva for 14 days at 37 degrees Celsius , and the dentin surfaces were conditioned and restored with Fuji IX GP Extra . After 24 hours in artificial saliva , the specimens were prepared for microtensile bond strength testing and stressed in tension at one mm per minute until failure . Mean bond strengths were compared using the paired t test . The failure mode was assessed with a stereomicroscope under 40X magnification . Results : The mean microtensile strength for the test group was 7.4 MPa ( SD=±5.1 ) and 6.3 ( ±4.6 ) for the control group ( P>0.05 ) . Most common failure mode was the mixed failure mode in both groups . Conclusion : Silver diamine fluoride does not adversely affect the bond strength between glass ionomer cement and carious primary dentin in vitro",
"OBJECTIVE To investigate the effect of silver diamine fluoride ( SDF ) and potassium iodide ( KI ) treatment on dentine discolouration and the shear bond strength ( SBS ) of glass ionomer cements ( GICs ) to artificial caries-affected dentine . MATERIAL S AND METHODS Dentine slices from human molars were demineralised to mimic caries-affected dentine . They were r and omly allocated for treatment ( n = 20 per treatment ) with SDF + KI , SDF ( positive control ) or water ( negative control ) . All slices were immersed in the artificial saliva for 24 hours after treatments . The colour of the treated surfaces was assessed using the CIELAB system . Lightness values were measured . Total colour change ( ∆E ) was calculated using water as the reference group , and was visible to the naked eyes if ∆E > 3.7 . All dentine slices were bonded with GICs . The SBS was assessed using a universal testing machine . Colour parameters and the SBS were analysed using a one-way ANOVA test . RESULTS The slices treated with SDF + KI had a higher lightness value those slices treated with water , whereas those treated with SDF presented a lower lightness value compared with those treated with water . The treatment with SDF + KI did not introduce any adverse colour effect to demineralised dentine ( ∆E = 14.4 ) , whereas the application of SDF alone caused significant staining ( ∆E = 24.6 ) . The SBS values ( mean ± SD ) after treatment with SDF + KI , SDF and water were 3.0 ± 1.4 MPa , 2.3 ± 0.9 MPa and 2.6 ± 1.1 MPa , respectively ( P = 0.217 ) . CONCLUSION The immediate application of KI solution after SDF treatment does not negatively affect adhesion of GICs to artificial caries-affected dentine . Moreover , KI treatment can reduce discolouration of demineralised dentine caused by SDF",
"OBJECTIVES To find out the effects of placement of atraumatic restorative treatment ( ART ) restorations on parental satisfaction and oral health related quality of life ( OHRQoL ) of preschool children with SDF-treated or untreated dentine caries lesions . METHODS In a r and omized controlled trial conducted in Hong Kong , preschool children who had cavitated dentine caries lesions were r and omly assigned to receive application of silver diamine fluoride ( SDF ) solution or placebo ( tonic water ) on their caries lesions 10 weeks before receiving ART restorations . Parents were asked to rate their satisfaction with their child 's teeth using a 5-point scale ( 5=very satisfied , 1=very dissatisfied ) before and six months after the restorative treatment . Besides , the Chinese version of Early Childhood Oral Health Impact Scale ( C-ECOHIS ) was used to assess the children 's OHRQoL. RESULTS A total of 194 children participated in this study , with 101 and 93 children receiving SDF and placebo application before ART restorations , respectively . There was no significant difference in parental satisfaction and C-ECOHIS score between the SDF and placebo groups at baseline . At the 6-month follow-up , the mean parental satisfaction score regarding their child 's dental health status increased significantly ( p 0.05 ) in C-ECOHIS scores were found in either of the two groups after ART restoration placement . CONCLUSIONS Placement of ART restorations can improve parental satisfaction with the health and appearance of their child 's teeth but has no significant effect on the OHRQoL. CLINICAL SIGNIFICANCE This study provides valuable information about the effects of ART restoration placement on SDF-treated or untreated dentine caries lesions regarding parental satisfaction and OHRQoL of preschool children"
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Background Recent systematic review s have suggested that pedometers may be effective motivational tools to promote walking . However , studies tend to be of a relatively short duration , with small clinical based sample s. Further research is required to demonstrate their effectiveness in adequately powered , community based studies . Objective Using a r and omized controlled trial design , this study assessed the impact of a 12-week graduated pedometer-based walking intervention on daily step-counts , self-reported physical activity and health outcomes in a Scottish community sample not meeting current physical activity recommendations . MethodS ixty-three women and 16 men ( 49.2 years ± 8.8 ) were r and omly assigned to either an intervention ( physical activity consultation and 12-week pedometer-based walking program ) or control ( no action ) group . Measures for step-counts , 7-day physical activity recall , affect , quality of life ( n = 79 ) , body mass , BMI , % body fat , waist and hip circumference ( n = 76 ) , systolic/diastolic blood pressure , total cholesterol and HDL cholesterol ( n = 66 ) were taken at baseline and week 12 . Analyses were performed on an intention to treat basis using 2-way mixed factorial analyses of variance for parametric data and Mann Whitney and Wilcoxon tests for non-parametric data . Results Significant increases were found in the intervention group for step-counts ( p time spent in leisure walking ( p = .02 ) and positive affect ( p = .027 ) . Significant decreases were found in this group for time spent in weekday ( p = .003 ) , weekend ( p = .001 ) and total sitting ( p = .001 ) with no corresponding changes in the control group . No significant changes in any other health outcomes were found in either group . In comparison with the control group at week 12 , the intervention group reported a significantly greater number of minutes spent in leisure time ( p = .008 ) , occupational ( p = .045 ) and total walking ( p = .03 ) , and significantly fewer minutes in time spent in weekend ( p = .003 ) and total sitting ( p = .022 ) . Conclusion A pedometer-based walking program , incorporating a physical activity consultation , is effective in promoting walking and improving positive affect over 12 weeks in community based individuals . The discussion examines possible explanations for the lack of significant changes in health outcomes . Continued follow-up of this study will examine adherence to the intervention and possible result ing effects on health outcomes
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"Background Scotl and has a policy aim ed at increasing physical activity levels in the population , but evidence on how to achieve this is still developing . Studies that focus on encouraging real world participants to start physical activity in their setting s are needed . The Walking for Well-being in the West study was design ed to assess the effectiveness of a pedometer-based walking programme in combination with physical activity consultation . The study was multi-disciplinary and based in the community . Walking for Well-being in the West investigated whether Scottish men and women , who were not achieving the current physical activity recommendation , increased and maintained walking behaviour over a 12 month period . This paper outlines the rationale and design of this innovative and pragmatic study . Methods Participants were r and omised into two groups : Group 1 : Intervention ( pedometer-based walking programme combined with a series of physical activity consultations ) ; Group 2 : Waiting list control for 12 weeks ( followed by minimal pedometer-based intervention ) . Physical activity ( primary outcome ) was measured using pedometer step counts ( 7 day ) and the International Physical Activity Question naire ( long version ) . Psychological processes were measured using question naires relating to the Transtheoretical Model of Behaviour Change , mood ( Positive and Negative Affect Schedule ) and quality of life ( Euroqol EQ-5D instrument ) . Physiological measures included anthropometric and metabolic outcomes . Environmental influences were assessed subjectively ( Neighbourhood Quality of Life Survey ) and objective ly ( neighbourhood audit tool and GIS mapping ) . The qualitative evaluation employed observation , semi-structured interviews and focus groups . A supplementary study undertook an economic evaluation . Discussion Data analysis is on-going . Walking for Well-being in the West will demonstrate if a pedometer based walking programme , in combination with physical activity consultation results in a sustainable increase in walking behaviour in this sample of Scottish adults over a 12 month period . The study will examine the complex relationships between behavioural change , health consequences and the role of the environment , in conjunction with the cost effectiveness of this approach and a detailed insight into the participants ' experiences of the intervention . Trial registration Current Controlled Trials IS RCT",
"Aims /hypothesisThe aim of this study was to investigate the effectiveness of physical activity counselling in promoting physical activity in people with Type 2 diabetes and to evaluate result ant physiological and biochemical effects . Methods A total of 70 inactive people with Type 2 diabetes were given st and ard exercise information and r and omised to receive physical activity counselling ( n=35 , experimental ) or not ( n=35 , control ) . Physical activity consultations were delivered at baseline and after 6 months , with follow-up phone calls after 1 , 3 , 6 and 9 months . Changes from baseline after 6 and 12 months were assessed for physical activity ( 7-day recall and accelerometer ) , for physiological characteristics ( body mass index and blood pressure ) and for biochemical variables ( HbA1c , lipid profile , fibrinogen , tissue plasminogen activator and microalbuminuria ) . Results Significant differences between groups were recorded for physical activity after 6 and 12 months ( p levels of physical activity from baseline to 6 months ( p0.05 ) . In the control group , accelerometer counts per week decreased from baseline to 12 months ( p=0.03 ) . Between-group differences ( p HbA1c ( experimental : 0.26 % decrease ; control : 0.15 % increase ) , for systolic blood pressure ( experimental : 7.7 mm Hg decrease ; control : 5.6 mm Hg increase ) and for fibrinogen ( experimental : 0.28 mmol/l decrease ; control : 1.43 mmol/l increase ) from baseline to 6 months , and for total cholesterol ( experimental : 0.33 mmol/l decrease ; control : 0.04 mmol/l increase ) from baseline to 12 months ( p activity counselling was effective in promoting physical activity in people with Type 2 diabetes . The counselling improved glycaemic control as well as the status of cardiovascular risk factors in these patients",
"Background : Few studies have considered the neighborhood as a context in which to examine the physical activity and quality of life relationship . Purpose : The goal of this study was to evaluate the effects of a neighborhood walking program on quality of life among older adults . It was design ed as a r and omized trial involving a multilevel design with neighborhoods corresponding to primary sampling units and residents to secondary units . Methods : Five hundred eighty-two communitydwelling senior residents ( 65 years of age or older ) in neighborhoods in the northeast metropolitan area of Portl and , Oregon , were recruited through telephone , direct mail , and referrals . The walking intervention was delivered at the neighborhood level . Neighborhoods ( N = 56 ) were r and omly assigned to a 6-month , 3 times per week , leader-led walking group activity ( n = 28 ) or an information-only control group ( n = 28 ) . Primary outcome measures included SF-12 ( Physical , Mental summary scores ) and life satisfaction ( SWLS ) ; the secondary outcome measure was neighborhood walking activity , assessed at baseline , 3 months , and 6 months of the study period . Results : Compared to the control neighborhoods , results from multilevel , longitudinal analyses indicated significant improvements in the primary outcomes of SF-12 Physical ( p SF-12 Mental ( p ( p of walking activity ( p neighborhood-based walking program of low to moderate intensity is feasible and beneficial for promoting quality of life among senior residents at a community level",
"Introduction The health benefits of regular cardiovascular exercise are well-known . Such exercise , however , has traditionally been defined as vigorous physical activity , such as jogging , swimming , or aerobic dance . Exercise of moderate intensity also promotes health , and many U.S. adults may be experiencing the health benefits of exercise through lifestyle activities of moderate intensity , such as yard work , housework , or walking for transportation . Until recently , public health surveillance systems have not included assessment s of this type of physical activity , focusing on exercise of vigorous intensity . We used an enhanced surveillance tool to describe the prevalence and amount of both moderate-intensity and vigorous-intensity physical activity among U.S. adults . Methods We analyzed data from the 2001 Behavioral Risk Factor Surveillance System , a state-based , r and om-digit – dialed telephone survey administered to U.S. adults aged 18 years and older ( n = 82,834 men and 120,286 women ) . Physical activity behavior was assessed using questions design ed to quantify the frequency of participation in moderate- or vigorous-intensity physical activities performed during leisure time or for household chores and transportation . Results Overall , 45 % of adults ( 48 % of men and 43 % of women ) were active at recommended levels during nonworking hours ( at least 30 minutes five or more days per week in moderate-intensity activities , equivalent to brisk walking , or at least 20 minutes three or more days per week in vigorous activities , equivalent to running , heavy yard work , or aerobic dance ) . Less than 16 % of adults ( 15 % of men and 17 % of women ) reported no moderate or vigorous activity in a usual week . Conclusion Integrating surveillance of lifestyle activities into national systems is possible , and doing so may provide a more accurate representation of the prevalence of recommended levels of physical activity . These results , however , suggest that the majority of U.S. adults are not active at levels associated with the promotion and maintenance of health",
"PURPOSE The aim of this study was to quantify pedometer-determined steps per day associated with 50 , 100 , and 150 % of the current public health recommendation for weekly physical activity in sedentary postmenopausal women . METHODS A sample of 111 women from the DREW ( Dose Response to Exercise in Women ) study provided data . We r and omly assigned women into one of three exercise groups expending 4 , 8 , or 12 kcal(-1).kg(-1).wk(-1 ) ( KKW ) . Participants exercised alternately on a treadmill and recumbent cycle ergometer for a 6-month training period . Only treadmill sessions done with zero grade , at slow to moderate speeds ( 48 - 97 m.min(-1 ) ) were used in this analysis . We controlled intensity at a HR equivalent to 50 % of VO(2peak ) . Participants wore pedometers at baseline and throughout the study to assess their free-living physical activity ( steps.d(-1 ) ) RESULTS Baseline averages were exercise training , free-living step counts remained Average speeds and distances per exercise session were 2.7 + /- 0.4 mph , 1.2 + /- 0.2 miles ( 4 KKW ) , 2.6 + /- 0.4 mph , 2.2 + /- 0.4 miles ( 8 KKW ) , and 2.8 + /- 0.3 mph , 2.7 + /- 0.4 miles ( 12 KKW ) . This yielded 2771 ( 4 KKW ) , 5457 ( 8 KKW ) , and 6534 ( 12 KKW ) steps per exercise session 3 - 4 d.wk(-1 ) . CONCLUSIONS Initially sedentary postmenopausal women can meet 50 % ( 4 KKW ) , 100 % ( 8 KKW ) , and 150 % ( 12 KKW ) of the current public health recommendation of weekly physical activity through planned moderate-intensity walking , accumulating an average of about 2800 ( 50 % ) , 5500 ( 100 % ) , and 6500 steps.d(-1 ) ( 150 % ) 3 - 4 d.wk(-1 )",
"OBJECTIVE : To conduct a r and omised trial of a physical activity ( PA ) intervention , The First Step Program ( FSP ) for adults with type II diabetes . DESIGN : A 16-week intervention study and 24-week follow-up assessment . PARTICIPANTS : A total of 47 overweight/obese , sedentary individuals ( age=52.7±5.2 y ; BMI = 33.3±5.6 kg/m2 ) recruited through a diabetes education centre . MEASUREMENTS : Primary outcome : daily PA assessed by pedometer ( steps/day ) . Secondary outcomes : anthropometric measures ( weight , BMI , waist girth , hip girth ) ; indicators of cardiovascular health ( resting heart rate and blood pressure ) ; glycemic control ( fasting glucose , insulin , HbA1c , glucose concentration 120 min postglucose load ) ; plasma lipid status ( total cholesterol , HDL cholesterol , LDL cholesterol , and triglycerides ) . RESULTS : Relative to the CONTROL group , FSP participants increased their PA > 3000 steps/day ( approximately 30 min/day ) during the intervention ( P decreased ( approximately 2–3 cm ) , but did not differ significantly between groups . Significant changes did not emerge for any of the other variables . CONCLUSIONS : The FSP is a practical intervention that elicits an immediate and profound change in walking behaviour . Such change is an important ‘ first step ’ towards increasing the volume and /or intensity of PA necessary to improve long-term health outcomes in this largely sedentary and overweight or obese population . Relapse by 24 weeks indicates that other strategies such as booster sessions are needed to maintain lifestyle change . Further research must determine realistic and responsive health outcomes for this population that are achievable through practical , real-world programming",
"OBJECTIVE to examine the effects and feasibility of educating and empowering older people with ischaemic heart disease using trained senior lay health mentors . DESIGN r and omised controlled trial with blinded evaluation . SETTING Falkirk and District Royal Infirmary . PARTICIPANTS in patients and out patients aged 60 or over attending secondary care with a diagnosis of angina or acute myocardial infa rct ion . Three-hundred and nineteen entered and 289 completed exit assessment s. The intervention group took part in mentoring groups for 1 year , meeting monthly for 2 hours , each led by two trained lay health mentors in addition to st and ard care . MAIN OUTCOME MEASURES primary outcome measures were changes in coronary risk factors , medication usage and actual use of secondary care health services . Secondary outcomes were total and cardiovascular events ; changes in medication compliance , non-medical support requirement , health status and psychological functioning , and social inclusion . RESULTS there were significant improvements in a reported current exercise score ( mean + 0.33 , + 0.02 to + 0.52 ) , in the average time spent walking per week by 72 minutes ( + 1 to + 137 minutes ) , and in the SF36 Physical Functioning Score ( + 6.1 , + 2.4 to + 9.5 ) . There was a 1.0 % reduction in total fat ( 95 % CI -3.0 % to -0.6 % ) and a 0.6 % reduction in saturated fat ( 95 % CI -1.5 % to -0.03 % ) . The intervention group showed reduced outpatient attendance for coronary heart disease ( -0.25 appointments , -0.61 to -0.08 ) . Attendance rates were high . Socio-economic grouping did not affect participation . CONCLUSIONS Lay Health Mentoring is feasible , practical and inclusive , positively influencing diet , physical activity , and health re source utilisation in older subjects with ischaemic heart disease without causing harm",
"PURPOSE To compare the effects of different patterns of regular brisk walking on fitness , risk factors for cardiovascular disease , and psychological well-being in previously sedentary adults . METHODS Twenty-one subjects ( 14 women ) , aged 44.5 + /- 6.1 yr ( mean + /- SD ) were r and omly assigned to two different , 6-wk programs of brisk walking in a cross-over design , with an interval of 2 wk . One program comprised one 30-min walk per day , 5 d.wk(-1 ) ( long bout ) and the other three 10-min walks per day , also 5 d.wk(-1 ) ( short bouts ) . All walking was at 70 - 80 % of predicted maximal heart rate . Maximal oxygen uptake ( (.)VO(2max ) ) , body composition , resting arterial blood pressure , fasting plasma lipoprotein variables , and psychological parameters were assessed before and after each program . RESULTS Overall , subjects completed 88.2 + /- 1.1 % and 91.3 + /- 4.1 % of prescribed total walking time in the short- and long-bout programs , respectively . Both programs increased plasma concentrations of high-density lipoprotein cholesterol , and decreased concentrations of triacylglycerol and total cholesterol ( all body mass , but the sum of four skinfolds , waist circumference , and hip circumference were decreased after both walking programs ( all P Predicted (.)VO(2max ) increased with both programs ( P tension/anxiety ( P brisk walking accumulated throughout the day are at least as effective as one continuous bout of equal total duration in reducing cardiovascular risk and improving aspects of mood in previously sedentary individuals",
"OBJECTIVE To evaluate effect of exercise consultation on physical activity and result ant physiological and biochemical variables at 6 months in people with type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 70 inactive people with type 2 diabetes were given st and ard exercise information and were r and omized to receive an exercise consultation ( n = 35 ) or not ( n = 35 ) . Exercise consultation , based on the transtheoretical model , combines motivational theory and cognitive behavioral strategies into an individualized intervention to promote physical activity . Changes from baseline to 6 months were assessed in 1 ) physical activity ( 7-day recall , accelerometer , cardiorespiratory fitness , stage , and processes of change ) , 2 ) physiological variables ( blood pressure and BMI ) , and 3 ) biochemical variables ( HbA(1c ) , lipid profile , and fibrinogen ) . RESULTS Between-group differences were recorded for the change in minutes of moderate activity ( P activity counts ( P activity counts per week and minutes of moderate activity per week ( P total exercise duration and peak gradient ( P HbA(1c ) ( P = 0.02 ) , systolic BP ( P = 0.02 ) , and fibrinogen ( P = 0.03 ) . CONCLUSIONS Exercise consultation increased physical activity and improved glycemic control and cardiovascular risk factors in people with type 2 diabetes",
"OBJECTIVE 1 . To demonstrate that combining pedometer use with cognitive and behavioral support material s has a positive effect on physical activity ( PA ) and attitudes towards pedometer use . 2 . To investigate how familiar the study sample is with pedometers and the ' 10,000 steps/day ' recommendation . METHODS From a r and om sample , drawn from the phone book , 304 volunteered ( 18 - 75 year ) to complete a question naire about familiarity with pedometers and the ' 10,000 steps/day ' recommendation . A sample of 103 participants agreed to wear a pedometer for 3 weeks , and was r and omly assigned to a condition with cognitive and behavioral support material s ( n=51 ) or without these material s ( n=52 ) . Participants completed the International Physical Activity Question naire before and after 21 days of pedometer use and an additional question naire on the attitudes towards pedometer use . RESULTS More than 58 % had never heard of a pedometer . In both conditions , walking ( F=10 , p=0.002 ) , moderate PA ( F=11 , p=0.001 ) , and vigorous PA ( F=14 , p interaction effects could be found . Significantly more participants in the condition with support material s had a positive attitude towards pedometer use . CONCLUSION Wearing a pedometer , with or without support material s , may increase PA . In our study , cognitive and behavioral support material s only affected attitudes towards pedometer use . PRACTICE IMPLICATION S More research is needed to investigate the effect of combining pedometer use with support material s on a longer time base and in less motivated people",
"This study reports an investigation of the effect of participating in moderate exercise ( three 40-min sessions of brisk walking a week for 6 months ) on mood state in 177 sedentary , mildly hypertensive volunteers . Mood was assessed by the Profile of Mood States , Bipolar Form ( POMS-BI ) , and no significant differences were found between control and exercise groups . The intervention group increased its exercise output more than the control group , but there was also a significant increase in exercise done by the control group . We conclude that exercise has no major effect on mood in hypertensive volunteers",
"BACKGROUND Pedometers have been identified as a potential motivational aid for increasing physical activity , but their efficacy has not been demonstrated in a community-based , non clinical sample . DESIGN A r and omized controlled trial was conducted from August to December 2005 . Analysis was completed in June 2006 . SETTING / PARTICIPANTS Inactive adults aged 30 - 65 years ( n=369 ) recruited from the community . INTERVENTION Comparison of a theoretically based self-help walking program ( WP ) and weekly diaries ( sent by mail ) ; the same walking program with a pedometer ( WPP ) ( also by mail ) ; and a no-treatment control group ( C ) . MEASURES Change in self-reported leisure time in any sports/recreation in the last 3 months , and all- purpose walking ( APW ) for exercise , recreation , and travel , and other moderate , vigorous physical activity in the last week . Proportions meeting physical activity recommendations ( equal to or greater than 150 minutes and equal to or greater than five sessions/week(-1 ) ) were determined . RESULTS A 3-month follow-up interview was conducted with 314 ( 85 % ) participants . Intention-to-treat analyses indicated significance within-group increases of APW and leisure-time walking ( LTW ) , but mean and median sessions and minutes changes were greatest in the WPP group . There were no significant between-group differences in regular LTW ( walked equal to or greater than 5 sessions/week(-1 ) for at least 30 minutes/session ) , but the WPP group increased significantly participation in other sports/recreations and was more likely than the control group to meet physical activity recommendations by all leisure-time physical activity ( adjusted odds ratio=2.40 , 95 % CI=1.17 - 4.93 ) , by APW ( adjusted odds ratio=1.75 95 % CI=0.92 - 3.34 ) and all physical activity ( adjusted odds ratio=1.59 95 % CI=0.92 - 2.79 ) in the last week . CONCLUSIONS Pedometers enhanced the effects of the self-help walking program . This low-cost intervention should be tested for sustainability",
"OBJECTIVES To determine whether a home-based pedometer-driven walking program with arthritis self-management education ( Walk + ) would increase physical activity , muscle strength , and functional performance in older adults with osteoarthritis ( OA ) of the knee as opposed to arthritis self-management education alone ( EDU ) . DESIGN A r and omized two-by-three ( group-by-time ) design with participants assigned to Walk + ( n = 17 , mean age + /- st and ard deviation = 69.6 + /- 6.7 ) or EDU ( n = 17 , age = 70.8 + /- 4.7 ) . SETTING Community located in the Baltimore-Washington area . PARTICIPANTS Thirty-four community-dwelling adults , aged 60 and older with symptomatic knee OA and self-reported functional impairment . INTERVENTIONS Both groups received 12 hours of the Arthritis Self-Management program over 12 weeks and were followed for an additional 12 weeks . In addition , the Walk + group received individualized instruction in the use of a pedometer , with the goal of increasing their step count by 30 % of their baseline step count . MEASUREMENTS The outcome measures were physical activity ( daily step counts and total activity vector magnitude as measured by a pedometer and Tritrac-R3D accelerometer ) , quadriceps femoris strength ( isometric peak torque ) , and functional performance tasks ( 100-foot walk-turn-walk , timed stair climb , timed chair rise , and pain status ) . RESULTS Daily steps walked showed a significant group-by-time interaction ( P = .04 ) after controlling for age . From baseline to completion of training , a 23 % increase in daily steps occurred in the Walk + group and a 15 % decrease in the EDU group . Although steps increased in the Walk + group , total activity vector magnitude was maintained , suggesting a more efficient gait . The Walk + group became quicker than the EDU group in the normal-pace walk-turn-walk ( P = .04 ) . An isometric strength gain of 21 % postintervention was seen in the Walk + group , compared with a loss of 3.5 % in the EDU group . CONCLUSION In older adults with symptomatic knee OA , Walk + appears to increase walking , with improvements in muscle strength and walking performance . The use of a home-based pedometer-driven program to increase physical activity , strength , and function in this population warrants further research",
"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 Physical activity ( PA ) has been shown to benefit glucose tolerance . Walking is a convenient low-impact mode of PA and is reported to be the most commonly performed activity for those with diabetes . The purpose of this study was to determine whether a recommendation to accumulate 10,000 steps/day for 8 weeks was effective at improving glucose tolerance in overweight , inactive women . METHODS Eighteen women ( 53.3 + /- 7.0 years old , 35.0 + /- 5.1 kg/m(2 ) ) with a family history of type 2 diabetes completed a 4-week control period followed by an 8-week walking program with no changes in diet . The walking program provided a goal of accumulating at least 10,000 steps/day , monitored by a pedometer . RESULTS During the control period , participants walked 4972 steps/day . During the intervention period , the participants increased their accumulated steps/day by 85 % to 9213 , which result ed in beneficial changes in 2-h postload glucose levels ( P AUC(glucose ) ( P = 0.025 ) , systolic blood pressure ( P diastolic blood pressure ( P = 0.002 ) . There were no changes in body mass , body fat percentage , and waist circumference during the walking intervention . CONCLUSIONS The 10,000 steps/day recommendation result ed in improved glucose tolerance and a reduction in systolic and diastolic blood pressure in overweight women at risk for type 2 diabetes . This demonstrates that activity can be accumulated throughout the day and does not have to result in weight loss to benefit this population",
"Voluntary employees ( N = 155 ) from nine different companies were screened by question naire for the study . They were r and omized into three study groups : counseling ( n = 52 ) , counseling + fitness testing ( n = 51 ) and control group ( n = 52 ) . The counseling was based on a goal -oriented conversation session for each participant and three follow-up appointments with an occupational nurse over a period of 1 year . The fitness tests were adapted from the UKK Health-related Fitness Test Battery . The outcome measures were the changes in the amount of leisure-time physical activity ( LTPA ) assessed by diary , pedometer and question naire at baseline and at 6 and 12 month follow-up visits . As a result , no statistically significant differences were detected between the three groups at either of the follow-up visits . It seemed , thus , that the two PA counseling methods implemented had no direct mid- or long-term effects on the LTPA of voluntary employees with no specific disease-related indication to increase LTPA",
"OBJECTIVE Using a r and omised control trial design , this study assessed the impact of two walking interventions , on the work day step counts and health of UK academic and administrative , university employees . METHOD A convenience sample of 58 women ( age 42+/-10 years ) and 6 men ( age 40+/-11 years ) completed baseline and intervention measures for step counts , % body fat , waist circumference and systolic/diastolic blood pressure , during a ten-week period ( October to December , 2005 ) . Before intervention , baseline step counts ( five working days ) were used to r and omly allocate participants to a control ( maintain normal behaviour , n=22 ) and two treatment groups ( \" walking routes \" , n=21 ; \" walking in tasks \" , n=21 ) . Intervention effects were evaluated by calculating differences between pre-intervention and intervention data . A one-way ANOVA analysed significant differences between groups . RESULTS A significant intervention effect ( p step counts , with mean differences indicating a decrease in steps for the control group ( -767 steps/day ) and increases in the \" walking routes \" ( + 926 steps/day ) and \" walking in tasks \" ( + 997 steps/day ) groups . Small , non-significant changes were found in % body fat , waist circumference and blood pressure . CONCLUSIONS Findings have implication s for work-based physical activity promotion and the development of walking interventions within the completion of work-based tasks",
"Because of their frequent encounters with sedentary patients , family physicians are poised to be on the forefront of the medical community 's response to physical inactivity . The purpose of this pilot study was to examine whether the addition of a pedometer to brief physician counseling could help patients increase their ambulatory activity . Ninety four participants recruited from a family medicine clinic were r and omly assigned to 2 groups . Both groups received a brief physician endorsement of regular physical activity , a h and out on the benefits of an active lifestyle , and 3 follow-up phone calls from a health educator . In addition , the intervention group received a pedometer and was instructed to record their steps daily over the 9-week study period . Measurements were taken for self-reported walking , walking stage-of-change , walking self-efficacy , and pedometer steps ( intervention group only ) . Among completers , mean daily step counts in the pedometer group rose from 6779 at baseline to 8855 at study end . Average individual improvement was 41 % over the study period . Both groups significantly increased blocks walked per day , stair climbing versus using the elevator , days per week walking > or = 30 minutes , and walking for fun/leisure . The frequency of walking short trips improved significantly more in the pedometer group relative to the comparison group . The results of this pilot study highlight the need for further research on the use of pedometers as a motivational tool in the context of medical encounters with inactive patients ",
"Recent physical activity recommendations call for activities that are of moderate intensity and can be performed intermittently during the day , such as walking . These proclamations were based partly on the assumption that moderate activities are generally more enjoyable than physically dem and ing ones , and they are , therefore , also more likely to be continued over the long haul . However , little is actually known about the affective outcomes of short bouts of walking and extant findings are equivocal . Four experimental studies examined the affective responses associated with short ( 10- to 15-min ) bouts of walking using a dimensional conceptual model of affect , namely , the circumplex . Results consistently showed that walking was associated with shifts toward increased activation and more positive affective valence . Recovery from walking for 10–15 min was associated with a return toward calmness and relaxation . This pattern was robust across different self-report measures of the circumplex affective dimensions , across ecological setting s ( field and laboratory ) , across time , and across sample",
"PURPOSE Walking is the most common leisure-time physical activity ( LTPA ) among U.S. adults . The purpose of this study was to estimate the prevalence of walking for physical activity and the proportion of walkers who met current public health physical activity recommendations . METHODS We analyzed data from the 1998 Behavioral Risk Factor Surveillance System , a collection of state-based , r and om-digit-dialed telephone surveys of adults . Physical activity measures included the type , frequency , and duration of the two LTPAs in which respondents engaged most often during the previous month . We calculated the prevalence of walking and the prevalence of three physical activity patterns defined by combinations of walking duration and frequency . We also examined the effect on these patterns of participating in a second LTPA . RESULTS In 1998 , an estimated 38.6 % of U.S. adults walked for physical activity . Among walkers , 21.3 % walked a minimum of 30 min five or more times per week . This approximates compliance with current physical activity recommendations . Compliance increased to 34.5 % when the criteria were relaxed to include at least 150 min of walking per week accumulated over three or more occasions . Relaxing the criteria further to include a minimum of 150 min.wk(-1 ) regardless of frequency produced only a small increase in compliance ( 37.6 % ) . However , compliance with each of these three activity patterns approximately doubled when a second LTPA was taken into account . CONCLUSIONS Less than 40 % of walkers complied through walking with even our most liberal physical activity pattern ( > or = 150 min.wk(-1 ) regardless of frequency ) . For walkers to meet current public health recommendations , many need to walk more frequently and /or to engage in additional physical activities",
"OBJECTIVE To evaluate a telephone counseling intervention that was design ed to help sedentary women begin and maintain a walking program . METHODS Females ( N = 197 ) were r and omly assigned to either an intervention , attention control , or no-attention control group . Assessment s were made at baseline and 6 months . RESULTS Women in the intervention group reported more time walked each day than did control women ( P women as well as for different income groups . CONCLUSION Overall , a counseling intervention via telephone appears to be a good way to help women begin a walking program",
"The main aim of this study was to assess the effects of a fitness assessment and exercise consultation on physical activity over 1 year in non-regularly active participants drawn from a socially and economically deprived community . Of 3000 people invited to volunteer for either intervention , 225 fitness assessment volunteers were r and omly assigned to an experimental or control group ; 145 exercise consultation volunteers were similarly assigned . Physical activity was measured at baseline , 4 weeks , 3 months ( plus an intervention re-test ) , 6 months and 1 year . Analysis of variance and follow-up Bonferroni analysis showed that , for those not regularly active at baseline , physical activity increased significantly to 4 weeks , was maintained to 6 months but had fallen by 1 year . Only those receiving an exercise consultation significantly increased their physical activity after 1 year . Compared with fitness assessment s , chi-square analysis showed that significantly more non-regularly active participants volunteered for an exercise consultation and those receiving an exercise consultation had significantly better long-term study adherence than those receiving a fitness assessment . The study also showed that , contrary to popular opinion , those in a socially and economically deprived community are not ' hard to reach ' and respond well to physical activity interventions",
"Objectives : To determine , using unsupervised walking programmes , the effects of exercise at a level lower than currently recommended to improve cardiovascular risk factors and functional capacity . Design : 12 week r and omised controlled trial . Setting : Northern Irel and Civil Service ; home-based walking . Participants : 106 healthy , sedentary 40 to 61 year old adults of both sexes . Interventions : Participants were r and omly allocated to a walking programme ( 30 minutes brisk walking three days a week ( n = 44 ) or five days a week ( n = 42 ) ) or a control group ( n = 20 ) . Participants could choose to walk in bouts of at least 10 minutes . They used pedometers to record numbers of steps taken . Intention to treat analysis of changes within groups was done using paired t tests ; extent of change ( baseline to 12 week measurements ) was compared between groups using analysis of variance and Gabriel ’s post hoc test . Main outcome measures : Blood pressure , serum lipids , body mass index , waist : hip ratio , and functional capacity ( using a 10 m shuttle walk test ) . Main results : 89 % ( 93/106 ) completed the study . Systolic blood pressure and waist and hip circumferences fell significantly both in the three day group ( 5 mm Hg , 2.6 cm , and 2.4 cm , respectively ) and in the five day group ( 6 mm Hg , 2.5 cm , and 2.2 cm ) ( p Functional capacity increased in both groups ( 15 % ; 11 % ) . Diastolic blood pressure fell in the five day group ( 3.4 mm Hg , p<0.05 ) . No changes occurred in the control group . Conclusions : This study provides evidence of benefit from exercising at a level below that currently recommended in healthy sedentary adults . Further studies are needed of potential longer term health benefits for a wider community from low levels of exercise",
"OBJECTIVE To investigate the link between a reduction in blood pressure ( BP ) and daily exercise . DESIGN Cross-sectional and longitudinal clinical intervention study with exercise education . SUBJECTS 43 overweight Japanese men aged 32 - 59 years ( BMI , 29.0+/-2.3 kg/m2 ) at baseline . Among the participants , a r and omly selected 23 overweight men ( BMI , 28.5+/-1.7 ) were further enrolled into the 10 months exercise program . MEASUREMENTS BP was measured every week and steps per day were also recorded every day throughout the observation period . Fat distribution was evaluated by visceral fat ( V ) and subcutaneous fat ( S ) areas measured with computed tomography ( CT ) scanning at umbilical level , at before , 5 months and after intervention . Anthropometric parameters were also measured at same point . Aerobic exercise level , muscle strength , flexibility and calorie intake and insulin resistance ( HOMA index ) were investigated at before and after the study . RESULTS In a cross sectional analysis , systolic BP ( SBP ) and diastolic BP ( DBP ) were significantly correlated with body composition . In a second longitudinal analysis , SBP was significantly reduced at 2 months and DBP was also reduced at 3 months , and almost maintained until the end of the observation period . Increasing daily walking was observed in 3 months and maintained until 10 months . Body composition , aerobic exercise level , muscle strength , flexibility and insulin resistance were significantly improved . There was positive correlation between DeltaDBP and Deltavisceral fat area ( 1 - 5 , 5 - 10 , 1 - 10 months ) . By stepwise multiple regression analysis , only Deltavisceral fat area was independently related to DeltaDBP at a significant level ( 1 - 10 months : DeltaDBP=-0.608 + 0.105Deltavisceral fat area , r2=0.227 , P=0.0334 ) . CONCLUSION The present study indicated daily exercise lowers BP and visceral fat area is the critical factor for BP change",
"BACKGROUND Although exercise parameters such as intensity and format have been shown to influence exercise participation rates and physiological outcomes in the short term , few data are available evaluating their longer-term effects . The study objective was to determine the 2-year effects of differing intensities and formats of endurance exercise on exercise participation rates , fitness , and plasma HDL cholesterol levels among healthy older adults . METHODS AND RESULTS Higher-intensity , group-based exercise training ; higher-intensity , home-based exercise ; and lower-intensity , home-based exercise were compared in a 2-year r and omized trial . Participants were 149 men and 120 postmenopausal women 50 to 65 years of age who were sedentary and free of cardiovascular disease . Recruitment was achieved through a r and om digit-dial community telephone survey and media promotion . All exercise occurred in community setting s. For higher-intensity exercise training , three 40-minute endurance training sessions per week were prescribed at 73 % to 88 % of peak treadmill heart rate . For lower-intensity exercise , five 30-minute endurance training sessions per week were prescribed at 60 % to 73 % of peak treadmill heart rate . Treadmill exercise performance , lipoprotein levels and other heart disease risk factors , and exercise adherence were evaluated at baseline and across the 2-year period . Treadmill exercise test performance improved for all three training conditions during year 1 and was successfully maintained during year 2 , particularly for subjects in the higher-intensity , home-based condition . Subjects in that condition also showed the greatest year 2 exercise adherence rates ( P HDL cholesterol were observed during year 1 , by the end of year 2 subjects in the two home-based training conditions showed small but significant HDL cholesterol increases over baseline ( P HDL cholesterol were associated with decreases in waist-to-hip ratio in both men and women ( P HDL cholesterol levels , the time frame needed to achieve HDL cholesterol change ( 2 years ) may be longer than that reported previously for younger population s. Frequency of participation may be particularly important for achieving such changes . Supervised home-based exercise regimens represent a safe , attractive alternative for achieving sustained participation",
"BACKGROUND Inactivity is a leading contributor to chronic health problems . Here , we examined the effects of a pedometer-based physical activity intervention ( Prince Edward Isl and -First Step Program , PEI-FSP ) on activity and specific health indices in 106 sedentary workers . METHODS Participants were recruited from five workplaces where most jobs were moderately-highly sedentary . Using subjects as their own control , physical activity ( pedometer-determined steps per day ) was compared before and after a 12-week intervention . Changes in body mass index ( BMI ) , waist girth , resting heart rate , and blood pressure were evaluated . RESULTS The PEI-FSP was completed by 59 % of participants . Steps per day increased from 7,029 + /- 3,100 ( SD ) at baseline to a plateau of 10,480 + /- 3,224 steps/day by 3.96 + /- 3.28 weeks of the intervention . The amount that participants were able to increase their steps per day was not related to their baseline BMI . On average , participants experienced significant decreases in BMI , waist girth , and resting heart rate . Reductions in waist girth and heart rate were significantly related to the increase in steps per day . In contrast , reductions in BMI were predicted by the initial steps per day . CONCLUSIONS The PEI-FSP increased physical activity in a sedentary population . Importantly , those with a higher BMI at baseline achieved relatively similar increases in their physical activity as participants with a lower BMI"
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BACKGROUND Physical inactivity is associated with poor outcomes in COPD , and as a result , interventions to improve physical activity ( PA ) are a current research focus . However , many trials have been small and inconclusive . OBJECTIVE The aim of this systematic review and meta- analysis was to study the effects of r and omized controlled trials ( RCTs ) targeting PA in COPD . METHODS Data bases ( Physiotherapy Evidence Data base [ PEDro ] , Embase , MEDLINE , CINAHL and the Cochrane Central Register for Controlled Trials ) were search ed using the following keywords : " COPD " , " intervention " and " physical activity " from inception to May 20 , 2016 ; published RCTs that aim ed to increase PA in individuals with COPD were included . The PEDro scale was used to rate study quality . St and ardized mean differences ( effect sizes , ESs ) with 95 % confidence intervals ( CIs ) were determined . Effects of included interventions were also measured according to the minimal important difference ( MID ) in daily steps for COPD ( 599 daily steps ) . RESULTS A total of 37 RCTs with 4,314 participants ( mean forced expiratory volume in one second ( FEV1 ) % predicted 50.5 [ SD=10.4 ] ) were identified . Interventions including exercise training ( ET ; n=3 studies , 103 participants ) significantly increased PA levels in COPD compared to st and ard care ( ES [ 95 % CI ] ; 0.84 [ 0.44 - 1.25 ] ) . The addition of activity counseling to pulmonary rehabilitation ( PR ; n=4 studies , 140 participants ) showed important effects on PA levels compared to PR alone ( 0.47 [ 0.02 - 0.92 ] ) , achieving significant increases that exceeded the MID for daily steps in COPD ( mean difference [ 95 % CI ] , 1,452 daily steps [ 549 - 2,356 ] ) . Reporting of method ological quality was poor in most included RCTs . CONCLUSION Interventions that included ET and PA counseling during PR were effective strategies to improve PA in COPD
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"Background : The benefits of pharmacotherapy with tiotropium H and iHaler 18 μg for patients with chronic obstructive pulmonary disease ( COPD ) have been previously demonstrated . However , few data exist regarding the treatment of moderate disease ( Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) stage II ) . Aims : To determine whether tiotropium improves lung function/patient-reported outcomes in patients with GOLD stage II COPD naive to maintenance therapy . Methods : A r and omised 24-week double-blind placebo-controlled trial of tiotropium 18 μg once daily ( via H and iHaler ) was performed in maintenance therapy – naive patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity ( FVC ) ratio Results : A total of 457 patients were r and omised ( 238 tiotropium , 219 placebo ; mean age 62 years ; FEV1 1.93 l ( 66 % predicted ) ) . Tiotropium was superior to placebo in mean change from baseline in post-dose FEV1 area under the curve from 0 to 3 h ( AUC0–3h ) at week 24 ( primary endpoint ) : 0.19 vs. −0.03 l ( least-squares mean difference 0.23 l , P were significantly improved with tiotropium versus placebo ( P with placebo , tiotropium provided numerical improvements in physical activity ( P = NS ) . Physician ’s Global Assessment ( health status ) improved ( P=0.045 ) with less impairment on the Work Productivity and Activity Impairment question naire ( P=0.043 ) at week 24 . The incidence of exacerbations , cough , bronchitis and dyspnoea was lower with tiotropium than placebo . Conclusions : Tiotropium improved lung function and patient-reported outcomes in maintenance therapy – naive patients with GOLD stage II COPD , suggesting benefits in initiating maintenance therapy early",
"Background In some patients with COPD , the disease is characterized by exacerbations . Severe exacerbations warrant a hospitalization , with prolonged detrimental effects on physical activity . Interventions after an exacerbation may improve physical activity , with longst and ing health benefits . Physical activity counseling and real-time feedback were effective in stable COPD . No evidence is available on the use of this therapeutic modality in patients after a COPD exacerbation . Methods Thirty patients were r and omly assigned to usual care or physical activity counseling , by telephone contacts at a frequency of 3 times a week and real-time feedback . Lung function , peripheral muscle strength , functional exercise capacity , symptom experience and COPD -related health status were assessed during hospital stay and 1 month later . Results Both groups significantly recovered in physical activity ( PAsteps : control group : 1013 ± 1275 steps vs intervention group : 984 ± 1208 steps ( p = 0.0005 ) ; PAwalk : control group : 13 ± 14 min vs intervention group : 13 ± 16 min ( p = 0.0002 ) ) , functional exercise capacity ( control group : 64 ± 59 m ( p = 0.002 ) vs intervention group : 67 ± 84 m ( p = 0.02 ) ) and COPD -related health status ( CAT : control group : −5 [ −7 to 1 ] ( p = 0.02 ) vs intervention group : −3 [ −10 to 1 ] points ( p = 0.03 ) ) . No differences between groups were observed . Conclusion From our pilot study , we concluded that telephone based physical activity counseling with pedometer feedback after an exacerbation did not result in better improvements in physical activity and clinical outcomes compared to usual care . Because of the difficult recruitment and the negative intermediate analyses , this study was not continued . Trial registration Clinical trials.gov NCT02223962 . Registered 4 September 2013",
"Introduction Chronic obstructive pulmonary disease ( COPD ) is associated with exercise limitation and physical inactivity , which are believed to have significant long-term negative health consequences for patients . While a number of COPD treatments and exercise training programmes increase exercise capacity , there is limited evidence for their effects on physical activity levels , with no clear association between exercise capacity and physical activity in clinical trials . Physical activity depends on a number of behaviour , environmental and physiological factors . We describe the design of the PHYSACTO trial , which is investigating the effects of bronchodilators , either alone or with exercise training , in combination with a st and ardised behaviour-change self-management programme , on exercise capacity and physical activity in patients with COPD . It is hypothesised that bronchodilators in conjunction with a behaviour-change self-management programme will improve physical activity and that this effect will be amplified by the addition of exercise training . Methods and analysis Patients are being recruited from 34 sites in Australia , New Zeal and , the USA , Canada and Europe . Patients receiving a multicomponent intervention design ed to support behaviour change related to physical activity are r and omised to four treatment arms : placebo , tiotropium , tiotropium+olo date rol , and tiotropium+olo date rol+exercise training . The primary outcome is improvement in exercise capacity after 8 weeks , measured by endurance time during a shuttle walk test . The secondary outcome is improvement in physical activity , including objective accelerometer assessment and patient-reported functioning using the Functional Performance Inventory — Short Form and the novel hybrid PROactive instrument . Additionally , the influence of moderating variables ( ie , factors influencing a patient 's choice to be physically active ) on increases in physical activity is also explored . Ethics and dissemination The study has been approved by the relevant Institutional Review Boards , Independent Ethics Committee and Competent Authority according to national and international regulations . The findings of the trial will be disseminated through relevant peer- review ed journals and international conference presentations . Trial registration number NCT02085161",
"Objectives To assess benefits of telephone-delivered health mentoring in community-based chronic obstructive pulmonary disease ( COPD ) . Design Cluster r and omised controlled trial . Setting Tasmanian general practice s : capital city ( 11 ) , large rural ( 3 ) , medium rural ( 1 ) and small rural ( 16 ) . Participants Patients were invited ( 1207 ) from general practitioner ( GP ) data bases with COPD diagnosis and /or tiotropium prescription , response rate 49 % ( 586 ) , refused ( 176 ) and excluded ( criteria : smoking history or previous study , 68 ) . Spirometry testing ( 342 ) confirmed moderate or severe COPD in 182 ( 53 % ) patients . R and omisation By r and om numbers code , block stratified on location , allocation by sequentially numbered , opaque and sealed envelopes . Intervention Health mentor ( HM ) group received regular calls to manage illness issues and health behaviours from trained community health nurses using negotiated goal setting : problem solving , decision-making and action planning . Control : usual care ( UC ) group received GP care plus non-interventional brief phone calls . Outcomes Measured at 0 , 6 and 12 months , the Short Form 36 ( SF-36 ) and St George ’s Respiratory Question naire ( SGRQ , primary ) ; Partners In Health ( PIH ) Scale for self-management capacity , Hospital Anxiety and Depression Scale ( HADS ) , Center for Epidemiologic Studies -Depression ( CES-D ) question naire , Post-Traumatic Stress Disorder Checklist , Satisfaction with life and hospital admissions ( secondary ) . Results 182 participants with COPD ( age 68±8 years , 62 % moderate COPD and 53 % men ) were r and omised ( HM=90 and UC=92 ) . Mixed model regression analysis accounting for clustering , adjusting for age , gender , smoking status and airflow limitation assessed efficacy ( regression coefficient , β , reported per 6-month visit ) . There was no difference in quality of life between groups , but self-management capacity increased in the HM group ( PIH overall 0.15 , 95 % CI 0.03 to 0.29 ; knowledge domain 0.25 , 95 % CI 0.00 to 0.50 ) . Anxiety decreased in both groups ( HADS A 0.35 ; 95 % CI −0.65 to −0.04 ) and coping capacity improved ( PIH coping 0.15 ; 95 % CI 0.04 to 0.26 ) . Conclusions Health mentoring improved self-management capacity but not quality of life compared to regular phone contact , which itself had positive effects where decline is generally expected",
"Objective To determine the feasibility and efficacy of a six-month , cell phone-based exercise persistence intervention for patients with chronic obstructive pulmonary disease ( COPD ) following pulmonary rehabilitation . Methods Participants who completed a two-week run-in were r and omly assigned to either MOBILE-Coached ( n = 9 ) or MOBILE-Self-Monitored ( n = 8) . All participants met with a nurse to develop an individualized exercise plan , were issued a pedometer and exercise booklet , and instructed to continue to log their daily exercise and symptoms . MOBILE-Coached also received weekly reinforcement text messages on their cell phones ; reports of worsening symptoms were automatically flagged for follow-up . Usability and satisfaction were assessed . Participants completed incremental cycle and six minute walk ( 6MW ) tests , wore an activity monitor for 14 days , and reported their health-related quality of life ( HRQL ) at baseline , three , and six months . Results The sample had a mean age of 68 ±11 and forced expiratory volume in one second 18 % predicted . Participants reported that logging their exercise and symptoms ( FEV1 ) of 40 ± was easy and that keeping track of their exercise helped them remain active . There were no differences between groups over time in maximal workload , 6MW distance , or HRQL ( p > 0.05 ) ; however , MOBILE-Self-Monitored increased total steps/day whereas MOBILE-Coached logged fewer steps over six months ( p = 0.04 ) . Conclusions We showed that it is feasible to deliver a cell phone-based exercise persistence intervention to patients with COPD post-rehabilitation and that the addition of coaching appeared to be no better than self-monitoring . The latter finding needs to be interpreted with caution since this was a purely exploratory study . Trial registration Clinical Trials.gov ( NCT00373932 )",
"Objectives Pulmonary rehabilitation ( PR ) provides benefit for patients with chronic obstructive pulmonary disease ( COPD ) in terms of quality of life ( QoL ) and exercise capacity ; however , the effects diminish over time . Our aim was to evaluate a maintenance programme for patients who had completed PR . Setting Primary and secondary care PR programmes in Norfolk . Participants 148 patients with COPD who had completed at least 60 % of a st and ard PR programme were r and omised and data are available for 110 patients . Patients had greater than 20 pack year smoking history and less than 80 % predicted forced expiratory volume in 1 s but no other significant disease or recent respiratory tract infection . Interventions Patients were r and omised to receive a maintenance programme or st and ard care . The maintenance programme consisted of 2 h ( 1 h individually tailored exercise training and 1 h education programme ) every 3 months for 1 year . Primary and secondary outcome measures The Chronic Respiratory Question naire ( CRQ ) ( primary outcome ) , endurance shuttle walk test ( ESWT ) , EuroQol ( EQ5D ) , hospital anxiety and depression score ( HADS ) , body mass index ( BMI ) , body fat , activity levels ( overall score and activity diary ) and exacerbations were assessed before and after 12 months . Results There was no statistically significant difference between the groups for the change in CRQ dyspnoea score ( primary end point ) at 12 months which amounted to 0.19 ( −0.26 to 0.64 ) units or other domains of the CRQ . There was no difference in the ESWT duration ( −10.06 ( −191.16 to 171.03 ) seconds ) , BMI , body fat , EQ5D , MET-minutes , activity rating , HADS , exacerbations or admissions . Conclusions A maintenance programme of three monthly 2 h sessions does not improve outcomes in patients with COPD after 12 months . We do not recommend that our maintenance programme is adopted . Other methods of sustaining the benefits of PR are required . Trial registration number NCT00925171",
"Background : Long-term non-invasive positive pressure ventilation ( NIPPV ) might improve the outcomes of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease ( COPD ) with chronic respiratory failure . A study was undertaken to investigate whether nocturnal NIPPV in addition to pulmonary rehabilitation improves health-related quality of life , functional status and gas exchange compared with pulmonary rehabilitation alone in patients with COPD with chronic hypercapnic respiratory failure . Methods : 72 patients with COPD were r and omly assigned to nocturnal NIPPV in addition to rehabilitation ( n = 37 ) or rehabilitation alone ( n = 35 ) . Outcome measures were assessed before and after the 3-month intervention period . Results : The Chronic Respiratory Question naire total score improved 15.1 points with NIPPV + rehabilitation compared with 8.7 points with rehabilitation alone . The difference of 7.5 points was not significant ( p = 0.08 ) . However , compared with rehabilitation alone , the difference in the fatigue domain was greater with NIPPV + rehabilitation ( mean difference 3.3 points , p the Maugeri Respiratory Failure question naire total score ( mean difference −10 % , p its cognition domain ( mean difference −22 % , p improved daytime arterial carbon dioxide pressure ( mean difference −0.3 kPa ; p and daily step count ( mean difference 1269 steps/day , p increased daytime minute ventilation ( mean difference 1.4 l ; p Conclusion : Non-invasive ventilation augments the benefits of pulmonary rehabilitation in patients with COPD with chronic hypercapnic respiratory failure as it improves several measures of health-related quality of life , functional status and gas exchange . Trial registration number : NCT00135538",
"Reference 1 . Burtin C , Langer D , van Remoortel H , Demeyer H , Gosselink R , Decramer M , et al. ( 2015 ) Physical Activity Counselling during Pulmonary Rehabilitation in Patients with COPD : A R and omised Controlled Trial . PLoS ONE 10(12 ) : e0144989 . doi : 10.1371/journal.pone.0144989 PMID : 26697853 Fig 2 . Relative changes in daily time spent walking , daily steps , daily time spent in at leastmoderate intense activities ( > 3.6metabolic equivalents ) and at least mild intense activities ( > 2.0metabolic equivalents ) after threemonths ( 3 m ) and after six months of rehabilitation ( 6 m ) compared to baseline . Data are expressed as percentage of change of least square means compared to baseline . No intervention*time effects were observed . * indicates time effect for the whole group ( p<0.05 compared to baseline )",
"The objective of this pilot study was to investigate the use of and satisfaction with a chronic obstructive pulmonary disease ( COPD ) telehealth program applied in both primary and secondary care . The program consisted of four modules : 1 ) activity coach for ambulant activity monitoring and real-time coaching of daily activity behavior , 2 ) web-based exercise program for home exercising , 3 ) self-management of COPD exacerbations via a triage diary on the web portal , including self-treatment of exacerbations , and 4 ) teleconsultation . Twenty-nine COPD patients were r and omly assigned to either the intervention group ( telehealth program for 9 months ) or the control group ( usual care ) . Page hits on the web portal showed the use of the program , and the Client Satisfaction Question naire showed satisfaction with received care . The telehealth program with decision support showed good satisfaction ( mean 26.4 , maximum score 32 ) . The program was accessed on 86 % of the treatment days , especially the diary . Patient adherence with the exercise scheme was low ( 21 % ) . Health care providers seem to play an important role in patients ’ adherence to telehealth in usual care . Future research should focus on full-scale implementation in daily care and investigating technological advances , like gaming , to increase adherence",
"Objective : To compare the effects of behavioral interventions targeting decreased sedentary behavior versus increased moderate-to-vigorous intensity physical activity ( MVPA ) in older adults . Method : Inactive older adults ( N = 38 , 68 ± 7 years old , 71 % female ) were r and omized to 12-week interventions targeting decreased sedentary behavior ( Sit Less ) or increased MVPA ( Get Active ) . The SenseWear armb and was used to objective ly assess activity in real time . Assessment s included a blinded armb and , the Community Health Activites Model Program for Senior ( CHAMPS ) question naire , 400-meter walk , and the Short Physical Performance Battery ( SPPB ) . Results : Objective ly measured MVPA increased in Get Active ( 75 ± 22 min/week , p .001 ) ; self-reported MVPA increased in both groups ( p did not change in either group ( all p > .05 ) . Only the Sit Less group improved the SPPB score ( 0.5 ± 0.3 , p = .046 ) . Discussion : Targeting reduced sedentary behavior had a greater effect on physical function among inactive but high functioning older adults over 12 weeks . Future studies of longer duration and combining increased MVPA with reduced sedentary behavior are needed",
"BACKGROUND Physical inactivity is significantly associated with more frequent hospitalizations and increased mortality in COPD even after adjusting for disease severity . While practice guidelines recommend regular physical activity for all patients with COPD , health systems are challenged in operationalizing an effective and sustainable approach to assist patients in being physically active . METHODS A pragmatic r and omized controlled trial design was used to determine the effectiveness of a 12-month home and community-based physical activity coaching intervention ( Walk On ! ) compared to st and ard care for 1650 patients at high risk for COPD exacerbations from a large integrated health care system . Eligible patients with a COPD -related hospitalization , emergency department visit , or observational stay in the previous 12months were automatically identified from the electronic medical records ( EMR ) system and r and omized to treatment arms . The Walk On ! intervention included collaborative monitoring of step counts , semi-automated step goal recommendations , individualized reinforcement from a physical activity coach , and peer/family support . RESULTS The primary composite outcome included all-cause hospitalizations , emergency department visits , observational stays , and death in the 12months following r and omization . Secondary outcomes included COPD -related utilization , cardio-metabolic markers , physical activity , symptoms , and health-related quality of life . With the exception of patient reported outcomes , all utilization and clinical variables were automatically captured from the EMR . CONCLUSIONS If successful , findings from this multi-stakeholder driven trial of a generalizable and scalable physical activity intervention , carefully design ed with sufficient flexibility , intensity , and support for a large ethnically diverse sample could re-define the st and ard of care to effectively address physical inactivity in COPD",
"Background Pulmonary rehabilitation is widely advocated for people with chronic obstructive pulmonary disease ( COPD ) to improve exercise capacity , symptoms and quality of life , however only a minority of individuals with COPD are able to participate . Travel and transport are frequently cited as barriers to uptake of centre-based programs . Other models of pulmonary rehabilitation , including home-based programs , have been proposed in order to improve access to this important treatment . Previous studies of home-based pulmonary rehabilitation in COPD have demonstrated improvement in exercise capacity and quality of life , but not all elements of the program were conducted in the home environment . It is uncertain whether a pulmonary rehabilitation program delivered in its entirety at home is cost effective and equally capable of producing benefits in exercise capacity , symptoms and quality of life as a hospital-based program . The aim of this study is to compare the costs and benefits of home-based and hospital-based pulmonary rehabilitation for people with COPD . Methods / Design This r and omised , controlled , equivalence trial conducted at two centres will recruit 166 individuals with spirometrically confirmed COPD . Participants will be r and omly allocated to hospital-based or home-based pulmonary rehabilitation . Hospital programs will follow the traditional outpatient model consisting of twice weekly supervised exercise training and education for eight weeks . Home-based programs will involve one home visit followed by seven weekly telephone calls , using a motivational interviewing approach to enhance exercise participation and facilitate self management . The primary outcome is change in 6-minute walk distance immediately following intervention . Measurements of exercise capacity , physical activity , symptoms and quality of life will be taken at baseline , immediately following the intervention and at 12 months , by a blinded assessor . Completion rates will be compared between programs . Direct healthcare costs and indirect ( patient-related ) costs will be measured to compare the cost-effectiveness of each program . Discussion This trial will identify whether home-based pulmonary rehabilitation can deliver equivalent benefits to centre-based pulmonary rehabilitation in a cost effective manner . The results of this study will contribute new knowledge regarding alternative models of pulmonary rehabilitation and will inform pulmonary rehabilitation guidelines for COPD .Trial registration Clinical Trials.gov : NCT01423227",
"Introduction Chronic obstructive pulmonary disease is generally progressive and associated with reduced physical activity . Both pharmacological therapy and exercise training can improve exercise capacity ; however , these are often not sufficient to change the amount of daily physical activity a patient undertakes . Behaviour-change self-management programmes are design ed to address this , including setting motivational goals and providing social support . We present and discuss the necessary method ological considerations when integrating behaviour-change interventions into a multicentre study . Methods and analysis PHYSACTO is a 12-week phase IIIb study assessing the effects on exercise capacity and physical activity of once-daily tiotropium+olo date rol 5/5 µg with exercise training , tiotropium+olo date rol 5/5 µg without exercise training , tiotropium 5 µg or placebo , with all pharmacological interventions administered via the Respimat inhaler . Patients in all intervention arms receive a behaviour-change self-management programme to provide an optimal environment for translating improvements in exercise capacity into increases in daily physical activity . To maximise the likelihood of success , special attention is given in the programme to : ( 1 ) the Site Case Manager , with careful monitoring of programme delivery ; ( 2 ) the patient , incorporating patient-evaluation/programme-evaluation measures to guide the Site Case Manager in the self-management intervention ; and ( 3 ) quality assurance , to help identify and correct any problems or shortcomings in programme delivery and ensure the effectiveness of any corrective steps . This paper documents the comprehensive methods used to optimise and st and ardise the behaviour-change self-management programme used in the study to facilitate dialogue on the inclusion of this type of programme in multicentre studies . Ethics and dissemination The study has been approved by the relevant Institutional Review Boards , Independent Ethics Committee and Competent Authority according to national and international regulations . The results of this study will be disseminated through relevant , peer- review ed journals and international conference presentations . Trial registration number NCT02085161",
"In 159 chronic obstructive pulmonary disease ( COPD ) patients ( 139 males , mean age 62 + /- 8 yrs , arterial oxygen tension ( PaO2 ) 7.2 + /- 0.9 kPa ) , on long-term oxygen therapy ( LTOT ) , we evaluated the effects of portable oxygen therapy both on the daily duration of oxygen therapy and on daily activities . They were given two types of LTOT at r and om : group A ( n = 75 ) , oxygen concentrators only ( OC ) ; group B ( n = 84 ) , either small oxygen cylinders plus OC ( B1 = 51 ) or liquid oxygen ( B2 = 33 ) . The patients were followed-up for one year by means of : a ) medical examination every three months ; b ) monthly home interviews concerning the daily duration of oxygen therapy , the utilization of the devices and the daily activities of the patients ; c ) a measurement of the daily oxygen usage . The results show that : 1 ) there are no significant clinical and functional differences between groups A and B at the onset of and throughout the study ; 2 ) in group B the daily use of oxygen therapy is significantly longer than in group A ( 17 + /- 3.5 h.day-1 vs 14 + /- 3 h.day-1 , p less than 0.01 ) without any difference between groups B1 and B2 ; 3 ) outdoor walking activities are different between groups A and B , at least in those patients using oxygen more than 18 h.day-1 . Only 60 % of patients in group B ( 55 % of B1 ; 67 % of B2 ) use their portable devices outdoors and for walking . No strict predictive criterion of this use is found in our study . ( ABSTRACT TRUNCATED AT 250 WORDS",
"Little is known about effects of community-based physiotherapeutic exercise programmes incorporated in COPD self-management programmes . In a r and omised trial , the effect of such a programme ( COPE-active ) on exercise capacity and various secondary outcomes including daily activity as a marker of behaviour change was evaluated . All patients attended four 2-h self-management sessions . In addition the intervention group participated in the COPE-active programme offered by physiotherapists of private practice s , consisting of a 6-month \" compulsory \" period ( 3 sessions/week ) and subsequently a 5-month \" optional \" period ( 2 sessions/week ) . Because COPE-active was intended to change behaviour with regard to exercise , one session/week in both periods consisted of unsupervised home-based exercise training . Of 153 patients , 74 intervention and 68 control patients completed the one-year follow-up . Statistically significant between-group differences in incremental shuttle walk test-distance ( 35.1 m ; 95 % CI ( 8.4 ; 61.8 ) ) and daily activity ( 1190 steps/day ; 95 % CI ( 256 ; 2125 ) ) were found in favour of the intervention group . Over the 12-month period a significant difference of the chronic respiratory question naire ( CRQ ) dyspnoea-score ( 0.33 points ; 95 % CI ( 0.01 ; 0.64 ) ) and a non-significant difference of the endurance shuttle walk test ( 135 m ( 95 % CI ( -29 ; 298 ) ) was found . No differences were found in the other CRQ-components , anxiety and depression scores and percentage of fat free mass . This study demonstrates that a community-based reactivation programme improves exercise capacity in patients with moderately to severe COPD . Even more important , the programme improves actual daily activity after one-year which indicates behaviour change with regard to daily exercise . Registered trail number : IS RCT N81447311",
"OBJECTIVES To evaluate the effectiveness of an exercise adherence intervention to maintain daily activity , adherence to exercise , and exercise capacity over 1 year after completion of an outpatient pulmonary rehabilitation program . DESIGN A 2-group , experimental design was used with r and omization into intervention and usual care groups . SETTING Outpatient pulmonary rehabilitation program in a university-affiliated medical center . PARTICIPANTS One hundred six subjects ( 98 men ; 98 with chronic obstructive pulmonary disease ) with a mean age of 67 years and chronic lung disease . INTERVENTION Twelve-week adherence intervention ( weekly phone calls and home visit ) including counseling on establishing , monitoring , and problem-solving in maintaining a home exercise program . MAIN OUTCOME MEASURES Primary outcomes included daily activity ( accelerometer ) , exercise adherence ( exercise diary ) , and exercise capacity ( six-minute walk test ) . All measures were performed at baseline , after the pulmonary rehabilitation program ( 8 wk ) , after the adherence intervention ( 20 wk ) , and at 1 year . RESULTS A rank-based analysis of covariance showed less decline at 20 weeks in exercise adherence ( intervention mean , + 3 min ; control mean , -13 min ; P=.015 ) and exercise capacity ( intervention mean , -10.7 m ; control mean , -35.4 m ; P=.023 ) . There were no differences in daily activity at 20 weeks or any differences in any primary variable at 1 year . CONCLUSIONS The intervention enhanced exercise adherence and exercise capacity in the short term but produced no long-term benefit . These findings are in part attributed to the disappointing measurement characteristics of the accelerometer used to measure daily activity . The intervention was acceptable to participants . Further study is needed to fashion interventions that have more persistent benefit",
"Background Pulmonary rehabilitation programs only modestly enhance daily physical activity levels in patients with chronic obstructive pulmonary disease ( COPD ) . This r and omised controlled trial investigates the additional effect of an individual activity counselling program during pulmonary rehabilitation on physical activity levels in patients with moderate to very severe COPD . Methods Eighty patients ( 66±7 years , 81 % male , forced expiratory volume in 1 second 45±16 % of predicted ) referred for a six‐month multidisciplinary pulmonary rehabilitation program were r and omised . The intervention group was offered an additional eight-session activity counselling program . The primary outcomes were daily walking time and time spent in at least moderate intense activities . Results Baseline daily walking time was similar in the intervention and control group ( median 33 [ interquartile range 16–47 ] vs 29 [ 17–44 ] ) whereas daily time spent in at least moderate intensity was somewhat higher in the intervention group ( 17[4–50 ] vs 12[2–26 ] min ) . No significant intervention*time interaction effects were observed in daily physical activity levels . In the whole group , daily walking time and time spent in at least moderate intense activities did not significantly change over time . Conclusions The present study identified no additional effect of eight individual activity counselling sessions during pulmonary rehabilitation to enhance physical activity levels in patients with COPD . Trial Registration clinical trials.gov",
"Background Indacaterol is a long-acting beta-2 agonist for once-daily treatment of COPD . We evaluated the effects of indacaterol 150 μg on lung hyperinflation compared with placebo and open-label tiotropium 18 μg . We measured physical activity during treatment with indacaterol 150 μg and matched placebo . Methods We performed a r and omized , three-period , cross-over study ( 21 days of treatment separated by two wash-out periods of 13 days ) with indacaterol 150 μg or matching placebo and tiotropium 18 μg . Lung function was assessed by body plethysmography and spirometry . Physical activity was measured for one week by a multisensory armb and at the end of both treatment periods with indacaterol/matched placebo . The primary endpoint was peak inspiratory capacity at the end of each treatment period . Results 129 patients ( mean age , 61 years ; mean post-bronchodilator FEV1 , 64 % ) , were r and omized and 110 patients completed the study . Peak inspiratory capacity was 0.22 L greater with Indacaterol at day 21 compared to placebo ( p improved other parameters of lung hyperinflation compared with placebo . All parameters of physical activity were significantly increased during treatment with indacaterol versus placebo . Conclusions Indacaterol 150 μg improved lung hyperinflation in patients with moderate COPD , which was associated with an increase of physical activity . Trial registration Clinical Trials.gov registration number : NCT01012765",
"Background In patients with COPD progressive dyspnoea leads to a sedentary lifestyle . To date , no studies exist investigating the effects of Nordic Walking in patients with COPD . Therefore , the aim was to determine the feasibility of Nordic Walking in COPD patients at different disease stages . Furthermore we aim ed to determine the short- and long-term effects of Nordic Walking on COPD patients ' daily physical activity pattern as well as on patients exercise capacity . Methods Sixty COPD patients were r and omised to either Nordic Walking or to a control group . Patients of the Nordic Walking group ( n = 30 ; age : 62 ± 9 years ; FEV1 : 48 ± 19 % predicted ) underwent a three-month outdoor Nordic Walking exercise program consisting of one hour walking at 75 % of their initial maximum heart rate three times per week , whereas controls had no exercise intervention . Primary endpoint : daily physical activities ( measured by a vali date d tri-axial accelerometer ) ; secondary endpoint : functional exercise capacity ( measured by the six-minute walking distance ; 6MWD ) . Assessment time points in both groups : baseline , after three , six and nine months . Results After three month training period , in the Nordic Walking group time spent walking and st and ing as well as intensity of walking increased ( Δ walking time : + 14.9 ± 1.9 min/day ; Δ st and ing time : + 129 ± 26 min/day ; Δ movement intensity : + 0.40 ± 0.14 m/s2 ) while time spent sitting decreased ( Δ sitting time : -128 ± 15 min/day ) compared to baseline ( all : p : p significantly increased compared to baseline ( Δ 6MWD : + 79 ± 28 meters ) as well as compared to controls ( both : p showed unchanged daily physical activities and 6MWD compared to baseline for all time points . Conclusions Nordic Walking is a feasible , simple and effective physical training modality in COPD . In addition , Nordic Walking has proven to positively impact the daily physical activity pattern of COPD patients under short- and long-term observation . Clinical trial registration Nordic Walking improves daily physical activities in COPD : a r and omised controlled trial - IS RCT",
"Physical inactivity is a cardinal feature of chronic obstructive pulmonary disease ( COPD ) , and is associated with increased morbidity and mortality . Pedometers , which have been used in healthy population s , might also increase physical activity in patients with COPD . COPD patients taking part in a 3-month individualised programme to promote an increase in their daily physical activity were r and omised to either a st and ard programme of physical activity encouragement alone , or a pedometer-based programme . Assessment s were performed by investigators blinded to treatment allocation . Change in average 1-week daily step count , 6-min walking distance ( 6MWD ) , modified Medical Research Council scale , St George ’s respiratory question naire ( SGRQ ) and COPD assessment test ( CAT ) were compared between groups . 102 patients were recruited , of whom 97 completed the programme ( pedometer group : n=50 ; control group : n=47 ) ; 60.8 % were male with a mean±sd age of 68.7±8.5 years , and forced expiratory volume in 1 s ( FEV1 ) 66.1±19.4 % and FEV1/forced vital capacity 55.2±9.5 % . Both groups had comparable characteristics at baseline . The pedometer group had significantly greater improvements in : physical activity 3080±3254 steps·day−1 versus 138.3±1950 steps·day−1 ( p ) ; SGRQ −8.8±12.2 versus −3.8±10.9 ( p=0.01 ) ; CAT score −3.5±5.5 versus −0.6±6.6 ( p=0.001 ) ; and 6MWD 12.4±34.6 versus −0.7±24.4 m ( p=0.02 ) than patients receiving activity encouragement only . A simple physical activity enhancement programme using pedometers can effectively improve physical activity level and quality of life in COPD patients . Pedometer-based programme produced clinical ly important improvements in physical activity and health status in COPD",
"Abstract Lightweight ambulatory oxygen devices are provided on the assumptions that they enhance compliance and increase activity , but data to support these assumptions are lacking . We studied 22 patients with severe chronic obstructive pulmonary disease receiving long-term oxygen therapy ( 14 men , average age = 66.9 y , FEV1 = 33.6%pred , PaO2 at rest = 51.7 torr ) who were using E-cylinders as their portable oxygen . Subjects were recruited at 5 sites and studied over a 2-week baseline period and for 6 months after r and omizing them to either continuing to use 22-lb E-cylinders towed on a cart or to carrying 3.6-lb aluminum cylinders . Utilizing novel electronic devices , ambulatory and stationary oxygen use was monitored continuously over the 2 weeks prior to and the 6 months following r and omization . Subjects wore tri-axial accelerometers to monitor physical activity during waking hours for 2–3 weeks prior to , and at 3 and 6 months after , r and omization . Seventeen subjects completed the study . At baseline , subjects used 17.2 hours of stationary and 2.5 hours of ambulatory oxygen daily . At 6 months , ambulatory oxygen use was 1.4 ± 1.0 hrs in those r and omized to E-cylinders and 1.9 ± 2.4 hrs in those using lightweight oxygen ( P = NS ) . Activity monitoring revealed low activity levels prior to r and omization and no significant increase over time in either group . In this group of severe chronic obstructive pulmonary disease patients , providing lightweight ambulatory oxygen did not increase either oxygen use or activity . Future efforts might focus on strategies to encourage oxygen use and enhance activity in this patient group . This trial is registered at Clinical Trials.gov ( NCT003257540 )",
"Background People with chronic obstructive pulmonary disease lead sedentary lives and could benefit from increasing their physical activity . The purpose of this study was to determine if an exercise-specific self-efficacy enhancing intervention could increase physical activity and functional performance when delivered in the context of 4 months of upper body resistance training with a 12-month follow-up . Methods In this r and omized controlled trial , subjects were assigned to : exercise-specific self-efficacy enhancing intervention with upper body resistance training ( SE-UBR ) , health education with upper body resistance training ( ED-UBR ) , or health education with gentle chair exercises ( ED-Chair ) . Physical activity was measured with an accelerometer and functional performance was measured with the Functional Performance Inventory . Forty-nine people with moderate to severe chronic obstructive pulmonary disease completed 4 months of training and provided valid accelerometry data , and 34 also provided accelerometry data at 12 months of follow-up . The self-efficacy enhancing intervention emphasized meeting physical activity guidelines and increasing moderate-to-vigorous physical activity . Results Differences were observed in light physical activity ( LPA ) after 4 months of training , time by group interaction effect ( P=0.045 ) . The SE-UBR group increased time spent in LPA by + 20.68±29.30 minutes/day and the other groups decreased time spent in LPA by −22.43±47.88 minutes/day and -25.73±51.76 minutes/day . Changes in LPA were not sustained at 12-month follow-up . There were no significant changes in moderate-to-vigorous physical activity , sedentary time , or functional performance . Subjects spent most of their waking hours sedentary : 72%±9 % for SE-UBR , 68%±10 % for ED-UBR , and 74%±9 % for ED-Chair . Conclusion The self-efficacy enhancing intervention produced a modest short-term increase in LPA . Further work is needed to increase the magnitude and duration of effect , possibly by targeting LPA",
"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",
"PURPOSE To compare the effects of short-term ( 3 months ) and long-term ( 18 months ) involvement in an exercise program on self-reported disability and physical function in patients with chronic obstructive pulmonary disease ( COPD ) . METHODS A total of 140 patients with COPD were studied in a r and omized , single-blinded clinical trial . Self-reported disability and physical function were assessed using a 21-item question naire , a 6-minute walk , timed stair climb , and an overhead task . RESULTS At the completion of the trial , participants in the long-term intervention reported 12 % less disability than those in the short-term intervention ( adjusted mean with 95 % confidence interval , 1.53 ( 1.43 - 1.63 ) versus 1.71 ( 1.61 to 1.81 ) units , respectively ; P=.016 ) , walked 6 % farther during 6-minutes ( 1,815.0 [ 1,750.4 - 1,879.6 ] vs 1,711.5 [ 1,640.7 - 1,782.3 ] feet , respectively ) , climbed steps 11 % faster ( 11.6 [ 11.0 - 12.2 ] vs 12.9 [ 12.3 - 13.5 ] seconds , respectively ) , and completed an overhead task 8 % faster ( 46.8 [ 44.4 - 49.2 ] vs 50.4 [ 47.8 - 53.0 ] seconds , respectively ) than those in the short-term intervention . CONCLUSION An 18 month exercise program results in greater improvements in self-reported disability and physical function in patients with COPD when compared with a 3-month exercise program . As such , long-term exercise should be recommended for all patients with COPD",
"Study objectives The aims of this study were to establish whether pulmonary rehabilitation ( PR ) improves domestic function and daily activity levels in COPD and whether individually targeted exercise is more effective than general exercise . Design Prospect i ve r and omized , controlled trial . Setting Outpatient PR program in secondary care . Participants One-hundred eighty patients ( mean [ ±SD ] age , 68.3 ± 8.6 years ; FEV 1 , 0.95 ± 0.4 L ; FEV 1 /FVC ratio , 0.51 ± 0.15 ; 111 male patients ; 69 female patients ) with stable COPD . One hundred twenty-one patients completed the study . Interventions Patients were r and omized to a conventional 7-week general exercise program ( [ GEP ] n=90 ) or an individually targeted exercise program ( [ ITEP ] n=90 ) . Measurement and results Daily activity was measured using ambulatory activity monitors ( Z80 –32k V1 Int ; Gaehwiler Electronics ; Hombrechtikon , Switzerl and ) . These were lightweight devices , which contained a uniaxial accelerometer . Domestic function was assessed by the Canadian Occupational Performance Measure ( COPM ) . Exercise performance was assessed by the incremental shuttle walk test ( ISWT ) and the endurance shuttle walk test and health status by the chronic respiratory question naire – self-reported . Activity monitor counts increased by 29.18 % ( 95 % confidence interval [ CI ] , 3.19 to 55.17 ; p=0.03 ) for the GEP and 40.63 % ( 95 % CI , 7.42 to 73.83 ; p=0.02 ) for the ITEP . Mean COPM performance scores increased by 1.71 ( 95 % CI , 1.37 to 2.05 ; p=0.0001 ) for the GEP and 1.46 ( 95 % CI , 1.05 to 1.87 ; p=0.0001 ) for the ITEP . Mean COPM satisfaction scores increased by 2.27 ( 95 % CI , 1.74 to 2.81 ; p=0.0001 ) for the GEP and 2.04 ( 95 % CI , 1.56 to 2.52 ; p=0.0001 ) for the ITEP . ISWT scores increased by 81.72 m ( range , 63.83 to 99.62 ) for the GEP and by 85.52 m ( range , 67.62 to 103.42 ) for the ITEP . No statistically significant difference was found between the general exercise group and the individually targeted exercise group for any outcome measure . Conclusions Pulmonary rehabilitation improves domestic function and physical activity . This study also demonstrates that general exercise training is as effective as individually targeted training",
"BACKGROUND : The effects of different exercise training programs on the level of physical activity in daily life in patients with COPD remain to be investigated . OBJECTIVE : In patients with COPD we compared the effects of 2 exercise/training regimens ( a high-intensity whole-body endurance- and -strength program , and a low-intensity calisthenics- and -breathing-exercises program ) on physical activity in daily life , exercise capacity , muscle force , health-related quality of life , and functional status . METHODS : We r and omized 40 patients with COPD to perform either endurance- and -strength training ( no. = 20 , mean ± SD FEV1 40 ± 13 % of predicted ) at 60–75 % of maximum capacity , or calisthenics- and -breathing-exercises training ( no. = 20 , mean ± SD FEV1 39 ± 14 % of predicted ) . Both groups underwent 3 sessions per week for 12 weeks . Before and after the training programs the patients underwent activity monitoring with motion sensors , incremental cycle-ergometry , 6-min walk test , and peripheral-muscle-force test , and responded to question naires on health-related quality of life and functional status ( activities of daily living , pulmonary functional status , and dyspnea ) . RESULTS : Time spent active and energy expenditure in daily life were not significantly altered in either group . Exercise capacity and muscle force significantly improved only in the endurance- and -strength group . Health-related quality of life and functional status improved significantly in both groups . CONCLUSIONS : Neither training program significantly improved time spent active or energy expenditure in daily life . The training regimens similarly improved quality of life and functional status . Exercise capacity and muscle force significantly improved only in the high-intensity endurance- and -strength group",
"BACKGROUND Pulmonary Rehabilitation ( \" Rehabilitation \" ) can improve both lung function and quality of life in patients suffering from chronic obstructive pulmonary disease ( COPD ) even if only a very small proportion of patients have access to Rehabilitation . Supplementation of Essential Amino Acids ( EAAs ) might allow COPD patients to achieve some typical Rehabilitation outcomes such as a better physical performance and an improved health status . METHODS 88 COPD out- patients ( GOLD class 3 - 4 ) with a body mass index ( BMI ) to receive EAAs ( n = 44 ) or placebo ( n = 44 ) for twelve weeks . Primary outcome measures were changes in both physical activities in daily life ( measured by Sense Wear Armb and in terms of mean steps walked in one week ) and in quality of life ( measured by the St George 's Respiratory Question naire , SGRQ ) . RESULTS After 12 weeks , the physical performance was significantly increased vs baseline only in patients who received EAAs ( 1140.33 + /- 524.69 and 638.68 + /- 662.1 steps/day , respectively ; p = 0.02 ) , being also the comparison vs the placebo group highly significant ( p = 0.003 ) . Similarly , the SGRQ score improved significantly only in EAA patients ( 69.35 + /- 9.51 vs baseline 72.04 + /- 8.62 ; p placebo , EAAs patients significantly increased their fat-free mass ( p = 0.04 ) , muscle strength ( p saturation of oxygen ( p = 0.05 ) , serum albumin ( p original cognitive dysfunction ( p = 0.02 ) . CONCLUSIONS Oral supplementation with EAAs contribute to improve the daily-life performance in domiciliary severe COPD patients who can not enter any Rehabilitation programme , together with their quality of life ; nutritional and cognitive status , and muscle strength",
"BACKGROUND Even after a rehabilitation program , levels of physical activity in COPD progressively decrease unless strategies to encourage activity are implemented . We analyzed the effects of the implementation of urban walking circuits on levels of physical activity and exercise capacity of patients with severe and very severe COPD after a rehabilitation program . METHOD A total of 83 patients were r and omized to either urban circuits group ( UCG ) or usual care in the non-circuit group ( NCG ) , after completing a 2-week rehabilitation program . Results were evaluated 9 months after completion of the rehabilitation program and were compared with a control group of 54 patients not enrolled in the rehabilitation program . RESULTS At the end of follow-up , UCG patients increased their physical activity by a mean of 32.4 ( SE = 5.9 ) min per day and 1.09 ( SE = 0.22 ) days walked per week ; 33.9 ( SE = 5.6 ) min per day and 1.12 ( SE = 0.24 ) days per week more compared to the NCG ( p 6-min walking test and minutes walked per day in the UCG ( r(2 ) = 0.52 , p 0.05 ) . Controls showed a significant decrease in exercise capacity and physical activity over the follow-up . CONCLUSIONS Urban circuits are an easy , inexpensive strategy , which demonstrated to be useful to stimulate physical activity in our population of severe and very severe COPD patients and result ed in increased exercise capacity even 9 months after completion of a rehabilitation program",
"BACKGROUND Chronic obstructive pulmonary disease ( COPD ) patients have lower levels of physical activity compared to age-matched controls , and they limit physical activities requiring normal exertion . Our purpose was to compare the effectiveness of a traditional exercise therapy ( TET ) program with a behavioral lifestyle activity program ( LAP ) in promoting physical activity . METHODS Moderate physical activity ( kcal/week ) was assessed in 176 COPD patients using the Community Health Activities Model for Seniors question naire . Patients were r and omized to either a three month TET program that meet thrice weekly or a LAP . The LAP was design ed to teach behavioral skills that encouraged the daily accumulation of self-selected physical activities of at least moderate intensity . Interventionist contact was similar ( 36 h ) between the two groups . Patients were assessed at baseline and 3 , 6 and 12 months . RESULTS Compared to baseline values , self-reported moderate physical activity increased three months post-r and omization with no significant difference ( p = 0.99 ) found between the TET ( 2501 + /- 197 kcal/week ) and the LAP ( 2498 + /- 211 kcal/week ) . At 6 and 12 months post-r and omization , there were no significant differences ( p = 0.37 and 0.69 , respectively ) in self-reported levels of moderate physical activity between the TET ( 2210 + /- 187 and 2213 + /- 218 kcal/week , respectively ) and the LAP ( 2456 + /- 198 and 2342 + /- 232 kcal/week , respectively ) . CONCLUSION Although there was no difference between treatment groups , the TET and the LAP were both effective at in increasing moderate levels of physical activity at 3 months and maintaining moderate physical activity levels 12 months post-r and omization . This clinical trial is registered with Clinical Trials.gov . Its identifier is NCT00328484",
"OBJECTIVE To study the effects of a lifestyle physical activity counseling program with feedback of a pedometer during pulmonary rehabilitation . METHODS Twenty-one chronic obstructive pulmonary disease ( COPD ) patients were r and omized to an experimental group that followed a regular rehabilitation program plus the counseling intervention or to a control group that only followed rehabilitation . The primary outcome was daily physical activity assessed by pedometers . Secondary outcomes were physical fitness , health-related quality of life , activities of daily living , depression and self-efficacy . RESULTS The experimental group showed an increase of 1,430 steps/day ( + 69 % from baseline ) , whereas the control group showed an increase of 455 steps/day ( + 19 % ) ( p = 0.11 for group x time interaction ) . The secondary outcomes showed no differences . CONCLUSION AND PRACTICE IMPLICATION S This study showed that the use of the pedometer , in combination with exercise counseling and the stimulation of lifestyle physical activity , is a feasible addition to pulmonary rehabilitation which may improve outcome and maintenance of rehabilitation results",
"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 .",
"Background Improvements in ventilatory mechanics with tiotropium increases exercise tolerance during pulmonary rehabilitation . We wondered whether tiotropium also increased physical activities outside of pulmonary rehabilitation . Methods COPD patients participating in 8 weeks of pulmonary rehabilitation were studied in a r and omized , double-blind , placebo-controlled trial of tiotropium 18 μg daily ( tiotropium = 47 , placebo = 44 ) . Study drug was administered for 5 weeks prior to , 8 weeks during , and 12 weeks following pulmonary rehabilitation . Patients completed a question naire documenting participation in pre-defined activities outside of pulmonary rehabilitation during the 2 weeks prior to each visit . Patients who su bmi tted an activity question naire at week 4 and on at least one subsequent visit were included in the analysis . For each patient , the number of sessions was multiplied with the duration of each activity and then summed to give overall activity duration . Results Patients ( n = 46 ) had mean age of 67 years , mean baseline FEV1 of 0.84 L ( 33 % predicted ) . Mean ( SE ) increase in duration of activities ( minutes during 2 weeks prior to each visit ) from week 4 ( prior to PR ) to week 13 ( end of PR ) was 145 ( 84 ) minutes with tiotropium and 66 ( 96 ) minutes with placebo . The increase from week 4 to week 25 ( end of follow-up ) was 262 ( 96 ) and 60 ( 93 ) minutes for the respective groups . Increases in activity duration from week 4 to weeks 17 , 21 , and 25 were statistically significant with tiotropium . No statistical differences over time were observed within the placebo-treated group and differences between groups were not significant . Conclusions Tiotropium appears to amplify the effectiveness of pulmonary rehabilitation as seen by increases in patient self-reported participation in physical activities ",
"AIM Aim of the study was to investigate whether or not oral supplementation of essential amino acids ( EAAs ) may improve body composition , muscle metabolism , physical activity , cognitive function , and health status in a population of subjects with severe chronic obstructive pulmonary disease ( COPD ) and sarcopenia . METHODS Thirty-two patients ( 25 males ) ( FEV1/FVC to receive 4 gr/bid EAAs or placebo according to a double-blind design . When entered the study ( T0 ) , after four ( T4 ) , and after twelve ( T12 ) weeks of treatments , body weight , fat free-mass ( FFM ) , plasma lactate concentration ( micromol/l ) , arterial PaCO2 and PaO2 , physical activity ( n degree steps/day ) , cognitive function ( Mini Mental State Examination ; MMSE ) , health status ( St. George 's Respiratory Question naire ; SGRQ ) were measured . RESULTS EAAs supplemented , but not patients assuming placebo , progressively improved all baseline variables overtime . In particular , at T12 of EAAs supplementation , body weight ( BW ) increased by 6 Kg ( p = 0.002 ) , FFM by 3.6 Kg ( p = 0.05 ) , plasma lactate decreased from 1.6 micromol/l to 1.3 micromol/l ( p = 0.023 ) , PaO2 increased by 4.6 mmHg ( p = 0.01 ) , physical activity increased by 80 % ( p = 0.01 ) . Moreover , the score for cognitive dysfunction improved from 19.1 scores to 20.8 ( p = 0.011 ) , while the SRGQ score also improved from 723 to 69.6 even though this trend did not reach the statistical significance . CONCLUSIONS . A three-month EAAs supplementation may have comprehensive effects on nutritional status ; muscle energy metabolism ; blood oxygen tension , physical autonomy ; cognitive function , and perception of health status in patients with severe COPD and secondary sarcopenia",
"BACKGROUND Low levels of physical activity ( PA ) are associated with poor outcomes in people with COPD . Interventions to increase PA could improve outcomes . METHODS We tested the efficacy of a novel Internet-mediated , pedometer-based exercise intervention . Veterans with COPD ( N = 239 ) were r and omized in a 2:1 ratio to the ( 1 ) intervention group ( Omron HJ-720 ITC pedometer and Internet-mediated program ) or ( 2 ) wait-list control group ( pedometer ) . The primary outcome was health-related quality of life ( HRQL ) , assessed by the St. George 's Respiratory Question naire ( SGRQ ) , at 4 months . We examined the SGRQ total score ( SGRQ-TS ) and three domain scores : Symptoms , Activities , and Impact . The secondary outcome was daily step counts . Linear regression models assessed the effect of intervention on outcomes . RESULTS Participants had a mean age of 67 ± 9 years , and 94 % were men . There was no significant between-group difference in mean 4-month SGRQ-TS ( 2.3 units , P = .14 ) . Nevertheless , a significantly greater proportion of intervention participants than control subjects had at least a 4-unit improvement in SGRQ-TS , the minimum clinical ly important difference ( 53 % vs 39 % , respectively , P = .05 ) . For domain scores , the intervention group had a lower ( reflecting better HRQL ) mean than the control group by 4.6 units for Symptoms ( P = .046 ) and by 3.3 units for Impact ( P = .049 ) . There was no significant difference in Activities score between the two groups . Compared with the control subjects , intervention participants walked 779 more steps per day at 4 months ( P = .005 ) . CONCLUSIONS An Internet-mediated , pedometer-based walking program can improve domains of HRQL and daily step counts at 4 months in people with COPD . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT01102777 ; URL : www . clinical trials.gov",
"Patients with chronic obstructive pulmonary disease ( COPD ) often suffer from weight loss . The aim of the present study was to gain insight into the energy balance of depleted ambulatory COPD patients , in relation to their habitual level of physical activity and consumption of oral nutritional supplements . Clinical ly stable and weight-stable patients ( n 20 ; BMI 19.8+/- SD 2.0 kg/m2 ) were studied 1 and 3 months after rehabilitation or recovery in the clinic and were at r and om assigned to a control or intervention group with regard to nutritional supplementation . Energy intake was measured with a 7 d food record . Energy expenditure was estimated from a simultaneous 7 d assessment of physical activity with a tri-axial accelerometer for movement registration in combination with measured BMR . Body mass was measured at several time points . The body mass remained stable in both groups after 1 or 3 months and mean energy balances were comparable for both groups . The mean body-mass change between month 1 and 3 was negatively related to the mean physical activity level ( r -0.49 ; P=0.03 ) . Weight change over the 3 months was negatively associated with the physical activity level . These results suggest that knowledge about the individual physical activity level is necessary for the estimation of the energy need of the COPD patient",
"Objective To investigate the long term effectiveness of integrated disease management delivered in primary care on quality of life in patients with chronic obstructive pulmonary disease ( COPD ) compared with usual care . Design 24 month , multicentre , pragmatic cluster r and omised controlled trial Setting 40 general practice s in the western part of the Netherl and s Participants Patients with COPD according to GOLD ( Global Initiative for COPD ) criteria . Exclusion criteria were terminal illness , cognitive impairment , alcohol or drug misuse , and inability to fill in Dutch question naires . Practice s were included if they were willing to create a multidisciplinary COPD team . Intervention General practitioners , practice nurses , and specialised physiotherapists in the intervention group received a two day training course on incorporating integrated disease management in practice , including early recognition of exacerbations and self management , smoking cessation , physiotherapeutic reactivation , optimal diagnosis , and drug adherence . Additionally , the course served as a network platform and collaborating healthcare providers design ed an individual practice plan to integrate integrated disease management into daily practice . The control group continued usual care ( based on international guidelines ) . Main outcome measures The primary outcome was difference in health status at 12 months , measured by the Clinical COPD Question naire ( CCQ ) ; quality of life , Medical Research Council dyspnoea , exacerbation related outcomes , self management , physical activity , and level of integrated care ( PACIC ) were also assessed as secondary outcomes . Results Of a total of 1086 patients from 40 clusters , 20 practice s ( 554 patients ) were r and omly assigned to the intervention group and 20 clusters ( 532 patients ) to the usual care group . No difference was seen between groups in the CCQ at 12 months ( mean difference –0.01 , 95 % confidence interval –0.10 to 0.08 ; P=0.8 ) . After 12 months , no differences were seen in secondary outcomes between groups , except for the PACIC domain “ follow-up/coordination ” ( indicating improved integration of care ) and proportion of physically active patients . Exacerbation rates as well as number of days in hospital did not differ between groups . After 24 months , no differences were seen in outcomes , except for the PACIC follow-up/coordination domain . Conclusion In this pragmatic study , an integrated disease management approach delivered in primary care showed no additional benefit compared with usual care , except improved level of integrated care and a self reported higher degree of daily activities . The contradictory findings to earlier positive studies could be explained by differences between interventions ( provider versus patient targeted ) , selective reporting of positive trials , or little room for improvement in the already well developed Dutch healthcare system . Trial registration Netherl and s Trial Register NTR2268",
"OBJECTIVE To evaluate the effects of whole-body resistance training on exercise capacity , health-related quality of life ( HRQOL ) , and muscle strength in patients hospitalized for exacerbation of chronic obstructive pulmonary disease . DESIGN R and omized controlled trial . SETTING University hospital . PARTICIPANTS Patients ( N=46 ) were r and omized to either a control group ( CG ) or training group ( TG ) , and 29 patients completed the study . INTERVENTION Training consisted of weight-lifting exercises for 6 muscle groups in the upper and lower limbs ( 2 sets of 8 repetitions each ) , and the initial load was set at 80 % of the 1-repetition maximum load . MAIN OUTCOME MEASURES Patients were evaluated on the second day of hospitalization , at hospital discharge , and 30 days postdischarge . Patients were evaluated on the basis of the 6-minute walking distance ( 6MWD ) , HRQOL , muscle strength , systemic inflammatory markers , and level of physical activity in daily life ( PADL ) . RESULTS The CG showed a reduction in the strength of lower-limb muscles ( P 6MWD ( P>.05 ) . In contrast , patients from the TG improved strength in the lower-limb muscles and 6MWD during and 30 days after hospitalization ( P impact domain in HRQOL after hospitalization . No improvement in PADL was observed in the TG . Finally , a reduction in the blood levels of inflammatory markers was observed only in the TG after hospitalization . CONCLUSIONS Our results suggest that resistance training during hospitalization improves the 6MWD , HRQOL , and lower-limb muscle strength , without altering the levels of systemic inflammation . However , future research should explore this intervention in larger r and omized trials",
"BACKGROUND The aim of this study was to examine patterns of domestic activity and ambulatory oxygen usage in patients with COPD in their domestic environment . METHODS Twenty patients ( 14 men ; mean age , 73.4 years [ SD , 6.8 years ] ; FEV1 , 1.0 L [ SD , 0.5 L ] ) with stable COPD were recruited after completing a 7-week pulmonary rehabilitation program . Patients were either hypoxic at rest or had desaturation during exercise . Patients were r and omized to an 8-week , double-blind , placebo-controlled trial of cylinder oxygen vs cylinder air . Total domestic physical activity and health-related quality of life ( HRQL ) measures were recorded before and after intervention . RESULTS There were no significant changes in domestic activity or HRQL measures after the intervention for either cylinder oxygen or cylinder air , except for a worsening of the Chronic Respiratory Question naire dyspnea domain on cylinder air . There was a significant increase in mean duration ( minutes per day ) of cylinder use ( p oxygen group . However , when comparing the two groups together , there were no between-group differences in cylinder use or time spent outside the home . Over the 8 weeks the majority of patients were using the cylinders in the home rather than outside , however , the number of times patients reported using the cylinders outside the home increased over the 8 weeks for the oxygen group . CONCLUSION In the short term , ambulatory oxygen therapy is not associated with improvements in physical activity , HRQL , or time spent away from home . However , the use of cylinder oxygen increased over the 8 weeks compared to cylinder air . Patients need time to learn how to use oxygen , and ambulatory oxygen appears to enhance activities rather than increase them",
"BACKGROUND We were interested in the effects of a physical activity ( PA ) counselling programme in three groups of COPD patients from general practice ( primary care ) , outpatient clinic ( secondary care ) and pulmonary rehabilitation ( PR ) . METHODS In this r and omized controlled trial 155 COPD patients , 102 males , median ( IQR ) age 62 ( 54 - 69 ) y , FEV1predicted 60 ( 40 - 75 ) % were assigned to a 12-weeks ' physical activity counselling programme or usual care . Physical activity ( pedometer ( Yamax SW200 ) and metabolic equivalents ) , exercise capacity ( 6-min walking distance ) and quality of life ( Chronic Respiratory Question naire and Clinical COPD Question naire ) were assessed at baseline , after three and 15 months . RESULTS A significant difference between the counselling and usual care group in daily steps ( 803 steps , p = 0.001 ) and daily physical activity ( 2214 steps + equivalents , p = 0.001 ) ) from 0 to 3 months was found in the total group , as well as in the outpatient ( 1816 steps , 2616 steps + equivalents , both p = 0.007 ) and PR ( 758 steps , 2151 steps + equivalents , both p = 0.03 ) subgroups . From 0 to 15 months no differences were found in physical activity . However , when patients with baseline physical activity>10,000 steps per day ( n = 8) , who are already sufficiently active , were excluded , a significant long-term effect of the counselling programme on daily physical activity existed in the total group ( p = 0.02 ) . Differences in exercise capacity and quality of life were found only from 0 to 3 months , in the outpatient subgroup . CONCLUSION Our PA counselling programme effectively enhances PA level in COPD patients after three months . Sedentary patients at baseline still benefit after 15 months . Clinical Trials.gov : registration number NCT00614796",
"OBJECTIVE To investigate whether a 12-week pedometer-based exercise counseling strategy is feasible and effectively enhances daily physical activity in outclinic Chronic Obstructive Pulmonary Disease ( COPD ) patients who do not participate in a rehabilitation program in a controlled way . METHODS 35 outclinic COPD patients ( 21 males , mean age 62 years , GOLD I-III , mean FEV(1)% predicted 64.7 ) were r and omized for a 12-week individual pedometer-based exercise counseling program promoting daily physical activities or usual care . Daily physical activity ( DigiWalker SW-200 ) , physical fitness , health-related quality of life , self-efficacy , fatigue , depression and motivation to be physically active were assessed before and after the intervention . RESULTS After the intervention , COPD patients in the exercise counseling group showed a significant increase in their mean number of steps/day ( from 7087 to 7872 ) , whereas the usual care group showed a decrease ( from 7539 to 6172 ) . Significant differences favoring the exercise counseling group were demonstrated in arm strength , leg strength , health-related quality of life and intrinsic motivation to be physically active . CONCLUSION Our study shows that a 12-week pedometer-based exercise counseling strategy is feasible and effectively enhances daily physical activity , physical fitness , health-related quality of life and intrinsic motivation in outclinic COPD patients who do not participate in a rehabilitation program . PRACTICE IMPLICATION S The feasibility of our exercise counseling strategy is good and patients were motivated to participate",
"The aim of this study was to investigate the impact of a physical activity (PA)-focused behavioural intervention during and after pulmonary rehabilitation ( PR ) on PA levels ( primary aim ) , health-related outcomes and self-efficacy ( secondary aims ) of patients with COPD . Thirty-two patients were r and omly assigned to an experimental group ( EG ) or control group ( CG ) . The EG received a PA-focused behavioural intervention during PR ( 3 months ) and follow-up support ( 3 months ) . The CG received PR ( 3 months ) . Daily PA was collected : number of steps ; time spent in moderate-to-vigorous PA ( MVPA ) , total PA and sedentary activities ( SA ) . Secondary outcomes comprised exercise capacity , muscle strength , health-related quality of life ( HRQOL ) and self-efficacy . Measures were collected at baseline , 3 and 6 months . Compared with the CG , the EG improved the number of steps ( p = 0.006 ) and time spent in MVPA ( p = 0.007 ) , total PA ( p = 0.014 ) and SA ( p = 0.018 ) at 3 months . Differences were maintained after follow-up support ( 0.025 ≤ p ≤ 0.040 ) , except for SA ( p = 0.781 ) . Exercise capacity , muscle strength and HRQOL were increased at 3 and 6 months ( p ≤ 0.002 ) with no between-group differences ( 0.148 ≤ p ≤ 0.987 ) . No changes were observed in self-efficacy ( p = 0.899 ) . A PA-focused behavioural intervention during and after PR may improve patients ' PA levels . Further research is warranted to assess the sustainability of the findings",
"PURPOSE : The success of long-term exercise training ( ExT ) programs resides in the integration between exercise prescription and patient compliance with home training . One of the crucial issues for the patients is the underst and ing of appropriate exercise intensity . We compared 2 methods of home ExT , based on walking . METHODS : Forty-seven patients with chronic obstructive pulmonary disease were recruited and underwent respiratory function , exercise capacity evaluation with a 6-minute walk test , and treadmill tests . Physical activity was monitored by a multisensor Armb and ( SenseWear , Body Media , Pittsburgh , PA ) . Patients were r and omly assigned to 2 different home training methods and assessed again after 6 and 12 months ; group A1 : speed walking paced by a metronome , and group A2 : walking a known distance in a fixed time . RESULTS : Thirty-six patients completed the study . All subjects showed a significant improvement in the 6-minute walk test after 1 year but the improvement was higher in A1 than in A2 ( P Physical activity levels were significantly higher at T12 versus baseline only in group A1 ( P metronome to maintain the rate of walking during home ExT seems to be beneficial , allowing patients to achieve and sustain the optimal exercise intensity , and result ing in greater improvement compared to simply using a fixed time interval exercise",
"CONTEXT People with chronic obstructive pulmonary disease experience dyspnea with activities despite optimal medical management . OBJECTIVES The purpose of this study was to test the efficacy of two 12-month dyspnea self-management programs ( DSMPs ) , Internet-based ( eDSMP ) and face-to-face ( fDSMP ) , compared with a general health education ( GHE ) control on the primary outcome of dyspnea with activities . METHODS Participants with chronic obstructive pulmonary disease were r and omized to eDSMP ( n=43 ) , fDSMP ( n=41 ) , or GHE ( n=41 ) . The content of the DSMPs were similar and focused on education , skills training , and coaching on dyspnea self-management strategies , including exercise , and only differed in the delivery mode . Dyspnea with activities was measured with the Chronic Respiratory Question naire at three , six , and 12 months . Secondary outcomes included exercise behavior and performance , health-related quality of life , self-efficacy for dyspnea management , and perception of support for exercise . The study was registered at Clinical trials.gov ( NCT00461162 ) . RESULTS There were no differences in dyspnea with activities across groups over 12 months ( P=0.48 ) . With the exception of arm endurance ( P=0.04 ) , exercise behavior , performance , and health-related quality of life did not differ across groups ( P>0.05 ) . Self-efficacy for managing dyspnea improved for the DSMPs compared with GHE ( P=0.06 ) . DSMP participants perceived high levels of support for initiating and maintaining an exercise program . CONCLUSION The DSMPs did not significantly reduce dyspnea with activities compared with attention control . However , the high participant satisfaction with the DSMPs combined with positive changes in other outcomes , including self-efficacy for managing dyspnea and exercise behavior , highlight the need for additional testing of individually tailored technology-enabled interventions to optimize patient engagement and improve clinical ly relevant outcomes",
"There is an urgent need for consensus on what defines a chronic obstructive pulmonary disease ( COPD ) self-management intervention . We aim ed to obtain consensus regarding the conceptual definition of a COPD self-management intervention by engaging an international panel of COPD self-management experts using Delphi technique features and an additional group meeting . In each consensus round the experts were asked to provide feedback on the proposed definition and to score their level of agreement ( 1=totally disagree ; 5=totally agree ) . The information provided was used to modify the definition for the next consensus round . Thematic analysis was used for free text responses and descriptive statistics were used for agreement scores . In total , 28 experts participated . The consensus round response rate varied r and omly over the five rounds ( ranging from 48 % ( n=13 ) to 85 % ( n=23 ) ) , and mean definition agreement scores increased from 3.8 ( round 1 ) to 4.8 ( round 5 ) with an increasing percentage of experts allocating the highest score of 5 ( round 1 : 14 % ( n=3 ) ; round 5 : 83 % ( n=19 ) ) . In this study we reached consensus regarding a conceptual definition of what should be a COPD self-management intervention , clarifying the requisites for such an intervention . Operationalisation of this conceptual definition in the near future will be an essential next step . Consensus of a conceptual definition of what should be a COPD self-management intervention with its requisites",
"AIMS To evaluate the effectiveness of a 6-month , partnership-based self-management programme for patients with mild and moderate chronic obstructive pulmonary disease . BACKGROUND Self-management is a widely valued concept used to address contemporary issues of chronic health problems . Findings of self-management programmes for people with chronic obstructive pulmonary disease are inconclusive . DESIGN Pragmatic r and omized control trial . METHODS Patients , 45 - 65 years old , with mild and moderate chronic obstructive pulmonary disease were invited with a family member . Experimental group ( n = 48 ) participated in a 6-month , partnership-based self-management programme consisting of : ( a ) three to four conversations between nurse and patient-family member ; ( b ) 6 months of smoking cessation ; and ( c ) interdisciplinary team-patient-family member group meeting . Control group ( n = 52 ) received usual care . Data were collected at months zero , six and 12 . The trial lasted from June 2009-March 2013 . RESULTS Patients with mild and moderate chronic obstructive pulmonary disease who participated in the partnership-based self-management programme perceived less intrusiveness of the disease and its treatment than patients in the control group . Patients in the experimental group did not have better health-related quality of life , less anxiety or depression , increased physical activity , fewer exacerbations or better smoking status than patients in the control group . Patients in both groups found participation in the research useful and important . CONCLUSION The partnership-based self-management programme had benefits concerning perception of the intrusiveness of chronic obstructive pulmonary disease and its treatment on lifestyles , activities and interests for young patients with the disease in its early stages . High satisfaction in control group , low family attendance and the relatively short treatment period may explain the less than expected benefits of the programme",
"AIM To determine the feasibility of recruiting patients with early chronic obstructive pulmonary disease ( COPD ) to the Health Enhancing Activity in Lung THerapy ( HEALTH ) exercise and education programme . METHODS Patients with early COPD were identified from general practice s. Those meeting the study inclusion criteria were administered tiotropium throughout the study period . Participants were r and omised to either an eight-week health enhancing and physical activity ( HEPA ) programme , or to a control group ( usual care ) . Behavioural , physiological and psychosocial outcome measures were reported pre and post-intervention . RESULTS Out of 27 practice s approached , 16 ( 59.3 % ) agreed to participate . Of 215 potentially eligible patients contacted , 60 ( 27.9 % ) replied . Twenty ( 33.3 % ) were r and omised to either HEPA intervention ( n=10 ) or usual care ( n=10 ) . Fourteen patients attended a postintervention assessment . CONCLUSION This study provides valuable information on the feasibility of conducting such a trial involving a physical activity intervention"
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OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) are frequently used as a first antidepressant for major depressive disorder but have response rates of 50 % to 60 % in daily practice . For patients with insufficient response to SSRIs , switching is often applied . This article aims to systematic ally review the evidence for switching pharmacotherapy after a first SSRI . DATA SOURCES A systematic literature search ( up date d until Feb. 10 , 2005 ) in MEDLINE , EMBASE , CINAHL , and PsychINFO ( all indexed years ) identified r and omized , controlled trials ( RCTs ) and open studies investigating switching strategies . In the absence of specific keywords for switching , we performed " sensitive " search es using free text words with wildcards ( $ ) : " switch$ " or ( " alternat$ " adj5 " treat$ " ) or ( " alternat$ " adj5 " therap$ " ) in combination with the Cochrane Collaboration search filter for RCTs , the Cochrane Collaboration Depression Anxiety and Neurosis Group search filter for major depressive disorder , and MeSH terms for antidepressants ( in combination with additional text words for all antidepressive agents ) . Additionally , we included 4 recent Sequenced Treatment Alternatives to Relieve Depression publications . We limited search es to adults and humans but did not apply language restrictions . STUDY SELECTION Relevant articles were retrieved and critically appraised . The methodology of the studies , the results on efficacy and dropouts due to side effects , and remarks were summarized in an evidence table . Three studies comparing a switch to venlafaxine or SSRIs were pooled . DATA SYNTHESIS Eight RCTs and 23 open studies were identified , study ing population s with different levels of treatment resistance . Definitions of response and remission rates varied between studies . Observed response rates after switching to any of the classes of antidepressants varied between 12 % and 86 % . Remission rates varied between 7 % and 82 % . The number of previous treatments with antidepressants was negatively correlated with treatment outcome . Rates of dropout due to side effects varied considerably across agents ( 5%-39 % ) . Switching to venlafaxine showed a modest and clinical ly equivocal benefit over SSRIs ( number needed to treat = 13 [ 95 % CI = 9.1 to 25.0 ] ) . CONCLUSIONS After a first SSRI , any switch within or between classes of antidepressants appears legitimate ( second SSRI , novel dual-acting antidepressants , selective norepinephrine or nor-adrenergic/dopaminergic agents , or tricyclic anti-depressant or mianserin ) . No unequivocal evidence is available to prove an advantage of a between-class switch . More guidance by r and omized empirical studies is needed . Clinical implication s and method ological considerations for future studies are discussed
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"Objective To compare the efficacy of imipramine and fluvoxamine in in patients from two centers suffering from a depressive disorder according to DSM IV criteria . Methods The study included 141 patients with a depressive disorder according to DSM IV criteria . After a drug-free and placebo run-in period of 1 week , patients were r and omized to imipramine or fluvoxamine ; doses of both drugs were adjusted to a predefined target blood level . Efficacy was evaluated 4 weeks after attaining predefined adequate plasma level . Results The mean age of the study group ( 47 males , 94 females ) was 51.8 ( range 19–65 ) years . Of these 141 patients , 56 had episode duration longer than 1 year , 48 had mood congruent psychotic features , and 138 patients received medication . Seven patients did not complete the medication trial . The total number of patients using concurrent medication was 12/138 ( 8.6 % ) . On the primary outcome criteria patients on imipramine improved significantly better on the change of illness severity score of the CGI ( χ2 exact trend test=4.089 , df=1 , P=0.048 ) . There was no significant difference in 50 % or more reduction on the HRSD , the other primary outcome criterion . On the secondary outcome criteria the mean reduction of the HRSD scores was significantly larger in the imipramine group than in the fluvoxamine group ( mean difference=3.1 , st and ard error (SE)=1.4 , t=2.15 , df=136 , P=0.033 ) . There was no significant difference in the number of patients with an HRSD ≤7 at the final evaluation . Conclusions In depressed in patients imipramine is more efficacious than fluvoxamine . Both drugs were well tolerated by all patients",
"Research on treatment-resistant depression in the elderly has been limited , and recommendations for clinical man agement have often been extrapolated from studies using nongeriatric patients . This report describes a series of 10 elderly patients with refractory depression who were treated with nortriptyline after failing to respond to an ade quate trial of a serotonin reuptake inhibitor . Seven ( 70 % ) of the patients responded to the addition or substitution of nortriptyline . All seven of the responders have remained on nortriptyline for maintenance therapy , none of whom have experienced recurrence of their depression after an average treatment duration of 1 year . Response to nor triptyline occurred in about 4 weeks in most patients . The mean daily dose of nortriptyline was 54 mg , and the mean plasma level was 97 ng/mL. Minor side effects occurred in three patients . No patients developed significant electrocardiogram changes . Nortriptyline , possibly due to its different mechanism of action , may be effective as either an adjunctive or replacement antidepressant in some cases of geriatric depression that are resistant to sero tonin reuptake inhibitors . ( J Geriatr Psychiatry Neurol 2001 ; 14:28 - 32 )",
"Tricyclic antidepressant ( TCA ) medications are among the most widely used pharmacologic treatments for depression . However , a substantial number of patients fail to respond to these agents . Few st and ardized trials of pharmacologic treatments for TCA nonresponders are available . Bupropion has an apparently different mechanism of action than TCAs and represents a possible treatment for the TCA nonresponder . Based on positive results from pilot studies , a st and ardized study evaluating bupropion in TCA nonresponders was conducted . Forty-one depressed out patients who had failed to respond to adequate documented TCA treatment , defined by specific criteria of dosage , duration , and plasma concentrations , entered a 1-week single-blind placebo phase , followed by an open 8-week bupropion treatment phase utilizing doses of up to the maximum daily dose of 450 mg . Response was measured by change on the Hamilton Depression Rating Scale ( HAM-D ) , Clinical Global Impressions-Severity ( CGI-S ) and Improvement ( CGI-I ) Scales , and the Hamilton Anxiety Rating Scale ( HAM-A ) . Bupropion treatment result ed in an improvement in depression on all outcome measures . Forty-nine percent were considered \" responders , \" in that they achieved > or = 50 % improvement on the 28-item HAM-D. Fifty-four percent were classified as responders based on a CGI-I rating of much or very much improved . Statistically significant improvement in depressive symptoms , measured by mean scores for the HAM-D , CGI-S , and HAM-A , was achieved at the end of the study ( as compared to baseline ) . Twelve patients ( 32 % ) had a HAM-D score of < or = 10 at termination . ( ABSTRACT TRUNCATED AT 250 WORDS",
"BACKGROUND Although clinicians frequently add a second medication to an initial , ineffective antidepressant drug , no r and omized controlled trial has compared the efficacy of this approach . METHODS We r and omly assigned 565 adult out patients who had nonpsychotic major depressive disorder without remission despite a mean of 11.9 weeks of citalopram therapy ( mean final dose , 55 mg per day ) to receive sustained-release bupropion ( at a dose of up to 400 mg per day ) as augmentation and 286 to receive buspirone ( at a dose of up to 60 mg per day ) as augmentation . The primary outcome of remission of symptoms was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression ( HRSD-17 ) at the end of this study ; scores were obtained over the telephone by raters blinded to treatment assignment . The 16-item Quick Inventory of Depressive Symptomatology -- Self-Report ( QIDS-SR-16 ) was used to determine the secondary outcomes of remission ( defined as a score of less than 6 at the end of this study ) and response ( a reduction in baseline scores of 50 percent or more ) . RESULTS The sustained-release bupropion group and the buspirone group had similar rates of HRSD-17 remission ( 29.7 percent and 30.1 percent , respectively ) , QIDS-SR-16 remission ( 39.0 percent and 32.9 percent ) , and QIDS-SR-16 response ( 31.8 percent and 26.9 percent ) . Sustained-release bupropion , however , was associated with a greater reduction ( from baseline to the end of this study ) in QIDS-SR-16 scores than was buspirone ( 25.3 percent vs. 17.1 percent , P QIDS-SR-16 score at the end of this study ( 8.0 vs. 9.1 , P dropout rate due to intolerance ( 12.5 percent vs. 20.6 percent , P bupropion or buspirone appears to be useful in actual clinical setting s. Augmentation with sustained-release bupropion does have certain advantages , including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events . ( Clinical Trials.gov number , NCT00021528 . )",
"About 30 % of depressed patients exhibit depression that is resistant to antidepressant treatment . This resistance may be primary or associated with a concomitant psychiatric or somatic disease . Venlafaxine has shown potent efficacy in certain severe depressions in in- patients and in patients presenting with resistant depression in an open-label study . It was considered of interest to compare , under double-blind , the efficacy of venlafaxine ( 200 to 300 mg/day ) and that of paroxetine ( 30 to 40 mg/day ) ( for 6 weeks ) in 123 patients presenting with major depression resistant to two correctly conducted antidepressant treatments in the course of an episode of depression of duration not exceeding 8 months . The patients were required not to present with organic disease , particularly endocrine disease . After 28 days of treatment , half of the patients receiving venlafaxine and one third of the patients receiving paroxetine showed a 50 % reduction in their total score on the Hamilton scale . In addition , the percentage of patients presenting with remission was significantly higher in the group receiving venlafaxine ( 42 % ) compared to that receiving paroxetine ( 20 % ) . These results require confirmation over the long term and in other forms of resistant depression",
"As psychiatric practice patterns evolve to take advantage of the growing list of treatments with proven efficacy , research studies with broader aims will become increasingly important . R and omized trials may need to accommo date multiple treatment options . In completely r and omized design s , patients are assigned at r and om to one of the options , requiring that patients and clinicians find each of the options acceptable . In \" clinician 's choice \" design s , patients are r and omized to a small number of broad strategies and the choice of specific option within the broad strategy is left up to the clinician . The clinician 's choice design permits some scope to patient and clinician preferences , but sacrifices the ability to make r and omization-based comparisons of specific options . We describe a new approach , which we call the \" equipoise stratified \" design , that merges the advantages and avoids the disadvantages of the other two design s for clinical trials . The three design s are contrasted , using the National Institute of Mental Health Sequenced Treatment Alternatives to Relieve Depression trial as an example",
"BACKGROUND We assessed the tolerability and utility of switching fluoxetine nonresponders to citalopram the day that fluoxetine therapy was stopped . METHOD Fifty-eight out patients with DSM-IV major depressive episode and prospect ively confirmed nonresponse to fluoxetine ( mean final dose = 31 mg/day ) were switched directly to citalopram ( 20 mg/day ) . Of the 58 patients , 44 ( 76 % ) had never been successfully treated with antidepressant medication . During a 12-week open-label treatment period , citalopram could be titrated up to a maximum dose of 60 mg/day . Response was evaluated using the Clinical Global Impressions ( CGI ) scale , the 24-item Hamilton Rating Scale for Depression , and several other measures . RESULTS Eighty-one percent ( N = 47 ) completed the trial , and citalopram ( mean dose = 38.8 mg/day ) was well tolerated . The intent-to-treat CGI response rate was 46 % ( 26/57 ) at week 6 and 63 % ( 36/57 ) at study endpoint ; the completer response rate was 76 % among the 47 patients who completed the 12-week trial . Improvement from baseline on all dependent measures was statistically significant after the first week of citalopram treatment . CONCLUSION Fluoxetine nonresponders can be quickly switched to citalopram , with good tolerability and reasonable chance of therapeutic benefit . Further work is necessary to assess the merits of this treatment strategy relative to other options",
"BACKGROUND Approximately half of patients who are prescribed selective serotonin re-uptake inhibitors ( SSRIs ) either do not respond to treatment or do not experience a sustained response . OBJECTIVE The purpose of this study was to assess the efficacy of venlafaxine immediate-release ( IR ) and extended-release ( XR ) in out patients who either did not respond to SSRI treatment or did not maintain a sustained response . METHODS Out patients who met the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( DSM-IV ) criteria for major depressive disorder who were previously treated with an SSRI ( fluoxetine > or = 20 mg/d ; sertraline > or = 50 mg/d ; paroxetine > or = 20 mg/d ) for > or = 6 weeks , but demonstrated an inadequate or unsustained response , were switched to venlafaxine ( IR or XR formulation , 50 - 400 mg/d , titrated from 37.5 mg/d ) for > or = 6 weeks . Response at 6 to 8 weeks was defined as total score modified 25-item Hamilton Depression ( HAM-D25 ) rating scale or total score > or = 5 on the 21-item Patient Global Improvement ( PGI-21 ) scale . Remission was defined as a HAM-D25 total score PGI-21 score > or = 7 . Tests were administered by an unblinded , board-certified psychiatrist . RESULTS A total of 73 patients ( 54 women , 19 men ; mean age , 38.6 years ) were enrolled and treated with venlafaxine IR ( n = 63 ) or venlafaxine XR ( n = 10 ) ; 33 were SSRI nonresponders and 36 had an unsustained response to SSRI treatment . Four patients receiving venlafaxine IR discontinued due to drug-related adverse events ( agitation , sedation , or nausea ) . Data from these patients were excluded from the analysis . After 6 to 8 weeks of treatment , 94.2 % ( 65/69 ) of patients were considered responders ( HAM-D25 or PGI-21 criteria ) ; 91.3 % ( 63/69 ) of patients responded to treatment as assessed by both measures . Eighty-seven percent ( 60/69 ) and 85.5 % ( 59/69 ) of patients achieved remission based on HAM-D,5 and PGI-21 criteria , respectively . Response/remission rates were comparable among patients treated with SSRIs , regardless of whether patients had failed to respond to treatment with 1 or 2 SSRIs . CONCLUSION Venlafaxine IR/venlafaxine XR may be effective in out patients with major depressive disorder who do not respond or have an unsustained response to SSRIs . However , r and omized , controlled trials are needed before any conclusions can be drawn about the efficacy of this agent in this population",
"In a double-blind study the selective monoamine oxidase-A inhibitor brofaromine was compared with the classical MAOI tranylcypromine in 39 patients with major depression resistant to treatment with tricyclic antidepressants . Concerning efficacy no significant differences were found . Ten out of 22 patients responded to brofaromine and 5 out of 17 patients to tranylcypromine . Adverse effects favoured brofaromine . Although orthostatic hypotension occurred in both groups , severe decrease in blood pressure and dizziness occurred significantly more with tranylcypromine . Both MAOIs caused a decrease in stage 4 and REM sleep and an increase in REM latency . In most patients receiving tranylcypromine REM sleep was completely abolished",
"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",
"BACKGROUND The long elimination half-lives of fluoxetine and norfluoxetine , the active metabolite of fluoxetine , are of potential consequence when alternative antidepressant agents are introduced after the termination of fluoxetine therapy . It is not known whether paroxetine , an antidepressant agent in the same pharmacologic class as fluoxetine , can be substituted for fluoxetine without the need for an intervening washout period . The objective of this trial was to assess the tolerability of an immediate switch from fluoxetine to paroxetine therapy . METHOD Patients who were treated for moderate to moderately severe major depressive disorder ( DSM-III-R 296.2 or 296.3 ) with a stable dose of fluoxetine for a minimum of 6 weeks ' duration were r and omized in a double-blind fashion to one of two treatment groups . One group ( N = 123 ) was started on 20 mg of paroxetine daily the morning after their last dose of fluoxetine , and the other group ( N = 119 ) was started on 20 mg of paroxetine daily following a 2-week placebo-washout period . Patient visits were scheduled at weekly intervals for a total of 4 weeks . Adverse experience monitoring was conducted at each visit . RESULTS There was no difference in the proportion of patients who discontinued prematurely from the trial due to an adverse experience . Eight patients in the immediate-switch group and 6 patients in the placebo-washout group withdrew from the trial in response to an adverse experience ( p = .63 , chi-square ) . The overall profile of adverse experiences was similar in the two treatment groups over the 4-week period . The incidence of adverse experiences in the first 2 weeks following the initiation of paroxetine was generally lower in the group with the intervening 2-week placebo-washout period . CONCLUSION The immediate switch from fluoxetine to paroxetine was as well tolerated as the switch to paroxetine after a 2-week placebo-washout period",
"BACKGROUND Patients with chronic forms of major depression are difficult to treat , and the relative efficacy of medications and psychotherapy is uncertain . METHODS We r and omly assigned 681 adults with a chronic nonpsychotic major depressive disorder to 12 weeks of outpatient treatment with nefazodone ( maximal dose , 600 mg per day ) , the cognitive behavioral- analysis system of psychotherapy ( 16 to 20 sessions ) , or both . At base line , all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression ( indicating clinical ly significant depression ) . Remission was defined as a score of 8 or less at weeks 10 and 12 . For patients who did not have remission , a satisfactory response was defined as a reduction in the score by at least 50 percent from base line and a score of 15 or less . Raters were unaware of the patients ' treatment assignments . RESULTS Of the 681 patients , 662 attended at least one treatment session and were included in the analysis of response . The overall rate of response ( both remission and satisfactory response ) was 48 percent in both the nefazodone group and in the psychotherapy group , as compared with 73 percent in the combined-treatment group . ( P 519 subjects who completed the study , the rates of response were 55 percent in the nefazodone group and 52 percent in the psychotherapy group , as compared with 85 percent in the combined-treatment group ( P rates of withdrawal were similar in the three groups . Adverse events in the nefazodone group were consistent with the known side effects of the drug ( e.g. , headache , somnolence , dry mouth , nausea , and dizziness ) . CONCLUSIONS Although about half of patients with chronic forms of major depression have a response to short-term treatment with either nefazodone or a cognitive behavioral- analysis system of psychotherapy , the combination of the two is significantly more efficacious than either treatment alone",
"Open study Twenty-eight adult patients ( seven males and 21 females ) comparable in terms of age and weight , who had a Hamilton Depression Rating Scale ( HAMD ) score of 18 or more while receiving alternative antidepressants ( mainly amitriptyline : 15 patients ) entered the six-week study without a washout period . All patients received 30 mg paroxetine once daily in the morning , and HAMD scores were measured at the end of weeks 1 , 2 , 4 , and 6 of treatment . Tolerability was also assessed and blood and urine sample s monitored",
"Antidepressant effects of mirtazapine and imipramine were compared in a r and omized , double blind , fixed blood-level study with in- patients in a single centre . Patients with a DSM-III-R diagnosis of major depression and a Hamilton ( 17-item ) score of ≥18 were selected . After a drug-free and a placebowashout period of 7 days in total , 107 patients still fulfilling the HRSD criterion of ≥18 , started on active treatment . The dose was adjusted to a predefined fixed blood level to avoid suboptimal dosing of imipramine . Concomitant psychotropic medication was administered only in a few cases because of intolerable anxiety or intolerable psychotic symptoms . Eight patients dropped out and two were excluded from analyses because of non-compliance ; 97 completed the study . According to the main response criterion ( 50 % or more reduction on the HRSD score ) 11/51 ( 21.6 % ) patients responded on mirtazapine and 23/46 ( 50 % ) on imipramine after 4 weeks ' treatment on the predefined blood level . Such a dramatic difference in efficacy between antidepressants has not often been reported before . The selection of ( severely ill ) in- patients , including those with suicidal or psychotic features , may have significance in this respect . Optimization of treatment with the reference drug imipramine through blood level control , exclusion of non-compliance for both drugs , exclusion of most concomitant medication and a low drop-out rate may also have contributed . It is concluded that imipramine is superior to mirtazapine in the patient population studied",
"Objective : To assess , in depressed patients , the clinical benefit of mianserin augmentation of fluoxetine or the the benefit of switching treatment from fluoxetine to mianserin ",
"The 16-item Quick Inventory of Depressive Symptomatology ( QIDS ) , a new measure of depressive symptom severity derived from the 30-item Inventory of Depressive Symptomatology ( IDS ) , is available in both self-report ( QIDS-SR(16 ) ) and clinician-rated ( QIDS-C(16 ) ) formats . This report evaluates and compares the psychometric properties of the QIDS-SR(16 ) in relation to the IDS-SR(30 ) and the 24-item Hamilton Rating Scale for Depression ( HAM-D(24 ) ) in 596 adult out patients treated for chronic nonpsychotic , major depressive disorder . Internal consistency was high for the QIDS-SR(16 ) ( Cronbach 's alpha = .86 ) , the IDS-SR(30 ) ( Cronbach 's alpha = .92 ) , and the HAM-D(24 ) ( Cronbach 's alpha = .88 ) . QIDS-SR(16 ) total scores were highly correlated with IDS-SR(30 ) ( .96 ) and HAM-D(24 ) ( .86 ) total scores . Item-total correlations revealed that several similar items were highly correlated with both QIDS-SR(16 ) and IDS-SR(30 ) total scores . Roughly 1.3 times the QIDS-SR(16 ) total score is predictive of the HAM-D(17 ) ( 17-item version of the HAM-D ) total score . The QIDS-SR(16 ) was as sensitive to symptom change as the IDS-SR(30 ) and HAM-D(24 ) , indicating high concurrent validity for all three scales . The QIDS-SR(16 ) has highly acceptable psychometric properties , which supports the usefulness of this brief rating of depressive symptom severity in both clinical and research setting",
"BACKGROUND We evaluated the efficacy of a second serotonin selective reuptake inhibitor ( SSRI ) in patients who had failed to respond to the first SSRI used . METHOD Fifty-five patients with major depression who had failed one of the SSRIs for their current depressive episode were included . After failing a trial of one SSRI , they received a second SSRI in an open clinical trial . RESULTS On the basis of the Clinical Global Impression-Improvement scale , 28 of 55 patients had a marked or complete antidepressant response . CONCLUSION These data provide preliminary clinical evidence that substituting a second SRI may be a useful clinical alternative in depressed patients who fail to respond to an adequate trial of an SSRI",
"The course of illness of 431 subjects with major depression participating in the National Institute of Mental Health Collaborative Depression Study was prospect ively observed for 5 years . Twelve percent of the subjects still had not recovered by 5 years . There were decreasing rates of recovery over time . For example , 50 % of the subjects recovered within the first 6 months , and then the rate of recovery declined markedly . Instantaneous probabilities of recovery reflect that the longer a patient was ill , the lower his or her chances were of recovering . For patients still depressed , the likelihood of recovery within the next month declined from 15 % during the first 3 months of follow-up to 1 % to 2 % per month during years 3 , 4 , and 5 of this follow-up . The severity of current psychopathology predicted the probability of subsequent recovery . Subjects with moderately severe depressive symptoms , minor depression , or dysthymia had an 18-fold greater likelihood of beginning recovery within the next week than did subjects who were at full criteria for major depressive disorder . Many subjects who did not recover continued in an episode that looked more like dysthymia than major depressive disorder",
"BACKGROUND After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor ( SSRI ) , it is not known whether switching to one antidepressant is more effective than switching to another . METHODS We r and omly assigned 727 adult out patients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSRI citalopram to receive one of the following drugs for up to 14 weeks : sustained-release bupropion ( 239 patients ) at a maximal daily dose of 400 mg , sertraline ( 238 patients ) at a maximal daily dose of 200 mg , or extended-release venlafaxine ( 250 patients ) at a maximal daily dose of 375 mg . The study was conducted in 18 primary and 23 psychiatric care setting s. The primary outcome was symptom remission , defined by a total score of 7 or less on the 17-item Hamilton Rating Scale for Depression ( HRSD-17 ) at the end of the study . Scores on the Quick Inventory of Depressive Symptomatology - Self Report ( QIDS-SR-16 ) , obtained at treatment visits , determined secondary outcomes , including remission ( a score of 5 or less at exit ) and response ( a reduction of 50 percent or more on baseline scores ) . RESULTS Remission rates as assessed by the HRSD-17 and the QIDS-SR-16 , respectively , were 21.3 percent and 25.5 percent for sustained-release bupropion , 17.6 percent and 26.6 percent for sertraline , and 24.8 percent and 25.0 percent for extended-release venlafaxine . QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion , 26.7 percent for sertraline , and 28.2 percent for extended-release venlafaxine . These treatments did not differ significantly with respect to outcomes , tolerability , or adverse events . CONCLUSIONS After unsuccessful treatment with an SSRI , approximately one in four patients had a remission of symptoms after switching to another antidepressant . Any one of the medications in the study provided a reasonable second-step choice for patients with depression . ( Clinical Trials.gov number , NCT00021528 . )",
"BACKGROUND Although various strategies have been proposed to treat antidepressant nonresponders , little controlled research has been published that examines prospect ively the use of switching to an alternate antidepressant . METHODS This was a multisite study in which out patients with chronic major depression ( with or without concurrent dysthymia ) , who failed to respond to 12 weeks of double-blind treatment with either sertraline hydrochloride ( n = 117 ) or imipramine hydrochloride ( n = 51 ) , were crossed over or switched to 12 additional weeks of double-blind treatment with the alternate medication . Outcome measures included the 24-item Hamilton Rating Scale for Depression and the Clinical Global Impressions -- Severity and Improvement scales . RESULTS The switch from sertraline to imipramine ( mean dosage , 221 mg/d ) and from imipramine to sertraline ( mean dosage , 163 mg/d ) result ed in clinical ly and statistically significant improvements . The switch to sertraline treatment was associated with fewer adverse effect complaints and significantly less attrition owing to adverse effects . Although sertraline treatment also result ed in significantly higher response rates in the intent-to-treat sample s ( 60 % in the sertraline group and 44 % in the imipramine group ) , neither the intent-to-treat remission rates nor the response and remission rates among study completers differed significantly . Moreover , after considering the effect of attrition , there were no significant treatment effects on the more comprehensive generalized estimating equation analyses of the continuous dependent measures . CONCLUSIONS More than 50 % of chronically depressed antidepressant nonresponders benefited from a switch from imipramine to sertraline , or vice versa , despite a high degree of chronicity . As in the initial trial , sertraline was generally better tolerated than imipramine . Switching to a st and ard antidepressant of a different class is a useful treatment strategy for antidepressant nonresponders and could be considered a st and ard of comparison for future studies of novel alternate strategies",
"BACKGROUND Recent reports describe discontinuation-emergent adverse events upon cessation of selective serotonin reuptake inhibitors including dizziness , insomnia , nervousness , nausea , and agitation . We hypothesized that interruption of fluoxetine treatment would be associated with fewer discontinuation-emergent adverse events than interruption of sertraline or paroxetine treatment , based on fluoxetine 's longer half-life . METHODS In this 4-week study , 242 patients with remitted depression receiving maintenance therapy with open-label fluoxetine , sertraline , or paroxetine for 4 - 24 months had their maintenance therapy interrupted with double-blind placebo substitution for 5 - 8 days . The Symptom Question naire ( SQ ) , the Discontinuation-Emergent Signs and Symptoms checklist , the 28-item Hamilton Depression Rating Scale , and the Montgomery-Asberg Depression Rating Scale were used to assess somatic distress and stability of antidepressant response . RESULTS Two hundred twenty patients ( 91 % ) completed the study . Following interruption of therapy , fluoxetine-treated patients experienced fewer discontinuation-emergent events than either sertraline-treated or paroxetine-treated patients ( p mean SQ somatic symptom scale score in fluoxetine-treated patients was significantly lower than that in sertraline-treated and paroxetine-treated patients ( p Fluoxetine-treated patients also experienced less reemergence of depressive symptoms than sertraline-treated or paroxetine-treated patients ( p somatic and psychological symptoms in patients treated with paroxetine and to a lesser degree sertraline , with few symptoms seen with fluoxetine",
"The number of available antidepressant medications has increased dramatically in the last 10 years . Furthermore , no single medication is a panacea for all depressed patients -a fact underscored by r and omized , controlled trial evidence showing that when one medication fails , an alternative may succeed . Thus , a key issue in the treatment of depression is how to optimally orchestrate available medication options to maximally benefit the greatest number of patients most rapidly . One approach is the use of consensus guidelines or medication algorithms . This paper discusses the rationale for and critical issues in the development of medication algorithms , and the timely use of symptom measures to ensure proper implementation . Once developed , guidelines must be appropriately implemented by clinicians , adhered to by patients , and supported by administrators . These three stakeholder groups often need education , incentives , and ongoing support to implement such guidelines . Whether guidelines actually improve outcome is largely uninvestigated , although a recent study of depressed patients in primary care found that using guidelines did improve outcome but at an increased treatment cost . The clinical and economic impact of guideline -driven treatment for the severe and persistently depressed deserves study",
"The aim of this study was to replicate the findings of a 1994 study , in which a 30 % response rate to venlafaxine was found in patients with treatment-refractory depression , as well as to examine for any predictors of such an outcome . The study was an 8-week , open-label , prospect i ve investigation of venlafaxine in doses up to 300 mg in 312 patients fulfilling criteria for either \" absolute \" or \" relative \" treatment resistance . By week 8 , 52.6 % of the patients had responded , which was defined as a 50 % reduction in scores on the Montgomery-Asberg Depression Rating Scale ; 49 % of those defined with \" absolute resistance \" demonstrated such an outcome . Forty-five percent of the patients with absolute resistance who had failed to respond to at least one tricyclic antidepressant responded to venlafaxine . Response rates were higher in those with an absence ( 57.5 % ) compared with the presence ( 31.0 % ) of any comorbid psychiatric disorder ( p baseline ratings on the patient-rated Clinical Global Impressions Scale ( p < 0.05 ) , and \" relative \" ( 61 % ) compared with \" absolute \" resistance ( 49 % ) ( p = 0.06 ) . Furthermore , improvement in scores of 20 % or 30 % at weeks 1 or 2 was associated with higher rates of final response ( p < 0.0005 ) . After logistic regression , both comorbid psychiatric illness ( p < 0.001 ) and early improvement ( p < 0.0001 ) remained significant and independent predictors of final response",
"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",
"Antidepressants are ineffective in about 30 % of the patients with major depression . Besides electroconvulsive therapy ( ECT ) and lithium , MAO inhibitors have been suggested as an alternative in such patients . In 2 controlled , partial crossover studies involving 47 patients with major depression who had already been treated unsuccessfully with at least 2 cyclic antidepressants , the effect of the MAO inhibitor tranylcypromine was studied . The first study was an open comparison with L‐5‐hydroxytryptophan ( L‐5HTP ) , the second study a double‐blind comparison with nomifensine . Neither the patients treated with L‐5HTP nor the patients treated with nomifensine , except one , improved . In contrast , tranylcypromine was effective in 50 % of the patients . The depressions of the responders to tranylcypromine appeared to be more endogenous ( according Newcastle Scale II ) and of shorter duration than those of the non‐responders . It is concluded that MAO inhibitors such as tranylcypromine are an effective alternative to ECT and lithium in patients with major depression who have failed to respond to cyclic antidepressants",
"OBJECTIVE ( 1 ) To directly compare the effectiveness of switching antidepressants with augmenting them in depressed patients who do not respond to an initial adequate trial and ( 2 ) to determine whether there is a decreased likelihood of response to a second switch or augmentation trial in those patients who did not respond to the first intervention for treatment-resistant depression . METHOD In a naturalistic , open-label design , all depressed out patients ( DSM-IV criteria ) who were treatment resistant were prospect ively assessed . Short- and long-term outcomes of switching versus augmentation were compared using the Clinical Global Impressions scale . RESULTS In the acute phase , 37 ( 50.0 % ) of 74 subjects responded to 1 of the 2 interventions for treatment-resistant depression . Forty-five percent ( N = 17 ) and 56 % ( N = 20 ) of the patients who had their antidepressant switched or augmented , respectively , responded to that intervention . Nearly three fourths ( 71.4 % ) of the acute responders maintained their response through 6 months of follow-up . In 18 patients who did not respond to the first switch or augmentation , 9 ( 50.0 % ) responded to a second trial . CONCLUSION Switching antidepressants was somewhat less effective than augmentation , although this difference was not statistically significant . For patients who do not respond to an augmentation or switch , our results suggest that a second trial for treatment-resistant depression may be as effective as the first",
"BACKGROUND The question was asked whether patients who discontinue one serotonin selective reuptake inhibitor ( SSRI ) because of side effects can be treated successfully with another SSRI . METHOD 113 patients with major depression who had discontinued fluoxetine because of side effects were enrolled in an open , multicenter , 8-week study design ed to evaluate the tolerability and efficacy of sertraline . After a washout period of at least 3 weeks following fluoxetine discontinuation and an additional 1-week , single-blind , placebo washout period , patients began treatment with 50 mg of sertraline once daily . Doses were titrated upward as necessary to a maximum daily dose of 200 mg . Depressive symptoms and adverse events were evaluated weekly . RESULTS Based on the Clinical Global Impressions Scale , 79 ( 71.8 % ) of 110 patients evaluated for efficacy were \" much \" or \" very much \" improved relative to baseline . Only 11 ( 9.8 % ) of 112 patients discontinued sertraline because of adverse reactions . CONCLUSION These results suggest that patients who discontinue one SSRI because of side effects can be treated successfully with another",
"We assessed the tolerability and antidepressant response to citalopram in a group of patients who could not tolerate a recent trial of paroxetine therapy . Sixty-one out patients with major depressive disorder and a confirmed history of intolerance to paroxetine ( mean final dose : 26.7 mg/day ) were switched after at least a 1 week washout to citalopram therapy ( 20 mg/day ) . During the 6-week , open label treatment protocol , citalopram could be titrated up to a maximum dose of 40 mg/day . Response was evaluated using the Clinical Global Impressions CGI scale , the 24-item Hamilton Rating Scale for Depression , and several other measures of symptoms and quality of life . Fifty-three patients ( 87 % ) completed 6 weeks of citalopram therapy ( mean intent-to-treat dose : 23.9 mg/day ) . The specific side effects that were reported to be intolerable during the earlier paroxetine trial typically recurred only less than 30 % of the time during citalopram therapy ; only 6 patients ( 10 % ) dropped out because of adverse events . The intent-to-treat CGI response rate was 56 % at study endpoint ; 62 % of the completers responded . Significant improvement from pretreatment was observed on various symptom measures after two weeks of citalopram therapy . Citalopram therapy was well tolerated , and more than one half of the patients who began treatment improved significantly . Although further work is necessary to assess the relative merits of this within-class switching strategy ( as compared to other options ) , these data provide further evidence that the various selective serotonin reuptake inhibitors do not have interchangeable tolerability profiles",
"CONTEXT Selective serotonin reuptake inhibitors ( SSRIs ) are the most commonly prescribed class of antidepressant , yet it is not known whether one SSRI is more effective than another . OBJECTIVE To compare the effectiveness of 3 SSRIs ( paroxetine , fluoxetine , and sertraline ) in depressed primary care patients . DESIGN Open-label , r and omized , intention-to-treat trial , with patient enrollment occurring in April-November 1999 . SETTING Thirty-seven clinics in 2 US primary care research networks . PATIENTS A total of 573 depressed adult patients for whom their primary care physician thought that antidepressant therapy was warranted and who completed a baseline interview . INTERVENTIONS Patients were r and omly assigned to receive paroxetine ( n = 189 ) , fluoxetine ( n = 193 ) , or sertraline ( n = 191 ) for 9 months . Primary care physicians were allowed to switch patients to a different SSRI or non-SSRI antidepressant if they did not adequately respond to or tolerate the initial SSRI . MAIN OUTCOME MEASURES The primary outcome measure was change in the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) Mental Component Summary score ( range , 0 - 100 ) , compared across treatment groups at 1 , 3 , 6 , and 9 months . Secondary outcomes included other depression and psychological measures , multiple measures of social and work functioning , and other domains of health-related quality of life , such as physical functioning , concentration and memory , vitality , bodily pain , sleep , and sexual functioning . RESULTS Follow-up interviews were successfully completed in 94 % of patients at 1 month , 87 % at 3 months , 84 % at 6 months , and 79 % at 9 months . Responses to the 3 SSRIs were comparable on all measures and at all time points . The mean change in the SF-36 Mental Component Summary score at 9 months was + 15.8 in the paroxetine group , + 15.1 in the fluoxetine group , and + 17.4 in the sertraline group . The drugs were also associated with similar incidences of adverse effects and discontinuation rates . CONCLUSIONS The SSRI antidepressants paroxetine , fluoxetine , and sertraline were similar in effectiveness for depressive symptoms as well as multiple domains of health-related quality of life over the entire 9 months of this trial",
"This was an 8-week , multicenter , open-label study of the efficacy and tolerability of venlafaxine in patients with treatment-resistant depression conducted in Canada . In patients or out patients aged 18 to 70 years with major depression were eligible if they had a 21-item Hamilton Rating Scale for Depression ( HAM-D-21 ) score of 2 > or = 18 and a documented history of unsatisfactory improvement after a minimum of 8 weeks of treatment with an adequate dose of an antidepressant . Treatment with venlafaxine was started at 37.5 mg twice daily , and the dose could be titrated upward to a maximum of 375 mg/day during the first 4 weeks on the basis of the investigator 's assessment of clinical response and tolerability . Of the 159 patients enrolled , 152 were evaluable for efficacy . The mean daily venlafaxine dose was 260 mg/day . The mean HAM-D-21 score decreased by 52 % , and the mean Montgomery-Asberg Depression Rating Scale score decreased by 50 % from baseline to day 56 . A response ( 50 % improvement from baseline ) was achieved by 58 % of patients on the HAM-D-21 , and a remission ( > or = 75 % improvement in the HAM-D-21 ) was observed in 28 % at day 56 . By day 56 , 88 % of patients had improved from baseline on the Clinical Global Impression Improvement scale . Only 8 % of the patients discontinued for adverse events . The most common adverse events were headache , insomnia , nausea , constipation , diaphoresis , and xerostomia . In conclusion , these results suggest that venlafaxine is effective and well tolerated for the management of patients with treatment-resistant major depression",
"Lithium augmentation , the most studied augmentation strategy for depression , has not been evaluated in patients with a history of non-response to multiple antidepressants . The objective of this study was to assess the efficacy of lithium augmentation for patients with a history of treatment resistant depression who also failed a prospect i ve trial of nortriptyline . We enrolled 92 subjects with treatment resistant depression . Treatment resistance was defined by at least one , but no more than five , adequate trials of antidepressants during the current episode . Subjects were treated with nortriptyline ( NT ) for 6 weeks . Those subjects who tolerated NT for 6 weeks and whose depression did not respond ( n=35 ) were r and omized to receive either lithium ( n=18 ) or placebo ( N=17 ) augmentation of nortriptyline for an additional 6 weeks . Response was defined as an equal to or greater than 50 % decrease in HAM-D-17 scores . After 6 weeks of double-blind augmentation , 12.5 % of subjects responded to lithium and 20.0 % to placebo . Our results revealed no significant difference between lithium and placebo augmentation . While lithium augmentation seems to be useful in depression refractory to a single medication in some studies , our data suggest limited usefulness of this option for patients refractory to multiple treatments . More definitive data await the outcome of the NIMH Sequential Treatment Alternatives to Relieve Depression ( STAR*D ) study",
"BACKGROUND This study was conducted to determine if patients with major depressive disorder who had previously failed treatment with one serotonin selective reuptake inhibitor ( SSRI ) would respond to a different SSRI . METHOD Adult out patients ( N = 106 ) with DSM-III-R major depressive disorder and a history of either intolerance ( N = 34 ) or nonresponse ( N = 72 ) to treatment with sertraline were treated with fluoxetine ( mean dose = 37.2 mg/day ) in a st and ardized , open-label , 6-week clinical trial . Outcome was assessed at each visit using the Hamilton Rating Scale for Depression ( HAM-D ) , the Clinical Global Impressions ( CGI-Improvement and CGI-Severity ) scales , and the Patient 's Global Improvement ( PGI ) scale . RESULTS Ninety-one patients ( 86 % ) completed the study . Sixty-seven patients ( 63 % ) responded to fluoxetine ( i.e. , experienced > or = 50 % reduction in HAM-D28 total score at endpoint versus baseline ) . In addition , clinical ly and statistically significant improvements were noted on all measures of depressive symptoms and global functioning . There was a nonsignificant trend for patients with a history of less vigorous sertraline trials to respond more favorably to fluoxetine . Fluoxetine therapy was generally well tolerated , and there were only slight differences in adverse events reported by patients who had been intolerant to sertraline versus those who were nonresponders . CONCLUSION These findings indicate that fluoxetine and sertraline , two widely used SSRIs , are not interchangeable . Patients who either have had trouble tolerating or have not responded to sertraline may do well on fluoxetine treatment",
"BACKGROUND Up to 30 % of patients with major depression fail to respond to an antidepressant trial , with most taking a selective serotonin reuptake inhibitor ( SSRI ) as initial treatment . While the tricyclic antidepressants might be effective for SSRI nonresponders , they have been relegated to third- and fourth-line treatment . This study assesses the efficacy of nortriptyline for patients with treatment-resistant major depression . METHOD 92 patients with treatment-resistant DSM-III-R major depression , with resistance defined by at least 1 , but no more than 5 , well-documented adequate trials of antidepressants during the current episode , were treated openly with nortriptyline for 6 weeks . Patients were titrated up to full target doses of nortriptyline within 1 week , with target blood levels of 100 ng/mL. Response was defined as a 50 % or greater decrease of baseline 17-item Hamilton Rating Scale for Depression score . We performed an intent-to-treat analysis with the last observation carried forward . RESULTS Approximately 40 % of patients were responders ( N = 39 ) and 12 % were remitters ( N = 11 ) after 6 weeks of nortriptyline . Over a third of patients were unable to complete the trial . CONCLUSION Nortriptyline was effective for over a third of patients with treatment-resistant depression , and nortriptyline should be considered as potential treatment if patients fail to respond to other antidepressants",
"Available evidence is review ed concerning the antidepressant efficacy of bupropion in patients who had failed to respond to or been unable to tolerate tricyclic antidepressants ( TCAs ) during prior episodes of depression . In patients classified as TCA nonresponders were r and omly assigned to double-blind treatment with bupropion ( N = 19 ) or placebo ( N = 11 ) . Patients receiving bupropion showed an excellent antidepressant response , whereas those receiving placebo showed minimal improvement ( p less than .001 ) . In patients who were classified as TCA responders responded well to double-blind treatment with bupropion , but also had a substantial , although significantly smaller ( p less than .05 ) , response to placebo . Out patients ( N = 33 ) with a history of nonresponse or nonresponse plus intolerance to TCAs showed marked improvement during open treatment with bupropion . The results from both double-blind and open treatment with bupropion demonstrate that this drug offers a promising alternative therapy for patients with a history of poor response to TCAs",
"Abrupt interruption or cessation of selective serotonin reuptake inhibitor ( SSRI ) treatment may result in discontinuation or treatment interruption symptoms . Recent reports suggested these symptoms occur more frequently with shorter half-life SSRIs . Previous studies indicated a 5–8-day treatment interruption result ed in fewer discontinuation-emergent adverse events in fluoxetine-treated patients than in paroxetine-treated patients . This study examines the effects of shorter treatment interruption ( 3–5 days ) , as would occur if patients miss just a few doses of medication . Patients successfully treated for depression with fluoxetine or paroxetine underwent treatment interruption in a double-blind fashion . Treatment interruption-emergent symptoms were assessed using the Discontinuation-Emergent Signs and Symptoms checklist . Other assessment s included the Montgomery – Åsberg Depression Rating Scale , Clinical Global Impressions-Severity scale and a social functioning question naire . Of 150 patients enrolled , 141 completed the study . Following treatment interruption , fluoxetine-treated patients experienced fewer treatment interruption-emergent events than did paroxetine-treated patients . The paroxetine treatment group also experienced significant increases in depressive symptoms , clinical global severity scores and difficulty in social functioning ; the fluoxetine treatment group did not . These results are consistent with reports suggesting abrupt interruption of treatment with paroxetine is more often associated with somatic and psychological symptoms than is abrupt interruption of fluoxetine . Patients treated with fluoxetine appeared to be protected by its longer half-life",
"CONTEXT The Texas Medication Algorithm Project is an evaluation of an algorithm-based disease management program for the treatment of the self-declared persistently and seriously mentally ill in the public mental health sector . OBJECTIVE To present clinical outcomes for patients with major depressive disorder ( MDD ) during 12-month algorithm-guided treatment ( ALGO ) compared with treatment as usual ( TAU ) . DESIGN Effectiveness , intent-to-treat , prospect i ve trial comparing patient outcomes in clinics offering ALGO with matched clinics offering TAU . SETTING Four ALGO clinics , 6 TAU clinics , and 4 clinics that offer TAU to patients with MDD but provide ALGO for schizophrenia or bipolar disorder . Patients Male and female out patients with a clinical diagnosis of MDD ( psychotic or nonpsychotic ) were divided into ALGO and TAU groups . The ALGO group included patients who required an antidepressant medication change or were starting antidepressant therapy . The TAU group initially met the same criteria , but because medication changes were made less frequently in the TAU group , patients were also recruited if their Brief Psychiatric Rating Scale total score was higher than the median for that clinic 's routine quarterly evaluation of each patient . MAIN OUTCOME MEASURES Primary outcomes included ( 1 ) symptoms measured by the 30-item Inventory of Depressive Symptomatology-Clinician-Rated scale ( IDS-C(30 ) ) and ( 2 ) function measured by the Mental Health Summary score of the Medical Outcomes Study 12-item Short-Form Health Survey ( SF-12 ) obtained every 3 months . A secondary outcome was the 30-item Inventory of Depressive Symptomatology-Self-Report scale ( IDS-SR(30 ) ) . RESULTS All patients improved during the study ( P ALGO patients had significantly greater symptom reduction on both the IDS-C(30 ) and IDS-SR(30 ) compared with TAU . ALGO was also associated with significantly greater improvement in the SF-12 mental health score ( P = .046 ) than TAU . CONCLUSION The ALGO intervention package during 1 year was superior to TAU for patients with MDD based on clinician-rated and self-reported symptoms and overall mental functioning ",
"BACKGROUND The effectiveness of monoamine oxidase inhibitors ( MAOIs ) in tricyclic resistant depression has received surprisingly little systematic study . METHOD Patients who failed to respond to sustained , adequate treatment with the tricyclic imipramine ( mean maximum dosage = 260 mg/day ) and interpersonal psychotherapy were withdrawn from imipramine and treated in a st and ardized , but open-label 6-week trial with either phenelzine ( N = 4 ; 60 mg/day ) or tranylcypromine ( N = 36 ; mean = 38.5 mg/day ) and continued interpersonal psychotherapy . RESULTS Forty of 42 patients ( 95 % ) completed the trial , of whom 23 ( 58 % ) responded to treatment . Highly significant improvement was documented on measures of depression , reversed neurovegetative symptoms , and somatic symptoms . Response was significantly correlated with severity of depression ( pre-MAOI score on the Hamilton Rating Scale for Depression ) , severity of a composite score of anergic and reversed neurovegetative features , and low levels of improvement during initial imipramine/interpersonal psychotherapy . Of patients who met criteria for proposed subforms of anergic or atypical depression , 67 % ( 18/27 ) responded ( p less than .05 ) ; 77 % ( 17/22 ) of patients who scored above the mean on the composite measure of anergic and reversed neurovegetative features responded ( p less than .01 ) . CONCLUSION These findings provide strong evidence of the utility of MAOIs in tricyclic-resistant depression , especially in patients with features such as fatigue , volitional inhibition , motoric retardation , hypersomnia , and /or weight gain",
"Following an initial double-blind , r and omized , parallel treatment group comparison of fluvoxamine , desipramine , and placebo in 89 out patients with major depression at two centers , double-blind crossover to fluvoxamine was offered to 13 of 22 desipramine-treated completers of the initial phase who were considered failures on desipramine . Twelve elected to cross over to blinded fluvoxamine , and eleven continued on fluvoxamine for at least eight weeks . Nine of these eleven improved , and overall there was a statistically significant decrease in average Hamilton Depression Scores , from 24 to 13 , for these fluvoxamine-treated desipramine-resistant patients",
"Given the potentially severe functional impairment , morbidity , and high costs associated with refractory depression , it is important to explore all treatment options that may benefit patients with this disorder . This is a retrospective , uncontrolled analysis of our experience with nefazodone therapy in treatment-resistant and treatment-intolerant depression . Potential c and i date s for nefazodone therapy were referred by their treating psychiatrist . Documentation of failure to respond to previous antidepressant therapy , a diagnosis of clinical depression according to criteria in the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , and completion of a Beck Depression Inventory ( BDI ) were required before initiation of nefazodone . A follow-up BDI was obtained after > or = 4 weeks of nefazodone therapy . A Clinical Global Inventory ( CGI ) score was obtained retrospectively based on documentation of target symptoms in the clinical record of the last clinic visit . The study group consisted of 20 patients with treatment-resistant or treatment-intolerant major depression who received nefazodone therapy . The mean ( + /- SD ) age of the group was 48.1+/-9.4 years . The mean number of previously failed antidepressant trials was 1.9+/-0.6 . Psychiatric comorbidity in this group was substantial , with posttraumatic stress disorder ( PTSD ) found in 11 ( 55 % ) patients , substance abuse in 3 ( 15 % ) patients , and personality disorder found in 2 ( 10 % ) patients . After treatment with nefazodone , 11 of 20 patients ( 55 % ) were rated on the CGI as much or very much improved . In addition , 9 patients ( 45 % ) had > 20 % improvement on BDI , 3 patients ( 15 % ) had 10 % to 20 % improvement , and 6 patients ( 30 % ) had nefazodone therapy due to adverse effects . Analysis of our experience with nefazodone therapy in a population with treatment-resistant depression and a high degree of psychiatric comorbidity suggests that approximately 50 % of patients may have substantial response to treatment , with a smaller proportion having a more modest clinical response . While receiving nefazodone therapy , most patients continued to take concurrently prescribed psychotropic medications , primarily anxiolytics or other antidepressants . Of interest was the positive drug response among a subgroup of individuals with depression and chronic , severe PTSD . Larger , controlled studies are needed to determine whether these preliminary observations are confirmed",
"INTRODUCTION Some studies suggest that venlafaxine , due to its pharmacodynamic characteristics , could be an effective drug in depression , resistant to other antidepressive agents . This investigation explores the efficacy and tolerability of venlafaxine in major depression , resistant to a selective serotonin reuptake inhibitor ( SSRI ) . METHODS A multicenter naturalistic study was performed during 6 months and included those patients diagnosed of major depression according to the criteria of DSM-IV who had a minimum score of 18 on the Hamilton Depression Rating Scale ( HAM-D ) and who had not responded to previous treatment with a SSRI at therapeutic doses for a minimum of 4 weeks . The assessment of efficacy was performed with the HAM-D scale , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Hamilton Anxiety Rating Scale ( HAM-A ) and the Global Clinical Impression ( GCI ) . Tolerability was evaluated by recording the adverse reactions and with the GCI score on overall drug tolerability . RESULTS A total of 69 patients , of which 59 were evaluable for efficacy ( they had fulfilled at least 4 weeks of treatment ) , were included . About 81 % of all of them obtained a reduction of at least 50 % in the HAM-D , 74 % were considered as \" quite improved \" or \" very improved \" in the GCI and 69 % met both criteria . The mean dose of venlafaxine used was 170.4 ( S.D.=43.8 ) mg . Of the 21 patients who did not complete the 6 months of treatment , 3 were due to lack of efficacy , 6 due to adverse effects and 12 for other reasons . About 89.2 % of side effects were considered as mild or moderate . CONCLUSION The results of our study support the efficacy and tolerability of venlafaxine in patients suffering from depression who have not responded to SSRI treatment ",
"The aim of the present study was to evaluate the efficacy and safety of an immediate switch to reboxetine , a selective noradrenaline reuptake inhibitor ( selective NRI ) , in patients with depression unresponsive to the selective serotonin reuptake inhibitor ( SSRI ) fluoxetine . The study included 128 adult out patients with DSM-IV major depressive disorder ( MDD ) who had not responded to at least 6 to 12 weeks of fluoxetine treatment , with at least 3 weeks of treatment on a minimum dose of 40 mg/d . Patients were switched , without a washout period , to reboxetine 4 mg twice daily , with the possibility of increasing the dose to 10 mg/d ( given in divided doses ) after 4 weeks of treatment . Efficacy was assessed using the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) and the Clinical Global Impression Improvement ( CGI-I ) and Severity ( CGI-S ) scales . Safety was evaluated by recording spontaneously reported adverse events . A statistically significant ( P mean total HAM-D-17 score was seen from baseline by week 1 of treatment with reboxetine , and the improvement continue to week 8 . CGI-I and CGI-S scores were similarly improved . The switch to reboxetine was well tolerated ; the most common treatment-emergent adverse events were insomnia , headache , dry mouth , diaphoresis , and constipation , all of which were mild to moderate in severity and decreased in frequency as the study progressed . Immediate switching to reboxetine appears to be a safe and effective treatment for patients with depression who have failed to respond to an adequate dose of fluoxetine",
"The antidepressive properties of the specific serotonin reuptake inhibitor fluvoxamine and the specific norepinephrine reuptake inhibitor oxaprotiline were investigated in a sequential design with the aim of evaluating the hypothesis that two distinct biochemical subtypes of depression exist . Responders were treated for 7 weeks with the compound to which they had responded . After 1 placebo week , the nonresponders were switched to the alternative compound . An evaluation of the data obtained during the 3-week treatment periods from 24 patients ( 37 trials ) with major depression revealed a highly significant reduction of Hamilton Scores with both compounds , oxaprotiline and fluvoxamine . If the patients with major depression are subdivided into two groups , endogenous depressives and neurotic depressives , there is no significant difference between the therapeutic improvements ( both compounds ) achieved in the two groups . The data shows that only about 20 % of the nonresponders on one compound responded to the alternative drug , whereas 90 % of responders ( within 3 weeks ) were still responders after 7 weeks . The data are at variance with the concept of two distinct biochemical subtypes of depression ( serotonergic vs. norepinephrinergic ) . Dexamethasone suppression tests , performed in 23 patients , gave no prognostic hint as to whether the patients reacted well to drug therapy or not",
"STAR*D is a multisite , prospect i ve , r and omized , multistep clinical trial of out patients with nonpsychotic major depressive disorder . The study compares various treatment options for those who do not attain a satisfactory response with citalopram , a selective serotonin reuptake inhibitor antidepressant . The study enrolls 4000 adults ( ages 18 - 75 ) from both primary and specialty care practice s who have not had either a prior inadequate response or clear-cut intolerance to a robust trial of protocol treatments during the current major depressive episode . After receiving citalopram ( level 1 ) , participants without sufficient symptomatic benefit are eligible for r and omization to level 2 treatments , which entail four switch options ( sertraline , bupropion , venlafaxine , cognitive therapy ) and three citalopram augment options ( bupropion , buspirone , cognitive therapy ) . Those who receive cognitive therapy ( switch or augment options ) at level 2 without sufficient improvement are eligible for r and omization to one of two level 2A switch options ( venlafaxine or bupropion ) . Level 2 and 2A participants are eligible for r and om assignment to two switch options ( mirtazapine or nortriptyline ) and to two augment options ( lithium or thyroid hormone ) added to the primary antidepressant ( citalopram , bupropion , sertraline , or venlafaxine ) ( level 3 ) . Those without sufficient improvement at level 3 are eligible for level 4 r and om assignment to one of two switch options ( tranylcypromine or the combination of mirtazapine and venlafaxine ) . The primary outcome is the clinician-rated , 17-item Hamilton Rating Scale for Depression , administered at entry and exit from each treatment level through telephone interviews by assessors masked to treatment assignments . Secondary outcomes include self-reported depressive symptoms , physical and mental function , side-effect burden , client satisfaction , and health care utilization and cost . Participants with an adequate symptomatic response may enter the 12-month naturalistic follow-up phase with brief monthly and more complete quarterly assessment",
"OBJECTIVE There are limited data comparing medication strategies in patients with treatment-resistant depression . In this study , we compared the effects of combining citalopram and bupropion-SR versus switching to the other monotherapy in treatment-resistant depression . METHOD This was a naturalistic , open-label cohort study . Patients with DSM-IV major depressive disorder who had not responded to at least 1 previous antidepressant and at least 6 weeks of treatment with citalopram or bupropion-SR were treated in a st and ard clinical protocol . In alternate months , eligible consecutive patients were treated by adding citalopram or bupropion-SR , or by switching to the other medication . Patients were assessed at baseline and after 6 weeks of treatment with the 29-item version of the Structured Interview Guide for the Hamilton Depression Rating Scale , Seasonal Affective Disorders Version ( SIGH-SAD ) . RESULTS A total of 61 patients completed the study : 32 in the combination condition and 29 in the monotherapy switch condition . The combination condition was superior to the monotherapy switch in the SIGH-SAD change score ( -14.8 vs. -10.1 , respectively , p proportion of patients in clinical remission ( 28 % vs. 7 % , p no differences in the proportion of patients who had side effects or in the severity of the side effects experienced . CONCLUSION The results of this cohort study suggest that combining citalopram and bupropion-SR is more effective than switching to a monotherapy . Combination treatment was well tolerated with no greater side effect burden than monotherapy . Limitations of this study include the nonr and omized design , open-label treatment , and small sample size",
"BACKGROUND Previous reports have described the effects of vagus nerve stimulation plus treatment as usual ( VNS+TAU ) during open trials of patients with treatment-resistant depression ( TRD ) . To better underst and these effects on long-term outcome , we compared 12-month VNS+TAU outcomes with those of a comparable TRD group . METHODS Admission criteria were similar for those receiving VNS+TAU ( n = 205 ) or only TAU ( n = 124 ) . In the primary analysis , repeated- measures linear regression was used to compare the VNS+TAU group ( monthly data ) with the TAU group ( quarterly data ) according to scores of the 30-item Inventory of Depressive Symptomatology-Self-Report ( IDS-SR(30 ) ) . RESULTS The two groups had similar baseline demographic data , psychiatric and treatment histories , and degrees of treatment resistance , except that more TAU participants had at least 10 prior major depressive episodes , and the VNS+TAU group had more electroconvulsive therapy before study entry . Vagus nerve stimulation plus treatment as usual was associated with greater improvement per month in IDS-SR(30 ) than TAU across 12 months ( p 24-item Hamilton Rating Scale for Depression ( last observation carried forward ) at 12 months were 27 % for VNS+TAU and 13 % for TAU ( p TAU ( drugs and electroconvulsive therapy ) during follow-up . CONCLUSIONS This comparison of two similar but nonr and omized TRD groups showed that VNS+TAU was associated with a greater antidepressant benefit over 12 months",
"Data regarding open-label treatment with fluoxetine following failure to respond to tricyclic antidepressants ( TCAs ) or intolerance of TCA side effects , suggest a response rate between 51.4 % and 62.1 % , depending on the definition of TCA refractoriness employed . Double-blind study of this issue would extend these findings . Fluoxetine is well tolerated in patients unable to tolerate TCAs . Within this population , more than 80 % of patients unable to tolerate TCAs found fluoxetine acceptable . Fluoxetine , as an alternative to polypharmaceutical augmentation , may represent a logical choice as the next step in therapy for a patient who has initially been treated with a TCA and has proven refractory or intolerant",
"BACKGROUND We assessed the tolerability of and response to citalopram in depressed patients who had discontinued fluoxetine treatment due to adverse events . METHOD Fifty-five out patients with DSM-IV major depressive disorder and a confirmed history of intolerance to fluoxetine ( mean final dose = 24.6 mg/day ) were switched to citalopram ( 20 mg/day ) after a 2- to 4-week single-blind placebo washout period . During a 6-week , open-label treatment protocol , citalopram could be titrated up to 40 mg/day . Safety and tolerability , including reemergence of symptoms that previously had been associated with fluoxetine , were assessed by recording all spontaneously reported or observed adverse events . Efficacy was evaluated using the Hamilton Rating Scale for Depression ( HAM-D ) , the Clinical Global Impressions ( CGI ) scale , and several other measures . Response was defined as a CGI-Improvement score at endpoint of 1 or 2 ( i.e. , very much or much improved ) . RESULTS Ninety-five percent of patients ( N = 52 ) completed the citalopram trial . The only adverse events reported by more than 5 patients ( > or= 10 % ) were pharyngitis ( 15 % ) and constipation ( 11 % ) , and none of the 3 early terminations were attributed to adverse events . The rate of recurrence of the fluoxetine-associated adverse events was low , with headache ( 3 [ 27 % ] of 11 cases ) , nausea ( 2 [ 22 % ] of 9 cases ) , and decreased libido ( 5 [ 18 % ] of 28 cases ) being the most common . Significant improvement from baseline HAM-D ( p citalopram therapy and continued until study end . The intent-to-treat CGI response rate was 65 % ( 36 of 55 patients ) at study endpoint ; 69 % ( 36 of 52 patients ) of the completers responded . CONCLUSION These data suggest that fluoxetine-intolerant patients can be treated effectively with citalopram",
"L-5HTP and tranylcypromine were compared in an open , but controlled and cross-over study , in patients suffering from major depression ; all were non-responders to several reuptake inhibitors , including oxaprotiline and fluvoxamine . After four unsuccessful sleep-deprivations , L-5HTP or tranylcypromine were given during four weeks in a crossover design . Of 17 patients given L-5HTP during both treatment periods , none responded , whereas of 26 patients treated with tranylcypromine , 15 responded . Thus , L-5HTP is not a therapeutically effective alternative in depressed patients who have not responded to reuptake inhibitors",
"Pre clinical investigations have shown that combined administration of the alpha 2-adrenergic receptor antagonist yohimbine hydrochloride and the tricyclic antidepressant desipramine hydrochloride produces a reduction in brain beta-adrenergic receptor function within four days . Since the ability of antidepressant treatments to reduce beta-adrenergic receptor function has been hypothesized to mediate antidepressant efficacy , it was predicted that combined desipramine-yohimbine treatment would be a more rapid-acting and potent antidepressant regimen than desipramine alone . In the present investigation , the effects of desipramine ( N = 11 ) and desipramine-yohimbine ( N = 10 ) treatment on depressive symptoms , norepinephrine turnover , and blood pressure were determined in patients with major depression who had a history of nonresponse to st and ard antidepressant treatments . Neither desipramine nor desipramine-yohimbine proved to be an effective treatment , although concomitant yohimbine administration did attenuate the ability of desipramine to decrease plasma free and 24-hour urinary 3-methoxy-4-hydroxyphenyl-ethyleneglycol levels and blood pressure . Fifteen of the 21 patients eventually had a good response to pharmacologic treatments , particularly a desipramine-lithium carbonate or lithium carbonate-tranylcypromine sulfate combination treatment ( 11 of 14 responded ) . This study provides evidence against the beta-adrenergic receptor hypothesis of antidepressant action",
"Serotonin-norepinephrine reuptake inhibitors ( SNRIs ) may be used as an alternative treatment for depressed patients who do not tolerate or respond adequately to treatment with a conventional antidepressant . This r and omized , open-label , multicenter study compared the effectiveness of the SNRI venlafaxine extended release ( VXR ) with that of conventional antidepressants ( CA ) in patients who were referred to an outpatient psychiatric specialty care setting for treatment after failure to tolerate or respond to at least 4 weeks of treatment with a CA in a primary care setting . Patients with a Hamilton Depression Rating Scale ( HAM-D17 ) score > or = 17 were r and omly assigned to treatment with an alternative CA or VXR . Remission was defined as a score Efficacy analyses were carried out on 3,097 patients from the intent-to-treat ( ITT ) population ( 1,632 VXR ; 1,465 CA ) . The antidepressants prescribed most frequently in the CA group were paroxetine ( 21.3 % ) , citalopram ( 20.1 % ) , sertraline ( 19.1 % ) , fluoxetine ( 17.0 % ) , and mirtazapine ( 7.9 % ) . After 24 weeks of treatment , the VXR group demonstrated a significantly higher remission rate than did the CA group ( 59.3 % VXR ; 51.5 % CA ; P<.0001 ; odds ratio : 1.37 ; 95 % CI : 1.19 - 1.58 ; P<.01 ) . Despite the limitations of the open design , the results of this study suggest that venlafaxine extended release may be more effective than the conventional antidepressants used in this study when treating depressed patients who do not tolerate or respond adequately to treatment with a conventional antidepressant",
"OBJECTIVE The purpose of this study was to compare the effectiveness and tolerability of tranylcypromine and combination treatment with extended-release venlafaxine and mirtazapine in patients with treatment-resistant major depression whose current depressive episode had not responded adequately to treatment in three prior prospect i ve medication trials . METHOD Adult out patients with nonpsychotic major depressive disorder who had not achieved remission or had withdrawn from treatment because of intolerance in three previous prospect i ve medication trials were r and omly assigned to receive open-label treatment with either tranylcypromine ( N=58 ) or extended-release venlafaxine plus mirtazapine ( N=51 ) . The primary outcome measure was whether patients achieved remission , which was defined as a score 17-item Hamilton Depression Rating Scale ( HAM-D ) . The HAM-D was administered by telephone by raters to whom treatment was masked . RESULTS Remission rates were not significantly different between the two treatment groups ( 6.9 % for the tranylcypromine group and 13.7 % for the venlafaxine plus mirtazapine group ) . The mean daily dose at exit for tranylcypromine was 36.9 mg ( SD=18.5 ) ; for venlafaxine , 210.3 mg ( SD=95.2 ) ; and for mirtazapine , 35.7 mg ( SD=17.6 ) . Tranylcypromine was associated with significantly less symptom reduction and greater attrition due to intolerance . CONCLUSIONS Remission rates were modest for both the tranylcypromine group and the extended-release venlafaxine plus mirtazapine group , and the rates were not statistically different between groups . The lower side effect burden , lack of dietary restrictions , and ease of use of venlafaxine and mirtazapine suggest that this combination may be preferred over tranylcypromine for patients with highly treatment-resistant depression who have not benefited adequately from several prior treatments",
"Antidepressants are ineffective in about 30 % of patients with major depression . Some authors then advise treatment of non‐responders with ( non‐tricyclic ) more selective reuptake inhibitors . In a double‐blind , partial crossover study , 71 patients were selected for treatment during 4 weeks with oxaprotiline and /or fluvoxamine , two non‐tricyclic antidepressants that are selective reuptake inhibitors of noradrenaline and serotonin respectively . All patients had failed to respond to earlier treatment with cyclic antidepressants during the current episode . Only 13 % of the patients responded , with 27 % of them responding to oxaprotiline and none to fluvoxamine . Moreover , a low response of 27 % was also obtained in the crossover phase , which included all non‐responders to the first treatment , oxaprotiline being effective in 39 % and fluvoxamine in 10 % of the patients . The results indicate that selective reuptake inhibitors are not an effective alternative for non‐responders to other cyclic antidepressants and that non‐responders to “ nor‐adrenergic ” antidepressants do not appear to have much chance of responding to “ serotonergic ” antidepressants and vice versa",
"In a multicentre , double blind , parallel group study 281 patients with DSM III-R diagnosis of dysthymia or a single episode of major depression in partial remission were r and omised to 3 months of treatment with amisulpride 50 mg/day or fluoxetine 20 mg/day . The baseline Montgomery and Asberg Depression Rating Scale ( MADRS ) total score was reduced by at least 50 % in 74.1 % of patients ( 103/139 ) with amisulpride and 67.4 % ( 87/129 ) with fluoxetine ( P = 0.230 ) . No significant differences between treatment groups were found in the reductions in mean total score with the MADRS , Widlöcher psychomotor retardation scale , Sheehan disability scale , and CGI . Anxiety measured by HAM-A total mean score decreased significantly more with amisulpride ( 63 % ) than with fluoxetine ( 54 % ; P = 0.021 ) . There were 13 dropouts due to adverse events with amisulpride and ten with fluoxetine . The number of patients reporting at least one adverse event was similar in the two groups ( amisulpride 47.5 % ; fluoxetine 40.9 % ) . As expected , in the amisulpride group endocrine-like adverse events in female patients were the most common , while nausea , dyspepsia , anorexia and insomnia occurred more frequently with fluoxetine",
"BACKGROUND At least 30 % of depressed patients fail to respond to adequate first-line anti-depressant medication . Several pharmacological strategies have been suggested to treat such refractory depression . There has been no survey of United Kingdom psychiatrists ' treatment preferences for refractory depression . This study was carried out to determine both experience and preference of various strategies for management of refractory depression . METHOD A total of 300 fellows , members and inceptors of the Royal College of Psychiatrists were r and omly selected and approached by postal question naire . They were asked to comment on management of a detailed clinical vignette of a case of depression with initial treatment failure . RESULTS The response rate was 63 % ( n = 175 ) . The most popular treatment choices were increasing dosage of tricyclic medication and change of medication of SSRI . The most rarely selected were augmentation with triiodothyronine ( T3 ) and augmentation with tryptophan or MAOIs . Treatment choice was significantly influenced by previous experience . A large number ( 39 % ) of psychiatrists were not confident in treating refractory depression . CONCLUSION Surprisingly few psychiatrists chose to use the best proven pharmacological treatments such as augmentation with lithium or T3 . In view of this and the considerable proportion of psychiatrists lacking confidence in the management of refractory depression , this topic deserves priority as a topic for continuing professional development ( CPD ) courses",
"OBJECTIVE Data from controlled studies concerning the response rates of patients to a second antidepressant medication after they have been unresponsive to a systematic trial of another antidepressant are extremely useful to clinicians for rational prescription of pharmacotherapy . Such information allows making an accurate prognosis , sustaining realistic hope in the patient , and achieving the best possible therapeutic outcome . This study was design ed to add to the scanty literature available on this subject . METHOD Eighty-nine mood-reactive , nonmelancholic , mainly chronically depressed out patients at a university research clinic who were unresponsive to vigorous double-blind trials of imipramine or phenelzine were crossed over to treatment with the other drug under double-blind conditions . RESULTS Of 46 patients previously unresponsive to imipramine who completed phenelzine treatment , 31 ( 67 % ) responded to phenelzine . Of 22 patients previously unresponsive to phenelzine who completed imipramine treatment , nine ( 41 % ) responded to imipramine . The difference in response rates was statistically significant . Even after they had shown no response to 7 weeks of placebo and 6 weeks of imipramine treatment , 10 ( 83 % ) of 12 patients who then completed treatment with phenelzine responded . CONCLUSIONS These data suggest that among chronically ill , mood-reactive depressed patients with many symptoms of atypical depression , phenelzine is strikingly effective in those who have been nonresponders to imipramine and should be tried in such patients",
"OBJECTIVE To evaluate the efficacy and safety of mirtazapine in depressed out patients who have shown nonresponse or intolerance to selective serotonin reuptake inhibitor ( SSRI ) therapy . METHOD In this open-label , 8-week study , the efficacy and safety of mirtazapine among 103 out patients with DSM-IV major depressive disorder who had failed previous therapy with an SSRI ( fluoxetine , paroxetine , or sertraline ) were evaluated . The primary efficacy measure was the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) , and safety assessment s included reported adverse events , routine laboratory assessment s , physical examinations , and assessment s of vital signs . A 4-day washout period followed by mirtazapine treatment was compared with an immediate switch from the SSRI to mirtazapine . RESULTS Based on mean HAM-D-17 scores at endpoint and response rates of 48 % based on the criterion of > or = 50 % reduction in HAM-D-17 score , mirtazapine was found to be an effective treatment for a substantial proportion of patients for whom an SSRI was ineffective and /or poorly tolerated . Mirtazapine was well tolerated , with sedation and appetite increase/weight gain the most commonly reported adverse events . In addition , no difference in efficacy , safety , or tolerability was observed for patients undergoing an immediate switch from an SSRI ( after having been tapered to the minimal effective dose ) to mirtazapine , compared with those undergoing the imposition of a 4-day drug-free washout . CONCLUSION These results suggest that an immediate switch to mirtazapine may be a valid therapeutic option among patients who can not tolerate or do not respond to SSRIs",
"Up to 50 % of patients with major depressive disorder ( MDD ) fail to respond to an antidepressant trial , with most taking a selective serotonin reuptake inhibitor ( SSRI ) as an initial treatment . Switching to bupropion , for depressed patients not responding to SSRIs , is a popular strategy among clinicians . This study assesses the efficacy of bupropion SR in the management of MDD resistant to a prospect i ve trial of fluoxetine . Twenty-nine patients with MDD refractory to an 8- to 12-week open-trial of fluoxetine were enrolled in an 8-week open-trial of bupropion SR . Both a completer analysis ( n = 20 ) and a modified intent-to-treat analysis ( n = 26 ) were performed to evaluate bupropion SR response rates . Using a completer analysis , seven patients ( 35.0 % ) were classified as responders , five ( 25.0 % ) partial responders , and eight ( 40.0 % ) nonresponders . A modified intent to treat analysis result ed in nine ( 34.6 % ) patients classified as responders , eight ( 30.8 % ) partial responders , and nine ( 34.6 % ) nonresponders . The overall proportion of remitters was 6/20 ( 30.0 % ) using a completer analysis and 6/26 ( 23.1 % ) using an MITT analysis . Approximately 60 % of patients with MDD resistant to a prospect i ve trial of fluoxetine experienced a full or partial response to bupropion SR . Bupropion SR should be considered as a potential treatment for patients who remain depressed despite treatment with",
"BACKGROUND The aim of this study was to examine whether phenelzine is a suitable alternative to tranylcypromine in antidepressant-resistant depression . METHOD A total of 77 severely depressed in- patients , meeting the DSM-IV criteria for major depressive disorder , who failed to respond to fixed plasma level treatment with either tricyclic antidepressants or fluvoxamine were withdrawn from psychotropic medication and included in a double-blind flexible-dose 5-week comparison of tranylcypromine and phenelzine . RESULTS Of the 77 patients , 67 ( 87 % ) completed the trial , of whom 35 ( 52 % ) responded . No significant differences in response between both drugs were observed . Seventeen ( 44 % ) of 39 patients responded to tranylcypromine and 18 ( 47 % ) of 38 to phenelzine ( > or = 50 % reduction in Hamilton Rating Scale for Depression [ HAM-D ] score ) . The mean reduction in HAM-D score was 10.4 + /- 8.3 for the tranylcypromine sample versus 8.3 + /- 8.4 for the phenelzine-treated patients . Only a few patients ( 10 % ) used concomitant psychotropic medication . A substantial number of patients experienced severe side effects , mainly dizziness , agitation , and insomnia ; the incidence was the same in both sample s ( 21 % ) . CONCLUSION No difference in efficacy was observed between both monoamine oxidase inhibitors in a sample of patients with severe antidepressant-refractory depression . Phenelzine appears to be a suitable alternative to tranylcypromine"
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4117a474-06ff-11f0-808a-c43d1ab1c353
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PURPOSE This paper focuses on the construct validity of instruments measuring impairments in body structures and function in rheumatic disorders . The objective is : 1 ) to make an inventory of constructs , based on the domains of the International Classification of Functioning , Disabilities and Health problems ( ICF ) , against which instruments measuring impairments in body structures and function were vali date d ; 2 ) to analyse whether validation against a similar construct result ed in higher correlation coefficients than validation against a dissimilar construct . METHODS In a systematic review papers were identified in which instruments measuring impairments in body structures and function for patients with rheumatic disorders were vali date d. The instruments identified were assessed on their method ological properties and the constructs against which they were vali date d. Subsequently , pooled ( interclass ) correlations of similar constructs and dissimilar constructs against which was vali date d were compared . An instrument was decided to have good construct validity , if the correlation coefficient was 0.50 or higher , and the measurement instrument in question is vali date d against similar constructs . RESULTS In total 216 papers were identified analysing the validity of 42 different instruments . Only 16 % of these instruments were vali date d against instruments that represent the most similar construct . In general , estimates of construct validity were lower when vali date d against dissimilar constructs , except for instruments measuring impairments in mental functions . CONCLUSION There is a trend that validation against a similar construct yields higher correlation coefficients than validation against a dissimilar construct . If an instrument measuring impairments is vali date d against the most similar construct , and a criterion of r > 0.50 is applied , only 10 out of the 42 identified instruments turned out to be valid
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[
"Health status measures are conceptually relevant to the assessment of clinical outcome in the rheumatic diseases , but their ability to detect meaningful changes in health has not been clearly demonstrated . This report describes the performance of a self-administered health status question naire in a r and omized , double-blind , 21-week comparison of placebo , oral gold , and injectable gold in rheumatoid arthritis patients . Outcome was assessed by st and ard clinical measures , including joint count , grip strength , and laboratory tests , and by the Arthritis Impact Measurement Scales , a reliable and valid health status measure that assesses physical disability , psychological status , and pain . Data from the clinical and health status measures produced highly similar conclusions : injectable and oral gold are more effective than placebo for rheumatoid arthritis , and injections are slightly more effective than oral gold . The health status measure was thus quite sensitive to clinical ly meaningful drug-induced improvements . These findings provide justification for the further application of health status measures to clinical trials of chronic disease",
"OBJECTIVE To determine the discriminant validity of the core set of outcome measures proposed by the American College of Rheumatology ( ACR ) and the Outcome Measures in Clinical Trials ( OMERACT ) conference committee to be used in clinical trials of rheumatoid arthritis ( RA ) . METHODS Utilizing data from a multicenter r and omized double-blind clinical trial of low-dose cyclosporine and placebo in RA , we estimated the relative efficiency ( RE ) of measures to detect a treatment effect ( relative to tender joint count , which was assigned a value of 1 ) . Four pain measures ( 10-cm visual analog scale [ VAS ] , 5-point categorical scale , Health Assessment Question naire [ HAQ ] pain index , Arthritis Impact Measurement Scales [ AIMS ] pain score ) and 3 quality -of-life measures ( Problem Elicitation Technique [ PET ] , HAQ , AIMS ) were compared . RESULTS Physician and patient global measures were the most responsive instruments , although neither was statistically superior to tender joint count . Swollen joint count , grip strength , pain measured on a 10-cm VAS , and functional status as measured by the PET and HAQ were all of intermediate responsiveness . Morning stiffness , 5-point pain scale , and erythrocyte sedimentation rate were the least responsive instruments . CONCLUSION This study provides further evidence to support the core set of outcome measures proposed by the ACR and OMERACT",
"Is the modified aneroid sphygmomanometer a valid instrument to measure isometric quadriceps strength ? Three techniques were compared : the cuff method , in which the original cuff and bladder were folded then secured by rubber b and s ; the bag method , in which the folded bladder was secured in a sewn bag ; and a st and ard method , employing weights . Using a design to control for method and order of measurement , five physiotherapists measured quadriceps muscle strength in five rheumatoid patients . The design features explained 97 % of the variation amongst the measurements . Order of observation and the observers had no effect on the measurements . Patients were quite different and methods of measurement were different . The cuff and bag methods obtained higher readings than the weights , and the bag readings were higher than the cuff . Compared to the st and ard weights , the sphygmomanometer methods were : equally sensitive and reproducible , performed in 16th of the time , independent of gravity and potentially adaptable to 24 different muscle groups",
"OBJECTIVE Disease activity has been defined using a self-administered instrument , focusing on fatigue , axial pain , peripheral pain , enthesopathy and morning stiffness [ Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) ] . This vali date d instrument is simple and takes 40 s to complete , but whether the index is an accurate expression of the component parts , or whether additional weighting would enhance its efficacy , is unclear . METHODS Four hundred and seventy-three patients with ankylosing spondylitis received placebo or active non-steroidal anti-inflammatory drug ( NSAID ) for 6 weeks , and changes between entry and completion were captured by BASDAI and the individual components . Principle component analysis ( PCA ) was used to explore the best combinations of variables in decreasing order of explained total dispersion and to assess whether a single sum ( or algebraic expression ) best defined disease activity status . RESULTS At entry , the correlation between BASDAI and the first axis was 0.99 , 0.11 with the second , and zero thereafter . Data at study end and relating to change revealed a 100 % correlation ( R = 1 ) between the first axis and the sum , with zero for the remainder . CONCLUSIONS The data support BASDAI as being a valid and appropriate composite to define disease activity in ankylosing spondylitis . Developed as a simple sum of its components , BASDAI has excellent content validity",
"A cross sectional analysis of the correlation between clinical , laboratory , and radiological markers of disease activity in 98 patients with classical rheumatoid arthritis ( RA ) is reported . The median age was 38 years , the median age at onset of disease 29 years , and the median duration of disease seven years . The Keitel function test ( KFT ) showed good correlation with the Ritchie articular index ( RAI ) ( p less than 0.0001 ; r = 0.5 ) and the disability question naire ( DQ ) ( p less than 0.0001 ; r = 0.6 ) . The RAI and DQ correlated weakly with laboratory variables , while the KFT showed significant correlation with the erythrocyte sedimentation rate ( ESR ) , C reactive protein ( CRP ) , and plasma viscosity ( PV ) ( p less than 0.001 ; r = 0.4 ; 0.3 ; 0.4 ) . Only the KFT showed significant correlations with bone mass measurements ( p less than 0.01 ; r = -0.3 ; -0.4 ) , and the Larsen index at the right wrist ( p less than 0.0001 ; r = 0.4 ) . Consensus analysis suggested that the KFT is a useful single clinical test of disease activity in RA . The h and functional index ( HFI ) , a component of the KFT , showed significant correlation with the total KFT ( r = 0.9 ) . Prospect i ve drug trials are needed to establish the value of the HFI in the monitoring of patients with RA",
"An articular index was devised for the sequential assessment of patients with osteoarthritis ( OA ) . Forty-eight joint units , chosen to reflect the characteristic pattern of the disease , were scored for tenderness on pressure or movement on a 4-point scale . Four observers examined patients to assess inter- and intraobserver error . The index was highly reproducible both within and between observers ; intraobserver error was , however , significantly smaller . In a double-blind , cross-over trial the index was sufficiently sensitive to detect a statistically significant difference between the responses of patients with OA to an anti-inflammatory agent and to a simple analgesic . It is likely to be a useful addition to current methods of measurement in osteoarthritis",
"To assess the effect of grading of tenderness on the interrater reliability of the Ritchie articular index ( RAI ) , 3 physicians recorded independent joint scores on each of 18 patients , examined in r and om order . Our results indicate that close agreement ( Intraclass Correlation Coefficient = 0.85 ) can be achieved on global RAI scores , and that raters can achieve reasonable agreement ( kappa = 0.40 - 0.59 ) on the absolute presence or absence of tenderness of individual joints . By contrast , interrater agreement hardly exceeds the chance level ( kappa = 0.008 - 0.148 ) when degree of tenderness is independently assessed . The grading system of the RAI may thus be implicated as an important source of the instrument 's interrater error",
"This study represents a long-term effort to find optimal techniques for evaluating outcome in patients who have undergone total joint arthroplasty . Sensitivity of five health status question naires was studied in a longitudinal evaluation of orthopedic surgery . The question naires ( Arthritis Impact Measurement Scales [ AIMS ] , Functional Status Index [ FSI ] , Health Assessment Question naire [ HAQ ] , Index of Well Being [ IWB ] , and Sickness Impact Profile [ SIP ] ) were administered to 38 patients with end-stage arthritis at three points in time : two weeks before hip or knee arthroplasty , and at three-month and 12- to 15-month follow-up . Response values ( i.e. , changes within patients ) were calculated on four scales : global health , pain , mobility , and social function . By the three-month follow-up , most instruments detected large mean responses in global health , pain scores , and mobility . Smaller changes on these scales were found between three and 12 to 15 months . Social function showed small to modest gains at successive follow-ups . St and ardized response means were calculated to assess sensitivity to detect change . Confidence intervals for these indices were constructed using a jackknife procedure , and significance tests were performed by pairing selected indices . Finally , the study projected sample sizes required to assess a new therapy , using each response . These statistical tools facilitated comparisons among instruments and may prove useful in other setting",
"Summary A simple pressure dolorimeter for the detection and quantification of joint tenderness is described and evaluated . The pressure dolorimeter was more sensitive than a modified Ritchie Index in measuring degree of joint tenderness and as sensitive in detecting tender joints . The interobserver error of the pressure dolorimeter was low , and in a drug withdrawal study , the pressure dolorimeter was able to detect change in joint tenderness whereas the conventional Ritchie Index was not . These results suggest that the pressure dolorimeter is a simple , reliable and sensitive instrument for measuring joint tenderness in patients with inflammatory joint disease . It is also inexpensive and readily available",
"Five health status instruments were administered in r and om order to 50 arthritis patients before and after total joint arthroplasty . Relative efficiency and sensitivity in measurement of change in pain , mobility and physical function , social role and social activity , and global health were assessed . The instruments had highly correlated scores , but had differences in certain dimensions . Inter-instrument differentials were larger for social and global outcomes than for pain or mobility . NO single instrument consistently outperformed the others . A method for determining relative efficiency is described",
"To assess the sensitivity of the Arthritis Impact Measurement Scales ( AIMS ) , we analyzed data from 3 clinical trials . One trial involving 255 patients with rheumatoid arthritis ( RA ) was a 12-week , r and omized controlled trail of diclofenac , naproxen , and aspirin . Two trials were open-label studies of 24 weeks duration that included 165 RA and 355 osteoarthritis ( OA ) patients , all of whom were treated with diclofenac . In addition to the AIMS , tender joint count , morning stiffness , and erythrocyte sedimentation rate were used as outcome measures in the trials . The AIMS results showed substantial improvements in Physical Function , Psychological Status , and Pain , as well as in overall Arthritis Impact . These improvements were detected by the time of the initial outcome assessment at 4 weeks or 8 weeks , and were detected in patients with either OA or RA . These AIMS results closely parallel improvements shown by traditional clinical measures , and demonstrate that the AIMS health status measure is sensitive to improvements in OA as well as in RA . The AIMS also detects responses produced by therapy with nonsteroidal antiinflammatory drugs ( NSAIDs ) , and these improvements can be demonstrated in as short a treatment time as 4 weeks . These findings confirm the utility of the AIMS for assessing outcome in rheumatic disease studies , and they have implication s for the design of future clinical trials of NSAIDs",
"OBJECTIVE Evaluation of joint range of motion ( ROM ) is important in the therapeutic approach to patients with rheumatoid arthritis ( RA ) . The reliability , construct validity and sensitivity to change of the Escola Paulista de Medicina (EPM)--range of motion scale that measures 10 distinct movements of small and large joints were examined . METHODS Fifty patients with active RA who were participating in an inpatient multidisciplinary treatment program were examined by 2 investigators . Twenty-five of the patients were examined both at admission and at discharge from the hospital . RESULTS The mean EPM-ROM score at study entry was 11.52 ( SD + /- 3.80 ) . The intra and inter-observer reliability of the EPM-ROM scale was high , with correlations of r = 0.91 and r = 0.85 , respectively . There was a good correlation between the EPM-ROM scale and measures of functional ability . Correlations with measures of disease activity were poor . After a mean duration of the treatment program of 4.2 weeks , patients generally improved in variables of functional status and disease activity . The improvement of the EPM-ROM score ( mean difference 1.58 , 95 % CI 0.84 - 2.32 ) was generally larger than improvement in other variables of functional status . CONCLUSION The EPM-ROM scale is a reliable instrument , and according to its correlation with measures of functional status , relevant to the performance of activities of daily living . It showed a good response to improvement of functional status and disease activity and was more sensitive to changes than other variables of functional status",
"Three widely used depression scales -- the Beck Depression Inventory ( BDI ) , Center for Epidemiological Studies Depression scale ( CES-D ) , and General Well-Being Schedule depression subscale (GWB-D)--were studied in rheumatoid arthritis ( RA ) . Twenty-three rheumatologists identified 19 of the 45 items on these three question naires as likely to differ in patients with RA and control subjects because of the presence of RA , regardless of psychological status . Responses to 13 of these 19 individual scale items , design ated as \" RA-related items , \" differed significantly in 41 RA patients versus 57 age-matched control subjects . Only three of the other 26 items differed significantly in the two groups . These data extend evidence that responses of people with RA on widely used depression scales might be affected by somatic disease regardless of psychological status",
"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",
"The intra-observer , inter-observer , day-to-day , week-to-week and diurnal variations in grip strength measurement have been studied in patients with rheumatoid arthritis . In addition , the changes in grip strength measurements in a double-blind , cross-over trial of Sodium Salicylate and Prednisolone are reported . An intra-observer error of up to 9 mmHg was found and , in addition , there was also considerable variation in grip strength measurements between different observers . Grip strength is responsive to Sodium Salicylate and Prednisolone therapy but the change in association with the former was minimal — indicating insensitivity of the test . In clinical trials , measurement of grip strength should not only be performed by one observer for each patient but measurements should be made at the same time of day because of its diurnal variation . The inherent errors in the method should be considered when interpreting results of grip strength measurement in such trials",
" We describe an index of functional impairment and a system of scoring joint tenderness for use in the assessment of ankylosing spondylitis . The functional index consists of 20 questions and the articular index is based on the scoring of a total of 10 joint responses after movement or firm digital pressure . These indices are simple to establish and not time consuming . They have a high degree of intra- and interobserver reproducibility . The indices showed changes in short term clinical trials of antiinflammatory drugs ; these changes were highly correlated with the patient 's overall assessment of his own clinical condition",
"The histopathological characteristic of ankylosing spondylitis ( AS ) is the presence of chronic enthesitis . Our aim was to develop a clinical measurement of the severity of tenderness over entheses . The scoring system was based on the patients ' response to palpation over entheses easily accessible to examination . The enthesis index ( EI ) correlated with pain ( r = 0.67 , p less than 0.01 ) and stiffness ( r = 0.46 , p less than 0.05 ) scores . A single , blind , crossover study was conducted to determine the sensitivity of the index to change in clinical state associated with non-steroidal antirheumatic drug therapy and to record the interobserver variability . The index showed significantly lower scores after one week 's drug treatment ( p less than 0.05 ) . The EI is a convenient , non-invasive measure of disease severity in patients with AS . Potential applications include the assessment of enthesitis in other polyarthritides and a means of distinguishing clinical ly between severity of enthesitis and synovitis in different types of polyarthritis ",
"OBJECTIVE To test the precision of a new electronic method for measuring joint tenderness . METHOD Joint tenderness was measured in 30 patients with rheumatoid arthritis , using an electronic dolorimeter . The results were compared with joint tenderness counts , which were made according to the American Rheumatism Association ( ARA ) methods . RESULTS The intra-observer variability using the electronic method was significantly decreased compared with the conventional ARA joint tenderness counts . CONCLUSION The electronic method is more efficient for use in clinical trials than is the conventional ARA joint tenderness count",
"OBJECTIVE To investigate the validity of the 28-joint count for assessment of joint involvement in patients with rheumatoid arthritis ( RA ) . METHODS Joint involvement as determined by the 28- and the 66/68-joint count was compared using data from 735 prospect ively studied RA patients . RESULTS The joints included in the 28-joint count were more commonly involved than other joints , and findings from the 28-joint count correlated highly with those from the 66/68-joint count in all analyses . CONCLUSION The 28-joint count is a reliable and valid measure for joint assessment . It is easier to perform than the 66/68-joint count , and it addresses the joints that are critically involved"
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4117a4b0-06ff-11f0-808a-c43d1ab1c353
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Objective To conduct a systematic review of published literature on advanced neuroimaging , fluid biomarkers and genetic testing in the assessment of sport-related concussion ( SRC ) . Data sources Computerised search es of Medline , PubMed , Cumulative Index to Nursing and Allied Health Literature ( CINAHL ) , PsycINFO , Scopus and Cochrane Library from 1 January 2000 to 31 December 2016 were done . There were 3222 articles identified . Study selection In addition to medical subject heading terms , a study was included if ( 1 ) published in English , ( 2 ) represented original research , ( 3 ) involved human research , ( 4 ) pertained to SRC and ( 5 ) involved data from neuroimaging , fluid biomarkers or genetic testing collected within 6 months of injury . Ninety-eight studies qualified for review ( 76 neuroimaging , 16 biomarkers and 6 genetic testing ) . Data extraction Separate review s were conducted for neuroimaging , biomarkers and genetic testing . A st and ardised data extraction tool was used to document study design , population , tests employed and key findings . Review ers used a modified quality assessment of studies of diagnostic accuracy studies ( QUADAS-2 ) tool to rate the risk of bias , and a modified Grading of Recommendations Assessment , Development , and Evaluation ( GRADE ) system to rate the overall level of evidence for each search . Data synthesis Results from the three respective review s are compiled in separate tables and an interpretive summary of the findings is provided . Conclusions Advanced neuroimaging , fluid biomarkers and genetic testing are important research tools , but require further validation to determine their ultimate clinical utility in the evaluation of SRC . Future research efforts should address current gaps that limit clinical translation . Ultimately , research on neurobiological and genetic aspects of SRC is predicted to have major translational significance to evidence -based approaches to clinical management of SRC , much like applied clinical research has had over the past 20 years
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"We conducted a prospect i ve study to identify genome-wide changes in peripheral gene expression before and after sports-related concussion ( SRC ) . A total of 253 collegiate contact athletes underwent collection of peripheral blood mononuclear cells ( P BMC s ) before the sport season ( baseline ) . Sixteen athletes who subsequently developed an SRC , along with 16 non-concussed teammate controls , underwent repeat collection of P BMC s within 6 h of injury ( acutely ) . Concussed athletes underwent additional sample collection at 7 days post-injury ( sub-acutely ) . Messenger RNA ( mRNA ) expression at baseline was compared with mRNA expression acutely and sub-acutely post-SRC . To estimate the contribution of physical exertion to gene changes , baseline sample s from athletes who subsequently developed an SRC were compared with sample s from uninjured teammate controls collected at the acute time-point . Clinical outcome was determined by changes in post-concussive symptoms , postural stability , and cognition from baseline to the sub-acute time-point . SRC athletes had significant changes in mRNA expression at both the acute and sub-acute time-points . There were no significant expression changes among controls . Acute transcriptional changes centered on interleukins 6 and 12 , toll-like receptor 4 , and NF-κB. Sub-acute gene expression changes centered on NF-κB , follicle stimulating hormone , chorionic gonadotropin , and protein kinase catalytic subunit . All SRC athletes were clinical ly back to baseline by Day 7 . In conclusion , acute post-SRC transcriptional changes reflect regulation of the innate immune response and the transition to adaptive immunity . By 7 days , transcriptional activity is centered on regulating the hypothalamic-pituitary-adrenal axis . Future efforts to compare expressional changes in fully recovered athletes with those who do not recover from SRC could suggest putative targets for therapeutic intervention",
"BACKGROUND AND PURPOSE Although concussion is common among athletes , evidence -based methods for clinical evaluation , treatment , and recovery are lacking . We used a prospect i ve , functional neuroimaging approach to assess sports-related concussion in which imaging was performed before injury so that brain changes result ing from concussion could be better understood . METHODS Neurophysiologic correlates of sports-related concussion were investigated in eight college football players by using functional MR imaging . Preseason baseline levels of blood oxygen level-dependent ( BOLD ) activity were acquired during the performance of a test battery that included mathematical , memory , and sensorimotor coordination tasks . Four players who had a concussion repeated these baseline procedures within 1 week of injury . The remaining control players were retested at the end of the season . RESULTS Specific neural signatures of concussion were detected in individual players by comparing postconcussion results to preconcussion baseline values . The validity of these indicators was confirmed by comparing them with the same measures in noninjured control subjects . When compared with control subjects , concussed players had marked within-subject increases in the amplitude and extent of BOLD activity during a finger-sequencing task . Effects were observed primarily in the parietal and lateral frontal and cerebellar regions . CONCLUSION Differences in neural functioning were observed in the absence of observed deficits in behavioral performance , suggesting that this approach may increase sensitivity to concussion compared with neuropsychological evaluation alone . Though preliminary , the proposed prospect i ve neuroimaging approach may have great potential for underst and ing mild traumatic brain injury and identifying mechanisms underlying recovery",
"Post-traumatic migraine ( PTM ) ( i.e. , headache , nausea , light and /or noise sensitivity ) is an emerging risk factor for prolonged recovery following concussion . Concussions and migraine share similar pathophysiology characterized by specific ionic imbalances in the brain . Given these similarities , patients with PTM following concussion may exhibit distinct electrophysiological patterns , although research ers have yet to examine the electrophysiological brain activation in patients with PTM following concussion . A novel approach that may help differentiate brain activation in patients with and without PTM is brain network activation ( BNA ) analysis . BNA involves an algorithmic analysis applied to multichannel EEG-ERP data that provides a network map of cortical activity and quantitative data during specific tasks . A prospect i ve , repeated measures design was used to evaluate BNA ( during Go/NoGo task ) , EEG-ERP , cognitive performance , and concussion related symptoms at 1 , 2 , 3 , and 4 weeks post-injury intervals among athletes with a medically diagnosed concussion with PTM ( n = 15 ) and without ( NO-PTM ) ( n = 22 ) ; and age , sex , and concussion history matched controls without concussion ( CONTROL ) ( n = 20 ) . Participants with PTM had significantly reduced BNA compared to NO-PTM and CONTROLS for Go and NoGo components at 3 weeks and for NoGo component at 4 weeks post-injury . The PTM group also demonstrated a more prominent deviation of network activity compared to the other two groups over a longer period of time . The composite BNA algorithm may be a more sensitive measure of electrophysiological change in the brain that can augment established cognitive assessment tools for detecting impairment in individuals with PTM",
"Background The incidence of concussion in professional direct-contact sports , particularly in rugby , has increased in recent years . To date , cognitive assessment is the most common means of determining whether a concussed player can return to the game . Serum S100B assay , an objective blood test known to be useful in brain injury management , may offer a novel additional approach to the management of concussed male rugby players . Objective The aim of this study was to investigate the S100B utility for the determination of concussion in a professional 15-players-a-side rugby team . Methods Thirty-nine male rugby players were included in a prospect i ve study during the 2014–2015 French championship season . Serum sampling was carried out several times at baseline and after a match and /or a concussion , at set times ( 2 , 36 h ) . Serum S100B concentrations were determined using chemiluminescence immunoassay on a Roche Diagnostics ® instrument . Results The players ’ basal serum S100B was stable during the season and was not correlated with anthropometric data , body composition , or creatine kinase concentration . A significant increase in S100B concentration within 2 h after a game ( without concussion ) was observed . This increase was correlated with the number of body collisions during a match . Seventy-seven assays were performed 36 h after a game , including the follow-up of five concussed players . Thirty-six hours after a match , an increase of a minimum of 20 % compared with individual basal concentrations identified concussion with 100 % sensitivity and 81 % specificity . ConclusionS 100B measured 36 h after a match is thus a discriminating test to identify concussion in a male rugby player , with a 100 % negative predictive value",
"Background Advanced neuroimaging studies in concussion have been limited to detecting group differences between concussion patients and healthy controls . In this small pilot study , we used brain magnetic resonance imaging ( MRI ) CO2 stress testing to longitudinally assess cerebrovascular responsiveness ( CVR ) in individual sports-related concussion ( SRC ) patients . Methods Six SRC patients ( three males and three females ; mean age = 15.7 , range = 15–17 years ) underwent longitudinal brain MRI CO2 stress testing using blood oxygen level-dependent ( BOLD ) MRI and model-based prospect i ve end-tidal CO2 targeting under isoxic conditions . First-level and second-level comparisons were undertaken using statistical parametric mapping ( SPM ) to score the scans and compare them to an atlas of 24 healthy control subjects . Results All tests were well tolerated and without any serious adverse events . Anatomical MRI was normal in all study participants . The CO2 stimulus was consistent between the SRC patients and control subjects and within SRC patients across the longitudinal study . Individual SRC patients demonstrated both quantitative and qualitative patient-specific alterations in CVR ( p brain MRI CO2 stress testing is capable of providing a longitudinal assessment of CVR in individual SRC patients . Consequently , larger prospect i ve studies are needed to examine the utility of brain MRI CO2 stress testing as a clinical tool to help guide the evaluation , classification , and longitudinal management of SRC patients",
"Background The on-field diagnosis of sports-related concussion ( SRC ) is complicated by the lack of an accurate and objective marker of brain injury . Purpose To compare subject-specific changes in the astroglial protein , S100B , before and after SRC among collegiate and semi-professional contact sport athletes , and compare these changes to differences in S100B before and after non-contact exertion . Study Design Longitudinal cohort study . Methods From 2009–2011 , we performed a prospect i ve study of athletes from Munich , Germany , and Rochester , New York , USA . Serum S100B was measured in all SRC athletes at pre-season baseline , within 3 hours of injury , and at days 2 , 3 and 7 post-SRC . Among a subset of athletes , S100B was measured after non-contact exertion but before injury . All sample s were collected identically and analyzed using an automated electrochemiluminescent assay to quantify serum S100B levels . Results Forty-six athletes ( 30 Munich , 16 Rochester ) underwent baseline testing . Thirty underwent additional post-exertion S100B testing . Twenty-two athletes ( 16 Rochester , 6 Munich ) sustained a SRC , and 17 had S100B testing within 3 hours post-injury . The mean 3-hour post-SRC S100B was significantly higher than pre-season baseline ( 0.099±0.008 µg/L vs. 0.058±0.006 µg/L , p = 0.0002 ) . Mean post-exertion S100B was not significantly different than the preseason baseline . S100B levels at post-injury days 2 , 3 and 7 were significantly lower than the 3-hour level , and not different than baseline . Both the absolute change and proportional increase in S100B 3-hour post-injury were accurate discriminators of SRC from non-contact exertion without SRC ( AUC 0.772 and 0.904 , respectively ) . A 3-hour post-concussion S100B > 0.122 µg/L and a proportional S100B increase of > 45.9 % over baseline were both 96.7 % specific for SRC . Conclusions Relative and absolute increases in serum S100B can accurately distinguish SRC from sports-related exertion , and may be a useful adjunct to the diagnosis of SRC",
"Our aim was to quantify with functional magnetic resonance imaging ( fMRI ) changes in brain activity in concussed athletes and compare the results with those of normal control subjects . Regional brain activations associated with a working memory task were obtained from a group of concussed athletes ( 15 symptomatic , 1 asymptomatic ) and eight matched control subjects , using blood oxygen level dependent ( BOLD ) fMRI . The average percent signal change from baseline to working memory condition in each region of interest was computed . Symptomatic concussed athletes demonstrated task-related activations in some but not all the regions of interest , even when they performed as well as the control subjects . Furthermore , several concussed athletes had additional increases in activity outside the regions of interest , not seen in the control group . Quantitative analysis of BOLD signals within regions of interest revealed that , in general , concussed athletes had different BOLD responses compared to the control subjects . The task-related activation pattern of the one symptom-free athlete was comparable to that of the control group . We also repeated the study in one athlete whose symptoms had resolved . On the first study , when he was still symptomatic , less task-related activations were observed . On follow-up , once his symptoms had disappeared , the task-related activations became comparable to those of the control group . These results demonstrate the potential of fMRI , in conjunction with the working memory task , to identify an underlying pathology in symptomatic concussed individuals with normal structural imaging results",
"Impact-related mild traumatic brain injuries ( mTBI ) are a major public health concern , and remain as one of the most poorly understood injuries in the field of neuroscience . Currently , the diagnosis and management of such injuries are based largely on patient-reported symptoms . An improved underst and ing of the underlying pathophysiology of mTBI is urgently needed in order to develop better diagnostic and management protocol s. Specifically , dynamic post-injury changes to the myelin sheath in the human brain have not been examined , despite ‘ compromised white matter integrity ’ often being described as a consequence of mTBI . In this preliminary cohort study , myelin water imaging was used to prospect ively evaluate changes in myelin water fraction , derived from the T2 decay signal , in two varsity hockey teams ( 45 players ) over one season of athletic competition . 11 players sustained a concussion during competition , and were scanned at 72 hours , 2 weeks , and 2 months post-injury . Results demonstrated a reduction in myelin water fraction at 2 weeks post-injury in several brain areas relative to preseason scans , including the splenium of the corpus callosum , right posterior thalamic radiation , left superior corona radiata , left superior longitudinal fasciculus , and left posterior limb of the internal capsule . Myelin water fraction recovered to pre-season values by 2 months post-injury . These results may indicate transient myelin disruption following a single mTBI , with subsequent remyelination of affected neurons . Myelin disruption was not apparent in the athletes who did not experience a concussion , despite exposure to repetitive subconcussive trauma over a season of collegiate hockey . These findings may help to explain many of the metabolic and neurological deficits observed clinical ly following mTBI",
"OBJECTIVE The relationship between athlete reports of symptoms , neurophysiological activation , and neuropsychological functioning is investigated in a sample of high school athletes . METHODS All athletes were evaluated using functional magnetic resonance imaging ( fMRI ) , a computer-based battery of neurocognitive tests , and a subjective symptom scale . Athletes were evaluated within approximately 1 week of injury and again after clinical recovery using all assessment modalities . RESULTS This study found that abnormal fMRI results during the first week of recovery predicted clinical recovery . As a group , athletes who demonstrated hyperactivation on fMRI scans at the time of their first fMRI scan demonstrated a more prolonged clinical recovery than athletes who did not demonstrate hyperactivation at the time of their first fMRI scan . CONCLUSION These results demonstrate the relationship between neurophysiological , neuropsychological , and subjective symptom data in a relatively large sample composed primarily of concussed high school athletes . fMRI represents an important evolving technology for the underst and ing of brain recovery after concussion and may help shape return-to-play guidelines in the future",
"Objective To investigate the clinical utility and sensitivity of a portable , automatic , frontal quantitative electroencephalographic ( QEEG ) acquisition device currently in development in detecting abnormal brain electrical activity after sport-related concussion . Design This was a prospect i ve , non-r and omized study of 396 high school and college football players , including cohorts of 28 athletes with concussion and 28 matched controls . All subjects underwent preseason baseline testing on measures of postconcussive symptoms , postural stability , and cognitive functioning , as well as QEEG . Clinical testing and QEEG were repeated on day of injury and days 8 and 45 postinjury for the concussion and control groups . Main Outcomes and Results The injured group reported more significant postconcussive symptoms during the first 3 days postinjury , which resolved by days 5 and 8 . Injured subjects also performed poorer than controls on neurocognitive testing on the day of injury , but no differences were evident on day 8 or day 45 . QEEG studies revealed significant abnormalities in electrical brain activity in the injured group on day of injury and day 8 postinjury , but not on day 45 . Conclusions Results from the current study on clinical recovery after sport-related concussion are consistent with early reports indicating a typical course of full recovery in symptoms and cognitive dysfunction within the first week of injury . QEEG results , however , suggest that the duration of physiological recovery after concussion may extend longer than observed clinical recovery . Further study is required to replicate and extend these findings in a larger clinical sample , and further demonstrate the utility of QEEG as a marker of recovery after sport-related concussion",
"Objective : To examine functional brain activation patterns before and after postconcussive symptoms ( PCS ) resolution . Design : Prospect i ve serial study with male athletes using functional magnetic resonance imaging ( fMRI ) . Setting : Hospital laboratory and imaging facility . Participants : 9 symptomatic concussed athletes who experienced persisting PCS at least 1 month postinjury and 6 healthy athletes . Interventions : All athletes filled out a PCS checklist and underwent an fMRI session during which they performed a working-memory task . Main outcome measurements : Behavioral outcomes were response speed and accuracy on the working memory tasks performed during the fMRI session . Functional imaging outcomes were blood oxygen level-dependent fMRI activation patterns associated with a working memory task . Results : There was no difference in behavioral performance between the groups . Despite normal structural MRI findings , all symptomatic concussed athletes initially showed atypical brain activation patterns in the dorsolateral prefrontal cortex ( DLPC ) . Compared to the initial postinjury evaluation , those athletes at follow-up with PCS resolved showed significant increases in activation in the left DLPC . Concussed athletes whose PCS status remained unchanged at follow-up continued to show atypical activation in DLPC . Healthy athletes showed remarkably clear and consistent brain activations in DLPC initially as well as in follow-up , highlighting the test-retest reliability of fMRI . Conclusions : The results demonstrate the feasibility of using fMRI to detect an underlying pathology in symptomatic concussed athletes with normal structural imaging results and its potential to document recovery . Such information may be of considerable value for clinical judgment and patient management",
"Abstract Objective : To determine genetic variability within the N-methyl-D-aspartate receptor 2A sub-unit ( GRIN2A ) gene promoter and its association with concussion recovery time . The hypothesis tested was that there would be a difference in allele and /or genotype distribution between two groups of athletes with normal and prolonged recovery . Methods : DNA was extracted from saliva collected from a total of 87 athletes with a physician-diagnosed concussion . The ( GT ) variable number t and em repeats ( VNTR ) within the promoter region of GRIN2A was genotyped . The long ( L ) allele was an allele with ≥25 repeats and the short ( S ) allele was an allele with recovery time was followed prospect ively and was categorized as normal ( ≤60 days ) or prolonged ( > 60 days ) . Results : LL carriers were 6-times more likely to recover longer than 60 days following the concussive event ( p = 0.0433 ) when compared to SS carriers . Additionally , L allele carriers were found more frequently in the prolonged recovery group ( p = 0.048 ) . Conclusion : Determining genetic influence on concussion recovery will aid in future development of genetic counselling . The clinical relevance of genotyping athletes could improve management of athletes who experience concussion injuries ",
"The diagnosis of sports-related concussion is mainly based on subjective clinical symptoms and neuropsychological tests . Therefore , reliable brain injury biomarkers to assess when it is safe to return to play are highly desirable . The overall objective of this study was to evaluate the utility of two newly described tau fragments for diagnosis and prognosis of sports-related concussions . This multi-center prospect i ve cohort study involved all 12 teams of the top professional ice hockey league in Sweden . A total of 288 players consented to participate in the study . Thirty-five players sustained concussions , of whom 28 underwent repeated blood samplings at 1 , 12 , 36 , and 144 h after the trauma , or when the player returned to play ( 7 to > 90 days ) . There was no significant increase in the levels of Tau-A in post-concussion sample s compared with preseason values . However , serum levels of Tau-C were significantly higher in post-concussion sample s compared with preseason . Further , levels of Tau-A correlated with the duration of post-concussive symptoms . Tau-A in serum , which is newly discovered biomarker , could be used to predict when it is safe to return to play after a sports-related concussion",
"CONTEXT Lack of empirical data on recovery time following sport-related concussion hampers clinical decision making about return to play after injury . OBJECTIVE To prospect ively measure immediate effects and natural recovery course relating to symptoms , cognitive functioning , and postural stability following sport-related concussion . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 1631 football players from 15 US colleges . All players underwent preseason baseline testing on concussion assessment measures in 1999 , 2000 , and 2001 . Ninety-four players with concussion ( based on American Academy of Neurology criteria ) and 56 noninjured controls underwent assessment of symptoms , cognitive functioning , and postural stability immediately , 3 hours , and 1 , 2 , 3 , 5 , 7 , and 90 days after injury . MAIN OUTCOME MEASURES Scores on the Grade d Symptom Checklist ( GSC ) , St and ardized Assessment of Concussion ( SAC ) , Balance Error Scoring System ( BESS ) , and a neuropsychological test battery . RESULTS No player with concussion was excluded from participation ; 79 players with concussion ( 84 % ) completed the protocol through day 90 . Players with concussion exhibited more severe symptoms ( mean GSC score 20.93 [ 95 % confidence interval [ CI ] , 15.65 - 26.21 ] points higher than that of controls ) , cognitive impairment ( mean SAC score 2.94 [ 95 % CI , 1.50 - 4.38 ] points lower than that of controls ) , and balance problems ( mean BESS score 5.81 [ 95 % CI , -0.67 to 12.30 ] points higher than that of controls ) immediately after concussion . On average , symptoms gradually resolved by day 7 ( GSC mean difference , 0.33 ; 95 % CI , -1.41 to 2.06 ) , cognitive functioning improved to baseline levels within 5 to 7 days ( day 7 SAC mean difference , -0.03 ; 95 % CI , -1.33 to 1.26 ) , and balance deficits dissipated within 3 to 5 days after injury ( day 5 BESS mean difference , -0.31 ; 95 % CI , -3.02 to 2.40 ) . Mild impairments in cognitive processing and verbal memory evident on neuropsychological testing 2 days after concussion resolved by day 7 . There were no significant differences in symptoms or functional impairments in the concussion and control groups 90 days after concussion . CONCLUSIONS Collegiate football players may require several days for recovery of symptoms , cognitive dysfunction , and postural instability after concussion . Further research is required to determine factors that predict variability in recovery time after concussion . St and ardized measurement of postconcussive symptoms , cognitive functioning , and postural stability may enhance clinical management of athletes recovering from concussion",
"BACKGROUND AND PURPOSE : DTI of normal-appearing WM as evaluated by conventional MR imaging in mTBI has the potential to identify important regional abnormalities that relate to PCS . VBA was used to examine WM changes in acute mTBI . MATERIAL S AND METHODS : WM was assessed between 1 and 6 days postinjury with voxel-based DTI analyses in 10 adolescent patients with mTBI and 10 age-matched control participants . In addition to the voxel-based group , analysis used to identify brain pathology across all patients with mTBI , 2 voxel-based linear regressions were performed . These analyses investigated the relation between 1 ) the ADC and PCS severity scores , and 2 ) ADC and scores on the BSI of emotional symptoms associated with mTBI . We hypothesized that frontotemporal WM changes would relate to symptoms associated with PCS and endorsed on the BSI . RESULTS : Patients with mTBI demonstrated significant reductions in ADC in several WM regions and in the left thalamus . As expected , no increases in ADC were found in any region of interest . All injury-affected regions showed decreased radial diffusivity , unchanged AD , and increased FA , which is consistent with axonal cytotoxic edema , reflective of acute injury . CONCLUSIONS : Whole-brain WM DTI measures can detect abnormalities in acute mTBI associated with PCS symptoms in adolescents",
"IMPORTANCE Lack of objective biomarkers for brain damage hampers acute diagnosis and clinical decision making about return to play after sports-related concussion . OBJECTIVES To determine whether sports-related concussion is associated with elevated levels of blood biochemical markers of injury to the central nervous system and to assess whether plasma levels of these biomarkers predict return to play in professional ice hockey players with sports-related concussion . DESIGN , SETTING , AND PARTICIPANTS Multicenter prospect i ve cohort study involving all 12 teams of the top professional ice hockey league in Sweden , the Swedish Hockey League . Two hundred eighty-eight professional ice hockey players from 12 teams contesting during the 2012 - 2013 season consented to participate . All players underwent clinical preseason baseline testing regarding concussion assessment measures . Forty-seven players from 2 of the 12 ice hockey teams underwent blood sampling prior to the start of the season . Thirty-five players had a concussion from September 13 , 2012 , to January 31 , 2013 ; of these players , 28 underwent repeated blood sampling at 1 , 12 , 36 , and 144 hours and when the players returned to play . MAIN OUTCOMES AND MEASURES Total tau , S-100 calcium-binding protein B , and neuron-specific enolase concentrations in plasma and serum were measured . RESULTS Concussed players had increased levels of the axonal injury biomarker total tau(median , 10.0 pg/mL ; range , 2.0 - 102 pg/mL ) compared with preseason values ( median , 4.5pg/mL ; range , 0.06 - 22.7 pg/mL ) ( P levels of the astroglial injury biomarker S-100 calcium-binding protein B were also increased in players with sports-related concussion(median , 0.075 μg/L ; range , 0.037 - 0.24 μg/L ) compared with preseason values ( median,0.045 μg/L ; range , 0.005 - 0.45 μg/L ) ( P concentrations of total tau and S-100 calcium-binding protein B were measured immediately after a concussion , and they decreased during rehabilitation . No significant changes were detected in the levels of neuron-specific enolase from preseason values ( median , 6.5 μg/L ; range,3.45 - 18.0 μg/L ) to postconcussion values ( median , 6.1 μg/L ; range , 3.6 - 12.8 μg/L ) ( P = .10 ) . CONCLUSIONS AND RELEVANCE Sports-related concussion in professional ice hockey players is associated with acute axonal and astroglial injury . This can be monitored using blood biomarkers , which may be developed into clinical tools to guide sport physicians in the medical counseling of athletes in return-to-play decisions",
"Abstract Primary objective : Visinin-like protein-1 ( VILIP-1 ) has shown potential utility as a biomarker for neuronal injury in cerebrospinal fluid . This study investigated serum VILIP-1 as a diagnostic and prognostic marker in sports-related concussion . Methods : This multi-centre prospect i ve cohort study involved the 12 teams of the professional ice hockey league in Sweden . A total of 288 players consented to participate in the study . Thirty-five players sustained concussions , of whom 28 underwent repeated blood samplings at 1 , 12 , 36 and 144 hours after the trauma or when the player returned to play ( 7–90 + days ) . Main outcomes and results : The highest levels of VILIP-1 were measured 1 hour after concussion and the levels decreased during rehabilitation , reaching a minimum level at the 36-hour sampling . However , the levels of serum VILIP-1 at 1 hour after concussion were not significantly higher than pre-season baseline values . Serum levels of VILIP-1 1 hour post-concussion did not correlate with the number of days for the concussion symptoms to resolve . Further , serum levels of VILIP-1 increased after a friendly game in players who were not concussed . Conclusions : These results provide evidence that serum VILIP-1 may not be a useful biomarker for diagnosis and prognosis of sports-related concussion",
"IMPORTANCE Animal models suggest that reduced cerebral blood flow ( CBF ) is one of the most enduring physiological deficits following concussion . Despite this , longitudinal studies documenting serial changes in regional CBF following human concussion have yet to be performed . OBJECTIVE To longitudinally assess the recovery of CBF in a carefully selected sample of collegiate athletes and compare time course of CBF recovery with that of cognitive and behavioral symptoms . DESIGN , SETTING , AND PARTICIPANTS A cohort of collegiate football athletes ( N = 44 ) participated in this mixed longitudinal and cross-sectional study at a private research institute specializing in neuroimaging between March 2012 and December 2013 . Serial imaging occurred approximately 1 day , 1 week , and 1 month postconcussion for a subset of participants ( n = 17 ) . All athletes reported no premorbid mood disorders , anxiety disorders , substance abuse , or alcohol abuse . MAIN OUTCOMES AND MEASURES Arterial spin labeling magnetic resonance imaging was used to collect voxelwise relative CBF at each visit . Neuropsychiatric evaluations and a brief cognitive screen were also performed at all 3 points . Clinicians trained in sports medicine provided an independent measure of real-world concussion outcome ( ie , number of days withheld from competition ) . RESULTS The results indicated both cognitive ( simple reaction time ) and neuropsychiatric symptoms at 1 day postinjury that resolved at either 1 week ( cognitive ; P CBF recovery in the right insular and superior temporal cortex . Importantly , CBF in the dorsal midinsular cortex was both decreased at 1 month postconcussion in slower-to-recover athletes ( t11 = 3.45 ; P = .005 ) and was inversely related to the magnitude of initial psychiatric symptoms ( Hamilton Depression Scale : r = -0.64 , P = .02 ; Hamilton Anxiety Scale : r = -0.56 , P = .046 ) , suggesting a potential prognostic indication for CBF as a biomarker . CONCLUSIONS AND RELEVANCE To our knowledge , these results provide the first prospect i ve evidence of reduced CBF in human concussion and subsequent recovery . The resolution of CBF abnormalities closely mirrors previous reports from the animal literature and show real-world validity for predicting outcome following concussion"
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OBJECTIVE The aim of this study was to identify if different types of indirect restorations used for single teeth had different biological and technical complications , as well as survival rates . METHOD An electronic search was performed in various electronic data bases to identify articles , published between 1980 and 2017 . The search terms were categorised into 4 groups : inlay , onlay , inlay/onlay and crown . Manual search es of published full-text articles and related review s were also performed . RESULTS A total number of 2849 papers were retrieved initially . After a detailed assessment for eligibility , 9 studies were selected for inclusion . The heterogeneity of the studies did allow neither a meta- analysis nor any meaningful comparison between types of restorations or material s. Only some pooling was performed for representative reasons . The mean survival rate of inlays was 90.89 % , while for onlays and crowns it was 93.50 % and 95.38 % , respectively . For the fourth study group , consisting of both inlays and onlays , the survival rate was found to be 99.43 % . Statistical analysis demonstrated caries to be the main biological complication for all types of restorations , followed by a root and /or tooth fracture incidence ( 11.34 % ) and endodontic incidence . Ceramic fractures represented the most common technical complication , followed by loss of retention and porcelain chipping . CONCLUSION The 5-year survival rate for crowns and inlays/onlays is very high , exceeding 90 % . An association between the kind of complications and different types of restorations could not be established . Nevertheless , a relatively high failure rate due to caries and ceramic fractures was noted
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"PURPOSE To clinical ly evaluate an all-ceramic restorative system ( Finesse All-Ceramic ) when used in conjunction with an ultra-low fusing porcelain ( Finesse ) using bonded esthetic resin cements ( Enforce & Calibra ) . METHODS This report describes the 3-year results of a prospect i ve , consecutive case clinical evaluation for Finesse All-Ceramic . Forty posterior and anterior crowns , 20 all ceramic inlays and onlays , and 26 veneers were placed in 43 patients at the initiation of this study . St and ard ceramic preparations were performed followed by conventional polyvinylsiloxane ( Aquasil ) impression techniques using cord retraction . The bonded resin cement was used to place the restorations following manufacturer 's instructions . RESULTS A majority of restorations ( 95 - 100 % ) were evaluated to be optimal at baseline ( B ) , 1 month , 12 , 24 and 36 months using a modified Ryge criteria for the following categories : color match , marginal adaptation , porcelain staining , secondary caries , postoperative sensitivity , and retention . Assessment of color match at 36 months result ed in 97 % of all crowns and 100 % of all veneers and onlays being rated alfa for shade match to Vita Lumin shade guide . The overall 3-year success rate at the 3-year recall ( inlay/onlays , crowns , and veneers ) was 98.57 % , with the success rate for crowns and veneers at this time period being 100 %",
"OBJECTIVES The purpose of this study was to investigate the durability of extensive dentin-enamel-bonded posterior ceramic coverages in a 15 years follow-up . METHODS All extensive dentin-enamel-bonded posterior partial and complete all-ceramic coverages placed during the period November 1992-December 1998 were included . In 121 patients , 252 coverages ( IPS Empress ) were placed . The adhesive bonding to dentin and enamel was performed with three 3-step and one 2-step etch and rinse bonding . In 106 restorations the classic Syntac was used in combination with the dual-cured resin composite Variolink . The other restorations were luted with the chemically cured resin composite Bisfil 2B and bonded with 3-step etch and rinse systems , classic Gluma ( 37 ) , Allbond 2 ( 57 ) , Syntac ( 32 ) or the 2-step etch and rinse system , One step ( 20 ) . The ceramics were evaluated yearly by modified USPHS criteria during 15 years . RESULTS Postoperative sensitivity was registered in 4 patients during bite forces lasting for 2 - 4 weeks . Fifty-five of 228 coverages ( 24.1 % ) failed . The mean observation period of the acceptable coverages was 12.6 years ( range 11 - 15 years ) . The main reasons for failure were lost restorations ( 18 ) , ceramic fracture ( 16 ) , and secondary caries ( 11 ) . Significant differences in failure rate were observed between the dentin bonding agents but not between the two luting agents . Ceramic coverages placed on non-vital teeth failed in 39 % and on vital teeth in 20.9 % ( p=0.014 ) . Logistic regression indicated three significant predictors for failure of the coverages : gender and parafunctional habits of the patient and non-vitality of the tooth . SIGNIFICANCE The technique investigated showed advantages like less destruction of healthy tissue , and avoiding of endodontic treatment and /or deep cervical placement of restoration margins to obtain retention",
"The aim of this r and omized controlled clinical trial was to compare the early clinical outcome of slip-cast glass-infiltrated Alumina/Zirconia and CAD/CAM Zirconia all-ceramic crowns . A total of 30 InCeram ® Zirconia and Cercon ® Zirconia crowns were fabricated and cemented with a glass ionomer cement in 20 patients . At baseline , 6-month , 1-year , and 2-year recall appointments , Californian Dental Association ( CDA ) quality evaluation system was used to evaluate the prosthetic replacements , and plaque and gingival index scores were used to explore the periodontal outcome of the treatments . No clinical sign of marginal discoloration , persistent pain and secondary caries was detected in any of the restorations . All InCeram ® Zirconia crowns survived during the 2-year period , although one nonvital tooth experienced root fracture coupled with the fracture of the veneering porcelain of the restoration . One Cercon ® Zirconia restoration fractured and was replaced . According to the CDA criteria , marginal integrity was rated excellent for InCeram ® Zirconia ( 73 % ) and Cercon ® Zirconia ( 80 % ) restorations , respectively . Slight color mismatch rate was higher for InCeram ® Zirconia restorations ( 66 % ) than Cercon ® Zirconia ( 26 % ) restorations . Plaque and gingival index scores were mostly zero and almost constant over time . Time-dependent changes in plaque and gingival index scores within and between groups were statistically similar ( p>0.05 ) . This clinical study demonstrates that single-tooth InCeram ® Zirconia and Cercon ® Zirconia crowns have comparable early clinical outcome , both seem as acceptable treatment modalities , and most importantly , all-ceramic alumina crowns strengthened by 25 % zirconia can sufficiently withst and functional load in the posterior zone",
"OBJECTIVES The literature demonstrates that conventional luting of metal-based restorations using zinc phosphate cements is clinical ly successful over 20 years . This study compared the clinical outcomes of metal-based fixed partial dentures luted conventionally with zinc phosphate and self-adhesive resin cement . METHODS Forty-nine patients ( mean age 54+/-13 years ) received 49 metal-based fixed partial dentures r and omly luted using zinc phosphate ( Richter & Hoffmann , Berlin , Germany ) or self-adhesive resin cement ( RelyX Unicem Aplicap , 3 M ESPE , Germany ) at the University Medical Center Regensburg . The core build-up material was highly viscous glass ionomer ; the finishing line was in dentin . The study included 42 posterior , 5 anterior crowns and two onlays . Forty-seven restorations were made of precious alloys , 2 of non-precious alloys . The restorations were clinical ly examined every year . The clinical performance was checked for plaque ( 0 - 5 ; PI , Quigley-Hein ) , bleeding ( 0 - 4 ; PBI ; Mühlemann ) and attachment scores . The examination included pulp vitality and percussion tests . STATISTICS Means of scores , st and ard deviation , cumulative survival and complication rates were calculated using life tables . RESULTS The mean observation time was 3.16+/-0.6 years ( min : 2.0 ; max : 4.5 years ) . During that time no restoration was lost , no recementation became necessary . One endodontic treatment was performed in the self-adhesive composite group after 2.9 years . At study end bleeding ( 1.44 RelyX Unicem vs. 1.25 zinc phosphate ) and plaque ( 1.64 RelyX Unicem vs. 1.0 zinc phosphate ) scores showed no statistically significant difference . SIGNIFICANCE The self-adhesive resin cement performed clinical ly as well and can be used as easily as zinc phosphate cement to retain metal-based restorations over a 38-month observation period",
"STATEMENT OF PROBLEM Few long-term clinical studies have reported data of modern posterior composites as direct and indirect restorations . PURPOSE This prospect i ve , long-term clinical trial ( 1 ) evaluated direct and indirect composite restorations for clinical acceptability as posterior restoratives in single or multisurface carious teeth and ( 2 ) provided a survey on the 2-year results . MATERIAL AND METHODS Nine dental students placed 88 composite restorations ( Tetric , blend-a-lux , Pertac-Hybrid Unifil ) , 43 direct composite restorations and 45 indirect inlays , under the supervision of an experienced dentist . The first clinical evaluation was performed 11 to 13 months after placement by 2 other experienced dentists , using modified USPHS criteria . A second follow-up of 60 restorations took place within 20 to 26 months after placement . RESULTS A total of 93 % of indirect and 90 % of direct composite restorations were assessed to be clinical ly excellent or acceptable . Two restorations ( 1 indirect composite inlay and 1 margin of a direct composite restoration ) failed during the second year because of fracture . Indirect inlays demonstrated a significantly better \" anatomic form of the surface \" than direct composite restorations . Premolars revealed a significantly better margin integrity and postoperative symptoms than molars . CONCLUSION Posterior composite restorations provided a satisfactory clinical performance over a 2-year period when placed by relatively inexperienced but supervised students",
"BACKGROUND Adhesively luted all-ceramic restorations preserve and stabilize weakened tooth structure , but there is little published information about the clinical performance of large , all-ceramic restorations . METHODS In this pilot study , the authors placed 58 large , single-tooth , all-ceramic restorations in 26 patients using a computer-aided design /computer-aided manufacturing , or CAD/CAM , system ( CEREC 2 , Sirona Dental Systems GmbH , Bensheim , Germany ) . They documented the maximum height of the restoration and remaining cementoenamel junction , or CEJ . In 21 cases , rubber dam isolation was not possible during adhesive luting . They re-evaluated the restorations after three years according to the U.S. Public Health Service criteria . RESULTS After three years , the authors rated 56 ( 97 percent ) of the 58 restorations as Bravo or better in regard to marginal integrity , secondary caries ( four could not be rated ) , discoloration and anatomical form . One restoration was rated as Charlie because of poor marginal integrity , and one restoration had to be replaced owing to a bulk fracture . The authors rated the adequacy of proximal contact and occlusal relationships as acceptable-to-good for all restorations . Neither the extent of the remaining enamel at the cavity margin nor application of a rubber dam had any statistically significant influence ( chi2 test , P > .05 ) on the clinical performance of the restorations after three years . CONCLUSIONS At the three-year recall appointment , the authors found that the adhesively luted all-ceramic restorations had successfully repaired large coronal defects , irrespective of the cavity margin location ( that is , coronal or apical to the CEJ ) . CLINICAL IMPLICATION S Tooth-colored , all-ceramic CAD/CAM-generated restorations are an alternative to conventional restorations if large coronal defects need to be treated",
"The gathering of clinical data on fractures of dental restorations through prospect i ve clinical trials is a labor- and time-consuming enterprise . Here , we propose an unconventional approach for collecting large data sets , from which clinical information on indirect restorations can be retrospectively analyzed . The authors accessed the data base of an industry-scale machining center in Germany and obtained information on 34,911 computer-aided design (CAD)/computer-aided manufacturing ( CAM ) all-ceramic posterior restorations . The fractures of bridges , crowns , onlays , and inlays fabricated from different all-ceramic systems over a period of 3.5 y were reported by dentists and entered in the data base . Survival analyses and estimations of future life revealed differences in performance among ZrO2-based restorations and lithium disilicate and leucite-reinforced glass-ceramics",
"Compomers , resin-modified glass ionomers , were developed to improve the physical properties and clinical h and ling of glass ionomers . Compomers can be design ed to be light-activated and used as restoratives or liners . This article reports data collected up to 12 months after placement of both compomer restorations and liners and is part of an ongoing study evaluating the performance of this material . Based on this data , the authors conclude that this new generation of light-activated glass-ionomer restoratives provides clinical results comparable to those recorded for composite resins at 12 months",
"AIM It is the aim of this paper to consider the factors associated with the need for re-intervention on a crown , and the times to re-intervention . METHODS A data set was established consisting of patients , 18 years or older , whose birthdays were included within a set of a r and omly selected date s , one of which was chosen in each possible year of birth and whose restoration records contained the placement of one or more indirect restorations on courses of treatment with last date on the cl aim form after 31st December 1990 , and with date of acceptance after September 1990 and before January 2002 . For each tooth treated with a crown , the subsequent history of intervention on that tooth was consulted , and the next date of intervention , if any could be found in the extended data set , was obtained . Thus , a data set was created of crowns which have been placed , with their date s of placement and their date s , if any , of re-intervention . RESULTS Data for over 80,000 different adult patients were analysed , of whom 46 % were male and 54 % female . A total of 47,474 crown restoration occasions were obtained from the data over a period of 11 years . Metal crowns were found to have the longest survival-68 % at 10 years , and all-porcelain crowns the shortest-48 % at 10 years . Factors which were found to influence outcome of crowns included type of crown , age of patient , patient payment exemption status , patient attendance pattern and placement of a root filling in the same course of treatment as a crown . CONCLUSIONS Full-coverage all-metal crowns have longer survival times before re-intervention than metal-ceramic crowns and all-ceramic crowns . Root fillings are associated with reduced survival time of the crowns examined in this study",
"OBJECTIVES Midterm-evaluation of a 5-year prospect i ve clinical splitmouth-investigation on survival rate and long-term behavior of all-ceramic partial coverage restorations ( PCRs ) on molars . Pressed ceramic and CAD/CAM fabricated PCRs were compared . METHODS 80 vital molars of 25 patients were restored with all-ceramic PCRs ( 40 IPS e.max Press*[IP ] and 40 ProCAD*[PC ] ) . IP-PCRs were heat pressed following the lost-wax method . PC-PCRs were fabricated with Cerec 3 * * and Cerec InLab * * CAD/CAM system ( * * Sirona Dental Systems , Bensheim , Germany ) . All PCRs were adhesively luted with a light-polymerizing composite ( Syntac*/Tetric * ) ( * Ivoclar Vivadent , Schaan , Liechtenstein ) . Clinical reevaluations were performed at baseline and 13 , 25 , and 36 months after insertion of the PCRs according to the modified United States Public Health Services ( USPHS ) criteria . Absolute failures were demonstrated by Kaplan-Meier survival rate . RESULTS After an observation time up to 3 years , survival rate of IP-PCRs was 100 % and 97 % for PC-PCRs due to one severe fracture . The PC-PCR had to be replaced after 9 months . Secondary caries and endodontic complications did not occur . Increased clinical service time result ed in significant decrease of marginal adaptation ( p=0.031 ) and enhanced marginal discoloration ( p deteriorations in color match ( p surface roughness ( p IP-PCRs were significantly more affected ( p < or = 0.005 ) . Regarding anatomic form IP-PCRs performed significantly better ( p=0.0012 ) . CONCLUSION Pressed ceramic and CAD/CAM fabricated partial coverage restorations exhibited a reliable treatment option to restore larger defects in posterior teeth . Marginal degradation of the resin cement and deterioration of the all-ceramic material s during clinical function determine the clinical long-term performance of partial coverage restorations"
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4117a532-06ff-11f0-808a-c43d1ab1c353
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Cognitive-behavioural therapy ( CBT ) and its effects on temporom and ibular disorders ( TMD ) have been examined in several studies . We are trying to combine results of these studies and to explore the effectiveness . MEDLINE , EMBASE , Cochrane Central Register of Controlled Trial , Pubmed and the Chinese Biomedical Literature Data were search ed to collect r and omised and semi-r and omised controlled trials ( RCTs ) , comparing CBT with any control group receiving other dental treatments . Two authors independently retrieved , extracted and assessed the quality of included studies . The search strategy result ed in 323 studies , of which five met the inclusion criteria , including three RCTs and two semi- RCTs . The quality of the included studies was diverse . Meta- analysis was not performed owing to five studies involving different comparison groups and follow-up periods . The effect of CBT on patients with TMD is inconsistent among the studies , so no firm conclusion could be drawn in this systematic review . There is insufficient evidence to make firm recommendations for the use of CBT over other intervention for the treatment of TMD . Further high- quality RCTs are clearly needed for this theme
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"Abstract Although cognitive – behavioral therapies ( CBT ) have been demonstrated to be effective for a variety of chronic pain problems , patients vary in their response and little is known about patient characteristics that predict or moderate treatment effects . Furthermore , although cognitive – behavioral theory posits that changes in patient beliefs and coping mediate the effects of CBT on patient outcomes , little research has systematic ally tested this . Therefore , we examined mediators , moderators , and predictors of treatment effects in a r and omized controlled trial of CBT for chronic temporom and ibular disorder ( TMD ) pain . Pre‐ to post‐treatment changes in pain beliefs ( control over pain , disability , and pain signals harm ) , catastrophizing , and self‐efficacy for managing pain mediated the effects of CBT on pain , activity interference , and jaw use limitations at one year . In individual mediator analyses , change in perceived pain control was the mediator that explained the greatest proportion of the total treatment effect on each outcome . Analyzing the mediators as a group , self‐efficacy had unique mediating effects beyond those of control and the other mediators . Patients who reported more pain sites , depressive symptoms , non‐specific physical problems , rumination , catastrophizing , and stress before treatment had higher activity interference at one year . The effects of CBT generally did not vary according to patient baseline characteristics , suggesting that all patients potentially may be helped by this therapy . The results provide further support for cognitive – behavioral models of chronic pain and point to the potential benefits of interventions to modify specific pain‐related beliefs in CBT and in other health care encounters",
"The purpose of this study was to evaluate the relative efficacy of different biopsychosocial treatment conditions on patients with chronic temporom and ibular disorder . Ninety-four patients with chronic temporom and ibular disorder were assigned to either a biofeedback treatment group , a cognitive-behavioral skills training ( CBST ) treatment group , a combined ( combination of biofeedback/CBST ) treatment group , or a no-treatment control group . Pain scores were analyzed pretreatment and posttreatment to determine group and within-subjects treatment effects . Results demonstrated that , in terms of a self-reported pain score , all three treatment groups had significantly decreased pain scores from pretreatment to posttreatment , while the no-treatment group did not . Moreover , patients in the biofeedback group were the most significantly improved compared to the no-treatment group . Finally , participants in the three treatment groups displayed significant improvement in mood states",
"& NA ; Temporom and ibular disorders ( TMD ) are currently viewed as an interrelated set of clinical conditions presenting with signs and symptoms in masticatory and related muscles of the head and neck , and the soft tissue and bony components of the temporom and ibular joint . Epidemiologie and clinical studies of TMD confirm its status as a chronic pain problem . In this report we present results from a r and omized clinical trial which compared , at 3‐ and 12‐month follow‐ups , the effects of usual TMD treatment on TMD pain and related physical and psychological variables with the effects of a cognitive‐behavioral ( CB ) intervention delivered to small groups of patients before usual TMD treatment began . The purpose of this study was to determine whether a minimal CB intervention followed by dental TMD treatment enhanced the effects of usual clinical dental treatment . A second purpose of the study was to determine whether patients classified as high in somatization and psychosocial dysfunction would respond less favorably to this minimal intervention than would those low in somatization and dysfunction . Patients who participated in the CB intervention followed by usual treatment showed greater long‐term decreases in reported pain level and pain interference in daily activities than did patients who received only usual treatment . The benefits of CB intervention were not seen when the CB and UT groups were compared at 3‐month follow‐up . During the 3–12‐month follow‐up interval , however , the UT group maintained essentially the same level of improvement in characteristic pain while the CB group continued to improve , as hypothesized . During this same follow‐up interval , the CB group also showed a strong trend toward continued improvement in pain interference . Such effects were not observed for depression , somatization , or clinical measures of jaw range of motion . Additionally , as hypothesized , dysfunctional chronic pain patients did not appear to benefit from the brief CB intervention . Intent to treat analyses were also performed to assess generalizability of the results",
"Laser therapy has been found effective in the management of pain associated with rheumatoid and degenerative joint arthritis and disease . The efficacy of mid-laser therapy has been tested specifically on patients with degenerative joint disease ( DJD ) involving the temporom and ibular joint ( TMJ ) . The following controlled clinical study was design ed to test the efficacy of mid-laser therapy to placebo therapy in the reduction of pain associated with TMJ disorders specific to arthralgic DJD",
"This study evaluated the relative long-term efficacy of biofeedback , cognitive – behavioral skills training ( CBST ) , combined biofeedback and CBST ( Combined ) , and no-treatment comparison groups in 108 patients suffering from chronic temporom and ibular disorder ( TMD ) . After an initial evaluation , patients were assigned to one of the four treatment conditions . The three biobehavioral treatment interventions consisted of 12 st and ardized sessions . Patients were reevaluated 1 year after completing treatment . Results demonstrated that patients who received the biobehavioral treatments reported significant improvement in subjective pain , pain-related disability , and m and ibular functioning 1 year after receiving treatment . The no-treatment comparison group did not demonstrate such improvements . The combined biofeedback and CBST treatment produced the most comprehensive improvements across all outcome measures . These results again demonstrate the heuristic value of adopting a biopsychosocial perspective to the assessment and treatment of chronic medical/dental disorders such as TMD",
"AIMS To test the usefulness of tailoring cognitive-behavioral therapy ( CBT ) for patients with temporom and ibular disorders ( TMD ) who demonstrated poor psychosocial adaptation to their TMD condition , independent of physical diagnosis . METHODS A r and omized clinical trial compared a 6-session CBT intervention delivered in conjunction with the usual TMD treatment to the usual conservative treatment by TMD specialist dentists . For study inclusion , Research Diagnostic Criteria for Temporom and ibular Disorders ( RDC/TMD ) , Axis II criteria , were used to target patients with elevated levels of TMD pain-related interference with daily activities , independent of physical diagnosis ( i.e. , Axis I ) . RESULTS At the post-treatment assessment , about 4 months after the baseline evaluations , the comprehensive care group , when compared to the usual treatment group , showed significantly lower levels of characteristic pain intensity , significantly higher self-reported ability to control their TMD pain , and a strong trend ( P = .07 ) toward lower pain-related interference in daily activities . From post-intervention to 1-year follow-up , all subjects showed improvement . At the 1-year follow-up , the comprehensive care group , while not losing any of its early gains , was not significantly different from the usual care group with regard to reported levels of pain , ability to control pain , and levels of interference in activities . For many of these psychosocially disabled TMD patients , pain and interference 1 year after treatment remained at the same or higher levels than those observed at baseline among a group of patients selected for a separate r and omized clinical trial on the basis of better psychosocial adaptation . CONCLUSION The 6-session CBT intervention for patients with heightened psychologic and psychosocial disability was effective in improving pain-related variables over the course of the CBT in conjunction with usual treatment , but was too brief an intervention to result in further improvement after the sessions ended . Patient ratings of treatment satisfaction and helfulness were high for both groups , but they were significantly higher for the comprehensive care group",
"BACKGROUND The authors conducted a r and omized clinical trial to evaluate the efficacy of a biopsychosocial intervention for patients who were at high risk ( HR ) of progressing from acute to chronic temporom and ibular disorder (TMD)-related pain . METHODS The authors classified subjects ' risk using a predictive algorithm and r and omized them into an early-intervention ( EI ) or a nonintervention ( NI ) group . The EI included cognitive behavioral skills training and biofeedback . The authors assessed pain and psychosocial measures at intake and at a one-year follow-up . Subjects ' self-reported pain levels were measured on an analog scale and as a response to palpation . RESULTS At one year , EI-group subjects had significantly lower levels of self-reported pain and depression . At one year , more NI-group subjects than EI-group subjects had utilized health care for jaw-related pain . NI-group subjects were 12.5 times as likely to have a somatoform disorder , more than seven times as likely to have an anxiety disorder , and 2.7 times more likely to have an affective disorder at one year , compared with EI-group subjects . CONCLUSIONS EI-group subjects had reduced pain levels , improved coping abilities and reduced emotional distress at one year . CLINICAL IMPLICATION S The TMD-related pain experience is complex and requires early identification with a biopsychosocial EI to achieve maximal , sustainable results",
"& NA ; We used patient daily electronic ratings of outcome ( activity interference , pain intensity , jaw use limitations , negative mood ) and process ( pain‐related beliefs , catastrophizing , and coping ) variables to evaluate a brief cognitive‐behavioral ( CB ) treatment for chronic temporom and ibular disorder ( TMD ) pain . TMD clinic patients ( N=158 ) were assigned r and omly to four biweekly sessions of either CB pain management training ( PMT ) or an education/attention control condition [ self‐care management ( SCM ) ] and were asked to complete electronic interviews three times daily for the 8‐week treatment . We analyzed diary data from 126 participants who completed > 50 % of requested interviews for > 6 weeks . Multilevel regression analyses indicated no statistically significant difference between the study groups in rate of within‐subject change over time on the daily outcome measures , but consistently greater within‐subject improvement in the PMT group on the daily process measures . Significantly ( P proportions of PMT than of SCM patients showed clinical ly important ( > 50 % ) improvement from weeks 1 to 8 in daily activity interference and jaw use limitations . This study is novel in its application of electronic diary methods for assessing outcome and process variables in a chronic pain treatment trial , and supports the feasibility and utility of such methods . The brief CB treatment was efficacious in decreasing catastrophizing and increasing perceived control over pain , and in improving activity interference and jaw use limitations for a subgroup of patients . Longer‐term follow‐ups are ongoing to determine if there is an impact on outcomes over time",
"Two decades of research suggest that self-help/minimal intervention strategies for smoking cessation * may be the preferred means by which smokers stop and can produce success rates approximating those of more formal programs , at lower cost and with greater access to relevant population s. In order to make the best possible use of these self-help/ minimal intervention approaches , the National Cancer Institute ( NCI ) supported a series of r and omized , controlled intervention trials and , in June of 1988 , convened an Expert Advisory Panel to address the question \" What are the essential elements of self-help/ minimal intervention strategies for smoking cessation ? \" . The panel 's recommendations were that : ( 1 ) Intervention efforts should focus on increasing smokers ' motivations to make serious quit attempts ; ( 2 ) Delivery of programs be broadened to include all smokers ; ( 3 ) Programs be targeted to stages of cessation and specific population s ; ( 4 ) All programs include ( a ) elements focused on health and social consequences of smoking , and ( b ) strategies and exercises aim ed at quitting , maintenance of nonsmoking , relapse preven tion , and recycling ; ( 5 ) Material s and programs be made widely available rather than \" fine tuning \" existing programs or developing new ones ; and ( 6 ) Programs make use of specific adjunctive strategies . In this way , a reacceleration of the decline in smoking prevalence may be realized in the 1990s and significantly contribute to the NCI 's Year 2000 goals and the Surgeon General 's aim of a smoke-free society",
"BACKGROUND The authors conducted a r and omized clinical trial to evaluate the cost-effectiveness of a biopsychosocial intervention with patients who are at high risk ( HR ) of progressing from acute to chronic TMD-related pain . METHODS The authors classified 96 patients with acute TMD ( less than six months ' duration ) as HR according to a predictive algorithm and r and omized them into an early intervention ( EI ) or a nonintervention ( NI ) group . The NI group received a biopsychosocial treatment that included cognitive behavioral skills training and biofeedback . Both groups were followed up for one year . The authors collected TMD cost data throughout the year . RESULTS The authors found that the EI group spent significantly fewer jaw-related health care dollars , relative to the NI group , from intake to the one-year follow-up . CONCLUSION AND CLINICAL IMPLICATION S The reduced jaw-related health care expenditures for patients in the EI group compared with expenditures for patients in the NI group at one year suggest that an early biopsychosocial intervention is a cost-effective measure in dealing with often unnecessarily costly TMD-related pain",
"Abstract We evaluated the short‐ and long‐term efficacy of a brief cognitive‐behavioral therapy ( CBT ) for chronic temporom and ibular disorder ( TMD ) pain in a r and omized controlled trial . TMD clinic patients were assigned r and omly to four sessions of either CBT ( n = 79 ) or an education/attention control condition ( n = 79 ) . Participants completed outcome ( pain , activity interference , jaw function , and depression ) and process ( pain beliefs , catastrophizing , and coping ) measures before r and omization , and 3 ( post‐treatment ) , 6 , and 12 months later . As compared with the control group , the CBT group showed significantly greater improvement across the follow‐ups on each outcome , belief , and catastrophizing measure ( intent‐to‐treat analyses ) . The CBT group also showed a greater increase in use of relaxation techniques to cope with pain , but not in use of other coping strategies assessed . On the primary outcome measure , activity interference , the proportion of patients who reported no interference at 12 months was nearly three times higher in the CBT group ( 35 % ) than in the control group ( 13 % ) ( P = 0.004 ) . In addition , more CBT than control group patients had clinical ly meaningful improvement in pain intensity ( 50 % versus 29 % showed ≥50 % decrease , P = 0.01 ) , masticatory jaw function ( P 0.001 ) , and depression ( P = 0.016 ) at 12 months ( intent‐to‐treat analyses ) . The two groups improved equivalently on a measure of TMD knowledge . A brief CBT intervention improves one‐year clinical outcomes of TMD clinic patients and these effects appear to result from specific ingredients of the CBT "
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4117a56e-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND Many r and omized controlled trials ( RCTs ) and observational studies have provided information on the association between vitamin B-12 intake and biomarkers . The use of these data to estimate dose-response relations provides a useful means to summarize the body of evidence . OBJECTIVE We systematic ally review ed studies that investigated vitamin B-12 intake and biomarkers of vitamin B-12 status and estimated dose-response relations with the use of a meta- analysis . DESIGN This systematic review included all RCTs , prospect i ve cohort studies , nested case-control studies , and cross-sectional studies in healthy adult population s published through January 2010 that supplied or measured dietary vitamin B-12 intake and measured vitamin B-12 status as serum or plasma vitamin B-12 , methylmalonic acid ( MMA ) , or holotranscobalamin . We calculated an intake-status regression coefficient ( ) for each individual study and calculated the overall pooled and SE ( ) by using r and om-effects meta- analysis on a double-log scale . RESULTS The meta- analysis of observational studies showed a weaker slope of dose-response relations than the meta- analysis of RCTs . The pooled dose-response relation of all studies between vitamin B-12 intake and status indicated that a doubling of the vitamin B-12 intake increased vitamin B-12 concentrations by 11 % ( 95 % CI : 9.4 % , 12.5 % ) . This increase was larger for studies in elderly persons ( 13 % ) than in studies in adults ( 8 % ) . The dose-response relation between vitamin B-12 intake and MMA concentrations indicated a decrease in MMA of 7 % ( 95 % CI : -10 % , -4 % ) for every doubling of the vitamin B-12 intake . The assessment of risk of bias within individual studies and across studies indicated risk that was unlikely to seriously alter these results . CONCLUSION The obtained dose-response estimate between vitamin B-12 intake and status provides complementary evidence to underpin recommendations for a vitamin B-12 intake of population
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"Objectives : To assess the effectiveness of a multivitamin ( MV ) tablet on nutritional status , quantitative heel ultrasound ( QUS ) , mobility , muscle strength and falls . The design comprised two groups matched on mobility levels , r and omized to receive a daily MV or placebo ( P ) tablet for 6 months . The setting was an Australian residential care facility . Subjects : A total of 92 aged care residents . Serum micronutrients , body weight , QUS , rate of falls , h and grip strength , and the timed up and go test were assessed at baseline and 6 months . Results : A total of 49 participants consumed a MV and 43 , a matched P for 6 months . There was a greater increase in the MV vs P group for serum 25(OH)D ( mean difference±st and ard error , 33.4±2.6 nmol l−1 ) , folate ( 13.4±2.8 nmol l−1 ) , and vitamin B12 ( 178.0±40.3 pmol l−1 ) ( all P ) . Adequate 25(OH)D concentrations ( ⩾50 nmol l−1 ) were found among 77 % of participants in the MV group vs 10 % taking P ( P the increase in QUS was greater in the MV vs P group ( 3.0±2.0 dB MHz−1 vs −2.9±2.1 dB MHz−1 , respectively , P=0.041 ) . There was a trend towards a 63 % lower mean number of falls in the MV vs P group ( 0.3±0.1 falls vs 0.8±0.3 falls , P=0.078 ) . Conclusions : MV supplementation raised serum vitamin B12 and folate concentrations and increased serum 25(OH)D , which was accompanied by an apparent positive effect on bone density . We also found a trend towards a reduction in falls and this could contribute to a reduction in fractures",
"BACKGROUND Vitamin B-12 deficiency is associated with cognitive impairment in older people . However , evidence from r and omized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive . OBJECTIVE The objective was to investigate whether daily supplementation with high doses of oral vitamin B-12 alone or in combination with folic acid has any beneficial effects on cognitive function in persons aged > /=70 y with mild vitamin B-12 deficiency . DESIGN In a double-blind , placebo-controlled trial , 195 subjects were r and omly assigned to receive 1000 microg vitamin B-12 , 1000 microg vitamin B-12 + 400 microg folic acid , or placebo for 24 wk . Vitamin B-12 status was assessed on the basis of methylmalonic acid , total homocysteine ( tHcy ) , and holotranscobalamin ( holoTC ) concentrations before and after 12 and 24 wk of treatment . Cognitive function was assessed before and after 24 wk of treatment with the use of an extensive neuropsychologic test battery that included the domains of attention , construction , sensomotor speed , memory , and executive function . RESULTS Vitamin B-12 status did not change significantly after treatment in the placebo group ; however , oral vitamin B-12 supplementation corrected mild vitamin B-12 deficiency . Vitamin B-12 + folic acid supplementation increased red blood cell folate concentrations and decreased tHcy concentrations by 36 % . Improvement in memory function was greater in the placebo group than in the group who received vitamin B-12 alone ( P = 0.0036 ) . Neither supplementation with vitamin B-12 alone nor that in combination with folic acid was accompanied by any improvement in other cognitive domains . CONCLUSION Oral supplementation with vitamin B-12 alone or in combination with folic acid for 24 wk does not improve cognitive function",
"BACKGROUND High homocysteine and low B vitamin concentrations have been linked to the risk of vascular disease , stroke , and dementia and are relatively common in older adults . OBJECTIVE We assessed the effect of breakfast cereal fortified with folic acid , vitamin B-6 , and vitamin B-12 on vitamin and homocysteine status . DESIGN A r and omized , double-blind trial was conducted in 189 volunteers aged 50 - 85 y. The subjects had no history of hypertension , anemia , asthma , cancer , or cardiovascular or digestive disease and did not regularly consume multiple or B vitamin supplements or highly fortified breakfast cereal . Subjects were r and omly assigned to consume 1 cup ( 0.24 L ) breakfast cereal fortified with 440 microg folic acid , 1.8 mg vitamin B-6 , and 4.8 microg vitamin B-12 or placebo cereal for 12 wk . Blood was drawn at 0 , 2 , 12 , and 14 wk . Methionine-loading tests were conducted at baseline and week 14 . RESULTS Final baseline-adjusted plasma homocysteine concentrations were significantly lower and B vitamin concentrations were significantly higher in the treatment group than in the placebo group ( P plasma folate concentrations vitamin B-12 concentrations vitamin B-6 concentrations homocysteine concentrations > 10.4 micromol/L ( women ) or > 11.4 micromol/L ( men ) from 6.4 % to 1.6 % . The percentage of control subjects with values beyond these cutoff points remained nearly constant or increased . CONCLUSIONS In this relatively healthy group of volunteers , consumption of 1 cup fortified breakfast cereal daily significantly increased B vitamin and decreased homocysteine concentrations , including post-methionine-load homocysteine concentrations",
"We have previously shown that a modest vitamin supplement containing folic acid , vitamin B-12 and vitamin B-6 is effective in reducing elevated plasma homocysteine concentrations . The effect of supplementation of the individual vitamins on moderate hyperhomocysteinemia has now been investigated in a placebo-controlled study . One hundred men with hyperhomocysteinemia were r and omly assigned to five groups and treated with a daily dose of placebo , folic acid ( 0.65 mg ) , vitamin B-12 ( 0.4 mg ) , vitamin B-6 ( 10 mg ) or a combination of the three vitamins for 6 wk . Folic acid supplementation reduced plasma homocysteine concentrations by 41.7 % ( P vitamin B-12 supplement lowered homocysteine concentrations by 14.8 % ( P plasma homocysteine concentrations . The combination of the three vitamins reduced circulating homocysteine concentrations by 49.8 % , which was not significantly different ( P = 0.48 ) from the reduction achieved by folate supplementation alone . Our results indicate that folate deficiency may be an important cause of hyperhomocysteinemia in the general population",
"BACKGROUND Low vitamin B-12 status is prevalent among the elderly , but few studies have examined the association between vitamin B-12 status and intake . OBJECTIVE We hypothesized that vitamin B-12 concentrations vary according to intake source . DESIGN Plasma concentrations and dietary intakes were assessed cross-sectionally for 2999 subjects in the Framingham Offspring Study . The prevalence of vitamin B-12 concentrations age group ( 26 - 49 , 50 - 64 , and 65 - 83 y ) , supplement use , and the following food intake sources : fortified breakfast cereal , dairy products , and meat . RESULTS Thirty-nine percent of subjects had plasma vitamin B-12 concentrations users were significantly less likely than non-supplement-users to have concentrations fortified cereal > 4 times/wk ( 12 % ) and those who consumed no fortified cereal ( 23 % ) and between those in the highest and those in the lowest tertile of dairy intake ( 13 % compared with 24 % , respectively ) , but no significant differences by meat tertile . Regression of plasma vitamin B-12 on log of intake , by source , yielded significant slopes for each contributor adjusted for the others . For the total group , b = 40.6 for vitamin B-12 from vitamin supplements . Among non-supplement-users , b = 56.4 for dairy products , 35.2 for cereal , and 16.7 for meat . Only the meat slope differed significantly from the others . CONCLUSIONS In contrast with previous reports , plasma vitamin B-12 concentrations were associated with vitamin B-12 intake . Use of supplements , fortified cereal , and milk appears to protect against lower concentrations . Further research is needed to investigate possible differences in bioavailability",
"We measured serum concentrations of thiamin , riboflavin , nicotinic acid , pyridoxine , folate , cyanocobalamin , ascorbic acid , retinol , tocopherol , zinc , magnesium , copper , iron , and ferritin as well as hemoglobin , hematocrit , percentage transferrin saturation , and total iron-binding capacity in athletes who ingested a multivitamin and mineral supplement for 3 mo . All blood variables were normal and except for pyridoxine and riboflavin there were no significant changes in the blood concentrations of any other vitamins or minerals measured . This may have been due to variable interactions between the vitamins and minerals in the supplement that prevented their being adequately absorbed . There were no signs or symptoms of serious toxic side effects . We conclude that multivitamin and mineral supplementation was without any measurable ergogenic effect and that such supplementation is unnecessary in athletes ingesting a normal diet",
"BACKGROUND M and atory fortification of flour with folic acid has reduced the number of neural tube defects in North America . Concerns that high intakes of folic acid might mask vitamin B-12 deficiency in older persons have delayed the introduction of fortification in many European countries . Cofortification of flour with folic acid and vitamin B-12 could simultaneously improve folate and vitamin B-12 status . OBJECTIVE The objective was to estimate the effect of the consumption of bread fortified with modest amounts of folic acid and vitamin B-12 on folate and vitamin B-12 status in healthy older persons living in the Netherl and s , where folic acid fortification is not taking place . DESIGN Men and women aged 50 - 75 y were r and omly assigned in this 12-wk double-blind , placebo-controlled trial to consume bread fortified with 138 mug folic acid and 9.6 mug vitamin B-12 daily ( n = 72 ) or unfortified bread ( n = 70 ) . RESULTS The consumption of fortified bread increased serum folate concentrations by 45 % ( mean : 6.3 nmol/L ; 95 % CI : 4.5 , 8.1 nmol/L ) and serum vitamin B-12 concentrations by 49 % ( mean : 102 pmol/L ; 95 % CI : 82 , 122 pmol/L ) relative to the placebo group . Fortified bread increased erythrocyte folate concentrations by 22 % and holotranscobalamin concentrations by 35 % ; it decreased homocysteine concentrations by 13 % and methylmalonic acid concentrations by 10 % . Consumption of fortified bread decreased the proportion of individuals with marginal serum vitamin B-12 concentrations ( fortified with modest amounts of folic acid and vitamin B-12 will improve folate and vitamin B-12 status and a considerable proportion of vitamin B-12 deficiency in older people . This trial was registered at clinical trials.gov as NCT00353353",
"BACKGROUND A high prevalence of cobalamin deficiency occurs in the elderly population , which may be treated orally or with injections . Little is known about the relative bioavailability of crystalline cobalamin added to food products . OBJECTIVE The objective was to assess the effect of supplementation with 1000 microg crystalline cobalamin , carried either by a milk product or a capsule , on cobalamin status in mildly cobalamin-deficient elderly Dutch persons . DESIGN Two double-blind r and omized controlled intervention studies , each covering a 12-wk supplementation period , were carried out in parallel . Mildly cobalamin-deficient elderly persons ( n = 112 ) were separately recruited for the milk and capsule trials . Mild cobalamin deficiency was defined as a cobalamin concentration between 100 and 300 pmol/L and a plasma methylmalonic acid ( MMA ) concentration > or = 0.30 micromol/L. Allocation to the placebo or cobalamin carrier was carried out independently in both trials . RESULTS In the fortified-milk group , the mean ( + /-SD ) increase in serum cobalamin was 250 + /- 96 pmol/L , the median ( 5th and 95th percentiles ) decrease in plasma MMA was 0.19 ( -0.76 , -0.04 ) micromol/L , and the median decrease in plasma homocysteine was 4.0 ( -7.3 , 3.0 ) micromol/L. All changes were significantly different from those in the placebo milk group ( P serum cobalamin was 281 + /- 136 pmol/L , the median decrease in plasma MMA was 0.18 ( -2.95 , 0.14 ) micromol/L , and the median decrease in plasma homocysteine was 1.8 ( -10.6 , 2.4 ) micromol/L ; all changes were significantly different from those in the placebo capsule group ( P 0.40 ) . CONCLUSION Crystalline cobalamin added to milk is an effective alternative to cobalamin capsules for improving cobalamin status",
"Elevated homocysteine has been identified as an independent risk factor for cardiovascular and cerebrovascular disease . Although multivitamin use has been associated with low plasma homocysteine concentrations in several observational studies , no clinical trials have been conducted using multivitamin/mineral supplements to lower homocysteine . We determined whether a multivitamin/mineral supplement formulated at about 100 % Daily Value will further lower homocysteine concentration and improve B-vitamin status in healthy older adults already consuming a diet fortified with folic acid . In this r and omized , double-blind , placebo-controlled trial , 80 free-living men and women aged 50 - 87 y with total plasma homocysteine concentrations of > or = 8 micromol/L received either a multivitamin/mineral supplement or placebo for 56 d while consuming their usual diet . After the 8-wk treatment , subjects taking the supplement had significantly higher B-vitamin status and lower homocysteine concentration than controls ( P : Plasma folate , pyridoxal phosphate ( PLP ) and vitamin B-12 concentrations were increased 41.6 , 36.5 and 13.8 % , respectively , in the supplemented group , whereas no changes were observed in the placebo group . The mean homocysteine concentration decreased 9.6 % in the supplemented group ( P : dietary intake during the intervention . Multivitamin/mineral supplementation can improve B-vitamin status and reduce plasma homocysteine concentration in older adults already consuming a folate-fortified diet",
"BACKGROUND In recent prospect i ve studies , higher homocysteine concentrations were shown to be a risk factor for osteoporotic fractures in older persons . Supplements containing folate and vitamins B-12 and B-6 lower homocysteine concentrations . OBJECTIVE The objective of the study was to determine in healthy older persons whether lowering homocysteine with B vitamins affects plasma biomarkers of bone turnover . DESIGN Healthy older persons ( n = 276 ; aged > or=65 y ) were r and omly assigned to receive either a daily supplement containing folate ( 1 mg ) , vitamin B-12 ( 500 microg ) , and vitamin B-6 ( 10 mg ) or a placebo for 2 y. Of these participants , we selected 135 with baseline homocysteine concentrations > 15.0 micromol/L , and we measured serum bone-specific alkaline phosphatase , a marker of bone formation , and bone-derived collagen fragments , a marker of bone resorption , at baseline and 2 y later . RESULTS At 2 y , plasma homocysteine concentrations were 5.2 mumol/L ( 95 % CI : 3.9 , 6.6 micromol/L ; P placebo group . No significant differences were found in either serum bone-specific alkaline phosphatase ( -0.3 microg/L ; 95 % CI : -2.8 , 2.1 microg/L ; P = 0.79 ) or bone-derived collagen fragments ( -0.0 microg/L ; 95 % CI : -0.1 , 0.1 microg/L ; P = 0.76 ) between the vitamin and placebo groups , respectively , with 2 y of supplementation . CONCLUSION Supplementation with folate and vitamins B-6 and B-12 lowered plasma homocysteine but had no beneficial effect on bone turnover at the end of 2 y , as assessed by biomarkers of bone formation and resorption",
"BACKGROUND Frail elders are at risk of suboptimal micronutrient status , functional decline , and neurologic disorders . The influence of oral multimicronutrients in physiologic doses and of moderately intense physical exercise on homocysteine ( Hcy ) , methylmalonic acid ( MMA ) , and neurologic functioning have not yet been investigated . OBJECTIVE Our goal was to determine the effects of enriched foods and exercise on blood vitamins , Hcy , MMA , and neuropsychological functioning in the frail . DESIGN A 17-wk r and omized controlled intervention trial was used to study 1 ) enriched foods plus a social program , 2 ) regular foods plus exercise , 3 ) enriched foods plus exercise , and 4 ) regular foods plus a social program . Enriched foods contained multiple micronutrients ( 25 - 100 % of the Dutch recommended dietary allowances ) ; exercises focused on strength , coordination , flexibility , and endurance . Vitamin ( cobalamin , red blood cell folate , and pyridoxal 5'-phosphate ) , Hcy , and MMA concentrations were measured and 2 neuropsychological tests were conducted . RESULTS Vitamin concentrations were higher in the supplemented groups than in the unsupplemented groups ( P total n = 130 ) . Compared with baseline , cobalamin in the supplemented groups was increased by 22 % , plasma folate by 101 % , red blood cell folate by 87 % , and pyridoxal 5'-phosphate by 68 % . Concentrations in the unsupplemented groups changed by -2 % , -6 % , 1 % , and -13 % , respectively . Hcy decreased by 25 % and MMA by 30 % in the supplemented groups , compared with a small increase in Hcy ( 2 % ) and decrease in MMA ( 9 % ) in the unsupplemented groups . Exercise did not significantly affect vitamin , Hcy , or MMA concentrations . No significant effect of either intervention was observed on the neuropsychological tests . CONCLUSIONS The decrease in Hcy and MMA in frail elders confirms a sub clinical metabolic deficiency state . Enriched foods containing physiologic amounts of micronutrients have a beneficial effect on these metabolites . No effects of B vitamins on mental health were identified",
"Objective : To assess the nutritional status for vitamins B6 and B12 and folate in an adult Mediterranean population , in order to identify patterns of intake , groups at risk for deficiency , and factors that might influence this risk . Design : A cross-sectional epidemiological survey . Setting : And alusia , a western Mediterranean region in southern Spain . Subjects : The study was carried out with a r and om sample of 3528 subjects ( 1813 men , 1715 women ) who were between 25 and 60 y of age . Blood sample s were obtained for biochemical assays in a r and om sub sample of 384 subjects ( 183 men , 201 women ) . Interventions : Food consumption was assessed by 48-h recall . Vitamin B6 was measured as alpha erythrocyte aspartate aminotransferase activation coefficient ( αEAST ) ; vitamin B12 and folate concentrations were measured in plasma . Results : Energy and vitamin intakes were significantly higher in men than in women . In men , intakes were below two-thirds of the RDA in 10.8 , 2.9 and 22.6 % for B6 , B12 and folate , respectively . The corresponding figures in women were 16.7 , 5.1 and 23.5 % for vitamins B6 , B12 and folate . Age , place of residence and educational level , alcohol use and smoking were also associated with differences in the intake of these nutrients . Biochemical analyses showed that vitamins B6 , B12 and folate status was acceptable in 75.7 , 89.1 and 57.6 % of the population , respectively . Plasma concentration of folate was significantly higher in women . Conclusion : Our results provide a precise estimate of the nutritional status for vitamins B6 , B12 and folate in the adult population of southern Spain . Factors such as age , place of residence , level of education and smoking can increase the risk of inadequate intake of some nutrients . However , these factors did not affect biochemical indexes of nutritional status in the present study .Sponsorship : Dirección General de Salud Pública and the Health Council of the And alusian Regional Government",
"BACKGROUND Elevated blood levels of homocysteine are associated with an increased risk of atherosclerotic cardiovascular disease . Although numerous studies have assessed the impact of vitamin supplements on homocysteine , the effect of dietary patterns on homocysteine has not been well studied . METHODS AND RESULTS During a 3-week run-in , 118 participants were fed a control diet , low in fruits , vegetables , and dairy products , with a fat content typical of US consumption . During an 8-week intervention phase , participants were then fed 1 of 3 r and omly assigned diets : the control diet , a diet rich in fruits and vegetables but otherwise similar to control , or a combination diet rich in fruits , vegetables , and low-fat dairy products and reduced in saturated and total fat . Between the end of run-in and intervention periods , mean change in homocysteine was + 0.46 micromol/L in the control diet , + 0.21 micromol/L in the fruits and vegetables diet ( P=0.47 compared with control ) , and -0.34 micromol/L in the combination diet ( P=0.03 compared with control , P=0.12 compared with the fruits and vegetables diet ) . In multivariable regression models , change in homocysteine was significantly and inversely associated with change in serum folate ( P=0.03 ) but not with change in serum vitamin B(12 ) ( P=0.64 ) or pyridoxal 5 ' phosphate , the coenzyme form of vitamin B(6 ) ( P=0.83 ) . CONCLUSIONS Modification of dietary patterns can have substantial effects on fasting levels of total serum homocysteine . These results provide additional insights into the mechanisms by which diet might influence the occurrence of atherosclerotic cardiovascular disease",
"BACKGROUND The results of observational studies suggest that plasma homocysteine concentrations are inversely related to cognitive function in older people . Our objective was to test the hypothesis that lowering the plasma homocysteine concentration improves cognitive function in healthy older people . METHODS We conducted a two-year , double-blind , placebo-controlled , r and omized clinical trial involving 276 healthy participants , 65 years of age or older , with plasma homocysteine concentrations of at least 13 micromol per liter . Homocysteine-lowering treatment was a daily supplement containing folate ( 1000 microg ) and vitamins B12 ( 500 microg ) and B6 ( 10 mg ) . Tests of cognition were conducted at baseline and after one and two years of treatment . Treatment effects were adjusted for baseline values , sex , and education . RESULTS On average , during the course of the study , the plasma homocysteine concentration was 4.36 micromol per liter ( 95 percent confidence interval , 3.81 to 4.91 micromol per liter ) lower in the vitamin group than in the placebo group ( P vitamin and placebo groups in the scores on tests of cognition . CONCLUSIONS The results of this trial do not support the hypothesis that homocysteine lowering with B vitamins improves cognitive performance . ( Australian Clinical Trials registry number , ACTR NO 12605000030673 . )",
"Summary Background Deficiency of folic acid , vitamin B6 and /or vitamin B12 can result in elevated total plasma homocysteine concentrations ( tHcy ) , which are considered to be a risk factor for vascular disease . Studies have shown that supplementation of the three vitamins can lower tHcy even in subjects with tHcy in the normal range . Aim of the study The aim of this study was to evaluate the effect of a 6 month supplementation with vitamin B6 , B12 and folate on the concentrations of total plasma homocysteine and serum methylmalonic acid ( MMA ) of elderly women . Methods The study was design ed as a r and omized placebo controlled doubleblind trial , and 220 healthy women ( aged 60–91 years ) were involved . The vitamin and mineral capsule contained pyridoxine ( 3.4 mg ) , folic acid ( 400 µg ) and cobalamin ( 9 µg ) in addition to other micronutrients . Blood concentrations of folate , cobalamin , tHcy , MMA and the activity coefficient of erythrocyte alpha-aspartic aminotransferase ( alpha-EAST ) were measured at baseline and after 6 months of supplementation . Dietary intake was evaluated at the beginning and the end of the intervention by two 3–day diet records . Results Median concentrations of serum cobalamin , serum folate and erythrocyte folate increased significantly and tHcy and alpha – EAST activity ( indicative of improved status of vitamin B6 ) coefficient decreased significantly in the supplemented group . Median MMA concentration of the supplemented group was significantly lower than that of the placebo group after the intervention . The vitamin supplementation had a greater decreasing effect on the tHcy concentration of volunteers with lower vitamin and higher tHcy initial concentrations . In a linear regression model , baseline tHcy , serum folate , age and alpha – EAST activity coefficient were significantly correlated with the change in tHcy . The change in MMA in the supplement group was significantly associated to the baseline MMA values . Conclusions Our results show that a 6 month supplementation including physiological dosages of B vitamins improves the status of these nutrients and reduces tHcy in presumed healthy elderly women",
"Background and Purpose — Folate metabolism has been implicated in stroke . However , the possibility of a role for folate and vitamin B12 , independent of their effects on homocysteine status , remains to be explored . The aim of this prospect i ve , nested case-referent study was to relate plasma and dietary intake levels of folate and vitamin B12 to risk of stroke , taking into consideration plasma homocysteine concentrations and methylenetetrahydrofolate reductase polymorphisms . Methods — Subjects were 334 ischemic and 62 hemorrhagic stroke cases and matched double referents from the population -based Northern Sweden Health and Disease Cohort . Results — Plasma folate was statistically significantly associated with risk of hemorrhagic stroke in an inverse linear manner , both in univariate analysis and after adjustment for conventional risk factors including hypertension ( odds ratio [ OR ] for highest versus lowest quartile 0.21 ( 95 % confidence interval [ CI ] , 0.06 to 0.71 ; P for trend=0.008 ) ) . Risk estimates were attenuated by inclusion of homocysteine in the model ( OR , 0.34 ; 95 % CI , 0.08 to 1.40 ; P for trend=0.088 ) . A similar pattern was observed for increasing folate intake ( multivariate OR , 0.07 ; 95 % CI , 0.01 to 0.55 ; P for trend=0.031 without homocysteine , and OR , 0.16 , 95 % CI , 0.02 to 1.23 ; P for trend=0.118 with homocysteine in the analysis ) . We found little evidence of an association between plasma or dietary folate and risk of ischemic stroke . Neither plasma nor dietary vitamin B12 was associated with risk of either stroke subtype . Conclusions — The results of this study suggest a protective role for folate , possibly in addition to its effects on homocysteine status , in hemorrhagic but not ischemic stroke",
"BACKGROUND In several epidemiologic investigations , folate intake has appeared to reduce the elevated risk of breast cancer associated with moderate alcohol consumption . However , data relating plasma folate levels to breast cancer risk are sparse . We investigated the association between plasma folate and other vitamins with breast cancer in a prospect i ve , nested case-control study . METHODS Blood sample s were obtained during 1989 and 1990 from 32 826 women in the Nurses ' Health Study who were followed through 1996 for the development of breast cancer . We identified 712 breast cancer case patients and selected 712 individually matched control subjects . Dietary information was obtained using food frequency question naires given in 1980 , 1984 , 1986 , and 1990 . Logistic regression was used to estimate the relative risks ( RRs ) of breast cancer ( after adjustment for potential risk factors ) , and a generalized linear model was used to calculate the Pearson correlation coefficients between plasma estimates of folate , vitamin B(6 ) , vitamin B(12 ) , and homocysteine , and intakes of folate , vitamin B(6 ) , and vitamin B(12 ) . All statistical tests were two-sided . RESULTS The multivariable RR comparing women in the highest quintile of plasma folate with those in the lowest was 0.73 ( 95 % confidence interval [ CI ] = 0.50 to 1.07 ; P(trend ) = .06 ) . The inverse association between plasma folate and breast cancer risk was highly statistically significant among women consuming at least 15 g/day ( i.e. , approximately 1 drink/day ) of alcohol ( multivariable RR = 0.11 , 95 % CI = 0.02 to 0.59 for highest versus lowest quintile ) in contrast with that of women consuming less than 15 g/day ( multivariable RR = 0.72 , 95 % CI = 0.49 to 1.05 ) . The multivariable RR comparing women in the highest quintile of plasma vitamin B(6 ) levels with those in the lowest quintile was 0.70 ( 95 % CI = 0.48 to 1.02 ; P(trend ) = .09 ) . Plasma vitamin B(12 ) levels were inversely associated with breast cancer risk among premenopausal women ( multivariable RR = 0.36 , 95 % CI = 0.15 to 0.86 for highest versus lowest quintile ) but not among postmenopausal women . Plasma homocysteine was not associated with breast cancer risk . CONCLUSIONS Higher plasma levels of folate and possibly vitamin B(6 ) may reduce the risk of developing breast cancer . Achieving adequate circulating levels of folate may be particularly important for women at higher risk of developing breast cancer because of higher alcohol consumption",
"Objective : We previously reported in an open-label pilot trial that a 24-ingredient multivitamin formula favorably influenced homocysteine concentration and LDL-C oxidation indices following 24 weeks of supplementation . Our current aim was to more thoroughly examine this same formula in a r and omized , placebo-controlled , clinical study . Methods : We examined 182 participants for selected plasma vitamin concentrations and clinical ly relevant variables including homocysteine , lipids and LDL-C oxidation indices at baseline and six months . Results : We found no significant differences between groups for any parameter at baseline . Following six months of vitamin supplementation , we observed elevations in plasma concentrations of vitamin B6 ( as pyridoxal 5′-phosphate ; PLP ) , vitamin B12 , folate , vitamin C , vitamin E and β-carotene ( p ( p decreased in the treatment ( 8.38 ± 2.9 vs. 6.93 ± 2.5 μmol/L ; p than placebo ( p were also improved as LDL-C oxidation rate was decreased ( −0.39 μmol/min/g protein ; p ) and LDL-C lag time increased ( 11.3 min ; p that LDL-C oxidation rate was lower ( p longer ( p the vitamin group than placebo treatment after six months . Conclusion : We conclude that a multi-ingredient vitamin formula with antioxidant properties has measurable effects on homocysteine and LDL-C oxidation indices ",
"Objective : We investigated the effects of mineral water fortified with folic acid , vitamins B6 , B12 , D and calcium on folate concentrations in serum and erythrocytes , serum vitamin B12 and plasma homocysteine concentrations in free-living subjects . In addition , we investigated the bioavailability of calcium added to mineral water by measuring urinary calcium excretion and serum alkaline phosphatase activity . Design : R and omized , controlled , double-blinded , parallel design . Setting : Outpatient dietary intervention with free-living subjects in Eastern Finl and .Subjects : Altogether , 66 subjects were recruited for the study . In all , 60 subjects completed the study . Interventions : The study began with a 2-week run-in period followed by an 8-week intervention period . During the intervention study , subjects consumed mineral water fortified with folic acid ( 563 μg/day ) , vitamins B6 ( 1 mg/day ) , B12 ( 7.5 μg/day ) , cholecalciferol ( 0.6 μg/day ) and calcium ( 563 mg/day ) or placebo mineral water . Results : The fortified mineral water increased serum and erythrocyte folate concentrations by 16.1±5.6 nmol/l ( P and decreased plasma homocysteine concentration by 1.6 μmol/l ( P for 24 h increased significantly ( P Conclusions : Mineral water fortified with folic acid , vitamins B6 , B12 and D and calcium enhanced folate status and reduced plasma homocysteine concentration in normohomocysteinemic subjects without folate deficiency . Indirect measures of calcium and bone metabolism indicated that the calcium used in the fortification of the mineral water was bioavailable . Sponsorship : Olvi PLC , Iisalmi , Finl and",
"The purpose of this study was to test whether low serum vitamin B-12 levels are associated with more rapid bone loss in elderly women . We archived sera and measured calcaneal bone mineral density ( BMD ) in community-dwelling white women , aged 65 yr and over , who participated in the Study of Osteoporotic Fractures . BMD of the hip and subregions was measured 2 yr later . Repeat measurements of calcaneal and hip BMD were obtained after 5.9 and 3.5 yr of follow-up , respectively . Serum vitamin B-12 assays were performed in 83 r and omly selected participants with initial and repeat measurements of BMD who were not taking estrogen replacement therapy at baseline . After adjusting for age , weight , and clinic site , women with vitamin B-12 levels at or below 280 pg/ml ( 207.2 pmol/liter ; lowest quintile ) experienced an annual change of -1.6 % ( 95 % confidence interval , -2.4 % to -0.8 % ) in total hip BMD , compared with -0.2 % ( -0.5 % to 0.2 % ) in women with levels above 280 pg/ml ( P = 0.003 ) . Results were similar when subregions of the hip were analyzed separately . Serum vitamin B-12 levels were not significantly associated with calcaneal bone loss . We conclude that low serum vitamin B-12 levels are associated with increased rates of hip , but not calcaneal , bone loss in older women",
"Objectives : To determine the prevalence of anaemia and the haemopoietic nutrient status of older mixed ancestry ( coloured ) South Africans . Design : A cross-sectional analytic study . Subjects : A r and om sample of 200 non-institutionalized subjects aged ≥65 y of age , resident in urban Cape Town , was drawn using a two-stage cluster design . Methods : Trained fieldworkers interviewed subjects to obtain demographic and lifestyle data . Dietary intake was assessed using a vali date d food frequency question naire . Fasting blood sample s were drawn for the determination of haematological parameters , serum vitamin B12 , serum folate , RBC folate and a full blood count . Results : The prevalence of anaemia was 13.9 % . Eight of the 26 cases of anaemia ( 31 % ) were associated with suboptimal haemopoietic nutrient status ; 2(25 ) and 3(38 ) cases of these 8 anaemic subjects had suboptimal vitamin B12 and folate status , respectively . Iron deficiency anaemia accounted for 5(63)% of the subjects with nutrition-related anaemia . Ten men and two women ( 6.5 % of subjects ) had raised serum ferritin concentrations , half of whom had abnormal biochemical parameters indicative of alcohol abuse . Conclusions : Older coloured South Africans , particularly women , should be encouraged to eat diets with a high nutrient density and to consume adequate amounts of foods high in iron , folate and vitamin B12 . Further investigation regarding the high prevalence of hyperferritinaemia found in the men in this population is indicated . Sponsorship : Financial assistance from the HSRC/UCT Centre for Gerontology , the South African Sugar Association , the Zerilda Steyn Memorial Trust and the Medical Research Council ( DL ) for this project is acknowledged",
"BACKGROUND Very high plasma homocysteine levels are characteristic of homocystinuria , a rare autosomal recessive disease accompanied by the early onset of generalized osteoporosis . We therefore hypothesized that mildly elevated homocysteine levels might be related to age-related osteoporotic fractures . METHODS We studied the association between circulating homocysteine levels and the risk of incident osteoporotic fracture in 2406 subjects , 55 years of age or older , who participated in two separate prospect i ve , population -based studies . In the Rotterdam Study , there were two independent cohorts : 562 subjects in cohort 1 , with a mean follow-up period of 8.1 years ; and 553 subjects in cohort 2 , with a mean follow-up period of 5.7 years . In the Longitudinal Aging Study Amsterdam , there was a single cohort of 1291 subjects , with a mean follow-up period of 2.7 years . Multivariate Cox proportional-hazards regression models were used for analysis of the risk of fracture , with adjustment for age , sex , body-mass index , and other characteristics that may be associated with the risk of fracture or with increased homocysteine levels . RESULTS During 11,253 person-years of follow-up , osteoporotic fractures occurred in 191 subjects . The overall multivariable-adjusted relative risk of fracture was 1.4 ( 95 percent confidence interval , 1.2 to 1.6 ) for each increase of 1 SD in the natural-log-transformed homocysteine level . The risk was similar in all three cohorts studied , and it was also similar in men and women . A homocysteine level in the highest age-specific quartile was associated with an increase by a factor of 1.9 in the risk of fracture ( 95 percent confidence interval , 1.4 to 2.6 ) . The associations between homocysteine levels and the risk of fracture appeared to be independent of bone mineral density and other potential risk factors for fracture . CONCLUSIONS An increased homocysteine level appears to be a strong and independent risk factor for osteoporotic fractures in older men and women",
"Forty-two female college students , age 18 - 29 yr . and consuming nutritionally balanced meals in the college cafeteria participated . Subjects discontinued all vitamin-mineral supplements ( VMS ) for 17 days and were r and omly assigned to one of two treatments , either a placebo , or VMS supplying the United States Recommended Daily Allowance ( USRDA ) of all vitamins , zinc , iron , iodine , copper , and 60 % of the USRDA of calcium , 50 % of magnesium and 45 % of phosphorus . Treatments were consumed for 77 days . Fasting pre- and post-treatment blood chemistries were compared . VMS yielded significant increases ( p less than 0.05 ) in serum vitamin B-12 ( + 25.05 pg/ml ) , vitamin C ( + 0.35 mg/dl ) and folate ( + 7.40 ng/ml ) . No significant changes ( p greater than 0.05 ) in hematological or other blood chemistries were observed . Significant decreases in the number of below-normal serum indicators of vitamin status ( p less than 0.05 ) and iron status ( p less than 0.005 ) were seen with VMS . No significant changes were seen with placebo ( p greater than 0.05 )",
"Objectives : To evaluate the acceptance of a multinutrient liquid nutrition supplement in psycho-geriatric nursing home patients and the effect on weight , plasma nutrients and activities of daily life . Design : Double-blind , placebo-controlled 12-week intervention study . Setting : Two nursing homes in Boxtel , The Netherl and s . Subjects : Forty-two ( body mass index ( BMI ) Interventions : Provision with a complete micronutrient-enriched liquid nutrition supplement of 125 ml and 0.6 MJ ( 135 kcal ) or placebo twice daily during daytime between main meals . Study parameters were assessed at 0 , 6 and 12 weeks . Main Outcome for Measures : Weight , Barthel index of daily activities , several plasma values ( albumin , C-reactive protein ( CRP ) , homocysteine , thiamine , thiamine diphosphate ( TDF ) , vitamin B6 , vitamin B12 , folic acid , vitamin D ) , bowel function . Results : The supplement was well accepted . Thirty-five patients completed the intervention period ( 16 control group ; 19 supplement group ) . Baseline daily nutrient intake was low . A statistically significant improvement was observed for body weight ( difference between groups 2.2 kg , P=0.03 ) , and homocysteine , vitamin B1 , TDF , vitamin B6 , vitamin B12 , folate and vitamin D in the supplement group compared to the placebo group . No significant difference was observed in the Barthel index ( mean difference −0.3±1.1 for both groups ) . No difference in occurrence of diarrhoea was observed . Conclusions : The study shows that nutritional supplementation is well accepted and can improve the nutritional status of psycho-geriatric nursing home patients .Sponsorship : Numico Research BV",
"OBJECTIVES To examine the association of cognitive impairment with platelet activation and reactive oxygen species and total homocysteine levels ; and to assess the biochemical efficacy of treatment with aspirin and vitamin supplements in people at high risk of dementia . SUBJECTS People with dementia or mild cognitive impairment . DESIGN AND INTERVENTION In a 2 x 2 x 2 factorial design trial , 149 people at high-risk of dementia were r and omized to receive either low-dose aspirin ( 81 mg ) or placebo ; and folic acid ( 2 mg ) plus vitamin B12 ( 1 mg ) or placebo ; and vitamins E ( 500 mg ) plus C ( 200 mg ) or placebo . Participants were seen twice before and once after 12 weeks of treatment . MAIN OUTCOME MEASURES At each visit , participants had their cognitive function assessed and had blood collected for homocysteine , folate and vitamin B12 determination and urine collected for markers of platelet activation ( 11-dehydro-thromboxane B2 ) and reactive oxygen species ( 8-epi-PGF2 alpha ) . RESULTS Prior to treatment , cognitive function was inversely related with homocysteine and with urinary thromboxane and isoprostane , and these associations were independent of age . Aspirin was associated with a median reduction in 11-dehydrothromboxane B2 of 73 % ( P B-vitamins lowered plasma homocysteine concentration by 30 % ( P isoprostane excretion by 26 % ( P cognitive function was detected . CONCLUSIONS Aspirin and B-vitamins were effective in reducing biochemical factors associated with cognitive impairment in people at risk of dementia . Large-scale trials are now required to assess the relevance of aspirin and B-vitamins for the maintenance of cognitive function in people at risk of dementia ",
"Objectives : To investigate , in an elderly population : ( 1 ) the effects of oral B-vitamin therapy on P-tHcys , S-MMA and Hb/MCV , ( 2 ) the appropriate decision limit for ‘ high ’ metabolite concentrations and ( 3 ) the estimated prevalence of vitamin B12/folate deficiency on the basis of different decision limits . Design : Double-blind placebo-controlled intervention study . Setting : Outpatient clinic . Subjects : A total of 209 community-dwelling subjects , median age 76 y ( range 70–93 ) y. Interventions : Four months of oral daily supplementation with 0.5 mg cyanocobalamin , 0.8 mg folic acid and 3 mg vitamin B6 . Results : High P- tHcys was found in 64 % of men and 45 % of women , high S-MMA in 11 % of both . Vitamin B12 deficiency was observed in 7.2 % and folate deficiency in 11 % of all subjects . Health-related upper reference limits for the metabolites at the start were higher than the laboratory 's upper reference limits . The latter were , however , similar to those of the vitamin replete group . There was a significant decrease in P-tHcys ( P S-MMA ( P=0.009 ) after 4 months of vitamin treatment . In a multivariate analysis , the P-Hcys change correlated positively with baseline P-tHcys and inversely with baseline P-folate and transferrin saturation ( Fe/TIBC ratio ) . The S-MMA change correlated with baseline S-MMA and inversely with baseline vitamin B12 and age . Conclusions : Suboptimal vitamin status is an important cause of elevated P-tHcys and S-MMA in apparently healthy elderly subjects . Oral B-vitamin therapy is an effective and convenient way to normalise P-tHcys and S-MMA.Sponsorship : Support — Recip AB",
"Homocysteine has been related to increased risk of CVD . Matrix degradation and inflammation may be involved in this link between hyperhomocysteinaemia and CVD . Recent studies suggest that cystatin C can modulate matrix degradation and inflammation . The present study measured cystatin C at protein ( plasma ) and mRNA levels ( peripheral blood mononuclear cells ( P BMC ) ) in hyperhomocysteinaemic individuals ( n 37 , female seven and male thirty , aged 20 - 70 years ) before and after B-vitamin supplementation for 3 months in a r and omised , placebo-controlled double-blind trial . In a cross-sectional study , seventeen of the hyperhomocysteinaemic subjects were age- and sex-matched to healthy controls ( n 17 ) . Our main findings were : ( i ) as compared with controls , hyperhomocysteinaemic subjects tended to have higher plasma concentrations of cystatin C and lower mRNA levels of cystatin C in P BMC ; ( ii ) compared with placebo , treatment of hyperhomocysteinaemic individuals with B-vitamins significantly increased plasma levels of cystatin C and mRNA levels of cystatin C in P BMC ; ( iii ) while plasma levels of cystatin C were positively correlated with plasma levels of TNF receptor-1 , mRNA levels of cystatin C in P BMC were inversely correlated with this TNF parameter . Taken together , our findings suggest that disturbed cystatin C levels may be a characteristic of hyperhomocysteinaemic individuals , potentially related to low- grade systemic inflammation in hyperhomocysteinaemic subjects , and that B-vitamins may modulate cystatin C levels in these individuals",
"OBJECTIVES To determine the effect of small doses of oral cyanocobalamin supplements in older patients with low or borderline serum vitamin B12 concentrations but no other evidence of pernicious anemia ( PA ) . DESIGN R and omized , double-blind , placebo-controlled study assessing the efficacy of oral cyanocobalamin 10 microg and 50 microg daily for 1 month . SETTING Two geriatric hospitals in the North Western Health Care Network , Melbourne , Australia . PARTICIPANTS Thirty-one in patients with serum vitamin B12 levels between 100 and 150 pmol/L , without PA , other malabsorption disorders , or progressive neurological or terminal illness . The mean age was 81.4 years . INTERVENTION After informed consent , a medical and drug history was taken and the Mini-Mental State Examination ( MMSE ) completed . A dietitian made assessment of oral cobalamin intake . Blood was taken for serum vitamin B12 , serum and red cell folate assay , full blood examination , fasting serum gastrin , parietal and intrinsic factor antibodies , fasting serum homocysteine , and creatinine . Patients were then r and omized to receive 10 microg oral cyanocobalamin , 50 microg oral cyanocobalamin , or placebo treatment for 1 month , after which the investigations and clinical examinations were repeated . MEASUREMENTS Percentage change in the level of vitamin B12 , homocysteine , folate , and red cell parameters and absolute changes in MMSE were calculated and compared between groups . The groups were compared on the number of responders who improved their level of B12 by 20 % . Chi-square calculations on changes in serum vitamin B12 concentration were also performed . RESULTS Mean serum vitamin B12 + /- st and ard deviation improved by 51.7 + /- 47.1 % in the 50-microg group , 40.2 + /- 34.4 % in the 10-microg group , and 11.7 + /- 24.5 % in the placebo group . The change in the 50-microg cyanocobalamin group was significantly greater than that in the placebo group ( P=.044 ) . The change in the 10-microg cyanocobalamin group was not significantly different from that in the placebo group ( P=.186 ) . Eight of 10 subjects in each treatment group were classified as responders , compared with two of 11 in the placebo group ( P=.004 ) . Homocysteine levels fell in patients receiving cyanocobalamin , but this fall failed to reach statistical significance . There were no significant changes in the other parameters measured . CONCLUSION Cyanocobalamin supplementation of 50 microg but not 10 microg daily produced a significant increase in serum vitamin B12 . This result has implication s for the management of patients with subnormal or borderline serum vitamin B12 concentrations and for food fortification with vitamin B12",
"People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine ( tHcy ) concentrations . In a proof of principle trial , we studied the effect of oral vitamin B12 ( 500 microg ) and /or 100 g cooked green leafy vegetables ( GLV ) every alternate day in a 2x2 factorial design over a 6-week period . Forty-two non-pregnant vegetarian women ( age 20 - 50 years ) were r and omly allocated to four study groups . Clinical measurements were made at the beginning and at the end of the study , and blood sample s were collected before , and 2 and 6 weeks after commencement of intervention . Forty women completed the trial . Twenty-six women had low vitamin B12 status ( 15 micromol/L ) . GLV supplementation did not alter plasma folate or tHcy . Vitamin B12 supplementation increased plasma vitamin B12 concentration ( 125 to 215 pmol/L , p tHcy concentration ( 18.0 to 13.0 micromol/L , p Plasma vitamin B12 and tHcy concentrations did not change in those who did not receive vitamin B12 , and there was no change in plasma folate concentration in any of the groups . Blood haemoglobin concentration increased marginally within first two weeks in those women who received vitamin B12 ( by 3 g/L , p macrocytosis decreased from 2 to zero . There was no change in vibration sensory threshold during the period of the study . High-dose per oral vitamin B12 supplementation significantly reduced plasma tHcy within 2 weeks but did not achieve normal plasma tHcy concentration even after 6 weeks . People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine ( tHcy ) concentrations",
"Elevated plasma homocysteine ( tHcy ) is a risk factor for Alzheimer 's disease ( AD ) , and thus B vitamins may have a role in the prevention of AD . The objective of this study was to determine if tHcy lowering vitamins decrease the circulating levels of A-beta protein 1 - 40 ( A beta 40 ) . We r and omized 299 older men to treatment with 2 mg of folate , plus 25 mg of B6 and 400 microg of B12 , or placebo . After 2 years of treatment the mean ( S.E. ) increase of A beta 40 was 7.0 pg/ml ( 8.4 ) in the vitamin group ( 4.9 % ) , and 26.8 pg/ml ( 7.7 ) ( 18.5 % ) in the placebo group . We conclude that B vitamins may decrease the plasma level of A beta 40 and have a role in the prevention of AD",
"Blood indicators of eight vitamins ( B1 , B2 , B6 , C , E , A , B12 , folate ) and six minerals ( Cu , Mg , Zn , Ca , P , Al ) were measured in 86 athletes before and after a 7- to 8-month period of training . During this period half consumed a multivitamin/mineral supplement and a matched group took a placebo . Following the supplementation period , blood biochemical indicators of B1 , B6 , B12 , and folate status all increased but there were no significant effects of supplementation on B2 , C , E , and A , or on the blood levels of any of the minerals . The supplementation had no effect on red or white cell counts or on hemoglobin levels . Irrespective of the supplementation , some blood measures varied according to sex , females evidencing significantly higher values than males for vitamins C , E , copper , magnesium , and aluminium , with B2 being higher in males . It is concluded that 7 to 8 months of multivitamin/mineral supplementation increased the blood nutritional status of some vitamins but did not affect any blood mineral levels , and that some blood nutritional indicators may vary according to sex",
"Objectives To determine whether in the current study the supply of a nutrient dense drink has a positive effect on mental and physical function of institutionalized elderly people . Design A 24-week , r and omized , double-blind , placebo-controlled , parallel-group , intervention trial . Setting Homes for the elderly and nursing homes in the Netherl and s. Participants Institutionalized elderly people older than 60 years , with a BMI ≤ 30 kg/m2 , and a Mini-Mental State Examination score of at least 10 points . InterventionIn addition to their usual diet the participants ( n=176 ) received either a nutrient dense drink or a placebo drink twice a day during 24 weeks . Measurements The functionality measures included cognitive function , mood , physical performance and the ability to perform activities of daily living . Results In the supplement group a favorable effect of the intervention drink on body weight ( 1.6 kg difference in change ; P = .035 ) , calf circumference ( 0.9 cm difference in change ; P = .048 ) , and blood values ( e.g. Hcy decreased from 16.8 to 11.2 µmol/L in the supplement group ) was found . In the total group no significant effect was found on functionality outcomes . However , a subgroup of participants with BMI at baseline below 24.4 kg/m2 performed better on the cognitive subscale of Alzheimer ’s Disease Assessment Scale ( P = .09 ) , and its language sub score ( P = .01 ) after 24 weeks of intervention . Conclusion The results in the total group of this trial suggest that the nutritional supplement used in this study improves nutritional status . Furthermore , the results of this trial suggest that it is effective as treatment for decreasing function in a subgroup of institutionalized elderly people with low BMI",
"PURPOSE Elevated C-reactive protein levels are associated with the risk of cardiovascular disease and diabetes . We examined whether multivitamins reduce C-reactive protein levels . METHODS We performed a post hoc subgroup analysis of a 6-month , r and omized , double-blind , placebo-controlled trial . Patients ( n = 87 ; mean age , 53 years ) for whom frozen plasma sample s were available ; who did not have an inflammatory condition at baseline ; and who were not hospitalized , taking antibiotics , smoking , or starting statin therapy during the study were included . C-reactive protein and plasma vitamin levels were measured at baseline and 6 months . RESULTS At 6 months , C-reactive protein levels were significantly lower in the multivitamin group than in the placebo group ( between-group difference = -0.91 mg/L ; 95 % confidence interval : -1.52 to -0.30 ; P= 0.005 ) . The reduction in C-reactive protein levels was most evident in patients who had elevated levels ( > or = 1.0 mg/L ) at baseline . Of the six vitamins measured ( C , E , B(6 ) , B(12 ) , folate , and beta carotene ) , only vitamin B(6 ) ( baseline : r = -0.31 , P= 0.003 ; 6 months : r = -0.29 , P= 0.006 ) and vitamin C ( baseline : r = -0.25 , P= 0.02 ) were inversely associated with C-reactive protein level . CONCLUSION In a post hoc analysis of a r and omized , double-blind , placebo-controlled study , multivitamin use was associated with lower C-reactive protein levels . Other similarly formulated multivitamins may yield comparable results",
"Objective : To determine the effect of folic acid , vitamin B6 and B12 fortified spreads on the blood concentrations of these vitamins and homocysteine . Design and setting : A 6-week r and omized , double-blinded , placebo-controlled , parallel trial carried out in a clinical research center . Subjects : One hundred and fifty healthy volunteers ( 50 % males ) . Interventions : For 6 weeks , the subjects consumed the test spreads ( 20 g/day ) : containing per 20 g ( 1 ) 200 μg folic acid , 2 μg vitamin B12 and 1 mg vitamin B6 , or ( 2 ) 400 μg folic acid , 2 μg vitamin B12 and 1 mg vitamin B6 or ( 3 ) no B-vitamins ( control spread ) . Results : The B-vitamin status increased on using the test spreads , with the largest effect on the serum folate concentration : 48 % in men and 58 % in women on spread 1 and 92 and 146 % , respectively , on spread 2 ( P-values all 0.05 ) . The plasma homocysteine decreased in the groups treated with the fortified spreads as compared to the control group . Average decreases were for males : 0.7±1.5 μmol/l ( 6.8 % ) on spread 1 and 1.7±1.7 μmol/l ( 17.6 % ) on spread 2 and for females : 1.4±1.2 μmol/l ( 14.2 % ) and 2.4±2.0 μmol/l ( 23.3 % ) , respectively ( P-values all with folic acid , vitamin B6 and vitamin B12 for 6 weeks significantly increases the blood concentrations of these vitamins and significantly decreases the plasma concentration of homocysteine . Fortified staple foods like spreads can contribute to the lowering of homocysteine concentrations . Sponsorship : Unilever Research and Development , Vlaardingen , The Netherl and"
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Sedentary behaviour has emerged as a unique determinant of health in adults . Studies in children and adolescents have been less consistent . We review ed the evidence to determine if the total volume and patterns ( i.e. breaks and bouts ) of objective ly measured sedentary behaviour were associated with adverse health outcomes in young people , independent of moderate-intensity to vigorous-intensity physical activity . Four electronic data bases ( EMBASE MEDLINE , Ovid EMBASE , PubMed and Scopus ) were search ed ( up to 12 November 2015 ) to retrieve studies among 2- to 18-year-olds , which used cross-sectional , longitudinal or experimental design s , and examined associations with health outcomes ( adiposity , cardio-metabolic , fitness , respiratory , bone/musculoskeletal , psychosocial , cognition/academic achievement , gross motor development and other outcomes ) . Based on 88 eligible observational studies , level of evidence grading and quantitative meta-analyses indicated that there is limited available evidence that the total volume or patterns of sedentary behaviour are associated with health in children and adolescents when accounting for moderate-intensity to vigorous-intensity physical activity or focusing on studies with low risk of bias . Quality evidence from studies with robust design s and methods , objective measures of sitting , examining associations for various health outcomes , is needed to better underst and if the overall volume or patterns of sedentary behaviour are independent determinants of health in children and adolescents
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"BACKGROUND Sedentary behavior is a risk factor for cardiometabolic disease . Regularly interrupting sedentary behavior with activity breaks may lower this risk . OBJECTIVE We compared the effects of prolonged sitting , continuous physical activity combined with prolonged sitting , and regular activity breaks on postpr and ial metabolism . DESIGN Seventy adults participated in a r and omized crossover study . The prolonged sitting intervention involved sitting for 9 h , the physical activity intervention involved walking for 30 min and then sitting , and the regular-activity-break intervention involved walking for 1 min 40 s every 30 min . Participants consumed a meal-replacement beverage at 60 , 240 , and 420 min . RESULTS The plasma incremental area under the curve ( iAUC ) for insulin differed between interventions ( overall P Regular activity breaks lowered values by 866.7 IU · L(-1 ) · 9 h(-1 ) ( 95 % CI : 506.0 , 1227.5 IU · L(-1 ) · 9 h(-1 ) ; P with prolonged sitting and by 542.0 IU · L(-1 ) · 9 h(-1 ) ( 95 % CI : 179.9 , 904.2 IU · L(-1 ) · 9 h(-1 ) ; P = 0.003 ) when compared with physical activity . Plasma glucose iAUC also differed between interventions ( overall P . Regular activity breaks lowered values by 18.9 mmol · L(-1 ) · 9 h(-1 ) ( 95 % CI : 10.0 , 28.0 mmol · L(-1 ) · 9 h(-1 ) ; P with prolonged sitting and by 17.4 mmol · L(-1 ) · 9 h(-1 ) ( 95 % CI : 8.4 , 26.3 mmol · L(-1 ) · 9 h(-1 ) ; P compared with physical activity . Plasma triglyceride iAUC differed between interventions ( overall P = 0.023 ) . Physical activity lowered values by 6.3 mmol · L(-1 ) · 9 h(-1 ) ( 95 % CI : 1.8 , 10.7 mmol · L(-1 ) · 9 h(-1 ) ; P = 0.006 ) when compared with regular activity breaks . CONCLUSION Regular activity breaks were more effective than continuous physical activity at decreasing postpr and ial glycemia and insulinemia in healthy , normal-weight adults . This trial was registered with the Australian New Zeal and Clinical Trials registry as ACTRN12610000953033",
"Background The activPAL has been identified as an accurate and reliable measure of sedentary behaviour . However , only limited information is available on the accuracy of the activPAL activity count function as a measure of physical activity , while no unit calibration of the activPAL has been completed to date . This study aim ed to investigate the criterion validity of the activPAL , examine the concurrent validity of the activPAL , and perform and vali date a value calibration of the activPAL in an adolescent female population . The performance of the activPAL in estimating posture was also compared with sedentary thresholds used with the ActiGraph accelerometer . Method ologies Thirty adolescent females ( 15 developmental ; 15 cross-validation ) aged 15–18 years performed 5 activities while wearing the activPAL , ActiGraph GT3X , and the Cosmed K4B2 . A r and om coefficient statistics model examined the relationship between metabolic equivalent ( MET ) values and activPAL counts . Receiver operating characteristic analysis was used to determine activity thresholds and for cross-validation . The r and om coefficient statistics model showed a concordance correlation coefficient of 0.93 ( st and ard error of the estimate = 1.13 ) . An optimal moderate threshold of 2997 was determined using mixed regression , while an optimal vigorous threshold of 8229 was determined using receiver operating statistics . The activPAL count function demonstrated very high concurrent validity ( r = 0.96 , p st and ing , and stepping between direct observation and the activPAL and ActiGraph were 100 % , 98.1 % , 99.2 % and 100 % , 0 % , 100 % , respectively . Conclusions These findings suggest that the activPAL is a valid , objective measurement tool that can be used for both the measurement of physical activity and sedentary behaviours in an adolescent female population",
"OBJECTIVE Observational studies show breaking up prolonged sitting has beneficial associations with cardiometabolic risk markers , but intervention studies are required to investigate causality . We examined the acute effects on postpr and ial glucose and insulin levels of uninterrupted sitting compared with sitting interrupted by brief bouts of light- or moderate-intensity walking . RESEARCH DESIGN AND METHODS Overweight/obese adults ( n = 19 ) , aged 45–65 years , were recruited for a r and omized three-period , three-treatment acute crossover trial : 1 ) uninterrupted sitting ; 2 ) seated with 2-min bouts of light-intensity walking every 20 min ; and 3 ) seated with 2-min bouts of moderate-intensity walking every 20 min . A st and ardized test drink was provided after an initial 2-h period of uninterrupted sitting . The positive incremental area under curves ( iAUC ) for glucose and insulin ( mean [ 95 % CI ] ) for the 5 h after the test drink ( 75 g glucose , 50 g fat ) were calculated for the respective treatments . RESULTS The glucose iAUC ( mmol/L ) ⋅ h after both activity-break conditions was reduced ( light : 5.2 [ 4.1–6.6 ] ; moderate : 4.9 [ 3.8–6.1 ] ; both P compared with uninterrupted sitting ( 6.9 [ 5.5–8.7 ] ) . Insulin iAUC ( pmol/L ) ⋅ h was also reduced with both activity-break conditions ( light : 633.6 [ 552.4–727.1 ] ; moderate : 637.6 [ 555.5–731.9 ] , P compared with uninterrupted sitting ( 828.6 [ 722.0–950.9 ] ) . CONCLUSIONS Interrupting sitting time with short bouts of light- or moderate-intensity walking lowers postpr and ial glucose and insulin levels in overweight/obese adults . This may improve glucose metabolism and potentially be an important public health and clinical intervention strategy for reducing cardiovascular risk ",
"Objectives Evaluate the predictive validity of ActiGraph energy expenditure equations and the classification accuracy of physical activity intensity cut-points in preschoolers . Methods Forty children aged 4–6 years ( 5.3±1.0 years ) completed a ∼150-min room calorimeter protocol involving age-appropriate sedentary , light and moderate-to vigorous-intensity physical activities . Children wore an ActiGraph GT3X on the right mid-axillary line of the hip . Energy expenditure measured by room calorimetry and physical activity intensity classified using direct observation were the criterion methods . Energy expenditure was predicted using Pate and Puyau equations . Physical activity intensity was classified using Evenson , Sirard , Van Cauwenberghe , Pate , Puyau , and Reilly , ActiGraph cut-points . Results The Pate equation significantly overestimated VO2 during sedentary behaviors , light physical activities and total VO2 ( P No difference was found between measured and predicted VO2 during moderate-to vigorous-intensity physical activities ( P = 0.072 ) . The Puyau equation significantly underestimated activity energy expenditure during moderate-to vigorous-intensity physical activities , light-intensity physical activities and total activity energy expenditure ( P no overestimation of activity energy expenditure during sedentary behavior was found . The Evenson cut-point demonstrated significantly higher accuracy for classifying sedentary behaviors and light-intensity physical activities than others . Classification accuracy for moderate-to vigorous-intensity physical activities was significantly higher for Pate than others . Conclusion Available ActiGraph equations do not provide accurate estimates of energy expenditure across physical activity intensities in preschoolers . Cut-points of ≤25counts⋅15 s−1 and ≥420 counts⋅15 s−1 for classifying sedentary behaviors and moderate-to vigorous-intensity physical activities , respectively , are recommended",
"Background Studies relating physical activity ( PA ) to weight gain in children have produced mixed results , although there is some evidence for stronger associations with more intense physical activities . The present study tested the hypothesis that weight gain over one year in 8–10 year olds would be more strongly predicted by moderate and vigorous physical activity ( MVPA ) than total physical activity ( total PA ) or sedentary behaviour . Methodology Participants were 280 children taking part in the Physical Exercise and Appetite in Children Study ( PEACHES ) . Weight status was assessed using body mass index ( BMI ) , fat mass index ( FMI ) , and waist circumference ( WC ) in school Year 4 ( baseline ; age 8.7 yrs ) and Year 5 ( follow-up ; age 9.7 yrs ) . Physical activity was measured at baseline using the Actigraph GT1 M accelerometer to assess total PA ( mean accelerometers counts per minute ) , MVPA ; ≥4000 counts per minute ) and sedentary time ( counts per minute ) . Principal Findings After adjustment for baseline BMI , SES , sex and ethnicity , MVPA was significantly associated with follow – up BMI ( adjusted β = −0.07 ; p = 0.002 ) . This association was independent of total PA or sedentary time . Similar results were observed for FMI ; again MVPA was significantly associated with follow up FMI ( β = −0.16 ; p = 0.001 ) independent of total PA or sedentary time . The pattern was similar for WC ( β = −0.07 ) , but the association between MVPA and WC did not reach significance at p = 0.06 . Conclusion The results of this study strongly support promotion of MVPA in children",
"Background Physical activity ( PA ) is associated with positive cardio-metabolic health and emerging evidence suggests sedentary behavior ( SB ) may be detrimental to children 's health independent of PA . The primary aim of the Transform-Us ! study is to determine whether an 18-month , behavioral and environmental intervention in the school and family setting s results in higher levels of PA and lower rates of SB among 8 - 9 year old children compared with usual practice ( post-intervention and 12-months follow-up ) . The secondary aims are to determine the independent and combined effects of PA and SB on children 's cardio-metabolic health risk factors ; identify the factors that mediate the success of the intervention ; and determine whether the intervention is cost-effective . Methods / design A four-arm cluster-r and omized controlled trial ( RCT ) with a 2 × 2 factorial design , with schools as the unit of r and omization . Twenty schools will be allocated to one of four intervention groups , sedentary behavior ( SB-I ) , physical activity ( PA-I ) , combined SB and PA ( SB+PA-I ) or current practice control ( C ) , which will be evaluated among approximately 600 children aged 8 - 9 years in school year 3 living in Melbourne , Australia . All children in year 3 at intervention schools in 2010 ( 8 - 9 years ) will receive the intervention over an 18-month period with a maintenance ' booster ' delivered in 2012 and children at all schools will be invited to participate in the evaluation assessment s. To maximize the sample and to capture new students arriving at intervention and control schools , recruitment will be on-going up to the post-intervention time point . Primary outcomes are time spent sitting and in PA assessed via accelerometers and inclinometers and survey . Discussion To our knowledge , Transform-Us ! is the first RCT to examine the effectiveness of intervention strategies for reducing children 's overall sedentary time , promoting PA and optimizing health outcomes . The integration of consistent strategies and messages to children from teachers and parents in both school and family setting s is a critical component of this study , and if shown to be effective , may have a significant impact on educational policies as well as on pedagogical and parenting practice s . Trial registration ACTRN12609000715279 ; Current Controlled Trials IS RCT",
"OBJECTIVE To examine the prospect i ve association between objective ly measured time spent sedentary and insulin resistance and whether this association is independent of moderate- and vigorous-intensity physical activity ( MVPA ) and other relevant confounders . RESEARCH DESIGN AND METHODS This was a population -based study ( Medical Research Council Ely study ) in 376 middle-aged adults ( 166 men ; 210 women ) over 5.6 years of follow-up . Physical activity and sedentary time were measured objective ly by individually calibrated minute-by-minute heart rate monitoring at both baseline and follow-up . Sedentary time was calculated as the heart rate observations ( in minutes ) below an individually predetermined threshold ( flex heart rate ) and expressed as a percentage of total monitored time during waking hours over 4 days . The percentage of time spent above 1.75 × resting heart rate represented MVPA . Fasting plasma insulin was used as a surrogate measure of insulin resistance . RESULTS Time spent sedentary at baseline was significantly and positively associated with log fasting insulin at follow-up ( β = 0.003 , 95 % CI 0.0006–0.006 , P = 0.015 ) independent of baseline age , sex , fat mass , fasting insulin , smoking status , and follow-up time . After further adjustment for MVPA , this association was somewhat strengthened ( β = 0.004 , 95 % CI 0.0009–0.006 , P = 0.009 ) . CONCLUSIONS Time spent sedentary predicts higher levels of fasting insulin independent of the amount of time spent at moderate- and vigorous-intensity activity levels . This highlights the importance of reducing sedentary time in order to improve metabolic health , possibly in addition to the benefits associated with a physically active lifestyle",
"BACKGROUND The importance of variation in total volume of physical activity or moderate- to vigorous-intensity physical activity ( MVPA ) to development of body fatness in childhood is unclear , and it is unclear if physical activity has a greater influence on adiposity in boys than girls . PURPOSE To assess relationships between 2-year changes in objective ly measured physical activity , sedentary behavior , and adiposity in English children . METHODS Prospect i ve cohort study , set in Northeast Engl and , of a socioeconomically representative sample of 403 children . Measures were change in accelerometer-determined physical activity and sedentary behavior from age 7 to 9 years ( data collected 2006/2007 and 2008/2009 ; analyzed in 2010 ) and concurrent change in adiposity ( fat mass index derived from bioelectric impedance ) and change in BMI Z-score . RESULTS Decline in MVPA was associated with a greater increase in fat mass index in boys but not girls . Declining MVPA was associated with increased BMI Z-score in boys but not girls . Increased sedentary behavior was not associated with increased BMI Z-score in either gender . CONCLUSIONS Avoiding mid-late childhood reductions in MVPA may reduce excessive fat gain , although such strategies may have greater impact on boys than girls",
"Background : Physical activity ( PA ) and sedentary time ( SED ) have both been suggested as potential risk factors for adiposity in children . However , there is paucity of data examining the temporal associations between these variables . Objective : This study aim ed to analyze the cross-sectional and prospect i ve associations between PA , SED and body composition in children . Methods : A total of 510 children ( age at baseline 10.1±0.8 , age at follow-up 11.8±0.9 ) from six Portuguese schools from the Oeiras Municipality participated in this study . PA and SED were measured by accelerometry and trunk fat mass ( TFM ) and body fat mass ( BFM ) were measured by dual energy X-ray absorptiometry . Fat mass index ( FMI ) was calculated as BFM divided by height squared . Several regression models adjusted for age , sex , maturity status , follow-up duration , baseline levels of the outcome variable and SED or moderate to vigorous PA ( MVPA ) were performed . Results : MVPA ( min per day ) was cross-sectionally inversely associated with adiposity indexes ( FMI , TFM and BFM ) . Adiposity indexes were inversely associated with time in MVPA . In prospect i ve analyses , MVPA was associated with a lower levels of FMI ( β=−0.37 , 95 % confidence interval ( CI ) : −0.49 to −0.26 , P TFM ( β=−0.20 , 95 % CI : −0.29 to −0.10 , P and BFM ( β=−0.37 , 95 % CI : −0.49 to −0.26 , P outcome variables MVPA remained a significant predictor of lower adiposity indexes ( FMI : β=−0.09 , 95 % CI : −0.16 to −0.01 , P 0.00 , P Adiposity was not associated with MVPA when modeled as the exposure in prospect i ve analyses . SED was not related with adiposity indexes , except for the relationship with FMI . Conclusions : In cross-sectional and prospect i ve analyses , MVPA is associated with lower adiposity independent of covariates and SED . Results suggest that promoting MVPA is important for preventing gain in adiposity in healthy children",
"Objective : To investigate the relationships between the time spent in specific intensities of activity and inactivity , cardiorespiratory fitness and body composition in children . Methods : A cross-sectional study was conducted in a r and om sample of schools . Height , weight and waist circumference were measured in 224 children aged 7–10 years . Cardiorespiratory fitness was estimated by the 20 m multistage running test , and physical activity was measured over 4 days by the RT3 ( a triaxial accelerometer ) . Time each day spent in moderate and vigorous intensities of activity was calculated . Results : Twelve schools agreed to participate in the study . Body composition and fitness data were obtained for 224 children and activity data for 152 children . Boys were found to take part in about twice as much vigorous and hard activity as girls ( mean ( 95 % confidence interval ) 64.3 ( 53.2 to 75.4 ) min in boys compared with 37 ( 33.1 to 40.9 ) min in girls ; p time spent in vigorous activity ( p between waist circumference and time spent in vigorous activity ( r = –0.31 , p . Time spent sedentary was positively correlated with waist circumference in boys ( r = 0.33 , p fitness and both body mass index ( r = –0.274 , p and waist circumference ( boys : r = –0.503 , p , body composition was inversely related to fitness and to vigorous activity and was positively related to inactivity . In girls , body composition was related to fitness but not to specific components of physical activity",
"The aim of this study is to examine sedentary and light activity in relation to overweight in adolescent girls . Adolescent girls were r and omly recruited from 36 schools participating in the Trial of Activity for Adolescent Girls ( TAAG ) . Assessment s included age , ethnicity , socioeconomic status , and body composition estimated from weight , height , and triceps skinfold . Sedentary and light activity was measured for 6 days using accelerometry in 6th and in 8th grade among two r and omly sample d cross-sections of girls . Sedentary activity increased from the 6th to 8th grade by 51.5 min/day . In the 8th grade , a significantly higher number of hours in sedentary activity for each of the 6-days of measurement were evident with higher tertiles of percent body fat ( 30 - 35 % , > 35 % fat ) ( P 95th percentiles ) . The increase in sedentary activity was observed on weekdays , but not on weekends for percent body fat tertiles . In the cohort of girls measured in both 6th and 8th grade s , the mean cross-sectional coefficient estimates were significant for percent body fat , but not BMI for sedentary and light activities . Adolescent girls from the 6th to 8th grade are shifting their time from light to more sedentary activity as measured by accelerometers . In addition , the increase in sedentary activity is not associated with an adverse effect on BMI or percent body fat . The eventual impact of this shift to a more sedentary lifestyle on body composition and other outcomes needs to be evaluated further",
"OBJECTIVE To report time and prevalence of leisure time sedentary and active behaviors in adolescents . METHOD Cross-sectional , stratified , r and om sample from schools in 14 districts in Scotl and , 2002 - 03 , using ecological momentary assessment ( n=385 boys , 606 girls ; mean age 14.1 years ; range 12.6 - 16.7 years ) . This is a method of capturing current behavioral episodes . We used 15 min time intervals . RESULTS Television viewing occupied the most leisure time . The five most time consuming sedentary activities occupied 228 min per weekday and 396 min per weekend day for boys , and 244 min per weekday and 400 min per weekend day for girls , with TV occupying one-third to one-half of this time . In contrast , 62 min was occupied by active transport and sports/exercise per weekday and 91 min per weekend day for boys , with 55 min per weekday and 47 min per weekend day for girls . A minority watched more than 4 h of TV per day , with more at weekends . Other main sedentary behaviors for boys were homework , playing computer/video games , and motorised transport and , for girls , homework , motorised transport , and sitting and talking . CONCLUSION Scottish adolescents engage in a variety of sedentary and active behaviors . Research into sedentary behavior must assess multiple behaviors and not rely solely on TV viewing",
"Objective : To determine if time spent in objective ly measured sedentary behavior is associated with a change in body mass index ( BMI ) between ages 9 and 15 years , adjusting for moderate-to-vigorous physical activity ( MVPA ) . Design : Prospect i ve observational study of children at ages 9 ( 2000 ) , 11 ( 2002 ) , 12 ( 2003 ) and 15 years ( 2006 ) . Longitudinal quantile regression was used to model the influence of predictors on changes at the 10th , 25th , 50th , 75th and 90th BMI percentiles over time . Subjects : Participants were enrolled in the National Institute of Child Health and Human Development ( NICHD ) Study of Early Child Care and Youth Development and include both boys and girls ( n=789 ) . Measurements : Objective ly measured BMI ( kg m–2 ) was the outcome variable and objective ly measured sedentary behavior was the main predictor . Adjustment was also made for MVPA , gender , race , maternal education , hours of sleep and healthy eating index . Results : Increases in BMI were observed at all percentiles , with the greatest increase observed at the 90th BMI percentile . Spending more time in sedentary behavior ( h per day ) was associated with additional increases in BMI at the 90th , 75th and 50th BMI percentiles , independent of MVPA and the other covariates ( 90th percentile=0.59 , 95 % confidence interval ( 95 % CI ) : 0.19–0.98 kg m–2 ; 75th percentile=0.48 , 95 % CI : 0.25–0.72 kg m–2 ; and 50th percentile=0.19 , 95 % CI : 0.05–0.33 kg m–2 ) . No associations were observed between sedentary behavior and changes at the 25th and 10th BMI percentiles . Conclusion : Sedentary behavior was associated with greater increases in BMI at the 90th , 75th and 50th BMI percentiles between ages 9 and 15 years , independent of MVPA . Preventing an increase in sedentary behavior from childhood to adolescence may contribute to reducing the number of children classified as obese",
"UNLABELLED The absence of comparative validity studies has prevented research ers from reaching consensus regarding the application of intensity-related accelerometer cut points for children and adolescents . PURPOSE This study aim ed to evaluate the classification accuracy of five sets of independently developed ActiGraph cut points using energy expenditure , measured by indirect calorimetry , as a criterion reference st and ard . METHODS A total of 206 participants between the ages of 5 and 15 yr completed 12 st and ardized activity trials . Trials consisted of sedentary activities ( lying down , writing , computer game ) , lifestyle activities ( sweeping , laundry , throw and catch , aerobics , basketball ) , and ambulatory activities ( comfortable walk , brisk walk , brisk treadmill walk , running ) . During each trial , participants wore an ActiGraph GT1 M , and V˙O2 was measured breath-by-breath using the Oxycon Mobile portable metabolic system . Physical activity intensity was estimated using five independently developed cut points : Freedson/Trost ( FT ) , Puyau ( PU ) , Treuth ( TR ) , Mattocks ( MT ) , and Evenson ( EV ) . Classification accuracy was evaluated via weighted κ statistics and area under the receiver operating characteristic curve ( ROC-AUC ) . RESULTS Across all four intensity levels , the EV ( κ=0.68 ) and FT ( κ=0.66 ) cut points exhibited significantly better agreement than TR ( κ=0.62 ) , MT ( κ=0.54 ) , and PU ( κ=0.36 ) . The EV and FT cut points exhibited significantly better classification accuracy for moderate- to vigorous-intensity physical activity ( ROC-AUC=0.90 ) than TR , PU , or MT cut points ( ROC-AUC=0.77 - 0.85 ) . Only the EV cut points provided acceptable classification accuracy for all four levels of physical activity intensity and performed well among children of all ages . The widely applied sedentary cut point of 100 counts per minute exhibited excellent classification accuracy ( ROC-AUC=0.90 ) . CONCLUSIONS On the basis of these findings , we recommend that research ers use the EV ActiGraph cut points to estimate time spent in sedentary , light- , moderate- , and vigorous-intensity activity in children and adolescents",
"Childhood obesity is a public health concern with significant health and economic impacts . We conducted a prospect i ve experimental study in 4 classrooms in central Texas to determine the effect of desks that encourage st and ing rather than sitting on caloric expenditure in children . Students were monitored with calorie expenditure-measuring arm-b and s worn for 10 days in the fall and spring . The treatment group experienced significant increases in calorie expenditure over the control group , a finding that has implication s for policy and practice"
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4117a5e6-06ff-11f0-808a-c43d1ab1c353
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BACKGROUND Functional training is a new training vision that was prepared from the gesture imitation of daily activities . Although your use has become popular in clinical practice , the influence of the several cardiorespiratory adjustments performed during the functional training in different population s and conditions is unknown . So , the aim of this systematic review was to gather information in the literature regarding the influence of functional training on cardiorespiratory parameters . METHODS We conducted search strategies on MEDLINE , PEDro , EMBASE , SportD iscus and Cochrane to identify r and omized controlled trials investigating the effects of functional training on cardiorespiratory parameters . Method ological quality of the included studies was assessed using the PEDro scale . Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) summarized the evidence . RESULTS Five original studies were included . Effects favoured functional training on oxygen consumption ( VO2 ) at intermediate-term follow-up : weighted mean difference -1·0 ( 95 % CI : 5·4 - 3·3 ) , P = 0·642 , and a small and not clinical ly important effect observed on VO2 favouring control at intermediate-term follow-up ( i.e. mean difference of 1·30 ( 95 % CI 1·07 - 1·53 ) , P that functional training is better than other interventions to improve cardiovascular parameters . This result encourages new search es about the theme
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"Background Although basic research has uncovered biological mechanisms by which exercise could maintain and enhance adult brain health , experimental human studies with older adults have produced equivocal results . Purpose This r and omized clinical trial aim ed to investigate the hypotheses that ( a ) the effects of exercise training on the performance of neurocognitive tasks in older adults is selective , influencing mainly tasks with a substantial executive control component and ( b ) performance in neurocognitive tasks is related to cardiorespiratory fitness . Methods Fifty-seven older adults ( 65–79 years ) participated in aerobic or strength- and -flexibility exercise training for 10 months . Neurocognitive tasks were selected to reflect a range from little ( e.g. , simple reaction time ) to substantial ( i.e. , Stroop Word – Color conflict ) executive control . Results Performance in tasks requiring little executive control was unaffected by participating in aerobic exercise . Improvements in Stroop Word – Color task performance were found only for the aerobic exercise group . Changes in aerobic fitness were unrelated to changes in neurocognitive function . Conclusions Aerobic exercise in older adults can have a beneficial effect on the performance of speeded tasks that rely heavily on executive control . Improvements in aerobic fitness do not appear to be a prerequisite for this beneficial effect",
"Objective : To compare the effects of aerobic and resistance exercise on weight , muscle strength , cardiovascular fitness , blood pressure and mood in obese women who were not on an energy-restricted diet . Design : R and omized , prospect i ve , controlled trial . Setting : Department of Physical Medicine and Rehabilitation , University Hospital . Subjects : Sixty obese women were assigned to one of three groups : aerobic exercise ( n=20 ) , resistance exercise ( n=20 ) and control group ( n=20 ) . Interventions : The aerobic exercise group performed both walking and leg cycle exercise with increasing duration and frequency . The resistance exercise group performed progressive weight-resistance exercises for the upper and lower body . Main outcome measures : Before and after a 12-week period , all subjects were evaluated by anthropometric measurement , rating of mood , cardiorespiratory capacity and maximum strength of trained muscles . Results : After a 12-week training period , subjects in the resistance group showed significant improvement in one-repetition maximum test of hip abductors ( 7.95±3.58 kg ) , quadriceps ( 14±7.18 kg ) , biceps ( 3.37± 2.84 kg ) and pectorals ( 8.75±5.09 kg ) compared with those in the control group ( P increased ( 0.51±0.40 ) and Beck Depression Scale scores decreased ( -5.40±4.27 ) in the aerobic exercise group compared with the control group , significantly ( P Only in hip abductor muscle strength was there a significant increase in the resistance exercise group compared with the aerobic exercise group ( P Both aerobic exercise and resistance exercise result ed in improved performance and exercise capacity in obese women . While aerobic exercise appeared to be beneficial with regard to improving depressive symptoms and maximum oxygen consumption , resistance exercise was beneficial in increasing muscle strength ",
"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",
"The authors investigated the effects of moderate-intensity resistance , aerobic , or combined exercise on blood pressure and arterial stiffness in overweight and obese individuals compared with no exercise . Participants were r and omized to 4 groups : control , aerobic , resistance , and combination . Assessment s were made at baseline , week 8 , and week 12 . In participant- design ated responders , those in the intervention groups who had improved levels of systolic blood pressure ( SBP ) or augmentation index ( AI ) , we observed a significant decrease of SBP in aerobic ( -4 % , P=.027 ) , resistance ( -5.1 % , P=.04 ) , and combination groups ( -6.3 % , P=.000 ) at week 8 and in the combination group ( -6.3 % , P=.005 ) at week 12 , compared with baseline . AI was significantly lower at week 12 in the aerobic ( -12 % , P=.047 ) , resistance ( -9.5 % , P=.036 ) , and combination ( -12.7 % , P=.003 ) groups compared with baseline , as well as in the combination group ( -10.7 % , P=.047 ) compared with the control group . We did not observe significant changes in SBP , DBP , or AI between the interventions when assessing the entire cohort , although there were significant improvements in a subgroup of responders . Thus , some but not all overweight and obese individuals can improve blood pressure and arterial stiffness by participating in regular combination exercise , decreasing the risk of developing cardiovascular disease",
"Background : Age-related postural misalignment , balance deficits and strength/power losses are associated with impaired functional mobility and an increased risk of falling in seniors . Core instability strength training ( CIT ) involves exercises that are challenging for both trunk muscles and postural control and may thus have the potential to induce benefits in trunk muscle strength , spinal mobility and balance performance . Objective : The objective was to investigate the effects of CIT on measures of trunk muscle strength , spinal mobility , dynamic balance and functional mobility in seniors . Methods : Thirty-two older adults were r and omly assigned to an intervention group ( INT ; n = 16 , aged 70.8 ± 4.1 years ) that conducted a 9-week progressive CIT or to a control group ( n = 16 , aged 70.2 ± 4.5 years ) . Maximal isometric strength of the trunk flexors/extensors/lateral flexors ( right , left)/rotators ( right , left ) as well as of spinal mobility in the sagittal and the coronal plane was measured before and after the intervention program . Dynamic balance ( i.e. walking 10 m on an optoelectric walkway , the Functional Reach test ) and functional mobility ( Timed Up and Go test ) were additionally tested . Results : Program compliance was excellent with participants of the INT group completing 92 % of the training sessions . Significant group × test interactions were found for the maximal isometric strength of the trunk flexors ( 34 % , p extensors ( 21 % , p lateral flexors ( right : 48 % , p left rotators ( 42 % , p for spinal mobility in the sagittal ( 11 % , p coronal plane ( 11 % , p = 0.06 ) directions , for stride velocity ( 9 % , p the coefficient of variation in stride velocity ( 31 % , p the Functional Reach test ( 20 % , p Up and Go test ( 4 % , p : CIT proved to be a feasible exercise program for seniors with a high adherence rate . Age-related deficits in measures of trunk muscle strength , spinal mobility , dynamic balance and functional mobility can be mitigated by CIT . This training regimen could be used as an adjunct or even alternative to traditional balance and /or resistance training",
"Background : The importance of maintaining strength in older adults is well documented and various training modalities have been recommended ; however , the effectiveness of various interventions with high translation to public health practice has not been completely characterized . Additionally , the interrelations among mode , strength , and lower extremity physical function ( LEPF ) changes in older adults warrant further investigation . Purpose : The primary aims were to examine the effectiveness of cardiovascular endurance training ( CVE ) compared with balance and flexibility training ( FLEX ) and to explore the relationship of muscle strength to LEPF . Methods : Fifty-five adults ( 69.1 ± 5.6 years , 35 female ) were r and omly assigned to 10 months of CVE or FLEX . Knee extension and flexion at 60 and 120 ° ·s–1 were measured using an isokinetic dynamometer . LEPF was measured using a battery of tasks . The CVE group exercised using treadmills , cycles , and elliptical trainers . The FLEX group participated in a group exercise class that incorporated flexibility and balance activities . Results : The CVE training group significantly improved peak oxygen consumption by 6 % ( p = 0.03 ) , while the FLEX training group showed no change ( p = 0.47 ) . Participants significantly improved peak torque at both speeds and muscle actions by 21–65 % ( p ≤ 0.05 ) , with no group effect ( p > 0.05 ) . Both groups also significantly improved performance on all LEPF tasks included in this study ( 4–7 % , p ≤ 0.05 ) . Significant correlations ( all p = 0.00 ) were found between improvements in strength and improvements in LEPF including timed walk and peak torque extension and flexion at 60 ° ·s–1 ( r = 0.40 and 0.27 , respectively ) , obstacle walk and peak torque extension and flexion at 60 and 120 ° ·s–1 ( r range 0.27–0.40 ) , and stair ascent and peak torque extension at 120 ° ·s–1 ( r = 0.37 ) . Conclusions : Sedentary older adults achieve similar improvements in strength and LEPF with either CVE or FLEX training with the latter being related to improvements in leg strength ",
"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",
"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",
"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 .",
"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",
"BACKGROUND Resistance exercise ( RE ) is an important part of cardiac rehabilitation . However , it is not known about the low intensity of RE training that could modify the heart rate variability ( HRV ) , muscular strength and endurance in patients with coronary artery disease ( CAD ) . AIM To investigate the effects of high repetition/low load resistance training ( HR/LL-RT ) program on HRV and muscular strength and endurance in CAD patients . DESIGN R and omized and controlled trial . SETTING Patients seen at the Cardiopulmonary Physical Therapy Laboratory between May 2011 and November 2013 . POPULATION Twenty male patients with CAD were r and omized to a training group ( 61.3±5.2 years ) or control group ( 61±4.4 years ) . METHODS 1 repetition maximum ( 1-RM ) maneuver , discontinuous exercise test on the leg press ( DET-L ) , and resting HRV were performed before and after 8 weeks of HR/LL-RT on a 45 ° leg press . RMSSD , SD1 , mean HR and ApEn indices were calculated . The HR/LL-RT program consisted of a lower limb exercise using a 45 ° leg press ; 3 sets of 20 repetitions , two times a week . The initial load was set at 30 % of the 1-RM load and the duration of the HR/LL-RT program was performed for 8 weeks . RESULTS After 8 weeks of HR/LL-RT there were significant increases of RMSSD and SD1 indices in the training group only ( P in mean HR after HR/LL-RT in the training group ( P higher ApEn after in the training group ( P on HRV , as well as muscle strength and endurance in CAD patients . CLINICAL REHABILITATION IMPACT Eight weeks of HR/LL-RT is an effective sufficient to beneficially modify important outcomes as HRV , muscle strength and endurance in CAD patients"
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4117a622-06ff-11f0-808a-c43d1ab1c353
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Neck pain occurs frequently in western societies . In the majority of cases , no specific cause can be identified . In order to gain insight into the clinical course and prognostic factors of non-specific neck pain , a systematic review was conducted . A computerized literature search was carried out to identify observational studies on non-specific neck pain and r and omized clinical trials ( RCTs ) on conservative treatment of non-specific neck pain . Two review ers scored independently , the method ological quality of all identified publications , using a st and ardized set of 13 criteria which were divided into five categories according to : study population , study design , follow-up , outcome measures and analysis / data presentation . To determine prognosis per study , an overall percentage of recovery for the most important outcome measures ( pain , general improvement , functional status , health care utilization and lost days of work ) was calculated . In total 23 eligible publications were identified ( six observational studies and 17 RCTs ) . Only seven of 23 studies scored 50 % or more of the 13 items , indicating a generally poor quality of methods . The most prevalent method ological shortcomings appeared to be selection of the study population , the sample size and analysis techniques . Most information regarding the clinical course is available for the group of patients with complaints for more than 6 months , who are treated in a secondary care or an occupational setting . In this group of patients , 46 % ( median ) had less pain , with a range of 22 - 79 % and a general improvement that ranged between 37 and 95 % ( 47 % median ) . The reduction in the use of analgesics ranged between 32 and 80 % ( 37 % median ) . Six studies reported on prognostic factors . Bearing in mind the limited number of studies and the low method ological quality , there are some indications that the localization ( radiation to the arms/neurologic signs ) and radiologic findings ( degenerative changes in the discs and joints ) are not associated with a worse prognosis . A higher severity of pain and a history of previous attacks however , seems to be associated with a worse prognosis
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"In the majority of patients with neck pain , symptoms will resolve spontaneously or quite quickly in response to therapy . However , some patients ' symptoms persist for a long period , irrespective of therapy . In this study , 20 patients with persistent ( greater than 8 weeks ) neck pain were enrolled in a double blind , placebo-controlled trial of low energy , pulsed electromagnetic therapy (PEMT)--a treatment previously shown to be effective in soft tissue injuries . For the first 3-week period , group A ( 10 patients ) received active PEMT units while group B ( 10 patients ) received facsimile placebo units . After 3 weeks , both pain ( visual analogue scale ( P less than .023 ) and range of movement ( P less than .002 ) had improved in the group on active treatment compared to the controls . After the second 3 weeks , during which both groups used active units , there were significant improvements in observed scores for pain and range of movement in both groups . PEMT , in the form described , can be used at home easily in the treatment of patients with neck pain . It is frequently successful and without side effects",
"A prospect i ve , controlled clinical trial was undertaken to assess the relative efficacies of physiotherapy and electroacupuncture in the treatment of cervical spondylosis . The results suggested that , while both methods were effective , electroacupuncture produced an earlier symptomatic improvement with increased neck movement , especially in patients with mild degenerative changes of the cervical spine",
"We present a double-blind trial in which a pulsed infrared beam was compared with a placebo in the treatment of myofascial pain in the cervical region . The patients were su bmi tted to 12 sessions on alternate days to a total energy dose of 5 J each . At each session , the four most painful muscular trigger points and five bilateral homometameric acupuncture points were irradiated . Those in the placebo group su bmi tted to the same number of sessions following an identical procedure , the only difference being that the laser apparatus was nonoperational . Pain was monitored using the Italian version of the McGill pain question naire and the Scott-Huskisson visual analogue scale . The results show a pain attenuation in the treated group and a statistically significant difference between the two groups of patients , both at the end of therapy and at the 3-month follow-up examination",
"A r and om sample including 2342 cases representative of all occupational back injuries in Quebec ( 1981 ) was followed up prospect ively over three years to assess the recurrence rate of back problems ( lumbar , thoracic , and cervical ) . Each medical and accident report was review ed to obtain the site of symptoms and occupation . Age , sex , industrial sector , and number of episodes of absence from work were abstract ed from the computerised Quebec Compensation Board files . The recurrence rate was 20.0 % at one year follow up and 36.3 % at three years . A multivariate analysis using a Poisson regression , was performed to model the risk of recurrence over time . Men had a higher chance of recurrence ( risk ratio = 1.85 , 95 % CI = 1.50 - 2.27 ) but among recurrent cases , the average total number of episodes was comparable between men and women . Age showed a protective effect on the probability of recurrence ( 10 years : RR = 0.93 , 95 % CI = 0.88 - 0.98 ) due to the lower recurrence rate in the 45 - 64 year old group ( 31.8 % ) . Cervical and lumbar symptoms had identical recurrence profiles whereas thoracic symptoms had a significantly lower recurrence rate . Drivers had the highest recurrence rate ( 42.1 % ) and nurses had the highest average number of recurrences ( 2.03 ) among recurrent cases . Both occupations had statistically significant excesses after controlling for the other variables",
"Thirty patients with acute cervical pain were r and omized into 3 groups and treated with neck collar , transcutaneous nerve stimulation , or manual therapy . The improvement was rapid in all groups , but the restoration of the cervical mobility was significantly more rapid in the transcutaneous nerve stimulation group . Some of the patients with manual therapy treatment had remarkably quick symptom reduction , although this was not significantly better than the collar alone . It is concluded that transcutaneous nerve stimulation is a valuable pain reducer and gives a more rapid restoration of cervical mobility in acute cervical pain",
"In this study 169 female office employees were interviewed and examined to determine the occurrence and severity of neck and shoulder symptoms . Forty-seven of those with symptoms who fulfilled the criteria taken as indicating need for treatment were enrolled in a controlled clinical trial and divided into two groups . One group participated in dynamic muscle training of neck and shoulder muscles ( active physiotherapy ) . The other patients were treated by means of surface heat , massage , and stretching ( passive physiotherapy ) . Pain in the neck and shoulder regions disappeared significantly more often just after active treatment as compared to passive treatment . Symptoms returned within three months in both groups . However , after 12 months , the incidence of headache was significantly less in the group that had received active physiotherapy . Maximal isometric muscle strength in relation to cervical lateral flexion and extension and grip strength and endurance force of shoulder muscles improved significantly after active physiotherapy , but only maximal isometric extension force increased significantly after passive physiotherapy . Numbers of tender points in neck and shoulder muscles decreased significantly after both types of physiotherapy . Pressure threshold levels increased but not significantly in both groups during treatment",
"Twenty-five out- patients with chronic neck pain participated in a prospect i ve , r and omized trial of acupuncture versus placebo transcutaneous nerve stimulation . A single-blind , non-cross-over design incorporated several outcome measures in an attempt to determine any particular facet of pain that responded to acupuncture . No significant difference between the two treatments was found either post-treatment or at follow-up . Whilst the small population studied limits the conclusions that may be drawn , these findings suggest that acupuncture may have no greater effect than that of a powerful placebo",
"This study was design ed to determine a cost-effective use of psychologist re sources in multimodal cognitive-behavioural treatments ( MMCBT ) for chronic neck/shoulder pain . A r and omised controlled trial was conducted with 66 patients divided in two groups . The first group ( A ) was treated following the approach of MMCBT with the clinical psychologist only functioning as a \" coach \" to the other health professionals . In this group , the psychologist had on average 5 hours of input per patients . The second group ( B ) was treated with the same inpatient MMCBT but with the behavioural component administered by the clinical psychologist directly to the patients . In this second group the psychologist had on average 17 hours of input per patient in the entire intervention . The outcome variables included physical , emotional and social factors , and sick-leave . Both groups showed significant improvements over time . The improvements were evident only in sub-groups , specifically in women . The only significant difference between the groups was in \" perceived helplessness \" favouring the \" psychologist contact \" setting . It is concluded that in terms of input of clinical psychology , the treatment setting with the \" coaching \" technique proved to be the most cost-effective use of the psychologist in the two treatment setting s investigated",
"The study was initiated to evaluate the effect of pain-reducing therapies on factors previously associated with work-related shoulder and neck pain , namely increased muscle activity in the upper trapezius and perceived general tension . Thirty-three women in three groups were assessed before and after an intervention period and by question naire 6 months later . The purpose of this study was primarily to investigate associations between upper trapezius muscle activity , perceived general tension and pain , and secondly , to compare effects of individually based physiotherapy and group exercise for workers with shoulder and neck myalgia . All three groups reported a significant alleviation of pain and perceived general tension , while the electromyographically ( EMG ) recorded upper trapezius muscle activity level remained unchanged or increased . Improvements were similar in all three treatment groups , but individual-based therapies were rated more beneficial on subjective measures . Significant correlation was found between pain and perceived general tension ( r = 0.66 , p < 0.01 ) , while there was no correlation between pain or perceived general tension and recorded muscle activity",
"A r and omized controlled trial of manipulation of the cervial spine was carried out on 52 patients in general practice , and the results were assessed symptomatically and goniometrically for three weeks . Manipulation produced a significant immediate improvement in symptoms in those with pain or stiffness in the neck , and pain/paraesthesia in the shoulder , and a nearly significant improvement in those with pain/paraesthesia in the arm/h and . Manipulation also produced a significant increase in measured rotation that was maintained for three weeks and an immediate improvement in lateral flexion that was not maintained . This is to our knowledge the first published formal trial of such manipulation and should increase interest in this form of treatment by the medical profession",
"Twenty-one patients with symptomatic cervical spondylosis or nonspecific neck pain were given an amnesic dose of diazepam before manipulation of the cervical spine . Eighteen patients served as controls and also received diazepam but no manipulation . Results were obtained in a r and omized , double-blind fashion . Statements of outcome by patients and mean visual analog scales for pain and activity showed no significant differences between manipulation and control groups , though both tests favored manipulation . Control subjects subsequently treated by manipulation showed no consistent favorable response . Question naires dealing with personality , life events , social and medical histories , etc . , provided no correlations with outcome , nor did radiographic findings . Diffuse local tenderness correlated with high pain scores after treatment . The authors conclude that the value of a single manipulation of the cervical spine has not been established and that further exploration of indications is needed . The use of intravenous diazepam should be considered because it allows a double-blind experimental design",
"The effects of group gymnastics on neck pain were studied among 44 women in a printing company . A r and omized cross-over design was used with two groups matched according to the work task , frequency of symptoms , and age . The treatment consisted of gymnastics for 45 min once a week for 10 weeks . Neck pain was rated by visual analogue scale and pressure pain sensitivity of the neck muscles was measured with an algometer . The results showed no clear effects of the group gymnastics program . An equal and significant reduction in pain ratings was seen in both groups after the first intervention in the spring . Recurrence of symptoms was seen in both groups in September , and no significant reduction in pain occurred during the second intervention in the autumn . The results suggest a seasonal variation in neck symptoms which has to be considered when planning or evaluating intervention studies",
" A cohort of3,342 cases constituting a r and om sample of all occupational back injuries compensated in Quebec ( Canada ) during 1981 was observed prospect ively for 3 years to study associations between cumulative duration of absence from work and sex , age , site of symptoms ( cervical , thoracic , and lumbar ) , and occupation . Of the cohort members , 287 ( 9.7 % ) cumulated 6 months of absence or more . A logistic regression model showed age and site of symptoms to be the two most important risk factors associated with absences of 6 months or more . No association was found with sex or occupation . The results showed discrepancies between measures of frequency distribution of back injuries and duration of absence from work , an important finding in terms of identifying health priorities",
"Head repositioning accuracy ( HRA ) after full range active motion was evaluated in 60 cervicalgic patients . The mean angular error was 7.7 degrees + /- 3.3 ( mean + /- SD ) and 82 % were outside a threshold value of 4.5 degrees . After r and omization 30 patients followed a rehabilitation program based on eye-head coupling ( RG ) and 30 served as a control group ( CG ) . At 10 week follow-up , a greater gain in HRA was observed in the RG ( 2 degrees + /- 2.7 , mean + /- SD ) than in the CG ( 0 + /- 2.6 , mean + /- SD ) ( p = 0.005 ) . Clinical parameters ( pain , drug intake , range of motion , and self assessed functional improvement ) were also more improved in the RG than in the CG . These data emphasize the role of a neck proprioception alteration in chronic neck pain and suggest that a rehabilitation program based on eye-head coupling should be included in most medical management of cervicalgic patients",
"The objective of the investigation was to study the course of neck and shoulder symptoms and the predictors for these symptoms among women in light sedentary work . Postal surveys were conducted among 351 tellers ( age 20 - 50 years ) of a bank company in September , December , March , and May. The response rates were 74 - 90 % . The outcome was the frequency of the symptoms during the previous three months . In the analysis , univariate explorations and r and om-effects logistic binomial regression for distinguishable responses were used . A change in the frequency of neck and shoulder symptoms was seen in 40.5 % of the subjects during the follow-up period from autumn to spring . The frequency of the symptoms decreased from autumn and winter towards spring . The stability of the frequency of the symptoms was positively associated with age . Seasonal variation in symptoms should be considered when preventive programs against neck and shoulder disorders are planned and evaluated"
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INTRODUCTION The use of drugs to enhance recovery ( " rehabilitation pharmacology " ) has been assessed . Amphetamine can improve outcome in experimental models of stroke , and several small clinical trials have assessed its use in stroke . METHODS Electronic search es were performed to identify r and omised controlled trials of amphetamine in stroke ( ischaemic or haemorrhagic ) . Outcomes included functional outcome ( assessed as combined death or disability/dependency ) , safety ( death ) and haemodynamic measures . Data were analysed as dichotomous or continuous outcomes , using odds ratios ( OR ) , weighted or st and ardised mean difference , ( WMD or SMD ) using r and om-effects models with 95 % confidence intervals ( 95 % CI ) ; statistical heterogeneity was assessed . RESULTS Eleven completed trials ( n=329 ) were identified . Treatment with amphetamine was associated with non-significant trends to increased death ( OR 2.78 ( 95 % CI , 0.75 - 10.23 ) , n=329 , 11 trials ) and improved motor scores ( WMD 3.28 ( 95 % CI -0.48 - 7.04 ) n=257 , 9 trials ) but had no effect on the combined outcome of death and dependency ( OR 1.15 ( 95 % CI 0.65 - 2.06 , n=206 , 5 trials ) . Amphetamine increased systolic blood pressure ( WMD 9.3 mmHg , 95 % CI 3.3 - 15.3 , n=106 , 3 trials ) and heart rate ( WMD 7.6 beats per minute ( bpm ) , 95 % CI 1.8 - 13.4 , n=106 , 3 trials ) . Despite variations in treatment regimes , outcomes and follow-up duration there was no evidence of significant heterogeneity or publication bias . CONCLUSION No evidence exists at present to support the use of amphetamine after stroke . Despite a trend to improved motor function , doubts remain over safety and there are significant haemodynamic effects , the consequences of which are unknown
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"Background and Purpose — Among patients with acute stroke , high blood pressure is often associated with poor outcome , although the reason is unclear . We analyzed data from the International Stroke Trial ( IST ) to explore the relationship between systolic blood pressure ( SBP ) , subsequent clinical events over the next 2 weeks , and functional outcome at 6 months in patients with acute stroke . Methods — We included in the analysis 17 398 patients from IST with confirmed ischemic stroke . A single measurement of SBP was made immediately before r and omization . Clinical events within 14 days of r and omization were recorded : recurrent ischemic stroke , symptomatic intracranial hemorrhage , death result ing from presumed cerebral edema , fatal coronary heart disease , and death . Survival and dependency were assessed at 6 months . Outcomes were adjusted for age , sex , clinical stroke syndrome , time to r and omization , consciousness level , atrial fibrillation , and treatment allocation ( aspirin , unfractionated heparin , both , or neither ) . Results — A U-shaped relationship was found between baseline SBP and both early death and late death or dependency : early death increased by 17.9 % for every 10 mm Hg below 150 mm Hg ( P rate of recurrent ischemic stroke within 14 days increased by 4.2 % for every 10–mm Hg increase in SBP ( P = 0.023 ) ; this association was present in both fatal and nonfatal recurrence . Death result ing from presumed cerebral edema was independently associated with high SBP ( P = 0.004 ) . No relationship between symptomatic intracranial hemorrhage and SBP was seen . Low SBP was associated with a severe clinical stroke ( total anterior circulation syndrome ) and an excess of deaths from coronary heart disease ( P = 0.002 ) . Conclusions — Both high blood pressure and low blood pressure were independent prognostic factors for poor outcome , relationships that appear to be mediated in part by increased rates of early recurrence and death result ing from presumed cerebral edema in patients with high blood pressure and increased coronary heart disease events in those with low blood pressure . The occurrence of symptomatic intracranial hemorrhage within 14 days was independent of SBP",
"Background and Purpose — Hemiparesis is the commonest disabling deficit caused by stroke . In animals , dextroamphetamine ( AMPH ) paired with training enhances motor recovery , but its clinical efficacy is uncertain . Methods — In a r and omized , double-blind , placebo-controlled trial , 71 stroke patients were stratified by hemiparesis severity and r and omly assigned to 10 sessions of physiotherapy coupled with either 10 mg AMPH or placebo . Study treatments were administered by 1 physiotherapist , beginning 5 to 10 days after stroke and continuing twice per week for 5 weeks . Outcomes were assessed by 1 physiotherapist at baseline , after each treatment session , at 6 weeks , and at 3 months . The primary outcome was motor recovery ( impairment level ) on the Fugl-Meyer ( FM ) scale . Secondary outcomes assessed mobility , ambulation , arm/h and function , and independence in activities of daily living . Results — Baseline hemiparesis was severe overall ( mean FM score 27.7±20.0 ) . Motor scores improved during treatment in both groups ( mean change , baseline to 3 months 29.5±16.6 ) . Repeated- measures ANOVA revealed no significant differences in recovery between the treatment groups for the entire cohort ( n=67 ) or for subgroups with a severe hemiparesis ( n=43 ) , moderate hemiparesis ( n=24 ) , or cortically based stroke ( n=26 ) . In the moderate subgroup , there was a significant drug × time interaction for upper extremity motor recovery ( F=5.14 ; P baseline imbalance in motor scores in this subgroup . Conclusion — In stroke patients with a severe motor deficit , 10 mg AMPH coupled with physiotherapy twice per week for 5 weeks in the early poststroke period provided no additional benefit in motor or functional recovery compared with physiotherapy alone . Patients with moderate severity hemiparesis deserve further investigation . Increased intensity and longer duration drug/therapy dosing regimens should be explored , targeting the upper and lower limbs separately",
"Despite advances in acute treatment of ischemic cerebrovascular events , the most common clinical outcome is disabling neurological impairment . Despite experimental evidence that psychostimulant treatment can positively affect recovery rate after focal brain lesions , beyond rehabilitation therapies there are no currently accepted medical treatments indicated for diminishing neurological impairment after clinical ly established stroke . To test the effect of amphetamine , task-specific training , limiting motor experience , and their interaction on motor recovery in a postacute animal model of stroke , animals were nonaversively trained in beam walking before a unilateral photochemical sensorimotor cortex lesion and tested for 10 days after lesion . Animals were r and omized to groups receiving : a single session of motor training 24 h after lesion ; a single injection of amphetamine 2 mg/kg 24 h after lesion ; beam-walking experience limited to testing on days 1 and 10 after lesion ; and groups that received amphetamine treatment combined with training or combined with limited experience . Motor recovery was maximally enhanced by training , delayed by amphetamine treatment , and most negatively affected by limiting beam-walking experience during the recovery period . These findings support physical training after stroke , indicating that limiting physical activity negatively affects motor recovery and raises questions about the role of stimulant treatment to enhance motor recovery in the postacute phase after stroke",
"Functional magnetic resonance imaging was used to evaluate the effects of oral d-amphetamine on brain activation elicited by auditory and simple motor tasks in ten normal right-h and ed subjects . We measured the percent signal change and number of voxels activated by a tone discrimination task and a right h and finger-tapping task after 20 mg of d-amphetamine and after placebo . Compared to placebo , amphetamine significantly increased the number of activated voxels in the left and right primary auditory cortices during the tone discrimination task and increased the number of activated voxels in the ipsilateral primary sensorimotor cortex and right middle frontal area during the motor task . Although highly specific vascular effects of drug can not be ruled out as an explanation , these results could also mean that amphetamine increases the neuronal activity associated with each of these two tasks",
"Background and Purpose — The baroreceptor reflex arc is important in the short-term regulation of the cardiovascular system , and small studies have reported impaired cardiac baroreceptor sensitivity ( BRS ) after acute stroke . However , the prognostic significance of impaired BRS is uncertain . Methods — One hundred twenty-four patients underwent simultaneous ECG and noninvasive beat-to-beat blood pressure ( BP ) monitoring within 72 hours of neuroradiologically confirmed acute ischemic stroke . Cardiac BRS was assessed from the combined & agr;-index by means of power spectral analysis techniques . Baseline data for acute stroke patients were compared with those of a control group matched for age , sex , and casual BP . Patients were followed up for a median of 1508 days ( range , 9 to 2656 days ) , and outcome was compared between patients with and without impaired BRS . Results — Median BRS values were significantly lower in stroke patients than in controls ( 5 [ interquartile range , 3.5 to 7.4 ] versus 6.2 [ interquartile range , 4.5 to 8.3 ] ms/mm Hg;P = 0.04 ) . Sixty-one ( 33 male ) patients ( mean age , 70.2 [ SD 10.5 ] years ) had impaired BRS ( ≤5.0 ms/mm Hg ) compared with 63 ( 35 male ) patients ( mean age , 70.6 [ SD 11.7 ] years ) without impaired BRS ( > 5.0 ms/mm Hg ) . Stroke patients with impaired BRS values had a significantly poorer prognosis ( 28 % versus 8 % mortality rate during the follow-up period ) although there were no differences in age , stroke severity , stroke type , or casual or 24-hour BP parameters between the 2 groups . Conclusions — Impaired cardiac BRS is associated with increased long-term mortality after acute ischemic stroke , irrespective of age , sex , stroke type , and BP . This may reflect cardiac arrhythmias , but the mechanisms underlying this association are unknown , although therapies that improve cardiac BRS after stroke warrant further investigation",
"PURPOSE To assess the effects of d-amphetamine on motor facilitation and recovery in stroke patients with mild arm paresis receiving the Arm Ability training . METHODS Thirty-one stroke patients with mild arm paresis were r and omly assigned to either ( a. ) receiving placebo or ( b. ) d-amphetamine twice a week 2 hours before Arm Ability training sessions for three weeks . MAIN OUTCOME MEASURE time needed to perform TEMPA tasks , a measure of upper extremity performance reflecting everyday life tasks . Secondary measures : aim ed movements , tapping , and a 10 m walkway as well as motor performance during training sessions . RESULTS The interim efficacy analysis of 26 stroke patients who completed the study intervention showed overall arm motor recovery both from pre to post test after 3 weeks of training and from pre test to follow-up 1 year later . No superior effect of d-amphetamine over placebo could be substantiated for either motor facilitation during training or motor recovery ( post training or long-term ) . D-amphetamine exerted mild effects on blood pressure . Serious adverse events were not observed . CONCLUSIONS d-Amphetamine failed to facilitate motor performance during training sessions , to promote skill acquisition with training tasks , and most importantly to enhance motor recovery among patients with mild arm paresis after stroke",
"Background and Purpose — Amphetamine is reported to enhance recovery after experimental stroke , but results from the first few trials in humans are inconclusive . Limited information is available on treatment safety . This study intended to investigate the safety and tolerability of dexamphetamine in patients with acute cerebral ischemia . Methods — Forty-five patients with cerebral ischemia were enrolled within 72 hours after onset of symptoms . Patients were r and omized to 1 of 3 dose levels ( 2.5 , 5 , or 10 mg orally twice daily ) or placebo for 5 consecutive days . Adverse events , blood pressure , heart rate , body temperature , consciousness level , and functional outcome measures were followed up daily during treatment . Follow-ups were made at day 7 and 1 and 3 months after stroke . Results — Mean systolic and diastolic blood pressures and heart rate increased 14 mm Hg , 8 mm Hg , and 9 bpm , respectively , with dexamphetamine treatment compared with placebo ( P ≤0.01 ) . There was no difference between dexamphetamine and placebo regarding adverse events , body temperature , or consciousness level . During treatment , there was a benefit of dexamphetamine in neurological and functional outcome ( P dexamphetamine was safe and well tolerated by patients with acute cerebral ischemia , but blood pressure and heart rate increased during treatment in comparison to placebo . These observations may be important in the future planning of amphetamine trials because changes in these variables have been observed to interfere with clinical outcome . The suggestions of improvement in outcome must be confirmed in further studies",
"Practice -dependent plasticity underlies motor learning in everyday life and motor relearning after lesions of the nervous system . Previous studies showed that practice -dependent plasticity is modifiable by neuromodulating transmitters such as norepinephrine ( NE ) , dopamine ( DA ) or acetylcholine ( ACh ) . Here we explored , for the first time comprehensively and systematic ally , the modifying effects of an agonist versus antagonist in each of these neuromodulating transmitter systems on practice -dependent plasticity in healthy subjects in a placebo-controlled , r and omized , double-blind crossover design . We found that the agonists in all three neuromodulating transmitter systems ( NE : methylpheni date ; DA : cabergoline ; ACh : tacrine ) enhanced practice -dependent plasticity , whereas the antagonists decreased it ( NE : prazosin ; DA : haloperidol ; ACh : biperiden ) . Enhancement of plasticity under methylpheni date and tacrine was associated with an increase in corticomotoneuronal excitability of the prime mover of the practice , as measured by the motor evoked potential amplitude , but with a decrease under cabergoline . Our findings demonstrate that agonists and antagonists in various neuromodulating transmitter systems produce significant and oppositely directed modifications of practice -dependent plasticity in human motor cortex . Enhancement of plasticity occurred through different strategies that either favoured extrinsic ( NE , ACh ) or intrinsic ( DA ) modulating influence on the motor cortical output network",
"Amphetamine enhances recovery after experimental ischaemia and has shown promise in small clinical trials when combined with motor or sensory stimulation . Amphetamine , a sympathomimetic , might have haemodynamic effects in stroke patients , although limited data have been published . Subjects were recruited 3–30 days post-ischaemic stroke into a phase II r and omized ( 1:1 ) , double-blind , placebo-controlled trial . Subjects received dexamphetamine ( 5 mg initially , then 10 mg for 10 subsequent doses with 3- or 4-day separations ) or placebo in addition to inpatient physiotherapy . Recovery was assessed by motor scales ( Fugl – Meyer ( FM ) ) , and functional scales ( Barthel index ( BI ) and modified Rankin score ( mRS ) ) . Peripheral blood pressure ( BP ) , central haemodynamics and middle cerebral artery blood flow velocity were assessed before , and 90 min after , the first two doses . Thirty-three subjects were recruited , aged 33–88 ( mean 71 ) years , males 52 % , 4–30 ( median 15 ) days post stroke to inclusion . Sixteen patients were r and omized to placebo and seventeen to amphetamine . Amphetamine did not improve motor function at 90 days ; mean ( s.d . ) FM 37.6 ( 27.6 ) vs control 35.2 ( 27.8 ) ( P=0.81 ) . Functional outcome ( BI , mRS ) did not differ between treatment groups . Peripheral and central systolic BP , and heart rate ( HR ) , were 11.2 mm Hg ( P=0.03 ) , 9.5 mm Hg ( P=0.04 ) and 7 beats per minute ( P=0.02 ) higher , respectively , with amphetamine , compared with control . A nonsignificant reduction in myocardial perfusion ( BUI ) was seen with amphetamine . Other cardiac and cerebral haemodynamics were unaffected . Amphetamine did not improve motor impairment or function after ischaemic stroke but did significantly increase BP and HR without altering cerebral haemodynamics ",
"Use-dependent plasticity , thought to contribute to functional recovery after brain injury , is elicited by motor training . The purpose of this study was to determine if administration of d-amphetamine facilitates the effects of motor training on use-dependent plasticity . Healthy human volunteers underwent a training period of voluntary thumb movements under the effects of placebo or d-amphetamine in different sessions in a r and omized double-blind , counterbalanced design . Previous work in a drug-naive condition showed that such training causes changes in the direction of thumb movements evoked by transcranial magnetic stimulation and in transcranial magnetic stimulation-evoked electromyographic responses . The endpoint measure of the study was the magnitude of training-induced changes in transcranial magnetic stimulation-evoked kinematic and electromyographic responses in the d-amphetamine and in the placebo conditions . Motor training result ed in increased magnitude , faster development and longer lasting duration of use-dependent plasticity under d-amphetamine compared to the placebo session . These results document a facilitatory effect of d-amphetamine on use-dependent plasticity , a possible mechanism mediating the beneficial effect of this drug on functional recovery after cortical lesions",
"UNLABELLED Functional brain imaging is a powerful tool for examining the central nervous system ( CNS ) response to pharmacologic challenges . Amphetamine is of interest both because of its role as a stimulant of the dopaminergic system and because of its use to alter mood in mood-disordered patients , particularly in patients suffering from depression . In this study , we report the effects of oral D-amphetamine relative to placebo on regional cerebral blood flow ( rCBF ) measured by SPECT in healthy volunteers to characterize the normal CNS response to this primarily dopaminergic stimulant . METHODS SPECT was used to assess changes in rCBF induced by amphetamine in 16 healthy volunteers . Subjects received placebo and then 0.4 mg/kg oral amphetamine in a fixed-order single-blind design and were imaged on a triple-head tomograph . Another six healthy volunteers received placebo at both times to assess normal rCBF variability . rCBF changes were assessed with a three-dimensional voxel-based analysis integrated into an automated co registration system . Data were automatically normalized to whole-brain counts and coregistered . Result ant rCBF changes were evaluated parametrically through the formation of an image whose voxel values were based on the paired t statistic . RESULTS Amphetamine increased rCBF in two mesial prefrontal zones ( Brodmann 's areas 8 and 10 ) , inferior orbital frontal lobe ( area 11 ) , brain stem ( ventral tegmentum ) , anteromesial temporal lobe ( amygdala ) , and anterior thalamus . Amphetamine decreased rCBF to motor cortex , visual cortex , fusiform gyrus , posterolateral temporal lobe , and right lateral temporal lobe . CONCLUSION Our data suggest that amphetamine induces focal increases and decreases in rCBF in healthy volunteers in areas primarily innervated by dopamine pathways and in areas with secondary ( primarily limbic ) affiliations . These data are consistent with glucose metabolic data from autoradiographic studies in animals , in which the largest increases are seen in brain stem , followed by striatum , thalamus , and frontal and sensory cortices . Frontopolar and temporal increases observed in our study appear to be unique to humans",
"Objective : To assess the effect of D-amphetamine on the recovery of activities of daily living and motor functions after stroke , Design : R and omized , placebo-controlled study , Setting : Inpatient rehabilitation centre , Subjects : Twenty-four stroke survivors after a first ischaemic supratentorial stroke within six weeks before study onset , severely to moderately affected , with a Barthel Index ( 0–100 ) ranging from 25 to 50 , no severe concomitant internal , neurological or psychiatric diseases , and participating in a comprehensive rehabilitation programme of 10–12 weeks , Interventions : Ten sessions with 10 mg D-amphetamine ( or placebo ) every fourth day totalling 100 mg in a time period of 36 days combined with physical therapy according to the neurodevelopmental concept within 60 minutes after drug intake . Main outcome measures : Barthel Index ( 0–100 ) served as the primary outcome measure and the Rivermead Motor Assessment Score with its three sections ( gross function , leg and trunk , and arm ) as the secondary outcome measure , assessed at days 0 , 20 , 36 , 90 , 180 and 360 . Results : The two groups did not differ with respect to clinical data and outcome measures at study onset . All patients improved significantly except for arm function over the intervention period and up to day 90 after study onset . The comparison between groups did not reveal any difference at any time ; amphetamine-treated patients did not show any increase in motor function or ADL compared with the control group . Conclusions : The placebo-controlled study failed to show any effect of D-amphetamine on stroke recovery compared with control . The small number of patients , the timing and content of physical therapy were limiting factors of the present study . Further trials are warranted",
"Background and Purpose — A number of studies suggest that drugs which increase the release of norepinephrine promote recovery when administered late ( days to weeks ) after brain injury in animals . A small number of clinical studies have investigated the effects of the noradrenergic agonist dextroamphetamine in patients recovering from motor deficits following stroke . To determine whether these findings extend to communication deficits subsequent to stroke , we administered dextroamphetamine , paired with speech/ language therapy , to patients with aphasia . Methods — In a prospect i ve , double-blind study , 21 aphasic patients with an acute nonhemorrhagic infa rct ion were r and omly assigned to receive either 10 mg dextroamphetamine or a placebo . Patients were entered between days 16 and 45 after onset and were treated on a 3-day/4-day schedule for 10 sessions . Thirty minutes after drug/placebo administration , subjects received a 1-hour session of speech/ language therapy . The Porch Index of Communicative Ability was used at baseline , at 1 week off the drug , and at 6 months after onset as the dependent language measure . Results — Although there were no differences between the drug and placebo groups before treatment ( P = 0.807 ) , by 1 week after the 10 drug treatments ended there was a significant difference in gain scores between the groups ( P = 0.0153 ) , with the greater gain in the dextroamphetamine group . The difference was still significant when corrected for initial aphasia severity and age . At the 6-month follow-up , the difference in gain scores between the groups had increased ; however , the difference was not significant ( P = 0.0482 ) after correction for multiple comparisons . Conclusions — Administration of dextroamphetamine paired with 10 1-hour sessions of speech/ language therapy facilitated recovery from aphasia in a small group of patients in the subacute period after stroke . Neuromodulation with dextroamphetamine , and perhaps other drugs that increase central nervous system noradrenaline levels , may facilitate recovery when paired with focused behavioral treatment"
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BACKGROUND Recent US and UK clinical practice guidelines recommend that second-generation antidepressants should be considered amongst the best first-line options when drug therapy is indicated for a depressive episode . Systematic review s have already highlighted some differences in efficacy between second-generation antidepressants . Citalopram , one of the first selective serotonin reuptake inhibitors ( SSRI ) introduced in the market , is one of these antidepressant drugs that clinicians use for routine depression care . OBJECTIVES To assess the evidence for the efficacy , acceptability and tolerability of citalopram in comparison with tricyclics , heterocyclics , other SSRIs and other conventional and non-conventional antidepressants in the acute-phase treatment of major depression . SEARCH METHODS We search ed The Cochrane Collaboration Depression , Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to February 2012 . No language restriction was applied . We contacted pharmaceutical companies and experts in this field for supplemental data . SELECTION CRITERIA R and omised controlled trials allocating patients with major depression to citalopram versus any other antidepressants . DATA COLLECTION AND ANALYSIS Two review ers independently extracted data . Information extracted included study characteristics , participant characteristics , intervention details and outcome measures in terms of efficacy ( the number of patients who responded or remitted ) , patient acceptability ( the number of patients who failed to complete the study ) and tolerability ( side-effects ) . MAIN RESULTS Thirty-seven trials compared citalopram with other antidepressants ( such as tricyclics , heterocyclics , SSRIs and other antidepressants , either conventional ones , such as mirtazapine , venlafaxine and reboxetine , or non-conventional , like hypericum ) . Citalopram was shown to be significantly less effective than escitalopram in achieving acute response ( odds ratio ( OR ) 1.47 , 95 % confidence interval ( CI ) 1.08 to 2.02 ) , but more effective than paroxetine ( OR 0.65 , 95 % CI 0.44 to 0.96 ) and reboxetine ( OR 0.63 , 95 % CI 0.43 to 0.91 ) . Significantly fewer patients allocated to citalopram withdrew from trials due to adverse events compared with patients allocated to tricyclics ( OR 0.54 , 95 % CI 0.38 to 0.78 ) and fewer patients allocated to citalopram reported at least one side effect than reboxetine or venlafaxine ( OR 0.64 , 95 % CI 0.42 to 0.97 and OR 0.46 , 95 % CI 0.24 to 0.88 , respectively ) . AUTHORS ' CONCLUSIONS Some statistically significant differences between citalopram and other antidepressants for the acute phase treatment of major depression were found in terms of efficacy , tolerability and acceptability . Citalopram was more efficacious than paroxetine and reboxetine and more acceptable than tricyclics , reboxetine and venlafaxine , however , it seemed to be less efficacious than escitalopram . As with most systematic review s in psychopharmacology , the potential for overestimation of treatment effect due to sponsorship bias and publication bias should be borne in mind when interpreting review findings . Economic analyses were not reported in the included studies , however , cost effectiveness information is needed in the field of antidepressant trials
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"Background Alcohol dependence comorbid with major depressive disorder poses a major challenge in the clinical setting . The results in the treatment with selective serotonin re-uptake inhibitors have been conflicting . Thus , we compared in alcohol-dependent patients with co-morbid major depressive disorder the selective serotonin re-uptake inhibitor escitalopram to a compound that acts on different transporter system and may reduce craving , the glutamate receptor antagonist memantine . Methods Eighty alcohol-dependent patients comorbid with major depressive disorder in municipal alcohol clinics were r and omized 1:1 to receive memantine 20 mg or escitalopram 20 mg in a double-blind manner . During the 26-week study period patients continued their routine treatment at the clinics . Abstinence was not required but encouraged . The patients attended visits weekly during the first month , and then at 3 and at 6 months . Outcome measures were Alcohol Use Disorders Identification Test ( AUDIT ) , Obsessive Compulsive Drinking Scale ( OCDS ) and Drinking Diary . Results The completion rate was high in both groups , especially among the patients who had been abstinent at the beginning of the study . However , among those patients who were not abstinent at baseline , 47 % in both groups discontinued the study . Numbers of abstinent days were high in both groups throughout the study . Alcohol consumption measured by the AUDIT QF ( quantity-frequency ) score was significantly reduced in both groups , as was the craving for alcohol measured by the OCDS . Early age at first alcohol intoxication predicted poor treatment outcomes in patients treated with escitalopram , and the same was seen with the early onset of the first depressive episode . The same predictive effects were not found in patients treated with memantine . Conclusion Our results indicate that both memantine and escitalopram are useful adjunct medications for the treatment of alcohol dependence co-morbid with major depression . Memantine was at least as effective with regard to drinking as escitalopram . We believe that a direct comparison of memantine , with the commonly used escitalopram , can provide useful information for clinicians on the treatment of alcohol dependency co-morbid with MDD.Trial registration Clinical Trials.gov Identifier #",
"Abstract The selective serotonin reuptake inhibitor citalopram was compared with clomipramine in a multicenter clinical study . From a total of 150 depressed patients ( age 18–65 years ) , 114 patients with a Hamilton Depression Scale ( HDS ) total score≧18 at the end of a 1 week placebo period were started on treatment with either citalopram ( 40 mg/day ) or clomipramine ( 150 mg/day ) ( fixed , single daily dose ) . Patients stratified according to diagnostic rating ( Newcastle Inventory , endogenous/non-endogenous ) were r and omly allocated to treatment groups using double blind principles . In total , 102 patients completed more than 2 weeks , treatment and were included in the analyses of therapeutic effect . The two drug groups were comparable in terms of sex , age , and departmental distribution . Categorical measurements of therapeutic effect based on the HDS total score showed that in the endogenously depressed patients a significantly higher percentage of patients on clomipramine ( n=37 ) than on citalopram ( n=38 ) were classified as complete responders ( HDS total≦7 ) after 3 , 4 and 5 weeks of treatment . In the non-endogenously depressed patients ( clomipramine : n=15 , citalopram : n=12 ) rather similar numerical differences were observed ( P clomipramine group ( n=52 ) and about 30 in the citalopram group ( n=50 ) ( P the sleep items , but other items covering depression , retardation and anxiety/agitation also contributed to the difference in total score that was also seen in patients with low initial scores on the sleep items . Citalopram was devoid of the typical autonomic side effects and orthostatic hypotension seen with clomipramine . Symptoms of nausea/vomiting and headache became somewhat worse in the citalopram- and somewhat better in the clomipramine-treated patients . Participating centers:1Department of Psychiatry , Odense University Hospital , Odense , 2Department of Psychiatry , Rigshospitalet , University of Copenhagen , Copenhagen , 3Departments of Psychiatry , Frederiksborg General Hospital , Hillerød , 4Department A and C , Psychiatric University Hospital , Århus , 5Department of Psychiatry , Bornholm General Hospital , Rønne , 6Department of Clinical Pharmacology , Odense University , Odense Participating clinicians : J. And ersen2 , P. Bech2,3 , S. Benjaminsen1 , M. Bjerre1 , S. Bøjholm5 , P. Christensen1 , A. Gjerris2 , L. Hansted4 , E. Jensen3 , P. Kragh-Sørensen1 , C.B. Kristensen1,3 , P. Kyneb4 , D. Loldrup3 , O.F. Madsen4 , O.L. Pedersen1 , O.J. Rafaelsen2 , S. Rasmussen3 , N. Reisby4 , F. Sevaj3 , P. Simonsen4 , H.Y. Thomsen1 , P. Vestergaard4Coordination and drug assay : L.F. Gram6Statistical consultants : O. Aaskoven , P. Allerup Data - collection and -processing : C. Sánchez Steering Committee : P. Bech , L.F. Gram ( chairman ) , P. Kragh-Sørensen , O.J. Rafaelsen , N. Reisby , P.",
"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",
"BACKGROUND Major depression is highly recurrent . Antidepressant maintenance treatment has proven efficacy against recurrent depression . AIMS Comparison of prophylactic efficacy of citalopram versus placebo in unipolar , recurrent depression . METHODS Patients 18 - 65 years of age with recurrent unipolar major depression ( DSM-IV ) , a Montgomery-Asberg Depression Rating Scale score of > or = 22 and two or more previous depressive episodes , one within the past 5 years , were treated openly with citalopram ( 20 - 60 mg ) for 6 - 9 weeks and , if responding , continued for 16 weeks before being r and omised to double-blind maintenance treatment with citalopram or placebo for 48 - 77 weeks . RESULTS A total of 427 patients entered acute treatment and 269 were r and omised to double-blind treatment . Time to recurrence was longer in patients taking citalopram than in patients taking placebo ( P: well tolerated . CONCLUSIONS Citalopram ( 20 , 40 and 60 mg ) is effective in the prevention of depressive recurrences . Patients at risk should continue maintenance treatment at the dose necessary to resolve symptoms in the acute treatment phase",
"Anecdotal and published case reports suggest that some patients taking selective serotonin reuptake inhibitors ( SSRI ) experience diminution in emotional responsiveness . This study aims to define the individual components of emotion disturbed in these patients . Fifteen patients reporting SSRI-induced sexual dysfunction completed the Laukes Emotional Intensity Scale ( LEIS ) , a question naire about various emotions . Compared to controls , patients reported significantly ( p ability to cry , irritation , care about others ' feelings , sadness , erotic dreaming , creativity , surprise , anger , expression of their feelings , worry over things or situations , sexual pleasure , and interest in sex . Total score on the LEIS did not correlate with total score on the Hamilton Depression Rating Scale . In our sample , 80 % of patients with SSRI-induced sexual dysfunction also describe clinical ly significant blunting of several emotions . Emotional blunting may be an under-appreciated side-effect of SSRIs that may contribute to treatment non-compliance and /or reduced quality of life",
"ABSTRACT — In a double‐blind trial , comprising 96 depressed patients , citalopram was compared with maprotiline . The trial period was 6 weeks with ratings ( MADRS , CGI ) and side effects recordings taking place at Weeks 0 , 1 , 2 , 4 , and 6 . Both drugs were administered as a single evening dose , 40 or 60 mg for citalopram , and 75 or 150 mg for maprotiline . MADRS total scores and CGI scores showed a highly significant reduction in both groups with no significant difference between them , whether the groups were considered as a whole or whether they were subdivided into endogenously/non‐endogenously depressed or melancholic/non‐melancholic patients . Side effects were not significantly different , but the maprotiline group showed more anticholinergic side effects , whereas the citalopram group showed more nausea , increased sweating and headache . Two patients on maprotiline were withdrawn because of side effects ( hypotension and somnolence in the one case ; tremor and insomnia in the other ) . One patient in each group was withdrawn because of increased transaminases , the citalopram‐treated patient having increased values , however , already at baseline . Apart from this , no cardiovascular side effects and no pathological laboratory values related to treatment were observed . The authors conclude that citalopram is a safe antidepressant drug and as effective as maprotiline",
"Selective serotonin reuptake inhibitors ( SSRIs ) have been reported to be useful in the treatment of depression in patients with Parkinson 's disease ( PD ) . However , a few reports have suggested that SSRIs may worsen parkinsonian motor symptomatology and extrapyramidal side effects have been reported in depressed patients treated with SSRIs . So far , no prospect i ve trial comparing the effects of different SSRIs in depressed patients with PD has been performed . The aim of the present study was to assess the effects of four SSRIs ( citalopram , fluoxetine , fluvoxamine , and sertraline ) on motor performance and their efficacy on depression in a group of patients with PD . Sixty-two consecutive nondemented , nonfluctuating , depressed patients with PD were included in four treatment groups ( 15 patiens received citalopram , 16 fluoxetine , 16 fluvoxamine , and 15 sertraline ) . The evaluation of extrapyramidal and depressive symptomatology was performed with use of the Unified Parkinson 's Disease Rating Scale ( UPDRS ) , Beck Depression Inventory , and Hamilton Depression Rating Scale at baseline and after 1 , 3 , and 6 months . Fifty-two patients completed the study . UPDRS scores were not significantly modified by the add-on therapy with each of the SSRIs studied . A significant improvement in depressive symptoms from baseline to the end of the trial was obtained with all SSRIs ( Beck and Hamilton scores improving;p extrapyramidal symptomatology and may ameliorate depression in patients with PD",
"BACKGROUND Antidepressants exhibit a variety of pharmacological actions including inhibition of the serotonin and noradrenaline transporters . We wished to investigate whether genetic variation could be used to target or personalise treatment , in a comparison of selective serotonin reuptake inhibitors ( SSRIs ) with noradrenaline reuptake inhibitors ( NARIs ) . AIMS To test the hypothesis that patients homozygous for the long ( insertion ) polymorphism of the serotonin transporter ( 5-HTTLPR ) have an increased response to SSRI antidepressants but not to NARI antidepressants . METHOD In an individually r and omised , parallel-group controlled trial , people meeting criteria for a depressive episode who were referred by their general practitioner were r and omised to receive either citalopram ( an SSRI ) or reboxetine ( an NARI ) . R and omisation was by means of a remote automated system accessed by telephone . The main outcome was depressive symptoms , measured by Beck Depression Inventory ( BDI ) total score 6 weeks after r and omisation . The trial was registered with the International St and ard R and omised Controlled Trials Number registry ( IS RCT N31345163 ) . RESULTS Altogether 298 participants were r and omised to receive citalopram and 303 were r and omised to reboxetine . At 6 weeks follow-up , complete data were available for 258 participants taking citalopram and 262 taking reboxetine . We found no evidence to support an influence of 5-HTTLPR on outcome following antidepressant treatment . The interaction term for BDI score at 6 weeks was 0.50 ( 95 % CI -2.04 to 3.03 , P = 0.70 ) , which indicated that responses to the SSRI and NARI were similar irrespective of 5-HTTLPR genotype . CONCLUSIONS It is unlikely that the 5-HTTLPR polymorphism alone will be clinical ly useful in predicting response to antidepressants in people with depression",
"Objective : The presence of co-morbid depressive symptoms may have a negative impact on the management of diabetes mellitus . Moreover , some antidepressants may adversely affect glycemic control . Selective serotonin reuptake inhibitors ( SSRIs ) may improve glycemic control and may be beneficial for patients with co-morbid depression and diabetes . We examined the safety and efficacy of s-citalopram therapy in patients with co-morbid depression and diabetes , and its ability to improve glycemic control . Research Design and Methods : 17 patients were enrolled into the trial and 14 patients received open-label s-citalopram therapy for up to 16 weeks . Clinical outcome measures included the 17-item Hamilton depression rating ( HAM-D 17 ) and the clinical global impressions severity ( CGI/S ) and change ( CGI/C ) ratings . In addition , fasting glucose , fructosamine , and glycosylated hemoglobin-A1C measures were obtained before and during s-citalopram therapy . Results : We observed a significant reduction in mean HAM-D 17 ( p s-citalopram therapy . We also observed a modest , non-significant reduction in fasting glucose , fructosamine , and glycosylated hemoglobin-A1C levels during s-citalopram therapy . Limitation : Limitations of this study include a modest patient sample size and a 16-week treatment duration which may have been insufficient to demonstrate the full effect of SSRI therapy on glycemic control . Conclusion : We observed a significant reduction in depressive symptoms and modest , non-significant reductions in fasting glucose , fructosamine , and glycosylated hemoglobin-A1C levels during SSRI therapy of co-morbid depression and diabetes",
"OBJECTIVE The aim of the study was to evaluate possible new treatments for major depressive disorder in patients with comorbid alcohol dependence in a municipal alcohol treatment unit . The efficacy of memantine , a noncompetitive glutamate N-methyl-D-aspartate (NMDA)-receptor blocker used for the treatment of moderate to severe Alzheimer 's disease , was compared with that of escitalopram , a selective serotonin reuptake inhibitor antidepressant . METHOD Eighty alcohol-dependent out patients with major depressive disorder ( DSM-IV criteria ) seeking treatment from municipal alcohol treatment clinics in Helsinki , Finl and , were r and omly assigned 1:1 to receive memantine 20 mg/day or escitalopram 20 mg/day . During the study period , patients continued their routine treatment at the clinics . Abstinence was not required . Concomitant interventions or imposed treatment goals were not offered by the study physician . The patients returned to the treatment clinics at weeks 1 , 2 , 4 , 12 , and 26 for data collection and for medication checking and dispensing . Outcome measures were the Montgomery-Asberg Depression Rating Scale ( MADRS ) and Beck Depression Inventory-II for depression , Hamilton Rating Scale for Anxiety ( HAM-A ) and Beck Anxiety Inventory for anxiety , Consortium to Establish a Registry for Alzheimer 's Disease test battery for cognitive functions , and Social and Occupational Functioning Assessment Scale for social and occupational functions and quality -of-life measures . Twenty-nine patients in each group completed the study . All primary and secondary outcome statistical analyses were performed by an independent source for intent-to-treat population s , which included all patients r and omly assigned to treatment . The study was conducted from December 2004 to May 2006 . RESULTS Both treatments significantly reduced the baseline level of depression and anxiety according to MADRS and HAM-A , which were the primary measures ( p memantine and escitalopram groups . Assessed cognitive functioning scores were primarily within the normative range and were unchanged in both groups . Quality -of-life outcomes equally improved in both treatment groups . CONCLUSIONS These data provide new evidence for the safety and potential efficacy of memantine and escitalopram for major depressive disorder in patients with comorbid alcohol dependence . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00368862",
"ABSTRACT Objective : The prevalence of and morbidity associated with treatment-resistant depression has motivated the exploration of treatment alternatives . In this study , quetiapine was compared with lithium in the augmentation of treatment-resistant depression . Research design and methods : Open-label , comparative study in 20 patients with major depression who had failed to respond after 4 weeks of treatment with an antidepressant at the maximal recommended dose . Patients were r and omised to either lithium or quetiapine in addition to the maximally dosed antidepressant and any other concurrent medications . Lithium was initiated at 600 mg/day ; quetiapine was titrated to 400 mg by day 7 . Results : Depression , measured by the Hamilton Depression Rating Scale ( HAM‑D ) , significantly improved from baseline in both quetiapine ( F1,90 = 25.11 , p and lithium ( F1,90 = 34.54 , p the Montgomery – Asberg Depression Rating Scale ( MADRS ) analysis , the difference between the quetiapine and lithium group was significant from day 28 onwards ( p ( p showed a significant decrease in the Widlocher Psychomotor Retardation Scale scores in the quetiapine ( p and lithium ( p study , quetiapine was an effective augmenting agent in treatment-resistant depression",
"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",
"The two diagnostic Newcastle Scales for depression have been evaluated in a drug trial with antidepressants . By use of latent structure analysis ( Rasch models ) it was found that two dimensions are necessary for describing the diagnosis of depression , one for endogenous features and one for reactive features . Of the depressed patients 50 % had a pure endogenous depression , 14 % had a pure reactive depression , 32 % had mixed endogenous and reactive depression , and 4 % had uncertain diagnosis . In the pure endogenous depression group 77 % had a monotonically non-decreasing improvement curve during treatment whereas in the other diagnostic categories around 50 % had such an improvement",
"Background Selective serotonin reuptake inhibitors ( SSRIs ) are popular medications for anxiety and depression , but their effectiveness , particularly in patients with prominent symptoms of loss of motivation and pleasure , has been question ed . There are few studies of the effect of SSRIs on neural reward mechanisms in humans . Methods We studied 45 healthy participants who were r and omly allocated to receive the SSRI citalopram , the noradrenaline reuptake inhibitor reboxetine , or placebo for 7 days in a double-blind , parallel group design . We used functional magnetic resonance imaging to measure the neural response to rewarding ( sight and /or flavor of chocolate ) and aversive stimuli ( sight of moldy strawberries and /or an unpleasant strawberry taste ) on the final day of drug treatment . Results Citalopram reduced activation to the chocolate stimuli in the ventral striatum and the ventral medial/orbitofrontal cortex . In contrast , reboxetine did not suppress ventral striatal activity and in fact increased neural responses within medial orbitofrontal cortex to reward . Citalopram also decreased neural responses to the aversive stimuli conditions in key “ punishment ” areas such as the lateral orbitofrontal cortex . Reboxetine produced a similar , although weaker effect . Conclusions Our findings are the first to show that treatment with SSRIs can diminish the neural processing of both rewarding and aversive stimuli . The ability of SSRIs to decrease neural responses to reward might underlie the question ed efficacy of SSRIs in depressive conditions characterized by decreased motivation and anhedonia and could also account for the experience of emotional blunting described by some patients during SSRI treatment",
"OBJECTIVE The purpose of this study was to identify genetic variants underlying the considerable individual differences in response to antidepressant treatment . The authors performed a genome-wide association analysis of improvement of depression severity with two antidepressant drugs . METHOD High- quality Illumina Human610-quad chip genotyping data were available for 706 unrelated participants of European ancestry treated for major depression with escitalopram ( N=394 ) or nortriptyline ( N=312 ) over a 12-week period in the Genome-Based Therapeutic Drugs for Depression ( GENDEP ) project , a partially r and omized open-label pharmacogenetic trial . RESULTS Single nucleotide polymorphisms in two intergenic regions containing copy number variants on chromosomes 1 and 10 were associated with the outcome of treatment with escitalopram or nortriptyline at suggestive levels of significance and with a high posterior likelihood of true association . Drug-specific analyses revealed a genome-wide significant association between marker rs2500535 in the uronyl 2-sulphotransferase gene and response to nortriptyline . Response to escitalopram was best predicted by a marker in the interleukin-11 ( IL11 ) gene . A set of 72 a priori-selected c and i date genes did not show pharmacogenetic associations above a chance level , but an association with response to escitalopram was detected in the interleukin-6 gene , which is a close homologue of IL11 . CONCLUSIONS While limited statistical power means that a number of true associations may have been missed , these results suggest that efficacy of antidepressants may be predicted by genetic markers other than traditional c and i date s. Genome-wide studies , if properly replicated , may thus be important steps in the elucidation of the genetic basis of pharmacological response",
"OBJECTIVE The authors hypothesized that age would moderate the response of patients with schizophrenia and subsyndromal depression ( SSD ) treated citalopram with depressive symptoms and other outcomes . Also , older patients would exhibit more side effects with citalopram . METHODS Participants of 40 years or older had schizophrenia or schizoaffective disorder with SSD . Patients r and omly received flexible dosing of citalopram or placebo augmentation of their antipsychotic medication . Linear regression determined whether age had any moderating effect on depressive symptoms , global psychopathology , negative symptoms , mental functioning , and quality of life . Age-related side effects were examined . RESULTS There were no significant drug group by age interaction in depressive or psychotic symptoms , mental Short Form-12 , or quality of life scores . Similarly , there were few age-related side effect differences . CONCLUSION Symptoms in younger and older patients with schizophrenia and SSD treated with citalopram seem to respond similarly . Adverse events do not seem to differ with age",
"BACKGROUND Major depressive disorder is a recurrent illness that often requires maintenance antidepressant treatment . Escitalopram is a selective serotonin reuptake inhibitor ( SSRI ) that has shown efficacy in both acute and continuation treatment of major depressive disorder . The current trial examined the efficacy of maintenance escitalopram treatment in preventing depression recurrence in patients who responded to acute SSRI therapy . METHOD Patients with recurrent DSM-IV-defined major depressive disorder ( > or= 2 previous episodes ; baseline Montgomery-Asberg Depression Rating Scale [ MADRS ] score > or= 22 ) who had responded ( MADRS score open-label treatment ( 8 weeks ) with 1 of 4 SSRIs ( fluoxetine , sertraline , paroxetine , or citalopram ) received open-label , flexible-dose continuation treatment ( 16 weeks ) with escitalopram ( 10 - 20 mg/day ) . At the end of continuation treatment , patients maintaining response criteria were r and omly assigned to 52 weeks of double-blind , fixed-dose maintenance treatment with escitalopram ( 10 or 20 mg/day ) or placebo . Recurrence was defined as a MADRS score > or= 22 or insufficient therapeutic response during the double-blind phase . The study was conducted between October 16 , 2000 , and February 4 , 2003 . RESULTS A total of 234 patients who responded to acute open-label treatment with 1 of 4 SSRIs received at least 1 dose of open-label escitalopram continuation treatment . Of 164 patients who completed escitalopram continuation treatment , 139 were r and omly assigned to double-blind maintenance treatment with escitalopram ( N = 73 ) or placebo ( N = 66 ) . Mean baseline MADRS scores at the start of the maintenance phase were placebo- and escitalopram-treatment groups . Time to recurrence was significantly longer in patients who received maintenance treatment with escitalopram compared with patients switched to placebo ( hazard ratio = 0.26 , 95 % CI = 0.13 to 0.52 , p escitalopram treatment was well tolerated . CONCLUSION Maintenance treatment with escitalopram was well tolerated and significantly reduced the risk for recurrence of depression . Patients with few residual symptoms following continuation treatment with escitalopram experienced a high rate of depression recurrence when switched to placebo , demonstrating the need for maintenance therapy of recurrent major depressive disorder beyond 4 to 6 months of initial symptom resolution even if few residual symptoms are present",
"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 : Severe depression is associated with an extensive economic burden on both the patient and society . OBJECTIVE : To estimate the cost-effectiveness in Austria of escitalopram compared with citalopram in the management of severe depression ( Montgomery — Åsberg Depression Rating Scale score ≥30 ) . METHODS : A decision model incorporated treatment paths and associated direct re source use ( psychiatric hospitalization , medications , general practitioner and psychiatrist visits , treatment discontinuation , suicide attempts ) associated with managing severe depression and the indirect cost of work absenteeism over a 6-month period . Main outcomes were clinical success ( remission at 6 mo ) and cost ( 2002 Euros equals ∼1.25 US ) of treatment . The analysis was performed from the Austrian societal and Social Healthcare Insurance System ( SHIS ) perspectives . Clinical input data were derived from a meta- analysis of 8-week r and omized clinical trials . Costs were derived from st and ard Austrian price lists or from the literature . RESULTS : Six months after the start of treatment , the overall clinical success remission rate was higher for escitalopram ( 53.7 % ) than for citalopram ( 48.7 % ) . From the SHIS perspective , the total expected cost per successfully treated severely depressed patient was € 924 ( 32.1 % ) lower for escitalopram ( € 2879 ) compared with citalopram ( € 3803 ) . From the societal perspective , the total expected cost per successfully treated severely depressed patient was € 1369 ( 24.4 % ) lower for escitalopram ( € 5610 ) than for citalopram ( € 6979 ) . Sensitivity analyses demonstrated that the model was robust and that , even if citalopram had no acquisition cost , escitalopram remained the dominant strategy for both perspectives . CONCLUSIONS : Treatment with escitalopram was the dominant strategy . These data suggest that escitalopram is a cost-effective antidepressant compared with citalopram in the management of severe depression in Austria",
"Milnacipran is a new antidepressive drug , a combined noradrenaline/serotonin ( NA/5‐HT ) reuptake inhibitor , which has been suggested to be as effective as and better tolerated than tricyclic antidepressants . Since long‐term studies are lacking , we compared the efficacy , safety and tolerability of milnacipran and clomipramine in a double‐blind , r and omized , parallel‐group study setting during 26 weeks of treatment in patients with major depression . A total of 107 patients were treated with either milnacipran ( n=52 ) or clomipramine ( n=55 ) . Due to active treatment of duration less than 12 days in four patients and protocol deviation in one patient , in total 47 milnacipran‐treated patients were eligible for efficacy analysis . Nine patients in the clomipramine group continued on active treatment for less than 12 days . Thus 46 clomipramine‐treated patients were finally included in the efficacy analysis . After 1 week of dose escalation , there was a fixed dosage regimen of either milnacipran ( 200 mg daily ) or clomipramine ( 150 mg daily ) during weeks 2 to 10 , followed by flexible dosing of milnacipran ( 100,150 or 200 mg daily ) or clomipramine ( 75 , 100 or 150 mg daily ) during weeks 11 to 26 . A total of 53 patients ( 49 % ) completed the 26‐week study period ; 21 % ( 11/52 ) of the patients in the milnacipran group and 38 % ( 21/55 ) of the patients in the clomipramine group discontinued their medication prematurely due to adverse events , whereas 19 % ( 10/52 ) of those on milnacipran and 7 % ( 4/55 ) of those on clomipramine treatment withdrew due to either lack of efficacy or clinical deterioration . The mean change ( ±SD ) in the Hamilton Depression Rating Scale ( HAMD ) score between the baseline and the last rating ranged from 23.7±3.1 to 12.0±9.5 in the milnacipran‐treated patients and from 23.1±3.5 to 8.0±8.5 in the clomipramine‐treated patients , revealing a significant difference in favour of clomipramine . In total 58 % of the milnacipran‐treated patients vs. 72 % of the clomipramine‐treated patients showed a ≥50 % reduction in their baseline HAMD scores and 45 % vs. 63 % had an HAMD score of ≤7 at the last rating , respectively . Moreover , the time to the onset of the antidepressant action ( defined as ≥50 % reduction of the baseline HAMD score ) showed a significant difference in favour of clomipramine . In addition , clomipramine was significantly more efficacious in patients with a baseline HAMD score of ≥24 as evidence d by the analysis of the HAMD score at week 6 and at the last rating . The Montgomery Åsberg Depression Rating Scale ( MADRS ) and the Clinical Global Impression ( CGI ) scale did not show significant differences between the treatment groups . The safety analysis did not reveal any differences of clinical significance in cardiovascular variables between the study drugs . Dry mouth was significantly less frequently reported by the milnacipran‐treated patients during the early and later phases ( weeks 6 to 26 ) of the study , while insomnia was more common in the milnacipran group during weeks 1 to 6 . In conclusion , milnacipran appeared to be less effective than clomipramine in the long‐term treatment of depression . The side‐effects of the drugs differed to a certain extent , and milnacipran tended to be somewhat better tolerated than clomipramine ",
"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",
"Serum sample s were selected r and omly from blood sample s drawn in the morning for other reasons in patients treated with citalopram , and the serum concentrations of citalopram ( S-citalopram ) and its major metabolite desmethylcitalopram were determined . A total of 44 patients , 13 males and 31 females , with a median age of 38.5 years ( range 18 - 89 ) entered the study . In 17 patients given 20 mg/day of citalopram the S-citalopram was ( median and range ) 153 nmol/l ( 83 - 237 ) . In 24 patients treated with citalopram 40 mg/day the S-citalopram was 240 nmol/l ( range 0 - 360 ) . In one serum sample no S-citalopram could be detected ( non-compliance ) and in another sample S-citalopram was just above the detection limit ( about 3 nmol/l ) . The latter may at least partly be due to treatment with 600 mg/day of carbamazepine , which is known to accelerate the metabolism of other drugs . The serum concentration of the major metabolite desmethylcitalopram averaged 28 % of S-citalopram and is most likely without clinical importance . It is concluded that determination of S-citalopram may be considered if there is doubt about the compliance of the patient , in drug interaction cases or if the clinical effect is poor . If high",
"A growing body of evidence implicates a derangement of zinc homeostasis in mood disorders . In general , unipolar depression is connected with low blood zinc levels that are increased by effective antidepressant therapy . A placebo-controlled , double blind pilot study of zinc supplementation in antidepressant therapy was conducted in patients who fulfilled DSM IV criteria for major ( unipolar ) depression . Patients received zinc supplementation ( 6 patients ; 25 mg of Zn2 + once daily ) or placebo ( 8 patients ) and were treated with st and ard antidepressant therapy ( tricyclic antidepressants , selective serotonin reuptake inhibitors ) . Hamilton Depression Rating Scale ( HDRS ) and Beck Depression Inventory ( BDI ) were used to assess efficacy of antidepressant therapy , and patients ' status was evaluated before the treatment and 2 , 6 and 12 weeks after its commencement . Antidepressant treatment significantly reduced HDRS scores by the 2nd week of treatment in both groups , and lowered BDI scores at the 6th week in zinc-treated group . Zinc supplementation significantly reduced scores in both measures after 6- and 12-week supplementation when compared with placebo treatment . This preliminary study is the first demonstration of the benefit of zinc supplementation in antidepressant therapy . The mechanism(s ) may be related to modulation of glutamatergic or immune systems by zinc ion",
"OBJECTIVE To examine the effects of citalopram augmentation of antipsychotics on suicidal ideation in middle-aged and older people with schizophrenia and subthreshold depressive symptoms . METHOD In this placebo-controlled trial conducted from September 1 , 2001 , to August 31 , 2007 , 198 out patients > or = 40 years old with DSM-IV-diagnosed schizophrenia or schizoaffective disorder and subthreshold depressive symptoms were r and omly assigned to flexible-dose citalopram ( n = 104 ) or placebo ( n = 94 ) augmentation of their antipsychotic for 12 weeks . Depression was measured with the Hamilton Depression Rating Scale ( HDRS ) and Calgary Depression Rating Scale ( CDRS ) . Primary suicidal ideation measures were the Clinical Global Impressions-Severity of Suicide scale ( CGI-SS ) and the InterSePT Scale for Suicidal Thinking ( ISST ) ; secondary outcomes were the Scale for Suicidal Ideation ( SSI ) , Beck Hopelessness Scale ( BHS ) , HDRS item 3 , and CDRS item 8 . RESULTS Compared to placebo , at the final visit , citalopram was associated with lower BHS scores ( 4.21 vs 4.98 ; P suicidal ideation on the ISST ( 17.7 % vs 38.7 % ; P 114 participants with no baseline suicidal ideation , there were no significant differences between citalopram and placebo regarding \" emergent \" ideation on either primary outcome . Among the 55 participants with baseline suicidal ideation , fewer treated with citalopram had endpoint ideation on the ISST ( 28.6 % vs 66.7 % ; P baseline suicidal ideation to no suicidal ideation on both the ISST ( 75.0 % vs 31.4 % ; P suicidal ideation was no more common with citalopram than placebo . In participants with baseline suicidal ideation , citalopram reduced suicidal ideation , especially in those whose depressive symptoms responded to treatment",
"The objective of this study was to determine if combined psychotherapy and pharmacotherapy reduces reported depressive symptoms compared to an assessment only condition for active drug injectors over nine months . Using a r and omized controlled trial at an outpatient academic research office , the research ers applied psychotherapy ( eight sessions of cognitive behavioral therapy ) plus pharmacotherapy ( citalopram ) to active injection drug users with a DSM-IV diagnosis of major depression , dysthymia , substance-induced mood disorder with symptoms persisting for at least three months , or major depression plus dysthymia , and a Modified Hamilton Rating Scale for Depression ( MHRSD ) score greater than 13 . The MHRSD scale scores were then assessed at the completion of three , six , and nine months . Participants ( n = 109 ) were 64 % male and 82 % Caucasian , with a mean baseline MHRSD score of 20.7 . Depression subtypes included major depression only ( 63 % ) , substance-induced depression ( 17 % ) , and double-depression ( 17 % ) . Study retention at nine months was 89 % . At the completion of three months of acute treatment , 26 % of combined treatment patients ( n = 53 ) , compared to 12 % of control patients ( n = 56 ) , were in remission ( p = .047 ) . At both six and nine months , the between-group differences in remission rates and mean MHRSD scores were insignificant , although the overall mean MHRSD score decreased from baseline ( p depression remission was significantly associated with lower heroin use . Among active drug injectors diagnosed with depression , symptoms decline over time . Combined treatment is superior to an assessment -only condition in depression remission rates at the end-of-treatment , but this difference does not persist",
"The antidepressant efficacy and tolerability of milnacipran , a dual action serotonin-noradrenaline reuptake inhibitor , were compared with those of the selective serotonin reuptake inhibitor , fluvoxamine , in 113 patients with moderate to severe major depression . Treatment with milnacipran , 50 mg b.d . for 6 weeks , produced a significantly greater reduction in Montgomery-Asberg Depression Rating Scale ( MADRS ) scores than fluvoxamine , 100 mg b.d . ( P = 0.007 ; 65.4 % versus 49.9 % , respectively ) ; significantly greater decreases were also seen on days 7 ( P = 0.04 ) and 28 ( P = 0.03 ) . The response rate ( the proportion of patients showing a decrease in MADRS scores of at least 50 % ) was 78.9 % in patients receiving milnacipran , compared with 60.7 % in fluvoxamine-treated patients ( P = 0.04 ) . Milnacipran also produced greater improvements in 24-item Hamilton Depression Rating Scale scores ( P = 0.05 ) . On the Clinical Global Impression Improvement scale , 77.2 % of milnacipran-treated patients were rated as considerably or markedly improved , compared with 60.7 % of patients receiving fluvoxamine ( P = 0.06 chi-squared ) . Both treatments were well tolerated ; the only significant difference between the two groups was a higher incidence of tremor and drowsiness in patients treated with fluvoxamine . It is concluded that milnacipran may offer some advantages over selective serotonin reuptake inhibitors , such as fluvoxamine , in the treatment of moderate to severe major depression",
"OBJECTIVE The aim of this study was to compare over 1 year the effect of sertraline and citalopram on depressive symptoms and cognitive functions of nondemented elderly patients with minor depressive disorder and subsyndromal depressive symptomatology . METHOD We recruited 138 consecutive non-demented out patients of either sex , aged > or = 65 years , who were classified as meeting research criteria for minor depressive disorder or sub-syndromal depressive symptomatology using the Structured Clinical Interview for DSM-IV . Subjects were assigned to receive citalopram 20 mg/day ( 66 patients ) or sertraline 50 mg/day ( 72 patients ) orally for 1 year . Patients were assessed at baseline and after 1 , 2 , 3 , and 6 months and at 1 year by raters masked with regard to patients ' treatment assignments . The Hamilton Rating Scale for Depression , the Geriatric Depression Scale , and the Global Assessment of Functioning were administered to assess the course of depressive symptoms and social functioning during the study . Cognitive measures included Trail Making Test-Parts A and B , Wechsler Memory Scale , Mini-Mental State Examination , and a verbal fluency test . Data were collected from March 2000 to March 2003 . RESULTS The overall completion rate was 72 % . Both treatments induced a significant , sustained , and comparable improvement in depressive symptoms and in social functioning . Nearly half of the subjects in the 2 groups achieved remitter status at study endpoint . Significant within-group improvements also were observed in all cognitive measures . Both drugs were well tolerated during the whole study period . CONCLUSION Our results suggest that sertraline and citalopram can improve depressive symptoms and cognitive functions of minor depressive disorder and subsyndromal depressive symptomatology in elderly nondemented patients",
"SUMMARY The antidepressant efficacy and safety of milnacipran , a dual action antidepressant drug which inhibits the reuptake of serotonin and noradrenaline , was compared with that of the tricyclic antidepressant , imipramine , in a multi-centre , double-blind , r and omised , parallel group , comparative trial in 5 hospital centres in Spain . One hundred patients hospitalised with a diagnosis of major depressive disorder according to the Diagnostic and Statistical Manual of the American Psychiatry Association ( third revision ) , with a minimum score of 25 on the Montgomery and Åsberg Depression Rating Scale were treated for 6 weeks with milnacipran ( 100 mg/day ) or imipramine ( 150 mg/day ) . Both treatments showed similar efficacy in reducing depressive symptoms . The frequency of most adverse events in the milnacipran-treated patients was lower than that observed in the imipramine group , particularly those related to anticholinergic symptoms . Dysuria and shivering , however , were more common with milnacipran . The results of this study support others which have demonstrated that milnacipran has equivalent efficacy but superior tolerability to a tricyclic antidepressant such as imipramine",
"Escitalopram , a selective serotonin reuptake inhibitor ( SSRI ) , was compared to placebo in a study of patients with major depressive disorder ( DSM-IV ) who had baseline Montgomery – Åsberg Depression Rating Scale ( MADRS ) total scores ≥22 and ≤40 . After a 1-week , single-blind placebo period , patients were r and omized to receive escitalopram 10 mg/day ( n = 191 ) or placebo ( n = 189 ) in an 8-week , double-blind period . The primary efficacy analysis of adjusted mean change in MADRS total score from baseline showed a statistically significantly larger effect for escitalopram than for placebo with a treatment difference at week 8 ( last observation carried forward , LOCF ) of 2.7 points ( SE 0.85;P = 0.002 ) . In further by-week efficacy analyses , the effect of escitalopram was consistently larger than that of placebo ( P ( Clinical Global Impression – Improvement score ) , week 2 ( MADRS score ) or week 3 ( Clinical Global Impression – Severity score ) . Escitalopram was very well tolerated with a low overall withdrawal rate similar to that for placebo . Nausea was the only adverse event reported significantly more in escitalopram-treated patients than in placebo-treated patients , although it was infrequent and transient . Escitalopram 10 mg/day had a statistically significantly better antidepressant effect than placebo as early as week 1 , and was safe and very well tolerated",
"OBJECTIVE The use of atypical antipsychotics ( AAPs ) for the treatment of unipolar and bipolar depression has been more and more frequently evaluated , and aripiprazole showed positive effects in the treatment of unipolar depression . However , no placebo-controlled studies of adjunctive aripiprazole for the treatment of bipolar depression have been performed yet . METHODS In this prospect i ve , double-blind , placebo-controlled , r and omized trial , 23 in patients with bipolar depression according to DSM-IV criteria were included . Before r and omization , patients had to be on a constant mood stabilizer treatment with lithium or valproate for at least 1 week . After inclusion , all patients were openly treated with additional citalopram and with additional aripiprazole or placebo for 6 weeks . The primary outcome parameter was the reduction in depressive symptoms according to the Hamilton Depression Rating Scale ( HDRS ) within 6 weeks . RESULTS After 6 weeks of treatment , the HDRS score decreased in both groups . There was no significant difference between both the groups at any point of time with respect to the HDRS . CONCLUSIONS Derived from this small pilot study , adjunctive aripiprazole does not seem to be a promising strategy for the acute treatment of bipolar depression . However , this lack of additional benefit seems to stem from the already good effectiveness of the control group , namely the treatment with citalopram",
"In this multicenter study , the clinical efficacy of citalopram was investigated in 98 patients with moderate AD/SDAT or VD using a combined double-blind and open technique with placebo and citalopram . Analyses were made for each diagnosis after four weeks of double-blind treatment . Patients with AD/SDAT treated with citalopram showed a significant improvement in emotional bluntness , confusion , irritability , anxiety , fear/panic , depressed mood and restlessness . Those improvements were not found after treatment with placebo . There were no significant improvements in patients with VD . No improvements were recorded in motor or cognitive impairment . Citalopram provoked few and comparatively mild side-effects . None of the changes observed during the double-blind withdrawal period were identified as withdrawal symptoms or rebound phenomena",
"From theoretical and clinical perspectives , it is important to know if selected serotonin-reuptake inhibitors ( SSRIs ) , often administered concurrently with electroconvulsive therapy ( ECT ) , modify seizure duration . In a study with a double-blind , cross-over design , the authors evaluated the effect of citalopram , the most selective SSRI available , on the length of electrically induced seizures and on hormone secretion during ECT . Ten depressed women were given either 20 mg citalopram or placebo orally 2 hours before the third and fourth ECT sessions . Seizure duration was assessed by the cuff technique and from electroencephalographic recordings , whereas blood for prolactin , thyrotropin , and cortisol assessment was sample d before ECT and 5 , 10 , 20 , 30 , 40 , and 60 minutes after ECT . No adverse effects after the administration of citalopram were recorded . The length of seizures was not statistically different in the citalopram ( 29.3 ± 8.4 seconds ) and placebo sessions ( 28.2 ± 9.4 seconds ) . Neither pre-ECT plasma hormone levels measured 2 hours after citalopram or placebo administration nor the patterns of ECT-induced hormone secretions differed between the two drug and placebo conditions . The lack of effect of citalopram on hormones in this study may be a result of possible deficiencies of the monoaminergic ( i.e. , serotoninergic ) systems in depression . Although safety and efficacy issues were not fully addressed by coadministering citalopram for the long term and throughout the course of ECT , these findings support the view that challenges the typical clinical practice of discontinuing SSRIs before ECT",
"Current treatments for Obsessive Compulsive Disorder ( OCD ) rely primarily on serotonergic mechanisms . However , approximately 30 % of patients do not respond to serotonin reuptake inhibitors and remain chronically ill . Given the behavioral similarities between some of the compulsive behaviors in OCD and addiction , we hypothesized that the opioid antagonist naltrexone might attenuate compulsions in OCD as well . The effect of naltrexone augmentation to SRI was compared to placebo in 10 OCD out patients who had not responded to an adequate dose of SSRI or clomipramine for at least 2 months . Participants underwent 5 weeks of treatment with naltrexone or placebo ( and 1 week of tapering ) in a r and omized , double-blind , cross-over design . Patients were evaluated weekly using the Y-BOCS , CGI , HAM-A , and MADRS scales . A two-way repeated measures MANOVA revealed no significant effect for Y-BOCS . However , while receiving naltrexone , patients had significantly higher scores on CGI , MADRS and HAM-A as compared to placebo . The lack of significant findings on OC symptoms could be due to either ceiling effect or alternatively , due to a non-specific exacerbation on anxiety and depression but not on OC symptoms",
"BACKGROUND Major depressive disorder ( MDD ) has been associated with alterations in immune function . Suppression of natural killer ( NK ) cell activity ( NKCA ) reliably characterizes immunological alterations observed in MDD . Antidepressant pharmacotherapy has been associated with modulation of NKCA . Previous investigations into antidepressant modulation of NKCA have not employed r and omized double-blind placebo controlled design s. Thus , it is unknown whether treatment-associated changes in immune function are due to drug , placebo , or spontaneous remission effects . The present investigation examined the effect of antidepressant treatment on NKCA utilizing a r and omized double-blind placebo controlled experimental design . METHOD Patients ( N = 16 ) met DSM-IV criteria for MDD and were r and omly assigned to drug ( N = 8 ; citalopram , 20 mg/day ) or placebo ( N = 8) under double-blind conditions . Severity and pattern of depressive symptoms were assessed by the Hamilton Depression Rating Scale ( HDRS ) . NK cell function was measured using a st and ard chromium-release assay and NK cell number assessed by flow cytometry . HDRS scores , NK cell function , and NK cell numbers were collected at 0 , 1 , 2 and 4 weeks of treatment . RESULTS Clinical response was associated with augmented NKCA independent of treatment condition . Failure to respond to treatment result ed in significantly reduced NKCA over treatment interval . CONCLUSIONS The present results suggest that alterations in the depressive syndrome , regardless of therapeutic modality , may be sufficient to modulate NKCA during antidepressant trials and thus may significantly impact on co-morbid health outcomes in MDD",
"The antidepressant selective serotonin transporter inhibitors ( SSRIs ) are clinical ly active after a delay of several weeks . Indeed , the rapid increase of serotonin ( 5-HT ) caused by SSRIs , stimulates the 5-HT(1A ) autoreceptors , which exert a negative feedback on the 5-HT neurotransmission . Only when autoreceptors are desensitized , can SSRIs exert their therapeutic activity . The 5-HT(1A ) receptor antagonist pindolol has been used to accelerate the clinical effects of antidepressant by preventing the negative feedback . Using the alpha-[(11)C]methyl-L-tryptophan/positron emission tomography ( PET ) , the goal of the present double-blind , r and omized study was to compare the changes in alpha-[(11)C]methyl-L-tryptophan trapping , an index of serotonin synthesis , in patients suffering from unipolar depression treated with the SSRI citalopram ( 20 mg/day ) plus placebo versus patients treated with citalopram plus pindol ( 7.5 mg/day ) . PET and Hamilton depression rating scale ( HDRS-17 ) were performed at baseline , and after 10 and 24 days of antidepressant treatment . Results show that the combination citalopram plus pindol , compared to citalopram alone shows a more rapid and greater increase of an index of 5-HT synthesis in prefrontal cortex ( BA 9 ) . This research is the first human PET study demonstrating that , after 24 days , the combination SSRIs plus pindolol produces a greater increase of the metabolism of serotonin in the prefrontal cortex , an area associated to depressive symptoms",
"CONTEXT Depression occurs in more than half of patients who have experienced a stroke . Poststroke depression has been shown in numerous studies to be associated with both impaired recovery in activities of daily living and increased mortality . Prevention of depression thus represents a potentially important goal . OBJECTIVE To determine whether treatment with escitalopram or problem-solving therapy over the first year following acute stroke will decrease the number of depression cases that develop compared with placebo medication . DESIGN , SETTING , AND PARTICIPANTS A multisite r and omized controlled trial for prevention of depression among 176 nondepressed patients was conducted within 3 months following acute stroke from July 9 , 2003 , to October 1 , 2007 . The 12-month trial included 3 groups : a double-blind placebo-controlled comparison of escitalopram ( n = 59 ) with placebo ( n = 58 ) , and a nonblinded problem-solving therapy group ( n = 59 ) . MAIN OUTCOME MEASURES The main outcome measure was the development of major or minor poststroke depression based on symptoms elicited by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders ( Fourth Edition ) ( DSM-IV ) and the diagnostic criteria from DSM-IV for depression due to stroke with major depressive-like episode or minor depression ( ie , research criteria ) . RESULTS Patients who received placebo were significantly more likely to develop depression than individuals who received escitalopram ( 11 major and 2 minor cases of depression [ 22.4 % ] vs 3 major and 2 minor cases of depression [ 8.5 % ] , adjusted hazard ratio [ HR ] , 4.5 ; 95 % confidence interval [ CI ] , 2.4 - 8.2 ; P problem-solving therapy ( 5 major and 2 minor cases of depression [ 11.9 % ] , adjusted HR , 2.2 ; 95 % CI , 1.4 - 3.5 ; P 27 patients who did not start r and omized treatment would have developed depression , and controlling for prior history of mood disorders , escitalopram was superior to placebo ( 23.1 % vs 34.5 % ; adjusted HR , 2.2 ; 95 % CI , 1.2 - 3.9 ; P = .007 ) , while problem-solving therapy was not significantly better than placebo ( 30.5 % vs 34.5 % ; adjusted HR , 1.1 ; 95 % CI , 0.8 - 1.5 ; P = .51 ) . Adverse events , including all-cause hospitalizations , nausea , and adverse effects associated with escitalopram were not significantly different between the 3 groups . CONCLUSIONS In this study of nondepressed patients with recent stroke , the use of escitalopram or problem-solving therapy result ed in a significantly lower incidence of depression over 12 months of treatment compared with placebo , but problem-solving therapy did not achieve significant results over placebo using the intention-to-treat conservative method of analysis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00071643",
"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",
"Many patients with major depressive disorder ( MDD ) present with concurrent substance use disorders ( SUDs ) , which has been thought to impair their response to antidepressants . Clinicians often delay antidepressant treatment until sustained sobriety has been established . Unfortunately , these comorbid subjects are typically excluded from depression treatment trials , leaving a gap in underst and ing the treatment outcomes . In the Sequenced Treatment Alternatives to Relieve Depression ( STAR*D ) study , 2876 adult out patients diagnosed with nonpsychotic MDD were prospect ively treated with the selective serotonin-reuptake inhibitor ( SSRI ) , citalopram , and returned for at least one post-baseline visit . Participants with SUD ( 29 % ) and without SUD ( 71 % ) were compared in regard to baseline clinical and sociodemographic features and treatment response . The group with MDD and SUD was further subdivided into those with alcohol only , drug only , and both alcohol and drug use . Despite clear sociodemographic and clinical differences , there were no significant differences between groups in the time to achieve response or rates of response to citalopram ; however , those who endorsed both alcohol and drug use had significantly reduced rates of remission and significantly increased times to reach remission compared to the MDD group without SUD . In addition , subjects with MDD and SUD had higher risk of psychiatric serious adverse events ( 3.3 % vs. 1.5 % ) and hospitalization ( 2.8 % vs. 1.2 % ) . The results indicate that first-line treatment with citalopram in depressed patients with alcohol or drug use respond as well as those without SUD . More intensive treatment is most likely needed for MDD patients with both drug and alcohol use disorders",
"OBJECTIVE Comparing the antidepressant effects of Citalopram with Fluoxetine and their effect on glycemic control in diabetic patients . METHODS Forty patients attending the Diabetes Research Center in Kermanshah University of Medical Sciences , Kermanshah , Iran from September 2006 to October 2007 with type II diabetes and suffering from major depression were r and omly assigned to 2 groups ( n=20 per group ) in a r and omized controlled trial method . They received up to 40 mg/d of Fluoxetine or Citalopram . Twelve weeks after treatment , patients were reassessed in terms of severity of depression and diabetic status . The Beck Depression Inventory ( BDI ) and psychiatric interview were used to measure the severity of depression and follow up the patients . Glycosylated hemoglobin ( HbA1c ) levels and fasting blood sugar ( FBS ) was obtained to monitor glycemic control . RESULTS After the 12-week treatment , both groups showed significant improvement in severity of depression , FBS , and HbA1c . There were no significant differences between the 2 groups in terms of improvement in depression and diabetic status . CONCLUSION Fluoxetine and Citalopram can effectively reduce the severity of depression in diabetic patients without an adverse effect on glycemic control",
"Major depression ( MD ) is underdiagnosed and undertreated in patients with temporal lobe epilepsy ( TLE ) . Side effects of some antidepressants , like increased risk of seizures and drug-drug interactions with anticonvulsants , contribute to undertreatment of MD in patients with TLE . We analyzed post hoc the data from 2 years of treatment of in patients with MD and TLE . Seventy-five patients received st and ard treatment with citalopram , mirtazapine , or reboxetine , respectively , at recommended dosage . Examinations were done with the Hamilton Rating Scale for Depression at admission and after 4 and 20 - 30 weeks . Plasma levels of anticonvulsants were examined at admission and discharge . Seizures were documented . The antidepressive treatment was efficacious in all antidepressant groups . No case of serious adverse event or drug interaction occurred . There was no increase in frequency or severity of seizures . At endpoint the dropout rate for mirtazapine was significantly higher than that for reboxetine or citalopram . Reboxetine showed a trend to be more efficacious than citalopram but not mirtazapine at Week 4",
"The present r and omized , double blind , parallel group , controlled , multi-centric trial was design ed to evaluate the efficacy and tolerability of escitalopram in comparison with citalopram and sertraline in the treatment of major depressive disorder . Out patients ( N=214 ) with an ongoing/newly diagnosed ICD-10 major depressive episode and a Hamilton Rating Scale for Depression ( HAM-D ) score of > 18 were r and omly assigned to citalopram , 20–40 mg/day ( 74 patients ) , escitalopram , 10–20 mg/day ( 69 patients ) and sertraline , 50 - 150 mg/day ( 71 patients ) , for a 4-week double-blind treatment period , with dosage adjustment ( after 2 weeks of treatment ) according to the response to treatment . Clinical response was evaluated by the 17 items HAM-D and the Clinical Global Impression ( CGI ) scales , which were recorded at baseline and at weekly intervals . Tolerability was evaluated by observed/spontaneously reported adverse changes in laboratory parameters ( baseline and after 4 weeks ) . Response rate was defined as a decrease in HAM-D score by 50 % from baseline and remission rate was defined as a HAM-D score of Response rate at the end of two week were 58 % for escitalopram ( 10mg/day ) , 49 % for citalopram ( 20mg/day ) and 52 % for sertraline ( 50 - 100mg/day ) . Response rate at the end of four week were 90 % for escitalopram ( 10 - 20mg/day ) , 86 % for citalopram ( 20 - 40mg/day ) and 97 % for sertraline ( 100 - 150mg/day ) . The Remission rates at the end of four weeks were 74 % for escitalopram , 65 % for citalopram and 77 % for sertraline . Adverse experiences were reported by 45 % of patients in escitalopram group , 58 % patients in citalopram and 56 % patients in the sertraline group . Additionally , there were lesser dropouts and lesser requirement for dose escalation in escitalopram than in citalopram and sertraline group . In conclusion Escitalopram , the Senantiomer of the citalopram is a safe and effective antidepressant in the Indian population . It has potentially superior efficacy than citalopram and a comparable efficacy to sertraline with fewer side effects than both citalopram and sertraline",
"Abstract Objective : To investigate if treatment outcome for severely depressed patients depends on their baseline level of anxiety . Research design and methods : Patients with a primary diagnosis of severe major depressive disorder ( n = 459 ) were r and omised to 24 weeks of double-blind treatment with escitalopram ( 20 mg ) or paroxetine ( 40 mg ) . Post hoc analyses of efficacy in patients with a baseline HAM-A total score ≤20 ( n = 171 ) or > 20 ( n = 280 ) were based on analysis of covariance ( ANCOVA ) ( ITT , LOCF ) . Results : At week 24 , the mean change from baseline in MADRS total scores was −24.2 for escitalopram-treated patients ( n = 141 ) and −21.5 for paroxetine-treated patients ( n = 139 ) ( p baseline in HAM-A total score was −17.4 ( escitalopram ) and −15.1 ( paroxetine ) ( p proportion of complete remitters ( CGI-S = 1 ) after 24 weeks of treatment , there was an increasing treatment difference as a function of baseline HAM-A total score in favour of escitalopram ( ITT , LOCF ) . There was no treatment difference in the low baseline anxiety group . Significantly more patients ( p paroxetine group ( 31 % ) than from the escitalopram group ( 17 % ) , partly as the result of significantly more withdrawals due to AEs ( p of AEs and withdrawals were not related to baseline anxiety and there were no significant differences in the incidence of individual AEs with escitalopram compared to paroxetine . Limitations : The post hoc nature of these analyses , the absence of placebo control group , and the requirement that patients should be suffering from severe depression , limit the generalisability of the results . Conclusion : Patients with severe depression together with comorbid anxiety symptoms responded significantly better to treatment with escitalopram 20 mg compared with paroxetine 40 mg . Contrary to paroxetine , escitalopram maintained its efficacy with increasing baseline anxiety levels ",
"CONTEXT Antidepressant-associated sexual dysfunction is a common adverse effect that frequently results in premature medication treatment discontinuation and for which no treatment has demonstrated efficacy in women . OBJECTIVE To evaluate the efficacy of sildenafil for sexual dysfunction associated with selective and nonselective serotonin reuptake inhibitors ( SRIs ) in women . DESIGN , SETTING , AND PARTICIPANTS An 8-week prospect i ve , parallel-group , r and omized , double-blind , placebo-controlled clinical trial conducted between September 1 , 2003 , and January 1 , 2007 , at 7 US research centers that included 98 previously sexually functioning , premenopausal women ( mean [ SD ] age 37.1 [ 6 ] years ) whose major depression was remitted by SRIs but who were also experiencing sexual dysfunction . INTERVENTION Forty-nine patients were r and omly assigned to take sildenafil or placebo at a flexible dose starting at 50 mg adjustable to 100 mg before sexual activity . MAIN OUTCOME MEASURES The primary outcome measure was the mean difference in change from baseline to study end ( ie , lower ordinal score ) on the Clinical Global Impression sexual function scale . Secondary measures included the Female Sexual Function Question naire , the Arizona Sexual Experience scale-female version , the University of New Mexico Sexual Function Inventory-female version , a sexual activity event log , and the Hamilton Depression Rating scale . Hormone levels were also assessed . RESULTS In an intention-to-treat analysis , women treated with sildenafil had a mean Clinical Global Impression-sexual function score of 1.9 ( 95 % confidence interval [ CI ] , 1.6 - 2.3 ) compared with those taking placebo ( 1.1 ; 95 % CI , 0.8 - 1.5 ) , with a mean end point difference of 0.8 ( 95 % CI , 0.6 - 1.0 ; P = .001 ) . Assigning baseline values carried forward to the 22 % of patients who prematurely discontinued result ed in a mean end point in the sexual function score of 1.5 ( 95 % CI , 1.1 - 1.9 ) among women taking sildenafil compared with 0.9 ( 95 % CI , 0.6 - 1.3 ) among women taking placebo with a mean end point difference of 0.6 ( 95 % CI , 0.3 - 0.8 ; P = .03 ) . Baseline endocrine levels were within normal limits and did not differ between groups . The mean ( SD ) Hamilton scores for depression remained consistent with remission in both groups ( 4.0 [ 3.6 ] ; P = .90 ) . Headache , flushing , and dyspepsia were reported frequently during treatment , but no patients withdrew because of serious adverse effects . CONCLUSION In this study population , sildenafil treatment of sexual dysfunction in women taking SRIs was associated with a reduction in adverse sexual effects . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00375297",
"The aim of this study was to determine predictors of the response to escitalopram , a selective serotonin re-uptake inhibitor antidepressant and memantine , a non-competitive glutamate NMDA receptor blocker , for the treatment of major depression comorbid with alcohol dependence . Eighty alcohol dependent treatment-seeking adult patients with comorbid major depressive disorder were r and omized to receive either memantine 20 mg or escitalopram 20 mg for 26 weeks . In both treatment groups , depression was reduced significantly . Comparisons were made between patients in remission ( final Montgomery-Asberg Depression Rating Scale (MADRS) age at onset of the first major depressive episode significantly correlated with the treatment response in the escitalopram group ; the mean age at onset of depression among patients on the non-responders group was 13.7+/-4.0 years and 31.9+/-11.9 years in remission . These results are significantly different from those with memantine . Our study provides evidence that the onset of the first major depressive episode might be a clinical ly relevant predictor of a response to escitalopram treatment in patients with major depression and comorbid alcohol dependence",
"This multicentre , double-blind , r and omised trial in 109 patients compared the efficacy and tolerance of the novel selective serotonin and noradrenaline reuptake inhibitor ( SNRI ) antidepressant milnacipran ( 50 mg twice daily , n=53 ) with the established tricyclic agent imipramine ( 75 mg twice daily , n=56 ) over a period of 6 weeks , in patients with major depression ( Montgomery-Asberg depression rating score ( MADRS ) > or = 25 ) . Initiation of antidepressant medication was conducted during a 2-week period of hospitalisation , after a 3- to 7-day washout period . Concomitant psychiatric medication was limited to lorazepam , cyamemazine , chloral hydrate and long-term uncomplicated lithium therapy . Assessment for efficacy using the MADRS and Hamilton rating scales of depression , a visual analogue scale and global evaluation revealed both agents to be highly effective ( P=0.0001 ) in this group of patients . Milnacipran was found to be of similar efficacy to imipramine . Tolerance , assessed by physiological and biochemical examinations with routine inventory and spontaneous report of adverse events , revealed a clear advantage for milnacipran . The incidence of anticholinergic events with milnacipran was about half that with imipramine and the overall incidence of adverse events by either reporting method was markedly lower with milnacipran than with imipramine . Furthermore , the patient drop-out rate with imipramine was double that experienced with milnacipran . Milnacipran appears to possess equal antidepressant efficacy to imipramine but with markedly superior tolerance . Therefore , milnacipran constitutes an important new treatment option in major depression",
"BACKGROUND The study objective was to evaluate variations in genes implicated in antidepressant mechanism of action for association with response to duloxetine treatment in major depressive disorder ( MDD ) . METHODS We assessed response over 6 weeks in 250 duloxetine-treated Caucasian patients in a r and omized , double-blind study of patients with MDD . Single nucleotide polymorphisms ( SNPs ) were genotyped in 19 c and i date genes selected based on evidence for involvement in antidepressant mechanism of action . Primary analysis examined baseline to end point reduction in the 17-item Hamilton Depression Rating Scale ( HAMD17 ) total score , using a set-based test for association for each gene . Follow-up analyses examined individual SNPs within any significant gene for association with reduction in HAMD17 and 30-item Inventory of Depressive Symptomatology-Clinician Rated ( IDS-C-30 ) . RESULTS After correction for multiple comparisons , only COMT was associated with change in HAMD17 ( experiment wide p = .018 ) . Peak association was detected with rs165599 ( p = .006 ) , which accounted for approximately 3 % of variance in HAMD17 change and > 4 % of variance in IDS-C-30 change ( p = .001 ) . The least-squared mean change ( SE ) in HAMD17 score by rs165599 genotype was -10.8 ( 1.2 ) , -8.7 ( .6 ) , and -6.5 ( .7 ) for patients with GG , GA , and AA genotypes , respectively . For SNPs in serotonin 2A receptor ( HTR2A ) previously associated with citalopram response , including rs7997012 , no significant evidence of association with duloxetine response was identified . CONCLUSIONS Single nucleotide polymorphisms in COMT were associated with symptom change in duloxetine-treated patients with MDD . If replicated , the magnitude of the COMT genotype effect is of clinical relevance",
"OBJECTIVE Chronic fatigue syndrome ( CFS ) is a debilitating disorder with prominent symptoms of malaise , fatigue , myalgia , arthralgia , and impaired concentration . The symptoms of CFS may often overlap those of Major Depressive Disorder ( MDD ) . Treatment of CFS has generally been disappointing . We hypothesized that s-citalopram therapy may improve the symptoms of both disorders in CFS patients with co-morbid depression . METHODS 16 patients received s-citalopram 10 mg to 20 mg daily for up to 12 weeks . Outcome measures of CFS included the Chalder Fatigue Question naire ( CFQ ) , the multi-dimensional Fatigue Impact Scale ( FIS ) , the CFS symptom rating ( CFS-SR ) 100 mm visual analogue scale , and the clinical global impressions severity ( CGI/S ) and change ( CGI/C ) ratings . Secondary outcomes of MDD included the Hamilton Depression Rating ( HAM-D ) , Beck Depression Inventory ( BDI ) , and the CGI/S and CGI/C ratings of MDD . RESULTS We observed reductions in the mean CFQ score ( p FIS score ( p CGI/S ( p CGI/C ( p CFS-SR symptoms : post-exertion malaise ( p=0.001 ) , headaches ( p un-refreshing sleep ( p impaired memory and concentration ( p mean HAM-D ( p BDI ( p CGI/S ( p=0.001 ) and CGI/C ( p CFS and co-morbid MDD symptom severity ratings , and improvement in 5 of 8 core somatic symptoms of CFS during s-citalopram therapy",
"OBJECTIVE The objective of this double-blind , r and omised , placebo-controlled , multicentre clinical study was to demonstrate the non-inferiority and safety of the hypericum extract STW3-VI in a once-daily dosage regime in the treatment of moderate depression . During the 6-week treatment phase , the course of depression was documented by use of HAMD ( items 1 - 17 ) , the von Zerssen 's Adjective Mood Scale ( BfS ) and the CGI scales . The primary objective of this 3-arm design study was to demonstrate the non-inferiority of hypericum extract STW3-VI ( 900 mg ) to the SSRI citalopram ( 20 mg ) and superiority of hypericum over placebo . METHODS Out patients ( N = 388 ) suffering from moderate depression were enrolled . The safety and tolerability of hypericum extract in comparison to citalopram and placebo was investigated on the basis of CGI , the occurrence of adverse events and the investigation of laboratory parameters and vital signs . RESULTS From almost identical baseline values of 21.9 + /- 1.2 points ( hypericum extract ) , 21.8 + /- 1.2 points ( citalopram ) and 22.0 + /- 1.2 points ( placebo ) , the HAMD score was reduced to 10.3 + /- 6.4 ( hypericum extract ) , 10.3 + /- 6.4 ( citalopram ) and 13.0 + /- 6.9 ( placebo ) , respectively . Based on this data , the statistical significant therapeutic equivalence of hypericum extract STW3-VI to citalopram ( p hypericum extract over placebo ( p ( hypericum extract ) , 55.9 % ( citalopram ) and 39.2 % ( placebo ) of the patients were assessed as therapy responders . The secondary efficacy parameters , change in BfS , CGI and amount of therapy responders showed that the hypericum group was not statistically different from the citalopram group , and significantly superior to the placebo group . Significantly more adverse events with \" certain \" , \" probable \" or \" possible \" relation to study medication were documented in the citalopram group ( hypericum : 17.2 % , citalopram : 53.2 % , placebo : 30 % ) . In most cases , the investigators assessed the tolerability of hypericum extract , citalopram and placebo as \" good \" or \" very good \" . CONCLUSION The non-inferiority of hypericum extract as compared to citalopram and the superiority of both active compounds to placebo were demonstrated , as well as a better safety and tolerability of hypericum extract in comparison to citalopram . These results revealed that hypericum extract STW3-VI is a good alternative to chemically defined antidepressants in the treatment of out patients with moderate depression",
"Drug-induced improvement of depression may be mediated by changes in sleep physiology . The aim of this study was to relate changes in sleep polygraphic variables to clinical state during treatment with citalopram , a highly specific serotonin uptake inhibitor . Sixteen patients took part . The study was single-blind and uncontrolled . A 1-week wash-out period was followed by 1 week of placebo administration , a medication period of 5 weeks , and a 1-week placebo period . For the entire group a significant decrease of rapid eye movement sleep ( REMS ) and a significant lengthening of REMS latency were observed initially as well as at the end of treatment . No changes in sleep continuity were found , but non-REMS stage 2 ( percentage ) was significantly increased . On the basis of clinical change , as expressed by the scores of the Hamilton Rating Scale for Depression , at the end of the citalopram treatment the patient group was split in two halves : eight less and eight more improved patients . The groups did not differ with respect to any sleep polygraphic varible",
"Background Depression is a leading cause of disability worldwide and depressive symptoms are common in later life . Observational evidence suggests that depression is more prevalent among people with high plasma homocysteine ( tHcy ) , but the results of r and omized trials to date have been unable to show that lowering tHcy through the supplementation of vitamins B6 , B12 and folate benefits depressive symptoms . We design ed the B-VITAGE trial to determine whether adjunctive treatment with vitamins B6 , B12 and folate increases the efficacy of st and ard antidepressant treatment . Methods / Design The B-VITAGE trial is a 12-month r and omized , double-blind , placebo-controlled trial of daily citalopram ( 20 to 40 mg ) plus B12(0.4 mg ) , B6 ( 25 mg ) and folic acid ( 2 mg ) or citalopram ( 20 to 40 mg ) plus placebo for the treatment of depression in later life . The trial aims to recruit over 300 older adults with major depression ( DSM-IV ) and has been powered to detect the impact of an intervention associated with moderate effect size . Depressive symptoms will be rated with the Montgomery-Åsberg Depression Rating Scale ( MADRS ) . The trial has two main outcomes of interest : a reduction of 50 % or more in the MADRS total score between baseline and week 12 and the remission of the depressive episode at weeks 12 , 26 and 52 according to DSM-IV criteria . We hypothesize that subjects r and omly allocated to the vitamin arm of the study will be more likely to show a clinical ly significant improvement and achieve and maintain remission of symptoms at 12 , 26 and 52 weeks . Secondary outcomes of interest include compliance with treatment , reduction in the severity of depressive symptoms , switching to different antidepressants , the use of non-pharmacological antidepressant treatments , response to treatment according to MTHFRC677 T genotype , and changes in cognitive function over 52 weeks . Conclusions The results of this trial will clarify whether the systematic use of B-vitamins improves the response of older adults to st and ard antidepressant treatment . We anticipate that our findings will have implication s for clinical practice and health policy development . Trial Registration The trial is registered with the Australian Clinical Trials Registry , trial number ( ())ACTRN12609000256279",
"Background In some r and omized trials successful laparoscopic cholecystectomy for cholecystitis is associated with an earlier recovery and shorter hospital stay when compared with open cholecystectomy . Other studies did not confirm these results and showed that the potential advantages of laparoscopic cholecystectomy for cholecystitis can be offset by a high conversion rate to open surgery . Moreover in these studies a similar postoperative programme to optimize recovery comparing laparoscopic and open approaches was not st and ardized . These studies also do not report all eligible patients and are not double blinded . Design The present study project is a prospect i ve , r and omized investigation . The study will be performed in the Department of General , Emergency and Transplant Surgery St Orsola-Malpighi University Hospital ( Bologna , Italy ) , a large teaching institutions , with the participation of all surgeons who accept to be involved in ( and together with other selected centers ) . The patients will be divided in two groups : in the first group the patient will be su bmi tted to laparoscopic cholecystectomy within 72 hours after the diagnosis while in the second group will be su bmi tted to laparotomic cholecystectomy within 72 hours after the diagnosis . Trial Registration TRIAL REGISTRATION NUMBER IS RCT N27929536 – The ACTIVE ( Acute Cholecystitis Trial Invasive Versus Endoscopic ) study . A multicentre r and omised , double-blind , controlled trial of laparoscopic versus open surgery for acute cholecystitis in adults",
"BACKGROUND clinicians have long noticed a correlation between physiological markers of inflammation and depression . The best-known example is the activation of the hypothalamus-pituitary-adrenal axis and cortisol secretion ; however more recent studies have demonstrated increased salivary prostagl and ins and plasma acute phase proteins in depressed patients . To date four r and omised controlled trials have used celecoxib or rofecoxib as adjuncts to serotonin selective reuptake inhibitors in the treatment of depression . These suggested a statistically significant decrease in depressive symptoms in the patients taking NSAIDs and SSRIs , compared to patients taking SSRIs alone . Interpretation of these results is limited by the small sample size and short duration of these preliminary studies . The research only considers depressed patients receiving treatment in secondary care ; no study has examined the effectiveness of NSAIDs as an adjunct in primary care , even though most cases of depression in the UK are managed in the community by general practitioners . PROPOSAL we propose a multi-centre double-blinded r and omised controlled trial with two objectives : to determine whether citalopram plus celecoxib dual therapy achieves a greater reduction in depressive symptoms ( quantified using the Hamilton Depression Rating Scale ( HDRS ) ) within four weeks , compared to citalopram monotherapy ; and to determine whether citalopram plus celecoxib dual therapy is more likely to achieve remission ( HDRS score ? 7 ) of moderate to severe depression within six months , compared with citalopram monotherapy . The endpoints will be the reduction in HDRS score after 4 weeks of treatment , and the HDRS score after 26 weeks of treatment . The study will enrol 452 participants from general practice s who have a moderate or severe , current or recurrent major depressive episode when medication with an SSRI is considered . The study population will be stratified according to age , sex , HDRS score , age of onset of first episode , number of previous depressive episodes and duration of current episode . The population will then be r and omised into two groups . Subjects will be interviewed to determine HDRS score , measure blood pressure , count pills and discuss side-effects . This will occur weekly for the first four weeks , and every four weeks thereafter",
"Introduction Erythropoietin ( Epo ) has neurotrophic effects and may be a novel therapeutic agent in the treatment of depression . We have found antidepressant-like effects of Epo on emotional processing and mood in healthy volunteers . Objective The current study aim ed to explore the effects of Epo on the neural processing of emotional information in depressed patients . Material s and methods Seventeen patients with acute major depressive disorder were r and omised to receive Epo ( 40,000 IU ) or saline iv in a double-blind , parallel-group design . On day 3 , we assessed neural responses to positive , negative and neutral pictures during fMRI followed by picture recall after the scan . Mood and blood parameters were assessed at baseline and on day 3 . Results Epo reduced neural response to negative vs. positive pictures 3 days post-administration in a network of areas including the hippocampus , ventromedial prefrontal and parietal cortex . After the scan , Epo-treated patients showed improved memory compared with those that were given placebo . The effects occurred in the absence of changes in mood or haematological parameters , suggesting that they originated from direct neurobiological actions of Epo . Conclusions These findings are similar to the effects of conventional antidepressants and opposite to the negative biases in depression . The central effects of Epo therefore deserve further investigation as a potential antidepressant mechanism",
"CONTEXT Mindfulness-based cognitive therapy ( MBCT ) is a group-based psychosocial intervention design ed to enhance self-management of prodromal symptoms associated with depressive relapse . OBJECTIVE To compare rates of relapse in depressed patients in remission receiving MBCT against maintenance antidepressant pharmacotherapy , the current st and ard of care . DESIGN Patients who met remission criteria after 8 months of algorithm-informed antidepressant treatment were r and omized to receive maintenance antidepressant medication , MBCT , or placebo and were followed up for 18 months . SETTING Outpatient clinics at the Centre for Addiction and Mental Health , Toronto , Ontario , Canada , and St Joseph 's Healthcare , Hamilton , Ontario . PARTICIPANTS One hundred sixty patients aged 18 to 65 years meeting DSM-IV criteria for major depressive disorder with a minimum of 2 past episodes . Of these , 84 achieved remission ( 52.5 % ) and were assigned to 1 of the 3 study conditions . INTERVENTIONS Patients in remission discontinued their antidepressants and attended 8 weekly group sessions of MBCT , continued taking their therapeutic dose of antidepressant medication , or discontinued active medication and were switched to placebo . MAIN OUTCOME MEASURE Relapse was defined as a return , for at least 2 weeks , of symptoms sufficient to meet the criteria for major depression on module A of the Structured Clinical Interview for DSM-IV . RESULTS Intention-to-treat analyses showed a significant interaction between the quality of acute-phase remission and subsequent prevention of relapse in r and omized patients ( P = .03 ) . Among unstable remitters ( 1 or more Hamilton Rating Scale for Depression score > 7 during remission ) , patients in both MBCT and maintenance treatment showed a 73 % decrease in hazard compared with placebo ( P = .03 ) , whereas for stable remitters ( all Hamilton Rating Scale for Depression scores ≤7 during remission ) there were no group differences in survival . CONCLUSIONS For depressed patients achieving stable or unstable clinical remission , MBCT offers protection against relapse/recurrence on a par with that of maintenance antidepressant pharmacotherapy . Our data also highlight the importance of maintaining at least 1 long-term active treatment in unstable remitters",
"Patients with major depressive disorder ( MDD ) usually suffer from altered cognitive functions of episodic memory , working memory , mental processing speed and motor response . Diverse studies suggest that different antidepressant agents may improve cognitive functions in patients with MDD . The aim of this work is to study the effects of serotonergic reuptake inhibitors ( SSRIs ) and serotonergic-noradrenergic reuptake inhibitors ( SNRIs ) treatments to improve the performance on memory tasks and mental processing speed in MDD . Seventy-three subjects meeting criteria for major depressive disorder were assessed with the Hamilton depression rating scale and a neuropsychological battery . The subjects were medicated with escitalopram ( n=36 ) or duloxetine ( n=37 ) for 24 weeks . At the end of the trial , the subjects were assessed again with the same neuropsychological battery used prior to the treatment . Both treatments improved importantly the episodic memory and to a lesser extent , working memory , mental processing speed and motor performance . Our results suggest that cognition is partially independent from improvement in clinical symptoms . Both groups achieved remission rates in the HAM-D-17 after 24 weeks of treatment , but SNRI was superior to SSRI at improving episodic and working memory . Our work indicates that the superiority of SNRI over the SSRI at episodic memory improvement is clinical ly relevant",
"Several previous studies , including a meta- analysis , reported no significant differences between various selective serotonin reuptake inhibitors ( SSRIs ) in the treatment of major depressive disorder . However , because of the different chemical structure of SSRIs and the difference in the frequency of serotonin transporter polymorphisms between ethnic groups , a head-to-head comparative study between SSRIs in different population s may be enlightening . We compared the efficacy and adverse effect profiles of citalopram and sertraline in a double-blinded r and omized clinical trial in a Chinese population of drug-naïve patients with first-episode major depressive disorder . Fifty-one patients were r and omly assigned to citalopram or sertraline treatment . The Montgomery-Åsberg Depression Rating Scale ( MADRS ) was used as the primary outcome . Efficacy and adverse effects were analyzed in an intent-to-treat population . Efficacy was analyzed using a last-observation-carried-forward method for early terminators . There were no significant differences in demographic characteristics at baseline . No significant differences were found in MADRS scores between citalopram and sertraline at baseline ( 36.6 ± 5.5 vs 38.2 ± 4.9 ; P = 0.322 ) or at the end of treatment ( week 6 ; 10.8 ± 10.0 vs 16.7 ± 11.3 ; P = 0.082 ) . However , MADRS scores in the citalopram group were significantly lower at week 1 ( 25.2 ± 8.5 vs 30.4 ± 6.1 ; P = 0.029 ) and week 3 ( 15.9 ± 10.0 vs 22.1 ± 8.7 ; P = 0.037 ) . Overall , treatment-emergent adverse effects were reported by 14.3 % and 28.6 % of patients in the citalopram and sertraline groups , respectively . In conclusion , citalopram and sertraline were both efficacious and well tolerated . However , citalopram exhibited a significantly faster onset than sertraline during the early weeks of treatment and tended to have a better efficacy in overall treatment , although the statistic was not significant",
"Pre- clinical studies , active-control clinical trials and meta-analyses indicate that escitalopram ( S-citalopram ) might be more effective than citalopram , the racemic mixture of S- and R-citalopram . The present study aim ed to confirm the superior efficacy of escitalopram over citalopram . A double-blind , r and omized clinical trial was performed in which general practitioners and psychiatrists compared fixed doses of escitalopram ( 20 mg/day ) with citalopram ( 40 mg/day ) over 8 weeks in out patients with major depressive disorder ( MDD ) [ baseline Montgomery – Asberg Depression Rating Scale ( MADRS ) score ≥30 ] . Primary efficacy parameter was change from baseline to last assessment in the MADRS total score . Out of 138 ( aged 44.1±10.9 years ; initial MADRS score 36.3±4.8 ) and 142 ( aged 46.2±11.1 years ; initial MADRS score 35.7±4.4 ) evaluable patients who were r and omized to escitalopram and citalopram , respectively , six and 15 withdrew prematurely ( P=0.05 ) . The MADRS score decreased more in the escitalopram than in the citalopram arm ( –22.4±12.9 versus –20.3±12.7 ; P with escitalopram ( 76.1 % ) than with citalopram ( 61.3 % , P rates were 56.1 % and 43.6 % , respectively ( P was similar in both groups . This r and omized double-blind trial confirms that escitalopram has a superior effect to citalopram in MDD",
"Orthostatic hypotension , the clinical ly most important side effect in treatment with tricyclic antidepressants , was investigated in a double-blind study with clomipramine and the selective serotonin reuptake inhibitor citalopram given for 5 weeks . All patients were initially given placebo for 1 week . In the clomipramine group ( n=17 ) a significant orthostatic drop in the systolic blood pressure was observed during treatment ; this remained significant over the whole investigational period . A curvilinear correlation was demonstrated between the orthostatic drop in systolic blood pressure and the plasma levels of clomipramine and desmethylclomipramine . The most pronounced orthostatic reaction was thus seen in 1–2 weeks , at plasma levels of 25–75 μg/l ( clomipramine ) . The correlation between the subjective symptoms and the measured orthostatic drop was poor , as was the correlation between the subjective symptoms and the plasma levels of the two active compounds . The change in orthostatic heart rate during clomipramine treatment was insignificant . In the citalopram group ( n=15 ) no significant changes in orthostatic blood pressure or heart rate were demonstrated during treatment and these patients had no orthostatic complaints ",
"OBJECTIVE This study examines whether continuation therapy with citalopram can prevent a relapse following remission of major depression due to traumatic brain injury . METHOD After 65 subjects with DSM-IV-diagnosed major depression following traumatic brain injury were treated with open-label citalopram ( 20 mg to 50 mg/d ) , 25 subjects ( 38.5 % ) met criteria for remission . Of those , 21 ( 84.0 % ) were r and omly assigned to either same-dose citalopram or placebo and followed monthly over 40 weeks . Remission was defined as a Hamilton Depression Rating Scale ( HDRS ) score of ≤ 7 or a Clinical Global Impressions-Improvement rating of \" much improved \" or better . The main outcome variable was the presence of relapse , as defined by meeting criteria for major depressive episode according to the DSM-IV and an HDRS score ≥ 16 . Data were collected from February 16 , 2005 , to May 5 , 2008 . RESULTS Ten subjects were r and omly assigned to citalopram and 11 to placebo . There were 3 dropouts , including 1 for adverse drug effects ( diarrhea ) . Relapse occurred in 11 subjects ( 52.4 % ) , with a mean ± SD time to relapse of 23.52 ± 16.6 weeks . The groups did not differ in relapse rates ( drug : 50.0 % [ 5/10 ] vs placebo : 54.5 % [ 6/11 ] , Fisher exact test , P = .835 ) or time to relapse ( log rank test χ² = 0.148 , P = .700 ) . CONCLUSIONS The present study suggests important limitations of continuation pharmacotherapy in the prevention of relapse of major depression following traumatic brain injury . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00162916",
"BACKGROUND It is well established that depressive disorders are more prevalent in women ; however gender differences in the pharmacological response to antidepressants are not a consistent finding in all reports . It is considered that this discrepancy can be explained by the fact that in most clinical trials drug use for comparative purpose s is not completely different . In this study gender differences in antidepressant response with citalopram ( CTP ) , a selective serotonin reuptake inhibitor and reboxetine ( RBX ) , a selective noradrenaline reuptake inhibitor were evaluated in a group of young men and premenopausal women . METHOD Eighty-six depressed patients 18 to 40 years old participated in an 8-week double-blind clinical trial . Subjects were divided in four groups according to sex and treatment assignation : females treated with CTP ( n = 25 ) or RBX ( n = 23 ) , and males treated with CTP ( n = 19 ) or RBX ( n = 19 ) . Response was determined using HDRS and BDI . RESULTS ANOVA analysis considering change in HDRS scores from baseline to last evaluation found a significant interaction between gender and type of treatment . Females treated with CTP showed a significantly greater response than females treated with RBX , while in men no differences were observed for both drugs . LIMITATIONS Replication using larger sample size and longer treatment periods is required . CONCLUSIONS These results support previous findings which show that premenopausal women respond better than men to serotonergic antidepressants . They also support that a plausible interaction between gonadal hormones and serotonin may explain gender differences in antidepressant response",
"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 The present study aim ed to 1 ) assess facial expression recognition in subjects with a previous history of major depressive disorder relative to subjects with no history of depression and 2 ) characterize the effects of acute citalopram infusion on recognition performance for both groups . METHOD Unmedicated euthymic women with a history of major depression and matched comparison subjects with no history of depression were given a facial expression recognition task following intravenous infusion of saline or citalopram ( 10 mg ) in a double-blind , between-group design . RESULTS Following saline infusion , subjects with a previous history of depression showed a selectively greater recognition of fear relative to the subjects with no history of depression . The abnormal fear processing observed in the subjects with a previous history of depression was normalized following citalopram infusion , an effect that was opposite to that seen with the subjects with no history of depression . CONCLUSIONS These results suggest that increased recognition of fear is a trait vulnerability marker for depression and that this is normalized following a single dose of citalopram",
"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",
"Two dose levels of citalopram , 10–30 mg and 20–60 mg , were compared with imipramine , 50–150 mg , in depressed patients treated in general practice . This was a multicentre study carried out in Denmark , Sweden , Norway , and Finl and . The duration of treatment was 6 weeks with an optional continuation phase of a further 16 weeks . The patients were assessed by means of the Hamilton Rating Scale for Depression ( HAMD ) , Clinical Global Impressions ( CGI ) , and a visual analogue self-rating scale for depression . Observed and spontaneously reported adverse events were recorded . A total of 472 patients were entered into the study and 400 patients completed the 6 week trial period . A total of 297 patients completed the optional 22 week double-blind period . A clear reduction of the HAMD total scores was seen in all three treatment groups with no significant differences between groups . A reduction of the HAMD anxiety factor and sleep factor scores was also seen with no significant differences between treatments . The imipramine-treated patients showed a higher frequency of adverse events , especially the anti-cholinergic type , than citalopram-treated patients . Most patients entered into the continuation phase remained well",
"Sleep disturbance is common in major depressive disorder ( MDD ) , and is often characterized by early-morning waking . Melatonin is a hypnotic and synchronizes circadian rhythms . It may also be an antidepressant . The melatonin agonists , ramelteon and agomelatine , have hypnotic and antidepressant properties , but there is a dearth of trials investigating the use of melatonin in MDD . This r and omized , controlled trial aim ed to determine whether exogenous melatonin is a sleep promoter and antidepressant . Thirty-three participants with a Diagnostic and Statistical Manual of Mental Disorders ( fourth edition ) diagnosis of MDD and early-morning waking were selected for a 4-week , r and omized , double-blind trial of slow-release melatonin ( 6 mg ; vs. placebo ) given at bedtime over 4 weeks . Sleep was measured subjectively using sleep diaries and the Leeds Sleep Evaluation Question naire and objective ly using wrist actigraphy . Of the 33 participants , 31 completed the trial . General Linear Modelling showed significant improvements in depression and sleep over time , but this was not specific to melatonin . However , there was a trend towards an improvement in mood with melatonin , and no adverse side effects were observed . In conclusion , melatonin may be beneficial for treating MDD , it seems to be safe and well tolerated , but its potential for treating depression in people who do not wish to take antidepressants requires further evaluation",
"Neuroendocrine challenge tests in depressed patients have revealed a blunted hormonal reaction to serotonergic stimuli . In the present study , citalopram was chosen as the serotonergic agent for neuroendocrine stimulation . Compared to earlier challenge agents , citalopram has the advantage of serotonergic selectivity , its application is well tolerated and the possibility of intravenous application reduces pharmacokinetic interference . Sixteen patients suffering from an acute episode of major depression and 16 healthy controls underwent the stimulation procedure with 20 mg of citalopram and placebo . Whereas significant differences in the secretion of prolactin and cortisol between citalopram and placebo challenge were observed in the control group , no differences were found in the group of depressed patients . Comparison of depressed patients and controls showed a significantly blunted prolactin secretion in patients . Differences in cortisol secretion following serotonergic stimulation with citalopram did not become significant . The stimulation procedure was well tolerated in all subjects , although a higher number of side effects was observed in the control group . The amount of side effects did not correlate with the hormone responses . These results are in line with the hypothesis of serotonergic hypofunction in depressed patients . In conclusion , the 20-mg citalopram challenge test is thought to be a promising tool for further investigation of serotonergic function in psychiatric illness",
"OBJECTIVES The authors previously reported that repetitive transcranial magnetic stimulation ( rTMS ) produced a response rate of 39.4 % among 62 patients with treatment resistant vascular depression . This study was undertaken to assess the outcome of continuation therapy to prevent relapse among these patients during 9 weeks after completion of rTMS . DESIGN Patients were r and omly assigned to 18,000 pulses of rTMS given over 3 weeks or sham treatment using double blind methods . After rTMS , all patients were given 20 mg/day of citalopram for 9 weeks and reevaluated at 3 , 6 , and 9 weeks . SETTING Outpatient continuation treatment trial . PARTICIPANTS Patients with vascular depression ( N = 62 ) , as determined by magnetic resonance imaging hyperintensities and three or more clinical risk factors for vascular disease without other major medical illness , were recruited . They had onset of major depression after age 50 and failed at least one trial of antidepressants . INTERVENTION After rTMS or sham treatment , all treatment responders were given citalopram for 9 weeks . RESULTS Among the 33 patients who were given rTMS , 13 responded ( i.e. , > 50 % decline in Hamilton Depression Scale score ) . Of these 13 , all completed the 9 weeks of continuation treatment . There were nine patients who continued to be responders and four who had a relapse of depression . CONCLUSION More effective methods are needed to treat elderly patients with treatment resistant vascular depression and to prevent relapse among treatment responders",
"Noninvasive electrophysiological neuroimaging applied to cognitive components of event-related potentials ( ERPs ) may differentiate between structural and energetic processes related to information processing . The structural level , revealed by the location of the local maxima of the current source density distribution , describes the time-dependent network of activated brain areas . The magnitude of the source strength , a measure of the energetic component , describes the allocation of processing re sources . ERPs were recorded in an odd-ball paradigm and low-resolution brain electromagnetic tomography ( LORETA ) was applied for st and ard and target ERP components . In a group of 60 menopausal depressed patients of 45 - 60 years of age , reduced P300 source strength was observed bilaterally , temporally and medially prefrontally reaching to rostal parts of the anterior cingulate , compared with 29 age-matched controls . In a double-blind , placebo-controlled study , 2 mg of the antidepressant citalopram induced a significant increase of P300 source strength in the ( left ) prefrontal cortex and precuneus compared with placebo , reaching to the posterior cingulate . Similar increases were observed after 800 mg S-adenosyl-L-methionine ( SAMe ) administered intravenously in ten young healthy subjects aged 22 - 33 , and they were even more pronounced in ten elderly healthy subjects aged 56 - 71 . Thus , ERP-tomography identified changes in energetic sources in brain areas predominantly involved in depression and in antidepressant action",
"Objective : To examine the efficacy and tolerability of escitalopram ( ESCIT ) compared to estrogen and progestogen therapy ( EPT ) for the treatment of symptomatic peri- and postmenopausal women . Design : Forty women ( aged 40 - 60 years ) with depressive disorders and menopause-related symptoms were r and omly assigned to an 8-week open trial with ESCIT ( flexible dose , 10 - 20 mg/day ; fixed dose , 10 mg/day for the first 4 weeks ) or estrogen plus progestogen therapy ( ethinyl estradiol 5 & mgr;g/day plus norethindrone acetate 1 mg/day ) . Primary outcome measures included Montgomery-Asberg Depression Rating Scale and the Greene Climacteric Scale at week 8 . Secondary outcome measures included the Clinical Global Impressions as well as sleep and quality of life assessment s. Results : Thirty-two women ( 16 on EPT , 16 on ESCIT ) were included in the analyses . Full remission of depression ( score of Montgomery-Asberg Depression Rating Scale ) was observed in 75 % ( 12/16 ) of subjects treated with ESCIT , compared to 25 % ( 4/16 ) treated with EPT ( P = 0.01 , Fisher 's exact tests ) . Remission of menopause-related symptoms ( > 50 % decrease in Greene Climacteric Scale scores ) was noted in 56 % ( 9/16 ) of women treated with ESCIT compared to 31.2 % ( 5/16 ) on EPT ( P = 0.03 , Pearson 's & khgr;2 tests ) . Improvement in sleep , hot flashes , and quality of life was observed with both treatments . Conclusions : ESCIT is more efficacious than EPT for the treatment of depression and has a positive impact on other menopause-related symptoms . ESCIT may constitute a treatment option for symptomatic menopausal women who are unable or unwilling to use hormone therapy",
"This study is a comparison across treatment setting s of two previously published trials , namely the Danish University Antidepressant Group ( DUAG ) study on citalopram vs. clomipramine in hospitalized patients with major depression , and the Nordic citalopram vs. imipramine study of depressed patients treated by their family doctors . The Hamilton Depression Scale ( HAM‐D ) had the same level of inter‐rater reliability and construct validity in the two setting s. Using a HAM‐D score of 7 or less as the criterion for full remission , clomipramine was superior to imipramine and citalopram . Using a reduction of the baseline HAM‐D score by 50 % or more as a response criterion , there were no differences between the three antidepressants after 5 or 6 weeks of treatment . Citalopram showed superior tolerability to the tricyclic antidepressants",
"OBJECTIVES This preliminary study examines the efficacy of 12-week home-delivered problem adaptation therapy ( PATH ) versus home-delivered supportive therapy ( ST ) in reducing depression and disability in 30 depressed , cognitively impaired , disabled older adults . DESIGN A 12-week r and omized clinical trial . Research assistants were unaware of the participants ' r and omization status . Assessment s were conducted at baseline , 6 weeks , and 12 weeks . SETTING Weill-Cornell Advanced Center for Interventions and Services Research . PARTICIPANTS Thirty elders with major depression , cognitive impairment , and disability were recruited through advertisement and the Home-Delivered Meals Program of the Westchester County Department of Senior Programs and Services . INTERVENTION PATH is a home-delivered intervention design ed to reduce depression and disability in depressed , cognitively impaired , disabled elders . PATH is based on problem-solving therapy and integrates environmental adaptation and caregiver participation . PATH is consistent with Lawton 's ecologic model of adaptive functioning in aging . MEASUREMENTS Depression and disability were measured with Hamilton Depression Rating Scale-24 items and Sheehan Disability Scale , respectively . Client Satisfaction Question naire was used to assess patient satisfaction with treatment . RESULTS Mixed-effects model analyses revealed that PATH was more efficacious than ST in reducing depression and disability at 12 weeks . Participants in both treatment groups were satisfied with treatment . CONCLUSIONS This preliminary study suggests that PATH is well accepted and efficacious in depressed elders with major depression , cognitive impairment , and disability . Because this population may not adequately respond to antidepressant medication treatment , PATH may provide relief to many patients who would otherwise remain depressed and continue to suffer",
"BACKGROUND MADRS cut-off scores for moderate and severe depression were estimated in relation to the Hamilton Depression Rating Scale ( HAMD(17 ) ) and the Clinical Global Impressions Scale ( CGI ) . METHOD HAMD(17 ) , MADRS , and CGI ratings from patients with major depression ( DSM-IV ) were analyzed ( N=85 ) . Receiver operating characteristics ( ROC ) curves were applied . RESULTS Mean age was 51.4+/-14.5 years , 69 % were female . Mean MADRS scores were 23.4+/-13.2 , HAMD(17 ) , MADRS , and CGI scores were highly correlated ( r>0.85 ; P MADRS score of 31 ( sensitivity 93.5 % , specificity 83.3 % ) . LIMITATIONS Studies to vali date severity gradations including DSM-IV or ICD-10 diagnostic severity categories are recommended . CONCLUSIONS Empirically based MADRS cut-off scores to separate moderate from severe depression on the basis of HAMD(17 ) and CGI severity ratings in patients with major depression were yielded",
"Simultaneous coexistence of anxiety with depressive disorders is probably one of the major current problems in Medicine . The pharmacological approach for Panic Disorder and Major Depression includes \" high-powered \" benzodiazepines for the rapid , but transitory relief of same symptoms and especially antidepressant compounds . Recently physical-instrumental approaches have been tested for the treatment of these complex diseases , like Cranial Electrotherapy Stimulation ( CES ) , Trans-cranial Magnetic Stimulation ( TMS ) , and Radio Electric Asymmetric Treatment ( REAC ) . The REAC apparatus was design ed to deliver an alternate current of several hundred picoamperes for a time span of 0.5 seconds by means of a small metallic probe directly connected to the properly fabricated electronic circuit in an AC/RF generator with frequency of 2.4 , 5.8 or 10.5 GHz and power of 20 mW. Compared the efficacy of REAC and Es-Citalopram in the treatment of simultaneous coexistence of Panic Disorder with Major Depression in 9-weeks open label naturalistic study . After the 1st week , patients treated with REAC therapy showed a significant relief of depressive symptoms compared with Es-Citalopram . For Panic Disorder , REAC treatment had more effective results than the drug especially after the 3rd week of observation . The REAC treatment obtained better results during the entire study , and its high safety and tolerability profile has been confirmed",
"OBJECTIVE Depression in older adults is often associated with cognitive abnormalities and may predict later development of a primary cognitive disorder . This double-blind , r and omized , placebo-controlled pilot study was design ed to assess the safety and efficacy of galantamine augmentation of antidepressant treatment for depressive and cognitive symptoms in older adults with major depression . METHODS Thirty-eight , non-demented older adults ( age > 50 ) with major depression were r and omized to receive galantamine or placebo augmentation of st and ard antidepressant pharmacotherapy ( venlafaxine XR or citalopram ) . Mood and cognitive status were monitored for 24 weeks using the 24-item Hamilton Rating Scale for Depression and the Repeatable Battery for the Assessment of Neuropsychological Status . RESULTS Both groups showed significant improvements in mood and cognition over 24 weeks , but no significant difference was found in change over time between groups . An exploratory post-hoc analysis suggested that patients r and omized to galantamine had lower depression scores compared to patients in the placebo group after 2 weeks of treatment . Dropout was high with more subjects r and omized to antidepressant plus galantamine withdrawing early from the study . CONCLUSIONS This pilot study failed to demonstrate a benefit for galantamine augmentation of antidepressant medication in the treatment of depression in older adults . Future studies should explore strategies for reducing dropout in such longitudinal trials and more carefully assess time to response with cholinesterase inhibitor augmentation",
"OBJECTIVE To evaluate the efficacy of rEEG( ® )-guided pharmacotherapy for the treatment of depression in those circumstances where rEEG and STAR*D provided different recommendations . MATERIAL S AND METHODS This was a r and omized , single-blind , parallel group , 12 center , US study of rEEG-guided pharmacotherapy vs. the most effective treatment regimens reported in the NIH sponsored STAR*D study . Relatively treatment-resistant subjects ≥18 years who failed one or more antidepressants were required to have a QIDS-16-SR score ≥13 and a MADRS score ≥26 at baseline . All subjects underwent a washout of all current medications ( with some protocol -specified exceptions ) for at least five half-lives before receiving a QEEG and rEEG report . Subjects r and omized to rEEG were assigned a regimen based on the rEEG report . Control subjects who had failed only SSRI 's in their current episode were r and omized to receive venlafaxine XR . Control subjects who had failed antidepressants from ≥2 classes of antidepressants were r and omized to receive a regimen from Steps 2 - 4 of the STAR*D study . Treatment lasted 12 weeks . The primary outcome measures were change from baseline for self-rated QIDS-SR16 and Q-LES-Q-SF . RESULTS A total of 114 subjects were r and omized and 89 subjects were evaluable . rEEG-guided pharmacotherapy exhibited significantly greater improvement for both primary endpoints , QIDS-SR16 ( -6.8 vs. -4.5 , p and Q-LES-Q-SF ( 18.0 vs. 8.9 , p role of rEEG-guided psychopharmacology in the treatment of depression . If these results were confirmed , rEEG-guided pharmacotherapy would represent an easy , relatively inexpensive , predictive , objective office procedure that builds upon clinical judgment to guide antidepressant medication choice",
"BACKGROUND Citalopram , the most selective serotonin reuptake inhibitor ( SSRI ) , is a bicyclic phthalane derivative with a chemical structure that is unrelated to that of other SSRIs and available antidepressants . The drug is approved for use in 69 countries . This 6-week , fixed-dose , placebo-controlled , parallel-arm , multicenter trial was performed to confirm its efficacy and safety in treatment of out patients with major depression in the United States . METHOD Six hundred and fifty adult out patients with moderate-to-severe major depression ( DSM-III-R ) were r and omly assigned to receive citalopram at doses of 10 mg ( N = 131 ) , 20 mg ( N = 130 ) , 40 mg ( N = 131 ) , or 60 mg ( N = 129 ) or placebo ( N = 129 ) once daily . Outcome assessment s were the 21-item Hamilton Rating Scale for Depression ( HAM-D ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the Clinical Global Impressions scale . RESULTS Between-group comparisons of the change from baseline to endpoint revealed significantly greater improvement in the citalopram patients relative to the placebo patients on all 3 efficacy measures . Patients r and omly assigned to 40 mg/day and 60 mg/day of citalopram showed significantly greater improvement than placebo on all efficacy measures , as well as on the HAM-D symptom clusters measuring depressed mood , melancholia , cognitive disturbance , and psychomotor retardation . Patients who received 10 mg/day and 20 mg/day of citalopram also showed consistent improvement relative to placebo on all efficacy ratings , with statistical significance demonstrated in the MADRS response rate , the HAM-D depressed mood item , and the HAM-D melancholia subscale . Citalopram was well tolerated , with only 15 % of patients discontinuing for adverse events . The side effects most commonly associated with citalopram treatment were nausea , dry mouth , somnolence , insomnia , and increased sweating . CONCLUSION Citalopram was significantly more effective than placebo in the treatment of moderate-to-severe major depression , especially symptoms of depressed mood and melancholia , with particularly robust effects shown at doses of 40 and 60 mg/day . Citalopram was well tolerated in spite of forced upward titration to fixed-dose levels , with a low incidence of anxiety , agitation , and nervousness",
"This placebo-controlled , double-blind , 1-year pilot study aim ed at investigating possible clinical advantages of combining initial light therapy with the selective serotonin reuptake inhibitor ( SSRI ) citalopram as well as the effects of continuous long-term administration of this drug in patients with seasonal affective disorder ( SAD ) . Eight physically healthy women who met the DSM-III-R criteria for SAD were included in the study . Four women were r and omized to the citalopram group receiving 40 mg citalopram daily from the first of 10 light treatment days and throughout the 1-year study . The remaining four women were allocated to the placebo group using the same double-blind repeated measures design . The clinical outcome was measured by using three versions of the Comprehensive Psychopathological Rating Scale ( CPRS ) and Visual Analog Scales ( VAS ) , respectively . Taking the initial rating scores into account in covariance analyses , no statistically significant group difference was found during the light treatment period . However , during the follow-up period the full version of the CPRS and the self-rating version of CPRS and the VAS-scales for global condition and depressed mood were statistically significantly lower in the citalopram group compared with the placebo group . Thus , in this small but carefully observed sample of SAD- patients combining initial light therapy and long-term citalopram treatment was clinical ly more effective over time than the placebo combination . Our findings support the notion that light therapy with concomitant and continued SSRI ( citalopram ) treatment is a useful strategy to achieve beneficial long-term effects in patients with the SAD syndrome",
"Purpose : Panic attacks may represent additional therapeutic problems in the elderly . The utility of citalopram in panic attacks has been widely investigated . Here , we compare the efficacy and safety of citalopram , with its S-enantiomer escitalopram at half dosage as to citalopram , in elderly patients who have panic attacks . Methods : This was an open community-based study . Forty patients who have panic attacks , according to Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria , were enrolled . Fifty percent of the patients were assigned for 8 weeks ' treatment with escitalopram , and the remaining 50 % were assigned to treatment with citalopram . The primary outcome measure was the weekly rate of panic attacks . The secondary outcome measures were the Hamilton scale for anxiety and depression and the Cooper Disability Scale . Analysis of variance by repeated measures was applied to calculate differences between groups . Results : A similar decrease in weekly rate of panic attacks , in the scores of Hamilton Scale for anxiety and depression and in the Cooper Disability Scale scores , was observed in both groups after 8 weeks , but a significant variation of outcome measures from baseline was observed already after 2 weeks in the escitalopram group ( P citalopram group ( P Escitalopram could be considered among the drugs of first choice in elderly patients with panic attacks because of its good efficacy and safety and for the advantage of reducing the total dose and of a more rapid onset of action as compared with citalopram , although further studies are needed to confirm these results",
"BACKGROUND The objectives of the study were to compare efficacy and tolerability of venlafaxine ER 75 - 150 mg/day with that of citalopram 10 - 20 mg/day in elderly patients with major depression according to DSM-IV criteria . METHODS A r and omised , double-blind , parallel group 6-month study . Efficacy was assessed by MADRS , CGI Global Improvement , CGI Severity of Illness and GDS-20 scores and safety by physical examinations , vital signs , adverse events and UKU side effect rating . Plasma levels of venlafaxine , its major metabolite O-desmethylvenlafaxine and citalopram were followed . RESULTS One hundred and fifty-one male and female patients ( 64 - 89 years ) were enrolled and 118 patients completed the study . Comparable improvements in MADRS , CGI Severity of Illness , CGI Global Improvement and GDS-20 were observed during venlafaxine and citalopram treatment . The MADRS remission rate was 19 % for venlafaxine and 23 % for citalopram . Side effects were common during both treatments but differed in tremor being more common during citalopram and nausea/vomiting during venlafaxine treatment . There were no clinical ly significant changes in blood pressure or body weight . CONCLUSION The observed benefits of venlafaxine treatment in elderly patients with major depression were similar to those observed in younger adults as were reported adverse events and side effects . Treatment with venlafaxine ER was well tolerated and induced beneficial effects of similar magnitude as those of citalopram",
"BACKGROUND Escitalopram is the single isomer responsible for the serotonin reuptake inhibition produced by the racemic antidepressant citalopram . The present r and omized , double-blind , placebo-controlled , fixed-dose multicenter trial was design ed to evaluate the efficacy and tolerability of escitalopram in the treatment of major depressive disorder . METHOD Out patients with an ongoing DSM-IV major depressive episode ( N = 491 ) were r and omly assigned to placebo , escitalopram , 10 mg/day , escitalopram , 20 mg/day , or citalopram , 40 mg/day , and entered an 8-week double-blind treatment period following a 1-week single-blind placebo lead-in . Clinical response was evaluated by the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the 24-item Hamilton Rating Scale for Depression ( HAM-D ) , the Clinical Global Impressions ( CGI ) scales , the Hamilton Rating Scale for Anxiety ( HAM-A ) , and patient-rated quality -of-life scales . RESULTS Escitalopram , at both doses , produced significant improvement at study endpoint relative to placebo on all measures of depression ; significant separation of escitalopram from placebo was observed within I week of double-blind treatment . Citalopram treatment also significantly improved depressive symptomatology compared with placebo ; however , escitalopram , 10 mg/day , was at least as effective as citalopram , 40 mg/day , at endpoint . Anxiety symptoms and quality of life were also significantly improved by escitalopram compared with placebo . The incidence of discontinuations due to adverse events for the escitalopram 10 mg/day group was not different from the placebo group ( 4.2 % vs. 2.5 % ; p = .50 ) , and not different for the escitalopram 20 mg/day group and the citalopram 40 mg/day group ( 10.4 % vs. 8.8 % ; p = .83 ) . CONCLUSION Escitalopram , a single isomer SSRI , is well-tolerated and has demonstrated antidepressant efficacy at a dose of 10 mg/day",
"BACKGROUND Intravenous administration is often beneficial in the treatment of severely depressed patients . It is mainly the tri- and tetracyclic antidepressant drugs that can be administered intravenously . However , these drugs have a less favourable safety profile than newer antidepressants , such as the selective serotonin reuptake inhibitors ( SSRIs ) . Citalopram is the only SSRI that is available in a formulation for infusion . This double-blind , r and omised , multicentre trial was design ed to compare the efficacy and tolerability of citalopram infusion ( 40 mg per day ) and citalopram tablet ( 40 mg per day ) . METHODS Patients were r and omised to receive either placebo tablet plus citalopram infusion ( the infusion group ; n=135 ) or citalopram tablet plus placebo infusion ( the tablet group ; n=119 ) . After receiving r and omised treatment for eight days , all patients entered an open treatment phase , during which they received oral citalopram 40 mg per day for five weeks . RESULTS Although there was no difference in Montgomery-Asberg Depression Rating Scale ( MADRS ) scores at the end of the r and omised treatment period , by the end of the open treatment phase the reduction in MADRS scores was significantly greater in the infusion group than in the tablet group ( p=0.015 ) . The infusion group also showed superior efficacy in Clinical Global Impressions assessment s. Citalopram was equally well tolerated in both treatment groups . CONCLUSIONS This trial confirmed the efficacy of citalopram 40 mg per day , and clearly supports the use of citalopram infusion in the treatment of severely depressed , hospitalised patients",
"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",
"Rationale and objective Depression is a significant complication of stroke . The effectiveness of antidepressant drugs in the management of post-stroke depression ( PSD ) has been widely investigated . However , the choice of antidepressant drug is critically influenced by its safety and tolerability and by its effect on concurrent pathologies . Here we investigate the efficacy and safety of a selective serotonin reuptake inhibitor ( SSRI ) , citalopram , and a noradrenaline reuptake inhibitor ( NARI ) , reboxetine , in post-stroke patients affected by anxious depression or retarded depression . Methods This was a r and omized double-blind study . Seventy-four post-stroke depressed patients were diagnosed as affected by anxious or retarded depression by using a synoptic table . R and omisation was planned so that 50 % of the patients in each subgroup were assigned for 16 weeks to treatment with citalopram and the remaining 50 % were assigned to treatment with reboxetine . The Beck Depression Inventory ( BDI ) , the Hamilton Depression Rating Scale ( HDRS ) and a synoptic table were used to score depressive symptoms . Results Both citalopram and reboxetine showed good safety and tolerability . Citalopram exhibited greater efficacy in anxious depressed patients , while reboxetine was more effective in retarded depressed patients . Conclusions Citalopram or other SSRIs and reboxetine may be of first choice treatment in PSD because of their good efficacy and lack of severe side effects . In addition , PSD patients should be classified according to their clinical profile ( similarly to patients affected by primary depression ) for the selection of SSRIs or reboxetine as drugs of choice in particular subgroups of patients",
"OBJECTIVE Depressed mothers of children with psychiatric illness struggle with both their own psychiatric disorder and the dem and s of caring for ill children . When maternal depression remains untreated , mothers suffer , and psychiatric illness in their offspring is less likely to improve . This r and omized , controlled trial compared the interpersonal psychotherapy for depressed mothers ( IPT-MOMS ) , a nine-session intervention based on st and ard interpersonal psychotherapy , to treatment as usual for depressed mothers with psychiatrically ill offspring . METHOD Forty-seven mothers meeting DSM-IV criteria for major depression were recruited from a pediatric mental health clinic where their school-age children were receiving psychiatric treatment and r and omly assigned to IPT-MOMS ( N=26 ) or treatment as usual ( N=21 ) . Mother-child pairs were assessed at three time points : baseline , 3-month follow-up , and 9-month follow-up . Child treatment was not determined by the study . RESULTS Compared to subjects assigned to treatment as usual , subjects assigned to IPT-MOMS showed significantly lower levels of depression symptoms , as measured by the Hamilton Depression Rating Scale , and higher levels of functioning , as measured by the Global Assessment of Functioning , at 3-month and 9-month follow-ups . Compared to the offspring of mothers receiving treatment as usual , the offspring of mothers assigned to IPT-MOMS showed significantly lower levels of depression as measured by the Children 's Depressive Inventory at the 9-month follow-up . CONCLUSIONS Assignment to IPT-MOMS was associated with reduced levels of maternal symptoms and improved functioning at the 3- and 9-month follow-ups compared to treatment as usual . Maternal improvement preceded improvement in offspring , suggesting that maternal changes may mediate child outcomes",
"Numerous studies have assessed the acute efficacy of antidepressants , including selective serotonin reuptake inhibitors , in treating dysthymic disorder ; however , escitalopram , the S-enantiomer of citalopram , has not been studied . Thirty-six out patients with Structured Clinical Interview for DSM-III-R-diagnosed dysthymic disorder , aged 23–65 years ( mean±SD=44.7±11 years ) , were r and omly assigned to double-blind escitalopram ( maximum dose 20 mg/day ) versus placebo for 12 weeks . Inclusion criteria included age 18–65 years and Hamilton Depression Rating Scale ( HDRS ) score ≥12 . We hypothesized that escitalopram would be superior to placebo in the HDRS-24 item total score at week 12 . We also hypothesized the superiority of escitalopram over placebo for secondary measures , including the percentage of participants classified as responders and remitters , as well as social functioning ( Social Adjustment Scale ) , clinical global impression-improvement , Global Assessment of Functioning Scale . Participants ' baseline HDRS-24 averaged 23.4±5.9 . Final HDRS-24 scores at last observation carried forward did not differ significantly between escitalopram-treated ( mean±SD=10.88±5.83 ) and placebo-treated individuals ( mean±SD=16.4±6.34 ) ( F=2.82 , degrees of freedom=1,32 , P=0.10 ) . Significant differences favoring active medication were found on the Social Adjustment Scale and the Clinical Global Impression Severity and Global Assessment of Functioning Scale , but not in the percentages of responders or remitters . A larger study sample or higher escitalopram dose may show more significant placebo – medication differences",
"UNLABELLED Depressive disorders in people older than 65 years seem to be a serious medical and social problem in many countries . The aim of the study was to evaluate efficiency and safety of citalopram and venlafaxine in treatment of depression in elderly patients . MATERIAL AND METHODS 89 elderly patients with a serious depressive episode were involved in the study . Observation was carried out for 42 days . The clinical state of patients was assessed by Hamilton rating scale ( HAM-D ) , a geriatric depressive scale ( GDS ) and a clinical general impression scale ( CGI ) . Cognitive functions were examined by Mini-Mental scale . 44 patients took citalopram , and 45 patients took venlafaxine . RESULTS On the 42nd day of treatment , citalopram therapy appeared successful in 34 ( 77.3 % ) patients , while venlafaxine therapy was successful in 30 ( 66.6 % ) patients . Citalopram was significantly more efficient than venlafaxine during the first 21 and 28 days of treatment . Neither drug caused disturbances of cognitive functions in the examined groups . CONCLUSIONS 1 . Citalopram and venlafaxine are similarly efficient in treatment of depressive disorders and are well tolerated by elderly patients . 2 . The onset of therapeutic activity of citalopram is potentially faster in depressive patients older than 65 years",
"Depression is one of the most common psychiatric disturbances in Parkinson 's disease ( PD ) . Recent review s have highlighted the lack of controlled trials and the ensuing difficulty in formulating recommendations for antidepressant use in PD . We sought to establish whether antidepressants provide real benefits and whether tricyclic and selective serotonin reuptake inhibitor ( SSRI ) antidepressants differ in their short-term efficacy , because the time to onset of therapeutic benefit remains an important criterion in depression . The short-term efficacy ( after 14 and 30 days ) of two antidepressants ( desipramine , a predominantly noradrenergic reuptake inhibitor tricyclic and citalopram , a SSRI ) was assessed in a double-blind , r and omized , placebo- controlled study of 48 nondemented PD patients suffering from major depression . After 14 days , desipramine prompted an improvement in the Montgomery Asberg Depression Rating Scale ( MADRS ) score , compared with citalopram and placebo . Both antidepressants produced significant improvements in the MADRS score after 30 days . Mild adverse events were twice as frequent in the desipramine group as in the other groups . A predominantly noradrenergic tricyclic antidepressant induced a more intense short-term effect on parkinsonian depression than did an SSRI . However , desipramine 's lower tolerability may outweigh its slight short-term clinical advantage",
"Some evidence suggests that medications that modulate both serotonin and norepinephrine may be more effective than selective serotonin-reuptake inhibitors ( SSRIs ) in severe major depressive disorder ( MDD ) . This prospect i ve pragmatic trial tests this hypothesis . Patients with severe MDD were r and omly assigned to either duloxetine ( a serotonin and norepinephrine-reuptake inhibitor ) or physicians ’ choice of four generic SSRIs . Nonblinded , flexibly dosed treatment was used to mimic clinical practice . To address potential investigator bias , the patient-reported Quick Inventory of Depressive Symptomatology Self-Report ( QIDS-SR ) was used as the primary efficacy outcome measure . A total of 750 out patients ( 19.2 % , African descent ; 14.8 % , Hispanic ) were r and omized . The primary outcome , remission at week 12 by QIDS-SR , was numerically greater for duloxetine compared with SSRIs ( 36 vs. 32 % ) , but this difference was not statistically significant . Mean changes in secondary outcomes were significantly superior in favor of duloxetine for the Hamilton Depression Scale-17 item , the Brief Pain Inventory , and the Sheehan Disability Scale . Remission superiority on the QIDS-SR was not achieved . Significantly greater benefit for duloxetine compared with SSRIs was demonstrated on measures of pain and functioning . Study demographics suggest a more generalizable racial and ethnic population than is typical in r and omized clinical trials",
"After 1 mg DST , 25 major depressive patients ( DSM-III ) received at r and om either a specific inhibitor of noradrenaline reuptake ( Maprotiline ) or an inhibitor of serotinin reuptake ( Indalpine or Citalopram ) . After at least 3 weeks of treatment , no difference was found in treatment response between suppressors and non suppressors . This study is unable to confirm the usefulness of the DST in selection of treatment according to its central activity on serotonin or noradrenaline-reuptake",
"Rationale S-citalopram ( escitalopram ) is the very active moiety of citalopram . It has been shown in many studies to be an effective and safe antidepressant for treating major depressive disorder ( MDD ) . Objective The aim of our study was to compare the efficacy and safety of escitalopram vs citalopram in Chinese MDD patients . Methods In the double-blind study , 240 MDD patients were r and omly assigned to treatment for 6 weeks either with escitalopram ( 10–20 mg/d ) or citalopram ( 20–40 mg/d ) . The primary efficacy measurement was the change of 17-item Hamilton Depression Rating Scale ( HAMD-17 ) total score from baseline to the end of study . The secondary efficacy measurements were response and remission rates . The adverse events ( AEs ) were recorded by the investigator . Results Two hundred and three ( 85 % ) patients completed the trial . The average dose was 13.9 mg/d in the escitalopram group and 27.6 mg/d in the citalopram group . No significant differences were found between the two groups in the change in HAMD-17 total score , response , and remission rate . These results were similar in severe MDD patients . No significant differences were found between the two groups in AEs . No serious AEs were observed in this study . Conclusions The study suggests that escitalopram 10–20 mg/d are as effective and safe as citalopram 20–40 mg/d in the short-term treatment for Chinese MDD patients",
"OBJECTIVE There is increasing evidence that cerebrovascular factors play a key role in the etiology of late-life depression . This study examined the severity of subcortical hyperintensities ( SH ) and the relationship between SH and depression characteristics in two sample s of elderly depressed out patients differing in age . METHODS The sample s consisted of 59 subjects age 60 and over , ( 69+/-5.6 years ) , who participated in a trial of sertraline , and 111 subjects age 75 and over , ( 79+/-4.1 years ) , who participated in a trial of citalopram . RESULTS The citalopram group was significantly older than the sertraline group and had more severe SH ( 72 % vs. 42 % high ratings ) . The High SH group was significantly older than the Low SH group in the sertraline study but there was no difference in age in the SH groups in the citalopram sample . There was no relationship between SH severity and baseline depression or age of onset . However , age strongly correlated with later age of onset . There was no relationship between SH severity and cardiovascular risk factors or treatment response in the sertraline sample . CONCLUSION Age is a major factor for the development of SH and late-life depression . There may not be an association between SH and depression severity , cardiovascular risk factors , or treatment response in geriatric depressed out patients . The etiologic factors and clinical course of late-life depression requires further study",
"Pretreatment plasma ratios of tryptophan ( Trp ) and tyrosine ( Tyr ) to other large neutral amino acids were determined in 27 depressed patients who completed a double-blind trial of citalopram , a selective serotonin uptake inhibitor , against maprotiline , a selective noradrenaline uptake inhibitor . The Trp ratio and the Tyr ratio were decreased in the total patient sample as compared with healthy controls . Plasma Tyr ratio was normal in the endogenous , but significantly decreased in the non-endogenous depressives . There was no significant relationship between the plasma Trp ratio and the probenecid-induced accumulation of 5-HIAA in the CSF , or between the plasma Tyr ratio and HVA level in CSF , whereas the CSF level of MHPG correlated significantly with the plasma Tyr ratio . There was a significantly positive correlation between the Trp ratio , the Tyr ratio , their sum and the final Hamilton depression score in 14 patients treated with citalopram ; on the whole , this association was evident also in the endogenous and non-endogenous subgroups . In 13 patients on maprotiline there was a significantly positive correlation between the plasma Tyr ratio and the percent reduction of Hamilton depression score ; this association was poor in the endogenous , whereas a trend towards a correlation remained in the non-endogenous subgroup . The results suggest that the plasma Trp and Tyr ratios may be determinants of clinical improvement in depressed patients to treatment with citalopram and maprotiline . However , further studies are needed on larger patient sample s to allow a firm conclusion",
"BACKGROUND Isolated reports suggest that escitalopram may be effective for impulsive-compulsive Internet usage disorder ( IC-IUD ) , an impulse-control disorder characterized by excessive time spent on the Internet at the expense of occupational , relationship , and social activities . To assess the safety and efficacy of escitalopram in IC-IUD , we conducted a 10-week , open-label trial followed by a 9-week , double-blind , placebo-controlled discontinuation phase . METHOD From December 2002 to October 2004 , 19 adult subjects with IC-IUD ( defined as time consuming , uncontrollable , distressing , and result ing in social , occupational , or financial difficulties ) were enrolled . Escitalopram was started at 10 mg/day , then increased and maintained at 20 mg/day for 10 weeks at the end of which completers were r and omly assigned to placebo or escitalopram for 9 additional weeks . Two key outcome measures were used : hours spent weekly in nonessential Internet use and overall clinical response ( subjects rated \" much improved \" or \" very much improved \" on the Clinical Global Impressions-Improvement scale [ CGI-I ] ) . RESULTS Fourteen subjects completed the entire study . At the end of the 10th week of open-label esci-talopram , Internet usage decreased significantly from a mean of 36.8 hours/week at baseline to 16.5 hours/week ( paired t test : t = 3.58 ; p = .002 ) . In addition , 64.7 % of the sample ( N = 11 ) were considered CGI-I responders . At the end of the double-blind phase , there were no significant differences in outcome measures between patients taking placebo compared to escitalopram ( analysis of variance with repeated measures , p > .05 ) . CONCLUSION Patients showed a significant improvement of IC-IUD symptoms during the open-label escitalopram phase . There was no significant difference between the escitalopram and placebo groups at the end of the subsequent double-blind phase ; both groups maintained the gains made in the initial open-label treatment . Larger controlled trials are needed to investigate the efficacy of this and other pharmacologic agents in the treatment of IC-IUD . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00565422",
"Abstract The aim of the present study was to evaluate the efficacy of short-term low-dose intravenous augmentative citalopram ( 10mg/d ) versus clomipramine ( 25 mg/d ) versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors ( SSRIs ) . Fifty-four patients with a Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , Text Revision , MDE and partial or no response to SSRIs per os ( 21-item Hamilton Depression Rating Scale [ HAM-D21 ] score reduction , and r and omized to citalopram ( n = 18 ) , clomipramine ( n = 18 ) , or placebo ( n = 18 ) intravenous augmentation . The augmentation regimen lasted 5 days during which patients were maintained on their previous treatment with oral SSRIs . Analyses of variance with repeated measures on HAM-D21 , collected daily in blind-raters design , were performed to detect any change of depressive symptoms between the 3 groups . In addition , the number of responders and remitters was computed in the 3 groups of treatment . At end point , a significant treatment effect ( F= 4.57 ; P = 0.015 ) and time-by-treatment effect ( F = 11.22 ; P on HAM-D21 total scores in favor of citalopram and clomipramine versus placebo , with a superiority of citalopram over clomipramine on overall symptoms ( P = 0.05 ) as well as on anxiety-somatization symptoms ( P = 0.027 ) . The number of responders was significantly superior in the active treatment groups versus the placebo group ( χ22 = 16.36 ; P considering the number of remitters ( χ22 = 13.50 ; P both clomipramine and citalopram intravenous augmentation at low doses and for a short period are well tolerated and superior to placebo in major depressives with partial or no response to oral SSRIs with a possible superiority of citalopram over clomipramine with regard to anxiety-somatization symptoms . The lack of double-blind conditions and the limited sample size may limit the confidence in the reported results , and larger r and omized controlled trials are warranted to confirm the present findings",
"& NA ; Two selective serotonin reuptake inhibitors ( SSRIs ) , citalopram and fluoxetine , both at a daily dose of 20 mg , were compared in patients with unipolar major depression treated in general practice . This was a multicentre , double‐blind , r and omized trial carried out in France . The duration of treatment was 8 weeks . Patients were assessed by means of the Montgomery‐Åsberg Depression Rating Scale ( MADRS ) , the 17 items Hamilton Depression Rating Scale ( HAMD ) and the investigator 's Clinical Global Impressions ( CGI ) . Observed and spontaneously reported adverse events were also recorded . A total of 357 patients of both sexes , aged between 21 and 73 years , entered the double‐blind phase of the trial . A clear reduction of both the MADRS and the HAMD mean total scores was observed in both treatment groups with no statistically significant differences between treatments . Apart from back pain recorded more frequently in the citalopram group , no significant difference was found between the two treatment groups with regard to adverse events , and both citalopram and fluoxetine were considered to be well tolerated . It was concluded that citalopram was as effective as fluoxetine in the treatment of unipolar major depression . Citalopram showed an earlier onset of recovery than fluoxetine",
"OBJECTIVE This study determined the efficacy of antidepressant medication for the treatment of depression in the \" old-old . \" METHOD This r and omized 8-week medication trial compared citalopram , 10 - 40 mg/day , to placebo in the treatment of patients 75 and older with unipolar depression . RESULTS A total of 174 patients who were 58 % women with a mean age of 79.6 years ( SD=4.4 ) and a mean baseline Hamilton Depression Rating Scale score of 24.3 ( SD=4.1 ) were r and omly assigned to treatment at 15 sites . There was a main effect for site but not for treatment condition . The remission rate , defined as a final Hamilton depression scale score citalopram and 33 % for the placebo groups . However , patients with severe depression ( baseline Hamilton depression scale score > 24 ) tended to have a higher remission rate with medication than with placebo ( 35 % versus 19 % ) . CONCLUSIONS In the oldest group of community-dwelling patients to be studied to date , medication was not more effective than placebo for the treatment of depression . However , given the considerable psychosocial support received by all patients , the placebo condition represents more than the ingestion of an inactive pill . Across sites , there was considerable range in response to medication , 18 % to 82 % , and to placebo , 16 % to 80 %",
"Increased levels of inflammatory cytokines such as tumor necrosis factor ( TNF ) and interleukin-6 ( IL-6 ) may play a role in depression . Mild depressive-like symptoms can be induced in humans through activation of the innate immune system with endotoxin . Whether preventive treatment with antidepressants can reduce endotoxin-induced symptoms has never been tested . In a double-blind , r and omized , placebo-controlled , cross-over study , we administered intravenous low-dose endotoxin ( 0.8 ng/kg ) or placebo to 11 healthy subjects who had received oral pre-treatment with citalopram ( 10 mg twice a day ) or placebo for 5 days . The Montgomery-Åsberg Depression Rating Scale , the State and Trait Anxiety Inventory , and a visual analog scale were used to measure depressive and anxiety symptoms and social anhedonia . Serum levels of TNF and IL-6 were measured with immunoassays . Compared to placebo , endotoxin administration increased serum levels of TNF and IL-6 , and caused mild depressive-like symptoms , in particular lassitude and social anhedonia . While citalopram pre-treatment had no effect on the innate immune response to endotoxin , it reduced the endotoxin-induced MADRS total score by 50 % , with a moderate effect size ( Cohen 's d=0.5 ) . Most of the MADRS total score was due to the lassitude item , and citalopram pre-treatment specifically reduced endotoxin-induced lassitude with a large effect size ( Cohen 's d=0.9 ) . These results suggest that subchronic pre-treatment with the serotonin-reuptake inhibitor citalopram blunts mood symptoms induced by acute immune system activation with endotoxin without inhibiting the peripheral immune response",
"This double-blind , r and omised , multicentre study compared the antidepressant efficacy and safety of two doses of milnacipran ( 100 mg/day and 200 mg/day ) and fluoxetine ( 20 mg/day ) in 289 in patients with endogenous depression . After a placebo washout period of 4–7 days , assessment s were performed weekly during ; the first 4 weeks , and then after 6 , 8 and 12 weeks , using the 17-itein Hamilton Depression Rating Scale ( HDRS ) . the Montgomery - Åsberg Depression Rating Scale ( MADRS ) and the Clinical Global Impression ( CGI ) . HDRS total score was reduced by a mean of 14.8 in the milnacipran 100 mg/day group , 12.9 in the milnacipran 200 mg/day group and 12.1 in the fluoxetine 20 mg/day group . MADRS total score decreased by 17.4 , 15.8 and 14.6 , respectively . No significant difference could be shown between the three treatment groups for either the HDRS or MADRS total scores . However , the time-by-time change showed a trend in favour of milnacipran 100 mg/day , which was found significantly superior to fluoxetine at day 28 for several converging parameters ( MADRS , CGI-3 ) . Overall , efficacy ratings for all parameters were highest for milnacipran 100 mg/day , followed by milnacipran 200 mg/day and fluoxetinc 20 mg/day . Side-effect profiles were not significantly different between groups except for a significantly greater frequency of dose-related increase hi heart rate ≥ 100 bpm in milnacipran recipients and a significantly greater weight loss in fluoxetine recipients",
"OBJECTIVE Selective serotonin reuptake inhibitors are commonly used to treat major depression ; however , the percentage of serotonin ( 5-HT ) transporter ( 5-HTT ) sites occupied during clinical dosing is unknown . This study measured the proportion of 5-HTT sites blocked during paroxetine and citalopram treatment of depression and assessed the relationship between serum paroxetine levels and the proportion of 5-HTT sites blocked . METHOD Twelve medication-free depressed patients completed a 6-week trial of either paroxetine ( N=8 ) or citalopram ( N=4 ) . Striatal 5-HTT binding potential was measured with [(11)C]DASB and positron emission tomography , before and after 4 weeks of treatment . The binding potential is proportional to receptor density . Striatal 5-HTT binding potential was measured twice in six healthy subjects and once in 11 healthy subjects . RESULTS A significant decrease in striatal 5-HTT binding potential was found after either treatment , compared to changes found over a 4-week period in healthy subjects . For patients treated with 20 mg/day of paroxetine ( N=7 ) , the mean proportion of 5-HTT sites occupied was 83 % . For patients treated with 20 mg/day of citalopram ( N=4 ) , the mean 5-HTT occupancy was 77 % . 5-HTT occupancy increased in a nonlinear relationship with serum levels of paroxetine such that a plateau of occupancy around 85 % occurred for serum paroxetine levels greater than 28 microg/liter . CONCLUSIONS During treatment with clinical doses of paroxetine or citalopram , approximately 80 % of 5-HTT receptors are occupied . This change in 5-HTT binding potential is greater than the known physiological range of changes in 5-HTT binding potential but may be necessary for some therapeutic effects",
"Objective : The aim of this single‐blind study was to examine the efficacy and tolerability of citalopram compared to nortriptyline in moderate to severe major depressive patients aged 60 years or over",
"OBJECTIVE Phase III clinical trials for depression enroll participants with major depressive disorder according to stringent inclusion and exclusion criteria . These patients may not be representative of typical depressed patients seeking treatment . This analysis used data from the Sequenced Treatment Alternatives to Relieve Depression ( STAR*D ) project -- which used broad inclusion and minimal exclusion criteria --to evaluate whether phase III clinical trials recruit representative depressed out patients . METHOD Of 2,855 participants , 22.2 % met typical entry criteria for phase III clinical trials ( efficacy sample ) and 77.8 % did not ( nonefficacy sample ) . These groups were compared regarding baseline sociodemographic and clinical features and the characteristics and outcomes of acute-phase treatment . RESULTS The efficacy sample had a shorter average duration of illness and lower rates of family history of substance abuse , prior suicide attempts , and anxious and atypical symptom features . Despite similar medication dosing and time at exit dose , the efficacy participants tolerated citalopram better . They also had higher rates of response ( 51.6 % versus 39.1 % ) and remission ( 34.4 % versus 24.7 % ) . These differences persisted even after adjustments for baseline differences . CONCLUSIONS Phase III trials do not recruit representative treatment-seeking depressed patients . Broader phase III inclusion criteria would increase the generalizability of results to practice , potentially reducing placebo response and remission rates ( reducing the risk of failed trials ) but at the risk of some increase in adverse events",
"It has been hypothesized that non-rapid eye movement ( NREM ) sleep facilitates declarative memory consolidation , and rapid eye movement ( REM ) sleep is particularly important in promoting procedural learning . The aim of this study was to examine the effects of pharmacological REM sleep suppression on performance in different neuropsychological tasks . For our baseline , we chose 41 moderately depressed patients ( age range 19 - 44 years ) , who were not taking antidepressants . In the morning after polysomnography , we tested memory recall and cognitive flexibility by assessment of verbal and figural fluency , a shift of attention task and the Trail Making Test B. After recording baseline values , patients were assigned r and omly to one of three treatment groups : medication with citalopram ; medication with reboxetine ; or exclusive treatment with psychotherapy . Retesting took place 1 week after onset of treatment . The main results were : ( 1 ) an association of slow-wave sleep with verbal memory performance at baseline ; ( 2 ) a suppression of REM sleep in patients taking citalopram and reboxetine ; ( 3 ) no differences regarding neuropsychological performance within the treatment groups ; and ( 4 ) no association of REM sleep diminution with decreases in memory performance or cognitive flexibility in patients treated with citalopram or reboxetine . In line with other studies , our results suggest that there are no negative effects of a decrease in REM sleep on memory performance in patients taking antidepressants",
"ABSTRACT Objective : A r and omized , double-blind , 24‐week fixed-dose study comparing the efficacy and safety of escitalopram to that of citalopram was conducted in primary care patients with moderate to severe major depressive disorder ( MDD ) . Research design and methods : This was a r and omized , double-blind , 24‐week fixed-dose study . Patients were r and omly assigned to treatment with escitalopram 10 mg/day ( n = 175 ) or citalopram 20 mg/day ( n = 182 ) . Clinical response was evaluated using the Montgomery – Åsberg Depression Rating Scale ( MADRS ) and Clinical Global Impression-Severity ( CGI‐S ) scale . The prospect ively defined primary parameter of antidepressant efficacy was the change from baseline in the mean MADRS total score during the 24 weeks of double-blind treatment , using a repeated measures analysis of variance to compare the treatment groups over all assessment points simultaneously . Results : Based on the primary parameter , escitalopram was at least as efficacious as citalopram . Based on the prospect ively defined secondary parameter , mean change from baseline in the CGI‐S score , escitalopram was statistically significantly superior to citalopram at Week 24 . The importance of long-term treatment could be demonstrated , in that more than half ( 55 % and 51 % ) of the patients who had not responded by Week 8 achieved remission by Week 24 . Both escitalopram and citalopram were safe and well tolerated in acute and long-term treatment , and the overall adverse event profiles for the two drugs were similar . For the intent-to-treat population , there were statistically significantly fewer withdrawals in the escitalopram group than in the citalopram group , particularly after Week 8 . Conclusion : Patients with MDD responded well to long-term treatment with either escitalopram or citalopram . This study demonstrated the importance of extending treatment of depression beyond 8 weeks",
"This paper investigates if the highly selective norepinephrine reuptake inhibitor reboxetine leads to a dose-dependent cortisol release and if this response depends on personality dimensions related to clinical depression in healthy volunteers . Twenty-four male subjects received placebo , 2 mg , or 4 mg reboxetine in a balanced , r and omized cross-over study . Cortisol was measured in saliva at six different time-points according to the kinetics of the drug . Furthermore , several measurements of cardiovascular parameters , emotional states , and possible side-effects were obtained . Subjects were divided into two groups scoring above or below the median of a depressiveness question naire scale [ n = 11 , low ( D- ) ; n = 13 , high ( D+ ) ] . Results clearly demonstrated , that reboxetine stimulates cortisol release . Whereas blood pressure was not affected , heart rate increased after 2 and 4 mg but not dose dependently . Subjects reported more non-specific arousal while the dimensions of tiredness-wakefulness and positive-negative emotional states were not affected by the drug . Somatic complaints were low and only non-specific complaints were statistically elevated but of negligible amount . Subjects classified as D+ can be characterized as high responders to the drug . This is especially true not only for cortisol increases but also for changes in heart rate and some ratings on physical complaints . Hot flushes , sweating and a throbbing sensation in blood vessels in the head were observed in D+ but only with the 4 mg dose . The results clearly demonstrate that reboxetine stimulates cortisol release and heart rate and that this is particularly pronounced in subjects scoring high on depression-related personality dimensions . Reboxetine , therefore , is a promising tool for investigating neuroendocrine response to noradrenergic challenge tests . The question whether increased responses in D+ are due to an up-regulation of receptor sensitivity as a consequence of low norepinephrine supply is discussed",
"The response of patients with major depressive illness to citalopram of amitriptyline was compared in a double-blind multi-centre trial . No differences in efficacy were observed , but citalopram had less hypnotic effect , and a remarkably lower profile of side-effects",
"St. John 's Wort ( Hypericum perforatum L. ) is a useful medication in the treatment of mild to moderate depression . By re analysis of the data obtained from a total of 154 patients , who responded in a r and omised , multicentric , double-blind , placebo-controlled study , to 6 weeks of treatment for an episode of moderate depression with either 20 mg citalopram or 900 mg Hypericum extract STW 3-VI , the duration of response and occurrence of relapse/recurrence were evaluated . Duration of response and occurrence of relapse/recurrence was measured by re-evaluating the responders in a controlled- clinical trial ( final score of ≤10 according to HAMD at the end of the clinical trial ) according to the Hamilton Rating Scale for Depression ( HAMD ) . In total , 30 ( 19.5 % ) of the 154 responders were diagnosed with a relapse . The numbers of patients with relapses were highest in the citalopram group ( 14 of 54 ) , whereas patients who were treated with Hypericum extract STW 3-VI showed the lowest relapse rate ( 8/54 ) ; patients from the placebo group showed a relapse rate of 8/46 . No difference in the severity of relapse could be observed . The duration of response was longest for the Hypericum group ( 1817 days ) , intermediate for the citalopram group ( 1755 days ) and shortest for the placebo group ( 802 days ) . Hypericum extract STW 3-VI is more efficient in lowering the relapse and recurrence rates of responders , when compared to citalopram and placebo . In addition , duration of response was increased in the group treated with Hypericum extract STW 3-VI",
"BACKGROUND The increasing cost of pharmaceuticals in the Czech Republic has led to the restriction on prescriptions of expensive new antidepressants . The aim of the study was to compare the costs and outcomes of using amitriptyline , citalopram and fluoxetine in the treatment of major depression . METHODS Ninety patients ( 69 women ) with a mean age of 44.5 years ( S.D. = 14.3 ) suffering from major depression were treated with amitriptyline ( N = 31 ) , citalopram ( N = 29 ) and fluoxetine ( N = 30 ) . Direct medical costs and effectiveness ( indicated by the number of hospitalization-free days ) were assessed in a prospect i ve , open , intent-to-treat study . RESULTS Neither cost nor effectiveness were significantly different among the treatment groups . CONCLUSION Amitriptyline treatment is not less expensive nor more effective than citalopram or fluoxetine therapies . There is no advantage in restricting patients from treatment with SSRIs , which have fewer adverse effects and a decreased risk of a lethal overdosage in comparison with tricyclic antidepressants",
"The objective of this study was to compare efficacy and tolerability of the selective noradrenalin reuptake inhibitor reboxetine with the selective serotonin reuptake inhibitor citalopram , in the treatment of major depressive disorder ( MDD ) . In total , 357 out patients with MDD were r and omized to treatment with reboxetine 8 - 10 mg or citalopram 20 - 40 mg per day during 24 weeks . Primary end-point was change from baseline in the Hamilton Depression Rating Scale ( HAM-D , 21 items ) . Sexual function/dysfunction was measured by the Sexual Function scale ( SF ) . Observed case analysis showed that both treatments yielded a gradual reduction of HAM-D scores : reboxetine with -21.4 and citalopram with -22.1 points ( NS ) . LOCF analysis showed a greater reduction of the HAM-D scores with citalopram compared with reboxetine ( -19.6 vs. -17.8 ; P = 0.034 ) . The response rate was 90.3 % for reboxetine and 92.7 % for citalopram ( NS ) . The most common side effect in the reboxetine group was dry mouth , and in the citalopram group sexual dysfunction . At week 24 , anorgasmia was reported by 5.9 % of the sexually active women in the reboxetine group vs 39 % in the citalopram group . The dropout number was 91 in the reboxetine group , and 54 in the citalopram group . To summarize , both treatments gave a satisfactory antidepressant effect . The side effect profile differed between the groups , with a notably high prevalence of sexual dysfunctions in the citalopram group . The high number of dropouts in the reboxetine group , is considered as a result of the non-titration starting dose of 8 mg reboxetine per day , which gave a high incidence of early side-effects . Depressive disorders including major depression ( MDD ) is very common , with a lifetime prevalence of at least 15 % in men and 25 % in women.1,2 Depression can be treated effectively by a range of antidepressant agents . Recent review s have suggested that the selective serotonin reuptake inhibitors ( SSRIs ) offer equal efficacy to the older antidepressant agents , such as tricyclic antidepressants , with the advantage of greater tolerability.3 - 5 Other review ers have reported that non-SSRI antidepressants , such as clomipramine , have been found to be significantly more effective than fluoxetine for the treatment of patients with severe depression.6 Reboxetine ( reboxetine mesylate , Edronax ; Pfizer , New York ) is a highly selective noradrenaline reuptake inhibitor , and the efficacy of reboxetine has been independently demonstrated in multiple r and omized , double-blind , placebo-controlled studies .7 - 9 In addition to improvements in depressive symptoms , treatment-associated improvements in social behavior ( measured using the Social Adaptation Self-evaluation Scale [SASS]),10 were noticed in one of these studies .8 In this study , reboxetine was statistically and clinical ly superior to both placebo and fluoxetine in improving social functioning . The primary objective of the current study was to assess efficacy and tolerability of reboxetine in comparison with those of citalopram ( Cipramil ; H. Lundbeck , Copenhagen , Denmark ) in patients with MDD . Citalopram is a highly SSRI . The antidepressant mechanism is presumed to be a result of stimulation of serotonergic neurotransmission in the central nervous system as a consequence of higher serotonin levels result ing from inhibition of the serotonin transporter . The therapeutic efficacy of citalopram in patients with MDD has been investigated in several placebo-controlled studies and in long-term and extension studies .11 The underlying rationale for this comparison was to study 2 different drug profiles , 1 drug being pure \" adrenergic \" and the other pure \" serotonergic . \" A secondary objective was to analyze the correlation between the types of depression ( ie , degree of melancholia and the efficacy of the 2 drugs )",
"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",
"OBJECTIVE Prescribing recommendations specify that lamotrigine should ordinarily be discontinued at the first sign of rash , regardless of its type and severity , unless the rash is clearly not drug related . This practice helps to ensure that lamotrigine is discontinued in instances of serious rash ( an event occurring in up to 0.13 % of cases in bipolar clinical trials ) but may lead to unnecessary discontinuation of lamotrigine for cases of nonserious rash arising from nondrug causes . Measures aim ed at reducing overall occurrence of dermatologic reactions might reduce the incidence of nonserious rash leading to premature lamotrigine discontinuation . This study assessed the impact of specific instructions design ed to decrease risk of dermatologic reactions , including nonserious rash , during initiation of and early treatment with lamotrigine in patients with bipolar I disorder . METHOD Out patients with DSM-IV-diagnosed bipolar I disorder > /= 13 years of age at 188 sites were r and omly assigned to receive Usual Care Pre caution s ( UCP ; pre caution s from the patient instructions in the prescribing information for reducing risk of rash including nonserious rash ) or Dermatologic Pre caution s ( DP ; pre caution s as above [ UCP ] plus additional pre caution s intended to decrease risk of any dermatologic reaction including nonserious rash ) during 12 weeks of adding open-label lamotrigine to concomitant medications . Patients with comorbid medical and psychiatric problems were not excluded unless , in the opinion of the investigators , these problems were sufficiently severe to preclude participation . Investigators and patients were blinded to which pre caution group patients were r and omly assigned . The primary outcome measure was the rate of rash during the treatment period . Secondary outcome measures included clinical response to lamotrigine , assessed with the investigator- and self-rated Clinical Global Impressions-Bipolar version ( CGI-BP ) and the Clinical Global Impressions-Efficacy Index ( CGI-EI ) . Data were collected from August 2003 to August 2004 . RESULTS 867 ( 74 % ) of 1175 patients completed the study . Only 182 ( 15 % ) of 1175 patients had an adverse event leading to discontinuation of study medication or withdrawal , including 62 ( 5.3 % ) of 1175 due to non-serious rash . No serious rashes were reported during the study in either group . The incidence of nonserious rash was similarly low in patients with UCP and DP ( 8.8 % and 8.6 % , respectively ) . CGI-BP-Severity and -Improvement scores indicated mood improvement when lamotrigine was added to existing therapy , and CGI-EI scores at weeks 5 and 12 reflected a favorable balance between control of mood symptoms and tolerability . At both weeks 5 and 12 , investigators reported that therapeutic effects of additional lamotrigine outweighed side effects in 74 % of subjects . CONCLUSION UCP and DP yielded low , similar non-serious rash rates , which were marginally lower than nonserious rash rates in prior clinical trials that did not utilize DP but marginally higher than that in a prior open case series using DP . Nevertheless , the results are encouraging : in this large study reflecting real-world use , lamotrigine was well tolerated with no serious rash and low incidences of nonserious rash and discontinuation due to rash , and lamotrigine therapy was associated with clinical improvement in a heterogeneous cohort of patients with bipolar I disorder",
"OBJECTIVES To evaluate clinical effectiveness at 4 weeks of antidepressant therapy for mothers with postnatal depression ( PND ) compared with general supportive care ; to compare outcome at 18 weeks of those r and omised to antidepressant therapy with those r and omised to listening visits as the first intervention ( both groups were to be allowed to receive the alternative intervention after 4 weeks if the woman or her doctor so decided ) ; and to assess acceptability of antidepressants and listening visits to users and health professionals . DESIGN A pragmatic two-arm individually r and omised controlled trial . SETTING Participants were recruited from 77 general practice s : 21 in Bristol , 21 in south London and 35 in Manchester . PARTICIPANTS A total of 254 women who fulfilled International Classification of Diseases version 10 criteria for major depression in the first 6 postnatal months were recruited and r and omised . INTERVENTIONS Women were r and omised to receive either an antidepressant , usually a selective serotonin reuptake inhibitor prescribed by their general practitioner ( GP ) , or non-directive counselling ( listening visits ) from a specially trained research health visitor ( HV ) . The trial was design ed to compare antidepressants with general supportive care for the first 4 weeks , after which women allocated to listening visits commenced their sessions . It allowed for women to receive the alternative intervention if they had not responded to their allocated intervention or wished to change to , or add in , the alternative intervention at any time after 4 weeks . MAIN OUTCOME MEASURES The duration of the trial was 18 weeks . Primary outcome , measured at 4 weeks and 18 weeks post r and omisation , was the proportion of women improved on the Edinburgh Postnatal Depression Scale ( EPDS ) , that is scoring EPDS measured as a continuous variable at 4 and 18 weeks , and scores on various other question naires . RESULTS At 4 weeks , women were more than twice as likely to have improved if they had been r and omised to antidepressants compared with listening visits , which started after the 4-week follow-up , i.e. after 4 weeks of general supportive care [ primary intention-to-treat ( ITT ) , 45 % versus 20 % ; odds ratio ( OR ) 3.4 , 95 % confidence interval ( CI ) 1.8 to 6.5 , p proportion of women improving was 11 % greater in the antidepressant group , but logistic regression analysis showed no clear benefit for one group over the other [ 62 % versus 51 % , OR 1.5 ( 95 % CI 0.8 to 2.6 ) , p = 0.19 ] . Overall , there was a difference between the groups in favour of the antidepressant group of about 25 percentage points at 4 weeks , which reduced at 18 weeks . No statistical support existed for a benefit of antidepressants at 18 weeks , but 95 % CIs could not rule out a clinical ly important benefit . It was difficult for GPs not to prescribe antidepressants to women r and omised to listening visits after the initial 4 weeks , so many women received both interventions in both groups by 18 weeks and consequently power was reduced . Qualitative interviews with women revealed a preference for listening visits but an acceptance that antidepressants might be necessary . They wished to be reassured that their GP and HV were offering continuity of care focusing on their particular set of circumstances . Interviews with GPs and HVs revealed lack of collaboration in managing care for women with PND ; neither professional group was willing to assume responsibility . CONCLUSIONS At 4 weeks , antidepressants were significantly superior to general supportive care . Trial design meant that by 18 weeks many of the women initially r and omised to listening visits were also receiving antidepressants , and more vice versa . The lack of evidence for differences at 18 weeks is likely to reflect a combination of reduced power and the considerable degree of switching across the two interventions . Qualitative study revealed that women found both antidepressants and listening visits effective depending on their circumstances and preferences . The trial indicates that early treatment with antidepressants leads to clinical benefit for women with PND",
"BACKGROUND Depression and chronic heart failure ( CHF ) are common conditions , both of which are clinical ly and economically highly relevant . Major depression affects 20 - 40 % of CHF patients and predicts adverse outcomes in terms of quality of life , morbidity and mortality as well as health care expenditure , independent of other factors of prognostic relevance . AIMS The purpose of the MOOD-HF trial is to clarify whether antidepressant pharmacotherapy improves outcome in CHF patients , and if so by which mechanism(s ) . METHODS MOOD-HF is a prospect i ve , r and omised , double-blind , placebo-controlled , 2-armed , parallel-group multicenter trial investigating the effects of the serotonin re-uptake inhibitor ( SSRI ) escitalopram on morbidity and mortality ( primary endpoint ) , severity of depression , anxiety , cognitive function , quality of life and health care expenditure in 700 patients with symptomatic systolic CHF and major depression diagnosed by structured clinical interview . All patients will receive optimised pharmacotherapy for CHF . Duration of follow-up , including close safety monitoring , is 12 - 24 months from r and omisation . PERSPECTIVE MOOD-HF is the first prospect i ve r and omised controlled trial to assess the effects of antidepressant pharmacotherapy on hard somatic endpoints , the mechanism(s ) of action of SSRI treatment , as well as safety in New York Heart Association functional class II-IV CHF patients . The results are expected to promote the development of evidence -based recommendations for managing depression in the context of CHF . TRIAL REGISTRATION ( IS RCT N.org ) . Identifier : IS RCT N33128015",
"OBJECTIVE The present study investigated the efficacy and tolerability of escitalopram in the prevention of relapse of major depressive disorder ( MDD ) in older patients who had responded to acute treatment with escitalopram . METHOD A total of 405 patients who were aged 65 years or older with a primary diagnosis of MDD ( according to Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria ) and a Montgomery-Asberg Depression Rating Scale ( MADRS ) total score of 22 or more received 12-week , open-label escitalopram 10 or 20 mg per day treatment . Remitters ( MADRS escitalopram or placebo . The primary efficacy parameter was the time to relapse , defined as either an increase in MADRS total score to 22 or more or lack of efficacy as judged by the investigator . RESULTS Three hundred five patients achieved remission and were r and omly assigned to treatment with escitalopram ( N = 152 ) or placebo ( N = 153 ) . The primary analysis showed a clear beneficial effect of escitalopram relative to placebo on the time to relapse ( log-rank test , chi(2 ) = 27.6 , df = 1 , p risk of relapse was 4.4 times higher for placebo- than for escitalopram-treated patients ( chi(2 ) test , chi(2 ) = 22.9 , df = 1 , p escitalopram-treated patients relapsed ( 9 % ) compared with placebo ( 33 % ) ( chi(2 ) test , chi(2 ) = 27.1 , df = 1 , p Escitalopram was well tolerated with 53 patients ( 13 % ) withdrawn as a result of adverse events during the open-label period and three ( 2 % ) escitalopram-treated patients and six ( 4 % ) placebo-treated patients during double-blind treatment ( not significant ) . The overall withdrawal rate , excluding relapses , was 7.2 % for escitalopram and 8.5 % for placebo during the double-blind period ( not significant ) . CONCLUSION Escitalopram was effective in preventing relapse of MDD in older patients and was well tolerated as continuation treatment",
"BACKGROUND It is estimated that major depressive disorder affects 0.9 % of community-dwelling older adults in the United States . However , as many as 18 % of older US adults reportedly suffer from depressive symptoms that do not necessarily fit the criteria for major depressive disorder ( eg , dysthmia , minor depression ) . OBJECTIVES The goals of this study were to describe patterns of antidepressant medication use in older adults with dysthymia or minor depression and to examine factors associated with the use of antidepressants at baseline . METHODS This was a secondary analysis using cross-sectional data collected during a r and omized controlled trial conducted from 2000 through 2003 . It involved community senior service agencies and in-home visits in Seattle , Washington . Adults aged > or=60 years who had minor depression or dysthymia and were receiving services through community senior service agencies or living in senior public housing were included . Study participants were classified as users or nonusers of antidepressants . Prescription medication use in the past 2 weeks was assessed at baseline and 6 and 12 months . Medication name , dose , and directions were recorded from the medication label . Logistic regression was used to examine variables associated with baseline antidepressant use . RESULTS A total of 138 patients ( mean age , 73.00 years ) were included ; the majority of study participants were female ( 779.00 % ) . Overall , 42.33 % were nonwhite ( 34.3 % black , 4.4 % Asian , 1.5 % American Indian/Alaskan Native , 0.7 % Hispanic , and 1.5 % other ) . At baseline , 36.2 % of study participants ( n = 50 ) were using antidepressants . Selective serotonin reuptake inhibitors were the most common class of antidepressants , used by 62.00 % , 70.22 % , and 71.11 % of antidepressant users at baseline , 6 , and 12 months , respectively . However , nortriptyline was the most common antidepressant at baseline , taken by 20.00 % of antidepressant users . Use of other prescription medications was associated with antidepressant use at baseline . CONCLUSIONS We found antidepressant use to be low in these relatively poor , community-dwelling , ethnically diverse older adults with dysthymia and minor depression in 2000 through 2003 , with 36.22 % of participants using antidepressants at baseline . Antidepressant users were more likely to be taking other prescription medications than nonusers",
"OBJECTIVE Pain and depression are two of the most prevalent and treatable cancer-related symptoms , each present in at least 20 - 30 % of oncology patients . Both symptoms are frequently either unrecognized or undertreated , however . This article describes a telecare management intervention delivered by a nurse-psychiatrist team that is design ed to improve recognition and treatment of pain and depression . The enrolled sample is also described . METHODS The Indiana Cancer Pain and Depression study is a National Cancer Institute-sponsored r and omized clinical trial . Four hundred five patients with cancer-related pain and /or clinical ly significant depression from 16 urban or rural oncology practice s throughout Indiana have been enrolled and r and omized to either the intervention group or to a usual-care control group . Intervention patients receive central ized telecare management coupled with automated home-based symptom monitoring . Outcomes will be assessed at 1 , 3 , 6 and 12 months by research assistants blinded to treatment arms . RESULTS Of 4465 patients screened , 2185 ( 49 % ) endorsed symptoms of pain or depression . Of screen-positive patients , about one-third were ineligible ( most commonly due to pain or depression not meeting severity thresholds or to pain that is not related to cancer ) . Of the 405 patients enrolled , 32 % have depression only , 24 % have pain only and 44 % have both depression and pain . At baseline , participants reported an average of 16.8 days out of the past 4 weeks during which they were confined to bed or had to reduce their usual activities by > or = 50 % due to pain or depression . Also , 176 ( 44 % ) reported being unable to work due to health reasons . CONCLUSIONS When completed , the Indiana Cancer Pain and Depression trial will test whether central ized telecare management coupled with automated home-based symptom monitoring improves outcomes in cancer patients with depression and /or pain . Findings will be important for both oncologists and mental health clinicians confronted with oncology patients ' depression or pain",
"ABSTRACT — In a controlled , clinical , multicentre trial comprising a total of 43 patients ( 17 men and 26 women ) citalopram was compared double‐blindly with amitriptyline . Nineteen patients of each group were classified as endogenously depressed , whereas four patients of the citalopram group and one of the amitriptyline group were classified as non‐endogenously depressed . The patients were seriously ill with a high frequency of previous depressive episodes and of mental disorders among their closest relatives . Thirteen of the patients in either group had received antidepressants without satisfactory effect before entry into the trial . Each patient was treated for a period of at least 3 weeks with daily citalopram doses of 30–60 mg or daily amitriptyline doses of 75–225 mg . A statistically significant reduction of MADRS scores ( total scores as well as each of the 10 individual items ) was recorded in both groups . The only difference between the groups was a trend towards a better effect on sleep disturbances in the amitriptyline group . Side‐effects were recorded more frequently in the amitriptyline group than in the citalopram group , global assessment of side effects being significantly different in favour of citalopram . It is concluded that citalopram is an effective and safe drug in the treatment of endogenous depression ‐ probably as efficacious as amitriptyline , but with fewer side effects",
"This paper presents new data addressing two important controversies in psychiatry : the construct of Minor Depression ( MinD ) and the efficacy of St. John 's Wort for milder forms of depressive disorders . Data are from a three-arm , 12 week , r and omized clinical trial of investigating the efficacy of St. John 's Wort ( 810 mg/day ) , citalopram ( 20 mg/day ) , or placebo for acute treatment of MinD. Due to a high placebo response on all outcome measures , neither St. John 's Wort nor citalopram separated from placebo on change in depressive symptom severity , quality of life , or well-being . However , systematic assessment of potential adverse effects ( AEs ) led to three important observations : ( 1 ) prior to the administration of study compound , 60 % of subjects endorsed items that would be characterized as AEs once study compound was administered , ( 2 ) St. John 's Wort and citalopram were each associated with a significant number of new or worsening AEs during treatment , and ( 3 ) using a structured interview for identifying AEs at baseline and during treatment is informative . MinD was not responsive to either a conventional antidepressant or a nutraceutical , and both compounds were associated with a notable side effects burden . Other treatment approaches for MinD should be investigated",
"Major Depressive Disorder ( MDD ) is a common illness that affects > 40 million people worldwide , and antidepressants are one of the top 5 leading classes of pharmaceuticals with annual sales in excess of $ 20 billion ( 1,2 ) . The current st and ard of care focuses on serotonin−norepinephrine reuptake inhibitors ( SNRI ) and selective serotonin reuptake inhibitors ( SSRI ) ; however , patients often respond poorly . In fact , the National Institute of Mental Health conducted a large-scale STAR*D study and found that 63 % of patients did not achieve remission with the SSRI Citalopram ( 1,3−5 ) . Citalopram was originally developed in Lundbeck in the late 1980s and sold as a racemate . Lundbeck , in collaboration with Forest Laboratories , has recently released an up date d version called Escitalopram ( also known as Lexapro ) , which is the single (S)-enantiomer of the racemic Citalopram , which provided new patent life . In 2009 , Lexapro garnered ∼$2.7 billion in sales in the US ( Figure (Figure1)1 ) ( 2 ) . Figure 1 Structures of Citalopram , Escitalopram , and TC-5214 . An alternative hypothesis for depression emerged over 30 years ago and suggests that a cholinergic imbalance ( hypercholinergic tone ) is a major factor in depression , and both clinical and pre clinical studies have implicated neuronal nicotinic cholinergic receptors ( NNRs ) rather than muscarinic receptors ( 5 ) . On the basis of these data , AstraZeneca and Targacept have explored the role of NNR antagonism in depressive disorders and recently announced the initiation of a phase III trial of TC-5214 , (S)-(+)-mecamylamine , as an adjunct therapy with Citalopram . TC-5214 is a low molecular weight ( 167.3 as free base , 203.8 as the HCl salt ) , basic ( pKa = 11.5 ) compound , freely soluble in water . While TC-5214 displays modest selectivity among the NNRs , its antidepressive properties are presumed to be the result of inhibition of the α4β2 NNRs . Pre clinical ly , TC-5214 demonstrated robust efficacy in rodent models of depression ( forced swim and behavioral despair ) and anxiety ( social interaction and light/dark chamber ) . The (S)-enantiomer showed a superior preclincial safety profile compared to that of either the racemic compound or the (R)-enantiomer . Furthermore , TC-5214 was well tolerated in both acute and chronic toxicity tests , displayed no mutagenic potential , and possessed pharmacokinetic properties suitable for development ( 3−5 ) . In 2009 , Targacept conducted a double blind , placebo controlled phase IIb trial in MMD patients with TC-5214 , as an adjunct treatment with Citalopram demonstrated superiority to placebo in both primary and secondary outcome measures ( 3−5 ) . This positive outcome led to a license agreement in December of 2009 with AstraZeneca for the global development and commercialization of TC-5214 . On June 23 , 2010 , AstraZeneca and Targacept announced the enrollment of the first patients in the phase III trial of TC-4214 . Coined the Renaissance Program , the trial will include two fixed dose and two flexible dose phase III studies of TC-5214 as an adjunct treatment for patients with poor response to st and ard SSRI or SNRI therapy . Each fixed dose and flexible dose phase III study will employ an initial open label phase wherein patients diagnosed with MDD receive one of seven marketed SSRIs or SNRIs for eight weeks to assess therapeutic response . Patients that respond poorly will then be r and omized into a double blind , placebo controlled second phase to receive a fixed or a flexible dose of TC-5214 or placebo , twice daily , while continuing the SSRI or SNRI therapy . A change from double blind baseline for TC-5214 on the Montgomery−Asberg Depression Rating Scale ( MADRS ) as compared to placebo is the primary outcome measure . The program will also include a double blind , placebo controlled study for long-term safety . The companies plan completion of the trial in time to file an IND with the FDA in late 2012 ( 3−5 ) . MMD is the leading cause of disability in the US for people 15−44 , and the burden for MDD in the US in 2000 was in excess of $ 83 billion ( 6 ) . When broken down , the workplace burden for lost time is ∼62 % , treatment costs account for ∼31 % , and suicide related costs average 7 % ( 6 ) . For those suffering from MDD with poor response to SSRIs and SNRIs , the phase III data is anxiously awaited",
"CONTEXT Little is known about selecting among second-step medications for major depressive disorder after intolerance or lack of remission with an initial selective serotonin reuptake inhibitor . OBJECTIVE To determine whether sociodemographic , clinical , or first-step treatment features predict remission with or intolerance overall or differentially to any 1 of 3 second-step medications after an unsatisfactory outcome with citalopram hydrobromide . DESIGN An equipoise stratified r and omized study . Participants were recruited from July 17 , 2001 , through April 20 , 2004 . SETTING Public or private sector primary care ( n = 18 ) and psychiatric care ( n = 23 ) setting s across the United States . PARTICIPANTS Representative out patients aged 18 to 75 years with nonpsychotic major depressive disorder ( N = 727 ) . INTERVENTIONS Sustained-release bupropion hydrochloride was started at 150 mg/d and incrementally increased to 400 mg/d . Sertraline hydrochloride was started at 50 mg/d and incrementally increased to 200 mg/d . Extended-release venlafaxine hydrochloride was started at 37.5 mg/d and incrementally increased to 375 mg/d . MAIN OUTCOME MEASURES The 16-item Quick Inventory of Depressive Symptomatology , Self-Rated and the Frequency , Intensity , and Burden of Side Effects Rating . RESULTS Remission was more likely among participants who were white , employed , cohabiting or married , or privately insured or who had prior intolerance to citalopram or at least a response to citalopram , and no prior suicide attempts . Remission was less likely among participants with concurrent generalized anxiety , obsessive-compulsive , panic , or posttraumatic stress disorders ; social phobia ; anxious or melancholic features ; or more severe depression . Intolerance was less likely for Hispanic participants , but more likely for participants with previous suicide attempts or intolerance to citalopram . Participants with concurrent substance use were less likely to remit ( odds ratio , 0.37 ) and more likely not to tolerate extended-release venlafaxine . Intolerance to citalopram was associated with intolerance to sertraline ( P = .04 ) . CONCLUSIONS Clinical , demographic , and treatment history were of little value in recommending 1 medication vs another as a second-step treatment for major depressive disorder . Participants most likely to remit in the second step had less Axis I psychiatric disorder comorbidity , less social disadvantage , and at least a response to citalopram in the first step . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00021528",
"Background : Interferon-induced depression represents a major complication in antiviral treatment of chronic hepatitis C virus ( HCV ) infection . Aim : To evaluate in a placebo-controlled study the efficacy of a selective serotonin reuptake inhibitor ( SSRI ) in HCV patients on antiviral therapy with interferon-associated depression . Methods : 100 HCV out patients were included in a r and omised , double-blind , placebo-controlled study . During interferon therapy ( peginterferon alfa-2b plus ribavirin ) , depression was monitored using the Hospital Anxiety and Depression Scale ( HADS ) . Patients with clinical ly relevant interferon-induced depression ( HADS ⩾9 ) were r and omly assigned to placebo or citalopram ( SSRI , 20 mg/day ) . Results : In 28 patients ( 28 % ) , HADS scores increased to > 8 during interferon therapy . They were treated with placebo ( n = 14 ) or SSRI ( n = 14 ) . HADS scores declined significantly in SSRI patients within four weeks of therapy ( p intolerable depression . Rescue medication ( 20 mg citalopram ) led to a significant decrease in HADS scores ( p = 0.008 ) . All citalopram patients were able to complete interferon therapy as planned . As an interim analysis showed a significant superiority of SSRI over placebo , the study was terminated prematurely . Three patients , who became depressed afterwards , were treated in an unblinded fashion with citalopram . Conclusions : The findings demonstrate clearly that citalopram treatment is highly effective in HCV patients on interferon therapy , when initiated after the onset of clinical ly relevant depressive symptoms . This suggests that a general SSRI prophylaxis is not necessary in these patients",
"Objective : This study assessed the efficacy , safety , and tolerability of the serotonin-norepinephrine reuptake inhibitor desvenlafaxine and the selective serotonin reuptake inhibitor escitalopram for major depressive disorder ( MDD ) in postmenopausal women . Methods : In this r and omized , double-blind study , postmenopausal out patients ( aged 40 - 70 y ) with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition MDD received flexible-dose desvenlafaxine ( 100 - 200 mg/d ) or escitalopram ( 10 - 20 mg/d ) for 8 weeks . Acute-phase responders , that is , women with a 50 % or greater reduction from baseline in the 17-item Hamilton Rating Scale for Depression ( HAM-D17 ) total score , were eligible to continue the same double-blind treatment in the 6-month continuation phase . The primary efficacy outcomes were mean change from baseline in HAM-D17 total score ( acute phase ) , analyzed using a mixed-effects model for repeated measures , and the proportion of women who maintained response ( continuation phase ) , analyzed using logistic regression . Results : Reductions in HAM-D17 total score at acute-phase endpoint were similar for desvenlafaxine- and escitalopram-treated women ( −13.6 vs −14.3 , respectively ; P = 0.24 ) . No significant difference was observed between groups at continuation-phase endpoint in the proportion of women who maintained response ( desvenlafaxine , 82 % ; escitalopram , 80 % ; P = 0.70 ) . In both phases , desvenlafaxine and escitalopram were generally safe and well tolerated . Conclusions : Among postmenopausal out patients with MDD , there were no significant differences in the efficacy of desvenlafaxine and escitalopram based on primary efficacy analyses . The results do not support the overall hypothesis that the serotonin-norepinephrine reuptake inhibitor desvenlafaxine has an efficacy advantage for the treatment of MDD in postmenopausal women because , in this particular subgroup , desvenlafaxine failed to prove superiority over escitalopram . Safety and tolerability were comparable",
"Objective : We have tested the relapse‐preventive effect of citalopram when compared with placebo in 282 patients with Seasonal Affective Disorder ( SAD ) responding to 1 week of light therapy",
"In r and omised controlled trials ( RCTs ) there are two types of validity : internal validity and external validity . Internal validity refers to the extent to which the observed difference between groups can be correctly attributed to the intervention under investigation . In other words , it is the extent to which the design and conduct of the trial eliminate error . Internal validity might be threatened by two types of errors : systematic error ( also called bias ) and chance error ( also called r and om error or statistical error ) ( Keirse & Hanssens , 2000 . Systematic error , or bias , may be the consequence of erroneous ways of collecting , analysing and interpreting data . This may produce differences between treatments that are not real , with an overestimation or an underestimation of the true beneficial or harmful effect of an intervention ( Juni et al. , 2001 ) . In RCTs there are four types of bias : selection bias ( when the groups differ in baseline characteristics because of the way participants are selected ) , performance bias ( when the care provided to the trial participants differs systematic ally between the experimental and control group ) , detection bias ( when there are systematic differences in outcome assessment ) , and attrition bias ( when the loss of participants from the study systematic ally differs between the experimental and control group ) . By contrast , chance error , or statistical error , is due to outcome variability that may arise by chance alone . Studies with small sample sizes are more likely to incur in this type of error than studies with large sample sizes . Thus , the risk of r and om error may be minimised by recruiting sufficiently large sample s of patients",
"Citalopram is a bicyclic phtalane derivative . In animal experiments , citalopram has been demonstrated to possess a potent and highly selective inhibitory effect on serotonin reuptake . Several studies in man have indicated that citalopram given in daily doses of 40–60 mg has antidepressant properties and few side effects . The present double-blind study investigated the effects of three doses of citalopram ( 5 mg , 25 mg , and 50 mg ) on depressive symptoms and various biochemical variables in 26 depressive patients . A significant reduction of the clinical ratings of depressive symptoms occurred at all dose levels . In endogenously depressed patients , a dose of 25 or 50 mg daily seemed to have the most pronounced antidepressive effect . The side effects were few and not related to dose level . A highly significant decrease in 5-HIAA in the CSF was found . MOPEG in the CSF was also significantly decreased , while HVA in the CSF was increased . In addition , a significant decrease in the plasma concentrations of valine , leucine , tyrosine , and histidine was found . None of the biochemical effects was dose-dependent . The complex pattern of biochemical effects indicate that the amelioration of depressive symptoms might be related to effects of citalopram on central monoaminergic mechanisms and peripheral amino acid concentrations",
"In making treatment decisions , doctors and patients must take into account relevant r and omised controlled trials ( RCTs ) and systematic review s. Relevance depends on external validity ( or generalisability)--ie , whether the results can be reasonably applied to a definable group of patients in a particular clinical setting in routine practice . There is concern among clinicians that external validity is often poor , particularly for some pharmaceutical industry trials , a perception that has led to underuse of treatments that are effective . Yet research ers , funding agencies , ethics committees , the pharmaceutical industry , medical journals , and governmental regulators alike all neglect external validity , leaving clinicians to make judgments . However , reporting of the determinants of external validity in trial publications and systematic review s is usually inadequate . This review discusses those determinants , presents a checklist for clinicians , and makes recommendations for greater consideration of external validity in the design and reporting of RCTs",
"BACKGROUND This study compares antidepressant efficacy and tolerability of citalopram given either orally or as a slow drop infusion . METHODS Citalopram ( 40 mg/day ) was administered double-blindly as tablets or slow-drop infusion during the first 10 days and then open , orally , up to treatment Day 42 . RESULTS In 60 moderately to severely depressed patients , the Hamilton depression total score ( 17-items ) at baseline was 23.9 and 23.6 in the active infusion ( n = 30 ) and active tablet ( n = 30 ) group , respectively . These scores dropped in both groups to 15.6 and 16.9 on Day 10 , and to 10.3 and 10.2 on Day 42 . Response rates ( delta Hamilton > or = 50 % ) amounted to 33.3 % and 17.9 % on Day 10 , and 66.2 % and 63.3 % on Day 42 , without a relevant group difference in citalopram plasma concentration . CONCLUSION Slow-drop infusion with citalopram shows a similar risk/benefit relationship to oral citalopram . The design of this study allowed us to evaluate pharmacological but not psychological factors which may contribute to response to slow-drop infusion",
"Escitalopram is the S-enantiomer of citalopram . In this study , we compared the efficacy of equivalent dosages of escitalopram and citalopram in the treatment of moderate to severe major depressive disorder ( MDD ) , based on data from two , pooled , r and omized , double-blind , placebo-controlled studies of escitalopram in which citalopram was the active reference . The primary efficacy parameter was the mean change from baseline in the Montgomery Åsberg Depression Rating Scale ( MADRS ) total score . Significant differences in favour of escitalopram were observed for the MADRS [ P Clinical Global Improvement – Severity of Illness scores ( CGI-S ; P Escitalopram separated from placebo at week 1 on the primary efficacy parameter , whereas citalopram first separated from placebo at week 6 . An analysis of time to response showed that escitalopram-treated patients responded significantly faster to treatment than citalopram-treated patients ( P achieved remission with escitalopram than to citalopram ( P The HAMD scale was only used in the fixed-dose study , where escitalopram-treated patients had a significant reduction in HAMD-17 total score at week 8 compared to citalopram-treated patients ( P population of severely ill patients ( MADRS≥30 ) , escitalopram-treated patients showed greater improvement than citalopram-treated patients ( P ) . Escitalopram showed consistently superior efficacy compared to citalopram in the treatment of moderate to severe MDD on all efficacy parameters , and was similarly well tolerated ",
"OBJECTIVE Predictors of treatment response to serotonergic versus nonserotonergic , e.g. , noradrenergic , antidepressants are of considerable clinical relevance as they could help to reduce the occurrence of patients ' receiving weeks or even months of unsuccessful treatment . Several studies show that the response to selective serotonin reuptake inhibitors can be successfully predicted by using the loudness dependence of auditory evoked potentials ( LDAEP ) , which denotes change in the amplitudes in response to different stimulus intensities and is to date one of the best vali date d indicators of the central serotonergic system . The aim of the current r and omized prospect i ve study was to investigate whether or not LDAEP also allows the differential prediction of treatment response to serotonergic versus noradrenergic antidepressants . METHOD Electrophysiologic recordings were performed on 48 subjects between 1999 and 2001 . After exclusions due to artifacts , the study sample consisted of 35 unmedicated in patients with a DSM-IV or ICD-10 diagnosis of major depressive disorder ( mean + /- SD age = 42.5 + /- 10.8 years ; 13 male , 22 female ; mean + /- SD score of 28.9 + /- 5.7 on the Hamilton Rating Scale for Depression [ HAM-D ] , the primary measure for psychopathology ) . The patients were then treated for 4 weeks with either the selective serotonin reuptake inhibitor citalopram or the noradrenaline reuptake inhibitor reboxetine . RESULTS Analysis of variance ( F = 5.05 , df = 1,31 ; p = .03 ) revealed that responders ( 50 % improvement in HAM-D score ) to the citalopram treatment were characterized by a strong LDAEP at baseline , and responders to reboxetine were characterized by a weak LDAEP at baseline . Non-responders to citalopram or reboxetine showed the inverse LDAEP characteristics , respectively . CONCLUSION This study is one of the first to demonstrate differential prediction of response to different classes of antidepressants . Patients at the beginning of an antidepressant treatment who show an initially strong LDAEP have a greater probability of responding to a serotonin-agonist antidepressant , whereas patients with a weak LDAEP will probably benefit more from a nonserotonergic , e.g. , noradrenergic , antidepressant . If these results were replicated in a larger sample , this simple electroencephalographic method could be more broadly used in clinical practice to support clinicians in replacing the trial and error method with a more targeted and individualized approach to antidepressant treatment",
"This study sought to investigate the efficacy of escitalopram at different dosages for the treatment of obsessive – compulsive disorder ( OCD ) . Thirty individuals were enrolled in a 16-week , open-label trial of escitalopram and r and omly assigned to the 20 or 30 mg study arm . Study measures assessing OCD symptoms , anxiety , depression , and quality of life were administered at baseline and weeks 2 , 4 , 8 , 12 , and 16 . For the 23 study completers , pretreatment and posttreatment analyses revealed significant improvements ( P clinician-rated and self-rated measures of OCD symptoms , quality of life , anxiety , and depression . Approximately half of the sample ( n = 12 ) satisfied full medication response criteria and less than one-quarter ( n = 5 ) were partial medication responders . Intention-to-treat analyses showed similar improvements ( P Yale – Brown Obsessive Compulsive Scale ( P baseline depression and anxiety scores were used as analysis covariates . These results suggest that the 30 mg ( vs. 20 mg ) dose of escitalopram may provide a superior reduction in OCD symptoms for those sufferers with comorbid depression and /or anxiety",
"The enhanced sensitivity of the elderly to the side effects produced by tricyclic antidepressants ( TCAs ) , and the frequency and type of adverse events , have made the treatment of depression in this group difficult . The selective serotonin reuptake inhibitors ( SSRIs ) have been reported to produce significantly fewer undesirable side effects and display better tolerance than TCAs . We compared the therapeutic actions and side effects produced by citalopram , the most selective SSRI available , with amitriptyline in a group of elderly patients ( aged 65 and older ) diagnosed with major depression . In a double-blind , double-dummy , parallel-group , multicenter comparison of citalopram ( 20 or 40 mg/day ) and amitriptyline ( 50 or 100 mg/day ) , patients who did not respond to placebo during a 1-week single-blind phase were r and omly assigned to receive citalopram or amitriptyline for 8 weeks . Efficacy measures included the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Hamilton Depression Scale ( HAMD ) , and Clinical Global Impressions . Both drug treatments produced equivalent time-related declines in severity of depression , so that by 8 weeks slightly more than 50 % of the patients in each group experienced marked recovery , defined as MADRS scores Amitriptyline produced a greater overall incidence of adverse events , including a significantly higher ( P dry mouth ( 34 % vs. 7 % ) , as well as a significantly higher ( P somnolence . Constipation and fatigue also occurred more frequently in the amitriptyline than in the citalopram group . For only one event ( nausea ) did the citalopram group report a significantly greater ( P = 0.012 ) incidence ( 12.8 % vs. 4.8 % ) . On the basis of these results , it was concluded that citalopram is as effective an antidepressant as amitriptyline in the treatment of the depressed elderly . Because of its low incidence and low magnitude of side effects , citalopram seems especially useful in private practice",
"Although serotonin reuptake inhibitors ( SRIs ) are the medications of choice in the treatment of obsessive-compulsive disorder ( OCD ) , only 50 - 60 % of patients respond to a single trial of any of these agents . Improved knowledge of the predictors of response to treatment may have important clinical implication s. Data from a large r and omized placebo-controlled trial of citalopram in OCD was analysed using logistic regression to determine predictors of response . Demographic ( age , sex ) , clinical ( OCD severity and duration , depression severity , prior treatment ) and trial variables ( citalopram dose , treatment duration ) were included . Subjects with longer duration of OCD , more severe OCD symptoms or previous selective SRI use were less likely to be responders in the citalopram trial . In contrast , subjects who received adequate medication doses for sufficient periods of time in the citalopram trial were more likely to be responders . Despite greater awareness of OCD in recent years , there is evidence that the disorder continues to be underdiagnosed and undertreated . The data here emphasize the crucial importance of early diagnosis and treatment of OCD , and of pharmacotherapy with appropriate dose and duration",
"BACKGROUND Timely administration/supplementation of a specific serotonin reuptake inhibitor with a second therapeutic agent could improve treatment outcome in patients with major depressive disorder ( MDD ) . The purpose of this study was to identify the optimal time at which to implement supplementation so as to maximize the likelihood of remission by 8 weeks and minimize overtreatment . METHOD Data from patients with MDD treated with sertraline ( n = 108 ) or citalopram ( n = 107 ) in a r and omized controlled trial were analyzed by multivariate logistic regression . The 21-item Hamilton Depression Scale scores at weeks 1 , 2 , 3 , 4 , and 6 ; sex ; age ; and baseline Hamilton Anxiety Scale score were used as predictors of remission by 8 weeks sustained for a further 4 weeks . RESULTS Regression models for weeks 2 , 3 , 4 , and 6 were significant ( area under the curve values , 0.73 - 0.91 ) . The models for weeks 3 to 6 yielded κ coefficients greater than 0.40 with the outcome variable . A Hamilton Depression Scale reduction score of 50 % at week 4 as a criterion for supplementation would have result ed in overtreatment of 4 % and 0 % of patients in the sertraline and citalopram groups , respectively , and none if applied at week 6 . The rates at which patients who should have received supplementation ( destined to be nonremitters at 8 weeks ) would have been missed would be 49%/54 % for sertraline/citalopram at week 4 and 43%/50 % at week 6 . LIMITATIONS The study limitations are as follows : secondary analysis of data , relatively low sertraline dose , and relatively small sample sizes . CONCLUSIONS It may be possible to identify patients treated with specific serotonin reuptake inhibitors who will not achieve sustained remission by 8 weeks . If supplementation were implemented accordingly , the number of overtreated patients would be small . However , a substantial number of patients who should be supplemented would be missed , indicating a need for greater sensitivity of the prediction model . Further studies are needed",
"BACKGROUND The S-enantiomer of citalopram ( escitalopram ) is the active moiety linked to the anti-depressant effects associated with citalopram ( the racemate ) . For escitalopram to be approved for the treatment of depression in Europe , findings from clinical trials of escitalopram are required to match previous results from studies of the racemate , citalopram . OBJECTIVE The aim of this study was to compare the efficacy and tolerability of escitalopram and citalopram in out patients with major depressive disorder ( MDD ) . METHODS This prospect i ve , r and omized , double-blind , active-controlled study was conducted at 8 psychiatric outpatient clinics in the Federation of Russia . Adult out patients aged 25 to 45 years with MDD and a total score > or = 25 on the Montgomery-Asberg Depression Rating Scale ( MADRS ) were eligible . Patients were r and omly assigned to receive 6 weeks of treatment with fixed daily doses of escitalopram 10 mg , citalopram 10 mg , or citalopram 20 mg . Efficacy assessment s were made at weeks 0 ( baseline ) , 1 , 4 , and 6 ( study end or last observation carried forward ) . The primary efficacy parameter was the change from baseline in MADRS total score . Secondary measures were the change from baseline in MADRS total score in a subgroup of severely depressed patients ( baseline MADRS total score , > or = 35 ) , MADRS core depression subscale score , and Clinical Global Impression-Severity and Improvement ( CGI-S and CGI-I ) scores ; and the proportions of patients classified as responders and remitters at study end . Tolerability was assessed using adverse events ( AEs ) recorded by the investigator . RESULTS Of 330 assessable r and omized patients , 8 withdrew , including 7 who withdrew consent and 1 who withdrew due to recurrence of a preexisting event . Thus , 322 patients were included in the assessment ( mean age , 35 years ; 41.6 % male ; all white ; escitalopram 10 mg , 108 patients ; citalopram 10 mg , 106 ; citalopram 20 mg , 108 ) . At study end , the mean ( SE ) change from baseline in MADRS total score was significantly greater in the escitalopram arm than in the 10- and 20-rag citalopram arms ( -28.70 [ 0.78 ] vs -20.11 [ 0.80 ] and -25.19 [ 0.78 ] ; both , P . Improvements were more marked in the severely depressed subgroup ( -30.33 [ 0.95 ] vs -20.87 [ 0.99 ] and -26.34 [ 0.91 ] ) . Changes in the CGI-S and CGI-I scores and the rates of response and remission were significantly greater in the escitalopram group compared with those in the citalopram 10- and 20-mg groups ( CGI-S : -2.60 [ 0.10 ] vs -1.61 [ 0.10 ] and -2.05 [ 0.10 ] ; CGI-I : + 1.58 [ 0.09 ] vs + 2.35 [ 0.10 ] and + 1.80 [ 0.09 ] ; response : 95.4 % vs 44.3 % and 83.3 % ; remission : 89.8 % vs 25.5 % and 50.9 % [ all , P subscale score were -19.00 ( 0.59 ) , -13.00 ( 0.60 ) , and -16.52 ( 0.58 ) with escitalopram , citalopram 10 mg , and citalopram 20 mg , respectively . The prevalence of AEs was significantly lower in the escitalopram group ( 7 ) compared with the citalopram groups ( 16 and 19 in the 10- and 20-mg groups , respectively ; both , P 0.05 ) . Nausea ( 2 [ 1.9 % ] , 5 [ 4.7 % ] , and 7 [ 6.5 % ] patients in the escitalopram and citalopram 10- and 20-mg groups , respectively ) and headache ( 1 [ 0.9 % ] , 2 [ 1.9 % ] , and 4 [ 3.7 % ] ) were the most frequently reported AEs . CONCLUSIONS The results from this study suggest that escitalopram 10 mg was more effective than citalopram 10 and 20 mg at 6 weeks in these adult out patients with MDD . All treatments were well tolerated",
"ABSTRACT – In a double‐blind trial , comprising 60 endogenously depressed patients , citalopram was compared with mianserin . Fifty‐eight patients completed the 6‐week trial period with ratings and side effect recordings at weeks 0 , 1 , 2 , 4 , and 6 . Both drugs were administered as a single evening dose , 20–80 mg ( most frequently 40 mg ) for citalopram and 60–120 mg ( most frequently 90 mg ) for mianserin . CPRS ( Subscale for Depression ) total scores showed a highly significant reduction in both groups with a significant difference in favour of citalopram after 1 and 2 weeks . Based on the Global Evaluation of the Severity of Illness there were 18 complete and three partial responders on citalopram and 13 complete and four partial responders on mianserin . Six patients on citalopram and one patient on mianserin showed mild or moderate side effects , but no cardiovascular side effects were recorded . The authors conclude that citalopram is a safe antidepressant drug , presumably better than mianserin ",
"& NA ; The abrupt discontinuation of antidepressants can result in a syndrome of adverse events , including somatic , mood and psychomotor reactions . This study examined the effects of discontinuing and resuming antidepressant treatment with four selective serotonin reuptake inhibitors ( SSRIs ) on cognitive and psychomotor function . Eighty‐seven patients receiving maintenance therapy with fluoxetine , sertraline , paroxetine or citalopram had their treatment interrupted for 4‐7 days using double‐blind placebo . Assessment s of aspects of cognitive and psychomotor performance , mood and symptoms were carried out at each visit . Following interruption of treatment , significant differences between the groups emerged . Paroxetine treated patients experienced significantly more cognitive failures ( P = 0.007 ) , poorer quality of sleep ( P = 0.016 ) , and an increase in depressive symptoms , as rated both subjectively , using the Zung scale ( P = 0.006 ) and by the clinician , using the Montgomery‐Asberg Depression Rating Scale ( P = 0.0003 ) and Clinical Global Impression ( P = 0.0003 ) , compared to some or all of the other drugs . All changes were reversed on reinstatement of treatment . Abrupt discontinuation of treatment with paroxetine leads to deterioration in various aspects of health and functioning , which may be related to the antidepressant discontinuation syndrome . These effects are not evident in patients receiving fluoxetine , sertraline and citalopram , suggesting they are not an SSRI class phenomenon . Int Clin Psychopharmacol 15:305‐318 © 2000 Lippincott Williams &",
"Post-hoc pooled analysis of data from two 6-month r and omised controlled trials in patients with major depressive disorder ( MDD ) revealed superior efficacy and tolerability of escitalopram when compared with paroxetine . Escitalopram ( n=394 ) produced a significantly ( p Montgomery-Asberg Depression Rating Scale ( MADRS ) total score , compared with paroxetine ( n=383 ) . Significant differences were also observed in Clinical Global Impression (CGI)--severity ( escitalopram , 2.1 ; paroxetine , 2.4 ; p CGI -- improvement ( escitalopram , 1.8 ; paroxetine , 2.0 : p severely depressed patients ( baseline MADRS > or = 30 ) , escitalopram showed further improved efficacy compared with paroxetine in all scores . This analysis supports previous observations of superior efficacy and tolerability of long-term escitalopram treatment ( 10 to 20 mg/day ) compared with paroxetine ( 20 to 40 mg/day ) . Escitalopram is a good therapeutic option for the long-term treatment of MDD , particularly in severely depressed patients",
"Abstract Aim : To assess the relative cost effectiveness of escitalopram compared with venlafaxine XR in patients with major depressive disorder ( MDD ) . Methods : An economic evaluation was conducted alongside a double-blind , multinational , r and omised clinical trial and examined the costs and quality of life of 251 patients taking escitalopram versus venlafaxine . Out patients fulfilling criteria for MDD were r and omised to receive oral escitalopram 10–20 mg/day or venlafaxine 75–150 mg/day for 8 weeks . Patient-reported outcomes ( EuroQOL question naire , Quality of Life Depression Scale ) , use of medical services and absence from work ( relating to the previous 3 months ) were recorded at baseline , with repeated measurements at week 8 . Unit costs in year values were applied to the re source utilisation data . A cost-effectiveness analysis was performed using the EuroQOL score as the effectiveness measure . The perspective was that of the healthcare payer , with a societal perspective considered in a sensitivity analysis . Results : Statistically significant improvements in patient-reported outcomes ( vs baseline ) were observed in both groups after 8 weeks ’ treatment . Patients treated with escitalopram tended to report fewer problems on the EuroQOL dimensions than venlafaxine recipients . Mean per-patient costs in euros ( € , year 2003 values ) for the escitalopram group , compared with the venlafaxine group , were 32 % lower ( € 110 vs € 161 ) from a healthcare perspective , although this was not a statistically significant difference . Differences were related to lower drug acquisition costs and fewer hospitalisations for escitalopram than venlafaxine recipients . A multivariate model adjusting for baseline characteristics showed that escitalopram reduced direct costs compared with venlafaxine ( p = 0.007 ) . Bootstrapped distributions of the incremental cost-effectiveness ratios also showed similar effectiveness but lower costs for escitalopram compared with venlafaxine . Inclusion of indirect costs led to similar results . Conclusion : This prospect i ve economic analysis suggests that escitalopram has similar effectiveness to venlafaxine in the treatment of MDD , but may be associated with lower healthcare costs . These findings are consistent with previously published economic evaluations",
"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",
"BACKGROUND This r and omized , open-label , rater-blinded , multicenter study compared treatment outcomes with the serotonin-norepinephrine reuptake inhibitor ( SNRI ) venlafaxine extended release ( ER ) with selective serotonin reuptake inhibitors ( SSRIs ) in primary care patients with major depressive disorder . METHOD Study data were collected from November 29 , 2000 , to March 4 , 2003 . Out patients who met diagnostic criteria for major depressive disorder according to the Mental Health Screener , a computer-administered telephone interview program that screens for the most common mental disorders , and had a total score on the 17-item Hamilton Depression Rating Scale ( HDRS(17 ) ) ≥ 20 were r and omly assigned to receive up to 6 months of open-label venlafaxine ER 75 - 225 mg/d ( n = 688 ) or an SSRI ( n = 697 ) : fluoxetine 20 - 80 mg/d , paroxetine 20 - 50 mg/d , citalopram 20 - 40 mg/d , and sertraline 50 - 200 mg/d . The primary outcome was remission ( HDRS(17 ) score ≤ 7 ) at study end point using the last-observation-carried-forward method to account for early termination . A mixed-effects model for repeated measures ( MMRM ) analysis evaluated secondary outcome measures . RESULTS Fifty-one percent of patients completed the study . Month 6 remission rates did not differ significantly for venlafaxine ER and the SSRIs ( 35.5 % vs 32.0 % , respectively ; P = .195 ) . The MMRM analysis of HDRS(17 ) scores also did not differ significantly ( P = .0538 ) . Significant treatment effects favoring the venlafaxine ER group were observed for remission rates at days 30 , 60 , 90 , and 135 and a survival analysis of time to remission ( P = .006 ) , as well as Clinical Global Impressions-severity of illness scale ( P = .0002 ) ; Hospital Anxiety and Depression Scale-Anxiety subscale ( P = .03 ) ; 6-item Hamilton Depression Rating Scale , Bech version ( P = .009 ) ; and Quick Inventory of Depressive Symptomatology-Self-Report ( P = .0003 ) . CONCLUSIONS Remission rates for patients treated with venlafaxine ER or an SSRI did not differ significantly after 6 months of treatment . Results of most secondary analyses suggested that SNRI treatment had a greater antidepressant effect versus the SSRIs studied",
"Depression is the most common psychiatric disorder among the elderly and in old age may interact with emotional and cognitive functioning . Depression in old age has been shown to be associated with degenerative changes in the brain . It is , therefore , important that in this patient population antidepressants with a favourable tolerability profile , such as the selective serotonin reuptake inhibitors ( SSRIs ) , are examined for both antidepressant efficacy and effect on cognitive function and emotional impairment . This r and omised , double-blind study compared the efficacy and tolerability of citalopram and mianserin in 336 elderly , depressed patients with or without dementia . Patients received either citalopram 20 - 40 mg/day or mianserin 30 - 60 mg/day for 12 weeks . The treatments were equivalent with respect to change in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score ; patients in both treatment groups responded well . Patients with dementia showed a smaller decrease in total MADRS score than patients without dementia . Both treatments were well tolerated with a relatively low incidence of adverse events . Fatigue and somnolence were more frequent with mianserin , while insomnia was more frequent with citalopram . Overall , this study showed that the two treatments were equivalent in efficacy , and that citalopram is an effective , well-tolerated and non-sedative treatment for elderly depressed patients with or without dementia",
"Alzheimer 's disease is the most frequent form of dementia , where behavioral and cognitive disruption symptoms coexist . Depression , apathy , anxiety , and other conduct disorders are the complaints most often reported by caregivers . Fifty subjects were referred to our Institute with a diagnosis of probable Alzheimer 's disease . Cognitive impairment was equally distributed among the subjects . Patients , aged 68 to 76 years old , were r and omized to receive inhibitors of cholinesterase ( Donepezil , 5 mg/ day ) alone , or inhibitors of cholinesterase plus selective seratonin reuptake inhibitors ( SSRIs ) ( citalopram HBr , 20 mg/day ) . We followed up all the patients for one year , with particular concern for neuropsychological aspects associated with eventual behavioral changes . Results indicate that SSRI intake seems to be effective for depression , decreasing it and improving quality of life for both patients and caregivers . Side effects in both groups were few , and there were no study withdrawals . This paper discusses the relationship between dementia- and depression , and presents our finding that depressive symptoms , if specifically treated , tend to reduce caregiver stress and improve well-being in patients with Alzheimer 's disease",
"Milnacipran is a new antidepressant with similar effects on the reuptake of noradrenaline and serotonin in vivo and in vitro . The present study was design ed to study the efficary and tolerability of long-term treatment of depressed patients with milnacipran in comparison with clomipramine . The study was design ed as a double-blind , r and omized parallel group comparison at 10 different hospitals in The Netherl and s. The duration of treatment was 6 weeks , with an extension period of 20 weeks . The entire study period of 26 weeks was done under double-blind conditions . There was 1 week of dose escalation after which the patients received either treatment with milnacipran 200 mg/day or clomipramine 150 mg/day in fixed doses during weeks 2 to 10 . This was followed by flexible dosing with 200 , 150 , or 100 mg/day milnacipran or 150 , 100 or 75 mg/day clomipramine during weeks 11 to 26 . Both milnacipran and clomipramine showed poor antidepressant activity in this patient sample . There were no significant differences between the two treatment groups with respect to antidepressant efficacy . Several method ological reasons might explain the lack of antidepressant efficacy in the present study . In 45 % of the patients in the present study , the duration of the current episode of depression was longer than 6 months , whereas 48 % of the patients used antidepressants before the study and 73 % of these appeared to be non-responders . This raises the possibility that the present sample consisted of treatment-resistant depressive patients",
"OBJECTIVE Citalopram and sertraline are widely prescribed selective serotonin reuptake inhibitors ( SSRIs ) . There is no conclusive evidence to show superiority of citalopram or sertraline in terms of efficacy or tolerability . Hence this study was design ed to compare short term efficacy and safety of citalopram and sertraline in major depressive disorder ( MDD ) in Indian patients . METHODS In an open , r and omized study , 100 patients were divided into two groups . In Group A ( n = 50 ) patients received citalopram ( 20 - 60 mg/day ) for 6 weeks . In Group B ( n = 50 ) patients received sertraline ( 50 - 150 mg/day ) for 6 weeks . Patients were evaluated at baseline and then at 1 , 2 , 3 , 4 , 5 , and 6 weeks . RESULTS There was significant improvement in Hamilton depression rating scale ( HDRS ) , Montgomery and Asberg depression rating scale ( MADRS ) and Amritsar depressive inventory ( ADI ) scores ( p citalopram ( p Onset of action of citalopram was earlier as compared to sertraline ( p number of responders and remitters was also more with citalopram ( p serious adverse event was reported in either of the groups . CONCLUSION Citalopram had shown better efficacy , earlier onset of action and more number of responders and remitters as compared to sertraline in MDD in Indian patients",
"Abstract There is evidence of derangement of oxidant and antioxidant defense systems in depression . The present study examined the effects of fluoxetine and citalopram , st and ard selective serotonin re-uptake inhibitors , on lipid peroxidation , superoxide dismutase ( SOD ) activity and ascorbic acid concentrations . For this , a prospect i ve open-labeled , r and omized design was utilized . Patients with major depression ( n = 62 ) were compared with age- and sex-matched healthy volunteers ( n = 40 ) . There was a significant increase in serum SOD , serum MDA and decrease in plasma ascorbic acid levels in patients of major depression as compared to control subjects . The trend reversed significantly after treatment with fluoxetine and citalopram . Results indicate a greater reduction in oxidative stress with citalopram than fluoxetine . The Hamilton Rating Scale for Depression ( HRSD ) score also improved with fluoxetine and citalopram treatment . These findings indicate that major depression is associated with increased levels of serum SOD , serum MDA and decreased levels of plasma ascorbic acid . Treatment with fluoxetine and citalopram reversed these biochemical parameters . This study can be used as a predictor of drug response by fluoxetine and citalopram in major depression",
"To investigate the safety and tolerability of the atypical antipsychotic quetiapine in anorexia nervosa patients , and to determine the effect of quetiapine treatment on anorexic psychopathology and other key outcome measures including weight and body image , we conducted a naturalistic , open-label , 12-week r and omized controlled trial of low-dose ( 100 - 400 mg/day ) quetiapine treatment versus treatment as usual in 33 anorexia nervosa patients from our Eating Disorder Clinics . To monitor the effects of treatment over the medium term , the participants were then followed up with assessment visits at 6 and 12 months after the end of the treatment phase . Low-dose quetiapine treatment result ed in both psychological and physical improvements , with minimal associated side-effects . Given the overall trend toward improvement that we observed , quetiapine appears to be a promising c and i date for the treatment of anorexia nervosa . Further large-scale placebo-controlled clinical trials will be necessary to fully evaluate the benefits of quetiapine treatment for this disorder",
"Patients with Major Depressive Disorder ( MDD ) may not respond to antidepressants for 8 weeks or longer . A biomarker that predicted treatment effectiveness after only 1 week could be clinical ly useful . We examined a frontal quantitative electroencephalographic ( QEEG ) biomarker , the Antidepressant Treatment Response ( ATR ) index , as a predictor of response to escitalopram , and compared ATR with other putative predictors . Three hundred seventy-five subjects meeting DSM-IV criteria for MDD had a baseline QEEG study . After 1 week of treatment with escitalopram , 10 mg , a second QEEG was performed , and the ATR was calculated . Subjects then were r and omly assigned to continue with escitalopram , 10 mg , or change to alternative treatments . Seventy-three evaluable subjects received escitalopram for a total of 49days . Response and remission rates were 52.1 % and 38.4 % , respectively . The ATR predicted both response and remission with 74 % accuracy . Neither serum drug levels nor 5HTTLPR and 5HT2a genetic polymorphisms were significant predictors . Responders had larger decreases in Hamilton Depression Rating Scale ( Ham-D(17 ) ) scores at day 7 ( P=0.005 ) , but remitters did not . Clinician prediction based upon global impression of improvement at day 7 did not predict outcome . Logistic regression showed that the ATR and early Ham-D(17 ) changes were additive predictors of response , but the ATR was the only significant predictor of remission . Future studies should replicate these results prior to clinical use",
"Approximately 30–45 % of patients with major depressive episode ( MDE ) do not fully respond to st and ard recommended treatments and further strategies of intervention , including pharmacological augmentation , have been proposed for these patients . This study was aim ed to evaluate the efficacy of short-term , low-dose ( 10 mg/day ) intravenous ( i.v . ) citalopram augmentation versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors ( SSRIs ) . Thirty-six patients with a Diagnostic and Statistical Manual for Mental Disorders , 4th edition , text revision criteria MDE and partial or no response to oral SSRIs were selected and r and omly assigned to citalopram ( n=18 ) or to placebo ( n=18 ) i.v . augmentation . The augmentation regimen lasted 5 consecutive days during which the patients were maintained on their current treatment with oral SSRIs . Analyses of variance with repeated measures on Hamilton Depression Rating Scale and Montgomery – Asberg Depression Rating Scale total scores , administered daily with blind-raters conditions , were done . With regard to the Hamilton Depression Rating Scale total scores , a significant time effect ( F=42.02 , P timextreatment effect ( F=21.17 , P . Similar results were obtained from the analysis on Montgomery – Asberg Depression Rating Scale total scores : time effect ( F=50.07 , P citalopram augmentation may be effective in depressed patients with partial or no response to oral SSRIs . Further controlled studies performed with double-blind conditions are warranted to confirm the present results",
"Abstract Objectives . Evidence in favour of switching between selective serotonin reuptake inhibitor ( SSRI ) and tricyclic ( TCA ) antidepressants in treatment resistant depression has been tested in a few studies only , consequently a prospect i ve study was undertaken to evaluate the impact of switching strategies . Methods . One hundred eighty-nine patients who failed to respond to a previous antidepressant were r and omised to four arms : firstly they received citalopram or desipramine for a 4-week period ; secondly , those who failed to respond were treated for a further 4-week period with the same antidepressant ( citalopram-citalopram and desipramine-desipramine arms ) or switched to the alternate one ( citalopram-desipramine and desipramine-citalopram arms ) . Results . There was no difference in the first 4-week phase between patients receiving citalopram versus desipramine in Hamilton Rating Scale for Depression ( HRSD ) , Montgomery – Asberg Depression Rating Scale ( MADRS ) , and Clinical Global Impression ( CGI ) scores . In the second 4-week phase remitter rates were higher among non-switched patients ( P = 0.04 ) . Moreover , considering HRSD and MADRS , switched patients reported significantly higher scores ( P ≤ 0.02 for both scales at each time-point ) . Conclusions . This study supports the thesis that switching from an SSRI to a TCA ( and vice versa ) in non-responders to a 4-week trial of an SSRI/TCA is not associated with improved response . The result goes in the opposite direction to that predicted by current guidelines",
"In this pilot study , the pharmacokinetics of citalopram ( CIT ) were examined in five hospitalized depressed patients after an abrupt discontinuation of a treatment with 40 mg/d of this selective serotonin reuptake inhibitor ( SSRI ) . During the 8-day study period , clinical ratings were regularly carried out . Between days 5 and 8 , the patients were treated with clomipramine ( 75 mg/d ) . The enantiomers of CIT and its metabolites , demethyl-CIT ( DCIT ) and CIT-propionic acid derivative ( CIT-PROP ) , were measured repeatedly from day 0 to day 8 by a stereoselective high-performance liquid chromatography ( HPLC ) procedure . The following drug plasma half-lives were measured ( means + /- SD ) : R-CIT : 66+/-11 h ; S-CIT : 42+/-13 h ; R-DCIT : 228+/-148 h ; S-DCIT : 93+/-35 h ; R-CIT-PROP : 82+/-31 h ; S-CIT-PROP : 186+/-93",
"Objective . Depression with psychotic features is a severe subtype of major depression associated with the presence of delusions , hallucinations and specific neurobiological features . Despite clinical consensus and guideline recommendations , data comparing the efficacy of combining antipsychotics with antidepressants compared to antidepressants alone remain inconclusive . The aim of the study was to investigate effectiveness and tolerability of the atypical antipsychotic olanzapine in acute depression with psychotic features . Methods . Seventeen in patients with major depressive disorder with psychosis ( MDDp ) were treated with a combination of an antidepressant and olanzapine for 6 weeks in a prospect i ve open-label study . Depressive and psychotic symptoms , extrapyramidal and general side effects were assessed every 2 weeks . Sixteen patients were eligible for final analysis . Results . The Brief Psychiatric Rating Scale ( BPRS ) showed a 30 % symptom reduction after week 2 , a 45 % symptom reduction after week 4 and no considerable improvement thereafter . Depressive symptoms ( Bech – Rafaelsen Melancholia Scale , BRMS ) receded by 37 % after week 2 and 50 % after week 4 . No extrapyramidal side effects occurred . Conclusion . Olanzapine is effective and tolerable in combination with an antidepressant in an MDDp inpatient sample . The results concur with data supporting good efficacy in negative and depressive symptoms of patients with schizophrenic and schizoaffective diseases",
"BACKGROUND Escitalopram has been proven safe and efficacious in the treatment of major depressive disorder ( MDD ) in short-term studies . The long-term clinical tolerability and response to treatment are presented from a 12-month open-label study with a total exposure time to escitalopram of 486 patient years . METHODS Patients ( n = 590 ) with MDD entered the study after completing one of two 8-week , double-blind , placebo-controlled , lead-in studies in primary care . Escitalopram was administered at doses of 10 or 20 mg/day ( dose based on physician 's clinical judgement ) with an average exposure to escitalopram of 315 days . The primary efficacy parameter was the Montgomery Asberg Depression Rating Scale ( MADRS ) total score . RESULTS The overall withdrawal rate was 26 % ; and the withdrawal rate due to adverse events was 9 % . The most common adverse events were headache , back pain , upper respiratory tract infection , rhinitis and nausea , with an incidence ranging from 11 % to 17 % . No new types of adverse events were seen after the acute period of 8 weeks , and the incidence declined with time . At baseline ( entry into the 12-month study ) , patients had a mean MADRS total score of 14.2 , which decreased to 10.5 after 8 weeks and 7.2 after 52 weeks ( LOCF ) . The percentage of patients in remission ( MADRS total score Escitalopram ( 10 to 20 mg/day ) demonstrated a favorable safety and tolerability profile over 12-months treatment , with further improvement in patient response",
"Antidepressants are used to treat chronic daily headache disorders such as migraine and chronic tension-type headache ( TTH ) , which are often associated with depression and anxiety . Here , we studied the efficacy and tolerability of amitriptyline and citalopram , given alone or in combination , in patients with ‘ triple ’ comorbidity of depression , TTH , and migraine . Eighty-eight patients were enrolled in the study and r and omly divided into two groups . The first group received amitriptyline and the second citalopram for 16 weeks . Patients were assessed at weeks 0 , 4 , 8 , and 16 . The two drugs were equally efficacious in relieving depressive symptoms , although amitriptyline was more efficacious than citalopram in reducing migraine and TTH attacks . Patients who did not respond to monotherapy ( improvement in depression , migraine and TTH without producing major side effects such as those commonly related to the ‘ serotonergic ’ syndrome . The results indicate that a combined therapy with amitriptyline and citalopram may be particularly beneficial for patients with TTH , migraine and comorbid depression that do not respond to monotherapy ",
"BACKGROUND This study examined the potential of an antidepressant drug , escitalopram , to improve depression , resilience to stress , and quality of life in family dementia caregivers in a r and omized placebo-controlled double-blinded trial . METHODS Forty family caregivers ( 43 - 91 years of age , 25 children and 15 spouses ; 26 women ) who were taking care of their relatives with Alzheimer disease were r and omized to receive either escitalopram 10 mg/day or placebo for 12 weeks . Severity of depression , resilience , burden , distress , quality of life , and severity of care-recipient 's cognitive and behavioral disturbances were assessed at baseline and over the course of the study . The Hamilton Depression Rating Scale scores at baseline ranged between 10 and 28 . The groups were stratified by the diagnosis of major and minor depression . RESULTS Most outcomes favored escitalopram over placebo . The severity of depression improved , and the remission rate was greater with the drug compared with placebo . Measures of anxiety , resilience , burden , and distress improved on escitalopram compared with placebo . DISCUSSION Among caregivers , this small r and omized controlled trial found that escitalopram use result ed in improvement in depression , resilience , burden and distress , and quality of life . Our results need to be confirmed in a larger sample",
"Negative cognitive structure ( particularly for interpersonal content ) has been shown in some research to persist past a current episode of depression and potentially to be a stable marker of vulnerability for depression ( D. J. A. Dozois , 2007 ; D. J. A. Dozois & K. S. Dobson , 2001a ) . Given that cognitive therapy ( CT ) is highly effective for treating the acute phase of a depressive episode and that this treatment also reduces the risk of relapse and recurrence , it is possible that CT may alter these stable cognitive structures . In the current study , patients were r and omly assigned to CT+ pharmacotherapy ( n = 21 ) or to pharmacotherapy alone ( n = 21 ) . Both groups evidence d significant and similar reductions in level of depression ( as measured with the Beck Depression Inventory-II and the Hamilton Rating Scale for Depression ) , as well as automatic thoughts and dysfunctional attitudes . However , group differences were found on cognitive organization in favor of individuals who received the combination of CT+ pharmacotherapy . The implication s of these results for underst and ing mechanisms of change in therapy and the prophylactic nature of CT are discussed"
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Moderate-to-vigorous physical activity ( MVPA ) is essential for disease prevention and health promotion . Emerging evidence suggests other intensities of physical activity ( PA ) , including light-intensity activity ( LPA ) , may also be important , but there has been no rigorous evaluation of the evidence . The purpose of this systematic review was to examine the relationships between objective ly measured PA ( total and all intensities ) and health indicators in school-aged children and youth . Online data bases were search ed for peer- review ed studies that met the a priori inclusion criteria : population ( apparently healthy , aged 5 - 17 years ) , intervention/exposure/comparator ( volumes , duration s , frequencies , intensities , and patterns of objective ly measured PA ) , and outcome ( body composition , cardiometabolic biomarkers , physical fitness , behavioural conduct/pro-social behaviour , cognition/academic achievement , quality of life/well-being , harms , bone health , motor skill development , psychological distress , self-esteem ) . Heterogeneity among studies precluded meta-analyses ; narrative synthesis was conducted . A total of 162 studies were included ( 204 171 participants from 31 countries ) . Overall , total PA was favourably associated with physical , psychological/social , and cognitive health indicators . Relationships were more consistent and robust for higher ( e.g. , MVPA ) versus lower ( e.g. , LPA ) intensity PA . All patterns of activity ( sporadic , bouts , continuous ) provided benefit . LPA was favourably associated with cardiometabolic biomarkers ; data were scarce for other outcomes . These findings continue to support the importance of at least 60 min/day of MVPA for disease prevention and health promotion in children and youth , but also highlight the potential benefits of LPA and total PA . All intensities of PA should be considered in future work aim ed at better elucidating the health benefits of PA in children and youth
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"OBJECTIVE To test for differences in prospect i ve associations between physical activity and obesity among black and white adolescent girls . DESIGN Prospect i ve cohort study using data from the National Heart , Lung , and Blood Institute Growth and Health Study . SETTING Multicenter study at the University of California ( Berkeley ) , Children 's Medical Center at the University of Cincinnati ( Cincinnati , Ohio ) , and Westat , Inc , and Group Health Association ( Rockville , Maryl and ) . PARTICIPANTS A total of 1148 adolescent girls ( 538 black and 610 white ) who provided valid data on levels of physical activity and obesity at ages 12 and 14 years . INTERVENTION Physical activity , assessed as accelerometer counts per day . MAIN OUTCOME MEASURES Three measurements of obesity were obtained using the Centers for Disease Control and Prevention definition of obesity ( at or above the age-specific 95th percentile of body mass index ) , the International Obesity Task Force reference body mass index cut points for obesity in children , and the sums of skinfold thickness ( with the cohort ≥90th percentile as indicative of obesity ) . RESULTS We found a strong negative dose-response association between quartiles of accelerometer counts per day at age 12 years and obesity at age 14 years ( using all 3 measurements of obesity ) in white but not black girls ( P ratios for obesity ( using the cohort ≥90th percentile for sums of skinfold thickness ) in adjusted models between the top and the bottom quartiles of accelerometer counts per day were 0.15 ( 95 % CI , 0.04 - 0.63 ; P = .03 for trend ) in white girls and 0.85 ( 95 % CI , 0.32 - 2.26 ; P = .93 for trend ) in black girls . CONCLUSIONS Higher levels of physical activity are prospect ively associated with lower levels of obesity in white adolescent girls but not in black adolescent girls . Obesity prevention interventions may need to be adapted to account for the finding that black girls are less sensitive to the effects of physical activity",
"BACKGROUND : In developed societies levels of daily physical activity ( PA ) among school-age children are decreasing . This implies risk factors for cardiovascular and metabolic diseases . Specific strategies to improve levels of PA are needed . In prepubertal boys there is evidence that strength training increases spontaneous PA outside of training . METHODS : A total of 102 schoolchildren ( age 10–14 years ) in Switzerl and were r and omly assigned to physical education classes or to participate twice weekly at a guided strength training program for 19 weeks . Spontaneous PA energy expenditure ( PAEE ; 3axial accelerometry for 7 days ) , leg and arm strength , and body composition ( dual energy radiograph absorptiometry ) were measured at baseline , after 19 weeks of training intervention , and after 3 months of washout . RESULTS : There were no significant differences between the groups at baseline . In the intervention group , PAEE increased by 10 % from baseline to end of training in boys ( P = .02 ) , but not in girls . Leg and arm strength were increased owing to training intervention in both boys and girls . All other variables were unchanged . Baseline PAEE was significantly negatively correlated with changes of PAEE . CONCLUSIONS : Targeted strength training significantly increases daily spontaneous PA behavior in boys . The less active children showed the greatest increase in spontaneous PAEE . Girls showed a similar increase in strength , but not in spontaneous PAEE . This may be explained by their earlier pubertal development . Strength training may be a promising strategy in schools to counteract decreasing levels of PA",
"Background . There is a shortage of reference values for cardiovascular risk factors such as serum lipids , glucose and insulin related to biological , social and lifestyle factors for Swedish children and adolescents . Such values are needed for planning and evaluation of public health activities , and for clinical use . Design and Methods . Data for this cross‐sectional , school‐based study were collected during a school year ( September to May ) . A r and om sample of 1137 girls and boys aged 9 and 15 years from two locations in central Sweden participated in the study , and blood sample s were taken from 969 of them . Methods . Fasting serum blood sample s were analysed for triglycerides , total cholesterol , high‐density lipoprotein cholesterol , glucose and insulin . Physical examination included measurement of height , weight and pubertal status . Question naires provided family background data . Total physical activity was measured by accelerometer registration . Results . Serum levels differed significantly between age and gender groups and were correlated to pubertal status . Neither genetic nor socio‐economic background nor smoking status influenced the serum levels . Insulin levels were elevated in subjects with a body mass index in the highest decentile , compared with the levels in the rest of the subjects . The insulin levels were inversely associated with total physical activity , and physical activity varied with season . Conclusions . Pubertal status ( biological age ) should to be considered in the interpretation of serum values in schoolchildren rather than chronological age . The interpretation of insulin values should include both body mass index and physical activity level , and perhaps also season . Previously described regional differences in serum lipid levels in Swedish adults seem to be present also in children",
"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",
"Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results",
"BACKGROUND It is unclear how moderate and vigorous intensities of physical activity ( PA ) are associated with cardiovascular fitness ( CVF ) and percentage of body fat ( % BF ) in adolescents . OBJECTIVE We tested the hypothesis that vigorous PA , to a greater degree than moderate PA , would be associated with better CVF and lower % BF . DESIGN This was a cross-sectional study of 421 black and white high school students ( x age : 16 y ) . PA was measured with 5 d of accelerometry and expressed in min/d of moderate or vigorous PA . CVF was measured with a multistage treadmill test and was expressed as the oxygen consumption at a heart rate of 170 bpm . % BF was measured with dual-energy X-ray absorptiometry . Multiple regressions were used to determine the degree to which variance in CVF and % BF was explained by PA , after control for age , sex , race , and the sex x race interaction . RESULTS A higher index for CVF was associated with higher amounts of moderate and vigorous PA ; more variance was explained by vigorous than by moderate PA . Lower % BF was associated with higher amounts of vigorous PA but not with the amount of moderate PA . CONCLUSION Black and white adolescents who engaged in relatively large amounts of free-living vigorous exercise were likely to be relatively fit and lean",
"OBJECTIVES To explore cross-sectional and longitudinal associations between self-reported and accelerometry-based physical activity ( PA ) and blood pressure ( BP ) between 11 and 14 years of age . METHODS Prospect i ve birth cohort study in Pelotas , Brazil . Participants were 427 cohort members who were followed up with at 11 , 12 , and 14 years of age , and had question naire data on PA and BP at 11 and 14 years , as well as accelerometry and question naire data on PA at 12 years . Outcome measures were continuous systolic and diastolic BP at 14 years , and change in BP from 11 to 14 years . RESULTS PA was unrelated to systolic BP in any analyses . PA measured by accelerometry at 12 years , but not question naire-derived PA , was inversely associated with diastolic BP at 14 years of age in fully adjusted models . Those who exceeded the 300-minutes PA threshold at all 3 visits had a 2.6 mmHg lower mean increase in DBP from 11 to 14 years compared with those classified below the threshold in all visits . CONCLUSIONS Accelerometry-based PA was longitudinally inversely associated with diastolic BP . This finding was not evident when analyzing self-reported PA at a given age , suggesting a possible underestimation of the association when using subjective data",
"PURPOSE This study was design ed to examine the associations of physical activity and body composition with cardiorespiratory fitness in eighth grade girls . METHODS A r and om sample of 1440 eighth grade girls at 36 schools participated in this cross-sectional investigation , which represented an ethnically and geographically diverse group . Cardiorespiratory fitness was assessed using a modified physical work capacity test on a cycle ergometer that predicted workload at a heart rate of 170 beats.min . Physical activity was assessed over 6 d in each girl using an accelerometer and body composition was estimated from body mass index and triceps skinfolds using a previously vali date d equation . Pearson correlations and multiple regression analyses were used to determine the relationships among fitness , physical activity , and body composition . RESULTS Significant linear relationships among cardiorespiratory fitness , body composition , and physical activity were found . The combination of fat and fat-free mass along with racial group and a race by fat-free-mass interaction accounted for 18 % ( R ) of the variation in physical fitness . Adding moderate-to-vigorous physical activity to the regression model increased the R to 22 % . Black girls had somewhat lower fitness levels ( P Physical activity , fat-free mass , and the interaction between fat-free mass and racial group are significantly associated with cardiorespiratory fitness in adolescent girls",
"PURPOSE To evaluate the relationship between depressive symptoms and physical activity in a geographically and ethnically diverse sample of sixth- grade adolescent girls . METHODS The Trial of Activity for Adolescent Girls ( TAAG ) baseline measurement included a r and om sample ( N = 1721 ) of sixth- grade girls in 36 schools at six field sites . Measurements were accelerometry and the 3-d Physical Activity Recall ( 3DPAR ) for physical activity , and the Center for Epidemiological Studies -Depression scale ( CES-D ) for depressive symptoms . RESULTS Girls with complete data ( N = 1397 ) , mean age 12 yr , had an average CES-D score of 14.7 ( SD = 9.25 ) and engaged in an average of about 460 min of sedentary activity , of moderate to vigorous physical activity ( MVPA ) , and min of vigorous physical activity ( VPA ) in an 18-h day . Thirty-minute segments of MVPA ranged in number from 3.9 to 1.2 , and METS for these segments ranged from > 3.0 to > 6.5 . Mixed-model regression indicated no relationship between depressive symptoms and physical activity ; however , a significant but modest inverse relationship between sedentary activity and depressive symptoms was observed . CONCLUSION A sufficient sample size , st and ardized procedures , and vali date d instruments characterized this study ; however , a relationship between depressive symptoms and physical activity was not observed for sixth- grade girls from diverse geographic locations . The average CES-D score was lower than is considered clinical ly meaningful for either adolescents or adults , and MET-minutes of sedentary activity were high . This combination of data may be different from other studies and could have contributed to the unexpected finding . This unexpected finding is informative , however , because it shows the need for additional research that includes a wider range of possible combinations of data , especially with young adolescent girls",
"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",
"A three-wave prospect i ve design was used to assess a model of motivation guided by self-determination theory ( Ryan & Deci , 2008 ) spanning the context s of school physical education ( PE ) and exercise . The outcome variables examined were health-related quality of life ( HRQoL ) , physical self-concept ( PSC ) , and 4 days of objective ly assessed estimates of activity . Secondary school students ( n = 494 ) completed question naires at three separate time points and were familiarized with how to use a sealed pedometer . Results of structural equation modeling supported a model in which perceptions of autonomy support from a PE teacher positively predicted PE-related need satisfaction ( autonomy , competence , and relatedness ) . Competence predicted PSC , whereas relatedness predicted HRQoL. Autonomy and competence positively predicted autonomous motivation toward PE , which in turn positively predicted autonomous motivation toward exercise ( i.e. , 4-day pedometer step count ) . Autonomous motivation toward exercise positively predicted step count , HRQoL , and PSC . Results of multi sample structural equation modeling supported gender invariance . Suggestions for future work are discussed",
"OBJECTIVE To evaluate an incentive-based physical activity intervention to increase physical activity and fitness among children in a 9-month cluster r and omized controlled trial . STUDY DESIGN Children aged 6 - 12 years were r and omized to control ( n = 138 from 106 families ) or intervention arm ( n = 147 from 106 families ) . The intervention included incentives for meeting step targets as measured by pedometers and structured weekend outdoor activities . Outcomes included trends in activity for the intervention group and between-group differences in pedometer steps , 6-minute walk test , body mass index , and parent-reported Pediatric Quality of Life Inventory . RESULTS At follow-up , children in the intervention group recorded significantly more pedometer steps than controls over the entire week ( 8660 vs 7767 ; P = .010 ) , on weekdays ( 8646 vs 7826 ; P = .041 ) , and on weekends ( 8779 vs 7684 ; P = .018 ) . Three different trajectory classes were identified . The first group increased activity but was not sustained , the second group met the target step levels , and the third group significantly surpassed the step goals . The intervention group showed trends toward longer 6-minute walk test times and higher Pediatric Quality of Life Inventory scores , but the differences were not statistically significant . CONCLUSION Incentives for increased step activity were effective in producing greater steps and showed a ( nonsignificant ) trend toward improvements in other health outcomes . Thus , future incentive trials should be incorporate greater step targets and longer follow-up periods to provide evidence of the long-term effect of these incentives on children 's health",
"Background This study examines associations between pedometer-determined steps/day and parent-reported child 's Body Mass Index ( BMI ) and time typically spent watching television between school and dinner . Methods Young people ( aged 5 - 19 years ) were recruited through their parents by r and om digit dialling and mailed a data collection package . Information on height and weight and time spent watching television between school and dinner on a typical school day was collected from parents . In total , 5949 boys and 5709 girls reported daily steps . BMI was categorized as overweight or obese using Cole 's cut points . Participants wore pedometers for 7 days and logged daily steps . The odds of being overweight and obese by steps/day and parent-reported time spent television watching were estimated using logistic regression for complex sample s. Results Girls had a lower median steps/day ( 10682 versus 11059 for boys ) and also a narrower variation in steps/day ( interquartile range , 4410 versus 5309 for boys ) . 11 % of children aged 5 - 19 years were classified as obese ; 17 % of boys and girls were overweight . Both boys and girls watched , on average , television between school and dinner on school days . Adjusting for child 's age and sex and parental education , the odds of a child being obese decreased by 20 % for every extra 3000 steps/day and increased by 21 % for every 30 minutes of television watching . There was no association of being overweight with steps/day , however the odds of being overweight increased by 8 % for every 30 minutes of additional time spent watching television between school and dinner on a typical school day . Discussion Television viewing is the more prominent factor in terms of predicting overweight , and it contributes to obesity , but steps/day attenuates the association between television viewing and obesity , and therefore can be considered protective against obesity . In addition to replacing opportunities for active alternative behaviours , exposure to television might also impact body weight by promoting excess energy intake . Conclusions In this large nationally representative sample , pedometer-determined steps/day was associated with reduced odds of being obese ( but not overweight ) whereas each parent-reported hour spent watching television between school and dinner increased the odds of both overweight and obesity",
"Abstract The aim of this study was to investigate the cross-sectional and prospect i ve associations between physical activity and body composition in adolescence . This is a prospect i ve study , including 4,103 adolescents belonging to the Pelotas ( Brazil ) 1993 birth cohort , who were followed up at the mean ages of 11.3 and 14.7 years . Sub sample analyses included 511 individuals with accelerometry and deuterium dilution data at 13.3 years . Sum of skinfolds at age 11.3 years was highly correlated with skinfolds at age 14.7 years ( rho = 0.74 , P Tracking of physical activity was considerably lower , although still significant ; the correlation was 0.24 ( P physical activity and body composition , neither in boys nor in girls . These None results were confirmed in the 511 individuals with accelerometry and deuterium data . We provide evidence of tracking of physical activity and particularly body composition during adolescence . Our results do not support the hypothesis that physical activity and fatness are strongly related in adolescents",
"Purpose Few studies have examined the association between physical activity ( PA ) , measured objective ly , and adolescent depressive symptoms . The aim of this study was to determine whether there is an association between objective measures of PA ( total PA and time spent in moderate and vigorous PA ( MVPA ) ) and adolescent depressive symptoms . Methods Data on 2,951 adolescents participating in ALSPAC were used . Depressive symptoms were measured using the self-report Mood and Feelings Question naire ( MFQ ) ( short version ) . Measures of PA were based on accelerometry . The association between PA and MFQ scores was modelled using ordinal regression . Results Adolescents who were more physically active ( total PA or minutes of MVPA ) had a reduced odds of depressive symptoms [ ORadj total PA ( tertiles ) : medium 0.82 ( 95 % CI : 0.69 , 0.97 ) ; high 0.69 ( 95 % CI : 0.57 , 0.83 ) ] ; ORadj per 15 min MVPA : 0.92 ( 95 % CI : 0.86 , 0.98 ) . In a multivariable model including both total PA and the percentage of time spent in MVPA , total PA was associated with depressive symptoms ( ORadj total PA ( tertiles ) : medium 0.82 ( 95 % CI : 0.70 , 0.98 ) ; high 0.70 ( 95 % CI : 0.58 , 0.85 ) but the percentage of time spent in MVPA was not independently associated with depressive symptoms [ ORadj MVPA ( tertiles ) medium 1.05 ( 95 % CI : 0.88 , 1.24 ) , high 0.91 ( 95 % CI : 0.77 , 1.09 ) ] . Conclusions The total amount of PA undertaken was associated with adolescent depressive symptoms , but the amount of time spent in MVPA , once total PA was accounted for , was not . If confirmed in longitudinal studies and r and omised controlled trials , this would have important implication s for public health messages",
"Background School-based intervention studies promoting a healthy lifestyle have shown favorable immediate health effects . However , there is a striking paucity on long-term follow-ups . The aim of this study was therefore to assess the 3 yr-follow-up of a cluster-r and omized controlled school-based physical activity program over nine month with beneficial immediate effects on body fat , aerobic fitness and physical activity . Methods and Findings Initially , 28 classes from 15 elementary schools in Switzerl and were grouped into an intervention ( 16 classes from 9 schools , n = 297 children ) and a control arm ( 12 classes from 6 schools , n = 205 children ) after stratification for grade ( 1st and 5th grade rs ) . Three years after the end of the multi-component physical activity program of nine months including daily physical education ( i.e. two additional lessons per week on top of three regular lessons ) , short physical activity breaks during academic lessons , and daily physical activity homework , 289 ( 58 % ) participated in the follow-up . Primary outcome measures included body fat ( sum of four skinfolds ) , aerobic fitness ( shuttle run test ) , physical activity ( accelerometry ) , and quality of life ( question naires ) . After adjustment for grade , gender , baseline value and clustering within classes , children in the intervention arm compared with controls had a significantly higher average level of aerobic fitness at follow-up ( 0.373 z-score units [ 95%-CI : 0.157 to 0.59 , p = 0.001 ] corresponding to a shift from the 50th to the 65th percentile between baseline and follow-up ) , while the immediate beneficial effects on the other primary outcomes were not sustained . Conclusions Apart from aerobic fitness , beneficial effects seen after one year were not maintained when the intervention was stopped . A continuous intervention seems necessary to maintain overall beneficial health effects as reached at the end of the intervention . Trial Registration ControlledTrials.com IS RCT",
"Objective To investigate associations between physical activity at age 12 and subsequent adiposity at age 14 . Design Prospect i ve birth cohort study with data collected between 2003 and 2007 . Setting Original recruitment in 1991 - 2 of 14 541 pregnant women living in the former County of Avon ( United Kingdom ) . Participants At age 12 , 11 952 children were invited to attend the research clinic . Of these , 7159 attended , and 4150 ( 1964 boys , 2186 girls ) provided sufficient data on exposure , outcome , and confounding variables . Main outcome measure Fat mass at age 14 , measured by dual emission x ray absorptiometry , associated with physical activity at age 12 , measured by accelerometry . Results Prospect i ve associations of fat mass at age 14 ( outcome ) with physical activity at age 12 ( exposure ) were strong for both total activity ( accelerometer counts/min ) and for daily amount of moderate-vigorous physical activity ( min/day ) . An extra 15 minutes of moderate-vigorous physical activity per day at age 12 was associated with lower fat mass at age 14 in boys ( by 11.9 % ( 95 % confidence interval 9.5 % to 14.3 % ) ) and girls ( by 9.8 % ( 6.7 % to 12.8 % ) ) . The proportion of physical activity due to moderate-vigorous physical activity was between 20 % and 30 % in boys and girls at the two ages . Conclusions Higher levels of physical activity , in particular activity of moderate to higher intensities , are prospect ively associated with lower levels of fat mass in early adolescence . Interventions to raise levels of physical activity in children are likely to be important in the fight against obesity",
"Background In a previous longitudinal analysis of our cohort as 8 to 10 year-olds , insulin resistance ( IR ) increased with age , but was not modified by changes in percent body fat ( % BF ) , and was only responsive to changes in physical activity ( PA ) in boys . We aim ed to determine whether these responses persisted as the children approached adolescence . Methods In this prospect i ve cohort study , 256 boys and 278 girls were assessed at ages 8 , 10 and 12 years for fasting blood glucose and insulin , % BF ( dual energy X-ray absorptiometry ) ; PA ( 7-day pedometers ) , fitness ( multistage run ) ; and pubertal development ( Tanner stage ) . Results From age 8 to 12 years , the median homeostatic model of IR ( HOMA-IR ) doubled in boys and increased 250 % in girls . By age 12 , 23 % of boys and 31 % of girls had elevated IR , as indicated by HOMA-IR greater than 3 . Longitudinal relationships , with important adjustments for covariates body weight , PA , % BF , Tanner score and socioeconomic status showed that , on average , for every 1 unit reduction of % BF , HOMA-IR was lowered by 2.2 % ( 95 % CI 0.04–4 ) in girls and 1.6 % ( 95 % CI 0–3.2 ) in boys . Furthermore , in boys but not girls , HOMA-IR was decreased by 3.5 % ( 95%CI 0.5–6.5 ) if PA was increased by 2100 steps/day . Conclusion Evidence that a quarter of our apparently healthy 12 year-old Australians possessed elevated IR suggests that community-based education and prevention strategies may be warranted . Responsiveness of IR to changes in % BF in both sexes during late preadolescence and to changes in PA in the boys provides a specific basis for targeting elevated IR . That body weight was a strong covariate of IR , independent of % BF , points to the importance of adjusting for weight in correctly assessing these relationships in growing children",
"Objective To assess the effectiveness of a school based physical activity programme during one school year on physical and psychological health in young schoolchildren . Design Cluster r and omised controlled trial . Setting 28 classes from 15 elementary schools in Switzerl and r and omly selected and assigned in a 4:3 ratio to an intervention ( n=16 ) or control arm ( n=12 ) after stratification for grade ( first and fifth grade ) , from August 2005 to June 2006 . Participants 540 children , of whom 502 consented and presented at baseline . Intervention Children in the intervention arm ( n=297 ) received a multi-component physical activity programme that included structuring the three existing physical education lessons each week and adding two additional lessons a week , daily short activity breaks , and physical activity homework . Children ( n=205 ) and parents in the control group were not informed of an intervention group . For most outcome measures , the assessors were blinded . Main outcome measures Primary outcome measures included body fat ( sum of four skinfolds ) , aerobic fitness ( shuttle run test ) , physical activity ( accelerometry ) , and quality of life ( question naires ) . Secondary outcome measures included body mass index and cardiovascular risk score ( average z score of waist circumference , mean blood pressure , blood glucose , inverted high density lipoprotein cholesterol , and triglycerides ) . Results 498 children completed the baseline and follow-up assessment s ( mean age 6.9 ( SD 0.3 ) years for first grade , 11.1 ( 0.5 ) years for fifth grade ) . After adjustment for grade , sex , baseline values , and clustering within classes , children in the intervention arm compared with controls showed more negative changes in the z score of the sum of four skinfolds ( −0.12 , 95 % confidence interval −0.21 to −0.03 ; P=0.009 ) . Likewise , their z scores for aerobic fitness increased more favourably ( 0.17 , 0.01 to 0.32 ; P=0.04 ) , as did those for moderate-vigorous physical activity in school ( 1.19 , 0.78 to 1.60 ; P ( 0.44 , 0.05 to 0.82 ; P=0.03 ) , and total physical activity in school ( 0.92 , 0.35 to 1.50 ; P=0.003 ) . Z scores for overall daily physical activity ( 0.21 , −0.21 to 0.63 ) and physical quality of life ( 0.42 , −1.23 to 2.06 ) as well as psychological quality of life ( 0.59 , −0.85 to 2.03 ) did not change significantly . Conclusions A school based multi-component physical activity intervention including compulsory elements improved physical activity and fitness and reduced adiposity in children . Trial registration Current Controlled Trials IS RCT N15360785",
"BACKGROUND The importance of variation in total volume of physical activity or moderate- to vigorous-intensity physical activity ( MVPA ) to development of body fatness in childhood is unclear , and it is unclear if physical activity has a greater influence on adiposity in boys than girls . PURPOSE To assess relationships between 2-year changes in objective ly measured physical activity , sedentary behavior , and adiposity in English children . METHODS Prospect i ve cohort study , set in Northeast Engl and , of a socioeconomically representative sample of 403 children . Measures were change in accelerometer-determined physical activity and sedentary behavior from age 7 to 9 years ( data collected 2006/2007 and 2008/2009 ; analyzed in 2010 ) and concurrent change in adiposity ( fat mass index derived from bioelectric impedance ) and change in BMI Z-score . RESULTS Decline in MVPA was associated with a greater increase in fat mass index in boys but not girls . Declining MVPA was associated with increased BMI Z-score in boys but not girls . Increased sedentary behavior was not associated with increased BMI Z-score in either gender . CONCLUSIONS Avoiding mid-late childhood reductions in MVPA may reduce excessive fat gain , although such strategies may have greater impact on boys than girls",
"Structural adaptations of bone to changing mechanical loads have recently been documented during adolescence . However , little is known about how bone adapts structurally during the earlier years . Using a longitudinal observational design spanning 6 years of growth ( age range 4 to 12 years ) , we investigated associations between everyday physical activity and hip geometry in a cohort of healthy Midwestern children ( n=468 ) . Femoral neck ( FN ) cross sectional area ( CSA , cm(2 ) ) and FN section modulus ( Z , cm(3 ) ) were used to describe hip geometry . CSA and Z , indices of axial and bending strength , were assessed using dual-energy X-ray absorptiometry ( DXA ) scans and the hip structure analysis ( HSA ) program . Moderate and vigorous physical activity ( MVPA ) was assessed using accelerometry-based activity monitors and calculated as the number of minutes > or = 3000 accelerometry movement counts . Data were analyzed using multilevel ( r and om- and fixed-effects ) regression models with adjustment for age ( year ) , height ( cm ) , and weight ( kg ) or lean mass ( kg ) . For boys and girls , MVPA was a positive independent predictor of CSA and Z ( p MVPA per day would be expected to have 3 % to 5 % greater CSA and Z than peers participating in 10 min of MVPA per day . Ten-minute increases in daily MVPA had similar effects on CSA in girls and Z in boys as did each additional 1 kg of body weight . When lean mass was substituted for weight , MVPA continued to be a positive independent predictor of CSA and Z for boys , but not girls . This study demonstrates that everyday amounts of physical activity in children are associated with indices of FN bone strength during childhood . Differences in lean mass mediate associations between physical activity and hip geometry in girls , but only somewhat in boys . These results suggest that physical activity is an important contributor to bone strength prior to adolescence and that increasing levels of physical activity during childhood are likely to enhance optimal bone strength",
"OBJECTIVE To explore the association between measures of insulin resistance with objective ly assessed physical activity . DESIGN School-based , cross-sectional study . SUBJECTS A r and omly selected sample of 589 children ( 310 girls , 279 boys , mean ( st and ard deviations , s.d . ) age=9.7 ( 0.44 ) y , weight=33.6 ( 6.4 ) kg , height=1.39 ( 0.06 ) m ) from Denmark . METHODS Fasting blood sample s were analysed for serum insulin and glucose . Physical activity was measured with the uniaxial Computer Science and Applications ( CSA ) model 7164 accelerometer , worn for at least 3 days ( > /=10 h day(-1 ) ) . Adiposity was assessed by the sum of four skinfolds . Multiple linear regression were performed to model insulin and glucose from average CSA output , adjusted for age , gender , puberty , ethnicity , birth weight , parental smoking , socioeconomic group , and CSA unit . In addition , we adjusted for skinfold thickness . RESULTS Mean fasting serum glucose ranged from 4.1 to 6.5 mmol l(-1 ) with a mean ( s.d . ) of 5.1 ( 0.37 ) mmol l(-1 ) . Fasting insulin was negatively correlated with CSA output on levels of adjustment . Fasting glucose was not significantly associated with physical activity . However , in girls both indices of insulin resistance were significantly related to activity , whereas in boys none of the associations were significant . CONCLUSION Physical activity is inversely associated with fasting insulin in the nondiabetic range of fasting glucose . The relationship was stronger for insulin than for glucose , indicating compensatory action by the beta cells . Our data emphasise the importance of physical activity in children for the maintenance of metabolic control",
"Purpose . To determine if an existing ballroom dance classroom program meets national recommendations to engage children in moderate to vigorous physical activity ( MVPA ) for ≥ 50 % of class time and to determine class effects on body mass index ( BMI ) . Design . Prospect i ve descriptive study . Setting . Two New York City public schools . Participants . Seventy-nine fourth and fifth grade students . Measurements . The System for Observing Fitness Instruction Time ( SOFIT ) and direct heart rate monitoring were used to determine participants ' MVPA levels during class time . Weight and height were measured to calculate BMI . Analysis . Means were calculated for continuous variables ; frequency counts and percentages were calculated for categorical variables . Change in BMI percentiles was assessed by using Bhapkar 's χ2 test of overall marginal homogeneity . Results . Data from SOFIT observations showed that a mean of 50.0 % and 67.0 % of class time in the first and second halves of the program , respectively , were spent in MVPA . Data from the heart rate monitoring revealed that 71.1 % of students were at ≥ 25 % heart rate reserve , which indicated MVPA for ≥ 50 % of class time . Improvement was seen in BMI percentile ( p = .051 ) . Conclusion . Ballroom dance provides MVPA in elementary school children for ≥ 50 % of class time and has a positive impact on BMI percentiles",
"Studies of youth athletics and interventions have shown some maintenance of bone mineral content ( BMC ; g ) after cessation of training , but less is known about sustained effects of everyday physical activity ( PA ) . Using a prospect i ve cohort , this report examined potential effects of childhood PA on adolescent BMC . Participants ( N=156 boys , 170 girls ) had exams at ages 5 , 13 , and 15 . Body size and maturity were determined using anthropometry . Moderate-to-vigorous-intensity PA ( MVPA ) and vigorous-intensity PA ( Vigorous PA ) were measured using accelerometry . BMC of the spine and hip was measured using dual-energy X-ray absorptiometry . Mixed regression models tested whether PA at age 5 affected BMC at ages 13 and 15 after adjustment for age ( year ) , height ( cm ) , weight ( kg ) , maturity ( pre-peak height velocity or post ) , and activity level ( min/day ) . Analysis was repeated to control for age 5 BMC . On average , boys participated in 59 , 52 , and 38 min of MVPA and 13 , 17 , and 11 min of Vigorous PA at ages 5 , 13 , and 15 , respectively . MVPA ( β=0.799 ) and Vigorous PA ( β=1.338 ) at age 5 predicted later spine BMC ( p . MVPA ( β=0.480 ) at age 5 predicted hip BMC . Girls participated in 47 , 33 , and 26 min of MVPA and 10 , 9 and 7 min of Vigorous PA at ages 5 , 13 , and 15 , respectively . Neither MVPA nor Vigorous PA predicted later spine BMC . MVPA ( β=0.302 ) at age 5 predicted hip BMC . After controlling for BMC at age 5 as well as the other covariates , the effect of MVPA ( β=0.695 ) and Vigorous PA ( β=1.079 ) at age 5 remained significant for boys at the spine . For girls , neither MVPA nor Vigorous PA at age 5 predicted spine or hip BMC . Children 's early PA appears to have a modest effect on adolescent BMC at the critical regions of spine and hip ; benefits may be greater for geometric changes , which future studies should include",
"OBJECTIVE To evaluate the effects of a comprehensive physical activity ( PA ) promotion programme in elementary schools on children 's total PA levels , leisure-time PA , physical fitness and psychosocial correlates of PA . DESIGN A pre-test-post-test design over two school years . SETTING AND SUBJECTS Sixteen elementary schools ( 764 children , mean age : 11.2 + /- 0.7 years ) were r and omly assigned to the intervention condition ( n = 8) and the control condition ( n = 8) . The intervention included a health-related physical education programme , an extracurricular PA promotion programme and classroom-based PA education lessons . In the total sample , leisure-time PA , psychosocial correlates of PA and physical fitness were measured using a PA question naire and the Eurofit test battery . In a sub- sample , total PA levels were measured using an accelerometer . RESULTS According to accelerometer data , children 's moderate PA and moderate-to-vigorous PA ( MVPA ) levels decreased less in the intervention schools than in the control schools ( P average time spent on MVPA decreased by 9 min per day in the intervention schools compared with 33 min per day in the control schools . Children in the intervention schools reported significantly more moderate PA in leisure time than the controls ( P physical fitness and no effects on the psychosocial correlates of PA were found . CONCLUSIONS The comprehensive PA promotion programme was successful in preventing a decline in children 's total activity levels . Furthermore , the intervention increased children 's PA engagement in leisure time . Therefore , implementation needs to be encouraged",
"PURPOSE To examine whether components of body composition ( size , fat mass , and fat-free mass ) were related to physical activity . METHODS A r and om sample of 60 eligible sixth grade girls at each of 36 schools ( six schools per region and six regions in total sample ) ; complete measurements on 1,553 girls . Physical activity was assessed over 6 d in each girl using an accelerometer , and body composition was assessed using a multiple regression equation using body mass index and triceps skinfold . Minutes of moderate-to-vigorous and vigorous physical activity were estimated from accelerometer counts per 30 s above threshold values determined from a previous study . RESULTS Significant inverse relationships were found for all measures of body size and composition and all physical activity indices . The combination of fat and fat-free mass expressed as a weight and as an index ( divided by height squared ) along with race , SES , site , and school were most highly associated with physical activity in multiple regression analysis , accounting for 14 - 15 % of the variance in physical activity . Fat mass was more closely related to moderate-to-vigorous physical activity ( MVPA ) and vigorous physical activity ( VPA ) than fat-free mass with higher st and ardized regression coefficients . CONCLUSION We conclude that both fat mass or fat mass index as well as fat-free mass or fat-free mass index make independent contributions in association with physical activity levels . These indices are recommended for future studies",
"The aim of this study is to examine sedentary and light activity in relation to overweight in adolescent girls . Adolescent girls were r and omly recruited from 36 schools participating in the Trial of Activity for Adolescent Girls ( TAAG ) . Assessment s included age , ethnicity , socioeconomic status , and body composition estimated from weight , height , and triceps skinfold . Sedentary and light activity was measured for 6 days using accelerometry in 6th and in 8th grade among two r and omly sample d cross-sections of girls . Sedentary activity increased from the 6th to 8th grade by 51.5 min/day . In the 8th grade , a significantly higher number of hours in sedentary activity for each of the 6-days of measurement were evident with higher tertiles of percent body fat ( 30 - 35 % , > 35 % fat ) ( P 95th percentiles ) . The increase in sedentary activity was observed on weekdays , but not on weekends for percent body fat tertiles . In the cohort of girls measured in both 6th and 8th grade s , the mean cross-sectional coefficient estimates were significant for percent body fat , but not BMI for sedentary and light activities . Adolescent girls from the 6th to 8th grade are shifting their time from light to more sedentary activity as measured by accelerometers . In addition , the increase in sedentary activity is not associated with an adverse effect on BMI or percent body fat . The eventual impact of this shift to a more sedentary lifestyle on body composition and other outcomes needs to be evaluated further",
"Abstract The purpose of this study was to establish whether an accumulated brisk walking programme , performed during the school day , is effective in changing body composition in primary school children aged 5–11 years . Altogether , 152 participants ( 79 boys and 73 girls ) took part in this repeated- measures intervention study , divided into groups of walkers and controls . The walkers took part in the intervention during school time , which involved brisk walking around the school grounds for 15 min in the morning and afternoon , at least three times a week for 15 weeks . This represented an additional 90 min of moderate physical activity per week . The controls undertook their usual school day activities . Pre- and post-intervention anthropometric and body composition measures were taken . Body fat ( −1.95 ± 2.6 % ) and fat mass ( −0.49 ± 1.0 kg ) were significantly reduced in the walkers after the intervention , whereas the controls showed no significant changes in these measures . Our results show that regular accumulated bouts of brisk walking during the school day can positively affect body composition in primary school children",
"OBJECTIVE We determined the effect of 4-month periods of physical training ( PT ) and detraining on percent fat ( percent fat ) and bone density of children with obesity . RESEARCH METHODS AND PROCEDURES Subjects were 79 7- to 11-year-old children with obesity ; 34 were white , 44 were black , and 1 was Asian , 26 were male and 53 were female . They were r and omly assigned to two groups : group 1 engaged in PT for the first 4 months , while group 2 engaged in PT during the second 4 months . Body composition was measured with dual energy absorptiometry , and diet was measured with 4 days of recall for each 4-month period . PT was offered 5 days/week for 40 minutes/session , heart rate monitors were worn , and no dietary information was given ; mean attendance was 80 % , and mean heart rate per session was 157 bpm . RESULTS Group by time interactions across the three time-points ( from analysis of variance ) were significant for percent fat ( p = bone density ( p = 0.045 ) . Both groups declined in percent fat during the periods of PT , by an average of 1.6 % fat units ; in the 4 months after cessation of PT , group 1 increased by 1.3 % fat . In both groups , bone density increased more during periods of PT ( 0.025 g/cm2 ) than during periods of no PT ( 0.010 g/cm2 ) . No significant PT vs. no-PT differences were found for dietary intake of energy , macronutrients , or calcium . DISCUSSION This study suggests that regular exercise , without dietary intervention , can enhance the body composition of children with obesity",
"UNLABELLED The absence of comparative validity studies has prevented research ers from reaching consensus regarding the application of intensity-related accelerometer cut points for children and adolescents . PURPOSE This study aim ed to evaluate the classification accuracy of five sets of independently developed ActiGraph cut points using energy expenditure , measured by indirect calorimetry , as a criterion reference st and ard . METHODS A total of 206 participants between the ages of 5 and 15 yr completed 12 st and ardized activity trials . Trials consisted of sedentary activities ( lying down , writing , computer game ) , lifestyle activities ( sweeping , laundry , throw and catch , aerobics , basketball ) , and ambulatory activities ( comfortable walk , brisk walk , brisk treadmill walk , running ) . During each trial , participants wore an ActiGraph GT1 M , and V˙O2 was measured breath-by-breath using the Oxycon Mobile portable metabolic system . Physical activity intensity was estimated using five independently developed cut points : Freedson/Trost ( FT ) , Puyau ( PU ) , Treuth ( TR ) , Mattocks ( MT ) , and Evenson ( EV ) . Classification accuracy was evaluated via weighted κ statistics and area under the receiver operating characteristic curve ( ROC-AUC ) . RESULTS Across all four intensity levels , the EV ( κ=0.68 ) and FT ( κ=0.66 ) cut points exhibited significantly better agreement than TR ( κ=0.62 ) , MT ( κ=0.54 ) , and PU ( κ=0.36 ) . The EV and FT cut points exhibited significantly better classification accuracy for moderate- to vigorous-intensity physical activity ( ROC-AUC=0.90 ) than TR , PU , or MT cut points ( ROC-AUC=0.77 - 0.85 ) . Only the EV cut points provided acceptable classification accuracy for all four levels of physical activity intensity and performed well among children of all ages . The widely applied sedentary cut point of 100 counts per minute exhibited excellent classification accuracy ( ROC-AUC=0.90 ) . CONCLUSIONS On the basis of these findings , we recommend that research ers use the EV ActiGraph cut points to estimate time spent in sedentary , light- , moderate- , and vigorous-intensity activity in children and adolescents",
"OBJECTIVES Examine : ( 1 ) the anthropometric , socio-demographic and use-of-time characteristics of thin adolescents , and ( 2 ) compare these characteristics to other weight status categories . METHODS Data were from the 2007 National Children 's Nutrition and Physical Activity Survey which collected data on a r and om sample of 2200 9 to 16 year old Australians from February to August 2007 . Seven socio-demographic variables , anthropometric data ( height and weight were measured ) and nine use-of-time variables were used , and compared across the weight status categories . Physical activity was measured using pedometers and the Multimedia Activity Recall for Children and Adults . RESULTS 5.3 % of adolescents were classified as thin , a percentage which did not significantly vary by age , sex , indigenous status , household income , education level or family structure . Relative to other adolescents , thin adolescents were shorter and lighter . Thin adolescents were less active than their normal weight peers , but walked further and accumulated significantly less screen and TV time than obese adolescents . CONCLUSION Thin adolescents were found in similar proportions across all socio-demographic b and s. Thin adolescents recorded similar physical activity levels to their normal weight peers , but were more active than obese adolescents . The findings from the study support in part the theory of thinness related developmental delay",
"OBJECTIVE To evaluate the impact of a multi-component school-based physical activity intervention ( Fit-4-Fun ) on health-related fitness and objective ly measured physical activity in primary school children . METHODS Four Hunter primary schools were recruited in April , 2011 and r and omized by school into treatment or control conditions . Participants included 213 children ( mean age = 10.72 years ± 0.6 ; 52.2 % female ) with the treatment group ( n = 118 ) completing the 8-week Fit-4-Fun Program . Participants were assessed at baseline and 6-month follow-up , with a 91 % retention rate . Cardio-respiratory fitness ( CRF ) ( 20 m shuttle run ) was the primary outcome , and secondary outcomes included body composition ( BMI , BMI ( Z ) ) , muscular fitness ( 7-stage sit-up test , push-up test , basketball throw test , St and ing Jump ) , flexibility ( sit and reach ) and physical activity ( 7 days pedometry ) . RESULTS After 6-months , significant treatment effects were found for CRF ( adjusted mean difference , 1.14 levels , p 0.001 ) , body composition ( BMI mean , -0.96 kg/m(2 ) , p BMI z-score mean -0.47 z-scores , p ) , flexibility ( sit and reach mean , 1.52 cm , p = 0.0013 ) , muscular fitness ( sit-ups ) ( mean 0.62 stages , p = 0.003 ) and physical activity ( mean , 3253 steps/day , p primary school-based intervention focusing on fitness education significantly improved health-related fitness and physical activity levels in children",
"Abstract The purpose of this study was to investigate by direct measurement the cross-sectional relationship between accelerometer-measured physical activity and peak oxygen uptake ( [Vdot]O2peak : ml · min−1 · kg−1 ) , in a population -based cohort of young children , since such data are scarce . The study included 468 children ( 246 boys , 222 girls ) aged 6.7 ± 0.4 years , recruited from a population -based cohort . Peak oxygen uptake was measured by indirect calorimetry during a maximal treadmill exercise test . Physical activity was assessed by accelerometers over a 4-day period . Minutes of sedentary , light , moderate , moderate-to-vigorous , and vigorous activity per day were calculated . Mean counts per minute were considered to reflect total physical activity . Pearson correlation coefficients indicated a weak relationship between daily physical activity variables and [Vdot]O2peak in boys ( r = 0.15–0.28 , P sedentary and light activity , which was not related to [Vdot]O2peak . None of the daily physical activity variables were related to [Vdot]O2peak in girls , with the exception of a very weak relationship for moderate activity ( r = 0.14 , P in [Vdot]O2peak in boys . In this population -based cohort , most daily activity variables were positively related to aerobic fitness in boys , whereas less clear relationships were observed in girls . Our finding that physical activity was only uniformly related to aerobic fitness in boys partly contradicts previous studies in older children and adolescents"
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Background There are plausible mechanisms whereby leisure time physical activity may protect against low back pain ( LBP ) but there have been no quality systematic review s and meta-analyses of the subject . Objective This review aims to assess the effect of leisure time physical activity on non-specific LBP . Methods Literature search es were conducted in PubMed , Embase , Web of Science , Scopus and Google Scholar data bases from their inception through July 2016 . Method ological quality of included studies was evaluated . A r and om-effects meta- analysis was performed , and heterogeneity and publication bias were assessed . Results Thirty-six prospect i ve cohort studies ( n=158 475 participants ) qualified for meta-analyses . Participation in sport or other leisure physical activity reduced the risk of frequent or chronic LBP , but not LBP for > 1 day in the past month or past 6–12 months . Risk of frequent/chronic LBP was 11 % lower ( adjusted risk ratio (RR)=0.89 , CI 0.82 to 0.97 , I2=31 % , n=48 520 ) in moderately/highly active individuals , 14 % lower ( RR=0.86 , CI 0.79 to 0.94 , I2=0 % , n=33 032 ) in moderately active individuals and 16 % lower ( RR=0.84 , CI 0.75 to 0.93 , I2=0 % , n=33 032 ) in highly active individuals in comparison with individuals without regular physical activity . For LBP in the past 1–12 months , adjusted RR was 0.98 ( CI 0.93 to 1.03 , I2=50 % , n=32 654 ) for moderate/high level of activity , 0.94 ( CI 0.84 to 1.05 , I2=3 % , n=8549 ) for moderate level of activity and 1.06 ( CI 0.89 to 1.25 , I2=53 % , n=8554 ) for high level of activity . Conclusions Leisure time physical activity may reduce the risk of chronic LBP by 11%–16 % . The finding , however , should be interpreted cautiously due to limitations of the original studies . If this effect size is proven in future research , the public health implication s would be substantial
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"Data from a community-based four-year prospect i ve study were used to test the hypothesis that heavy physical work is a stronger predictor of low back pain in smokers than in non-smokers . Of 708 working responders without low back pain during the entire year prior to 1990 , 562 ( 79 % ) completed a question naire four years later in 1994 . A job involving heavy lifting and much st and ing in 1990 was a strong predictor of low back pain in smokers four years later [ odds ratio ( OR ) = 5.53 , 95 % confidence interval ( CI ) = 1.93 - 15.84 , p heavy lifting and much st and ing was not associated with low back pain . One explanation may be that smoking leads to reduced perfusion and malnutrition of tissues in or around the spine and causes these tissues to respond inefficiently to mechanical stress",
"OBJECTIVES To identify risk factors for back pain leading to restricted activity ( restricting back pain ) in older persons . DESIGN Prospect i ve cohort study . SETTING Greater New Haven , Connecticut . PARTICIPANTS A total of 731 men and women aged 70 years or older , who were community living and nondisabled in essential activities of daily living at baseline . MEASUREMENTS C and i date risk factors were ascertained every 18 months for 108 months during comprehensive home-based assessment s. Restricting back pain was assessed during monthly telephone interviews for up to 126 months . Incident episodes of ( 1 ) short-term ( 1 episode lasting 1 month ) restricting back pain ; and ( 2 ) persistent ( 1 episode lasting 2 or more months ) or recurrent ( 2 or more episodes of any duration ) restricting back pain were determined during each 18-month interval . The associations between the c and i date risk factors and short-term and persistent/recurrent restricting back pain , respectively , were evaluated using a multivariable Cox model . RESULTS The cumulative incidence was 21.3 % ( 95 % confidence interval [ CI ] 19.6%-23.1 % ) for short-term restricting back pain and 20.6 % ( CI 18.6%-22.9 % ) for persistent/recurrent restricting back pain over a median follow-up of 109 months . In a recurrent event multivariable analysis , female sex ( hazard ratio [ HR ] 1.30 ; 1.07 - 1.58 ) , weak grip strength ( HR 1.24 ; 1.01 - 1.52 ) , and hip weakness ( HR 1.19 ; 1.07 - 1.32 ) were independently associated with an increased likelihood of having short-term restricting back pain , whereas female sex ( HR 1.48 ; CI 1.13 - 1.94 ) , depressive symptoms ( HR 1.57 ; 1.23 - 2.00 ) , 2 or more chronic conditions ( HR 1.38 ; 1.08 - 1.77 ) , and arthritis ( HR 1.66 ; 1.31 - 2.09 ) were independently associated with persistent/recurrent restricting back pain . CONCLUSION In this prospect i ve study , several factors were independently associated with restricting back pain , including some that may be modifiable and therefore potential targets for interventions to reduce this common and often recurrent condition in older persons",
"OBJECTIVE All occupations expose workers to varied and unique conditions . The nature of work has been recognized as influencing the health of workers . Whether predictors for chronic neck and low back pain would be occupation-specific is unknown . This study aim ed to identify predictors for chronic neck and low back pain in a cohort of office workers . METHODS A prospect i ve study was carried out among 669 healthy office workers . At baseline , risk factors were assessed using a question naire and st and ardized physical examination . A symptomatic case was defined as an individual who reported pain greater than 30 mm on a 100-mm VAS , and chronic pain was defined as experiencing ongoing neck or low back pain for greater than 3 months over the past 6 months . Two regression models were built to analyze the risk factors for developing chronic neck and low back pain . RESULTS Of the sample , 17 and 27 % of office workers who reported a new onset of neck or low back pain developed chronicity , respectively . Predictors for chronic neck pain were high body mass index , frequent neck extension during the work day , high initial pain intensity , and high psychological job dem and s. The development of chronic low back pain was associated with history of low back pain and high initial pain intensity . CONCLUSIONS The findings suggest that predictors for chronic musculoskeletal pain in a sub population may be a subset of predictors identified in a general population or occupation specific . Successful management to prevent chronic musculoskeletal pain may also need to consider the patient 's occupation",
"BACKGROUND CONTEXT Association between low physical fitness and low back pain ( LBP ) is contradictory in previous studies . PURPOSE The objective of the present prospect i ve cohort study was to investigate the predictive associations of various intrinsic risk factors in young conscripts for LBP , with special attention to physical fitness . STUDY DESIGN A prospect i ve cohort study . PATIENT SAMPLE A representative sample of Finnish male conscripts . In Finl and , military service is compulsory for male citizens and 90 % of young men enter into the service . OUTCOME MEASURES Incidence of LBP and recurrent LBP prompting a visit at the garrison health clinic during 6-month military training . METHODS Four successive cohorts of 18- to 28-year-old male conscripts ( N=982 ) were followed for 6 months . Conscripts with incidence of LBP were identified and treated at the garrison clinic . Predictive associations between intrinsic risk factors and LBP were examined using multivariate Cox proportional hazard models . RESULTS The cumulative incidence of LBP was 16 % , the incidence rate being 1.2 ( 95 % confidence interval [ CI ] , 1.0 - 1.4 ) per 1,000 person-days . Conscripts with low educational level had increased risk for incidence of LBP ( hazard ratio [ HR ] , 1.6 ; 95 % CI , 1.1 - 2.3 ) . Conscripts with low dynamic trunk muscle endurance and low aerobic endurance simultaneously ( ie , having coimpairment ) at baseline also had an increased risk for incidence of LBP . The strongest risk factor was coimpairment of trunk muscular endurance in tests of back lift and push-up ( HR , 2.8 ; 95 % CI , 1.4 - 5.9 ) . CONCLUSIONS The increased risk for LBP was observed among young men who had a low educational level and poor fitness level in both muscular and aerobic performance",
"Purpose To investigate whether depression symptomatology is associated with low back pain ( LBP ) in twins aged 70 + and whether this effect depends on a person ’s physical activity ( PA ) status . Methods This prospect i ve cohort and nested case – control study used a nationally representative sample of twins . Data on depression symptomatology ( modified Cambridge Mental Disorders Examination ) and self-reported PA were obtained from the Longitudinal Study of Aging Danish Twins using twins without LBP at baseline . Associations between depression symptomatology ( highest quartile ) at baseline and LBP two years later were investigated using logistic regression analyses adjusted for sex . To examine the moderating effect of PA , we tested its interaction with depression . Associations were analysed using the complete sample of 2446 twins and a matched case – control analysis of 97 twin pairs discordant for LBP at follow-up . Odds ratios ( OR ) with 95 % confidence intervals ( CI ) were calculated . Results Using the whole sample , high depression scores were associated with an increased probability of LBP ( OR 1.56 , 95 % CI 1.22–1.99 , P ≤ 0.01 ) . There was no statistically significant interaction of light PA and depression symptomatology ( OR 0.78 , 95 % CI 0.46–1.35 , P = 0.39 ) and strenuous PA and depression symptomatology ( 0.84 , 95 % CI 0.50–1.41 , P = 0.51 ) . The case – control analysis showed similar ORs , although statistically insignificant . Conclusions High depression symptomatology predicted incident LBP . This effect is supposedly not attributable to genetic or shared environmental factors . Physical activity did not moderate the effect of depression symptomatology on LBP",
"STUDY OBJECTIVE : To explore the previously stated hypothesis that risk factors for atherothrombotic disease are associated with back pain . DESIGN : Prospect i ve ( mean of four years of follow up ) and retrospective analyses using two main outcome measures : ( a ) short ( or = 7 days ) and long ( > 7 days ) spells of sickness absence because of back pain reported separately in men and women ; ( b ) consistency of effect across the result ing four duration of spell and sex cells . SETTING : 14 civil service departments in London . PARTICIPANTS : 3506 male and 1380 female white office-based civil servants , aged 35 - 55 years at baseline . MAIN RESULTS : In age adjusted models , low apo AI was associated with back pain across all four duration -sex cells and smoking was associated across three cells . Six factors were associated with back pain in two cells : low exercise and high BMI , waist-hip ratio , triglycerides , insulin and Lp(a ) . On full adjustment ( for age , BMI , employment grade and back pain at baseline ) , each of these factors retained a statistically significant effect in at least one duration -sex cell . Triglycerides were associated with short and long spells of sickness absence because of back pain in men in fully adjusted models with rate ratios ( 95 % confidence intervals ) of 1.53 ( 1.1 , 2.1 ) and 1.75 ( 1.0 , 3.2 ) respectively . There was little or no evidence of association in age adjusted models with : fibrinogen , glucose tolerance , total cholesterol , apoB , hypertension , factor VII , von Willebr and factor , electrocardiographic evidence of coronary heart disease and reported angina . CONCLUSIONS : In this population of office workers , only modest support was found for an atherothrombotic component to back pain sickness absence . However , the young age of participants at baseline and the lack of distinction between different types of back pain are likely to bias the findings toward None . Further research is required to ascertain whether a population sub-group of atherothrombotic back pain can be identified",
"Introduction . The aim of the present study was to determine the closeness of agreement between a self-reported and an objective measure of physical activity in low back pain patients and healthy controls . Beyond , influencing factors on overestimation were identified . Methods . 27 low back pain patients and 53 healthy controls wore an accelerometer ( objective measure ) for seven consecutive days and answered a question naire on physical activity ( self-report ) over the same period of time . Differences between self-reported and objective data were tested by Wilcoxon test . Bl and -Altman analysis was conducted for describing the closeness of agreement . Linear regression models were calculated to identify the influence of age , sex , and body mass index on the overestimation by self-report . Results . Participants overestimated self-reported moderate activity in average by 42 min/day ( p = 0.003 ) and vigorous activity by 39 min/day ( p Self-reported sedentary time was underestimated by 122 min/day ( p overestimation of physical activity . Low back pain patients were more likely to underestimate sedentary time compared to healthy controls . Discussion . In rehabilitation and health promotion , the application-oriented measurement of physical activity remains a challenge . The present results contradict other studies that had identified an influence of age , sex , and body mass index on the overestimation of physical activity",
"Study Design . Prospect i ve cohort study of twins . Objectives . To investigate associations between physical activity , physical function , and incident low back pain ( LBP ) in an elderly population . Summary of Background Data . The relationship between an active lifestyle and LBP in seniors is unknown . Methods . Participants in the population -based Longitudinal Study of Aging Danish Twins free from LBP at baseline ( no LBP during the past month ) were included , and interview data on physical activity , overall physical function , and LBP at baseline and follow-up were obtained . Associations between levels of physical activity and LBP were estimated using logistic regression for the entire cohort , and using a matched case-control design for twin pairs discordant for physical activity . Absolute risk and relative risks for incident LBP in relation to physical activity were calculated for participants with higher or lower than average physical function at baseline . Absolute risk for LBP was also calculated for participants based on whether they remained active or inactive between baseline and follow-up or changed activity level . Results . A total of 1387 persons aged 70–100 at baseline were included in the analyses , including 86 twin pairs discordant for physical activity at baseline . In the total sample , 83 % were engaged in light physical activity , and 42 % of men and 35 % of women were engaged in strenuous physical activity at least weekly . Being engaged in strenuous physical activity at baseline was strongly protective in relation to both having had any LBP ( odds ratio 0.21 , 95 % confidence interval 0.12–0.37 for intra-pair analysis ) and having had LBP lasting more than 30 days altogether during the past year at follow-up ( odds ratio 0.08 , 95 % confidence interval 0.03–0.18 for intra-pair analysis ) . Statistically significant dose-response associations between increasing frequency of strenuous physical activity and magnitude of this protective effect were found . Participants with poor initial physical function experienced the strongest protective effect of strenuous physical activity . Finally , LBP does not appear to be an important factor affecting whether participants remained engaged in strenuous physical activity at baseline and follow-up or vice versa . Conclusions . Strenuous physical activity at least once a week is protective for incident LBP in seniors",
"Background The association between leisure time physical activity and low back pain in young adults is unclear and is in the need of prospect ively obtained evidence . This study examined the course of low back pain and the association between low back pain and leisure time physical activity in a cohort of young adults in their transition from school to working life . Methods Both low back pain and leisure time physical activity was monitored over a 6.5 year period in 420 subjects starting out as students within hairdressing , electrical installation and media/ design . The association between physical activity and low back pain was investigated through the follow-up period by using linear mixed models analysis . Results Low back pain was significantly influenced by time and overall there was a decreasing trend of low back pain prevalence throughout the follow-up . Analysis showed a weak trend of decreasing low back pain with moderate/high physical activity levels , but this association was not significant . Conclusions Low back pain decreased during follow-up with baseline as reference . Findings in our study did show non-significant trends of reduced low back pain with increased leisure time physical activity . Still , we could not support the theory of moderate/high levels of physical activity acting protective against low back pain in young adults entering working life . Our results , in combination with previous relevant research , can not support a clear relationship between physical activity and low back pain for young adults . Thus , recommendations regarding effect of physical activity on reducing low back pain for this group are not clear",
"BACKGROUND CONTEXT The available evidence regarding low back pain ( LBP ) incident episodes is not consistent . Such knowledge can add information for the potential contribution of preventive programs . PURPOSE a ) To evaluate annual incident episodes of LBP among the general population . b ) To evaluate the contribution of demographic , lifestyle , and back pain history to LBP incident episodes . STUDY DESIGN A community-based longitudinal study . PATIENT SAMPLE A r and omized sample of individuals , free of LBP at a previous cross-sectional survey . OUTCOME MEASURES Low back pain during the past year . METHODS Subjects were followed up after 1 year . Baseline data included back pain history , perception of general health , physical activity , smoking , work satisfaction , and demographic characteristics . RESULTS Annual incident episodes of LBP were 18.4 % . Those who experienced LBP during the past year had a lower baseline perception of general health and were less involved in sporting activities than those free of pain . Those without history of LBP were more likely to be free of back pain after 1 year . CONCLUSIONS The annual incident episodes of LBP are relatively high and relate indirectly to baseline perception of general health and to level of sporting activities . Those without history of LBP are more likely to be free of back pain after 1 year . These results raise the potential of LBP preventive programs for adult population",
"STUDY DESIGN A prospect i ve population -based cohort study performed in South Manchester , United Kingdom . OBJECTIVES To determine whether nonoccupational physical activity and indicators of physical stress on the spine predict low back pain in the short term . SUMMARY OF BACKGROUND DATA There is evidence that physical activity outside the workplace helps to protect against low back pain in the long term . However , such activity may injure or stress the spine in the short term . METHODS A baseline survey question naire identified 2715 adults , aged 18 - 75 years , with no low back pain at the time of the survey . Information on potential predictors of low back pain also was obtained . New episodes of back pain were identified during the subsequent year . RESULTS A new low back pain episode occurred in 34 % of men and 37 % of women . Poor general health at baseline was the strongest predictor of a new episode of pain ( men : relative risk ( RR ) 1.5 , 95 % confidence intervals ( CI ) 0.8 , 2.7 ; women : RR 2.2 , 95 % CI 1.2 , 4.0 ) . High weight was associated with subsequent low back pain in women ( RR 1.4 ; 95 % CI 1.0 , 2.0 ) , but neither height nor weight predicted low back pain in men . A self-rated low level of physical activity was not consistently linked with subsequent low back pain , nor were specific nonoccupational physical activities , apart from home-improvement work in men and regular sports in women . CONCLUSION Although some specific activities may be hazardous to the back , physical activity outside the workplace does not increase the short-term risk of low back pain overall . Leisure-time physical activity is not a hazard to the back , whereas poor physical health in both genders and heavier weight in women do increase the risk of new low back pain episodes in the short term",
"BACKGROUND Low back pain is common among nurses . Previous studies have shown that the risk of low back pain increases rapidly with greater amounts of physical work and psychological stress , but is inversely related to leisure activities . However , these previous studies were predominantly retrospective in design and not many took account of three factors simultaneously . AIMS This 12-month prospect i ve study examined the relationships between work activities , work stress , sedentary lifestyle and new low back pain . METHODS A total of 144 nurses from six Hong Kong district hospitals completed a face-to-face baseline interview , which was followed-up by a telephone interview . The main study measures were demographic characteristics , work activities , work stress , physical leisure activities and the nature of new low back pain during the 12-month follow-up period . Level of work stress , quality of relationships at work , level of enjoyment experienced at work , and work satisfaction were self-reported . RESULTS Fifty-six ( 38.9 % ) nurses reported experiencing new low back pain . Sedentary leisure time activity was not associated with new low back pain . Being comparatively new on a ward ( adjusted relative risk 2.90 ) , working in bending postures ( adjusted relative risk 2.76 ) and poor work relationships with colleagues ( adjusted relative risk 2.52 ) were independent predictors of new low back pain . CONCLUSION The findings of this study suggest that low back pain is a common problem in the population of nurses in Hong Kong . Being comparatively new on a ward , bending frequently during work and having poor work relationships with colleagues are independent predictors of new low back pain . Training for high-risk work activities and ergonomic assessment of awkward work postures are essential . Moreover , relaxation and team-building workshops for nurses , especially those who are less experienced in the type of work on their current ward , are recommended",
"BACKGROUND The evidence on the impact of physical activity on back pain in children and adolescents has been contradicting . It has also been shown that the physical activity can not accurately be estimated in children using question naires . PURPOSE The aim of this study was to establish if physical activity in childhood had any impact on back pain reporting in early adolescence ( 3 years later ) , using an objective instrumental measurement of physical activity . STUDY DESIGN Prospect i ve cohort study . PATIENT SAMPLE Representative r and om sample of Danish children from the city of Odense sample d at age 9 years and followed-up at age 12 years . OUTCOME MEASURES The 1-month period prevalence of back pain ( neck pain , mid back pain , and low back pain ) was established using a structured interview . METHODS Physical activity was assessed with the MTI-accelerometer . The accelerometer provides a minute-by-minute measure of the physical activity performed . An overall measure of physical activity and time spent in high activity were studied in relation to back pain using logistic regression . The analyses were performed on the total sample and then stratified on back pain ( yes/no ) at baseline . RESULTS High physical activity ( HPA ) levels seem to protect against future low back pain and appear to actually \" treat \" and reduce the odds of future mid back pain . When comparing the least active children to the most active children , the least active had a multivariate odds ratio of 3.3 of getting low back pain and 2.7 of getting mid back pain 3 years later . When stratified on back pain at baseline , this effect on mid back pain was especially noticeable in children who had had mid back pain already at baseline , with an odds ratio of 7.2 . CONCLUSIONS HPA in childhood seems to protect against low back pain and mid back pain in early adolescence . Larger prospect i ve studies with repetitive follow-ups and preferably intervention studies should be performed , to see if these findings can be reproduced",
"OBJECTIVES This study examined predictors of low back pain onset in a British birth cohort . METHODS Univariate and multivariate analyses focused on individuals who experienced onset of low back pain at 32 to 33 years of age ( n= 571 ) and individuals who were pain free ( n = 5210 ) . Participants were members of the 1958 British birth cohort . RESULTS Incident pain was elevated among those with psychological distress at 23 years of age ( adjusted odds ratio [ OR ] = 2.52 , 95 % confidence interval [ CI ] = 1.65 , 3.86 ) and among persistent moderate or heavy smokers ( adjusted OR = 1.63 , 95 % CI = 1.23 , 2.17 ) . Significant univariate associations involving other factors ( e.g. , social class , childhood emotional status , body mass index , job satisfaction ) did not persist in multivariate analyses . CONCLUSIONS This prospect ively studied cohort provides evidence that psychological distress more than doubles later risk of low back pain , with smoking having a modest independent effect . Other prospect i ve studies are needed to confirm these findings before implication s for low back pain prevention can be assessed",
"UNLABELLED The aim of this study was to examine whether treatments based on different theories change pain catastrophizing and internal control of pain , and whether changes in these factors mediate treatment outcome . Participants were 211 patients with nonspecific chronic low back pain ( CLBP ) participating in a r and omized controlled trial , attending active physical treatment ( APT , n = 52 ) , cognitive-behavioral treatment ( CBT , n = 55 ) , treatment combining the APT and CBT ( CT , n = 55 ) , or waiting list ( WL , n = 49 ) . Pain catastrophizing decreased in all 3 active treatment groups and not in the WL . There was no difference in the change in internal control across all 4 groups . In all the active treatment groups , patients improved regarding perceived disability , main complaints , and current pain at post-treatment , and no changes were observed in the WL group . Depression only changed significantly in the APT group . Change in pain catastrophizing mediated the reduction of disability , main complaints , and pain intensity . In the APT condition , pain catastrophizing also mediated the reduction of depression . Not only cognitive-behavioral treatments but also a physical treatment produced changes in pain catastrophizing that seemed to mediate the outcome of the treatment significantly . The implication s and limitations of these results are discussed . PERSPECTIVE This article shows that treatment elements that do not deliberately target cognitive factors can reduce pain catastrophizing . Reduction in pain catastrophizing seemed to mediate the improvement of functioning in patients with chronic low back pain . The results might contribute to the development of more effective interventions",
"Summary Physical and psychological work‐related factors pertaining to the 5‐year incidence of multiple body sites musculoskeletal pain ( MSP ) may be gender specific . In particular , psychological factors seem to be predictive of onset of MSP , but only in women . Only the physical work factor ( ie , forceful effort constraints ) was an important robust predictor of multisite MSP , but only in men . ABSTRACT The role of psychosocial and physical factors in the development of musculoskeletal pain ( MSP ) has now been clearly demonstrated . However , it is unclear whether these factors contribute to specific regional MSP or to multisite pain . The main goal of this study was to assess the impact of work‐related factors according to gender on the development of regional and multisite MSP . A total of 12,591 subjects ( 65 % men and 35 % women ) who were born in 1938 , 1943 , 1948 , and 1953 and were participating in a French longitudinal prospect i ve epidemiological survey ( ESTEV ) in 1990 to 1995 were eligible . Personal factors and work exposure were assessed by self‐administered question naires . Statistical associations between chronic MSP ( regional body site or multisite ) , personal factors , and occupational factors were analyzed using logistic regression modeling . The incidence of regional MSP and multisite pain in 1995 were , respectively , 17 % and 25.6 % . For women , highly repetitive movements predicted neck/shoulder pain ; posture and vibrations predicted arm and low back pain ; and effort with tools predicted arm pain . For men , forceful effort and vibrations predicted neck/shoulder pain ; posture and forceful effort predicted lower limb and low back pain ; and forceful effort and effort with tools predicted arm pain . Physical constraints ( ie , forceful effort or vibrations ) were associated with multisite pain in both genders . Only for women , psychological factors were risk factors predictive of upper limb pain and in 3 or 4 painful anatomical sites . These results support the hypothesis that some physical and psychological work‐related factors are predictive of regional or multisite MSP but differ according to gender . Gender differences and risk factors for work‐related musculoskeletal pain should be also taken into account to more effectively target preventive measures",
"OBJECTIVES Risk factors for low-back pain are known to co-occur , but their joint effect has not often been studied . Little is also known about the variation of the risk factors or their effects with age . METHODS This prospect i ve study assessed the 1-year incidence of low-back pain by age group in a Finnish industrial population . The effects of the baseline variables on the risk of low-back pain in the follow-up were estimated with a log-binomial regression . RESULTS Among 2256 blue- and white-collar workers free of low-back pain 12 months preceding the baseline , 21 % reported low-back pain after 1-year of follow-up . Physical work load ( sum of heavy lifting , awkward postures , and whole-body vibration ) predicted low-back pain among those younger than 50 years [ highest relative risk ( RR ) 2.4 , 95 % confidence interval ( 95 % CI ) 1.4 - 4.2 ] , whereas health behavior ( sum of smoking , overweight , and lack of physical exercise ) increased the risk only among those 50 years or older ( RR up to 2.8 , 95 % CI 1.4 - 5.4 ) . Mental stress , dissatisfaction with life , and sleep problems were significant predictors in the group of 40- to 49-year-old workers . Work-related psychosocial factors were not associated with the outcome . CONCLUSIONS In this study , workers of different ages were affected by slightly different risk factors . The results support the provision of health promotion and stress management as part of programs to prevent work-related low-back pain . In particular , aging workers may benefit from such an integrated approach . More prospect i ve studies on the joint effects of age-specific risk factors of low-back pain are warranted",
"BACKGROUND The long-term course of long-st and ing low back pain is largely unknown since long-term data are scarce . OBJECTIVE We examined the course of self-reported low back pain in the prospect i ve population -based Doetinchem cohort over a period of 10years . METHODS Between 1993 and 2007 , around 5700 r and omly selected men and women in four age groups of originally 20 - 29 , 30 - 39 , 40 - 49 , 50 - 59years were measured three times . Logistic regression analysis was used to study the association of sociodemographic ( gender , age , education , work status ) and lifestyle characteristics ( BMI , smoking , physical activity ) with persistent and new episodes of long-st and ing low back pain . RESULTS The prevalence of long-st and ing low back pain is quite stable over a 10year period , approximately 20 % on population level . On individual level , around 30 % of the population was completely free of low back pain during the entire period , 6 % can be characterized as persistent back pain sufferers . Individuals with persistent and a varying pattern have a more unhealthy lifestyle ( BMI and smoking ) than those without low back pain . Age , smoking , obesity and not having a paid job are associated with 10-year persistent back pain in the general population , whereas age and not having a paid job are associated in those with long-lasting back pain at baseline . New episodes of long-st and ing back pain are relatively frequent among women and smokers . CONCLUSIONS Low back pain in the population is characterized as very dynamic which challenges epidemiological studies highly . Long-term information on the course of back pain is needed to define severe subgroups",
"Study Design . A prospect i ve cohort study . Objective . To study if low level of physical fitness was associated with increased low back pain ( LBP ) intensity at 30-month follow-up . Summary of Background Data . The evidence of low physical fitness as a risk factor for LBP is inconclusive due to contradictory results . Methods . Study participants were 327 employees ( women = 271 , men = 56 ) at institutions for physically and mentally disabled persons . Physical fitness was measured by tests of : back extension and flexion endurance , flexibility and balance ; and by self-assessed aerobic fitness , muscle strength , endurance , flexibility and balance , using visual analogue scales . Low back pain , lifestyle parameters , and physical and psychosocial work factors were assessed by question naires at baseline and at follow-up . Outcome was defined as an increase above 2 steps in average LBP intensity during the previous year ( 0–10 ) . Results . Persons with low level back endurance showed an insignificantly higher risk of increased LBP intensity ( OR = 2.4 , P = 0.076 ) , whereas persons with medium level back endurance were at significantly higher risk ( OR = 2.7 , P = 0.034 ) compared with those with high level back endurance . The general association between isometric back extension endurance and increased LBP intensity was insignificant ( P = 0.067 ) . Persons with medium level self-assessed aerobic fitness were at lower risk of increased LBP intensity compared with those with high level ( OR = 0.37 , P = 0.02 ) , although the general association of aerobic fitness was insignificant ( 0.066 ) . Performance-based back flexion endurance , flexibility , and balance ; and self-assessed muscle strength , endurance , flexibility , and balance were not associated with increased LBP intensity . Conclusion . The significant association between medium level back extension endurance and increased LBP intensity supports the finding of other studies that particularly back extension endurance is an important physicalfitness component in preventing LBP and that the subcomponents of physical fitness are related in different ways to LBP",
"Objective : Quantify the relationship between physical activity and development of incident low back pain ( LBP ) . Methods : This nested prospect i ve cohort study utilized an objective measure of physical activity in 68 participants with 30 incident cases of LBP . Physical activity was divided into tertiles and quartiles . Univariate and multivariate relative risks and hazard ratios were calculated . Results : Comparing highest to middle tertile of light activity demonstrated a statistically significant relative risk of 3.68 for developing incident LBP . Lowest and highest tertile of minutes of moderate/vigorous activity yielded statistically significant relative risks of 4.60 and 6.14 , respectively . Multivariate analyses demonstrated similar associations . Conclusions : Moderate amounts of physical activity were protective for the development of LBP in this cohort , after adjustment for risk factors . This nonlinear relationship suggests higher levels of activity do not confer increased LBP prevention",
"Chronic musculoskeletal pain constitutes a large socioeconomic challenge , and preventive measures with documented effects are warranted . The authors ' aim in this study was to prospect ively investigate the association between physical exercise , body mass index ( BMI ) , and risk of chronic pain in the low back and neck/shoulders . The study comprised data on approximately 30,000 women and men in the Nord-Trøndelag Health Study ( Norway ) who reported no pain or physical impairment at baseline in 1984 - 1986 . Occurrence of chronic musculoskeletal pain was assessed at follow-up in 1995 - 1997 . A generalized linear model was used to calculate adjusted risk ratios . For both females and males , hours of physical exercise per week were linearly and inversely associated with risk of chronic pain in the low back ( women : P-trend = 0.02 ; men : P-trend risk of chronic pain in both the low back and the neck/shoulders . Exercising for 1 or more hours per week compensated , to some extent , for the adverse effect of high BMI on risk of chronic pain . The authors conclude that physical inactivity and high BMI are associated with an increased risk of chronic pain in the low back and neck/shoulders in the general adult population",
"BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application",
"Objectives Prevention of occupational low back pain ( LBP ) in nurses is a research priority . Recent research suggests intervening before commencing nursing employment is ideal ; however , identification of modifiable risk factors is required . The objective of this study was to investigate modifiable personal characteristics that predicted new-onset LBP in nursing students . Methods This prospect i ve study was conducted on female nursing students ( n=117 ) without LBP at baseline to predict new-onset LBP ( an episode of significant LBP during the follow-up period ) . At the 12-month follow-up , participants with ( n=31 ) and without new-onset LBP ( n=76 ) were compared across baseline social or lifestyle , psychologic ( distress , back pain beliefs , coping strategies , and catastrophising ) , and physical ( spinal postures and spinal kinematics in functional tasks , leg and back muscle endurance , spinal repositioning error , and cardiovascular fitness ) characteristics . Results Participants response rate at follow-up was excellent ( 91 % ) . After controlling for earlier LBP , age , and BMI , regression analysis showed that modifiable social or lifestyle , psychologic and physical characteristics ( namely , smoking , increased physical activity , higher stress , reduced back muscle endurance , greater posterior pelvic rotation in slump sitting , and more accurate spinal repositioning in sitting ) were significant and independent predictors of new-onset LBP at follow-up . Inclusion of these factors in multivariate logistic regression analysis , with significant new-onset LBP as the outcome , result ed in a substantial model R2 of 0.45 . Discussion Modifiable personal characteristics across multiple domains are associated with new-onset LBP in female nursing students . These findings may have implication s for the development of prevention and management interventions for LBP in nurses",
"Design . Cross-sectional analysis of the factors influencing self-rated disability associated with chronic low back pain and prospect i ve study of the relationship between changes in each of these factors and in disability following active therapy . Objectives . To examine the relative influences of pain , psychological factors , and physiological factors on self-rated disability . Summary of Background Data . In chronic LBP , the interrelationship between physical impairment , pain , and disability is particularly complicated , due to the influence of various psychological factors and the lack of unequivocal methods for assessing impairment . Investigations using new “ belief ” question naires and “ sophisticated ” performance tests , which have shown promise as discriminating measures of impairment , may assist in clarifying the situation . Previous studies have rarely investigated all these factors simultaneously . Methods . One hundred forty-eight patients with cLBP completed question naires and underwent tests of mobility , strength , muscle activation , and fatigability , and ( in a subgroup ) erector spinae size and fiber size/type distribution . All measures were repeated after 3 months active therapy . Relationships between each factor and self-rated disability ( Rol and and Morris question naire ) at baseline , and between the changes in each factor and changes in disability following therapy , were examined . Results . Stepwise linear regression showed that the most significant predictors of disability at baseline were , in decreasing order of importance : pain ; psychological distress ; fear-avoidance beliefs ; muscle activation levels ; lumbar range of motion ; gender . Only changes in pain , psychological distress , and fear-avoidance beliefs significantly accounted for the changes in disability following therapy . Conclusion . A combination of pain , psychological and physiological factors was best able to predict baseline disability , although its decrease following therapy was determined only by reductions in pain and psychological variables . The active therapy programm — in addition to improving physical function — appeared capable of modifying important psychological factors , possibly as a result of the positive experience of completing the prescribed exercises without undue harm",
"Study Design R and omized clinical trial . Background Motor control exercises are believed to improve coordination of the trunk muscles . It is unclear whether increases in trunk muscle thickness can be facilitated by approaches such as the McKenzie method . Furthermore , it is unclear which approach may have superior clinical outcomes . Objectives The primary aim was to compare the effects of the McKenzie method and motor control exercises on trunk muscle recruitment in people with chronic low back pain classified with a directional preference . The secondary aim was to conduct a between-group comparison of outcomes for pain , function , and global perceived effect . Methods Seventy people with chronic low back pain who demonstrated a directional preference using the McKenzie assessment were r and omized to receive 12 treatments over 8 weeks with the McKenzie method or with motor control approaches . All outcomes were collected at baseline and at 8-week follow-up by blinded assessors . Results No significant between-group difference was found for trunk muscle thickness of the transversus abdominis ( -5.8 % ; 95 % confidence interval [ CI ] : -15.2 % , 3.7 % ) , obliquus internus ( -0.7 % ; 95 % CI : -6.6 % , 5.2 % ) , and obliquus externus ( 1.2 % ; 95 % CI : -4.3 % , 6.8 % ) . Perceived recovery was slightly superior in the McKenzie group ( -0.8 ; 95 % CI : -1.5 , -0.1 ) on a -5 to + 5 scale . No significant between-group differences were found for pain or function ( P = .99 and P = .26 , respectively ) . Conclusion We found no significant effect of treatment group for trunk muscle thickness . Participants reported a slightly greater sense of perceived recovery with the McKenzie method than with the motor control approach . Level of Evidence Therapy , level 1b- . Registered September 7 , 2011 at www.anzctr.org.au ( ACTRN12611000971932 ) . J Orthop Sports Phys Ther 2016;46(7):514 - 522 . Epub 12 May 2016 . doi:10.2519/jospt.2016.6379",
"OBJECTIVE To determine the onset of low back pain ( LBP ) in schoolchildren and to investigate the role of mechanical and psychosocial factors as risk factors for its onset . METHODS A prospect i ve population -based cohort study was conducted of 1046 schoolchildren , aged 11 to 14 years at baseline , identified as being free of LBP , from 39 secondary schools in Northwest Engl and . New onset of LBP at 1-year follow-up was measured . RESULTS Children who reported high levels of psychosocial difficulties were more likely to develop LBP than their peers ( relative risk : 1.6 ; 95 % confidence interval : 1.1 - 2.3 ) . An excess risk was , in particular , associated with conduct problems ( 2.5 ; 1.7 - 3.7 ) . Similarly , children who reported high numbers of somatic symptoms at baseline were at greater risk of developing LBP : abdominal pain ( 1.8 ; 1.1 - 3.0 ) , headaches ( 1.6 ; 0.97 - 2.8 ) , and sore throats ( 1.5 ; 0.8 - 2.6 ) . In contrast , we have been unable to demonstrate a strong association between daily mechanical load ( schoolbag weight ) and the short-term risk of new-onset LBP ( highest versus lowest quintile : 1.2 ; 0.7 - 2.1 ) . CONCLUSIONS In children who were initially free of LBP , adverse psychosocial factors and the presence of other preexisting somatic pain symptoms were predictive of future LBP , reflecting findings in adults . In contrast , there was little evidence of an increase in short-term risk associated with mechanical load across the range of weights commonly carried by children to school"
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