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[ "BACKGROUND The efficacy and safety of testosterone treatment for hypoactive sexual desire disorder in postmenopausal women not receiving estrogen therapy are unknown . METHODS We conducted a double-blind , placebo-controlled , 52-week trial in which 814 women with hypoactive sexual desire disorder were r and omly assigned to receive a patch delivering 150 or 300 microg of testosterone per day or placebo . Efficacy was measured to week 24 ; safety was evaluated over a period of 52 weeks , with a subgroup of participants followed for an additional year . The primary end point was the change from baseline to week 24 in the 4-week frequency of satisfying sexual episodes . RESULTS At 24 weeks , the increase in the 4-week frequency of satisfying sexual episodes was significantly greater in the group receiving 300 microg of testosterone per day than in the placebo group ( an increase of 2.1 episodes vs. 0.7 , P placebo , both doses of testosterone were associated with significant increases in desire ( 300 microg per day , P in distress ( 300 microg per day , P rate of and rogenic adverse events - primarily unwanted hair growth - was higher in the group receiving 300 microg of testosterone per day than in the placebo group ( 30.0 % vs. 23.1 % ) . Breast cancer was diagnosed in four women who received testosterone ( as compared with none who received placebo ) ; one of the four received the diagnosis in the first 4 months of the study period , and one , in retrospect , had symptoms before undergoing r and omization . CONCLUSIONS In postmenopausal women not receiving estrogen therapy , treatment with a patch delivering 300 microg of testosterone per day result ed in a modest but meaningful improvement in sexual function . The long-term effects of testosterone , including effects on the breast , remain uncertain . ( Clinical Trials.gov number , NCT00131495 .", "OBJECTIFS : Le role physiologique de la dehydro-epi and rosterone ( DHEA ) chez l'etre humain reste incertain . L'insuffisance surrenale entraine un deficit en DHEA . L'administration de DHEA a des sujets âges en bonne sante entraine une augmentation de la densite osseuse , de la force musculaire , de la sensation de bien-etre et des concentrations du facteur de croissance « insuline-like » ( IGF-I ) . Mais ces etudes n'ont pas utilise de question naires valides de bien-etre et la plupart etaient ouvertes sans comparaison au placebo . L'objectif de l'essai est d'evaluer les effets de la supplementation en DHEA chez des patientes ayant une insuffisance surrenale sur le bien-etre et la sexualite . METHOD ES : Vingt quatre femmes ayant une insuffisance surrenale , ont ete incluses dans un essai croise , en double insu , et ont recu 50 mg de DHEA per os chaque matin pendant 4 mois et le placebo chaque matin pendant 4 mois , l'ordre des traitements etant attribue par la r and omisation . Une periode de 1 mois sans traitement separait les 2 periodes de traitement . Ont ete mesures les hormones steroides seriques , l'IGF-I , les lipides et l'hormone « sex-binding globulin » ( SBG ) . Ont egalement ete evaluees la sensation de bien-etre et la sexualite , a l'aide de question naires psychologiques valides et d'echelles visuelles analogiques . Les femmes ont ete evaluees avant le debut du traitement , apres 1 mois et 4 mois de traitement par DHEA , apres 1 mois et 4 mois de traitement par placebo , et 1 mois apres la fin de la deuxieme periode de traitement . PATIENTS : L'âge moyen des 24 femmes est de 42 ± 9 ans , l'anciennete de l'insuffisance surrenale est de 9 ± 2 ans . L'insuffisance surrenale est primitive pour 14 femmes et secondaire pour 10 femmes . Toutes les femmes prenaient une dose reguliere de glucocorticoides et 14 prenaient egalement des mineralocorticoides . Sept femmes etaient menopausees , 3 avaient un hypogonadisme primitif et 7 un hypogonadisme secondaire . Parmi ces 17 femmes , 13 recevaient un traitement hormonal substitutif par estroprogestatifs . RESULT ATS : Le traitement par DHEA augmente les taux seriques initiaux bas de sulfate de DHEA , d ' and rostenedione et de testosterone jusqu'a des taux normaux . Les concentrations seriques de SBG , de cholesterol total , de lipoproteines de haute densite diminuent significativement . La DHEA ameliore significativement le score global de bien-etre , de meme que les scores de depression et d'anxiete . Ainsi , le score global s'ameliore de -0,18 ± 0,29 par rapport au debut du traitement dans le groupe DHEA , contre 0,03 ± 0,29 dans le groupe placebo ( p = 0,02 ) . Comparee au placebo , la DHEA augmente significativement la frequence des pensees sexuelles ( p = 0,006 ) , de l'interet sexuel ( p = 0,002 ) et la satisfaction avec la sexualite ( p = 0,02 ) . CONCLUSION : La DHEA ameliore le bien-etre et la sexualite chez des femmes ayant une insuffisance surrenale", "Aging in women and men is characterized by a progressive decline of circulating dehydroepi and rosterone ( DHEA ) levels and its sulfate ester ( DHEAS ) . The improvement of wellbeing described in postmenopausal women treated with DHEA suggests that this steroid may exert specific actions on the central nervous system ( CNS ) . The postmenopausal period is associated with several neuroendocrine modifications . The decrease of circulating levels of beta-endorphin is considered a hormonal marker of those changes . The aim of the present study was to investigate neuroendocrine and behavioral effects of three months of DHEAS supplementation in postmenopausal women . Postmenopausal women ( n = 22 ) were divided in three groups : the first group was treated with oral DHEAS ( n = 8) ( 50 mg/day ) , the second treated with the same dose of oral DHEAS + transdermal estradiol ( n = 8) ( DHEAS ) 50 mg/day , estradiol 50 micrograms/patch ) and the third with transdermal estradiol alone ( n = 6 ) ( 50 micrograms/day ) . Before and after 1 , 2 and 3 months of therapy , the following circulating steroid and protein hormone levels were evaluated : DHEA , DHEAS , and rostenedione , testosterone , estrone , estradiol , 17-hydroxyprogesterone , sex hormone-binding globulin ( SHBG ) , follicle-stimulating hormone ( FSH ) , luteinizing hormone ( LH ) , beta-endorphin , growth hormone ( GH ) and cortisol , and a Kupperman score was performed . Before and after treatments , plasma beta-endorphin levels were evaluated in response to three neuroendocrine tests : ( a ) clonidine , an alpha 2-presynaptic adrenergic agonist ( 1.25 mg i.v . ) ( b ) naloxone , an opioid receptor antagonist ( 4 mg i.v . ) and ( c ) fluoxetine , a serotonin selective reuptake inhibitor ( 30 mg p.o . ) . In both groups of women treated with DHEAS , mean basal serum DHEA , DHEAS , and rostenedione , and testosterone levels significantly increased after treatment , while no changes were shown in the group receiving estradiol alone . Serum estradiol , estrone , GH and plasma beta-endorphin levels significantly increased progressively for the three months of treatment , with higher levels for estrone and estradiol in subjects receiving estradiol alone or plus DHEAS . Serum SHBG , cortisol , and 17-hydroxyprogesterone did not show significant variations under any treatment . Serum LH and FSH levels showed a significant decrease in groups treated with estradiol alone or plus DHEAS at the second and third months . The Kupperman score showed that all treatments were associated with similar and progressive improvement . Before therapy clonidine , naloxone and fluoxetine stimuli failed to modify circulating beta-endorphin levels . After each of the treatments , the beta-endorphin response was completely restored and was similar , independent of the kind of therapy . Restoration of the beta-endorphin response to specific stimuli suggests that DHEAS and /or its active metabolites modulates the neuroendocrine control of pituitary beta-endorphin secretion , which may support the therapeutic efficacy of the DHEAS on behavioral symptoms", "Menopause is associated with decreased lean body mass and increased fat due to aging and declining hormone secretion . Estrogens or estrogen-progestins have been used to alleviate vasomotor symptoms . However , estrogen- and rogen ( E/A ) therapy is also used for vasomotor symptom relief and has been shown to increase lean body mass while decreasing fat mass . The objective of this 16-wk , double-blind , r and omized , parallel group clinical trial was to compare esterified estrogen plus methyltestosterone ( 1.25 mg estrogen + 2.5 mg methyltestosterone/d ; E/A group ) vs. esterified estrogen alone ( 1.25 mg/d ; E group ) on body composition . Forty postmenopausal women ( mean age , 57 yr ) participated . Compared with estrogen treatment alone , women in the E/A group increased their total lean body mass and reduced their percentage fat for all body parts ( P E/A treatment , there were statistically significant increases in lean body mass by 1.232 kg [ 0.181 + /- 0.004 , 0.81 + /- 0.057 , and 0.24 + /- 0.009 kg in the upper body ( P = 0.021 ) , trunk ( P = 0.001 ) , and lower body ( P = 0.047 ) , respectively ] . In the E group , the increase was 0.31 + /- 0.004 , 0.021 + /- 0.03 , and 0.056 + /- 0.05 kg in the upper body , trunk , and lower body , respectively . In the E/A group , body fat was reduced by 0.90 kg ( P = 0.18 for the trunk only ) , and percentage body fat declined by 7.4 % ( P Lower body strength increased by 23.1 kg ( 51 lb ) in the E/A group vs. only 11 kg ( 24.25 lb ) in the E group ( P = 0.002 between groups ) . A statistically significant increase in weight ( 2.7 + /- 5.1 vs. 0.1 + /- 4.6 lb ; P E/A group compared with the E group . When subjects were given self-reporting question naires , more improvement was noted in sexual functioning and quality of life in the E/A group when compared with patients receiving E alone . There were no noteworthy side effects . In conclusion , E/A replacement therapy can improve body composition , lower-body muscle strength , quality of life , and sexual functioning in postmenopausal women", "OBJECTIVES This single-dose study compares three dehydroepi and rosterone delivery methods ( oral crystalline steroid , micronized steroid , and vaginal administration ) to ascertain whether physiologic levels of circulating dehydroepi and rosterone and dehydroepi and rosterone sulfate can be obtained while increases in testosterone are minimized . STUDY DESIGN Two r and omized , double-blind , placebo-controlled single-dose comparisons were made . For oral micronized versus crystalline dehydroepi and rosterone 300 mg doses of micronized or crystalline dehydroepi and rosterone were administered , followed by 6 hours of blood sampling ( n=7 ) . Serum dehydroepi and rosterone , dehydroepi and rosterone sulfate , and testosterone levels were measured ; areas under the curve and mean peak values were analyzed by Student-Newman-Keuls tests . For oral versus vaginal micronized dehydroepi and rosterone 150 mg oral or vaginal doses of micronized dehydroepi and rosterone were administered , followed by blood sampling over 12 hours ( n=5 ) . Data analysis was as described . RESULTS Oral micronized and unmicronized dehydroepi and rosterone result ed in increases in serum dehydroepi and rosterone , dehydroepi and rosterone sulfate , and testosterone . Micronization increased the area-under-the-curve ratios for dehydroepi and rosterone sulfate/dehydroepi and rosterone and dehydroepi and rosterone sulfate/testosterone . Vaginal administration provided equivalent serum dehydroepi and rosterone ; however , it failed to increase dehydroepi and rosterone sulfate or testosterone over placebo . CONCLUSION Micronization of oral dehydroepi and rosterone diminishes bioconversion to testosterone . Vaginal dehydroepi and rosterone delivers equivalent dehydroepi and rosterone but substantially diminishes dehydroepi and rosterone bioconversion", "INTRODUCTION We have previously observed that intravaginal prasterone ( dehydroepi and rosterone , DHEA ) improved all domains of female sexual dysfunction ( FSD ) . AIM Investigate the influence of moderate/severe pain at sexual activity ( dyspareunia ) ( MSD ) at baseline on FSD following prasterone administration . METHODS The effect of daily administration of prasterone ( 0 , 3.25 mg , 6.5 mg or 13 mg ) for 12 weeks on FSD in 215 postmenopausal women with or without MSD at baseline was evaluated in a prospect i ve , r and omized , double-blind , and placebo-controlled phase III clinical trial . MAIN OUTCOME MEASURES Differences were examined on desire , arousal and orgasm . RESULTS Comparable benefits were observed in women not having MSD ( n = 56 ) vs. those having MSD ( n = 159 ) . The benefits over placebo in prasterone-treated women for desire , avoiding intimacy and vaginal dryness as well as for the total sexual domain of the MENQOL ( Menopause Specific Quality of Life ) question naire , ranged between 18.0 % and 38.2 % with P values of arousal/sensation , arousal/lubrication and summary score of the ASF ( Abbreviated Sexual Function ) question naire , in the MSD+ group , improvements of 64.2 % ( P = 0.01 ) , 118 % ( P = 0.001 ) and 31.1 % ( P = 0.03 ) were observed over placebo , respectively , while similar differences ( 58.0 % , 67.6 % and 32.1 % ) did not reach statistical significance in the MSD- group having up to only 44 prasterone-treated women compared with 119 in the MSD+ group . CONCLUSIONS No MSD at baseline does not apparently affect the effects of intravaginal prasterone on sexual dysfunction . Knowing the absence of significant effects of estrogens on FSD , the present data suggest that vulvovaginal atrophy ( VVA ) and vulvovaginal sexual dysfunction ( VVSD ) are two different consequences of sex steroid deficiency at menopause which can respond independently . In addition , the present data seriously question the justification of pain being part of FSD as well as the separation of FSD into separate domains", "The present investigation was design ed to provide the first empirical examination of the effects of acute dehydroepi and rosterone ( DHEA ) administration on subjective and physiological sexual arousal in women . The primary purpose was to assess whether DHEA influences vaginal blood flow response in sexually functional women . Subjective ( self-report ) and physiological ( vaginal photoplethysmograph ) sexual responses to erotic stimuli were measured following DHEA ( 300 mg ) and placebo administration in 12 sexually functional , premenopausal women , using a single-blind protocol . Acute DHEA significantly increased blood levels of dehydroepi and rosterone sulfate ( DHEA-S ) 30 min following drug administration but had no significant effect on either vaginal pulse amplitude responses or subjective responses to the erotic films . Acute DHEA does not appear to substantially influence sexual responding among sexually functional , premenopausal women", "OBJECTIVE To demonstrate bioavailability of 3 weeks of oral micronized DHEA and to delineate changes induced on insulin sensitivity , morphometric indexes , and lipoprotein profiles . DESIGN Oral micronized DHEa ( 50 mg/d ) was administered in 3-week treatments to 11 postmenopausal women in a prospect i ve , placebo-controlled , r and omized , blinded , crossover trial with an interarm washout . After dose ( 23 hour ) serum DHEA , DHEAS , T , and cortisol levels were measured , as were fasting lipoproteins , oral glucose tolerance tests ( OGTT ) , T-lymphocyte insulin binding and degradation , and urine collagen cross-links . Morphometric changes were determined by hydrostatic weighing . RESULTS Dehydroepi and rosterone sulfate , DHEA , T , and free T increased up to two times premenopausal levels with treatment . Fasting triglycerides declined ; no change in collagen cross-links or morphometric indexes was noted . Oral glucose tolerance test parameters did not change , but both T-lymphocyte insulin binding and degradation increased with DHEA . CONCLUSION Fifty milligrams per day of oral DHEA gives suprahysiologic and rogen levels ; 25 mg/d may be more appropriate . Dehydroepi and rosterone enhanced tissue insulin sensitivity and lowered serum triglycerides . Rationale is provided for postmenopausal replacement therapy with this and rogen", "OBJECTIVE This study tests the hypothesis that dehydroepi and rosterone or its metabolic products are immunomodulatory in postmenopausal women with relative adrenal and rogen deficiency . STUDY DESIGN A prospect i ve , r and omized , double-blind , crossover study of 11 subjects with 3-week treatment arms separated by a 2-week washout period was performed . Immunologic evaluation at the beginning and end of the treatment arms consisted of flow cytometry to delineate T-cell population s , in vitro T-cell mitogenic response and cytokine production , and natural killer cell cytotoxicity . Statistical analysis was based on a split-plot design with analysis of variance with repeated measures . RESULTS Dehydroepi and rosterone supplementation decreased CD4 + ( helper ) T cells and increased CD8+/CD56 + ( natural killer ) cells . Although T-cell mitogenic and interleukin-6 responses were inhibited , natural killer cell cytotoxicity increased dramatically . CONCLUSIONS These data provide the first in vivo evidence in human for an immunomodulatory effect of dehydroepi and rosterone . The salutary immune changes could account for clinical and experimental evidence of antioncogenic effects of this steroid . This study provides a strong rationale for further clinical studies on dehydroepi and rosterone supplementation in adrenal and rogen-deficient states", "OBJECTIVE Patients with fibromyalgia ( FM ) consistently have adrenal hyporesponsiveness and low dehydroepi and rosterone ( DHEA ) levels . DHEA is promoted for and used by patients with FM . We tested the efficacy and safety of DHEA supplementation in ameliorating the symptoms of FM . METHODS In a double-blind crossover study , postmenopausal women with FM were r and omized to DHEA supplementation ( 50 mg/day ) or placebo for 3 months , with a one-month washout period in between . Patients were assessed monthly for well-being and pain and by medical evaluations at the beginning and the end of each treatment period . The primary outcome was well being ; secondary outcomes were pain , fatigue , cognition , sexuality , functional impairment , depression , and anxiety . RESULTS A total of 52 patients were r and omized , 47 patients completed the DHEA treatment period , and 45 the placebo treatment period . After 3 months of treatment with 50 mg of DHEA , median DHEA sulfate blood levels had tripled , but there was no improvement in well-being , pain , fatigue , cognitive dysfunction , functional impairment , depression , or anxiety , nor in objective measurements made by physicians . And rogenic side effects ( greasy skin , acne , and increased growth of body hair ) were more common during the DHEA treatment period ( p = 0.02 ) . CONCLUSION DHEA does not improve quality of life , pain , fatigue , cognitive function , mood , or functional impairment in FM", "CONTEXT Despite decades of accumulated observational evidence , the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain . OBJECTIVE To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States . DESIGN Estrogen plus progestin component of the Women 's Health Initiative , a r and omized controlled primary prevention trial ( planned duration , 8.5 years ) in which 16608 postmenopausal women aged 50 - 79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993 - 1998 . INTERVENTIONS Participants received conjugated equine estrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOMES MEASURES The primary outcome was coronary heart disease ( CHD ) ( nonfatal myocardial infa rct ion and CHD death ) , with invasive breast cancer as the primary adverse outcome . A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke , pulmonary embolism ( PE ) , endometrial cancer , colorectal cancer , hip fracture , and death due to other causes . RESULTS On May 31 , 2002 , after a mean of 5.2 years of follow-up , the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits . This report includes data on the major clinical outcomes through April 30 , 2002 . Estimated hazard ratios ( HRs ) ( nominal 95 % confidence intervals [ CIs ] ) were as follows : CHD , 1.29 ( 1.02 - 1.63 ) with 286 cases ; breast cancer , 1.26 ( 1.00 - 1.59 ) with 290 cases ; stroke , 1.41 ( 1.07 - 1.85 ) with 212 cases ; PE , 2.13 ( 1.39 - 3.25 ) with 101 cases ; colorectal cancer , 0.63 ( 0.43 - 0.92 ) with 112 cases ; endometrial cancer , 0.83 ( 0.47 - 1.47 ) with 47 cases ; hip fracture , 0.66 ( 0.45 - 0.98 ) with 106 cases ; and death due to other causes , 0.92 ( 0.74 - 1.14 ) with 331 cases . Corresponding HRs ( nominal 95 % CIs ) for composite outcomes were 1.22 ( 1.09 - 1.36 ) for total cardiovascular disease ( arterial and venous disease ) , 1.03 ( 0.90 - 1.17 ) for total cancer , 0.76 ( 0.69 - 0.85 ) for combined fractures , 0.98 ( 0.82 - 1.18 ) for total mortality , and 1.15 ( 1.03 - 1.28 ) for the global index . Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events , 8 more strokes , 8 more PEs , and 8 more invasive breast cancers , while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures . The absolute excess risk of events included in the global index was 19 per 10 000 person-years . CONCLUSIONS Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women . All-cause mortality was not affected during the trial . The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases , and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD", "OBJECTIVE Because dehydroepi and rosterone ( DHEA ) is an adrenal steroid hormone with weak intrinsic and rogenic properties that can be converted in peripheral tissues into more potent sex hormones , one might expect a positive effect of DHEA on bone mineral density ( BMD ) . We evaluated the effects on lumbar BMD of oral DHEA , 200 mg/day , for 1 year in female patients with quiescent systemic lupus erythematosus ( SLE ) . METHODS The study subjects were 60 women with SLE . All participants gave informed consent to participate in a double-blind , placebo-controlled study on the effects of DHEA on fatigue and general well-being . BMD was measured with dual-energy x-ray absorptiometry ( DEXA ) at baseline and after 12 months . RESULTS Fifty-eight patients ( mean age 42.6 years ) could be evaluated ; 2 patients ( both in the DHEA group ) refused to undergo DEXA a second time . In premenopausal women , DHEA did not influence BMD significantly . There was a significant increase in BMD with use of DHEA in postmenopausal women who were not receiving bisphosphonates or estrogen-containing medications . This increase was not observed in the group receiving placebo . CONCLUSION In premenopausal women with quiescent SLE , use of DHEA does not have a significant effect on BMD . DHEA may increase BMD in postmenopausal SLE patients if they are not already protected from bone loss by use of estrogens or bisphosphonates . Small numbers , due to the absence of stratification for menopausal status , and the use of antiresorptive agents at r and omization preclude firmer conclusions based on the results of this study", "OBJECTIVE To determine the effect of administering 6 months of oral postmenopausal DHEA therapy on serum DHEA , DHEAS , and T levels and on physiologic endpoints including lipoproteins and insulin-like growth factor-I ( IGF-I ) . DESIGN R and omized , double-blind , parallel trial . SETTING Academic referral practice . PATIENT(S ) Thirteen normal-weight or overweight , healthy , nonsmoking , postmenopausal women . INTERVENTION(S ) Administration of oral micronized DHEA ( 25 mg/d ) . MAIN OUTCOME MEASURE(S ) Monthly fasting 23 hours postdose levels of serum DHEA , DHEAS , T , lipoproteins , IGF-I , IGF binding protein-3 ( IGFBP-3 ) , and liver function tests . Morphometric indices by dual-energy x-ray absorptiometry scan ( percent body fat ; lean body mass ) , immune indices , and insulin sensitivity . RESULT ( S ) Levels of DHEA , DHEAS , and T all rose into premenopausal ranges , but after 6 months , levels of DHEA and T did not differ from baseline or placebo . At 3 months , the ratio of IGF-I to IGFBP-3 rose by 36.1 % + /- 12.7 % , but it fell to placebo values by 6 months . High-density lipoprotein and apolipoprotein A1 levels declined . CONCLUSION ( S ) Patients appeared to tolerate 6 months of DHEA therapy well . Given the small study size , no statistically significant differences in morphometric indices , immune indices , or insulin-sensitizing properties were observed , but significant attenuation of bioavailability occurred . Supplementation with DHEA increased IGF-I/IGFBP-3 levels at 3 months and decreased high-density lipoprotein and apolipoprotein A1 levels at 6 months", "Data regarding the efficacy of dehydroepi and rosterone ( DHEA ) in the treatment of hypoactive sexual desire disorder ( HSDD ) are scarce and inconsistent . We aim ed to determine possible gender differences in the efficacy of DHEA as a treatment for HDSS . Postmenopausal women ( n=27 ) , and men ( n=21 ) with HSDD , were r and omized to receive either DHEA 100 mg daily or placebo for 6 weeks in a controlled , double blind study . Primary outcome measures were sexual function question naires . Hormone serum levels of DHEAS , total and bioavailable testosterone , estradiol , and urine levels of DHEA and and rosterone were also measured . Participants on active treatment showed a significant increase in circulating serum levels of DHEAS , while bioavailable testosterone levels increased in women only . In women only , significant interaction effects were observed for sexual arousal ( p satisfaction ( p cognition ( trend ; p=0.06 ) . For arousal , a significant improvement was observed for the DHEA treated group at 6 weeks ( p=0.001 ) . Significant correlations were observed between bioavailable T and sexual cognitions , arousal and orgasm , while DHEAS was correlated with satisfaction . In the men , significant correlations were observed between testosterone and arousal ( r=.45 ) , sexual drive ( r=.50 ) and orgasm ( r=.55 ) . In women with HSDD , DHEA treatment had a significant beneficial effect on arousal , whereas no efficacy was demonstrated in men , indicating a possible gender difference . This improvement seems to be mediated via DHEA 's metabolism to testosterone . Our positive results suggest that the neurosteroid DHEA may be effective as a treatment for women with HSDD if administered at a dose of at least 100 mg per day", "OBJECTIVES Because dehydroepi and rosterone may protect against neoplasia , osteoporosis , and cardiac disease , we investigated the bioavailability of oral micronized dehydroepi and rosterone , anticipating its adjunctive use in postmenopausal steroid replacement . STUDY DESIGN Eight postmenopausal women r and omly received either a placebo or 150 or 300 mg of oral micronized dehydroepi and rosterone in a lipid matrix . Serum dehydroepi and rosterone , dehydroepi and rosterone sulfate , testosterone , and estradiol were measured periodically over the 12 hours after each dose . All treatments , all doses , and mean serum dehydroepi and rosterone , dehydroepi and rosterone sulfate , and testosterone were compared with analysis of variance for repeated measures and Newman-Keuls a posteriori test of statistical significance . RESULTS Mean peak steroid concentrations after 150 mg ( 300 mg ) doses were dehydroepi and rosterone 1617 ( 2639 ) ng/dl , 7 (11.5)-fold above placebo ; dehydroepi and rosterone S 1185 ( 1688 ) micrograms/dl , 14 (20)-fold above placebo ; and testosterone 183 ( 311 ) ng/dl , 4 (7)-fold above placebo . Estradiol concentrations remained less than 20 pg/ml , but and rogen concentrations rose by 1 hour and remained elevated through the twelfth hour . Peak and rogen concentrations and areas under the curves exhibited proportionality with both doses . A testosterone radioimmunoassay with celite chromatography revealed a 300 % overestimation for testosterone in the direct-assay method used in this study . Thus after appropriate readjustment maximum testosterone concentrations were observed consistently within physiologic premenopausal ranges after the 150 mg dose . CONCLUSIONS Micronized dehydroepi and rosterone may provide a steroidal postmenopausal replacement that is adjunctive to estrogens and worthy of further investigation", "OBJECTIVE To evaluate the effects of combination estrogen/ and rogen therapy on muscle mass , strength and endurance , serum hormone and lipid profiles , and quality of life measures in postmenopausal women . METHODS Prospect i ve , r and omized , placebo-controlled pilot study at a tertiary care medical center . Fifty postmenopausal women were r and omized to a 12-week course of ( 1 ) dehydroepi and rostenedione ( DHEA ) 50 mg daily , ( 2 ) conjugated equine estrogen ( CEE ) 0.625 mg daily , ( 3 ) DHEA 50 mg+CEE 0.625 mg daily , or ( 4 ) placebo . Main outcome measures of lower extremity muscle ( calf ) mass , functional muscle parameters , serum hormone and lipid levels , and quality of life ( QOL ) were obtained at baseline and after treatment . Statistical analysis compared percent change from baseline values and treatment differences among outcomes . RESULTS Significant increases in mean DHEA , DHEA sulfate ( DHEA-S ) , testosterone , and and rostenedione levels were noted with DHEA alone or combined DHEA/CEE treatments when compared with placebo . Compared with no hormone therapy , none of the supplemental hormone groups caused significant changes in muscle mass , muscle strength , muscle endurance , feelings of well-being , sleep , or sexual function . CONCLUSIONS And rogen replacement therapy , with DHEA , to menopausal women increases serum and rogen levels without any appreciable effect on muscle cross-sectional area , muscle strength , muscle function , or improvement in health-related QOL", "Objective To examine the effect of intravaginal dehydroepi and rosterone ( DHEA ) on pain at sexual activity ( dyspareunia ) identified as the most bothersome symptom of vaginal atrophy in postmenopausal women at both screening and day 1 . Methods This prospect i ve , r and omized , double-blind and placebo-controlled phase III clinical trial studied the effect of prasterone ( DHEA ) applied locally in the vagina on the severity of dyspareunia in 114 postmenopausal women who had identified dyspareunia as their most bothersome symptom of vaginal atrophy , while meeting the criteria for superficial cells ≤ 5 % and pH > 5.0 at both screening and day 1 . Results At the st and ard duration of 12 weeks of treatment , increasing doses of 0.25 % , 0.5 % and 1.0 % DHEA decreased the percentage of parabasal cells by 48.6 ± 6.78 % , 42.4 ± 7.36 % and 54.9 ± 6.60 % ( p effects on superficial cells and pH were also highly significant compared to placebo at all DHEA doses . The severity score of pain at sexual activity decreased by 0.5 , 1.4 , 1.6 and 1.4 units in the placebo and 0.25 % , 0.5 % and 1.0 % DHEA groups , respectively , with the p value of differences from placebo ranging from 0.0017 to effect on pain at sexual activity without systemic exposure of the other tissues , thus avoiding the recently reported systemic effects of estrogens", "Objective : The objective of this study was to provide evidence that the transformation of DHEA into both and rogens and /or estrogens locally in cells of the three layers of the vagina ( epithelium , lamina propria , and muscularis ) would have effects of greater impact , including effects on sexual function , than only effects on superficial epithelial cells as achieved with estrogens . Methods : This prospect i ve , r and omized , double-blind , and placebo-controlled phase III clinical trial has evaluated the effect of daily local intravaginal application of Prasterone ( dehydroepi and rosterone ; DHEA ) for 12 weeks on the domains of sexual dysfunction , namely , desire/interest , arousal , orgasm , and pain at sexual activity , in 216 postmenopausal women with moderate to severe symptoms of vaginal atrophy . Results : A time- and dose-dependent improvement of the four domains of sexual function was observed . At the 12-week time interval , the 1.0 % DHEA dose led , compared with placebo , to 49 % ( P = 0.0061 ) and 23 % ( P = 0.0257 ) improvements of the desire domains in the Menopause Specific Quality of Life and Abbreviated Sex Function question naires , respectively . Compared with placebo , the Abbreviated Sex Function arousal/sensation domain was improved by 68 % ( P = 0.006 ) , the arousal/lubrication domain by 39 % ( P = 0.0014 ) , orgasm by 75 % ( P = 0.047 ) , and dryness during intercourse by 57 % ( P = 0.0001 ) . Conclusions : By a local action in the vagina , DHEA applied daily at doses at which serum steroids remain well within normal postmenopausal values exerts relatively potent beneficial effects on all four aspects of sexual dysfunction . Such data indicate that combined and rogenic/estrogenic stimulation in the three layers of the vagina exerts important beneficial effects on sexual function in women without systemic action on the brain and other extravaginal tissues", "BACKGROUND Published data regarding the negative risk-benefit ratio of traditional estrogen/progesterone hormone replacement therapy for menopausal symptoms have indicated the need for alternative treatments . Dietary supplements and herbal products are popularly used for menopausal control without a large evidence base . Therefore , a prospect i ve pilot trial using 50 mg of dehydroepi and rosterone ( DHEA ) once daily for 4 weeks following a baseline week was developed to explore whether DHEA has any efficacy in reducing hot flashes . Safety issues were also evaluated . PATIENTS AND METHODS Twenty-eight women were enrolled in this study , 22 of whom are evaluable . The primary outcome was the reduction in hot flash score ( frequency multiplied by average severity ) from baseline as measured by vali date d self-report daily hot flash diaries . RESULTS The mean hot flash score decreased 50 % from baseline , and there were no side effects that were significantly worse compared with baseline . Quality of life related to hot flashes showed statistically significant improvement after 4 weeks of DHEA therapy . CONCLUSION This pilot study provides data supporting the hypothesis that DHEA is well tolerated and can reduce hot flashes . Dehydroepi and rosterone should be studied further in a larger , placebo-controlled trial", "OBJECTIVES To examine the effects of dehydroepi and rosterone ( DHEA ) supplementation on cognitive function and quality of life in healthy older adults . DESIGN Double-blind , r and omized , controlled clinical trial . SETTING Clinical research facility . PARTICIPANTS One hundred ten men and 115 women aged 55 to 85 ( mean + /- st and ard deviation 68 + /- 8) . INTERVENTION Fifty milligrams daily oral DHEA versus placebo for 1 year . MEASUREMENTS Six cognitive function tests at baseline and 12 months , the Beck Depression Inventory ( BDI ) , the Medical Outcomes Study 36-item Short Form Survey ( SF-36 ) , the Life Satisfaction Index-Z , the Satisfaction with Life Scale , the Female Sexual Function Index ( in women ) , and the 15-item International Index of Erectile Function ( in men ) at baseline and 3 , 6 , and 12 months . RESULTS There were no differences between the DHEA and placebo groups in change over time in cognitive function ( P>.10 ) . Over time , BDI scores decreased for men ( P=.006 ) and women ( P=.02 ) , and Satisfaction with Life Scale scores increased for women ( P=.004 ) , but there were no differences between the DHEA and placebo groups over time on these measures or the SF-36 , Life Satisfaction Index-Z scale , or sexual function scales ( P>.10 ) . CONCLUSION DHEA supplementation has no benefit on cognitive performance or well-being in healthy older adults , and it should not be recommended for that purpose in the general population", "OBJECTIVE To assess prevention of bone mineral density ( BMD ) loss and durability of the response during treatment with prasterone in women with systemic lupus erythematosus ( SLE ) receiving chronic glucocorticoids . METHODS 155 patients with SLE received 200 mg/day prasterone or placebo for 6 months in a double-blind phase . Subsequently , 114 patients were re-r and omized to receive 200 or 100 mg/day prasterone for 12 months in an open-label phase . Primary efficacy endpoints were changes in BMD at the lumbar spine ( L-spine ) from baseline to Month 6 and maintenance of BMD from Month 6 to 18 for patients who received prasterone during the double-blind phase . RESULTS In the double-blind phase , there was a trend for a small gain in BMD at the L-spine for patients who received 200 mg/day prasterone for 6 months versus a loss in the placebo group ( mean + /- SD , 0.003 + /- 0.035 vs -0.005 + /- 0.053 g/cm(2 ) , respectively ; p = 0.293 between groups ) . In the open-label phase , there was dose-dependent increase in BMD at the L-spine at Month 18 between patients who received 200 versus 100 mg/day prasterone ( p = 0.021 ) . For patients who received 200 mg/day prasterone for 18 months , the L-spine BMD gain was 1.083 + /- 0.512 % ( p = 0.042 ) . There was no overall change in BMD at the total hip over 18 months with 200 mg/day prasterone treatment . The safety profile reflected the weak and rogenic properties of prasterone . CONCLUSION This study suggests prasterone 200 mg/day may offer mild protection against bone loss in women with SLE receiving glucocorticoids . ( Clinical Trials.gov Identifiers NCT00053560 and NCT00082511 )", "BACKGROUND The age-related decline of dehydroepi and rosterone ( DHEA ) has prompted research on its experimental replacement in women . Although no relationship to sexual functioning in healthy women has been shown to date , DHEA replacement has potential for affecting sexual response . METHODS To investigate DHEA effects , 16 sexually functional postmenopausal women participated in a r and omized , double-blind , crossover protocol in which oral administration of DHEA ( 300 mg ) or placebo occurred 60 minutes before the presentation of an erotic video segment . Blood DHEA sulfate ( DHEAS ) changes , subjective and physiological sexual responses , as well as affective responses were measured in response to videotaped neutral and erotic video segments . RESULTS The concentration of DHEAS increased 2 - 5-fold following DHEA administration in all 16 women . Subjective ratings across DHEA and placebo conditions showed significantly greater mental ( p and physical ( p sexual arousal to the erotic video with DHEA vs. placebo . Positive affect also increased during the erotic video across drug conditions . Vaginal pulse amplitude ( VPA ) and vaginal blood volume ( VBV ) demonstrated a significant increase ( p ( DHEA and placebo ) but did not differentiate drug conditions . CONCLUSION In sum , increases in mental and physical sexual arousal ratings significantly increased in response to an acute dose of DHEA in postmenopausal women", "In this article , the theoretical distinction between recognition memory decision and discrimination processes is used to explore the effect of dehydroepi and rosterone ( DHEA ) in postmenopausal women . DHEA is an adrenal steroid that diminishes with aging . It has enhanced memory in laboratory animals . An 8-week placebo-controlled , double-blind experiment in which 30 women ( ages 39–70 ) received a 50-mg/day oral dose of DHEA for 4 weeks demonstrated that DHEA made subjects more conservative ( i.e. , less likely to call test items “ old ” ) in their recognition memory decisions and enhanced recognition memory discrimination for items presented briefly . The former result may reflect an empirical regularity ( Hirshman , 1995 ) in whichrecent strong memory experiences make participants more conservative . The latter result may reflect the effect of DHEA on visual perception , with consequent effects on memory . These results suggest the method ological importance of focusing on decision processes when examining the effects of hormones on memory", "DHEA-S treatment is used as an anti-aging and anti-obesity hormone therapy in adults ; however , it mechanisms of action are not clearly eluci date d. The objective of the present work was to analyze the effect of a replacement therapy , which included a daily single oral dose of DHEA-S for three months , on the composition of human plasma fatty acids ( FAs ) in obese women . In the first study , a r and omized , double-blind , placebo-controlled trial was conducted involving 61 postmenopausal women , who were assigned to receive 100mg/day of DHEA-S ( n = 41 ) or placebo ( n = 20 ) orally for 3 months . In a second study , the effect of DHEA-S treatment on postmenopausal obese women ( n = 41 ) was compared to that in premenopausal obese women ( n = 20 ) . Blood sample s were collected at the beginning and at the end of the treatment . Plasma FAs were analyzed by gas chromatography . DHEA-S treatment produced significant changes in plasma FAs of both post- and premenopausal women with a reduction of total saturated FAs ( SFA ) as well as an increase in n-6 polyunsaturated FA ( PUFA ) . Particularly , in premenopausal women the DHEA-S treatment also increased the plasma n-3 PUFA percentage . Regarding estimation of desaturase activity , our data showed that Δ6-desaturase was significantly decreased in postmenopausal women after DHEA-S treatment , whereas Δ5-desaturase was increased in the premenopausal group . In conclusion , DHEA-S treatment in obese women modifies plasma FA composition towards a potentially better metabolic profile , mainly by decreasing SFA and increasing n-6 PUFA in both postmenopausal and premenopausal women", "CONTEXT Serum levels of the sex steroid prohormones dehydroepi and rosterone ( DHEA ) and DHEA sulfate ( DHEA-S ) decline upon aging and are reduced in primary Sjogren 's syndrome . OBJECTIVE Our aim was to investigate : 1 ) effects of 50 mg oral DHEA/day on changes in serum levels of DHEA and 12 of its metabolites ; 2 ) relationships between steroid levels and disease characteristics ; and 3 ) whether these parameters were influenced by DHEA . DESIGN Twenty-three postmenopausal women with primary Sjogren 's syndrome and subnormal levels of DHEA-S were included in a r and omized , 9-month , controlled , double blind crossover study . Liquid chromatography/mass spectrometry (MS)/MS and gas chromatography/MS were used to measure the sex steroids . Anti-SS-A/Ro and /or anti-SS-B/La , salivary gl and focus score , salivary flow rates , dry mouth and eye symptoms , and routine laboratory tests were assessed . RESULTS Baseline erythrocyte sedimentation rate was inversely correlated with testosterone ( Testo ) , dihydrotestosterone , and DHEA-S ( rs = -0.42 , -0.45 , and -0.58 , respectively ) . Dry mouth symptoms correlated with low Testo and and rostenedione , whereas dry eyes correlated with low estrogens , most strongly estrone ( rs = -0.63 ) . Presence of anti-SS-A and /or anti-SS-B was independently associated with low estradiol ( area under the receiver operating characteristic curve , 0.82 ) . All metabolites increased during DHEA but not during placebo . The relative increases were less for estrogens and Testo compared to dihydrotestosterone and glucuroni date d and rogen metabolites . Dry mouth symptoms decreased during DHEA therapy . CONCLUSIONS Disease manifestations in primary Sjogren 's syndrome were associated with low sex hormone levels , dry mouth symptoms with low and rogens , and dry eyes with low estrogens . Exogenous DHEA was preferentially transformed into and rogens rather than into estrogens", "The physiological role of dehydroepi and rosterone ( DHEA ) is not well understood , but studies suggest positive effects on subjective health and bone metabolism . We have conducted a clinical trial with DHEA replacement in adrenal failure with the primary aim of evaluating effects on subjective health status and sexuality . Thirty-nine women with adrenal failure were r and omized to 9 months of treatment with 25 mg DHEA ( n = 19 ) or placebo ( n = 20 ) . Treatment effects were assessed by vali date d question naires of subjective health and sexuality . DHEA replacement yielded a wide variation of effects on the subjective health scales , which were not different from the effects of placebo . Almost all patients receiving DHEA obtained normal and rogen levels . Eighty-nine percent of the patients receiving DHEA experienced side-effects , in particular increased sweat odor and scalp itching . DHEA replacement did not significantly change the levels of blood lipids , IGF-I , and markers of bone metabolism . In conclusion , we do not find evidence of beneficial effects of DHEA on subjective health status and sexuality in adrenal failure . However , DHEA may be beneficial for subgroups of patients with adrenal failure , but these remain to be identified . Premenopausal and rogen levels can be restored with 25 mg DHEA daily in most female patients , but side-effects are frequent", "OBJECTIVE The aim of this study was to evaluate the safety of 52 weeks of DHEA 50 mg daily oral dose given to postmenopausal women with low libido to improve sexual function . METHOD 93 postmenopausal women were enrolled in a 52-week r and omised , double-blind , placebo-controlled trial and received either DHEA 50 mg or placebo ( PL ) daily . The effects of DHEA versus placebo on lipid profile , insulin-glucose homeostasis and the endomentrium were assessed over 52 weeks . RESULTS Oral DHEA , 50mg/day , was not associated with any effects on blood lipids or insulin resistance . The pattern of breakthrough bleeding did not substantially differ between the DHEA and PL groups and no significant adverse endometrial effects were apparent . CONCLUSIONS The use of 50 mg oral DHEA did not significantly alter lipid profile , insulin sensitivity or adversely affect the endometrium in postmenopausal women", "CONTEXT Recent studies disputed the widely promoted anti-aging effect of dehydroepi and rosterone ( DHEA ) supplementation ; however , conflicting data exist on whether physiological DHEA supplementation enhances exercise training effects on body composition , physical performance , and cardiometabolic risk in healthy postmenopausal women . OBJECTIVE The aim of this study was to determine whether 12 wk of DHEA supplementation ( 50 mg/d ) in postmenopausal women enhances exercise-related changes in body composition , physical performance , and cardiometabolic risk . DESIGN AND SETTING This study was a 12-wk r and omized double-blind , placebo-controlled trial and took place at the Mayo Clinic General Clinical Research Center ( Rochester , MN ) . PARTICIPANTS Thirty-one sedentary , postmenopausal , Caucasian women ( mean + /- sem age 64.6 + /- 1.0 yr ) completed the study . INTERVENTION Participants were r and omized to one of two 12-wk interventions : 1 ) exercise training plus 50 mg/d of DHEA ( n = 17 ) , or 2 ) exercise training plus placebo ( n = 14 ) . The exercise intervention consisted of both endurance ( 4 d/wk ) and resistance ( 3 d/wk ) exercise components . MAIN OUTCOME MEASURES The main outcomes were measures of body composition , physical performance , and measures of cardiometabolic risk . RESULTS DHEA treatment with exercise result ed in increases in circulating sulfated DHEA ( 650 % ) , total testosterone ( 100 % ) , estradiol ( 165 % ) , estrone ( 85 % ) , and IGF-I ( 30 % ) ( all P physical performance , body composition , and insulin sensitivity , administration of DHEA provided no additional benefits . CONCLUSIONS Twelve weeks of combined endurance and resistance training significantly improved body composition , physical performance , insulin sensitivity , and low-density lipoprotein cholesterol particle number and size , whereas DHEA had no additional benefits", "Dehydroepi and rosterone ( DHEA ) is an adrenal and rogen precursor of sex steroids with effects on a variety of physiological events [ 1 ] . DHEA and its sulfate ( DHEAS ) , as well as and rostendione , have minimal and rogenic activity [ 2 ] . It has been reported that serum levels of DHEA and DHEA-S substantially decrease with age , and experimental studies have demonstrated benefit with DHEA substitution at physiologic doses [ 3 ] . DHEA and DHEA-S are abundant in the circulation . DHEA-S accounts for more than 99 % of the steroid in the serum , with less than 1 % of free DHEA . Their main actions have been related to cellular control , immunoregulation , obesity and lipid metabolism [ 2 ] . Estrogen and and rogen replacement therapy date s to 1941 , when Geist and Salmon used and rogen therapy to treat climacteric symptoms [ 4 ] . DHEA has also been used as part of hormone therapy . In a study in which women from 60 to 70 years age received DHEA , a significant increase was observed in bone mineral density at the hip . This was followed by an increase in serum osteocalcin ( a bone formation marker ) , which was supposed to be due to DHEA and rogenic action . These results suggest that DHEA can be useful in the prevention and treatment of osteoporosis [ 5 ] . In another study , DHEA was given in a dose of 50 mg/day for 6 months to men and women aged 40 to 70 years . No changes were observed in estrone ( E ) and estradiol ( E2 ) serum levels in either sex . In women , there was a decrease in high-density lipoprotein cholesterol ( HDL-C ) levels without changes in the other lipids . Insulin sensitivity and mean body fat were not modified , and an increase in subjective physical well-being was cl aim ed in 67 % of men and in 84 % of women [ 6 ] . When DHEA was applied percutaneously in women from 60 to 70 years age for 12 months , no changes were observed in body weight . However , there was a 3.8 % decrease of body fat and an increase of 3.5 % in the muscular mass at the femoral level . HDL-C levels decreased 8 % , but the HDL-C/total cholesterol ratio did not change due to a parallel decrease of total cholesterol [ 7 ] . It then appears that the literature is controversial about DHEA effects . Commercial DHEA formulations are frequently used in Mexico , as in other countries . Therefore , the objective of this study was to evaluate a formulation of DHEA ( Siscelar plus  ) , commercially available in Mexico , on hormone and lipid levels and on climacteric symptoms after administration to postmenopausal women", "The objective of this study was to explore , for the first time , the changes in the pangenomic profile induced in human skin in women treated with dehydroepi and rosterone ( DHEA ) applied locally . Sixty postmenopausal women participated in this phase II prospect i ve , r and omized , double-blind and placebo-controlled study . Women were r and omized to the twice daily local application of 0 % ( placebo ) , 0.3 % , 1 % or 2 % DHEA cream . Changes in the pangenomic expression profile were studied using Affymetrix Genechips . Significant changes ( p DHEA-responsive probe sets corresponding to 52 well-characterized genes and 9 unknown gene sequences were identified . A dose-dependent increase in the expression of several members of the collagen family was observed , namely COL1 , COL3 and COL5 as well as the concomitant modulation of SPARC , a gene required for the normal deposition and maturation of collagen fibrils in the dermis . Several genes involved in the proliferation and differentiation of keratinocytes were also modulated . In addition , topical DHEA reduced the expression of genes associated with the terminal differentiation and cornification of keratinocytes . Our results strongly suggest the possibility that DHEA could exert an anti-aging effect in the skin through stimulation of collagen bio synthesis , improved structural organization of the dermis while modulating keratinocyte metabolism", "ABSTRACT Background Sexual desire is affected by endocrine and psychosocial factors . Menopausal hormonal changes are relevant to the causes of sexual dysfunction during reproductive aging . Aim To evaluate the effects of different types of hormonal replacement therapy ( HRT ) on sexual function , frequency of sexual intercourse , and quality of relationship in early postmenopausal women . We recruited 48 healthy postmenopausal women aged 50–60 years ( mean age 54.5 ± 3.3 years ) . Women with climacteric symptoms were uniformly r and omized into three groups receiving either dehydroepi and rosterone ( DHEA 10 mg ) daily , or daily oral estradiol ( 1 mg ) plus dihydrogesterone ( 5 mg ) , or daily oral tibolone ( 2.5 mg ) for 12 months . Women who refused hormonal therapy were treated with oral vitamin D ( 400 IU ) . Efficacy was evaluated using the McCoy Female Sexuality Question naire before treatment and after 12 months . We evaluated the hormonal profile before treatment and after 3 , 6 and 12 months . Results The groups receiving DHEA or HRT reported a significant improvement in sexual function compared to baseline ( p the McCoy total score . The quality of relationship was similar at baseline and after 3 , 6 and 12 months of treatment . There were significant increases in the numbers of episodes of sexual intercourse in the previous 4 weeks in women treated with DHEA , HRT and tibolone in comparison with the baseline value ( p No changes in the McCoy score occurred in women receiving vitamin D. Conclusions Daily oral DHEA therapy at the dose of 10 mg , HRT and tibolone all provided a significant improvement in comparison with vitamin D in sexual function and in frequency of sexual intercourse in early postmenopausal women", "Objective : Because a previous 1-week study has shown no or minimal changes in the serum levels of dehydroepi and rosterone ( DHEA ) and its metabolites after up to daily 1.8 % ( 23.4 mg ) intravaginal DHEA , the objective of the present study was to investigate the serum steroid levels during a 12-week daily intravaginal administration of 0 % , 0.25 % , 0.5 % , and 1.0 % DHEA ( Prasterone ) 1.3 mL ovules . Methods : In a double-blind , placebo-controlled phase III study , 218 postmenopausal women ( age range , 42 - 74 y ) were r and omized to receive daily one of four DHEA concentrations intravaginally . Serum steroids were measured by a Good Laboratory Practice -vali date d mass spectrometry technology in sample s obtained at time of visit . Results : The serum levels of DHEA and 11 of its metabolites measured at screening , day 1 , and weeks 2 , 4 , 8 , and 12 in women showed no or minimal changes during the whole observation period , with all values remaining well within the limits of normal postmenopausal women . No accumulation of the steroid metabolites nor change in DHEA bioavailability was detected . Conclusions : The present data show that local daily intravaginal DHEA administration at DHEA doses of 3.25 - 13 mg was able to rapidly and efficiently achieve correction of all the signs and symptoms of vaginal atrophy and improve sexual function and caused no or minimal changes in serum sex steroid levels , which all remain within the normal postmenopausal range , thus avoiding the risks of all estrogen formulations", "Objective : Because the secretion of dehydroepi and rosterone ( DHEA ) , the exclusive source of sex steroids in postmenopausal women , is already decreased by 60 % and continues to decline at the time of menopause , the objective of this study was to examine the effect of intravaginal DHEA on the symptoms and signs of vaginal atrophy . Methods : This prospect i ve , r and omized , double-blind and placebo-controlled phase III clinical trial studied the effect of Prasterone ( DHEA ) applied locally in the vagina on the signs and symptoms of vaginal atrophy in 216 postmenopausal women . Results : All three doses ( 0.25 % , 0.5 % , and 1.0 % ) of DHEA ovules applied daily intravaginally induced a highly significant beneficial change in the percentage of vaginal parabasal and superficial cells and pH as well as in the most bothersome symptom at 2 weeks . At the st and ard 12-week time interval , 0.5 % DHEA caused a 45.9 ± 5.31 ( P vs placebo ) decrease in the percentage of parabasal cells , a 6.8 ± 1.29 % ( P increase in superficial cells , a 1.3 ± 0.13 unit ( P 0.0001 ) decrease in vaginal pH , and a 1.5 ± 0.14 score unit ( P the severity of the most bothersome symptom . Similar changes were seen on vaginal secretions , color , epithelial surface thickness , and epithelial integrity . Comparable effects were observed at the 0.25 % and 1.0 % DHEA doses . Conclusions : Local Prasterone , through local and rogen and estrogen formation , causes a rapid and efficient reversal of all the symptoms and signs of vaginal atrophy with no or minimal changes in serum steroids , which remain well within the normal postmenopausal range . This approach avoids the fear of systemic effects common to all presently available estrogen formulations and adds a novel physiological and rogenic component to therapy", "INTRODUCTION Dehydroepi and rosterone ( DHEA ) and its sulfate DHEAS , which are the most abundant steroids in women , decline with age . We have shown association between low sexual function and low circulating DHEAS levels in women . AIM The aim of this study was to evaluate whether restoration of circulating DHEA levels in postmenopausal women to the levels seen in young individuals improves sexual function . METHODS Ninety-three postmenopausal women not using concurrent estrogen therapy were enrolled in a 52-week r and omized , double-blind , placebo controlled trial and received either DHEA 50 mg or placebo ( PL ) daily . MAIN OUTCOME MEASURES Efficacy was assessed through 26 weeks . The main outcome measures were the change in total satisfying sexual events ( SSE ) and the change in the Sabbatsberg Sexual Self-Rating Scale ( SSS ) total score . Secondary measures were the Psychological General Well-Being Question naire ( PGWB ) , and the Menopause-Specific Quality of Life Question naire ( MENQOL ) . Hormonal levels , adverse events ( AEs ) , serious adverse events ( SAEs ) and clinical labs were evaluated over 52 weeks . RESULTS Eighty-five participants ( 91 % ) were included in the 26-week efficacy analysis . There were no significant differences between the DHEA and PL groups in the change in total SSE per month or the SSS , PGWB , and MENQOL change scores . Overall AE reports and number of withdrawals as a result of AEs were similar in both groups ; however more women in the DHEA group experienced and rogenic effects of acne and increased hair growth . CONCLUSIONS In this study treatment of postmenopausal women with low sexual desire with 50 mg/day DHEA result ed in no significant improvements in sexual function over PL therapy over 26 weeks", "Following the compelling data obtained in a pivotal phase III clinical trial performed in 218 postmenopausal women suffering from vaginal atrophy who received daily intravaginal 0.25 , 0.5 or 1.0 % DHEA ( dehydroepi and rosterone ) ovules for 12 weeks , we have performed analysis of the four co- primary objectives at each site of that multicentre U.S. and Canadian trial . Comparison was made of the change in percentage of parabasal and superficial cells , vaginal pH and severity of the most bothersome symptom . The site-by-site ( seven sites ) analysis has shown that 10–13 women per group are generally sufficient to obtain a significant or highly statistically significant decrease in vaginal pH and percentage of parabasal cells and increased percentage of superficial cells at p values ranging from 0.02 to vaginal pain as the most bothersome symptom , a statistically significant difference from baseline was found at six out of seven sites . The exceptionally high consistency between all sites in this phase III study and high potency of the compound permit to obtain a clinical ly and statistically significant to highly significant effect of treatment on all parameters of vaginal atrophy with the 0.5 % DHEA daily intravaginal dose which does not significantly affect the serum levels of oestrogens , thus avoiding systemic risks" ]

[ "BACKGROUND The French- Language Society of Paediatric Anaesthesiologists ( ADARPEF ) design ed a 1-year prospect i ve , multicenter and anonymous study to up date both epidemiology and morbidity of regional anesthesia in children . METHODS From November 2005 to October 2006 , data from participating hospitals were recorded using an identification form , a data recording form , and a complication form . Information collected included the characteristics of the hospitals , the number and type of regional anesthetics ( RA ) , the age of the involved children as well as the incidence , and type of complications . RESULTS Data collected in 47 institutions included 104,612 pure general anesthesias ( GAs ) , 29,870 GAs associated with regional blocks , and 1262 pure regional blocks . Central blocks accounted for 34 % of all RA . Peripheral blocks ( 66 % ) were upper or lower limb blocks ( 29 % of peripheral blocks ) , trunk blocks , and face blocks ( 71 % ) . In children aged ≤3 years , the percentage of central blocks was similar to the peripheral ones ( 45 % vs 55 ) , while in older children , peripheral blocks were more than four times used than central ones . Complications ( 41 involving 40 patients ) were rare and usually minor . They did not result in any sequelae . The study revealed an overall rate of complication of 0.12 % ; CI 95 % [ 0.09 - 0.17 ] , significantly six times higher for central than for peripheral blocks . CONCLUSIONS As a result of the low rate of complications , RA techniques have a good safety profile and can be used to provide postoperative analgesia . In addition , the results should encourage anesthesiologists to continue to use peripheral instead of central ( including caudal ) blocks as often as possible when appropriate", "PURPOSE : Colorectal surgery is associated with postoperative ileus , which contributes to delayed discharge . This study was design ed to investigate the effect of thoracic epidural anesthesia and analgesia on gastrointestinal function after colorectal surgery under st and ardized controlled postoperative care . METHODS : Forty-two patients diagnosed with either colonic cancer , diverticulitis , polyps , or adenoma , and scheduled for elective colorectal surgery , were r and omly assigned to either postoperative patient-controlled analgesia ( PCA ) with intravenous morphine ( n=21 ) or epidural analgesia with a mixture of bupivacaine and fentanyl ( n=21 ) . Postoperative early oral feeding and assistance to mobilization were offered to all patients . Pain visual analog scale ( 1–100 mm ) , passage of flatus and bowel movements , length of hospital stay , and readiness for discharge were recorded . RESULTS : Pain visual analog scale ( visual analog scale , 1–100 mm ) at rest , on coughing , and daily on mobilization was significantly lower in the epidural group compared with the patient-controlled analgesia group . Median values for the visual analog scale group were 7 ( 95 percent confidence interval , 2–18 ) mm , 19 ( 95 percent confidence interval , 4–38 ) mm , and 10 ( 95 percent confidence interval , 5–33 ) mm , respectively , and , for the patient-controlled analgesia group , were 24 ( 95 percent confidence interval , 18–51 ) mm , 59 ( 95 percent confidence interval , 33–74 ) mm , and 40 ( 95 percent confidence interval , 29–79 ) mm , respectively ( P ) . Intake of protein and calories and time out of bed were similar in both groups . Mean time intervals ± st and ard deviation from surgery to first flatus and first bowel movement occurred earlier in the epidural group , 1.9±0.6 days and 3.1±1.7 days , respectively , compared with patient-controlled analgesia , 3.6±1.5 days and 4.6 ± 1.6 days , respectively ( P occurred in 33 percent of the patient-controlled analgesia group and 28 percent of the epidural group . There was no significant difference in length of hospital stay between the two groups with a mean of 7.3±3.7 days in the patient-controlled analgesia group and 8.5±4.2 days in the epidural group . Readiness for discharge was similar in both groups . CONCLUSION : Thoracic epidural analgesia has distinct advantages over patient-controlled analgesia morphine in providing superior quality of analgesia and shortening the duration of postoperative ileus . However , discharge home was not faster , indicating that other perioperative factors influence the length of hospital stay", "UNLABELLED Anesthetic methods used during cesarean section have advantages and disadvantages to both mothers and infants and may result in short and long term neonatal effects . OBJECTIVE To determine the effects of general and regional anesthesia on the infants , a prospect i ve , r and omized trial was performed in Siriraj Hospital , Mahidol University . MATERIAL AND METHOD 341 uncomplicated pregnant women who were to be delivered at term by Cesarean section were recruited and r and omized to receive general anesthesia , GA ( 103 ) ; epidural anesthesia , EA ( 120 ) and spinal anesthesia , SA ( 118 ) . The immediate fetal and neonatal effects were assessed by cord blood gas analysis and the infant 's Apgar scores . The Neurologic and Adaptive Capacity Scores ( NACS ) was performed within 4 hours after birth by two pediatricians who were blind to the anesthetic method . RESULT Maternal age , weight , height , duration of the operation and infants ' birth weight were not different among the study groups . In the EA and SA group , maternal systolic blood pressure decreased more than 20 per cent from the baseline in more than half . The infants ' Apgar scores at 1 and 5 minutes were 8.3 + /- 1.9 ; 8.2 + /- 1.6 ; 6.7 + /- 2.8 , and 9.7 + /- 0.9 ; 9.8 + /- 0.7 ; 9.2 + /- 1.6 in EA , SA and GA group respectively . The adaptive capacity , active tone , passive tone , general assessment and primary reflexes of the NACS were not statistically different . CONCLUSION Apgar scores of the infants whose mothers received general anesthesia were lower than infants whose mothers received regional anesthesia but the NACS were not statistically different among the three study groups", "The actual incidence of neurologic dysfunction result ing from hemorrhagic complications associated with neuraxial blockade is unknown . Although the incidence cited in the literature is estimated to be less than 1 in 150,000 epidural and less than 1 in 220,000 spinal anesthetics , recent epidemiologic surveys suggest that the frequency is increasing and may be as high as 1 in 3000 in some patient population s. Overall , the risk of clinical ly significant bleeding increase with age , associated abnormalities of the spinal cord or vertebral column , the presence of an underlying coagulopathy , difficulty during needle placement , and an indwelling neuraxial catheter during sustained anticoagulation ( particularly with st and ard heparin or low-molecular weight heparin ) . The need for prompt diagnosis and intervention to optimize is also consistently reported . In response to these patient safety issues , the American Society of Regional Anesthesia and Pain Medicine ( ASRA ) convened its Third Consensus Conference on Regional Anesthesia and Anticoagulation . Practice guidelines or recommendations summarize evidence -based review s. However , the rarity of spinal hematoma defies a prospect i ve r and omized study , and there is no current laboratory model . As a result , the ASRA consensus statements represent the collective experience of recognized experts in the field of neuraxial anesthesia and anticoagulation . These are based on case reports , clinical series , pharmacology , hematology , and risk factors for surgical bleeding . An underst and ing of the complexity of this issue is essential to patient management", "Colonic surgery patients were studied to measure : the influence of continuous thoracic epidural analgesia ( TEA ) on a postoperative pain score , the time till onset of defaecation , blood loss , postoperative temperature elevations , rate of bacterial contamination of wounds and urine , and general surgical complications . Group I patients ( n = 57 ) received general anaesthesia and TEA for the operation , followed by continuous TEA ( 0·25 per cent bupivacaine ) for 72 h. Group II patients ( n = 59 ) received general anaesthesia for the operation , followed by systemic analgesia on request . Significant beneficial effects of TEA in group I were demonstrated by lower pain scores in the first 24 h after surgery and earlier defaecation . However , there were fewer temperature elevations in group II . There was no significant difference between the groups in terms of positive bacteriological cultures , blood loss , need for postoperative mechanical ventilation and complications . However , there was a trend toward a higher rate of rectal anastomotic breakdown , increased blood replacement and intensive care therapy , and longer hospitalization in group I. These results do not suggest any significant beneficial therapeutic effect of continuous TEA in colonic surgery compared with a conventional systemic analgesic regimen . In selected patients ( i.e. those with severe pain or those prone to develop postoperative ileus ) continuous TEA may be beneficial", "We have studied the effect of extradural analgesia on postoperative venous thrombosis in patients undergoing knee arthroplasty . Forty-eight patients were allocated r and omly to receive either general anaesthesia or extradural analgesia with local anaesthetics for 3 days . All patients wore compressive elastic stockings and no anticoagulant drugs were administered . Bilateral venography was performed 10 days after surgery . Continuous extradural analgesia did not impede mobilization of the patients . One case of nonfatal pulmonary embolism occurred in a patient who received general anaesthesia . The use of continuous extradural analgesia result ed in a significant difference in the total incidence of deep vein thrombosis ( 18 % compared with 59 % after general anaesthesia ( P = 0.02 ] . The incidence of calf vein thrombosis was 12 % compared with 45 % after general anaesthesia ( P = 0.05 )", "Ninety healthy parturients undergoing elective caesarean section were r and omly allocated to receive either general ( n = 30 ) , epidural ( n = 30 ) or spinal ( n = 30 ) anaesthesia . Acid-base status , Apgar score and neurobehavioural status , using the neurologic and adaptive capacity scoring ( NACS ) system , were studied in the newborn . Apgar scores and acid-base parameters were similar in all the three groups . NACS testing revealed significantly more vigorous babies in the spinal anaesthesia group than in the other two groups at 15 min and 2 h interval after delivery , despite a higher incidence of maternal hypotension . We conclude that newborns tend to have a better neurobehavioural status in the early post-delivery period if their mothers receive spinal anaesthesia rather than general or epidural anaesthesia for caesarean section", "Twenty-two patients undergoing upper abdominal surgery were entered into a r and omized , double-blind study to receive extradural ( T7-T8 ) 0.5 % bupivacaine 9 ml followed by 25 mg h-1 with or without additional extradural morphine ( bolus 4 mg plus 0.5 mg h-1 ) , for 16 h after operation . Addition of morphine was associated with total alleviation of pain , and a stable level of sensory analgesia , but not with changes in blood glucose and cortisol concentrations or postoperative impairment of lung function ( PEFR , FEV1 , FVC ) . Two patients were withdrawn because of hypotension or respiratory depression", "The effects of thoracic epidural anesthesia ( TEA ) on total body oxygen supply-dem and ratio are complex due to potential influences on both O2 delivery ( & OV0422;O2 ) and consumption ( & OV0312;O2 ) . One hundred and five patients undergoing abdominal aortic surgery were r and omly assigned to one of three groups to compare the cardiovascular and metabolic responses associated with ( 1 ) thoracic epidural anesthesia plus light general anesthesia ( group TEA ) ; ( 2 ) general anesthesia with halothane ( group H ) ; and ( 3 ) neuroleptanalgesia ( group NLA ) . Values of cardiac index ( CI ) and & OV0422;O2 were less intra operatively in the TEA group than in the H or NLA groups , while & OV0312;O2 values were similar . & OV0312;O2 during recovery was greater in both the TEA and NLA groups than in the H group . Consequently the oxygen supply-dem and ratio ( & OV0422;O2/&OV0312;O2 ) was less in the TEA group throughout the perioperative period and about 30 % below baseline values during early recovery . At comparable & OV0312;O2 , CI and mixed venous O2 saturation were always less in the TEA group than in the NLA group . Heart rate was slowest intra operatively during TEA , and stroke work was less with TEA than with NLA . As cardiac filling pressure and systemic vascular resistance did not differ among the three groups , reduced adaptation of CI to tissue O2 needs during TEA was attributed to negative inotropic and chronotropic effects of the sympathetic blockade . We conclude that in patients undergoing abdominal aortic surgery , TEA has no apparent advantage over general anesthesia", "The rate of absorption of paracetamol following oral administration was used as an indirect measure of the rate of gastric emptying . This was to determine the effect on gastric motility of the addition of fentanyl to a solution of local anaesthetic given into the epidural space to provide pain relief following Caesarean section . Thirty subjects were r and omly allocated to receive either bupivacaine plus fentanyl or bupivacaine alone . The area under the curve of the graph of plasma paracetamol concentration versus time was calculated for each subject at 45 and 90 minutes after administration of the epidural injection , and this value was used as an index of the rate of gastric emptying . This study demonstrated that gastric emptying may be normal immediately following Caesarean section under epidural anaesthesia , but that if fentanyl is added to the epidural solution , gastric emptying is significantly slower in the first 45 minutes following surgery ( p < 0.05 )", "BACKGROUND This study was undertaken to determine if thoracic epidural analgesia is of practical benefit after bowel resection . METHODS Patients were prospect ively r and omized to receive either a thoracic epidural or patient-controlled analgesia for pain control after bowel resection . A st and ardized postoperative protocol was instituted after surgery . RESULTS Pain scores were significantly lower in the epidural group . Return of bowel function , and interval to discharge was not different between groups . Cost and complication rates were significantly higher in the epidural group . CONCLUSIONS Although pain scores were significantly lower in the epidural group , this did not translate into a quicker return of bowel function or earlier discharge of the patient . Furthermore , the epidural group had a significantly higher complication rate and cost . Therefore , while thoracic epidural analgesia provides superior pain control , it does not offer a significant advantage over patient-controlled analgesia in return of bowel function after bowel resection", "The endocrine response , and the relief of pain , following the extradural administration of morphine or a local anaesthetic agent bupivacaine ( 0.5 % ) were studied for 24h after abdominal surgery and compared with a control group given conventional i.v . morphine after operation . Sample s were taken before and at 2 , 4 , 6 , 12 and 24 h after skin incision . Pain relief in both extradural groups was significantly better when compared with the control group . In all three groups , the plasma concentration of cortisol was increased immediately after surgery . Thereafter , significantly lower values were seen in the extradural groups . Plasma adrenaline concentration was lower immediately after surgery only in the group given the extradural local anaesthetic . Plasma noradrenaline concentration remained unchanged after extradural local anaesthesia while an intermediate increase occurred after extradural morphine . Plasma noradrenaline concentration was significantly greater in the controls compared with both extradural groups . Our results indicate that extradural analgesia with a local anaesthetic drug can suppress the increases in the plasma concentrations of the catecholamines and cortisol after surgery . In contrast to extradural local anaesthetic extradural morphine can not suppress the endocrine response immediately after surgery . However , later in the postoperative period , extradural morphine can suppress the endocrine response , thus indicating that postoperative pain is a factor involved in the stress response following surgery", "Objective : To compare general , epidural and combined spinal-epidural anesthesia with respect to short-term outcome of newborns delivered by elective Cesarean section of healthy parturients with normal pregnancies . Study design : A total of 238 eight pregnant women admitted to our institution between January 1998 and July 2002 , for whom elective Cesarean section was planned after 38 weeks ' gestation , were grouped according to the kind of anesthesia used for the procedure . Maternal characteristics , birth weight , Apgar scores , and maternal and umbilical artery ( UA ) acid-base parameters were analyzed . Results : Maternal pH was significantly lower and pCO2 and pO2 were significantly higher in the general anesthetic group , compared to the other two groups ( 7.38 ± 0.03 vs. 7.43 ± 0.02 and 7.43 ± 0.05 , respectively ; 35.03 ± 3.88 mmHg vs. 29.25 ± 5.05 mmHg and 29.64 ± 4.16 mmHg , respectively ; and 224.56 ± 86.77 mmHg vs. 151.28 ± 38 mmHg and 157.36 ± 53.51 mmHg , respectively , p was higher in the general anesthetic group , compared to the spinal-epidural group ( 7.29 ± 0.02 vs. 7.26 ± 0.06 , p were higher when general anesthetic was administered , compared to the two regional modalities ( 15.60 ± 5.48 mmHg vs. 9.29 ± 4.41 mmHg and 9.20 ± 4.06 mmHg , respectively ; and 17.37 ± 9.79 % vs. 7.87 ± 4.98 % and 6.90 ± 5.22 % , respectively , p fell to zero in some cases in the combined spinal-epidural group , without an evident effect on fetal well-being . No fetal acidemia was noted in any group . Neonatal outcomes were similar in the three groups studied . Conclusions : Type of anesthesia does not influence short-term outcomes in infants born via elective Cesarean section , although differences in acid-base status of both the mother and especially the newborn recommend careful use of spinal anesthesia", "Background Several previous surveys have estimated the rate of major complications that occur after regional anesthesia . However , because of the increase in the use of regional anesthesia in recent years and because of the introduction of new techniques , re appraisal of the incidence and the characteristics of major complications is useful . Methods All French anesthesiologists were invited to participate in this 10-month prospect i ve survey based on ( 1 ) voluntary reporting of major complications related to regional anesthesia occurring during the study period using a telephone hotline service available 24 h a day and managed by three experts , and ( 2 ) voluntary reporting of the number and type of regional anesthesia procedures performed using pocket booklets . The service was free of charge for participants . Results The participants ( n = 487 ) reported 56 major complications in 158,083 regional anesthesia procedures performed ( 3.5/10,000 ) . Four deaths were reported . Cardiac arrest occurred after spinal anesthesia ( n = 10 ; 2.7/10,000 ) and posterior lumbar plexus block ( n = 1 ; 80/10,000 ) . Systemic local anesthetic toxicity consisted of seizures only , without cardiac toxicity . Lidocaine spinal anesthesia was associated with more neurologic complications than bupivacaine spinal anesthesia ( 14.4/10,000 vs. 2.2/10,000 ) . Most neurologic complications were transient . Among 12 that occurred after peripheral nerve blocks , 9 occurred in patients in whom a nerve stimulator had been used . Conclusion This prospect i ve survey based on a free hotline permanent telephone service allowed us to estimate the incidence of major complications related to regional anesthesia and to provide a detailed analysis of these complications", " Fifty-five patients presenting with fractured neck of femur were r and omly allocated to either a st and ard general anaesthetic or spinal block in the lateral position combined with light sedation . The comparability of the two groups was established . There was little difference in the intra-operative course of postoperative morbidity in the two groups . There was a statistically significant difference in post-operative mortality between two groups , the general anaesthetic group showing a much higher mortality than the spinal group", "OBJECTIVE To compare general and spinal anesthesia with respect to the short-term outcome of newborns born by elective cesarean deliveries . METHODS Pregnant women admitted to our hospital from January 1999 to July 2000 , for whom elective repeat cesareans were planned after 37 weeks gestation , were allocated r and omly after their informed consent to spinal anesthesia or general anesthesia . Maternal age , gestational age , birth weight , Apgar 's score , hospital stay duration , and duration of cesarean section time were all noted . The rate of the neonatal respiratory depression , perinatal asphyxia , and admittance to the neonatal intensive care unit of the infants were documented . We also studied arterial sample s withdrawn from the cord for the pH , bicarbonate , PaO(2 ) ( oxygen pressure , arterial ) , and PaCO(2 ) ( carbon dioxide pressure , arterial ) . The serum levels of creatine kinase with myocardial-specific isoform , aspartate aminotransferase , alanine aminotransferase , and total cortisol levels of the newborns were measured and served in ruling out perinatal stress and in confirming the diagnosis of perinatal asphyxia ( and of myocardial damage ) . Statistical analyses was performed with the use of an unpaired Student 's t-test , Chi-square test , and a power calculation was done . RESULTS From the r and omly selected patients , we had 38 ( 45.2 % ) infants for general anesthesia and 46 ( 54.8 % ) for spinal anesthesia . None of our primary endpoints favored any of the study groups , and the clinical short-term outcome of the infants was similar in the neonates born both by spinal and general anesthesia ( P>0.05 ) . The biochemical assays did not rule out or confirm any differences in the occurrence of perinatal stress ( P>0.05 ) . CONCLUSION Anesthesia type does not seem to influence the short-term outcome of the newborn infants for the elective cesarean deliveries . We believe that both spinal and general anesthesia could be performed in elective term cesarean deliveries without any risk to the newborn infants", " One hundred and one patients were r and omly allocated to have their peripheral vascular surgery performed under general anaesthesia ( 51 patients ) or spinal anaesthesia ( 50 patients ) . Intraoperative haemodynamic changes were markedly different between the two groups with a higher incidence of hypotension in the spinal group ( 72 % vs 31 % ) and a higher incidence of hypertension in the general anaesthesia group ( 22 % vs 0 % ) . Blood loss was significantly less in the spinal group ( 560 , SD 340 , ml vs 792 , SD 440 , ml ) . Postoperatively three patients from the general anaesthesia group died from causes unrelated to the anaesthesia , and one had a myocardial infa rct . Two patients in the spinal group had myocardial infa rcts , both had been treated for bradycardia and hypotension intraoperatively , and one died . There was a significantly higher incidence of postoperative chest infection in the general anaesthesia group ( 33 % vs 16 % ) . There was no significant difference between the groups in the incidence of postoperative confusion , or lower limb amputation rate or need for further surgery prior to hospital discharge", "Three solutions administered by continuous extradural infusion for postoperative analgesia were compared in a r and omized , double-blind manner . All patients underwent major abdominal gynaecological surgery and received 0.125 % bupivacaine in 0.9 % saline , diamorphine in 0.9 % saline ( 0.5 mg in 15 ml ) or diamorphine mixed with 0.125 % bupivacaine ( 0.5 mg in 15 ml ) , at a rate of 15 ml h-1 . The bupivacaine-diamorphine mixture provided significantly superior analgesia compared with either bupivacaine or diamorphine alone . No major side effects were encountered", "Forty elderly patients ( mean age 78.9 years ) undergoing acute surgery for hip fracture were given at r and om either spinal analgesia with bupivacaine 0.75 % or general anaesthesia with diazepam , fentanly and N2O/O2 . Mental function was studied pre‐operatively with an abbreviated mental test and 1 week and 3 months postoperatively in both groups . Mortality and number of complications was similar in the two groups , but a shorter time of ambulation was seen in the spinal group compared to the general anaesthetic group . No persistent impairment in mental function was found after acute hip surgery under spinal or general anaesthesia and the only advantage of regional technique was a shorter time of ambulation", "We assessed the efficacy and side effects of postoperative analgesia with three different pain regimens in 90 patients undergoing major abdominal surgery . The patients were r and omly assigned to one of three groups : epidural morphine ( EM ) or sufentanil ( ES ) , both combined with bupivacaine , or IM morphine ( IM ) at fixed intervals . Before incision , patients in the epidural groups received sufentanil or morphine in bupivacaine via a thoracic catheter , followed by a continuous infusion 1 h later . General anesthesia consisted of N2 O/O2 and isoflurane for all groups . Patients in all groups received IV sufentanil as part of their anesthetic management . Patients in the IM group received IV sufentanil 1 [ micro sign]g/kg before incision , and patients in all groups received sufentanil 10 [ micro sign]g for inadequate analgesia . Postoperatively , the epidural or IM treatment was continued for > or = to5 days . Postoperative analgesia at rest and during coughing and movement was significantly better in the epidural groups than in the IM group during the 5 consecutive days . There were no significant differences between the epidural groups . The incidence of most side effects was similar in all groups . We conclude that epidural analgesia provided better pain relief than IM analgesia , even if the latter was optimized by fixed-dose administration at fixed intervals and included adjustments on dem and . Epidural sufentanil and morphine , both combined with bupivacaine , seemed to be equally effective with similar side effects . Implication s : Postoperative analgesia with epidural sufentanil or morphine and bupivacaine after major abdominal surgery seemed to be better than the conventional method of IM morphine treatment , despite optimal administration , i.e. , fixed doses at fixed intervals with regular adjustments . Analgesic efficacy and side effects of epidural sufentanil and morphine were similar . ( Anesth Analg 1998;87:1346 - 53", "BACKGROUND AND OBJECTIVES This prospect i ve r and omized study was design ed to determine the hemodynamic effects and quality of combined lumbar and sacral plexus block compared with plain bupivacaine spinal anesthesia in the elderly for repair of proximal femoral fractures . METHODS Twenty-nine elderly patients ranging in age from 68 to 97 years were r and omly assigned to 2 groups : a spinal anesthesia group with single-shot 3 mL 0.5 % plain bupivacaine , and a combined block group with 30 mL lidocaine 1.33 % with epinephrine for the posterior lumbar plexus block and 10 mL same mixture for the parasacral block and an iliac crest block with 5 mL lidocaine 1 % . RESULTS No need for general anesthesia was encountered in either group . Anesthesia was judged unsatisfactory in 1 of 15 patients in the combined block group . The initial decrease of mean arterial pressure was 38 % in the spinal group and 27 % in the block group and was not significantly different . A more prolonged hemodynamic effect was found in the spinal group , indicated by the more frequent use of ephedrine to stabilize blood pressure ( P Patients over 85 years had a significantly larger decrease in blood pressure than younger patients ( P Plain bupivacaine spinal anesthesia and combined lumbar/sacral plexus block provided adequate anesthesia for repair of hip fracture in the elderly . Hypotension was induced by both the combined peripheral nerve block and plain bupivacaine spinal anesthesia in aged patients ; hypotension was found to be longer lasting after spinal anesthesia and of a larger magnitude in patients over 85 years of age ", "The incidence of inguinal hernia is higher in premature infants , particularly in low birth weight neonates . This latter group may also incur increased postoperative respiratory complications and inpatient admissions . The purpose of this study was to compare the effects of general and spinal anaesthesia on postoperative respiratory morbidity and on the length of hospital stay in high‐risk infants undergoing inguinal herniorrhaphy . Forty patients , all high‐risk infants who underwent unilateral or bilateral herniorrhaphies , were r and omly assigned to receive general anaesthesia ( n = 20 ) or spinal anaesthesia ( n = 20 ) . There was a significant difference in respiratory morbidity between the two groups , as well as a significant difference in the inpatient hospital stay . The present study suggests that spinal anaesthesia can be used safely for high‐risk infants , preterm or formerly preterm , undergoing inguinal hernia repair", "We performed a prospect i ve , r and omized , double-blind study of continuous epidural analgesia for 72 hours after major abdominal procedures . Patients were r and omly assigned to one of five treatment groups : epidural morphine , epidural bupivacaine , a combination of morphine and bupivacaine , epidural saline solution , and no epidural catheter . All patients received supplemental morphine sulfate or meperidine hydrochloride , intramuscularly or intravenously , as needed . Epidural infusion was begun at 2 to 4 ml/hr , depending on age and height , with two increments of 1 ml/hr allowed if pain relief was insufficient . All pain management decisions were made by nurses , who also monitored epidural function . Performance was measured four ways : pain as measured at regular intervals in the 72-hour period with a visual analog , pain as measured after 72 hours with the McGill Pain Question naire , amount of supplemental narcotics needed , and recovery of respiratory function and ambulation as percent of preoperative levels . The group that received the combination of morphine and bupivacaine did best on all measures ; in most instances the difference between the results seen with the combination regimen and those seen with saline solution or no catheter were significant at the 0.05 level . With the exception of pruritus , complications were evenly distributed among all treatment groups , including noncatheterized controls . We conclude that epidural analgesia with the combination of morphine and bupivacaine is safe , is easily managed , and gives pain relief superior to that provided by traditional , systemic administration of narcotics", "It has long been held that the acute-phase and neuroendocrine response to stress requires afferent neural input for its propagation . To further clarify the role of afferent neural impulses in this process and to determine the ability of epidural anesthesia to attenuate the normal perioperative stress response , 39 patients undergoing uncomplicated abdominal aortic replacement were r and omized to receive either general anesthesia with postoperative patient-controlled intravenous morphine ( n = 19 ) or combined regional/general anesthesia with intraoperative epidural catheter anesthesia using Bupivacaine to the T4 dermatome level followed by postoperative epidural morphine ( n = 20 ) . The stress response was quantitated by blinded measurement of baseline and postoperative ( 0 , 12 , 24 , 48 , and 72 hours ) serum cortisol , epinephrine norepinephrine , total catecholamines , interleukin (IL)-1beta , IL-6 , tumor necrosis factor (TNF)-alpha , and C-reactive protein ( CRP ) . Total operative time ( 4.2 + /- 0.3 vs 4.3 + /- 0.4 hours ) , 72-hour fluid requirement ( 7.0 + /- 0.6 vs 6.8 + /- 0.71 mL ) , and length of hospitalization ( 7.8 + /- 1.4 vs 8.1 + /- 1.2 days ) were not different between groups . All patients showed a significant increase in cortisol , epinephrine , norepinephrine , total catecholamines , CRP , and IL-6 in the postoperative period ( P IL-1beta and TNF-alpha were less predictable and undetectable in most patients . There was no difference in any of the stress response indices between those patients receiving patient-controlled or epidural catheter anesthesia . In fact , the only parameter that was predictive of increased activation of the stress response was the length of operation , irrespective of anesthetic method . Those patients with operative times greater than 5 hours ( n = 10 ) developed significantly higher CRP , IL-1beta , IL-6 , and TNF-alpha levels ( P < 0.05 ) at 12 and 24 hours postoperatively than those with total operative times less than 4 hours ( n = 16 ) . The neuroendocrine response to major surgical stress is propagated normally despite epidural blockade and is intensified with prolonged operative times . The inflammatory cytokines appear to play a major role in this process", "OBJECTIVE To evaluate both effectiveness and incidence of side effects of two techniques of postoperative pain treatment : intravenous and epidural PCA . DESIGN Prospect i ve analysis of data from two groups of r and omized patients . SETTING S Orthopedic and trauma center . PATIENTS Figty ASA class II-III patients undergoing total hip replacement under combined Spinal-Epidural Anesthesia . METHODS Patients were divided into 2 groups who received different postoperative pain treatment . One group ( group PCA ) received a patient-controlled intravenous analgesia with morphine 30 mg and ketorolac 90 mg in 100 ml of saline ( back-ground infusion 2 - 4 ml , according to body weith , bolus 1 ml , lockout 5 min , 4 h dose limit 40 ml ) . PCEA group received a patient-controlled epidural analgesia with morphine 4 mg and bupivacaine 0.125 % 100 ml , ( background infusion 3 - 4 ml , according to patient ' height , bolus 1 ml , lockout 10 min , 4 h dose limit 25 ml ) . Postoperative pain intensity was evaluated , through 24 postoperative hours , by a verbal analogue scale ( VPS = 0 to 3 ) and a total pain score ( TOTPAR ) was calculated for each patient at 6 and 24 postoperative hours . Side effects were recorded and their incidence was obtained for each group . Statistical data analysis was performed by one-way ANOVA and non-parametric tests for ordinal data . Nominal data were analyzed by chi 2 test . p PCEA showed a significant ( p incident pain , while VPS at rest was similar in the two groups . TOTPAR VPS was lower ( p PCEA group both at 6 and 24 postoperative hours . Somnolence was observed more often in PCA patients ( 8 % vs 2 % ; p 0.05 ) , while no significant differences were noted among other side effects incidence . CONCLUSIONS Our data show a better control of postoperative pain arising from total hip replacement during PCEA when compared to PCA . It should be emphasized that incident pain is far more decreased by PCEA , so that this technique is particularly indicated when an early postoperative mobilization is required", "BACKGROUND Continuous passive motion after major knee surgery optimizes the functional prognosis but causes severe pain . The authors tested the hypothesis that postoperative analgesic techniques influence surgical outcome and the duration of convalescence . METHODS Before st and ardized general anesthesia , 56 adult scheduled for major knee surgery were r and omly assigned to one of three groups , each to receive a different postoperative analgesic technique for 72 h : continuous epidural infusion , continuous femoral block , or intravenous patient-controlled morphine ( dose , 1 mg ; lockout interval , 7 min ; maximum dose , 30 mg/4 h ) . The first two techniques were performed using a solution of 1 % lidocaine , 0.03 mg/ml morphine , and 2 microg/ml clonidine administered at 0.1 ml x kg(-1 ) x h(-1 ) . Pain was assessed at rest and during continuous passive motion using a visual analog scale . The early postoperative maximal amplitude of knee flexion was measured during continuous passive motion at 24 h and 48 h and compared with the target levels prescribed by the surgeon . To evaluate functional outcome , the maximal amplitudes were measured again on postoperative day 5 , at hospital discharge ( day 7 ) , and at 1- and 3-month follow-up examinations . When the patients left the surgical ward , they were admitted to a rehabilitation center , where their length of stay depended on prospect ively determined discharge criteria RESULTS The continuous epidural infusion and continuous femoral block groups showed significantly lower visual analog scale scores at rest and during continuous passive motion compared with the patient-controlled morphine group . The early postoperative knee mobilization levels in both continuous epidural infusion and continuous femoral block groups were significantly closer to the target levels prescribed by the surgeon than in the patient-controlled morphine group . On postoperative day 7 , these values were 90 degrees ( 60 - 100 degrees)(median and 25th-75th percentiles ) in the continuous epidural infusion group , 90 degrees ( 60 - 100 degrees ) in the continuous femoral block group , and 80 degrees ( 60 - 100 degrees ) in the patient-controlled morphine group ( P duration s of stay in the rehabilitation center were significantly shorter : 37 days ( range , 30 - 45 days ) in the continuous epidural infusion group , 40 days ( range , 31 - 60 days ) in the continuous femoral block group , and 50 days ( range , 30 - 80 days ) in the patient-controlled morphine group ( P Side effects were encountered more frequently in the continuous epidural infusion group . CONCLUSION Regional analgesic techniques improve early rehabilitation after major knee surgery by effectively controlling pain during continuous passive motion , thereby hastening convalescence", "In this r and omized , double-blind study of 60 patients , we have assessed the analgesic efficacy of extradural bupivacaine and extradural fentanyl , either alone or in combination , after Caesarean section . Patients received 0.1 % bupivacaine ( group B ) , fentanyl 4 micrograms ml-1 ( group F ) or 0.05 % bupivacaine combined with fentanyl 2 micrograms ml-1 ( group BF ) by patient-controlled extradural analgesia ( PCEA ) . Adding fentanyl to bupivacaine reduced the dose of bupivacaine by up to 68 % , improved analgesia at rest and decreased PCEA use . Motor and sensory block were decreased , but there was more pruritus . Overall patient satisfaction was increased . Adding bupivacaine to fentanyl reduced the dose of fentanyl by up to 57 % without altering pain scores or PCEA use . Sensory block increased but pruritus did not decrease . Bupivacaine 0.05 % produced clinical ly significant leg weakness in three patients . Overall patient satisfaction was not altered . There was a significant additive analgesic effect between 0.05 % bupivacaine and fentanyl but no clinical benefit was demonstrated from using the combination compared with fentanyl alone for this group of postoperative patients", "Forty-seven healthy parturients undergoing elective Caesarean section were r and omly allocated to either general anaesthesia ( n = 24 ) or epidural anaesthesia ( n = 23 ) under st and ardized anaesthetic and surgical conditions . Seven women of the epidural group required additional systemic analgesia or sedation following delivery of the neonate . Nine of 24 newborns obtained 1-min Apgar scores below 7 after general anaesthesia compared to only 3/23 after epidural anaesthesia . The time period to establish normal colour in the babies was 2.2 min after epidural and 4.9 min after general anaesthesia . Three of the 24 general-anaesthesia newborns demonstrated a tendency to hypotonia compared to only one in the epidural group . Twenty-four hours and 7 days after delivery all infants of both groups were completely normal . At the time of delivery maternal PO2 was higher in the general anaesthesia compared to the epidural group , due to higher inspired oxygen concentrations . Comparable results were obtained in umbilical PO2 venous values ; lower pH values , however , were observed in the umbilical artery after general anaesthesia . There were no significant differences in the glucose levels between the groups . A significant correlation was established between uterine incision-delivery interval and 1-min neonatal Apgar scores in the general-anaesthesia group , but not in the epidural group . Our investigation did not show either the incision-delivery interval or the start of operation-delivery interval to play a role in neonatal outcome . Epidural anaesthesia is superior to general anaesthesia in Caesarean section under normal conditions with regard to neonatal outcome . Whether this is also true for critical conditions can not be concluded from this study", "Background There are no r and omized studies on neonatal outcome after spinal versus general anesthesia for cesarean delivery in preeclamptic patients with a nonreassuring fetal heart trace . This study examined both markers of neonatal hypoxia and maternal hemodynamics . Methods Seventy patients were r and omized to general ( n = 35 ) or spinal anesthesia ( n = 35 ) . The general anesthesia group received thiopentone , magnesium sulfate , and suxamethonium intravenously before intubation , followed by 50 % nitrous oxide in oxygen , 0.75–1.5 % isoflurane , and morphine after delivery . The target end-tidal partial pressure of carbon dioxide ( Pco2 ) was 30–34 mmHg . The spinal anesthesia group received 1.8 ml hyperbaric bupivacaine plus 10 & mgr;g fentanyl at the L3–L4 interspace . Heart rate and blood pressure were measured at specific time points . Hypotension was treated with ephedrine . Maternal arterial and neonatal umbilical arterial blood gas sample s were taken at delivery . Resuscitation requirements were recorded . Results In both groups , hemodynamic measures remained within acceptable limits . Spinal anesthesia patients required more ephedrine ( 13.7 vs. 2.7 mg ) . Maternal Paco2 was lower in the spinal group ( 28.9 vs. 32.4 mmHg ) . One-minute Apgar scores were lower after general anesthesia . Base deficit was greater ( 7.13 vs. 4.68 mEq/l ) and neonatal umbilical arterial pH was lower ( 7.20 vs. 7.23 ) after spinal anesthesia . Post hoc analysis showed that if maternal diastolic blood pressure on admission was greater than 110 mmHg , neonatal umbilical arterial base deficit was greater after spinal anesthesia . There was no difference in the number of patients with Apgar scores less than 7 at 1 or 5 min or umbilical arterial pH less than 7.2 or in the requirements for resuscitation . Conclusions In preeclamptic patients with a nonreassuring fetal heart trace , spinal anesthesia for cesarean delivery was associated with a greater mean neonatal umbilical arterial base deficit and a lower median umbilical arterial pH. The clinical significance remains to be established . Maternal hemodynamics were similar and acceptable with either anesthetic technique", "Evidence of pre‐emptive analgetic effect of opioid would offer great potential benefit to patients with postoperative pain , a better pain relief with less opioid . The aim of this double blind r and omised trial was to study the effect of intramuscular morphine premedication on postoperative pain", "BACKGROUND Influence of the type of anesthesia on postoperative delirium was examined in geriatric patients with femoral neck fracture . METHODS Forty patients aged 70 or more were r and omly allocated to receive either general anesthesia ( sevoflurane , nitrous oxide in oxygen , G group , n = 21 ) or spinal anesthesia ( 0.5 % bupivacaine , S group , n = 19 ) . G group received the oxygen therapy during the 12-hour postoperative period . Postoperative assessment s included the rate of postoperative delirium during the 4-day postoperative period , oxygen saturation during the 18-hour postoperative period , the value of hemoglobin at 1 postoperative day and the number of analgesics requirements during the 4-day postoperative period . RESULTS The rate of postoperative delirium was similar between the two groups during the 4-day postoperative period . However , that of S group tended to be higher during the 1-day postoperative period . Postoperative analgesic effect and the value of hemoglobin at 1 postoperative day were similar between the two groups . Oxygen saturation was similar between the two groups except 6 hours after the operation . CONCLUSIONS The type of anesthesia , general or spinal , does not affect the postoperative delirium in geriatric patients with femoral neck fracture", "Background and Objectives . Gastric emptying is delayed during the first days after abdominal surgery . Studies with volunteers have shown that epidural morphine delays gastric emptying but epidural analgesia with bupivacaine does not . The aim of this study was to evaluate whether these differences in healthy volunteers are also found after cholecystectomy when epidural morphine or epidural bupivacaine is used for postoperative pain relief . Methods . Eighteen healthy patients were r and omly allocated into two groups . Nine patients received postoperative analgesia with epidural morphine and nine with thoracic epidural bupivacaine . Acetaminophen absorption was used as an indirect measure of the rate of gastric emptying , measured 22 hours after surgery and again 4 weeks later , so that each patient served as their own control . During epidural morphine , serum acetaminophen concentrations were lower , and the area under the concentration time curve from 0 to 60 minutes ( AUC60 ) was smaller ( p maximum serum acetaminophen concentration ( Cmax ) was lower ( p time taken to reach the maximum concentration ( Tmax ) was longer ( p bupivacaine . There were no statistically significant differences in AUC60 , Cmax , and Tmax between the two groups during the control study . Conclusions . Postoperative gastric emptying was significantly delayed after epidural analgesia with morphine compared to thoracic epidural bupivacaine . Compared to the control situation , epidural bupivacaine did not influence gastric emptying", "In 1987 , Yeager et al. reported that intraoperative epidural anesthesia with local anesthetics and postoperative epidural analgesia with opiates diminished postoperative morbidity . In our first clinical trial on this topic , the better postoperative analgesia with epidural bupivacaine-fentanyl failed to improve the outcome after major abdominal operations over that obtained with parenteral piritramide . This r and omized controlled investigation was design ed to assess whether intraoperative epidural anesthesia with bupivacaine plus light general anesthesia and postoperative epidural analgesia with morphine would diminish the overall rate of postoperative complications after major abdominal operations compared with general anesthesia ( without epidural ) followed by patient controlled analgesia with morphine , and with intraoperative epidural anesthesia with bupivacaine and light general anesthesia followed by postoperative bupivacaine-morphine analgesia . METHODS . A total of 292 patients undergoing infrarenal aortic bypass operation , gastric resection , gastrectomy , duodenum-preserving pancreatic resection , Whipple 's operation or cystectomy and neobladder formation were r and omly divided into three groups : 1 . PCA group ( patient controlled analgesia , n = 107 ) : patients were operated on under general anesthesia ( midazolam , fentanyl , N2O/O2 , if necessary with addition of halothane , enflurane or isoflurane ; muscle relaxation with pancuronium bromide ) . Postoperative management consisted in patient-controlled analgesia with morphine ( Prominject ) , bolus 2 mg , lock-out 5 min ( recovery room , intensive care unit ) or 15 min ( surgical ward ) . 2 . EBM group ( epidural bupivacaine+morphine , n = 95 ) : operation under light general anesthesia ( midazolam , low-dose fentanyl , N2O/O2 , pancuronium bromide ) . In addition , a mixture of bupivacaine ( 0.25 % ) and morphine ( 60 micrograms/ml ) was infused ( approximately 0.1 ml/kg.h ) via an epidural catheter during and after the operation ( approximately 72 h ) . 3 . EM group ( epidural morphine , n = 90 ) : operation under the same kind of general-epidural anesthesia as in the EBM group . Postoperatively , epidural injection of morphine ( 0.05 mg/kg in 10 ml of saline ) on request up to the 3rd postoperative day . Quality of analgesia ( at rest and when patients coughed vigorously ) , strength of cough , and rate-pressure product were recorded at 8:00 h , 12:00 noon , 16:00 h and 20:00 h on the 1st , 2nd and 3rd postoperative days . Incidence and intensity of all postoperative complications ( cardiovascular , pulmonary , renal and other organ failure , reoperations , major infection , sepsis , thromboembolism , metabolic and mental disturbances ) were assessed from the day of operation until discharge or death ( n = 10 ) , respectively . RESULTS AND DISCUSSION . In the PCA and EM groups analgesia was equal but of slightly inferior quality compared with the EBM group . The ability to cough was best in the EBM group and significantly worse in the PCA and EM groups , with no difference between the last two . ( ABSTRACT TRUNCATED AT 400 WORDS", "Background and objective : This prospect i ve , r and omized study was conducted to compare unilateral spinal block using small doses of hyperbaric bupivacaine and single-agent anaesthesia with sevoflurane in elderly patients undergoing hip surgery . Methods : Thirty patients ( > 65 yr ) undergoing hip fracture repair were r and omly allocated to receive unilateral spinal anaesthesia with hyperbaric bupivacaine 7.5 mg 0.5 % ( Group Spinal , n = 15 ) or volatile induction and maintenance anaesthesia with sevoflurane ( Group SEVO , n = 15 ) . General anaesthesia was induced by increasing the inspired concentration to 5 % . A laryngeal mask airway was placed without muscle relaxants , and the end-tidal concentrations of sevoflurane were adjusted to maintain cardiovascular stability . Hypotension ( decrease in systolic arterial pressure > 20 % from baseline ) , hypertension or bradycardia ( heart rate ) requiring treatment , and the length of stay in the postanaesthesia care unit was recorded . Cognitive functions were evaluated the previous day , and 1 and 7 days after surgery with the Mini Mental State Examination test . Results : Hypotension occurred in seven patients of Group Spinal ( 46 % ) and in 12 patients of Group SEVO ( 80 % ) ( P = 0.05 ) . Phenylephrine was required to control hypotension in three spinal patients ( 21 % ) and four SEVO patients ( 26 % ) ( n.s . ) . SEVO patients had lower heart rates than spinal patients from 15 to 60 min after anaesthesia induction ( P = 0.01 ) . Bradycardia was observed in three SEVO patients ( 22 % ) . Discharge from the postanaesthesia care unit required 15 ( range 5 - 30 ) min in Group Spinal and 55 ( 15 - 80 ) min in Group SEVO ( P = 0.0005 ) . Eight patients in Group Spinal ( 53 % ) and nine patients in Group SEVO ( 60 % ) showed cognitive decline ( Mini Mental State Examination test decreased ⩾ 2 points from baseline ) 24 h after surgery ( n.s . ) . Seven days after surgery , confusion was still present in one patient of Group Spinal ( 6 % ) and in three patients of Group SEVO ( 20 % ) ( n.s . ) . Conclusions : In elderly patients undergoing hemiarthroplasty of the hip , induction and maintenance with sevoflurane provide a rapid emergence from anaesthesia without more depression of postoperative cognitive function compared with unilateral spinal anaesthesia . This technique represents an attractive option when patient refusal , lack of adequate co-operation or concomitant anticoagulant therapy contraindicate the use of spinal anaesthesia", "Eighteen formerly premature infants scheduled for inguinal herniorrhaphy and who were less than 51 wk postconceptional age were assigned to either the general anesthesia group ( GA : atropine , halothane , and nitrous oxide ) or the spinal anesthesia group ( SA : hyperbaric tetracaine ) . Twelve-hour , three-channel continuous recordings of respiratory rate ( chest wall impedance ) , electrocardiogram ( ECG ) , and hemoglobin O2 saturation ( Spo2 ) were obtained preoperatively and after surgery . These were analyzed for short ( 11 - 15 s ) and long ( > 15 s ) apnea spells , periodic breathing , and episodes of hemoglobin oxygen desaturation and bradycardia . Infants in the GA group had lower postoperative minimum Spo2 ( 68.7 % + /- 11.4 % ) and minimum heart rate ( 79 bpm + /- 19 ) than infants in the SA group ( 80.7 % + /- 9.2 % , and 109 bpm + /- 30 , respectively ; P postoperative minimum Spo2 and minimum heart rate than they had preoperatively ( 79.0 % + /- 13.7 % , and 93 bpm + /- 31 , respectively ; P incidence of postoperative central apnea . We conclude that spinal anesthesia reduces postoperative hemoglobin oxygen desaturation and bradycardia in formerly premature infants undergoing inguinal herniorrhaphy . ( Anesth Analg 1995;80:7 - 13", "Epidural analgesia with local anaesthetic minimizes the catabolic response to surgery . To determine whether this could enhance the rate of recovery following orthopaedic surgery , 51 patients undergoing bilateral one-stage total knee arthroplasty were allocated to receive infusions of either continuous epidural bupivacaine/fentanyl or continuous intravenous fentanyl to compare the efficacy of these modes of pain relief on postoperative clinical outcomes and rates of rehabilitation . Infusions were maintained for 36 to 48 hours in a post-anaesthesia care unit ( PACU ) . Postoperatively , pain relief ( visual analogue scale ) , attainment of physical therapy goals and cardiopulmonary complications were measured daily for 7 days . Epidural analgesia with a combination of bupivacaine and fentanyl did not result in any measurable improvement in rehabilitation milestones or reduction in postoperative complications following bilateral total knee arthroplasty than with fentanyl infusions alone", "We prospect ively studied the post-operative recovery profile of 28 ex-premature infants undergoing inguinal herniotomy . All infants had a post-conceptual age of less than 46 weeks at the time of surgery and were r and omized to receive either sevoflurane ( group 1 , 14 patients ) or spinal anaesthesia ( group 2 , 14 patients ) . All patients received supplemental caudal analgesia before skin incision . Cardiorespiratory function was continuously recorded in all patients before and after surgery . A blinded observer analysed each paired recording for predefined episodes of apnoea , hypoxaemia or bradycardia and the reports were used to compare the two groups . Spinal anaesthesia was attempted unsuccessfully in four patients in group 2 . Five patients in group 1 demonstrated an ' excess ' number of episodes ( median 4 , range 3 - 12 ) of clinical ly silent post-operative cardiorespiratory complications . ( ' Excess ' in our study was defined as a 3-fold or greater increase in the number of post-operative episodes of bradycardia or apnoea relative to pre-operative occurrence ) . Three of these patients had pre-existing abnormal respiratory function and accounted for 80 % of the episodes ( 26/32 ) of post-operative bradycardia and all five episodes of post-operative apnoea identified . All episodes of bradycardia and apnoea were temporally unrelated . None of the remaining patients in group 2 demonstrated an unacceptable number of post-operative cardiorespiratory complications . Our limited study suggests that general anaesthesia with an inhalational agent such as sevoflurane may induce or unmask abnormalities of cardiopulmonary function in predisposed infants . Spinal anaesthesia may be preferable but it is potentially stressful for the infant and associated with a clinical ly significant failure rate", "In this r and omized double-blinded study , we sought to determine an optimal dose-combination of sufentanil with ropivacaine 0.2 % wt/vol as postoperative epidural analgesics . One hundred twenty patients undergoing major abdominal surgery under general and thoracic epidural anesthesia ( T9 - 11 ) were assigned to groups receiving patient-controlled epidural analgesia with ropivacaine 0.2 % wt/vol ( R ) , ropivacaine 0.2 % wt/vol + sufentanil 0.5 & mgr;g/mL ( R+S0.5 ) , 0.75 & mgr;g/mL ( R+S0.75 ) , 1.0 & mgr;g/mL ( R+S1 ) . A visual analog score of less than 40 was considered effective , and all side effects were recorded . In r and omized subgroups ( 10 patients per group ) , plasma pharmacokinetic data were obtained for both epidural drugs . Four patients in Group R and two in Group R+S0.5 were excluded because of inadequate analgesia . The drug infusion rates ( range of means : 5.4–5.9 mL/h ) were similar in all patients . Analgesia was superior for sufentanil 0.75 & mgr;g/mL with no further enhancement by the larger sufentanil concentration of 1 & mgr;g/mL. Sufentanil plasma levels were within the range of the minimal effective concentrations ( highest in R+S1 ) , and there was no covariation between plasma levels and pain relief . Free ropivacaine plasma concentrations remained stable for 96 h. No severe side effects were detected , although pruritus correlated with an increasing dose of sufentanil . We conclude that the combination of ropivacaine 0.2 % wt/vol and 0.75 & mgr;g/mL sufentanil provided the best analgesia with the fewest side effects of the three combinations tested . Implication s : Sufentanil is added to epidural infusions of ropivacaine 0.2 % wt/vol to improve the effectiveness of postoperative pain management . Regarding the risk of side effects , however , it is still unclear what concentration of sufentanil should be added to the local anesthetic . For postoperative thoracic epidural analgesia after major abdominal surgery , the combination of ropivacaine 0.2 % wt/vol and 0.75 & mgr;g/mL sufentanil result ed in an appropriate cost : benefit ratio between good analgesia and side effects", "The authors conducted a r and omized controlled clinical trial to evaluate the effect of epidural anesthesia and postoperative analgesia ( EAA ) on postoperative morbidity in a group of high-risk surgical patients . A total of 53 patients were admitted to the study , 28 received EAA , and 25 received st and ard anesthetic and analgesic techniques without EAA . Surgical “ risk ” was evaluated preoperatively and found to be comparable in the two groups . When compared to control patients , patients who received EAA had a reduction in the overall postoperative complication rate ( P = 0.002 ) and in the incidence of cardiovascular failure ( P = 0.007 ) and major infectious complications ( P = 0.007 ) . Urinary cortisol excretion , a marker of the stress response , was significantly diminished during the first 24 postoperative hours in the group receiving EAA ( P = 0.025 ) . Finally , hospital costs were significantly reduced for patients who received EAA ( P = 0.02 ) . The authors conclude that EAA exerted a significant beneficial effect on operative outcome in a group of high risk surgical patients", "UNLABELLED The aim of our study was to compare epidural anesthesia and analgesia ( EDA ) with ropivacaine versus general anesthesia followed by IV patient-controlled analgesia with morphine ( GA/PCA ) after hip replacement regarding pain , side effects , and discharge from the postanesthesia care unit . After ethics committee approval , r and omization , and informed consent , 90 patients were enrolled . In Group EDA , epidural anesthesia ( ropivacaine 10 mg/mL , 15 - 25 mL ) was followed by an epidural infusion ( 2 mg/mL , 4 - 6 mL/h for 24 h , plus top-up doses of 6 - 10 mL for 48 h ) . GA/PCA patients received general anesthesia ( isoflurane/N2O/fentanyl ) followed by IV patient-controlled analgesia with morphine postoperatively . Pain was assessed by using visual analog scales ( 0 - 100 mm ) at rest and during physiotherapy . Pain at rest was less in the EDA ( n = 43 ) group than in the GA/PCA ( n = 45 ) group ( at 10 h : 11.8+/-12.9 vs. 28.4+/-17.1 [ P discharge from the postanesthesia care unit earlier than GA/PCA patients ( 5.6+/-8.9 vs. 39.7+/-41.5 min ) , the actual discharge time was comparable . The median time for first passage of flatus was shorter in the EDA group than in the GA/PCA group ( 26 vs. 47 h ) . Nausea and vomiting were more common in the GA/PCA group than in the EDA group ( 16 % vs. 28 % and 11 % vs. 22 % , respectively ) , whereas hypotension ( 11 % vs. 4 % ) and bradycardia ( 14 % vs. 2 % ) were less frequent . Under the conditions of the present study , EDA with ropivacaine provided pain control after hip replacement superior to that provided by IV patient-controlled analgesia with morphine , particularly during the first 24 h. Both approaches to pain management were equally safe . IMPLICATION S Compared with general anesthesia and postoperative IV patient-controlled analgesia with morphine , epidural anesthesia and analgesia with the new local anesthetic ropivacaine enables patients to be discharged sooner from a postanesthesia care unit and provides superior pain relief during the first 24 h after hip replacement", " Forty – two patients scheduled for total knee arthroplasty ( n = 20 ) or hip arthroplasty ( n = 22 ) were r and omly allocated to receive either continuous epidural bupivacaine/morphine for 48 h postoperatively plus oral piroxicam , or general anaesthesia followed by a conventional intramuscular opioid and acetaminophen regimen . Patients undergoing knee– or hip arthroplasty treated with epidural analgesia had significantly lower pain scores during mobilization under the 48 h epidural infusion compared with patients receiving conventional treatment , while no important differences were observed after cessation of the epidural regimen . However , the achieved pain relief had no impact on postoperative convalescence parameters , such as ambulation , patient activity including need for nursing care , fatigue or hospital stay . Late postoperative pain , fatigue and conservative attitudes and routines in the postoperative care , were the most important reasons limiting mobilization and activity . We conclude that effective early ( 48 h ) postoperative pain relief with balanced analgesia does not per se lead to important improvements in convalescence and hospital stay", "A comparison was made of the effects of continuous epidural analgesia with bupivacaine and intermittent epidural morphine on bowel function after abdominal hysterectomy . The duration of postoperative ileus was assessed as the time from the end of operation to the first postoperative passage of flatus and feces . Twenty – two patients were r and omly allocated to two equal groups . An “ epidural morphine ” group received general anesthesia and epidural morphine for postoperative pain relief , and an “ epidural bupivacaine ” group was given combined general anesthesia and epidural anesthesia with 0.5 % bupivacaine intraoperatively and epidural analgesia with 0.25 % bupivacaine postoperatively . Epidural morphine or bupivacaine was given for 42 h postoperatively . Pain intensity ( visual analog scale ) was low in both groups , but lower ( P bupivacaine group . The time to first passage of flatus was 22 16 h in the epidural bupivacaine group and 56 22 h in the epidural morphine group ( P The time to first postoperative passage of feces was shorter ( P bupivacaine group started intake of oral fluids earlier ( P morphine group . It is concluded that the duration of postoperative ileus after hysterectomy is shorter when epidural bupivacaine is given for postoperative pain relief than when this is achieved by epidural morphine", "Summary Twenty-one patients who had undergone total hip replacement were r and omly assigned to one of three groups in order to compare a single dose of 1 mg/kg of pethidine i m ( I ) and 20 mg ( II ) or 60 mg of extradural pethidine ( III ) in a double-blind design .The degree of analgesia , the adverse effects , and the kinetics were studied for 18 h. Pain was monitored using a visual analogue scale ( VAS ) . Supplementary doses of oxycodone if required were given no earlier than 0.75 h after pethidine . Plasma concentrations of pethidine were measured with gas chromatography mass spectrometry ( GCMS ) . Hypoalgesia to pin prick test was evaluated . Low pain scores were observed in the extradural groups between 0.25 and 1.5 h after the dose . A significant difference in pain score compared with the i m group was found after the higher extradural dose only between 0.5 and 1 h (p area under the curve ( AUC ) of pain score versus time ( 0–18 h ) was not significantly different between groups . The recorded adverse effects were minor in all three groups . The terminal half-lives and plasma clearances of pethidine , and the time to peak concentration were not different between the groups . Single patients in the extradural groups showed hypoalgesia to pin prick in parallel to the effect . The present study shows that extradural pethidine produces shortlived analgesia , in contrast to the long-lasting effect of morphine found in other studies", "Cardiovascular and hormonal responses to reconstructive abdominal aortic surgery were studied in 20 patients anaesthetized either with moderate-dose fentanyl ( 20 micrograms kg-1 ) combined with isoflurane , nitrous oxide and oxygen ( n = 10 ) , or with thoracolumbar epidural bupivacaine combined with isoflurane , nitrous oxide and oxygen ( n = 10 ) . After the start of operation , hypotension occurred in four patients in the epidural group . In both groups , the aortic cross-clamping caused slight increases both in mean arterial pressure and in calculated systemic vascular resistance , and a significant decrease in cardiac index . At the same time , a marked increase in plasma vasopressin was seen in the fentanyl group . Plasma catecholamines were low in both groups . After aortic declamping , the cardiac index improved in both groups , although two patients in the fentanyl group and four patients in the epidural group were hypotensive . Post-operatively , eight patients in the fentanyl group were hypertensive , versus none in the epidural group , in which bupivacaine-fentanyl was administered epidurally . At the same time , plasma vasopressin and adrenaline increased significantly in both groups , whereas plasma noradrenaline did so only in the fentanyl group . The results suggest that thoracolumbar epidural bupivacaine combined with low-dose isoflurane in nitrous-oxide-oxygen prevents intra-operative hypertension and tachycardia , but it may cause hypotension . Post-operative hypertension and tachycardia as well as the increase in plasma noradrenaline are prevented by epidural administration of bupivacaine-fentanyl", "The efficacy of epidurally administered tramadol hydrochloride , a weak central ly acting analgesic , was studied for the relief of postoperative pain . Sixty patients undergoing abdominal surgery were r and omly allocated to three treatment groups to be given the following agents by the epidural route : group 1 tramadol 50 mg ; group 2 tramadol 100 mg ; group 3 10 ml of bupivacaine 0.25 % . The drugs were administered at the patients ' request with each patient being allowed four doses in the first 24 h following surgery . Blood pressure , pulse rate , respiratory rate , arterial blood gas analyses , pain scores , the interval between doses and the occurrence of any side effects were recorded . Pain scores ( assessed using a visual analogue scale ) were significantly less ( p tramadol 100 mg than in those receiving tramadol 50 mg or bupivacaine . The mean interval between doses for groups 1 , 2 and 3 was 7.40 h , 9.36 h and 5.98 h respectively . The mean interval in group 2 was significantly longer than in group 3 ( p nausea and vomiting in group 2 was significantly higher than in group 3 ( p < 0.05 )", "In a primary analysis of a large recently completed r and omized trial in 915 high-risk patients undergoing major abdominal surgery , we found no difference in outcome between patients receiving perioperative epidural analgesia and those receiving IV opioids , apart from the incidence of respiratory failure . Therefore , we performed a selected number of predetermined subgroup analyses to identify specific types of patients who may have derived benefit from epidural analgesia . We found no difference in outcome between epidural and control groups in subgroups at increased risk of respiratory or cardiac complications or undergoing aortic surgery , nor in a subgroup with failed epidural block ( all P > 0.05 ) . There was a small reduction in the duration of postoperative ventilation ( geometric mean [ SD ] : control group , 0.3 [ 6.5 ] h , versus epidural group , 0.2 [ 4.8 ] h ; P = 0.048 ) . No differences were found in length of stay in intensive care or in the hospital . There was no relationship between frequency of use of epidural analgesia in routine practice outside the trial and benefit from epidural analgesia in the trial . We found no evidence that perioperative epidural analgesia significantly influences major morbidity or mortality after major abdominal surgery", "Background Choice of perioperative analgesia may affect the rate of recovery of gastrointestinal function and thus duration and cost of hospitalization after colonic surgery", "UNLABELLED Influence of anesthetic technique on mental status in elderly patients su bmi tted to major orthopedic procedures of lower limbs . Mental impairment is a common occurrence in elderly patients after major orthopedic surgery . Few studies have been published so far on this topic in spite of its relevant clinical and economic implication s. OBJECTIVE 1 ) To verify whether anesthesia has a causative role in postoperative mental confusion in elderly patients ; 2 ) to compare the effects of General Anesthesia ( GA ) and Spinal Anesthesia ( SA ) on mental status . DESIGN Controlled , comparative study . PATIENTS Sixty patients aged > or = 70 , ASA I-II , su bmi tted to femoral neck repair . SETTING Anesthesia Dept . and Orthopedic Dept . of a District Hospital in Italy . METHOD The day before surgery the mental status of elected patients was evaluated employing a modified Organic Brain Syndrome ( OBS ) scale ( Gustafsson ) . The better the mental status , the lesser the OBS score . It was possible therefore to distinguish \" oriented \" from \" confuse \" patients ( 38 vs 22 ) if they scored 6 respectively . Patients from each group were than r and omly assigned to receive either GA or selective SA . Neither group was premedicated . GA was induced with propofol 1 mg/kg and maintained with O2/N2O 40/60 % and isoflurane ; atracurium was employed to facilitate mioresolution . Spinal anesthesia was performed with hyperbaric 1 % bupivacaine . All patients were monitored in the Recovery Room ( RR ) for at least one hour . Occurrence of hypotension and /or hypoxia in the Operating Room ( OR ) or the RR was immediately treated . Mental status was reassessed on the 1st and 2nd postoperative day and results were compared with the corresponding preoperative OBS scores both in GA patients and in SA patients . RESULTS No statistically significant differences were found between pre- and postoperative OBS scores in both GA and SA group , whether \" oriented \" or \" confuse \" . CONCLUSIONS Mental status of elderly patients su bmi tted to femoral neck repair does n't seem to be influenced by the anesthetic technique chosen , independent of preoperative psychic conditions", "Thirty-six former preterm infants undergoing inguinal hernia repair were studied . All were less than or equal to 51 weeks postconceptual age at the time of operation . Patients were r and omly assigned to receive general or spinal anesthesia . Group 1 patients received general inhalational anesthesia with neuromuscular blockade . Group 2 patients received spinal anesthesia using 1 % tetracaine 0.4 - 0.6 mg/kg in conjunction with an equal volume of 10 % dextrose and 0.02 ml epinephrine 1:1000 . In the first part of the study , infants r and omized to receive spinal anesthesia also received sedation with i m ketamine 1 - 2 mg/kg prior to placement of the spinal anesthetic ( group 2 A ) . The remainder of group 2 patients did not receive sedation ( group 2 B ) . Respiratory pattern and heart rate were monitored using an impedance pneumograph for at least 12 h postoperatively . Tracings were analyzed for evidence of apnea , periodic breathing and /or bradycardia by a pulmonologist unaware of the anesthetic technique utilized . None of the patients who received spinal anesthesia without ketamine sedation developed postoperative bradycardia , prolonged apnea , or periodic breathing . Eight of nine infants ( 89 % ) who received spinal anesthesia and adjunct intraoperative sedation with ketamine developed prolonged apnea with bradycardia . Two of the eight infants had no prior history of apnea . Five of the 16 patients ( 31 % ) who received general anesthesia developed prolonged apnea with bradycardia . Two of these five infants had no prior history of apnea . When infants with no prior history of apnea were analyzed separately , there was no statistically significant increased incidence of apnea in children receiving general versus spinal anesthesia with or without ketamine sedation . Because of the small numbers of patients studied , and the multiple factors that may influence the incidence of postoperative apnea ( e.g. , prior history of neonatal apnea ) , st and ard postoperative respiratory monitoring of these high-risk infants is still recommended following all anesthetic techniques", " A clinical trial was performed to compare the effects of intramuscular dihydrocodeine with caudal bupivacaine on postoperative pain and recovery in 181 children who had undergone either circumcision , inguinal herniotomy or orchidopexy performed under general anaesthesia . Linear analogues were used to assess level of consciousness and apparent pain . Recovery of consciousness was slower after caudal analgesia . For 90 minutes following circumcision there was significantly less pain with caudal analgesia , but better pain relief could not be demonstrated following inguinal herniotomy and orchidopexy", "Objective To evaluate the maternal and fetal effects of three anesthetic methods used r and omly in women with severe preeclampsia who required cesarean delivery . Methods Eighty women with severe preeclampsia , who were to be delivered by cesarean , were r and omized to general ( 26 women ) , epidural ( 27 ) , or combined spinalepidural ( 27 ) anesthesia . The mean preoperative blood pressure ( BP ) was approximately 170/110 mmHg , and all women had proteinuria . Anesthetic and obstetric management included antihypertensive drug therapy and limited intravenous ( IV ) fluid and drug therapy . Results The mean gestational age at delivery was 34.8 weeks . All infants were born in good condition as assessed by Apgar scores and umbilical arterial blood gas determinations . Maternal hypotension result ing from regional anesthesia was managed without excessive IV fluid administration . Similarly , maternal BP was managed without severe hypertensive effects in women undergoing general anesthesia . There were no serious maternal or fetal complications attributable to any of the three anesthetic methods . Conclusion General as well as regional anesthetic methods are equally acceptable for cesarean delivery in pregnancies complicated by severe preeclampsia if steps are taken to ensure a careful approach to either method", "Purpose The goal of this r and omized study was to determine whether combined general and epidural anaesthesia with postoperative epidural analgesia , compared with general anaesthesia and postoperative intravenous analgesia , reduced the incidence of perioperative myocardial ischaemia in patients undergoing elective aortic surgery . Method Patients were r and omly assigned to one of two groups . One group ( EPI , n = 48 ) received combined general and epidural anaesthesia and postoperative epidural analgesia for 48 hrs . The other group ( GA , n = 51 ) received general anaesthesia followed by postoperative intravenous analgesia . Anaesthetic goals were to maintain haemodynamic stability ( ± 20 % of preoperative values ) , and a stroke volume > 1 ml · kg−1 . A Holter monitor was attached to each patient the day before surgery . Leads 11 , V2 , and V5 were monitored . Myocardial ischaemia was defined as ST segment depression > 1 mm measured at 80 millisec beyond the J point or an elevation of 2 mm 60 millisec beyond the J point which lasted > 60 sec. An event that lasted > 60 sec but returned to the baseline for > 60 sec and then recurred , was counted as two separate events . The Holter tapes were review ed by a cardiologist blind to the patient ’s group . Results There were no demographic differences between the two groups . Myocardial ischaemia was common ; it occurred in 55 % of patients . In hospital , preoperative ischaemia was uncommon ( CA = 3 , EP1 = 8) . Intraoperative ischaemia was common ( GA = 18 , EP1 = 25 ) . Mesenteric traction produced the largest number of ischaemic ( GA = 11 , EP1 = 11 ) events . Postoperative ischaemia was most common on the day of surgery . Termination of epidural analgesia produced a burst of ischaemia ( 60 events in 9 patients ) Conclusion Combined general and epidural anaesthesia and postoperative epidural analgesia do not reduce the incidence of myocardial ischaemia or morbidity compared with general anaesthesia and postoperative intravenous analgesia . RésuméObjectifDéterminer avec une élude r and omisée si l’anesthésie générale et épidurale combinée suivie d’une analgésie épidurale postopératoire comparée à l’anesthésie générale suivie d’une analgésie intraveineuse postopératoire diminuait l’incidence de l’ischémie myocardique périopératoire chez des patients soumis à une chirurgie aortique non urgente . MéthodeLes patients étaient répartis au hasard en deux groupes . Un groupe ( IEP1 , n = 48 ) recevait une anesthésie générale et épidurale combinée et une analgésie épidurale postopératoire pendant 48 h. L’autre groupe ( AG , n = 51 ) recevait une anesthésie générale suivie d’une analgésie intraveineuse postopératoire . Les objectifs anesthésiques étaient de maintenir la stabilité hémodynamique ( ± 20 % des valeurs préopératoires ) , et un volume d’éjection > 1 ml · kg−1 . Un jour avant l’intervention , un moniteur de Holter avec les dérivations 11 , V2 et V5 était relié au patient . Une depression du segment ST plus gr and e que 1 mm mesurée 80 millisec après le point J ou une élévation de 2 mm mesurée 60 millisec après le point J était considérée comme une ischémie myocardique si elle durait plus de 60 sec. Un épisode de plus de 60 sec avec un retour à la ligne de base pendant 60 sec et plus avec récurrence , était considéré comme 2 épisodes séparés . Les bobines du Holter était révisée par un cardiologue neutre . RésultatsLes données démographiques étaient entre les groupes . L’ischémie myocardique était fréquente , survenant chez 55 % des patients . A l’hôpital , l’ischémie préopératoire était rare ( AG = 3 , EP1 = 8) . L’ischémie peropératoire était fréquente ( AG = 18 , EP1 = 25 ) . La traction mésentérique provoquait le plus gr and nombre d’épisodes d’ischémie ( AG = 11 , EP1 = 11 ) . L’ischémie postopératoire survenait le plus fréquemment le jour même de la chirurgie . L’arrêt de l’analgésie épidurale provoquait des poussées ischémiques ( 60 épisodes chez 9 patients ) . Conclusion L’anesthésie générale et épidurale combinée à l’analgésie épidurale ne réduit pas l’incidence de l’ischémie myocardique et de la morbidité comparativement à l’anesthésie générale suivie d’une l’analgésie intraveineuese", " Background : After total knee arthroplasty , patients regularly suffer from severe pain . It is unclear whether epidural or systemic pain therapy is superior in terms of postoperative pain relief , patients ’ comfort and side effects . A new therapeutic approach , intraarticular opioids , has been suggested with the detection of opioid receptors in inflamed tissue . This method has proven suitable for clinical use in small operations ( e.g. knee arthroscopy ) . In this study , we compared epidural analgesia and intraarticular application of morphine plus “ on‐dem and ” intravenous analgesia to “ on‐dem and ” intravenous analgesia alone", "Background Despite evidence that regional anesthesia may be associated with fewer perioperative complications than general anesthesia , most studies that have compared cardiac outcome after general or regional anesthesia alone have not shown major differences . This study examines the impact of anesthetic choice on cardiac outcome in patients undergoing peripheral vascular surgery who have a high likelihood of associated coronary artery disease . Methods Four hundred twenty‐three patients , between 1988 and 1991 , were r and omly assigned to receive general ( n = 138 ) , epidural ( n = 149 ) , or spinal anesthesia ( n = 136 ) for femoral to distal artery bypass surgery . All patients were monitored with radial artery and pulmonary artery catheters . Postoperatively , patients were in a monitored setting for 48–72 h and had daily electrocardiograms for 4–5 days and creatine phosphokinase/isoenzymes every 8 h x 3 , then daily for 4 days . Cardiac outcomes recorded were myocardial infa rct ion , angina , and congestive heart failure . Results Baseline clinical characteristics were not different between anesthetic groups . Overall , the patient population included 86 % who were diabetic , 69 % with hypertension , 36 % with a history of a prior myocardial infa rct ion , and 41 % with a history of smoking . Cardiovascular morbidity and overall mortality were not significantly different between groups when analyzed by either intention to treat or type of anesthesia received . In the intention to treat analysis , incidences of cardiac event or death for general , spinal , and epidural groups were 16.7 % , 21.3 % , and 15.4 % , respectively . The absolute risk difference observed between general and all regional anesthesia groups for cardiac event or death was ‐1.6 % ( 95 % confidence interval ‐9.2 % , 6.1 % ) This reflected a nonsignificant trend for lower risk of postoperative events with general anesthesia . Conclusions The choice of anesthesia , when delivered as described , does not significantly influence cardiac morbidity and overall mortality in patients undergoing peripheral vascular surgery", "In a prospect i ve study , patients undergoing cholecystectomy were r and omly allocated to receive ( a ) intermittent intramuscular morphine ( n = 25 ) , ( b ) continuous intravenous morphine infusion ( n = 25 ) or ( c ) epidural bupivacaine ( n = 25 ) for postoperative pain relief . Morphine by intravenous infusion provided comparable pain relief to intermittent intramuscular morphine ; there was no significant difference in the incidence of postoperative pulmonary complications . Patients receiving epidural bupivacaine for 12 h had better analgesia than patients receiving morphine ( P Arterial oxygen tensions were also significantly higher in the epidural group for the first three postoperative days ( P incidence of pulmonary complications ( P chest infection ( P < 0.05 )", "Umbilical arterial blood gas analysis is the most objective method to assess fetal well being at birth , is the gold st and ard assessment of uteroplacental function and fetal oxygenation/acid-base status at birth , and it excludes the diagnosis of birth asphyxia in approximately 80 % of depressed newborns at term . This study was design ed to determine the effect of the type of delivery on umbilical cord blood gases and on free radical activity together with antioxidation in the fetus . Ninety-six pregnant women between 37 and 42 weeks of gestation were included to the study and r and omly assigned to the one of three groups : Group 1 ( n = 40 ) were vaginally delivered , Group 2 ( n = 26 ) had cesarean section with epidural anaesthesia , and Group 3 ( n = 30 ) had cesarean section under general anaesthesia . Umbilical artery blood gas analysis was performed just after the delivery of the fetus together with melondealdehyde and glutathione . The umbilical arterial PO2 was found to be higher in Group 3 , and malondealdehyde and glutathione levels were lower in newborns of Group 2 . It can be concluded that cesarean section with epidural anaesthesia is safer when lipid peroxides are concerned", "We evaluated changes in dementia rating scale scores in the revised version of Hasegawa 's dementia scale ( HDS-R ) , and rated dementia , 2 days before and 7 days after surgery in the elderly patients with femoral neck fracture . The 50 patients examined ranged in age from 70 years to 101 years . A perfect score in the HDS-R is 30 points , and a score below 20 points strongly suggests dementia . The results were as follows . In septuagenarian and octogenarian patients , the scale score was higher after surgery than the value before the surgery . Although the preoperative and postoperative scores of the patients who had been under epidural anesthesia were not significantly different , the score of patients who had been under general anesthesia was higher in the postoperative period than in the preoperative period . In octogenarian patients , there was a negative correlation between \" postoperative score minus preoperative score \" and \" the number of the days from suffering fracture to surgery \" . These results showed that general anesthesia is more advantageous than epidural anesthesia from the viewpoint of the intellectual faculty in septuagenarian and octogenarian patients with femoral neck fracture , and it is within the bounds of possibility that the intellectual faculty may decline if an octogenarian patient is operated after a long delay from the occurrence of fracture . To prevent this decline , patients must be operated on as soon as possible", "In this prospect i ve , r and omised , double-blind study , we investigated the effect of epidural anaesthesia and an antifibrinolytic agent , Aprotinin ( 500,000 KIU in bolus before surgery and 500,000 KIU h-1 in drip form during surgery ) , on intra and postoperative blood loss and transfusion requirements in total hip arthroplasty . Sixty patients were allocated r and omly to four groups ( A : epidural + general anesthesia + Aprotinin , B : epidural + general anesthesia + placebo ( equal volume ) , C : general anaesthesia + Aprotinin , D : general anaesthesia + placebo ) . Postoperative analgesia : epidural analgesia in groups A and B , systemic analgesia with opiates in groups C and D. Blood loss during surgery was monitored and salvaged with the Compact-A Dideco , and postoperative blood loss with the BT 797 Recovery Dideco for the first 24 hours . Perioperative blood loss , frequency and quantity of transfusions were significantly higher in group D ( p Total blood loss was reduced by 31.3 % by epidural anaesthesia , 20.4 % by Aprotinin and 51.4 % using a combination of the two techiniques", "There are few consistent guidelines in choosing anesthesia for cesarean section for a parturient with placenta previa . This prospect i ve r and omized trial was organized to compare the maternal hemodynamics , blood loss and neonatal outcome of general versus epidural anesthesia for cesarean section with the diagnosis of grade 4 placenta previa . After giving informed consent , 12 patients received general anesthesia and 13 received epidural . Intraoperative blood pressures demonstrated a more stable course in the epidural group than in the general group . Blood loss did not differ significantly between the groups ( 1622 + /- 775 mL vs. 1418 + /- 996 mL ) . General anesthesia result ed in lower immediate postoperative hematocrit level ( 28.1 + /- 3.5 % vs. 32.5 + /- 5.0 % , P transfusion than the epidural group ( 1.08 + /- 1.6 vs. 0.38 + /- 0.9 units , P Apgar scores at 1 and 5 min were similar in the two groups ( 8 [ 4 - 9 ] vs. 8 [ 7 - 9 ] and 10 [ 6 - 10 ] vs. 9 [ 9 - 10 ] , respectively ) . We concluded that epidural anesthesia is superior to general anesthesia in elective cesarean section for grade 4 placenta previa with regard to maternal hemodynamics and blood loss . There was no difference in neonatal outcome", "Sixty patients scheduled for colonic surgery were r and omly allocated to four groups according to postoperative pain medication : I. Control group , the patients received oxycodone intramuscularly ( 0.15 mg kg1 ) on request . II . Epidural bupivacaine ( 0.25 % ) continuously administered by infusion pump , 66 ml h‐1 , for 48 h. III . Epidural morphine , 2–6 mg , at the end of operation and repeated on the first and second postoperative mornings . IV . Epidural morphine , 2–6 mg per die , administered for 48 h continuously by infusion pump . All patients received a balanced anaesthesia with enflurane , fentanyl and vecuronium . Postoperatively , intramuscular oxycodone was given on request . There were no significant differences between the groups in changes in peak flow , spirometry and blood‐gas analyses postoperatively . Pain intensity ( visual analogue scale ) was lower in Groups II and III at 3 h and in Group IV at 24 h compared to the control Group I. All the epidurally treated groups needed less additional analgesics than the control Group I. Postoperatively bowel movements occurred on the second day in Group II ( bupivacaine ) as compared to the fourth day in all other groups ( P < 0.05 )", "We have compared the incidence of preoperative and postoperative oxygen desaturation in 20 elderly patients undergoing dynamic hip screw insertion for fractured neck of femur , allocated r and omly to two groups to receive subarachnoid anaesthesia ( SA , n = 10 ) or a general anaesthetic ( GA , n = 10 ) . Oximetry data were recorded during the preoperative night and the first 48 hours after surgery using Satmaster . ™ Data associated with zero amplitude signal were automatically invali date d by the software and decreases in SpO2 which were preceded by contemporaneous changes in signal amplitude which conformed to a previously described template were assumed to be artefactual and were discarded from final data analysis . Data demonstrated a wide interpatient variability . However , those patients who desaturated preoperatively continued to do so in the postoperative period . The differences between the preoperative and postoperative oximetry profiles were examined for each patient and demonstrated a significantly longer time spent with SpO2 in the GA group compared with the SA group , in all the recorded time periods , except on the day of surgery . The SA group showed an improvement in oxygen saturation postoperatively when compared to the preoperative night , spending less time with an SpO2 subarachnoid anaesthetic technique was associated with a lower incidence of postoperative oximetry desaturation when compared with general anaesthetic for these elderly patients undergoing repair of fractured neck of femur", "Background Improvement in patient outcome and reduced use of medical re sources may result from using epidural anesthesia and analgesia as compared with general anesthesia and intravenous opioids , although the relative importance of intraoperative versus postoperative technique has not been studied . This prospect i ve , double-masked , r and omized clinical trial was design ed to compare alternate combinations of intraoperative anesthesia and postoperative analgesia with respect to postoperative outcomes in patients undergoing surgery of the abdominal aorta . Methods One hundred sixty-eight patients undergoing surgery of the abdominal aorta were r and omly assigned to receive either thoracic epidural anesthesia combined with a light general anesthesia or general anesthesia alone intraoperatively and either intravenous or epidural patient-controlled analgesia postoperatively ( four treatment groups ) . Patient-controlled analgesia was continued for at least 72 h. Protocol s were used to st and ardize perioperative medical management and to preserve masking intraoperatively and postoperatively . A uniform surveillance strategy was used for the identification of prospect ively defined postoperative complications . Outcome evaluation included postoperative hospital length of stay , direct medical costs , selected postoperative morbidities , and postoperative recovery milestones . Results Length of stay and direct medical costs for patients surviving to discharge were similar among the four treatment groups . Postoperative outcomes were similar among the four treatment groups with respect to death , myocardial infa rct ion , myocardial ischemia , reoperation , pneumonia , and renal failure . Epidural patient-controlled analgesia was associated with a significantly shorter time to extubation ( P = 0.002 ) . Times to intensive care unit discharge , ward admission , first bowel sounds , first flatus , tolerating clear liquids , tolerating regular diet , and independent ambulation were similar among the four treatment groups . Postoperative pain scores were also similar among the four treatment groups . Conclusions In patients undergoing surgery of the abdominal aorta , thoracic epidural anesthesia combined with a light general anesthesia and followed by either intravenous or epidural patient-controlled analgesia , offers no major advantage or disadvantage when compared with general anesthesia alone followed by either intravenous or epidural patient-controlled analgesia", "Ketamine has been compared with ' relaxant ' anaesthesia in operations for fractured neck of femur in elderly women . Ketamine was found to reduce early mortality principally by a reduction in thromboembolic complications , but at the expense of more unsatisfactory surgical results . It is suggested that the mortality after relaxant anaesthesia for these operations is unacceptable", "Background : Perioperative morbidity may be modifiable in high risk patients by the anesthesiologist 's choice of either regional or general anesthesia . This clinical trial compared outcomes between epidural ( EA ) and general ( GA ) anesthesia/analgesia regimens In a group of patients at high risk for cardiac and other morbidity who were undergoing similarly stressful surgical procedures . Methods : One hundred patients scheduled for elective vascular reconstruction of the lower extremities were r and omized to receive either EA for surgery followed by epidural analgesia , or GA for surgery followed by intravenous patient-controlled analgesia . Hemodynamic monitoring , blood pressure , and heart rate limits were determined prior to r and omization . Management of anesthesia in the immediate postoperative period was st and ardized . The data collected included continuous electrocardiographic monitoring from the day before surgery through the third postoperative day , serial electrocardiograms , and cardiac enzymes . Cardiac ischemia , myocardial infa rct ion , unstable angina , and cardiac death were identified by a cardiologist blinded to the type of anesthesia received . Other major morbidity was determined at the time of hospital discharge and at 1 and 6 months after surgery . Results : Eleven patients who received GA required regrafting or an embolectomy during their hospital stay , compared with two patients who received EA . This association of GA with reoperation remained significant after adjustment for baseline differences . Cardiac outcomes were similar in the two groups with respect to perioperative death ( 1 EA and 1 GA ) , death within 6 months ( 4 EA and 3 GA ) , nonfatal myocardial infa rct ion within 7 days ( 2 EA and 2 GA ) , unstable angina ( 0 EA and 2 GA ) , and myocardial ischemia following r and omization ( 17 EA and 23 GA ) . Rates of major infections in the two groups ( 1 EA and 2 GA ) , renal failure ( 3 EA and 3 GA ) , and pulmonary complications ( 3 EA and 7 GA ) also were similar . Conclusions : Carefully conducted epidural and general anesthesia appear to be associated with comparable rates of cardiac and most other morbidity in patients undergoing lower extremity vascular surgery . However , compared with general anesthesia , epidural anesthesia is associated with a lower incidence of reoperatlon for inadequate tissue perfusion and , therefore , may be advantageous for this surgical population", "We assessed the influence of anesthetic technique for cesarean section on neonatal outcome . Thirty parturient women ( ASA I/II ) were r and omly allocated into two groups . In Group GA general anesthesia was induced with 4 mg·kg–1 thiopental and 1.5 mg·kg–1 succinylcholine . In group EA epidural anesthesia was performed with 20 ml 0.375 % bupivacaine through L3–4 inter-space . 1-min Apgar scores were significantly higher in group EA ( p ) . Neurologic and Adaptive Capacity scores at 2 and 24 h were higher in group EA ( p terms of blood gas values , umbilical arterial pH and pO2 values were higher in group EA ( p The first breast-feeding intervals were found to be shorter in group EA ( p of better Apgar and NAC scores , acid-base status and earlier initiation of breast-feeding , the epidural anesthesia may be preferred to general anesthesia in cesarean section", "The effects of cementation on arterial blood pressure , arterial oxygen tension and plasma levels of cortisol were studied in 30 patients with femoral neck fracture treated with the Thompson prosthesis in spinal ( n = 15 ) or general ( n= 15 ) anaesthesia . In spinal anaesthesia hypotension of clinical importance was observed coincidentally with the use of methylmethacrylate , while the levels of plasma cortisol remained unchanged . A significant rise was noted in arterial blood pressure and plasma levels of cortisol after cementation in general anaesthesia . Arterial oxygen tension fell in both groups . These findings indicate that the hypotension frequently reported in connection with cementation is triggered by a complex mechanism which can be modified by the anaesthetic technique", "In a prospect i ve , r and omized study , continuous infusion of epidural fentanyl citrate ( group E ) was compared with patient-controlled intravenously administered morphine sulfate ( group P ) for analgesia in 66 men after radical retropubic prostatectomy . Although both methods provided satisfactory analgesia , the mean comfort level scores were lower ( that is , greater comfort ) in group E than in group P at all observation times . The difference in mean resting comfort level scores between groups E and P was statistically significant ( P comfort level scores were noted at 8 of the 11 observation times during deep breathing , 5 of 11 during coughing , and 3 of 9 during ambulation . Maximal and minimal comfort level scores recorded by each patient during the course of the study were significantly lower ( that is , less pain ) in group E than in group P for all four categories of activity . The percentage of patients who reported no pain was significantly higher in group E than in group P at 9 of 11 observation times during resting and 5 of 11 observation times during deep breathing . No significant differences were noted in side effect profiles or duration of hospital stay . In summary , when two effective methods of analgesia used after radical retropubic prostatectomy were compared prospect ively , patients who received epidural infusion of fentanyl were more comfortable than those with patient-controlled intravenous administration of morphine , as evidence d by lower mean , maximal , and minimal comfort level scores and a greater proportion of patients with complete relief of pain", "OBJECTIVE A prospect i ve r and omized trial was organized to compare the effectiveness of general and regional anesthesia for cesarean section ( C/S ) . METHOD Three hundred and forty-one patients were r and omized into the general anesthesia group ( GA ) , epidural anesthesia group ( EA ) and spinal anesthesia group ( SA ) . The effectiveness of interest was success rate , blood loss and patient satisfaction . RESULT We found that the success rates of EA and SA were lower than GA . Success in EA should be improved by using an epidural catheter to add more local anesthetic drug instead of a single shot ; and the surgeon should allow more time for the block to work adequately . Success in SA should be improved by using bupivacaine instead of lidocaine . GA result ed in significantly more blood loss , lower postoperative hematocrit , and higher proportion of patients who had postoperative hematocrit than EA and SA . The patients ' satisfaction scores were not different among the 3 techniques . This meant that , given adequate explanation and perioperative care , Thai women were satisfied with regional anesthesia . CONCLUSION Regional anesthesia is a better choice of anesthesia for C/S than general anesthesia . However , the availability of different techniques and ability to change the technique when needed were very useful and important . If GA is chosen , all safety procedures must be followed . Oxygen supplement and endotracheal intubation facilities must be available in all techniques . Guidelines of anesthesia for C/S at a national level should be agreed upon , including the type of personnel , monitoring equipment and postoperative care", "Thirty patients who had undergone elective abdominal aortic surgery were studied in a prospect i ve , r and omised double‐blind comparison of thoracic epidural 0.2 % bupivacaine alone , thoracic epidural fentanyl alone and thoracic epidural 0.2 % bupivacaine combined with fentanyl . Pain relief , pulmonary function , cardiovascular stability and side effects were assessed . Pain relief was excellent in the combined bupivacaine‐fentanyl series , being significantly better than the other groups ( p hypotension . Forced expiratory parameters were reduced in all groups throughout the study to 50–60 % of the pre‐operative values , but there were no significant differences between groups . The incidence of side effects attributable to either epidural bupivacaine or fentanyl was low . This study supports the increasing use of epidural infusion analgesia for postoperative pain management after abdominal surgery", "One hundred and twenty women undergoing gynaecological abdominal operations were r and omized to receive either epidural bupivacaine 0.0625%+fentanyl 3.3μg/ml infusion ( Group EPI , n=57 ) , or patient-controlled intravenous morphine analgesia ( Group PCA , n=54 ) for postoperative pain relief . The groups were comparable in demographic data , types and duration of operation . Group EPI achieved significantly lower verbal rating scale of pain ( VRS ) at rest at 0 , 4 , 12 , 16 , 20 , 28 and 40th postoperative hours . The VRS during cough were also significantly lower in Group EPI at 0 , 4 , 8 , 12 , 28 and 36th postoperative hours . None of the patients had respiratory depression or hypotension . Nausea/vomiting occurred in 52.6%/33.3 % of patients in Group EPI and 52.7%/37.0 % in Group PCA . Most patients ( 84.2 % in Group EPI and 72.2 % in Group PCA ) rated their pain management as “ good ” . We conclude that epidural infusion of bupivacaine 0.0625 % and fentanyl 3.3μg/ml provide better analgesia than patient-controlled intravenous morphine after gynaecological", "Twenty – one ASA I or II patients undergoing upper abdominal surgery were studied for 24 hours after operation . They were entered into a prospect i ve , r and omised study of patient – controlled intravenous morphine compared with continuous thoracic epidural fentanyl combined with 0.2 % bupivacaine . Pain relief was superior in the bupivacaine series ( P pulmonary ventilation compared with the PCA series . Forced expiratory parameters were reduced in both series after the operation but significantly less so in the epidural group . There was a reduced incidence of emetic symptoms in the epidural group ( P incidence of other minor side effects did not differ significantly . Thoracic epidural fentanyl/bupivacaine results in significantly better analgesia than patient – controlled intravenous morphine", "Background : Gastric emptying is delayed in patients receiving postoperative pain relief with epidural morphine compared to patients receiving epidural bupivacaine . The electrophysiological basis for this effect is unknown . The aim of this study was to compare the effects of epidural morphine with epidural bupivacaine on gastroduodenal myoelectric activity ( EMG ) in patients after surgery", "During a period of one year , all patients above the age of 60 with surgical repair of fractured neck of femur were investigated in a prospect ively r and omized design . A follow-up study included a total number of 56 patients , 32 were allocated to halothane anaesthesia with intubation , 24 received spinal anaesthesia . In addition , 15 patients of the halothane group and 17 patients with spinal anaesthesia were investigated with regard to endocrine stress response . Total mortality was 12.5 % , and different anaesthetic management had no influence on the postoperative course . During the operation , adrenaline and ADH increased in both groups . This increase was attenuated by spinal anaesthesia . Noradrenaline was markedly increased even before the operation , and concentrations increased in the halothane group in the course of the operation . There was a linear correlation to time between accident and the beginning of the operation . With regard to endocrine parameters , prompt surgical treatment is beneficial", "Sixty patients with fractured neck of femur and scheduled for surgical correction were r and omly allocated to receive one of three anaesthetic techniques : general anaesthesia ; spinal analgesia ; psoas compartment block . The patients in the local anaesthetic groups also received a light general anaesthetic . There was little difference in the pre‐ , intra‐ and postoperative events , and no difference in postoperative mortality", "In a prospect i ve r and omized multi-centre study , the mortality following internal fixation surgery for fracture of the upper femur was investigated in 538 elderly patients allocated to receive subarachnoid blockade or general ( narcotic-relaxant ) anaesthesia . The 28-day mortality was 6.6 % with subarachnoid , and 5.9 % with general , anaesthesia . The difference was not significant ( 95 % confidence limits : -3.5 to + 4.8 ) . At 1 year following surgery , the mortality was 20.4 % . Increasing age , ischaemic heart disease , cardiac failure , preoperative arrhythmias and poor ASA status were all associated with increases in early and long term mortality . A delay to surgery of more than 24 h from admission was also associated with an increased 28-day mortality . Senile dementia and admission other than from the patient 's own home , were factors associated with a poorer long term outcome . From the point of view of mortality , subarachnoid anaesthesia did not appear to confer any advantages over general anaesthesia in non-prosthetic surgery for hip fracture in the elderly", " Fifty-seven patients , all over the age of 64 , with femoral neck fracture were r and omized to receive epidural or halothane anesthesia to see if the anesthetic technique influenced the incidence of postoperative confusion . All patients were lucid on admission . Using the American Psychiatric Association 's Diagnostic and Statistical Manual of Mental Disorders ( DSM-III ) as criteria for confusion , we found that 44 % of the patients developed confusion that correlated closely to a history of mental depression ( P incidence of confusion between the two anesthetic groups . In patients given halothane , however , early postoperative hypoxemia was associated with confusion ( P postoperative complications and almost four times longer hospitalization times . It is concluded that anticholinergic medication and a history of mental depression are predominant risk factors for development of postoperative confusion and in this respect are more important than the anesthetic technique", "The analgesic efficacy and side‐effects of combined epidural infusion of bupivacaine and morphine , in comparison with these drugs alone , for postoperative analgesia after hysterectomy ( 60 patients ) were evaluated . Before general anaesthesia , all patients had an epidural catheter placed ( Th11‐12 ) and 20 ml of 0.5 % bupivacaine was injected . In r and om order , epidural infusion was continued for 24 h with either 0.25 % bupivacaine 4 ml‐ h‐1 ( BUPI‐group ) , a bolus of 2 mg of morphine followed by morphine 0.2 mg‐ h‐1 ( MO‐group ) , or a combination of the two drugs ( COMB‐group ) . A urinary bladder catheter was kept for 24 h. Supplementary postoperative pain medications were i.m . morphine 0.1 mg‐ kg‐1 or rectal indomethacin 50 mg , on request . Immediately after awakening from general anaesthesia and transfer to the recovery room , 18/20 of the BUPI‐group patients , 17/20 of the MO‐group patients and 19/20 of the COMB‐group patients were pain‐free . In the postoperative evening and the first postoperative morning , the corresponding figures were 7/20 and 10/20 in the BUPI‐group , 15/20 and 15/20 in the MO‐group , and 18/20 and 15/20 in the COMB‐group ( postop . evening ; P ) . The number of patients requiring supplementary analgesics ( morphine and indomethacin ) during the first 24 h was greatest in the BUPI‐group ( P . The number of patients who vomited during the 24‐h period was 3 in the BUPI‐group , 9 in the MO‐group and 5 in the COMB‐group . Postoperatively , normal bowel function was restored after 1.9 days in the BUPI‐group , 2.2 days in the MO‐group and 2.6 days in the COMB‐group , on average ( P COMB ) . Recatheterization of the urinary bladder ( once ) was required in 4 patients in the MO‐group and 2 in the COMB‐group , but in none of the BUPI‐group . It is concluded that although the morphine‐containing epidural infusions ( 6.8 mg 24 h‐1 ) were superior to that containing bupivacaine alone with respect to postoperative analgesia after hysterectomy , the occurrence of disturbing emetic and urinary side‐effects made the therapy not totally satisfactory", "Objective To test the hypothesis that epidural anesthesia and postoperative epidural analgesia decrease the incidence of death and major complications during and after four types of intraabdominal surgical procedures . Summary Background Data Even though many beneficial aspects of epidural anesthesia have been reported , clinical trials of epidural anesthesia for outcome of surgical patients have shown conflicting results . Methods The authors studied 1,021 patients who required anesthesia for one of the intraabdominal aortic , gastric , biliary , or colon operations . They were assigned r and omly to receive either general anesthesia and postoperative analgesia with parenteral opioids ( group 1 ) or epidural plus light general anesthesia and postoperative epidural morphine ( group 2 ) . The patients were monitored for death and major complications during and for 30 days after surgery , as well as for postoperative pain , time of ambulation , and length of hospital stay . Results Overall , there was no significant difference in the incidence of death and major complications between the two groups . For abdominal aortic surgical patients , unlike the other three types of surgical patients , the overall incidence of death and major complications was significantly lower in group 2 patients ( 22 % ) than in group 1 patients ( 37 % ) , stemming from differences in the incidence of new myocardial infa rct ion , stroke , and respiratory failure between the two groups . Overall , group 2 patients received significantly less analgesic medication but had better pain relief than group 1 patients . In group 2 aortic patients , endotracheal intubation time was 13 hours shorter and surgical intensive care stay was 3.5 hours shorter . Conclusions The effect of anesthetic and postoperative analgesic techniques on perioperative outcome varies with the type of operation performed . Overall , epidural analgesia provides better postoperative pain relief . Epidural anesthesia and epidural analgesia improve the overall outcome and shorten the intubation time and intensive care stay in patients undergoing abdominal aortic operations", "Purpose To compare caudal and penile block for post-operative analgesia in children undergoing circumcision with respect to efficacy , complication rates , and parental satisfaction . Methods The study population consisted of 100 ASA 1 and 2 boys aged 3 to 8 years who were undergoing circumcision for religious reasons . In all participants , inhalation anesthesia was administered with oxygen : nitrous oxide ( 1 : 2 ) and halothane . The participants were allocated r and omly into two groups of 50 children each . Group 1 received penile block and Group 2 caudal block . The penile block was achieved by injecting bupivacaine into the two compartments of the subpubic space , with an additional ventral infiltration of a small volume of bupivacaine along the raphe of the penis . For caudal block , 1 ml·kg−1 body weight of 0.25 % bupivacaine was administered . Results Penile block shortened the induction-incision time and enabled earlier discharge home compared with caudal block . One patient undergoing penile block and nine patients undergoing caudal block vomited . Conclusions Penile and caudal block are equally effective for postcircumcision analgesia and neither is associated with serious complications . Anesthesiologist preference should be the deciding factor in choosing one technique over the other", "BACKGROUND Ketamine has been shown to prolong analgesia produced by caudal local anaesthetic block and is now in common use . This study compares caudal block using bupivacaine/ketamine with dorsal nerve block of the penis . METHODS Sixty boys undergoing elective circumcision were given either 0.5 ml x kg-1 of bupivacaine 0.15 % with ketamine 0.5 mg x kg-1 ( n = 30 ) or dorsal nerve block of the penis with bupivacaine 0.5 % ( n = 30 ) as a supplement to general anaesthesia . Postoperative pain was assessed by parents using a modified objective pain score , and the time taken to first requirement of analgesia was recorded . Motor weakness , time to first micturition , postoperative nausea and vomiting ( PONV ) , eating habits , sleep disturbance and behaviour were also assessed . RESULTS There was no difference between the groups in time to first requirement for analgesia or number of doses of paracetamol given in the first 24 h. Almost half the boys in the caudal group had motor weakness , and there was a significant increase in time to first micturition in that group . There was no difference between the groups in PONV , eating , sleeping or behavioural disturbance . CONCLUSIONS Caudal anaesthesia with bupivacaine/ketamine does not confer any advantage over a dorsal nerve block with the doses used in this study . Because of the higher incidence of side-effects and technique failure in the caudal group , dorsal nerve block is perhaps the preferred technique", "Quantitative assessment of myocardial ischaemia during incremental spinal , single-dose spinal and general anaesthesia may provide guidelines for the choice of anaesthetic technique for osteo synthesis of hip fractures in the elderly atherosclerotic individual . Forty-three patients with coronary artery disease were allocated to receive either incremental spinal anaesthesia ( bupivacaine 0.5 % plain ) ( A ) , single-dose spinal anaesthesia ( 2.5 mL of bupivacaine 0.5 % plain ) ( B ) or general anaesthesia ( fentanyl , thiopentone , atracurium , enflurane , N2O/O2 ) ( C ) for hip surgery . ST segment monitoring was performed from the induction of anaesthesia and for the following 48 h , and perioperative hypotension , blood loss and fluid therapy were recorded . ST depression developed in two out of 14 ( A ) , seven out of 15 ( B ) and six out of 14 ( C ) patients ( P = 0.14 ) . In ( A ) , a total of seven ST depressions occurred in the observation period as opposed to 125 in ( B ) and 16 in ( C ) ( P ST depression only occurred in ( B ) . Three ( A ) , 33 ( B ) and 40 ( C ) hypotensive events were recorded ( P ST depression compared with 10 % of normotensive patients ( P bupivacaine were used as opposed to the fixed 2.5 mL dose in ( B ) ( P mortality was higher in ( B ) ( P mortality between the three groups . The incidence of hypotension and myocardial ischaemia was lowest in the group receiving incremental spinal anaesthesia", "Fifty patients undergoing elective abdominal aortic surgery were r and omised to receive either combined epidural and general anaesthesia and postoperative epidural analgesia ( CEGA ) or general anaesthesia and postoperative intravenous morphine infusion ( GA ) . Prospect i ve data was collected in order to compare the two groups . This included intraoperative cardiovascular changes and postoperative complications . The use of intraoperative vasopressors was significantly higher in the CEGA group ( P intravenous glyceryl trinitrate was significantly lower ( P no significant difference between groups in regard to blood loss , volume replacement or in the number of patients requiring postoperative ventilation . Two patients in the CEGA group died postoperatively compared to one in the GA group ( not significant ) . There was no significant difference between groups in the total number or type of postoperative complications . Combining epidural anaesthesia with general anaesthesia altered intraoperative cardiovascular management but did not affect postoperative outcome", "Postoperative hypothermia initiates an increased oxygen dem and in the postoperative period and may endanger patients with restricted cardiopulmonary reserves . In order to compare net heat losses and gains , we studied 28 women undergoing hip fracture surgery , using either general anaesthesia or spinal analgesia . The superficial and central temperatures were followed in the per‐ and postoperative period . Total body heat was calculated from temperature measurements . Temperature changes were unrelated to the type of anaesthesia . Large net heat losses occurred on transfer to the recovery room", "In this study , we assessed the influence of three analgesic techniques on postoperative knee rehabilitation after total knee arthroplasty (TKA).Forty-five patients scheduled for elective TKA under general anesthesia were r and omly divided into three groups . Postoperative analgesia was provided with IV patient-controlled analgesia ( PCA ) with morphine in Group A , continuous 3-in-1 block in Group B , and epidural analgesia in Group C. Immediately after surgery , the three groups started identical physical therapy regimens . Pain scores , supplemental analgesia , side effects , degree of maximal knee flexion , day of first walk , and duration of hospital stay were recorded . Patients in Groups B and C reported significantly lower pain scores than those in Group A. Supplemental analgesia was comparable in the three groups . Compared with Groups A and C , a significantly lower incidence of side effects was noted in Group B. Significantly better knee flexion ( until 6 wk after surgery ) , faster ambulation , and shorter hospital stay were noted in Groups B and C. However , these benefits did not affect outcome at 3 mo . We conclude that , after TKA , continuous 3-in-1 block and epidural analgesia provide better pain relief and faster knee rehabilitation than IV PCA with morphine . Because it induces fewer side effects , continuous 3-in-1 block should be considered the technique of choice . Implication s : In this study , we determined that , after total knee arthroplasty , loco-regional analgesic techniques ( epidural analgesia or continuous 3-in-1 block ) provide better pain relief and faster postoperative knee rehabilitation than IV patient-controlled analgesia with morphine . Because it causes fewer side effects than epidural analgesia , continuous 3-in-1 block is the technique of choice . ( Anesth Analg 1998;87:88 - 92", "In a prospect i ve r and omized trial the effects of continuous peridural analgesia on gastrointestinal motility and the postoperative course was studied in 48 consecutive patients with elective colorectal resections . 24 patients had peridural analgesia ( PDA ) with bupivacaine while 24 patients received intravenous analgesia ( IVA ) with pentazocine . With PDA the first passage of flatus and faeces was significantly accelerated . PDA was not associated with an increased rate of anastomotic breakdown and there were no respiratory complications in the PDA group", "Background The efficacy and effects of epidural analgesia compared with patient-controlled analgesia ( PCA ) have not been reported in patients undergoing major vascular surgery . We compared the effects of epidural bupivacaine-morphine with those of intravenous PCA morphine after elective infrarenal aortic surgery . Methods Forty patients classified as American Society of Anesthesiologists physical status 2 or 3 received general anesthesia plus postoperative PCA using morphine sulfate ( group PCA ; n = 21 ) or general anesthesia plus perioperative epidural morphine - bupivacaine ( group EPI ; n = 19 ) during a period of 48 h. During operation , EPI patients received 0.05 mg/kg epidural morphine and 5 ml 0.25 % bupivacaine followed by an infusion of 0.125 % bupivacaine with 0.1 % morphine ( 0.1 mg/ml ) ; group PCA received 0.1 mg/kg intravenous morphine sulfate . Continuous electrocardiographic monitoring ( V4 and V5 leads ) was performed from the night before surgery until 48 h afterward . Respiratory inductive plethysmographic data were recorded after tracheal extubation . Visual analog pain scores at rest and after movement were performed every 4 h after extubation . Results Nurse-administered intravenous morphine and time to tracheal extubation were less in group EPI , as were visual analog pain scores at rest and after movement from 20 to 48 h. Complications and the duration of intensive care unit and hospital stay were comparable . There was a similar , low incidence of postoperative apneas , slow respiratory rates , desaturation , and S-T segment depression . Conclusions Epidural morphine-bupivacaine is associated with reduced early postoperative intravenous opioid requirements , more rapid tracheal extubation , and superior analgesia after abdominal aortic surgery , with comparable respiratory effects", "The analgesic effects of systemically administered diamorphine , caudal analgesia with 0.5 % bupivacaine plain and caudal analgesia with 0.5 % bupivacaine plain to which morphine sulphate had been added were studied in boys undergoing circumcision . Postoperative analgesia was assessed using a linear analogue scale . The time interval between operation and subsequent analgesic administration and the number of analgesic doses in 24 h were compared . The frequency of vomiting was noted . All three methods provided satisfactory results . The only detectable difference between the groups was a more rapid , but transient , recovery in the group receiving plain bupivacaine only . The frequency of vomiting was high in all groups . Caudal analgesia , with or without the addition of morphine , did not confer any advantage over injected diamorphine , and did not justify the extra time , risk and expense required to carry it out", "In a double-blind , r and omized study , we have compared the effects of i.v . ketoprofen 200 mg followed by 12.5 mg h-1 over 13 h , with those of extradural morphine 4 mg in 32 patients after hip and knee arthroplasty . A visual analogue scale was used to score pain before analgesic administration ( first complaint after operation ) , 1 h after and every 2 h subsequently . Pain reduction 1 h after the start of analgesia was mean 44 % ( SEM 17 % ) in the extradural morphine group and 54 % ( 9 % ) in the ketoprofen group ( ns ) . There were no significant differences between groups in pain scores , pain reduction and additional analgesia requirement ( i.v . paracetamol ) . Naloxone 5 micrograms kg-1 h-1 was required for hypercapnia exceeding 6.0 kPa in three patients in the extradural morphine group ( vs none in the ketoprofen group ; ns ) . There were no differences between groups in side effects , except for urinary retention , which was more frequent in the extradural morphine group ( P ketoprofen and extradural morphine , we conclude that ketoprofen may be an efficient alternative to extradural morphine after hip and knee arthroplasty", "A prospect i ve r and omised double blind study was carried out to compare the use of epidural methadone , morphine and bupivacaine for pain relief after Caesarean section . The results indicate that methadone is the most effective agent with few side effects . Subsequently this method was used routinely for postoperative analgesia in all patients undergoing Caesarean section . A retrospective study of 178 patients having this method of analgesia was carried out and indicated that epidural methadone is an effective and safe method of postoperative pain relief" ]

[ "PURPOSE The purpose of this study was to compare the effectiveness of 5 % sodium hypochlorite ( NaOCl ) to that of ferric sulfate ( FeSO4 ) as a pulpotomy medicament in decayed primary molars . METHODS Healthy subjects between 4 and 9 years with at least 2 primary molars needing pulpotomy consented to receive either NaOCl or FeSO4 and restoration with IRM base/stainless steel crown in a prospect i ve , r and omized design . Clinical and radiographic signs/symptoms were recorded at 0 , 6 , and 12 months . RESULTS Twenty-three subjects were recruited . Six-month results are based on the first 32 teeth in the NaOCl group and 28 teeth in the FeSO4 group . Twelve-month results are based on 13 teeth in the FeSO4 group and 14 in the NaOCl group . Results show 100 % restoration retention in both groups and no signs/symptoms of pain at 6 and 12 months . At 6 months , 100 % clinical success was found with both FeSO4 and NaOCl . Radiographic success for FeSO4 was 68 % , with internal resorption being the most common finding . The NaOCl group showed 91 % radiographic success , P = .050 . At 12 months , FeSO4 had 85 % clinical success and 62 % radiographic success . NaOCl had 100 % clinical success and 79 % radiographic success . CONCLUSION Preliminary evidence shows that NaOCl can be used successfully as a pulpotomy medicament", "PURPOSE The purpose of this study was to investigate the outcomes of vital primary molar pulpotomy when there is no direct contact between eugenol and the vital pulp . Four pulpotomy techniques were compared : ( 1 ) ferric sulfate ( FS ) pulpotomy ; ( 2 ) eugenol-free FS pulpotomy ; ( 3 ) mineral trioxide aggregate ( MTA ) pulpotomy ; and ( 4 ) FS/MTA pulpotomy . METHODS The pulpotomy technique assigned to each molar was determined by r and om selection . Two blinded , disinterested raters classified each molar into 1 of 3 radiographic outcomes : ( 1 ) N = normal molar without pathologic change ; ( 2 ) Po = pathologic change present , follow-up recommended ; ( 3 ) Px = pathologic change present , extract . RESULTS A total of 92 patients with 227 pulpotomy-treated molars returned for at least 1 recall examination . Median follow-up for molars was 24 months ( range=12 - 38 months ) . MTA molars demonstrated significantly fewer Px radiographic outcomes than FS molars ( P=.002 , chi-square test ) . Eugenol-free FS molars demonstrated significantly more Px radiographic outcomes than MTA ( P survival was demonstrated for eugenol-free FS molars compared to MTA molars ( P=.02 , log-rank test ) over 6 to 38 months . CONCLUSIONS Outcomes for mineral trioxide aggregate pulpotomy were superior to ferric sulfate and eugenol-free ferric sulfate pulpotomy after a median follow-up of 2 years", "Purpose The aim of this study was to compare the effect of white mineral trioxide aggregate ( MTA ) to that of formocresol ( FC ) as pulp dressing agents in pulpotomised primary molars . Methods In this clinical trial study , 60 lower second primary molars of 46 children were treated by a conventional pulpotomy technique . The teeth were r and omly assigned to the MTA ( experimental ) and FC ( control ) groups by r and om numbered table . Following removal of the coronal pulp and haemostasis , the pulp stumps were covered with an MTA paste in the experimental group . In the control group , FC was placed with a cotton pellet over the pulp stumps . The teeth of both groups were restored with stainless steel crowns . Children arrived for clinical and radiographic follow-up evaluation after 6 , 12 and 24 months . Results The treated teeth in FC group ( n = 18 ) were clinical ly and radiographically successful after 24 months . The radiographic follow-up evaluation revealed one failure ( furcation involvement ) in 18 molars treated with MTA after 24 months . The treated teeth in MTA group were clinical ly successful 24 months postoperatively . Pulp canal obliteration was observed in one of the teeth treated with MTA and four of the teeth treated with FC . Conclusion MTA could be used as a safe medicament for pulpotomy in cariously exposed primary molars and could be a substitute for FC", "Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed", "Pulpotomies were performed on 83 primary molars in 62 patients . Ferric sulfate or formocresol was placed on the pulpal stumps , and teeth were followed for 3- , 6- , and 12-month periods . After the one-year follow-up , 28 of 29 teeth treated with ferric sulfate ( FS group ) were considered successful and 21 of 27 teeth treated with formocresol ( FC group ) were judged to be successful . The FS group demonstrated greater combined clinical and radiographic success than the FC group at the one-year recall ( P < 0.05 ) . Although the results of this study are promising , further study with longer observation periods is warranted before this technique can be recommended", "AIM To compare the treatment outcomes of calcium-enriched mixture ( CEM ) cement and mineral trioxide aggregate ( MTA ) as pulp dressing bio material s in vital pulpotomy of carious primary molars . STUDY DESIGN split-mouth r and omised clinical trial . MATERIAL S AND METHODS Forty children aged 4 - 8 years with 2 carious teeth requiring pulpotomy were selected and r and omly assigned to MTA ( n = 40 ) or CEM ( n = 40 ) groups . After coronal pulp removal , the remaining radicular pulp was covered with an appropriate bio material ; the teeth were then permanently restored . Clinical /radiographic success/failures were blindly evaluated at 6- , 12- and 24-month follow-ups . STATISTICS the recorded data were analyzed with McNemar test and GEE . RESULTS A total of 36 , 33 and 35 patients were available for 6- , 12- and 24-month follow-ups , respectively . At the 12-month follow-up only one and three teeth in the CEM and MTA groups had pathologic external root resorption , respectively . The resorbed teeth were then missed due to extraction /exfoliation at the 24-month follow-up ; all other treated teeth were sign/symptom-free . Overall , clinical and radiographic outcomes in both MTA/CEM groups were comparable at the three follow-ups without significant differences . Time had no significant effect on the success . CONCLUSION MTA and CEM demonstrated favourable treatment outcomes for pulpotomy of carious primary molars ; CEM may be an effective pulp dressing bio material", "AIM To compare the outcome after 6 months of the application of formocresol ( FC ) or mineral trioxide aggregate ( MTA ) during pulpotomy in primary molar teeth . METHODOLOGY A maximum of 126 children ( aged 5 - 9 years ) with carious primary teeth that required pulpotomy were selected . Following r and omization , a st and ard pulpotomy preparation was undertaken , and the coronal pulp removed and bleeding arrested . In the FC group , cotton balls , soaked in FC , were placed for 5 min , and then the pulp chamber was filled with Zonalin , a pulpotomy agent . In the MTA group , a 1-mm-thick paste of MTA was used as a pulpotomy agent . The crowns in both groups were restored with amalgam or glass ionomer . The teeth of 100 patients were evaluated and compared clinical ly and radiographically after 3 and 6 months . RESULTS No signs of clinical failure were observed at the 3- and 6-month follow-up appointments in either group . There were no significant differences in the radiographic findings of the teeth and surrounding tissue at the 3-month follow-up . However , at the 6-month follow-up , significantly more cases ( P = 0.036 ) with root resorption were seen in the FC group ; no cases of resorption occurred amongst the MTA cases . The surrounding tissue showed radiographic signs of post-treatment disease in four FC cases ; none was seen in the MTA cases . CONCLUSION After 6 months , pulpotomy with MTA was associated with fewer cases of root resorption and post-treatment disease . MTA appears to be a reliable alternative material for pulpotomy in primary molar teeth", "OBJECTIVES Although previous studies have examined the electrosurgical pulpotomy technique for primary teeth , no well-controlled , clinical human trials have been published . The purpose of this study was to prospect ively compare electrosurgical pulpotomies vs. formocresol pulpotomies in human vital primary molar teeth . DESIGN Fifty children were r and omly divided into two groups , 25 receiving an electrosurgical pulpotomy and 25 receiving a formocresol pulpotomy . RESULTS After at least 5 months postoperative observation time , the clinical and radiographic success rates for the electrosurgical groups were 96 and 84 % , respectively ; and for the formocresol group , 100 and 92 % , respectively . CONCLUSION There were no statistically significant differences between the success rates for the two groups at the P success rate between the electrosurgical and formocresol pulpotomy techniques", "PURPOSE The aim of this study was to compare the effect of mineral trioxide aggregate ( MTA ) to that of formocresol ( FC ) as pulp dressing agents in pulpotomized primary molars with carious pulp exposure . METHODS Forty-five primary molars of 26 children were treated by a conventional pulpotomy technique . The teeth were r and omly assigned to the MTA ( experimental ) or FC ( control ) group by a toss of a coin . Following removal of the coronal pulp and hemostasis the pulp stumps were covered with an MTA paste in the experimental group . In the control group , FC was placed with a cotton pellet over the pulp stumps for 5 minutes and removed ; the pulp stumps were then covered by zinc oxide-eugenol ( ZOE ) paste . The teeth of both groups were restored with stainless steel crowns . Eighteen children with 32 teeth arrived for clinical and radiographic follow-up evaluation ranging from 6 to 30 months . RESULTS The follow-up evaluations revealed only one failure ( internal resorption detected at a 17 months postoperative evaluation ) in a molar treated with formocresol . None of the MTA-treated teeth showed any clinical or radiographic pathology . Pulp canal obliteration was observed in 9 of 32 ( 28 % ) evaluated molars . This finding was detected in 2 out of the 15 teeth treated with FC ( 13 % ) and in 7 out of the 17 treated with MTA ( 41 % ) . CONCLUSION MTA showed clinical and radiographic success as a dressing material following pulpotomy in primary teeth and seems to be a suitable replacement for formocresol in primary teeth", "AIM : To compare the clinical and radiographic success rates of two vital pulpotomy agents : formocresol ( FC ) and Ankaferd Blood Stopper ® ( ABS ) , in primary molars during a 12-month follow-up period . STUDY DESIGN : A r and omised , single-blind study design was used in a sample of 30 healthy 6–9 year old children with 60 carious primary molars without clinical or radiographic evidence of pulp degeneration . METHODS : The pulpotomy agents were assigned as follows : Group 1 was 1:5 diluted Buckley ’s formocresol ( FC ) and Group 2 was ABS . Clinical and radiographic follow-up at 3 , 6 , and 12 months used the following criteria : pain , swelling , sinus tract , mobility , internal root resorption , and furcation and /or periapical bone destruction . STATISTICS : The data were analysed using Chi-square tests . RESULTS : The clinical and radiographic evaluation at 3 months revealed total success rates of 100 % in the FC and ABS groups . Success rates in FC and ABS groups at 6 months were 96.7 % and 93.3 % respectively . At the 12-month follow-ups , the total success rates in the FC , and ABS groups were 89.3 % and 85.7 % , respectively . When the groups were compared according to the time intervals , no significant differences were observed between the 3 , 6 , and 12 month values . The success rates of the material s decreased over time . CONCLUSIONS : FC and ABS were found successful as pulp dressings in primary molars . ABS appears to be an alternative pulpotomy agent but periodical follow-ups must be considered to evaluate long term success rates", "OBJECTIVE The aim of this study was to compare the clinical and radiographic success rates of 3 pulpotomy techniques : formocresol , calcium hydroxide , and calcium hydroxide/iodoform . STUDY DESIGN The pulpotomies were performed by fifth-year undergraduate dental students . Members of senior staff at the clinics supervised all of the procedures . Informed consent was obtained from each child 's parents . The teeth were r and omly assigned to the experimental ( calcium hydroxide and calcium hydroxide/iodoform ) or control ( formocresol ) groups . After coronal pulp removal and hemostasis , remaining pulp tissue was covered with calcium hydroxide or calcium hydroxide/iodoform paste in the experimental groups . In the control group , formocresol was placed with a cotton pellet over the pulp tissue for 5 minutes and removed ; the pulp tissue was then covered with zinc oxide-eugenol . All teeth were restored with stainless-steel crowns . Clinical and radiographic successes and failures were recorded at 1- , 3- , 6- , and 12-month follow-ups by the authors . Data were statistically analyzed using chi-squared tests . RESULTS The follow-up evaluations revealed that the clinical success rates were 89.7 % for formocresol , 33.3 % for calcium hydroxide , and 17.2 % for calcium hydroxide/iodoform . The radiographic success rates were 89.7 % for formocresol , 33.3 % for calcium hydroxide , and 13.8 % for calcium hydroxide/iodoform . CONCLUSIONS Formocresol was superior to calcium hydroxide and calcium hydroxide/iodoform pastes for primary molar pulpotomies . Internal resorption was the most common radiographic failure in all 3 pulpotomy techniques", "Pulpotomy is the accepted therapy for the management of cariously exposed pulps in symptom-free primary molars ; however , evidence is lacking about the most appropriate technique . The aim of this study was to compare the relative effectiveness of the Er : YAG laser , calcium hydroxide , and ferric sulfate techniques with that of dilute formocresol in retaining such molars symptom-free . Two hundred primary molars in 107 healthy children were included and r and omly allocated to one of the techniques . The treated teeth were blindly re-evaluated after 6 , 12 , 18 , and 24 months . Descriptive data analysis and logistic regression analysis , accounting for each patient ’s effect by a generalized estimating equation ( GEE ) , were used . After 24 months , the following total and clinical success rates were determined ( % ) : formocresol 85 ( 96 ) , laser 78 ( 93 ) , calcium hydroxide 53 ( 87 ) , and ferric sulfate 86 ( 100 ) . Only calcium hydroxide performed significantly worse than formocresol ( p = 0.001 , odds ratio = 5.6 , 95 % confidence interval 2.0–15.5 ) . In conclusion , calcium hydroxide is less appropriate for pulpotomies than is formocresol", "A pulpotomy is the therapy for management of pulp exposures due to caries in symptom-free primary molars . The aim was to longitudinally compare the relative effectiveness of the Er : YAG laser , calcium hydroxide and ferric sulphate techniques with dilute formocresol in retaining symptom-free molars . Two hundred primary molars in 107 healthy children were included and r and omly allocated to one technique . The treated teeth were blindly reevaluated after 6 , 12 , 18 , 24 and 36 months . Descriptive data analysis and logistic regression analysis accounting for multiple observations per patient by generalised estimating equation were used . Additionally , various influences including tooth type , upper and lower jaws , type of anaesthesia , operator and the final restoration on treatment success were evaluated ( Wald chi-square test ) . After 36 months , the following total ( considering clinical and clinical ly symptom-free radiographic failures ) and clinical success rates were determined ( in percent ) : Formocresol 72 ( 92 ) , laser 73 ( 89 ) , calcium hydroxide 46 ( 75 ) , ferric sulphate 76 ( 97 ) . No significant differences were detected between formocresol and any other technique after 36 months . However , the odds ratio of failure appeared to be three times higher for calcium hydroxide than for formocresol . No significant differences in total success rates were seen regarding the aforementioned influencing clinical parameters . The correct diagnosis of the pulpal status , bleeding control and the specific technique are highly important for long-term success of pulpotomies in primary molars . According to the presented long-term data , pulpotomies using ferric sulphate revealed the best treatment outcome among the used techniques , while calcium hydroxide result ed in the lowest success rates after 3 years . Therefore , we can recommend ferric sulphate for easy and successful treatment of primary molars with caries-exposed pulps", "BACKGROUND Vital pulpotomy is a single-stage procedure defined as the surgical amputation of the coronal portion of exposed vital pulp , usually as a means of preserving the vitality and function of the remaining radicular portion . OBJECTIVES The aim of this study was to compare the clinical and radiographic success rates for electrosurgical vs formocresol pulpotomy in human primary molar teeth . SETTING S AND DESIGN This was a prospect i ve , r and omized clinical trial . MATERIAL S AND METHODS In this r and omized clinical trial , pulpotomies were performed on 70 primary molars in children aged 5 - 10 years . The teeth were treated using either a conventional formocresol ( 35 teeth ) or electrosurgical technique ( 35 teeth ) . Following the pulpotomy procedure , the teeth were evaluated for clinical and radiographic success for three , six and nine months . The teeth were evaluated for the presence of pain , abscess , fistula , mobility , internal and external resorption , and radiolucency . STATISTICAL ANALYSIS The data were assessed with Fishers ' Exact test . RESULTS After nine months of follow-up , the clinical and radiographic success rates were 96 and 84 % respectively in the electrosurgical group and 100 and 96.8 % respectively in the formocresol group . There was no statistically significant difference between the success rates in the two groups ( P > 0.05 ) . CONCLUSIONS Our results showed the failure rates for electrosurgical pulpotomy to be equal to those for formocresol pulpotomy . Although electrosurgical pulpotomy is a nonpharmacological technique giving favorable results , it is still a preservative technique . Further studies using larger sample s and longer evaluation periods are recommended", "PURPOSE The purpose of this multisite , multioperator , prospect i ve , r and omized , controlled clinical trial was to evaluate 2-year outcomes of diluted formocresol ( DFC ) compared to gray mineral trioxide aggregate ( GMTA ) as pulpotomy medicaments . METHODS Following the st and ard pulpotomy procedure , the pulp stumps of 252 primary molars in 168 healthy children were r and omly covered with GMTA or DFC . Pulp chambers were filled with Intermediate Restorative Material ( IRM ( ® ) ) and teeth were restored with stainless steel crowns . At each follow-up appointment , the clinical status of the treated tooth was assessed and radiographs were taken . A total of 694 clinical and radiographic evaluations were analyzed . RESULTS Gender , study site , arch type , and tooth type did not influence treatment outcome . At the combined 6- to 24-month follow-up , clinical success in the DFC group was no different than for the GMTA group . Radiographically , a significantly lower success rate was found in the DFC group vs the MTA group at all time points ( P ) . Dentin bridge formation was observed at a significantly higher frequency among the GMTA group ( P while internal root resorption was observed at a higher frequency in the DFC group ( P<.01 ) . CONCLUSION At the combined 6- to 24-month follow-up , gray mineral trioxide aggregate demonstrated significantly better radiographic outcomes vs diluted formocresol as pulpotomy medicaments", "Seventy primary molar teeth , carious exposed , symptom free , without any sign of root resorption in children aged from 3 to 6 years ( main age 4.3 yr ) were treated with conventional pulpotomy procedures . Ferric sulfate 15.5 % solution ( applied for 15 second for 35 teeth ) and formocresol solution ( five minute procedure of Buckley 's formula for next 35 teeth ) have been used as pulpotomy agents . In both groups , pulp stumps were covered with zinc-oxide eugenol paste . Permanent restorations were stainless steel crowns . Clinical check up was every three-months and radiographic follow-up time was six and twenty months after treatment . Our results within this period revealed 100 % clinical success rate in both groups . Radiographic success rate was in both groups 97.2 % , while in 2.8 % cases has shown internal root resorption . On the basis of these results , we can recommend ferric sulfate as a pulpotomy agent in primary teeth in substitution for formocresol at the moment", " The aim of this study was to compare the efficacy of lyophilized freeze dried platelet derived preparation with calcium hydroxide as pulpotomy agents in primary molars . Fifty six primary molars in 28 children were treated by a conventional pulpotomy technique . 28 teeth were treated by lyophilized freeze-dried platelet derived preparation and another 28 by calcium hydroxide . Clinical evaluation was carried out out at 1 , 3 , and 6-months interval and the radiographic evaluation was carried out at 1 and 6-months . The success rate of lyophilized freeze-dried platelet derived preparation proved better than calcium hydroxide", "PURPOSE The aim of this study was to use clinical , radiographic , and histologic examinations to compare the relative success of gray mineral trioxide aggregate ( MTA ) , white MTA , and formocresol as pulp dressings in pulpotomized primary teeth . METHODS Twenty-four children , each with at least 3 primary molars requiring pulpotomy , were selected for this study 's clinical and radiographic portion . An additional 15 carious primary teeth planned for serial extraction were selected for this study 's histologic portion . All selected teeth were evenly divided into 3 test groups and treated with pulpotomies . Gray MTA was used as the pulp dressing for one third of the teeth , white MTA was the dressing for one third , and the remaining one third were treated with formocresol . The treated teeth selected for the clinical and radiographic evaluations were monitored periodically for 12 months . The treated teeth selected for histologic study were monitored periodically and extracted 6 months postoperatively . RESULTS Four children with 12 pulpotomized teeth failed to return for any follow-up evaluations in the clinical and radiographic study . Of the remaining 60 teeth in 20 patients , 1 tooth ( gray MTA ) exfoliated normally and 6 teeth ( 4 white MTA and 2 formocresol ) failed due to abscesses . The remaining 53 teeth appeared to be clinical ly and radiographically successful 12 months postoperatively . Pulp canal obliteration was a radiographic finding in 11 teeth treated with gray MTA and 1 tooth treated with white MTA . In the histologic study , both types of MTA successfully induced thick dentin bridge formation at the amputation sites , while formocresol induced thin , poorly calcified dentin . Teeth treated with gray MTA demonstrated pulp architecture nearest to normal pulp by preserving the odontoblastic layer and delicate fibrocellular matrix , yet few inflammatory cells or isolated calcified bodies were seen . Teeth treated with white MTA showed a denser fibrotic pattern , with more isolated calcifications in the pulp tissue along with secondary dentin formation . CONCLUSIONS Gray MTA appears to be superior to white MTA and formocresol as a pulp dressing for pulpotomized primary teeth", "PURPOSE The purpose of this study was to evaluate the total success rates of mineral trioxide aggregate ( MTA ) , ferric sulfate ( FS ) , and formocresol ( FC ) as pulpotomy agents in primary molars . METHODS A r and omized , split-mouth study design was used in 32 healthy 5- to 7-year-old children with 128 carious primary molars without clinical or radiographic evidence of pulp degeneration . The pulpotomy agents were assigned as follows : Group 1=MTA ; Group 2=FS ; Group 3=1:5 diluted Buckley 's FC ; and Group 4=zinc oxide eugenol ( ZOE ) base . Clinical and radiographic follow-up at 6 , 12 , and 24 months used the following criteria : pain ; swelling ; sinus tract ; mobility ; internal root resorption ; and furcation and /or periapical bone destruction . The data were analyzed using chi-square . RESULTS No significant differences in success rates were found among the groups at 6 and 12 months . Success rates in groups 1 to 4 at 24 months were 96 % , 88 % , 88 % , and 68 % respectively . There was a significant difference ( P MTA and ZOE groups at 24 months . CONCLUSIONS ZOE , as the only pulpotomy medicament , had a significantly lower success rate than MTA . No significant differences were observed , among the 3 experimental material s ( MTA , FC , and FS ) at 2 years follow-up", "AIM To evaluate and compare mineral trioxide aggregate ( MTA ) and formocresol as pulpotomy medicaments by clinical and radiographic assessment s and to assess the histological features of both pulpotomy medicaments in deciduous teeth . MATERIAL S AND METHODS This study was performed on 100 m and ibular deciduous molar teeth requiring pulpotomy treatment . Children between age four and six years were r and omly selected and divided into formocresol or MTA group . The patients were recalled after 3 , 6 , 9 , 12 months respectively and evaluated clinical ly and radiographically . Histological assessment was done on lower deciduous canine teeth , which were undergoing serial extraction for interceptive orthodontic purpose . Pulpotomy was done on four teeth with formocresol and another four teeth with MTA . The teeth were extracted after six months following pulpotomy procedure and histologically evaluated . Two freshly extracted carious teeth were taken as controls . RESULTS Clinical and radiographic criteria were laid and Chi analysis revealed significant difference in mobility ( P≤0.05 ) , periodontal ligament widening ( P≤0.01 level ) and inter - radicular radiolucency ( P≤0.02 level ) between two groups at the end of 12 months . Histologically , in MTA group , a layer of new dentine formation with less dentinal tubules at the pulpotomized site was found . In formocresol group , increased inflammatory cells , a zone of atrophy , were noted in radicular portion of pulp . CONCLUSION MTA is superior to formocresol clinical ly , radiographically . Histological analysis showed better reparative ability with hard tissue barrier formation with MTA compared to formocresol", "The purpose of this study was to compare the clinical and radiographic success rates of two different pulpotomy agents : one novel agent , the biologically active odontogenic protein enamel matrix derivative ( EMD ) versus formocresol ( FC ) . A r and omized , single-blind , split-mouth study was used with a sample of 15 children aged 4 to 7 years ( mean age , 5 + /- 0.73 years ) . A total of 15 pairs of teeth , 1 pair per child , were selected for treatment . One tooth from each pair was r and omly assigned to either the EMD pulpotomy group or the FC pulpotomy group . All teeth were followed up clinical ly and radiographically at 2 , 4 , and 6 months . After 6 months , the clinical success rates for the FC and EMD groups were 67 % and 93 % , respectively . Although most likely clinical ly relevant , the clinical success rate difference after 6 months was not statistically significant . After 6 months , the radiographic success rates for the FC and EMD groups were 13 % and 60 % , respectively . There was a statistically significant difference at p clinical and radiographic assessment of EMD pulpotomized teeth in this study offers preliminary evidence that EMD is a promising material which may be as successful , or more so , than other pulpotomy agents", "OBJECTIVE The purpose of this study was to investigate whether a diode laser pulpotomy with mineral trioxide aggregate ( MTA ) sealing could be an acceptable alternative to the conventional formocresol pulpotomy and zinc oxide eugenol ( ZOE ) sealing in human primary teeth . METHODS A r and omized , single-blind , split-mouth study was used with a sample of 16 children aged from 3 to 8 years ( mean age=5.10 years ) . A total of 26 pairs of teeth from these 16 patients were selected based on clinical and radiographic criteria . One tooth from each pair was r and omly assigned to either the laser-MTA pulpotomy group or the formocresol-ZOE pulpotomy group . All teeth were followed up clinical ly and radiographically at 2.3 , 5.2 , 9.5 and 15.7 months . All extracted failures were sectioned and photographed to assess possible reasons for this . RESULTS A total of seven laser-MTA-treated teeth were deemed to be radiographic failures ( mean time until failure=9.1 months ) compared to three formocresol-ZOE treated teeth ( mean time until failure=12.5 months ) . These results were not significant using Fisher 's exact test ( P>0.05 ) . Six of the laser-MTA failures and all three formocresol-ZOE failures exhibited furcal and /or periapical radiolucencies with or without pathologic root resorption . One of the laser-MTA failures displayed premature root resorption and is being observed for exfoliation . Analysis of photographs of teeth available for extraction revealed errors in clinical technique in addition to expected signs of a disease process such as the presence of granulation tissue and areas of pathologic root resorption . CONCLUSIONS The laser-MTA pulpotomy showed reduced radiographic success rates compared to the formocresol-ZOE pulpotomy at 15.7 months ; however , these results were not statistically significant . Improved success rates among a larger patient sample and a longer follow-up period would be required for the laser-MTA pulpotomy to be considered a routine alternative to the conventional formocresol-ZOE procedure . Meticulous restorative techniques must be followed to ensure the success of laser-MTA pulpotomies", "The purpose of this study was to compare the effects of Nd : YAG laser pulpotomy to formocresol pulpotomy on human primary teeth . Patients with a primary tooth that required pulpotomy because of pulpal exposure to caries , were selected for this study . After removal of coronal pulpal tissue , Nd : YAG laser at 2 W , 20 Hz , 100 mJ or a 1:5 dilution of formocresol was introduced into the canal orifice for complete hemostasis . IRM paste was then placed over the pulp stump , and the tooth was restored either with composite resin or stainless steel crown . Sixty-eight teeth were treated with Nd : YAG laser and followed up for 6 to 64 months . Clinical success was achieved in 66 out of the 68 teeth ( 97 % ) , and 94.1 % were radiographically successful . In the control group , 69 primary molars were treated with formocresol and followed up for 9 to 66 months ; 85.5 and 78.3 % achieved clinical and radiographic success , respectively . The success rate of Nd : YAG laser pulpotomy was significantly higher than that of formocresol pulpotomy . The permanent successors of the laser-treated teeth erupted without any complications", "Post-operative clinical and x-ray findings on 80 primary molars were evaluated . These molars had undergone pulpal therapy by 2 techniques : pulpotomy with formocresol and with electrosurgery . The sample was selected from children between the ages of 4 and 7 . A criterion for inclusion was each child must have at least 2 primary molars with pulp exposed by caries . Experimental molars with 1 or more of the following clinical or radiographic signs and symptoms were excluded : mobility , sensitivity to percussion , the presence of fistulae , groove drainage , apical or internal resorption , fetid smell and compromised furcation . Also excluded were patients previously diagnosed with diabetes , cardiopathy and renal alterations . Initially , a dinical and radiographic examination was carried out , followed by another at 1 , 3 and 6 months after application of the techniques . No significant differences were found at the end of the period . However , electrosurgery had an advantage : it was faster to apply and dispensed with the use of formocresol . Further research is suggested , using larger sample s and shorter evaluation periods", "The objectives of this study were to clinical ly evaluate the effectiveness of 2 % buffered glutaraldehyde in pulpotomies of human primary molars and to compare the success rate of glutaraldehyde with calcium hydroxide and glutaraldehyde with zinc oxide eugenol as dressing material on the radicular pulp . Pulpotomies were completed on 61 primary molars in 19 children . The teeth were divided into two groups by r and om allocation . One group had a dressing of zinc oxide-eugenol base ( IRM ) incorporated with one drop of 2 % buffered glutaraldehyde while the other group had a dressing of calcium hydroxide base incorporated with one drop of 2 % buffered glutaraldehyde after the initial placement of 2 % buffered glutaraldehyde on cotton pellet for 3 min . All teeth had light-curing compomer ( Dyract ) placed over the dressing material followed by a stainless steel crown restoration within 1 or 2 weeks after the pulpotomy . Blind clinical and radiographic evaluations of 57 teeth available after 12 months showed a success rate of 92.9 % and 73.6 % respectively . The clinical and radiographic success rates for glutaraldehyde/zinc oxide eugenol pulpotomies were 96.5 % and 75.8 % respectively while those for glutaraldehyde-calcium hydroxide were 89.2 % and 71.4 % . There was no statistically significant difference between the two groups either clinical ly or radiographically . The overall clinical success rate suggested that 2 % buffered glutaraldehyde was an effective agent in the pulpotomy of human primary molars " ]

[ "OBJECTIVE Increased oxidative stress and immune dysfunction are implicated in preeclampsia ( PE ) and may contribute to the two- to fourfold increase in PE prevalence among women with type 1 diabetes . Prospect i ve measures of fat-soluble vitamins in diabetic pregnancy are therefore of interest . RESEARCH DESIGN AND METHODS Maternal serum carotenoids ( α- and β-carotene , lycopene , and lutein ) and vitamins A , D , and E ( α- and γ-tocopherols ) were measured at first ( 12.2 ± 1.9 weeks [ mean ± SD ] , visit 1 ) , second ( 21.6 ± 1.5 weeks , visit 2 ) , and third ( 31.5 ± 1.7 weeks , visit 3 ) trimesters of pregnancy in 23 women with type 1 diabetes who subsequently developed PE ( DM PE+ ) and 24 women with type 1 diabetes , matched for age , diabetes duration , HbA1c , and parity , who did not develop PE ( DM PE− ) . Data were analyzed without and with adjustment for baseline differences in BMI , HDL cholesterol , and pr and ial status . RESULTS In unadjusted analysis , in DM PE+ versus DM PE− , α-carotene and β-carotene were 45 and 53 % lower , respectively , at visit 3 ( P in β-carotene at visit 3 remained significant . Most participants were vitamin D deficient ( D levels were lower in DM PE+ versus DM PE− throughout the pregnancy , although this did not reach statistical significance . CONCLUSIONS In pregnant women with type 1 diabetes , low serum α- and β-carotene were associated with subsequent development of PE , and vitamin D deficiency may also be implicated", "Objective : Vitamin D deficiency is well recognized in selected Middle Eastern countries , but neonatal vitamin D status is not well studied in Jordan and other nearby countries . The aim of this study is to determine the prevalence of vitamin D deficiency in Jordanian newborns and risk factors associated with low levels . Methods : This is a prospect i ve cohort study of newborn infants who were delivered at the Al Bashir Government Hospital in Amman , Jordan , from January 31 , 2010 , to January 27 , 2011 . Heel stick blood sample s for 25-hydroxyvitamin D [ 25(OH)D ] levels were obtained within 96 hours of birth . Maternal dress pattern , vitamin supplementation , smoke exposure during pregnancy , mode of delivery , gestational age , and birth weight were documented . Results : Sample s were obtained from 3,731 newborns . Median gestational age was 39 weeks , median birth weight was 3.1 kilograms , median maternal age was 27 years , and median newborn 25(OH)D level was 8.6nmol/L. A total of 3,512 newborns ( 94.1 % ) in this study were vitamin D deficient ( Lower gestational age , maternal smoke exposure , and birth during winter months were associated with lower infant vitamin D levels , while vitamin D supplementation and time spent outside during pregnancy were associated with higher vitamin D levels . Conclusions : The prevalence of severely low vitamin D levels in newborn infants in Amman , Jordan , is substantial , even in newborns born during the spring and summer months . Vitamin D supplementation is needed in this population", "OBJECTIVE : To determine the vitamin D dose necessary to achieve serum 25-hydroxyvitamin D ( 25(OH)D ) concentration ≥20 ng/mL during infancy . METHODS : A r and omized , double-blind , placebo-controlled trial in New Zeal and . Pregnant mothers , from 27 weeks ’ gestation to birth , and then their infants , from birth to age 6 months , were r and omly assigned to 1 of 3 mother/infant groups : placebo/placebo , vitamin D3 1000/400 IU , or vitamin D3 2000/800 IU . Serum 25(OH)D and calcium concentrations were measured at enrollment , 36 weeks ’ gestation , in cord blood , and in infants at 2 , 4 , and 6 months of age . RESULTS : Two-hundred- and -sixty pregnant women were r and omized . At enrollment , the proportions with serum 25(OH)D ≥20 ng/mL for placebo , lower-dose , and higher-dose groups were 54 % , 64 % , and 55 % , respectively . The proportion with 25(OH)D ≥20 ng/mL was larger in both intervention groups at 36 weeks ’ gestation ( 50 % , 91 % , 89 % , P the proportion of infants with 25(OH)D ≥20 ng/mL was larger in both intervention groups to age 4 months : cord blood ( 22 % , 72 % , 71 % , P CONCLUSIONS : Daily vitamin D supplementation during pregnancy and then infancy with 1000/400 IU or 2000/800 IU increases the proportion of infants with 25(OH)D ≥20 ng/mL , with the higher dose sustaining this increase for longer", "Background Vitamin D has a potential role in slowing HIV disease progression and preventing mortality based on its extensive involvement in the immune system ; however , this relationship has not been examined in large studies or in re source -limited setting s. Methodology /Principal Findings Vitamin D levels were assessed in 884 HIV-infected pregnant women at enrollment in a trial of multivitamin supplementation ( not including vitamin D ) in Tanzania . Women were followed up for a median of 69.5 months , and information on hemoglobin levels , HIV disease progression , and mortality was recorded . Proportional hazard models and generalized estimating equations were used to assess the relationship of these outcomes with vitamin D status . Conclusions / Significance Low vitamin D status ( serum 25-hydroxyvitamin D vitamin D status and T-cell counts during follow-up . Women with low vitamin D status had 46 % higher risk of developing severe anemia during follow-up , compared to women with adequate vitamin D levels ( RR : 1.46 ; 95 % CI : 1.09 , 1.96 ) . Women in the highest vitamin D quintile had a 42 % lower risk of all-cause mortality , compared to the lowest quintile ( RR : 0.58 ; 95 % CI : 0.40 , 0.84 ) . Vitamin D status had a protective association with HIV disease progression , all-cause mortality , and development of anemia during follow-up in HIV-infected women . If confirmed in r and omized trials , vitamin D supplementation could represent a simple and inexpensive method to prolonging the time to initiation of antiretroviral therapy in HIV-infected patients , particularly in re source -limited setting", "BACKGROUND We previously found a high prevalence of vitamin D deficiency and low medication regimen compliance in Arab and East Indian women residing in the United Arab Emirates ( UAE ) . The appropriate dosing regimen for improving vitamin D status in this population is not known . OBJECTIVE We aim ed to determine the efficacy of daily and monthly supplementation with vitamin D2 , the only high-dose calciferol available in the UAE , in lactating and Noneiparous women . DESIGN Healthy lactating ( n = 90 ) and Noneiparous ( n = 88 ) women were r and omly assigned to consume 2000 IU vitamin D2/d or 60,000 IU vitamin D2/mo for 3 mo . Serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations were measured by radioimmunoassay at baseline and every month . RESULTS Most women had vitamin D deficiency [ ie , 25(OH)D study entry . Mean + /- SD 25(OH)D concentrations at 3 mo were significantly higher than baseline in both lactating ( 39.8 + /- 12.4 and 25.2 + /- 10.7 nmol/L , respectively ) and Noneiparous ( 40.4 + /- 23.4 and 19.3 + /- 12.2 nmol/L , respectively ) women ( P vitamin D supplementation was effective in achieving serum 25(OH)D concentrations of > or=50 nmol/L in 21 ( 30 % ) of 71 women at endpoint . CONCLUSIONS Oral vitamin D2 supplementation with 2000 IU/d or 60,000 IU/mo for 3 mo was safe , and it increased serum 25(OH)D concentrations significantly ; however , only a small proportion of the women studied achieved concentrations of > or=50 nmol/L. This suggests that , when sunlight exposure is limited , doses of vitamin D2 higher than those currently studied may be needed . Monthly dosing appears to be a safe and effective alternative to daily dosing", "BACKGROUND The cholecalciferol inputs required to achieve or maintain any given serum 25-hydroxycholecalciferol concentration are not known , particularly within ranges comparable to the probable physiologic supply of the vitamin . OBJECTIVES The objectives were to establish the quantitative relation between steady state cholecalciferol input and the result ing serum 25-hydroxycholecalciferol concentration and to estimate the proportion of the daily requirement during winter that is met by cholecalciferol reserves in body tissue stores . DESIGN Cholecalciferol was administered daily in controlled oral doses labeled at 0 , 25 , 125 , and 250 micro g cholecalciferol for approximately 20 wk during the winter to 67 men living in Omaha ( 41.2 degrees N latitude ) . The time course of serum 25-hydroxycholecalciferol concentration was measured at intervals over the course of treatment . RESULTS From a mean baseline value of 70.3 nmol/L , equilibrium concentrations of serum 25-hydroxycholecalciferol changed during the winter months in direct proportion to the dose , with a slope of approximately 0.70 nmol/L for each additional 1 micro g cholecalciferol input . The calculated oral input required to sustain the serum 25-hydroxycholecalciferol concentration present before the study ( ie , in the autumn ) was 12.5 micro g ( 500 IU)/d , whereas the total amount from all sources ( supplement , food , tissue stores ) needed to sustain the starting 25-hydroxycholecalciferol concentration was estimated at approximately 96 micro g ( approximately 3800 IU)/d . By difference , the tissue stores provided approximately 78 - 82 micro g/d . CONCLUSIONS Healthy men seem to use 3000 - 5000 IU cholecalciferol/d , apparently meeting > 80 % of their winter cholecalciferol need with cutaneously synthesized accumulations from solar sources during the preceding summer months . Current recommended vitamin D inputs are inadequate to maintain serum 25-hydroxycholecalciferol concentration in the absence of substantial cutaneous production of vitamin", "OBJECTIVE The objective of the study was to examine changes of 25-hydroxy-vitamin D ( 25OHD ) and PTH blood levels 4 and 20 wk after low-calorie diet-induced weight loss . METHODS Forty-four obese women [ aged 40.6 + /- 11.4 yr , body mass index ( BMI ) 36.7 + /- 4.9 kg/m(2 ) ] and 25 controls ( BMI 22.9 + /- 1.5 kg/m(2 ) ) were examined . Anthropometric and cardiometabolic parameters and 25OHD and PTH levels were determined at baseline and 4 and 20 wk after a low-calorie diet . RESULTS At baseline , 25OHD levels were lower in obese compared with control subjects ( 17 + /- 6.0 vs. 23.8 + /- 8.7 ng/ml , P PTH levels . In all women , a negative correlation was found between 25OHD levels and body weight ( BW ) ( r -0.32 , P BMI ( r -0.37 , P waist circumference ( r -0.26 , P percent fat mass ( r -0.38 , P = 0.001 ) as determined by bioelectrical impedance analysis . The 4-wk low-calorie diet ( n = 37 ) reduced BW and led to significant improvements in the homeostasis model assessment ( HOMA ) index and lipid levels . The 20-wk low-calorie diet ( n = 26 ) result ed in reduction of BW and BMI by 10 % , HOMA index ( 4.7 + /- 3.8 vs. 3.10 + /- 1.7 , P lipids levels ( except high density lipoprotein cholesterol ) and increase in 25OHD ( 15.4 + /- 6.0 vs. 18.3 + /- 5.1 ng/ml , P PTH levels were unchanged . The increase of 25OHD levels was associated with the reduction of insulin levels and HOMA index ( r -0.43 , P Blood 25OHD levels were low in obese women and correlated inversely with severity measures of obesity . Weight loss of 10 % after low-calorie diet increased 25OHD levels , and this increase was mainly associated with improvement of insulin resistance", "The need , safety , and effectiveness of vitamin D supplementation during pregnancy remain controversial . In this r and omized , controlled trial , women with a singleton pregnancy at 12 to 16 weeks ' gestation received 400 , 2000 , or 4000 IU of vitamin D(3 ) per day until delivery . The primary outcome was maternal/neonatal circulating 25-hydroxyvitamin D [ 25(OH)D ] concentration at delivery , with secondary outcomes of a 25(OH)D concentration of 80 nmol/L or greater achieved and the 25(OH)D concentration required to achieve maximal 1,25-dihydroxyvitamin D(3 ) [ 1,25(OH)(2)D(3 ) ] production . Of the 494 women enrolled , 350 women continued until delivery : Mean 25(OH)D concentrations by group at delivery and 1 month before delivery were significantly different ( p relative risk ( RR ) for achieving a concentration of 80 nmol/L or greater within 1 month of delivery was significantly different between the 2000- and the 400-IU groups ( RR = 1.52 , 95 % CI 1.24 - 1.86 ) , the 4000- and the 400-IU groups ( RR = 1.60 , 95 % CI 1.32 - 1.95 ) but not between the 4000- and . 2000-IU groups ( RR = 1.06 , 95 % CI 0.93 - 1.19 ) . Circulating 25(OH)D had a direct influence on circulating 1,25(OH)(2)D(3 ) concentrations throughout pregnancy ( p safety measure . Not a single adverse event was attributed to vitamin D supplementation or circulating 25(OH)D levels . It is concluded that vitamin D supplementation of 4000 IU/d for pregnant women is safe and most effective in achieving sufficiency in all women and their neonates regardless of race , whereas the current estimated average requirement is comparatively ineffective at achieving adequate circulating 25(OH)D concentrations , especially in African Americans", "Introduction and aims : Calcium and vitamin D play major roles in calcium homeostasis and skeletal development , especially during pregnancy . This study was conducted to determine changes in calcium , 25 hydroxy [ 25(OH ) ] vitamin D3 and other biochemical factors ( PTH , osteocalcin , alkaline phosphatase , magnesium , phosphorus ) related to calcium homeostasis and bone turnover during pregnancy and compare the values to those of non-pregnant women . Material s and Methods : In a cohort study , 48 pregnant women , in their first trimester of pregnancy ( 12±2.7 weeks ) , from 5 prenatal care centers , and 47 non-pregnant women r and omly selected from the Tehran Lipid and Glucose Study ( TLGS ) population were enrolled . These pregnant women were followed in their second ( 26±1.9 weeks ) and third trimesters ( 37±3.2 weeks ) of pregnancy . Sample s were drawn from June 2002 to March 2003 . Including criteria were healthy women with no background of disease . Women using photo protection and calcium and vitamin D supplementation were excluded . A question naire was used to obtain demographic information for both groups . Venous blood sample s were taken after 12–14 h of overnight fasting to measure serum calcium , phosphorus , magnesium , alkaline phosphatase , PTH , 25 ( OH ) vitamin D3 and serum osteocalcin levels . The repeated measures analysis of variance and t-test were used for statistical analysis . Data were matched for age and weight in both the case ( in the first trimester ) and control groups . Results : Significant differences were found in the mean serum levels of osteocalcin and alkaline phosphatase between the three trimesters of pregnancy ( p ) . Osteocalcin was significantly higher in the first trimester as compared to second and third trimesters of pregnancy . Alkaline phosphatase was significantly lower in the first trimester as compared to the second and third trimesters of pregnancy and their controls . There was also a significant difference in osteocalcin in the second and third trimesters and alkaline phosphatase in the first and third trimesters of pregnancy in comparison to the control group . The mean values of osteocalcin were 12.7±8.5 , 8.1 ±6.9,5.6±5.0 and 13.9±7.9 ng/ml , respectively , and mean values for alkaline phosphatase were 115±38 , 125±37 , 174±61 and 134±35.0 Iu/l , respectively . In the first trimester , alkaline phosphatase was lower and osteocalcin was higher than in the second and third trimesters . In the first trimester of pregnancy , 20 and 40 % of women had 25(OH ) vitamin D3 serum calcium levels calcium supplements with vitamin D in pregnant women be stressed for these individuals", "BACKGROUND & AIMS Hypovitaminosis D [ serum 25 vitamin D serum 25 vitamin D ( s25(OH)D ) in a healthy Brazilian population after the winter and after the summer . METHODS 603 ( 118 M and 485F ) healthy Brazilian volunteers aged 18 - 90 years from a universitary hospital were selected after the winter of 2006 . From the initial sample , 209 volunteers ( 31 M and 178F ) accepted to participate in a second health check after the subsequent summer . RESULTS After the winter , median s25(OH)D was 21.4 ng/mL and 77.4 % of the population presented hypovitaminosis D. s25(OH)D was significantly related to age , BMI , PTH and race . In multivariate linear regression analysis , s25(OH)D was significantly and independently dependent on age , glycemia and skin color . Significant increase in s25(OH)D was verified after summer [ 10.6 ( 3.7 - 19.3 ng/ml ) ; p hyperparathyroidism prevalence ( 20.8 % vs. 4.9 % ; P Paulo , at the end of winter , we observed a high prevalence of hypovitaminosis D and secondary hyperparathyroidism in healthy adults . s25(OH)D was dependent on age and skin color . After summer , we observed a decrease in the prevalence of hypovitaminosis D. This unexpected finding emphasizes the need for a strong recommendation to monitor s25(OH)D , even in a sunny country such as Brazil", "Background Patterns of gene expression of human pregnancy are poorly understood . In a trial of vitamin D supplementation in pregnant women , peripheral blood transcriptomes were measured longitudinally on 30 women and used to characterize gene co-expression networks . Objective Studies suggest that increased maternal Vitamin D levels may reduce the risk of asthma in early life , yet the underlying mechanisms have not been examined . In this study , we used a network-based approach to examine changes in gene expression profiles during the course of normal pregnancy and evaluated their association with maternal Vitamin D levels . Design The VDAART study is a r and omized clinical trial of vitamin D supplementation in pregnancy for reduction of pediatric asthma risk . The trial enrolled 881 women at 10–18 weeks of gestation . Longitudinal gene expression measures were obtained on thirty pregnant women , using RNA isolated from peripheral blood sample s obtained in the first and third trimesters . Differentially expressed genes were identified using significance of analysis of microarrays ( SAM ) , and clustered using a weighted gene co-expression network analysis ( WGCNA ) . Gene-set enrichment was performed to identify major biological pathways . Results Comparison of transcriptional profiles between first and third trimesters of pregnancy identified 5839 significantly differentially expressed genes ( FDR Weighted gene co-expression network analysis clustered these transcripts into 14 co-expression modules of which two showed significant correlation with maternal vitamin D levels . Pathway analysis of these two modules revealed genes enriched in immune defense pathways and extracellular matrix reorganization as well as genes enriched in notch signaling and transcription factor networks . Conclusion Our data show that gene expression profiles of healthy pregnant women change during the course of pregnancy and suggest that maternal Vitamin D levels influence transcriptional profiles . These alterations of the maternal transcriptome may contribute to fetal immune imprinting and reduce allergic sensitization in early life . Trial Registration clinical trials.gov", "Prospect i ve longitudinal study of vitamin D status and its risk factors in 75 pregnant women from early pregnancy until 6 months postpartum , by serial measurement of serum 25 ( OH ) vitamin D levels . The serum levels at booking were not significantly different between nationalities ( p = 0.06 ) , parity ( p = 0.2 ) , education levels ( p = 0.4 ) , dress code ( p > 0.5 ) , consumption of vitamin D fortified milk ( p = 0.2 ) or , fatty fish ( p = 0.5 ) , sun-exposed body surface area ( p = 0.3 ) , weekly time exposed to the sun ( p = 0.08 ) or the sun exposure index ( p = 0.2 ) . Vitamin D status progressively worsened as the proportion with adequate serum levels fell from 31 % at the antenatal visit , to 23 % after birth and 17 % , 6 months later ( p = 0.02 ) . While 80 % of mothers who were exclusively breast-feeding had low vitamin D levels 6 months after delivery , this occurred in only 67 % of those partially breast-feeding ( p = 0.6 )", "Background : The Middle East and North Africa ( MENA ) region registers some of the highest rates of hypovitaminosis D worldwide . Aim : We systematic ally review ed the prevalence of hypovitaminosis D , rickets and osteomalacia , their predictors and impact on major outcomes , in the region . Methods : Medline , Pubmed and Embase search engines , entering keywords and concepts , combined with individual countries of interest , were used . Search was limited years 2000–2012 ; and review articles were used for the period preceding year 2000 . Results : Rickets and osteomalacia still occur in this sunny region . Hypovitaminosis D prevails , with rates varying 30–90 % , considering a desirable serum 25 hydroxy-vitamin D [ 25(OH)D ] of 20 ng/ml . Advancing age , female gender , multi-parity , clothing style , season , socio-economic status and urban living are recognized predictors of hypovitaminosis D in adults . Prolonged breastfeeding without vitamin D supplementation and low dietary calcium intake are the recognized risk factors for rickets and hypovitaminosis D in children .. Associations with pain score and disease activity in rheumatologic disorders , viral load and interleukins in hepatitis C , BMI , lipids and insulin sensitivity , blood pressure , heart failure and mortality are described . Sun exposure in adults decreased prevalence of metabolic syndrome in one study . Few r and omized vitamin D trials revealed that the majority of mothers or children failed to achieve a desirable 25(OH)D level , even with doses by far exceeding current recommendations . A trial in adolescent girls reveals substantial bone and lean mass increments . Conclusion : Hypovitaminosis D is prevalent in MENA . The lack of population s based studies , gaps in studies in infants , pre-pubertal children and pregnant women , hinder the development of region specific guidelines and constitute a major obstacle to impact this chronic and most often sub clinical disease", "Introduction . This study aims to assess the factors associated with 25-hydroxy vitamin D ( 25(OH)D ) levels in pregnant women and their newborns in a sunny region . Material s and Methods . This cross-sectional study was conducted in 2012 in Isfahan , Iran . It comprised 100 Noneiparous singleton pregnant women , selected by r and om cluster sampling . Laboratory tests were assessed before delivery in mothers and after delivery in their infants ' umbilical cord blood . The P for trend of variables was assessed across the air quality index ( AQI ) quartiles . The associations of AQI and 25(OH)D were assessed by multiple linear regression after adjustment for age , body mass index , and dietary intake . Results . Sera of 98 mothers and an equal number of newborns were analyzed . The median ( interquartile range , IQR ) of serum 25(OH)D of mothers and neonates was 15.1(12.6 , 18.2 ) ng/mL in mothers and 15.7(12.0 , 18.1 ) ng/mL in neonates , respectively . AQI had an inverse association with serum 25(OH)D ( Beta = −0.58 , P = 0.04 ) . The corresponding figure was also inverse and significant for newborns ( Beta (SE)= −0.51(0.04 ) , P = 0.01 ) . Conclusion . The independent inverse association of 25(OH)D with air quality can explain the high prevalence of hypovitaminosis D in pregnant women living in this sunny region", "Scientific data pertaining to vitamin D supplementation during lactation are scarce . The daily recommended intake for vitamin D during lactation has been arbitrarily set at 400 IU/d ( 10 microg/d ) . This recommendation is irrelevant with respect to maintaining the nutritional vitamin D status of mothers and nursing infants , especially among darkly pigmented individuals . Our objective was to examine the effect of high-dose maternal vitamin D2 supplementation on the nutritional vitamin D status of mothers and nursing infants . Fully lactating women ( n = 18 ) were enrolled at 1 mo after birth to 1 of 2 treatment arms , ie , 1600 IU vitamin D2 and 400 IU vitamin D3 ( prenatal vitamin ) or 3600 IU vitamin D2 and 400 IU vitamin D3 , for a 3-mo study period . High-dose ( 1600 or 3600 IU/d ) vitamin D2 supplementation for a period of 3 mo safely increased circulating 25-hydroxyvitamin D [ 25(OH)D ] concentrations for both groups . The antirachitic activity of milk from mothers receiving 2000 IU/d vitamin D increased by 34.2 IU/L , on average , whereas the activity in the 4000 IU/d group increased by 94.2 IU/L. Nursing infant circulating 25(OH)D2 concentrations reflected maternal intake and the amount contained in the milk . With limited sun exposure , an intake of 400 IU/d vitamin D would not sustain circulating 25(OH)D concentrations and thus would supply only limited amounts of vitamin D to nursing infants in breast milk . A maternal intake of 2000 IU/d vitamin D would elevate circulating 25(OH)D concentrations for both mothers and nursing infants , albeit with limited capacity , especially with respect to nursing infants . A maternal intake of 4000 IU/d could achieve substantial progress toward improving both maternal and neonatal nutritional vitamin D status", "The present prospect i ve study examined the association between maternal consumption of dairy products , calcium , and vitamin D during pregnancy and the risk of wheeze and eczema in the infants aged 16–24 months . Subjects were 763 Japanese mother – child pairs . Data on maternal intake during pregnancy were assessed with a diet history question naire . Symptoms of wheeze and eczema were based on criteria of the International Study of Asthma and Allergies in Childhood . Higher maternal intake of total dairy products , milk , cheese and calcium during pregnancy was significantly related to a decreased risk of infantile wheeze , but not eczema ( adjusted ORs ( 95 % CI ) between extreme quartiles were 0.45 ( 0.25−0.79 ) , 0.50 ( 0.28−0.87 ) , 0.51 ( 0.31−0.85 ) , and 0.57 ( 0.32−0.99 ) , respectively ) . When maternal vitamin D consumption during pregnancy was categorised into two groups using a cut-off point at the 25th percentile , children whose mothers had consumed ≥4.309 μg·day−1 had a significantly reduced risk of wheeze and eczema ( adjusted ORs ( 95 % CI ) were 0.64 ( 0.43−0.97 ) and 0.63 ( 0.41−0.98 ) , respectively ) . Higher consumption of calcium and dairy foods other than yoghurt during pregnancy may reduce the risk of infantile wheeze . Higher vitamin D intake during pregnancy may be protective against childhood wheeze and eczema ", "Although vitamin D ( vD ) deficiency is common in breastfed infants and their mothers during pregnancy and lactation , a st and ardized global comparison is lacking . We studied the prevalence and risk factors for vD deficiency using a st and ardized protocol in a cohort of breastfeeding mother-infant pairs , enrolled in the Global Exploration of Human Milk Study , design ed to examine longitudinally the effect of environment , diet and culture . Mothers planned to provide breast milk for at least three months post-partum and were enrolled at four weeks postpartum in Shanghai , China ( n = 112 ) , Cincinnati , Ohio ( n = 119 ) , and Mexico City , Mexico ( n = 113 ) . Maternal serum 25(OH)D was measured by radioimmunoassay ( Serum 25(OH)D was measured in a subset of infants ( 35 Shanghai , 47 Cincinnati and 45 Mexico City ) seen at 26 weeks of age during fall and winter seasons . Data collected prospect ively included vD supplementation , season and sun index ( sun exposure × body surface area exposed while outdoors ) . Differences and factors associated with vD deficiency were evaluated using appropriate statistical analysis . vD deficiency in order of magnitude was identified in 62 % , 52 % and 17 % of Mexican , Shanghai and Cincinnati mothers , respectively ( p vD supplementation ( p obesity ( p = 0.03 ) , season ( p = 0.001 ) and sites ( p vD deficiency in order of magnitude was found in 62 % , 28 % , and 6 % of Mexican , Cincinnati and Shanghai infants , respectively ( p higher sun index ( p = 0.085 ) predicted higher infant vD status . vD deficiency appears to be a global problem in mothers and infants , though the prevalence in diverse population s may depend upon sun exposure behaviors and vD supplementation . Greater attention to maternal and infant vD status starting during pregnancy is warranted worldwide", "Background : During pregnancy , Low serum 25-hydroxyvitamin-D [ 25(OH)D ] concentration is even more critical . This deficiency leads to higher incidences of preeclampsia , gestational diabetes , preterm birth , bacterial vaginosis , and also affects the health of the infants . The aim of this study was to evaluate the relationships between serum levels of 25-hydroxyvitamin D ( 25[OH]D ) and gestational diabetes mellitus ( GDM ) and differences in high-risk pregnant women and women without risk factors for GDM . Methods : This cross sectional study including 155 pregnant women , who are still in the first trimester of pregnancy ( less than 12 weeks gestation ) , were r and omized to two groups of high and low risk for GDM . For these people , once at the gestational age less than 12 times a week and once at for 24 to 28 weeks of pregnancy , tests of FBS / BS / HbA1C / 25OHD / insulin / Ca / Albumin was requested . Besides , the OGTT test was performed with 75 g glucose at 24 and 28 weeks of pregnancy to diagnose GDM . Results : Serum levels of 25(OH)D in the second trimester of pregnancy ng / ml ( 24.1 ± 39.5 ) was significantly lower than that of the first trimester ng / ml ( 25.9 ± 45.6 ) ( p ) . But serum 25(OH)D levels in the first and second trimester of pregnancy was significantly different in women at high risk for GDM than women who had no risk factors ( p = 0.584 and p = 0.99 ) . Serum levels of 25(OH)D has an inverse and significant relationship with HbA1C at the beginning of pregnancy ( p=0.007 ) . In addition , a significant and inverse relationship was shown between serum levels of 25(OH)D in the second trimester with insulin ( p=0.047 ) and blood sugar 2 hours after ingestion of 75 g glucose ( p=0.045 ) at 24 - 28 weeks of gestation . Conclusion : Regarding to the relationship between serum levels of 25(OH)D and blood sugar and insulin at the second trimester of pregnancy , it is recommended for pregnant women to take vitamin D supplementation", "Background and objectives : Vitamin D deficiency is very common in pregnant women . Deficiencies have been prevalent even in studies where over 90 % of the women took prenatal vitamins . The current guidelines for vitamin D intake during pregnancy of 200–400 IU has little scientific support and has been recently challenged . We conducted this study to determine the prevalence of vitamin D deficiency among pregnant women and to evaluate the effectiveness and level of weekly oral 50,000 IU of vitamin D supplementation for the mother and the newborn . Setting and design : Prospect i ve study at Hamad Medical Corporation outpatient unit and delivery room . Patients and Methods : Ninety seven pregnant women were recruited in their first trimester between December 2007 and March 2010 . Weekly oral vitamin D ( 50,000 IU ) were prescribed after an initial testing for serum level of 25-hydroxyvitamin D , parathyroid hormone , calcium , phosphorus , total protein and albumin . Other multivitamins supplementations were allowed during pregnancy . The same tests were repeated at each trimester . Umbilical cords vitamin D levels were determined at birth . Results : Out of 97 patients , 8 patients dropped out from the study for several reasons , and 19 patients had pregnancy loss . Data were available for 97 women in the first trimester , 78 women in the second trimester and 61 women in the third trimester . The mean level of vitamin D level in the first trimester and prior to starting vitamin D supplementation was 17.15 ng/ml , 29.08 ng/ml in the second trimester , 27.3 ng/ml in third trimester and 22.36 ng/ml in newborns . There were no toxic levels of vitamin D in any of the women at the second or third trimesters or in the newborns . The mean levels of vitamin D in the second and third trimester were not significantly different in those women who were taking multivitamin supplementation and those who were not . Conclusion : Weekly doses of 50,000 vitamin D during pregnancy maintains acceptable vitamin D level during pregnancy and the newborn 's vitamin D level correlates with the mother 's levels", "Background Inadequate radiation or insufficient cutaneous absorption of UVB is one of the cardinal causes of vitamin D deficiency . The aim of this study is to determine whether air pollution and low ground level of ultra-violet B light ( UVB ; 290 - 315 ) can deteriorate the body vitamin D status in healthy women . Methods In this cross sectional study 200 , free-living , housewives , aged between 20 to 55 years , from Tehran ( high polluted area ) and Ghazvin ( low polluted area ) were included . The Tehranian women were selected r and omly from participants of the Tehran Lipid and Glucose Study ( TLGS ) and the Ghazvinian females from patients who came to public health centers . Participants were excluded for disease and drugs which affect vitamin D status and also if they were pregnant or breast feeding . We measured the ground level of UVB using a Haze meter as a surrogate of air pollution . In order to calculate the adjusted mean difference of 25-OH-D , ANCOVA analysis was used . Moreover , Binary logistic regression model was developed to determine the odds of living in Tehran for having serum 25-OH-D less than 20 ng/ml . Results The mean ± SD of serum 25-OH-D was significantly higher in Ghazvinian women ( ( 18 ± 11 vs. 13 ± 7 ) , P-value The prevalence of 25-OH-D less than 10 ng/ml , and 25-OH-D between 10 and 20 ng/ml were higher in Tehranian group ( 36 % and 54 % vs. 31 % and 32 % in respectively ) . Secondary hyperparathyroidism was also significantly higher in Tehranian women ( 47 % vs. 32 % ) . In ANCOVA analysis , after adjustment , the mean of 25-OH-D in the Ghazvinian group was still statistically significantly higher than Tehranians ( 13 vs. 17 ng/ml P-value = 0.04 ) . In addition , in binary logistic model , the odd of living in Tehran for having serum 25-OH-D less than 20 ng/ml was 5.22 ( 95 % confidence interval 2.2 - 12.2 , P-value < 0.001 ) . Conclusion We found that living in a polluted area plays a significant independent role in vitamin D deficiency and hence , residence can be one of the main reasons of vitamin D status of the women", "Abstract Objectives : To determine the association between air pollution and vitamin D status in young children living in a sunny region . Methods : This cross-sectional study of 100 children aged 4–10 years in Isfahan was conducted during 2011–2012 . This industrial city has an arid climate and is the second most air-polluted city in Iran . Children were selected by r and om cluster sampling from various areas with different levels of air pollution . The air quality index ( AQI ) was recorded and demographic variables , dietary habits and levels of physical activity were determined by vali date d question naires . Serum concentrations of 25-hydroxyvitamin D [ 25(OH)D ] , calcium , phosphate , alkaline phosphatase and parathyroid hormone were measured . The P for trend for median ( interquartile range ) of variables was assessed across the AQI quartiles . The associations between AQI and biochemical values were assessed by multiple linear regression after adjustment for age , gender , BMI , diet and pattern of physical activity . Results : Ninety-seven children ( 46·4 % boys ) completed the study . The median ( interquartile range , IQR ) of serum 25(OH ) D was 37·4 ( 22·5 , 81·6 ) nmol/L. Median dietary vitamin D intake was 11·7 μg/day , i.e. 78 % of the required daily amount . Vitamin D deficiency and insufficiency were detected in 37·9 % and 46·3 % of children , respectively . Median ( IQR ) exposure to ultraviolet B radiation in the AQI Quartile 4 area was significantly lower than in the Quartile 1 area [ 0·36 ( 0·35–0·38 ) watts per square metre ( W/m2 ) vs 0·41 ( 0·39–0·44 ) W/m2 , respectively , P = 0·04 ] . Likewise , the corresponding figure for serum 25(OH)D was 35·2 ( 22·5–45·2 ) vs 52·7 ( 44·9–81·6 ) nmol/L , respectively , P = 0·04 . AQI was inversely associated with serum 25(OH)D , which remained significant after adjustment for the above-mentioned confounding factors ( β = 0·61 , P = 0·01 ) . Conclusion : The independent inverse association of AQI with 25(OH)D explains the high prevalence of vitamin D deficiency in children in Isfahan . Dietary intake of vitamin D was not sufficiently low to explain the very low level of serum 25(OH)D. In regions with plenty of sunlight , air pollution should be considered to be a factor in the causation of hypovitaminosis", "Recent findings suggest that maternal vitamin D insufficiency during pregnancy has consequences for the offspring 's bone health in later life . To investigate whether maternal vitamin D insufficiency affects fetal femur growth in ways similar to those seen in childhood rickets and study the timing during gestation of any effect of maternal vitamin D status , we studied 424 pregnant women within a prospect i ve longitudinal study of maternal nutrition and lifestyle before and during pregnancy ( Southampton Women 's Survey ) . Using high-resolution 3D ultrasound , we measured fetal femur length and distal metaphyseal cross-sectional area , together with the ratio of femoral metaphyseal cross-sectional area to femur length ( femoral splaying index ) . Lower maternal 25-hydroxyvitamin vitamin D concentration was not related to fetal femur length but was associated with greater femoral metaphyseal cross-sectional area and a higher femoral splaying index at 19 weeks ' gestation [ r = -0.16 , 95 % confidence interval ( CI ) -0.25 to -0.06 and r = -0.17 , 95 % CI -0.26 to -0.07 , respectively ] and at 34 weeks ' gestation ( r = -0.10 , 95 % CI -0.20 to 0.00 and r = -0.11 , 95 % CI -0.21 to -0.01 , respectively ) . Three groups of women were identified with 25-hydroxyvitamin vitamin D concentrations that were sufficient/borderline ( > 50 nmol/L , 63.4 % ) , insufficient ( 25 to 50 nmol/L , 30.7 % ) , and deficient ( geometric mean femoral splaying indices at 19 weeks ' gestation increased from 0.074 ( sufficient/borderline ) to 0.078 ( insufficient ) and 0.084 ( deficient ) . Our observations suggest that maternal vitamin D insufficiency can influence fetal femoral development as early as 19 weeks ' gestation . This suggests that measures to improve maternal vitamin D status should be instituted in early pregnancy", "OBJECTIVES Our objectives were to 1 ) assess cord blood vitamin D concentrations from healthy term newborns , 2 ) ascertain whether cord blood vitamin D insufficiency precludes optimal induction of the Toll-like receptor ( TLR ) antimicrobial pathway in monocytes , and 3 ) determine whether in vitro supplementation with 25-hydroxyvitamin D(3 ) [ 25(OH)D(3 ) ] and /or 1,25-dihydroxyvitamin D(3 ) [ 1,25(OH)(2)D(3 ) ] restores TLR-induced antimicrobial responses . STUDY DESIGN Plasma concentrations of 25(OH)D and 1,25(OH)(2)D were measured from cord blood of 23 newborns . Human monocytes were cultured in cord blood plasma and stimulated with TLR2 and TLR4 lig and s , and then antimicrobial gene expression was analyzed using quantitative PCR . RESULTS Cord blood 25(OH)D and 1,25(OH)(2)D concentrations were positively correlated to each other ( r = 0.78 ; P 75 nmol/liter ] , monocytes cultured in severely vitamin D-deficient plasma [ 25(OH)D TLR-induced cathelicidin expression ( P Supplementation in vitro of vitamin D-deficient plasma with 25(OH)D(3 ) increased antimicrobial peptide gene expression . CONCLUSIONS Cord blood vitamin D deficiency , by its effects on TLR-induced antimicrobial production , altered in vitro monocyte responses . The observation that exogenous 25(OH)D(3 ) in vitro recovered TLR-induced antimicrobial responses suggests the need for additional prospect i ve investigations to further delineate the role of vitamin D in the newborn immune response", "Low maternal vitamin D status has been associated with reduced intrauterine long bone growth and shorter gestation , decreased birth weight , as well as reduced childhood bone-mineral accrual . Despite data from other countries indicating low maternal vitamin D status is common during pregnancy , there is a dearth of information about vitamin D status during pregnancy in the Irish female population . Therefore , we prospect ively assessed vitamin D nutritive status and the prevalence of suboptimal vitamin D status in a cohort of Irish pregnant women . The mean ( SD ) daily intake of vitamin D by the group of pregnant women was 3.6 ( 1.9 ) microg/day . None of the women achieved the recommended daily vitamin D intake value for Irish pregnant women ( 10 microg/day ) . Taking all three trimesters collectively , 14.3 - 23.7 % and 34.3 - 52.6 % of Irish women had vitamin D deficiency ( serum 25 ( OH ) D insufficiency ( serum 25 ( OH ) D 25 - 50 nmol/l ) , respectively during pregnancy . Both the levels of serum 25 ( OH ) D and the prevalence of vitamin D deficiency/adequacy were dramatically influenced by season , with status being lowest during the extended winter period and best during the extended summer period . These findings show that inadequate vitamin D status is common in Irish pregnant women", "Racial disparity in pregnancy outcomes is one of the most striking and poorly understood inequalities in American health . Genetic variability may be an important host factor influencing disparate birth outcomes between non‐Hispanic black ( NHB ) and non‐Hispanic white ( NHW ) women . Race‐specific allelic frequencies in the vitamin D receptor ( VDR ) gene suggest its potential as a gene involved in health disparities . The Healthy Pregnancy , Healthy Baby Study is a prospect i ve cohort of pregnant women aim ed at identifying genetic , social , and environmental contributors to disparities in pregnancy outcomes in Durham , NC . VDR haplotype tagging single nucleotide polymorphisms ( SNPs ) were genotyped via Taqman assays for 615 women . Analysis of variance was used to examine the association between maternal genotype and infant birthweight . Eight of 38 SNPs examined showed nominal significance among NHB women , with one VDR SNP ( rs7975232 ) surpassing the multiple testing significance threshold . rs7975232 , an anonymous polymorphism , is part of a VDR gene haplotype associated with variation in mRNA stability . mRNA stability can affect the amount of protein produced , thus directly affecting vitamin D levels and calcium homeostasis . In contrast to NHBs , there was no association between any VDR SNP and birthweight for NHWs . Genetic factors contributing to disparities in birth outcomes are not expected to be explained entirely by variation in a single gene . Nevertheless , our results suggest that maternal VDR gene polymorphisms do influence birthweight with differential effects accruing across racial groups . Further research identifying the functionality of VDR gene polymorphisms in pregnant women will improve our underst and ing of the underlying mechanisms influencing birthweight . © 2011 Wiley‐Liss ,", "OBJECTIVES Postpartum depression ( PPD ) is a common disorder that affects 10 - 15 % of postpartum women , and it can have negative effects on both the mother and newborn . Recent studies have suggested that low levels of vitamin D are associated with poor mood and depression . The aim of this prospect i ve study was to evaluate a possible association between PPD and serum levels of 25-hydroxy vitamin D3 ( 25(OH)D3 ) , a reliable measurement of vitamin D , during mid-pregnancy . STUDY DESIGN The source population consisted of all pregnant women between 24 and 28 gestational weeks from June 2012 to October 2012 at Bornova Health Research and Application Hospital , Sifa University . In order to better evaluate a possible effect between vitamin D levels and PPD , individuals with characteristics that put them at risk for developing PPD were excluded from the study . Serum 25(OH)D3 levels were evaluated mid-pregnancy in the study group . Serum 25(OH)D3 concentrations ≤20ng/mL ( 50nmol/L ) were classified as a mild deficiency and those ≤10ng/mL ( 25nmol/L ) were classified as a severe deficiency . Pregnant subjects having complications during birth or with the newborn after delivery were excluded from the study . The Edinburgh Postnatal Depression Scale ( EPDS ) was used to assess maternal PPD 1 week , 6 weeks , and 6 months after delivery . A Pearson correlation was used to measure the strength of the associations between the EPDS scores and vitamin D levels analyzed during the three time periods . A logistic regression analysis was used to determine the independent effects of vitamin D on PPD . RESULTS Six hundred and eighty-seven pregnant women were included in this study . After excluding women due to PPD risk factors ( in two stages ) , 179 pregnant women were screened for vitamin D levels during mid-pregnancy and in the 6th month postpartum . Eleven percent of our study group had severe vitamin D deficiency and 40.3 % had mild vitamin D deficiency . The frequency of PPD was 21.6 % at the 1st week , 23.2 % at 6th week , and 23.7 % at the 6th month . There was a significant relationship between low 25(OH)D3 levels in mid-pregnancy and high EPDS scores , which is indicative of PPD for all three follow-up periods ( p=0.003 , p=0.004 and p between vitamin D levels and EDPS at all three time points ( r=-0.2 , -0.2 , -0.3 , respectively ) . CONCLUSIONS Vitamin D deficiency in mid-pregnancy may be a factor affecting the development of PPD . More extensive studies are required to be carried out on this subject", "Osteoporotic fractures , falls and obesity are major health problems in developed nations . Evidence suggests that there are antenatal factors predisposing to these conditions . Data are emerging from Australia and elsewhere to suggest that maternal vitamin D status in pregnancy affects intrauterine skeletal mineralisation and skeletal growth together with muscle development and adiposity . Given that low levels of vitamin D have been documented in many urbanised population s , including those in countries with abundant sunlight , an important issue for public health is whether maternal vitamin D insufficiency during pregnancy has adverse effects on offspring health . The developing fetus may be exposed to low levels of vitamin D during critical phases of development as a result of maternal hypovitaminosis D. We hypothesise that this may have adverse effects on offspring musculoskeletal health and other aspects of body composition . Further research focused on the implication s of poor gestational vitamin D nutrition is warranted as these developmental effects are likely to have a sustained influence on health during childhood and in adult life . We suggest that there is a clear rationale for r and omised clinical trials to assess the potential benefits and harmful effects of vitamin D supplementation during pregnancy", "OBJECTIVE To test the hypothesis that lower 25-hydroxyvitamin D ( 25[OH]D ) levels in late pregnancy are associated with poorer glucose control in gestational diabetes mellitus ( GDM ) . DESIGN AND SETTING Retrospective cross-sectional study , in a GDM clinic at a tertiary referral centre . PATIENTS Women attending the GDM clinic at Westmead Hospital from 1 February 2007 to 1 February 2008 , excluding those with prepregnancy glucose intolerance . MAIN OUTCOME MEASURES Levels of glycated haemoglobin ( HbA(1c ) ) and 25(OH)D measured during the third trimester ; maternal age , ethnicity , body mass index ( BMI ) and occupational status ; and results of oral glucose tolerance testing ( OGTT ) . RESULTS 147 women with a mean gestational age of 35 ± 2 weeks were included , of whom 41 % had insufficient or deficient levels of 25(OH)D ( ≤ 50 nmol/L ) . Ethnicity , occupational status and season significantly influenced 25(OH)D levels ( P BMI did not . 25(OH)D levels were inversely associated with fasting and 2-hour blood glucose levels during OGTT ( Spearman r = - 0.16 ; P = 0.05 for both ) and with log[HbA(1c ) ] ( Spearman r = - 0.32 ; P 0.001 ) . BMI and insulin doses were also associated with HbA(1c ) levels . Multivariable analysis identified 25(OH)D and blood glucose levels during the OGTT as independent predictors of HbA(1c ) levels . CONCLUSIONS Lower 25(OH)D levels are independently associated with poorer glycaemic control . Future r and omised trials are needed to determine whether vitamin D plays a role in glycaemic control in GDM . Regardless , maternal vitamin D insufficiency has adverse effects including neonatal hypocalcaemia and rickets . The 41 % prevalence of inadequate 25(OH)D levels in the women in our study is unacceptably high . We propose routine 25(OH)D testing of all pregnant women at screening for GDM or earlier , and treatment of women who are found to be deficient", "BACKGROUND : Respiratory syncytial virus ( RSV ) is the most important pathogen causing severe lower respiratory tract infection ( LRTI ) in infants . Epidemiologic and basic studies suggest that vitamin D may protect against RSV LRTI . OBJECTIVE : To determine the association between plasma vitamin D concentrations at birth and the subsequent risk of RSV LRTI . DESIGN : A prospect i ve birth cohort study was performed in healthy term neonates . Concentrations of 25-hydroxyvitamin D ( 25-OHD ) in cord blood plasma were related to RSV LRTI in the first year of life , defined as parent-reported LRTI symptoms in a daily log and simultaneous presence of RSV RNA in a nose-throat specimen . RESULTS : The study population included 156 neonates . Eighteen ( 12 % ) developed RSV LRTI . The mean plasma 25-OHD concentration was 82 nmol/L. Overall , 27 % of neonates had 25-OHD concentrations Cord blood 25-OHD concentrations were strongly associated with maternal vitamin D3 supplementation during pregnancy . Concentrations of 25-OHD were lower in neonates who subsequently developed RSV LRTI compared with those who did not ( 65 nmol/L versus 84 nmol/L , P = .009 ) . Neonates born with 25-OHD concentrations risk of RSV LRTI in the first year of life compared with those with 25-OHD concentrations ≥75 nmol/L. CONCLUSIONS : Vitamin D deficiency in healthy neonates is associated with increased risk of RSV LRTI in the first year of life . Intensified routine vitamin D supplementation during pregnancy may be a useful strategy to prevent RSV LRTI during infancy", "BACKGROUND Vitamin D ( vD ) deficiency in pregnancy is a global health problem and the amount of vD supplementation to prevent vD deficiency is controversial . OBJECTIVE The objective of the study was to determine effectiveness and safety of prenatal 2000 IU and 4000 IU/d compared with 400 IU/d vD3 supplementation in a r and omized controlled trial in population in which vD deficiency is endemic . DESIGN / METHODS Arab women were r and omized at 12 - 16 weeks of gestation to 400 , 2000 , and 4000 IU/d vD3 , which were continued to delivery . Serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations were measured during pregnancy and at delivery . The primary outcome was the maternal and cord blood 25(OH)D , and the secondary outcomes were the achievement of sufficient serum 25(OH)D of 32 ng/mL or greater ( ≥80 nmol/L ) at delivery . SETTING The locations were primary care and tertiary perinatal care centers . RESULTS Of 192 enrolled , 162 ( 84 % ) continued to delivery . Mean serum 25(OH)D of 8.2 ng/mL ( 20.5 nmol/L ) at enrollment was low . Mean serum 25(OH)D concentrations at delivery and in cord blood were significantly higher in the 2000 and 4000 IU than the 400 IU/d group ( P group . Safety measurements were similar by group and no adverse event related to vD supplementation . CONCLUSIONS Vitamin D supplementation of 2000 and 4000 IU/d appeared safe in pregnancy , and 4000 IU/d was most effective in optimizing serum 25(OH)D concentrations in mothers and their infants . These findings could apply to other population s in which vD deficiency is endemic", "Abstract Objective : We aim ed to explore the risk factors that may lead to vitamin D deficiency in pregnant women living in moderately high-altitude regions . Methods : The study was conducted prospect ively between November 2012 and July 2013 . City of Erzurum is located at an altitude of 1900–2200 m , north Turkey at 39 ° 4′ latitude . Healthy mothers that gave birth after completing 37th week of their pregnancies and healthy neonates weighting > 2500 g were included in the study . For 25-hydroxyvitamin D ( 25(OH)D ) analyses venous blood sample s of 2 ml were obtained from the umbilical cord and the mother . Question naires were developed covering the demographical characteristics and possible risk factors for mothers . Results : Totally 81 mothers and neonates were included into the study . The mean 25(OH)D level of mothers was 7.1 ± 6.5 ng/ml . It was noted that 45 ( 55.7 % ) mothers had severe deficiency . Multivariate linear regression analysis showed that the dressing style and the level of sunlight received by the house were independent factors affecting the level of 25(OH)D. Conclusion : Our findings showed that cultural factors had significant effects on vitamin D levels . We believe that appropriate dose of vitamin D prophylaxis should be administered to pregnant women , considering the risk factors as well as the geographical features", "This article summarizes the new 2011 report on dietary requirements for calcium and vitamin D from the Institute of Medicine ( IOM ) . An IOM Committee charged with determining the population needs for these nutrients in North America conducted a comprehensive review of the evidence for both skeletal and extraskeletal outcomes . The Committee concluded that available scientific evidence supports a key role of calcium and vitamin D in skeletal health , consistent with a cause- and -effect relationship and providing a sound basis for determination of intake requirements . For extraskeletal outcomes , including cancer , cardiovascular disease , diabetes , and autoimmune disorders , the evidence was inconsistent , inconclusive as to causality , and insufficient to inform nutritional requirements . R and omized clinical trial evidence for extraskeletal outcomes was limited and generally uninformative . Based on bone health , Recommended Dietary Allowances ( RDAs ; covering requirements of ≥97.5 % of the population ) for calcium range from 700 to 1300 mg/d for life-stage groups at least 1 yr of age . For vitamin D , RDAs of 600 IU/d for ages 1–70 yr and 800 IU/d for ages 71 yr and older , corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng/ml ( 50 nmol/liter ) , meet the requirements of at least 97.5 % of the population . RDAs for vitamin D were derived based on conditions of minimal sun exposure due to wide variability in vitamin D synthesis from ultraviolet light and the risks of skin cancer . Higher values were not consistently associated with greater benefit , and for some outcomes U-shaped associations were observed , with risks at both low and high levels . The Committee concluded that the prevalence of vitamin D inadequacy in North America has been overestimated . Urgent research and clinical priorities were identified , including re assessment of laboratory ranges for 25-hydroxyvitamin D , to avoid problems of both undertreatment and overtreatment" ]

[ "BACKGROUND To know the effectiveness and tolerance of weekly cisplatin added to radiotherapy ( RT ) in advanced carcinoma of oropharynx and nasopharynx . PATIENTS AND METHODS Stage II-IV cancer patients were r and omly assigned to either radical RT , 70 Gy/35 fractions over 7 weeks ( RT arm ) , or chemoradiotherapy ( CRT ) , cisplatin 40 mg/m² weekly for seven doses plus RT . Primary end points were ( i ) the responses , ( ii ) toxicity profile , and ( iii ) overall survival ( OS ) in two groups . Study period was from June 2003 to July 2005 . RESULTS One hundred and fifty-three patients were r and omly allocated to the study , 76 in RT arm and 77 in CRT arm . Seventy-one in each arm completed the planned treatment ; complete response ( CR ) : 67.1 % versus 80.5 % in RT and CRT arms ( P = 0.04 ) . Grade III and IV toxicity were 16 % and 40 % in RT and CRT arms , respectively ( P = 0.01 ) . There were frequent treatment interruptions ( 9.3 % versus 28.9 % ; P = 0.003 ) and hospitalization ( 20 % versus 40.8 % ) in the CRT group . OS was superior in the CRT arm ( P = 0.02 ) : 27 months [ 95 % confidence interval ( CI ) 15.2 - 36.8 ] for RT versus not reached for CRT . Three-year OS was 42 % for RT and 62 % for CRT group . CRT and CR were independent prognostic factors . CONCLUSION This trial on Indian head and neck squamous cell carcinoma patients confirms that the use of weekly cisplatin is safe and CRT is superior to RT alone result ing in higher OS", "Abstract Cabazitaxel provided a survival advantage compared with mitoxantrone in patients with castration-resistant prostate cancer refractory to docetaxel . Grade 3 to 4 ( G3–4 ) neutropenia and febrile neutropenia were relatively frequent in the registrative XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer ( TROPIC ) trial , but their incidence was lower in the Exp and ed Access Program ( EAP ) . Although cumulative doses of docetaxel are associated with neuropathy , the effect of cumulative doses of cabazitaxel is unknown . In this retrospective review of prospect ively collected data , the authors assessed “ per cycle ” incidence and predictors of toxicity in the Italian cohort of the EAP , with a focus on the effect of cumulative doses of cabazitaxel . The study population consisted of 218 Italian patients enrolled in the cabazitaxel EAP . The influence of selected variables on the most relevant adverse events identified was assessed using a Generalized Estimating Equations model at univariate and multivariate analysis .“Per cycle ” incidence of G 3 to 4 neutropenia was 8.7 % , whereas febrile neutropenia was reported in 0.9 % of cycles . All events of febrile neutropenia occurred during the first 3 cycles . Multivariate logistic regression analysis showed that higher prior dose of cabazitaxel was associated with decreased odds of having G3 to 4 neutropenia ( OR = 0.90 ; 95 % CI : 0.86–0.93 ; P febrile neutropenia ( OR = 0.52 ; 95 % CI : 0.34–0.81 ; P G3 to 4 anemia ( OR = 0.93 ; 95 % CI : 0.86–1 ; P = 0.07 ) . Patients with a body surface area > 2 m2 presented increased odds of having G 3 to 4 neutropenia ( OR = 0.93 ; 95 % CI : 0.86–1 ; P = 0.07 ) , but decreased odds of having G3 to 4 anemia . Among the toxicities assessed , the authors did not identify any that appeared to be associated with a higher number of cabazitaxel cycles delivered . Prior cumulative dose was associated with reduced G3 to 4 neutropenia and anemia . The apparent protective effect associated with higher doses of cabazitaxel is likely to be affected by early dose reduction and early toxicity-related treatment discontinuation . Because this analysis is limited by its retrospective design , prospect i ve trials are required to assess the optimal duration of cabazitaxel treatment", "OBJECTIVE The 7-year follow-up of the US oncology 9735 trial demonstrated the superiority of TC [ docetaxel (DTX)/cyclophosphamide ( CPA ) ] to doxorubicin/CPA therapy . To introduce TC therapy in Japan , the verification of the safety and tolerability is essential . We performed a collaborative prospect i ve safety study with Okayama University to introduce TC therapy . METHODS The subjects were 53 patients aged from 33 to 67 years at intermediate risk based on the St Gallen risk classification who underwent radical surgery for primary breast cancer between August 2007 and December 2008 . As post-operative adjuvant chemotherapy , four cycles of TC ( DTX 75 mg/m(2 ) + CPA 600 mg/m(2 ) ) were administered at 3-week intervals . Adverse events were evaluated based on National Cancer Institute-Common Terminology Criteria for Adverse Events ver . 3.0 . The safety and completion rate were evaluated as the primary and secondary endpoints , respectively . RESULTS Regarding hematological toxicity , Grade ( G ) 4 neutropenia occurred in 71.7 % and G3 in 26.4 % . G3 - 4 leukopenia developed in 32.1 % and 56.6 % , respectively , G4 anemia in 1.9 % and G1 - 2 anemia in 26.4 % . Regarding non-hematological toxicity , systemic malaise , skin eruption , edema , myalgia , arthralgia and nausea were noted in most patients . The completion rate was 94.3 % , dose reduction was necessary in 7.5 % and granulocyte colony-stimulating factor ( G-CSF ) support was required in 17.0 % . On comparison between patients aged 65 years or older and younger than 65 years , the completion rate , dose reduction and incidence of febrile neutropenia ( FN ) were higher in the elderly patients . G-CSF support was more often needed in this subgroup . CONCLUSIONS TC therapy is tolerable for Japanese patients , but attention should be paid to the development of FN and neutropenia . The completion rate was lower in the elderly patients , showing that tolerability was not necessarily favorable", "BACKGROUND This study aim ed to determine the clinical benefit of neoadjuvant methotrexate , doxorubicin , vinblastine , and cisplatin ( MVAC ) in patients with muscle-invasive bladder cancer ( MIBC ) treated with radical cystectomy . PATIENTS AND METHODS Patients with MIBC ( T2 - 4aN0M0 ) were r and omised to receive two cycles of neoadjuvant MVAC followed by radical cystectomy ( NAC arm ) or radical cystectomy alone ( RC arm ) . The primary end point was overall survival ( OS ) . Secondary end points were progression-free survival , surgery-related complications , adverse events during chemotherapy , proportion with no residual tumour in the cystectomy specimens , and quality of life . To detect an improvement in 5-year OS from 45 % in the RC arm to 57 % in the NAC arm with 80 % power , 176 events were required per arm . RESULTS Patients ( N = 130 ) were r and omly assigned to the RC arm ( N = 66 ) and the NAC arm ( N = 64 ) . The patient registration was terminated before reaching the initially planned number of patients because of slow accrual . At the second interim analysis just after the early stoppage of patient accrual , the Data and Safety Monitoring Committee recommended early publication of the results because the trial did not have enough power to draw a confirmatory conclusion . OS of the NAC arm was better than that of the RC arm , although the difference was not statistically significant [ hazard ratio 0.65 , multiplicity adjusted 99.99 % confidence interval 0.19 - 2.18 , one-sided P = 0.07 ] . In the NAC arm and the RC arm , 34 % and 9 % of the patients had pT0 , respectively ( P OS in almost all subgroups was in favour of NAC . CONCLUSIONS This trial showed a significantly increased pT0 proportion and favourable OS of patients who received neoadjuvant MVAC . NAC with MVAC can still be considered promising as a st and ard treatment . UMIN CLINICAL TRIALS REGISTRY IDENTIFIER C000000093", "PURPOSE This multicenter , r and omized trial compared capecitabine plus oxaliplatin ( XELOX ) with bolus fluorouracil ( FU ) and folinic acid ( FA ) as adjuvant therapy for patients with stage III colon cancer . PATIENTS AND METHODS Patients who had undergone curative resection were r and omly assigned to XELOX ( oxaliplatin 130 mg/m(2 ) on day 1 plus capecitabine 1,000 mg/m(2 ) twice daily on days 1 to 14 every 3 weeks for 24 weeks ) or a st and ard bolus FU/FA adjuvant regimen ( Mayo Clinic for 24 weeks or Roswell Park for 32 weeks ) . The primary study end point was disease-free survival ( DFS ) . RESULTS The intention-to-treat population comprised 1,886 patients ; 944 patients were r and omly assigned to XELOX and 942 to FU/FA ( Mayo Clinic , n = 664 ; Roswell Park , n = 278 ) . After 57 months of follow-up for the primary analysis , 295 patients ( 31.3 % ) in the XELOX group had relapsed , developed a new primary colon cancer , or died compared with 353 patients ( 37.5 % ) in the FU/FA group ( hazard ratio [ HR ] for DFS , 0.80 ; 95 % CI , 0.69 to 0.93 ; P = .0045 ) . The 3-year DFS rate was 70.9 % with XELOX and 66.5 % with FU/FA . The HR for overall survival ( OS ) for XELOX compared to FU/FA was 0.87 ( 95 % CI , 0.72 to 1.05 ; P = .1486 ) . The 5-year OS for XELOX and FU/FA were 77.6 % and 74.2 % , respectively . Follow-up is ongoing . Preplanned multivariate and subgroup analyses supported the robustness of these findings . CONCLUSION The addition of oxaliplatin to capecitabine improves DFS in patients with stage III colon cancer . XELOX is an additional adjuvant treatment option for these patients", "Background Evidence that chemotherapy improves survival and quality of life in patients with stage IIIB & IV non small cell lung cancer ( NSCLC ) is based on large r and omized controlled trials . The purpose of this study was to determine eligibility of patients with advanced NSCLC for major chemotherapy trials . Methods Physicians treating stage IIIB/IV NSCLC at Sydney Cancer Centre assessed patient eligibility for the E1594 , SWOG9509 and TAX326 trials for patients presenting from October 2001 to December 2002 . A review of the centre 's registry was used to obtain missing data . Results 199 patients with advanced NSCLC were registered during the 14-month period . Characteristics of 100 patients were defined prospect ively , 85 retrospectively : 77 % males , median age 68 ( range 32–88 ) , 64 % stage IV disease . Only 35 % met trial eligibility for E1594 and 28 % for SWOG9509 and TAX326 . Common reasons for in eligibility were : co-morbidities 75(40 % ) ; ECOG Performance Status ≥2 72(39 % ) ; symptomatic brain metastasis 15(8 % ) ; and previous cancers 21(11 % ) . Many patients were ineligible by more than one criterion . Conclusion The majority of patients with advanced NSCLC were ineligible for the large chemotherapy trials . The applicability of trial results to advanced lung cancer population s may be limited . Future trials should be conducted in a more representative population", "PURPOSE The Arimidex , Tamoxifen Alone or in Combination ( ATAC ) study was a double-blind r and omized trial in which postmenopausal women with early-stage breast cancer were assigned to receive anastrozole , tamoxifen , or the combination . We have conducted a retrospective analysis to examine the effects of comorbidities and age on treatment received , breast cancer-related mortality , and competing causes of mortality . PATIENTS AND METHODS The current analyses were based on 10-year median follow-up data in the two monotherapy arms ( anastrozole , n = 3,092 ; tamoxifen , n = 3,094 ) of the ATAC study . Baseline comorbidities and tumor and treatment characteristics were compared between women age less than 70 years and women age ≥ 70 years . The cumulative incidence of breast cancer-related and non-breast cancer-related mortality was assessed according to age and comorbidities . RESULTS One thous and six hundred sixty-two patients ( 27 % ) were age ≥ 70 years at study entry . Older women were more likely to undergo mastectomy ( odds ratio [ OR ] , 1.92 ; 95 % CI , 1.71 to 2.16 ) and less likely to receive radiotherapy ( OR , 0.49 ; 95 % CI , 0.44 to 0.55 ) or chemotherapy ( OR , 0.24 ; 95 % CI , 0.18 to 0.29 ) . Women age ≥ 70 years had an increased risk of recurrence compared with women age less than 70 years ( hazard ratio [ HR ] , 1.21 ; 95 % CI , 1.08 to 1.37 ) and a substantially increased risk of death without recurrence ( HR , 4.13 ; 95 % CI , 3.53 to 4.83 ) . The risk of death without recurrence increased with comorbidity score ( 10-year estimates of 8.4 % , 20.0 % , and 30.4 % for Satariano score 0 , 1 , and 2 + , respectively ; P the risk of recurrence , and age and comorbidities significantly influence the risk of death without recurrence . Formal assessment of comorbidities should be incorporated into decisions regarding adjuvant therapies", "CONTEXT Adjuvant fluorouracil has been shown to be of benefit for patients with resected pancreatic cancer . Gemcitabine is known to be the most effective agent in advanced disease as well as an effective agent in patients with resected pancreatic cancer . OBJECTIVE To determine whether fluorouracil or gemcitabine is superior in terms of overall survival as adjuvant treatment following resection of pancreatic cancer . DESIGN , SETTING , AND PATIENTS The European Study Group for Pancreatic Cancer (ESPAC)-3 trial , an open-label , phase 3 , r and omized controlled trial conducted in 159 pancreatic cancer centers in Europe , Australasia , Japan , and Canada . Included in ESPAC-3 version 2 were 1088 patients with pancreatic ductal adenocarcinoma who had undergone cancer resection ; patients were r and omized between July 2000 and January 2007 and underwent at least 2 years of follow-up . INTERVENTIONS Patients received either fluorouracil plus folinic acid ( folinic acid , 20 mg/m(2 ) , intravenous bolus injection , followed by fluorouracil , 425 mg/m(2 ) intravenous bolus injection given 1 - 5 days every 28 days ) ( n = 551 ) or gemcitabine ( 1000 mg/m(2 ) intravenous infusion once a week for 3 of every 4 weeks ) ( n = 537 ) for 6 months . MAIN OUTCOME MEASURES Primary outcome measure was overall survival ; secondary measures were toxicity , progression-free survival , and quality of life . RESULTS Final analysis was carried out on an intention-to-treat basis after a median of 34.2 ( interquartile range , 27.1 - 43.4 ) months ' follow-up after 753 deaths ( 69 % ) . Median survival was 23.0 ( 95 % confidence interval [ CI ] , 21.1 - 25.0 ) months for patients treated with fluorouracil plus folinic acid and 23.6 ( 95 % CI , 21.4 - 26.4 ) months for those treated with gemcitabine ( chi(1)(2 ) = 0.7 ; P = .39 ; hazard ratio , 0.94 [ 95 % CI , 0.81 - 1.08 ] ) . Seventy-seven patients ( 14 % ) receiving fluorouracil plus folinic acid had 97 treatment-related serious adverse events , compared with 40 patients ( 7.5 % ) receiving gemcitabine , who had 52 events ( P progression-free survival or global quality -of-life scores between the treatment groups . CONCLUSION Compared with the use of fluorouracil plus folinic acid , gemcitabine did not result in improved overall survival in patients with completely resected pancreatic cancer . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00058201", "BACKGROUND Whether adjuvant chemotherapy improves survival of patients with non-small-cell lung cancer ( NSCLC ) is not known . We aim ed to compare the effect of adjuvant vinorelbine plus cisplatin versus observation on survival in patients with completely resected NSCLC . METHODS 840 patients with stage IB-IIIA NSCLC from 101 centres in 14 countries were r and omly assigned to observation ( n=433 ) or to 30 mg/m(2 ) vinorelbine plus 100 mg/m(2 ) cisplatin ( n=407 ) . Postoperative radiotherapy was not m and atory and was undertaken according to every centre 's policy . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N95053737 . FINDINGS 367 patients in the chemotherapy group and 431 in the control group received their assigned treatment . 301 ( 36 % ) patients had stage IB disease , 203 ( 24 % ) had stage II disease , and 325 ( 39 % ) had stage IIIA disease . Tolerance to chemotherapy mainly included neutropenia in 335 ( 92 % ) patients and febrile neutropenia in 34 ( 9 % ) ; seven ( 2 % ) toxic deaths were also recorded . Compliance was greater with cisplatin than with vinorelbine ( median dose intensity 89 % [ range 17 - 108 ] vs 59 % [ 17 - 100 ] ) . After a median follow-up of 76 months ( range 43 - 116 ) , median survival was 65.7 months ( 95 % CI 47.9 - 88.5 ) in the chemotherapy group and 43.7 ( 35.7 - 52.3 ) months in the observation group . Adjusted risk for death was significantly reduced in patients assigned chemotherapy compared with controls ( hazard ratio 0.80 [ 95 % CI 0.66 - 0.96 ] ; p=0.017 ) . Overall survival at 5 years with chemotherapy improved by 8.6 % , which was maintained at 7 years ( 8.4 % ) . INTERPRETATION Adjuvant vinorelbine plus cisplatin extends survival in patients with completely resected NSCLC , better defining indication of adjuvant chemotherapy", "BACKGROUND We conducted a multinational , r and omized study to compare radiotherapy alone with radiotherapy plus cetuximab , a monoclonal antibody against the epidermal growth factor receptor , in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck . METHODS Patients with locoregionally advanced head and neck cancer were r and omly assigned to treatment with high-dose radiotherapy alone ( 213 patients ) or high-dose radiotherapy plus weekly cetuximab ( 211 patients ) at an initial dose of 400 mg per square meter of body-surface area , followed by 250 mg per square meter weekly for the duration of radiotherapy . The primary end point was the duration of control of locoregional disease ; secondary end points were overall survival , progression-free survival , the response rate , and safety . RESULTS The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone ( hazard ratio for locoregional progression or death , 0.68 ; P=0.005 ) . With a median follow-up of 54.0 months , the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone ( hazard ratio for death , 0.74 ; P=0.03 ) . Radiotherapy plus cetuximab significantly prolonged progression-free survival ( hazard ratio for disease progression or death , 0.70 ; P=0.006 ) . With the exception of acneiform rash and infusion reactions , the incidence of grade 3 or greater toxic effects , including mucositis , did not differ significantly between the two groups . CONCLUSIONS Treatment of locoregionally advanced head and neck cancer with concomitant high-dose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck . ( Clinical Trials.gov number , NCT00004227 .", "CONTEXT Postmenopausal women aged 55 years and older have 66 % of incident breast tumors and experience 77 % of breast cancer mortality , but other age-related health problems may affect tumor prognosis and treatment decisions . OBJECTIVE To document the comorbidity burden of postmenopausal breast cancer patients and evaluate its relationship with age on disease stage , treatment , and early mortality . DESIGN AND SETTING Data were collected on breast cancer patients ' comorbidities by retrospective hospital medical records review and merged with information on patients ' tumor characteristics collected from 6 regional National Cancer Institute Surveillance , Epidemiology , and End Results cancer registries . Patients were followed up until death or for 30 months from breast cancer diagnosis . PARTICIPANTS Population -based r and om sample of 1800 postmenopausal breast cancer patients diagnosed in 1992 stratified by 3 age groups : 55 to 64 years , 65 to 74 years , and 75 years and older . MAIN OUTCOME MEASURES Extent of disease , therapy received , comorbidity , cause of death , and survival . RESULTS Seventy-three percent ( 1312 of 1800 ) of the sample was diagnosed with stage I and II breast cancer , 10 % ( n = 188 ) with stage III and IV breast cancer , and 17 % ( n = 300 ) did not have a stage assignment . Of the 1017 patients with stage I and stage II node-negative breast cancer , 95 % received therapy in agreement with the National Institutes of Health consensus statement recommendation for early-stage breast cancer . Patients in older age groups were less likely to receive therapy consistent with the consensus statement ( P axillary lymph node dissection as determined by logistic regression analysis ( P Diabetes , renal failure , stroke , liver disease , a previous malignant tumor , and smoking were significant in predicting early mortality in a statistical model that included age and disease stage . Breast cancer was the underlying cause of death for 135 decedents ( 51.3 % ) . Heart disease ( n = 45 , 17.1 % ) and previous cancers ( n = 22 , 8.4 % ) were the next major underlying causes . In the 30-month follow-up period , 263 patients ( 15 % ) died . CONCLUSION Patient care decisions occur in the context of breast cancer and other age-related conditions . Comorbidity in older patients may limit the ability to obtain prognostic information ( ie , axillary lymph node dissection ) , tends to minimize treatment options ( eg , breast-conserving therapy ) , and increases the risk of death from causes other than breast cancer", "CONTEXT The role of adjuvant therapy in resectable pancreatic cancer is still uncertain , and no recommended st and ard exists . OBJECTIVE To test the hypothesis that adjuvant chemotherapy with gemcitabine administered after complete resection of pancreatic cancer improves disease-free survival by 6 months or more . DESIGN , SETTING , AND PATIENTS Open , multicenter , r and omized controlled phase 3 trial with stratification for resection , tumor , and node status . Conducted from July 1998 to December 2004 in the outpatient setting at 88 academic and community-based oncology centers in Germany and Austria . A total of 368 patients with gross complete ( R0 or R1 ) resection of pancreatic cancer and no prior radiation or chemotherapy were enrolled into 2 groups . INTERVENTION Patients received adjuvant chemotherapy with 6 cycles of gemcitabine on days 1 , 8 , and 15 every 4 weeks ( n = 179 ) , or observation ( [ control ] n = 175 ) . MAIN OUTCOME MEASURES Primary end point was disease-free survival , and secondary end points were overall survival , toxicity , and quality of life . Survival analysis was based on all eligible patients ( intention-to-treat ) . RESULTS More than 80 % of patients had R0 resection . The median number of chemotherapy cycles in the gemcitabine group was 6 ( range , 0 - 6 ) . Grade 3 or 4 toxicities rarely occurred with no difference in quality of life ( by Spitzer index ) between groups . During median follow-up of 53 months , 133 patients ( 74 % ) in the gemcitabine group and 161 patients ( 92 % ) in the control group developed recurrent disease . Median disease-free survival was 13.4 months in the gemcitabine group ( 95 % confidence interval , 11.4 - 15.3 ) and 6.9 months in the control group ( 95 % confidence interval , 6.1 - 7.8 ; P Estimated disease-free survival at 3 and 5 years was 23.5 % and 16.5 % in the gemcitabine group , and 7.5 % and 5.5 % in the control group , respectively . Subgroup analyses showed that the effect of gemcitabine on disease-free survival was significant in patients with either R0 or R1 resection . There was no difference in overall survival between the gemcitabine group ( median , 22.1 months ; 95 % confidence interval , 18.4 - 25.8 ; estimated survival , 34 % at 3 years and 22.5 % at 5 years ) and the control group ( median , 20.2 months ; 95 % confidence interval , 17 - 23.4 ; estimated survival , 20.5 % at 3 years and 11.5 % at 5 years ; P = .06 , log-rank ) . CONCLUSIONS Postoperative gemcitabine significantly delayed the development of recurrent disease after complete resection of pancreatic cancer compared with observation alone . These results support the use of gemcitabine as adjuvant chemotherapy in resectable carcinoma of the pancreas . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N34802808", "BACKGROUND The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established . We compared chemoradiotherapy followed by surgery with surgery alone in this patient population . METHODS We r and omly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin ( doses titrated to achieve an area under the curve of 2 mg per milliliter per minute ) and paclitaxel ( 50 mg per square meter of body-surface area ) for 5 weeks and concurrent radiotherapy ( 41.4 Gy in 23 fractions , 5 days per week ) , followed by surgery . RESULTS From March 2004 through December 2008 , we enrolled 368 patients , 366 of whom were included in the analysis : 275 ( 75 % ) had adenocarcinoma , 84 ( 23 % ) had squamous-cell carcinoma , and 7 ( 2 % ) had large-cell undifferentiated carcinoma . Of the 366 patients , 178 were r and omly assigned to chemoradiotherapy followed by surgery , and 188 to surgery alone . The most common major hematologic toxic effects in the chemoradiotherapy-surgery group were leukopenia ( 6 % ) and neutropenia ( 2 % ) ; the most common major nonhematologic toxic effects were anorexia ( 5 % ) and fatigue ( 3 % ) . Complete resection with no tumor within 1 mm of the resection margins ( R0 ) was achieved in 92 % of patients in the chemoradiotherapy-surgery group versus 69 % in the surgery group ( P pathological complete response was achieved in 47 of 161 patients ( 29 % ) who underwent resection after chemoradiotherapy . Postoperative complications were similar in the two treatment groups , and in-hospital mortality was 4 % in both . Median overall survival was 49.4 months in the chemoradiotherapy-surgery group versus 24.0 months in the surgery group . Overall survival was significantly better in the chemoradiotherapy-surgery group ( hazard ratio , 0.657 ; 95 % confidence interval , 0.495 to 0.871 ; P=0.003 ) . CONCLUSIONS Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer . The regimen was associated with acceptable adverse-event rates . ( Funded by the Dutch Cancer Foundation [ KWF Kankerbestrijding ] ; Netherl and s Trial Register number , NTR487 . )", "BACKGROUND The st and ard adjuvant treatment of colon cancer is fluorouracil plus leucovorin ( FL ) . Oxaliplatin improves the efficacy of this combination in patients with metastatic colorectal cancer . We evaluated the efficacy of treatment with FL plus oxaliplatin in the postoperative adjuvant setting . METHODS We r and omly assigned 2246 patients who had undergone curative resection for stage II or III colon cancer to receive FL alone or with oxaliplatin for six months . The primary end point was disease-free survival . RESULTS A total of 1123 patients were r and omly assigned to each group . After a median follow-up of 37.9 months , 237 patients in the group given FL plus oxaliplatin had had a cancer-related event , as compared with 293 patients in the FL group ( 21.1 percent vs. 26.1 percent ; hazard ratio for recurrence , 0.77 ; P=0.002 ) . The rate of disease-free survival at three years was 78.2 percent ( 95 percent confidence interval , 75.6 to 80.7 ) in the group given FL plus oxaliplatin and 72.9 percent ( 95 percent confidence interval , 70.2 to 75.7 ) in the FL group ( P=0.002 by the stratified log-rank test ) . In the group given FL plus oxaliplatin , the incidence of febrile neutropenia was 1.8 percent , the incidence of gastrointestinal adverse effects was low , and the incidence of grade 3 sensory neuropathy was 12.4 percent during treatment , decreasing to 1.1 percent at one year of follow-up . Six patients in each group died during treatment ( death rate , 0.5 percent ) . CONCLUSIONS Adding oxaliplatin to a regimen of fluorouracil and leucovorin improves the adjuvant treatment of colon cancer", "PURPOSE The French Adjuvant Study Group 05 ( FASG-05 ) showed that fluorouracil 500 mg/m2 , cyclophosphamide 500 mg/m2 , and epirubicin 100 mg/m2 ( FEC 100 ) was superior to the same regimen with epirubicin 50 mg/m2 ( FEC 50 ) in terms of disease-free survival ( DFS ) and overall survival ( OS ) in adjuvant treatment of early breast cancer . We report 10-year data on efficacy , and long-term side effects for FASG-05 . PATIENTS AND METHODS We r and omly assigned 565 patients to treatment with FEC 50 or FEC 100 after surgery . Postmenopausal patients also received tamoxifen for 3 years , and almost all patients ( 96 % ) also received radiotherapy . RESULTS Median follow-up was 110 months . The 10-year DFS was 45.3 % ( 95 % CI , 41.9 % to 48.7 % ) with FEC 50 and 50.7 % ( 95 % CI , 47.3 % to 54.1 % ) with FEC 100 ( Wilcoxon P = .036 ; log-rank P = .08 ) . The 10-year OS was 50.0 % ( 95 % CI , 46.7 % to 53.3 % ) with FEC 50 and 54.8 % ( 95 % CI , 51.3 % to 58.3 % ) with FEC 100 ( Wilcoxon P = .038 ; log-rank P = .05 ) . Delayed cardiac toxicity ( before relapse ) occurred in four patients ( 1.5 % ) in the FEC 50 arm and three patients ( 1.1 % ) in the FEC 100 arm . Cardiac toxicity after relapse occurred in six ( 4.3 % ) and five ( 4.1 % ) patients treated with FEC 50 and FEC 100 , respectively . CONCLUSION Treatment with adjuvant FEC 100 demonstrated superior DFS and OS versus FEC 50 at 10 years of follow-up . This survival advantage was not offset by long-term complications such as cardiac toxicity and second malignancy . Given the risk-benefit ratio , FEC 100 is a more optimal regimen for long-term survival in patients with poor prognosis", "BACKGROUND Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer . The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II ( axillary lymph node-positive ) breast cancer . METHODS Within 6 weeks of surgery ( radical mastectomy , modified radical mastectomy , or lumpectomy ) , 1550 patients with unilateral breast cancer were r and omly assigned to one of three treatment arms : high- , moderate- , or low-dose intensity . The patients received cyclophosphamide , doxorubicin , and 5-fluorouracil on day 1 of each chemotherapy cycle , with 5-fluorouracil administration repeated on day 8 . The high-dose arm had twice the dose intensity and twice the drug dose as the low-dose arm . The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose . Disease-free survival and overall survival were primary end points of the study . RESULTS At a median follow-up of 9 years , disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm ( two-sided P disease-free or overall survival between the moderate- and the high-dose arms . At 5 years , overall survival ( average + /- st and ard error ) is 79 % + /- 2 % for patients on the high-dose arm , 77 % + /- 2 % for the patients on the moderate-dose arm , and 72 % + /- 2 % for patients on the low-dose arm ; disease-free survival is 66 % + /- 2 % , 61 % + /- 2 % , and 56 % + /- 2 % , respectively . CONCLUSION Within the conventional dose range for this chemotherapy regimen , a higher dose is associated with better disease-free survival and overall survival", "BACKGROUND The purpose of this study was to report response rates , survival and toxicity in advanced non-small-cell lung cancer ( NSCLC ) following docetaxel and carboplatin , and to explore potential differences in these end points between Caucasian and Asian patients . PATIENTS AND METHODS Sixty-eight patients of good performance status with Stage IIIB or IV NSCLC were entered on a phase II study at three sites in Australia and Singapore . Docetaxel 75 mg/m2 and carboplatin AUC 6 were given every 3 weeks . Response to treatment and toxicity were grade d by st and ard criteria . The Kaplan-Meier method was used to estimate survival rates , and subgroups compared by the log-rank test . Cox 's proportional hazards regression was used to determine which potentially explanatory variables independently affected the outcome . RESULTS The response rate was 39 % ( 95 % confidence interval 27 % to 52 % ) , and 42 % in evaluable patients . Response occurred in 65 % of Asian and 31 % of Caucasian patients ( P = 0.01 ) . Ethnicity was the only significant predictor of response in multivariate analysis . The 1-year survival rate was 53 % . Performance status ( P = 0.021 ) , ethnicity ( P = 0.035 ) and presence of bone or liver metastases ( P = 0.011 ) were independent predictors of overall survival . Neutropenia ( grade IV in 73 % of patients ) , febrile neutropenia ( 26 % patients ) and diarrhea ( grade III/IV in 11 % of patients ) were the major treatment related toxicities . A high rate ( three of six ) of febrile neutropenia in Singapore , including one treatment-related death in the initial patients treated , result ed in a reduction in the carboplatin dose to AUC 4.5 at that site . CONCLUSIONS This regimen is active in advanced NSCLC . The potential impact of ethnicity on efficacy and toxicity of treatment requires further investigation", "Combination chemotherapy with docetaxel ( T ) , cisplatin ( P ) , fluorouracil ( 5-FU ) and leucovorin has been reported to have major activity against squamous cell carcinoma of the head and neck ( SCCHN ) administered as a 4-day ( TPFL4 ) or 5-day ( TPFL5 ) regimen . The purpose of this study was to evaluate the efficacy and toxicity of a modified TPFL regimen ( m-TPFL ) for locally advanced SCCHN , consisting of a modified dosage with docetaxel , cisplatin , 5-FU and l-leucovorin ( l-LV ) design ed for Japanese patients . Organ preservation of the primary tumor site was also assessed . Thirty-four Japanese patients with locally advanced SCCHN were eligible . Docetaxel was administered as a 1-h i.v . infusion at 48 mg/m2 on day 1 ; cisplatin , 24 mg/m2/day ; 5-FU , 560 mg/m2/day and l-LV , 125 mg/body/day were delivered on days 1–4 by continuous i.v . infusion . This regimen was administered every 28 days . Patients who achieved a complete response ( CR ) after induction chemotherapy underwent radiation therapy alone . Ninety-one cycles were administered . The main hematological toxicity was neutropenia , classified as grade III or IV in 18.7 % of cycles . The most common non-hematologic toxicities included anorexia , stomatitis and alopecia . The clinical overall response rate to m-TPFL was 88.2 % , with 58.8 % CRs and 29.4 % partial responses . After definitive locoregional therapy , 25 of 34 patients were disease-free with preserved primary tumor site anatomy . Overall and progression-free survival rates at the 2-year follow-up are 92.8 and 75.3 % , respectively . Our m-TPFL regimen design ed for Japanese patients yielded excellent response rates with an acceptable toxicity profile in good-performance-status patients", "PURPOSE The primary aim of National Surgical Adjuvant Breast and Bowel Project ( NSABP ) B-28 was to determine whether four cycles of adjuvant paclitaxel ( PTX ) after four cycles of adjuvant doxorubicin/cyclophosphamide ( AC ) will prolong disease-free survival ( DFS ) and overall survival ( OS ) compared with four cycles of AC alone in patients with resected operable breast cancer and histologically positive axillary nodes . PATIENTS AND METHODS Between August 1995 and May 1998 , 3,060 patients were r and omly assigned ( AC , 1,529 ; AC followed by PTX [ AC -- > PTX ] , 1,531 ) . Patients > or = 50 years and those younger than 50 years with estrogen receptor ( ER ) or progesterone receptor ( PR ) -positive tumors also received tamoxifen for 5 years , starting with the first dose of AC . Postlumpectomy radiotherapy was m and ated . Postmastectomy or regional radiotherapy was prohibited . Median follow-up is 64.6 months . RESULTS The addition of PTX to AC significantly reduced the hazard for DFS event by 17 % ( relative risk [ RR ] , 0.83 ; 95 % CI , 0.72 to 0.95 ; P = .006 ) . Five-year DFS was 76 % + /- 2 % for patients r and omly assigned to AC -- > PTX compared with 72 % + /- 2 % for those r and omly assigned to AC . Improvement in OS was small and not statistically significant ( RR , 0.93 ; 95 % CI , 0.78 to 1.12 ; P = .46 ) . Five-year OS was 85 % + /- 2 % for both groups . Subset analysis of the effect of paclitaxel according to hormone receptors or tamoxifen administration did not reveal statistically significant interaction ( for DFS , P = .30 and P = .44 , respectively ) . Toxicity with the AC -- > PTX regimen was acceptable for the adjuvant setting . CONCLUSION The addition of PTX to AC result ed in significant improvement in DFS but no significant improvement in OS with acceptable toxicity . No significant interaction between treatment effect and receptor status or tamoxifen administration was observed", "PURPOSE The primary treatment modality for patients with carcinoma of the esophagus or gastroesophageal junction has been surgery , although primary radiation therapy with concurrent chemotherapy produces similar results . As both have curative potential , there has been great interest in the use of trimodality therapy . To this end , we compared survival , response , and patterns of failure of trimodality therapy to esophagectomy alone in patients with nonmetastatic esophageal cancer . PATIENTS AND METHODS Four hundred seventy-five eligible patients were planned for enrollment . Patients were r and omly assigned to either esophagectomy with node dissection alone or cisplatin 100 mg/m(2 ) and fluorouracil 1,000 mg/m(2)/d for 4 days on weeks 1 and 5 concurrent with radiation therapy ( 50.4 Gy total : 1.8 Gy/fraction over 5.6 weeks ) followed by esophagectomy with node dissection . RESULTS Fifty-six patients were enrolled between October 1997 and March 2000 , when the trial was closed due to poor accrual . Thirty patients were r and omly assigned to trimodality therapy and 26 were assigned to surgery alone . Patient and tumor characteristics were similar between groups . Treatment was generally well tolerated . Median follow-up was 6 years . An intent-to-treat analysis showed a median survival of 4.48 v 1.79 years in favor of trimodality therapy ( exact stratified log-rank , P = .002 ) . Five-year survival was 39 % ( 95 % CI , 21 % to 57 % ) v 16 % ( 95 % CI , 5 % to 33 % ) in favor of trimodality therapy . CONCLUSION The results from this trial reflect a long-term survival advantage with the use of chemoradiotherapy followed by surgery in the treatment of esophageal cancer , and support trimodality therapy as a st and ard of care for patients with this disease", "BACKGROUND Previous studies have demonstrated that African-Americans with colon cancer have worse overall and stage-specific survival rates than Caucasians . Such differences could reflect variation in access to health care , in tumor biology , or in treatment efficacy . Little is known about potential differences in chemotherapy-related toxicities between African-Americans and Caucasians . In this study , we examined survival and toxic effects among African-American and Caucasian patients enrolled in a large , r and omized phase III trial of adjuvant chemotherapy for resected colon cancer . METHODS We analyzed data on 3380 patients ( 344 African-Americans and 3036 Caucasians ) enrolled in a r and omized trial of adjuvant 5-fluorouracil-based chemotherapy in patients with stage II ( high risk ) and stage III colon cancer to evaluate differences in outcomes and toxicity . We compared disease-free survival ( DFS ) and overall survival ( OS ) between African-Americans and Caucasians by the Kaplan-Meier method , computed Cox proportional hazards by multivariable analysis , and compared treatment-related toxicity rates by Fisher 's exact test . All statistical tests were two-sided . RESULTS We found no differences in DFS or OS between African-American and Caucasian patients . Five-year DFS was 57 % ( 95 % confidence interval [ CI ] = 52 % to 62 % ) for African-Americans and 58 % ( 95 % CI = 56 % to 60 % ) for Caucasians ( P = .15 ) , and 5-year OS was 65 % ( 95 % CI = 60 % to 70 % ) for African-Americans and 66 % ( 95 % CI = 64 % to 68 % ) for Caucasians ( P = .38 ) . On multivariable analysis , no statistically significant difference in disease recurrence or death was detected between the racial/ethnic groups ( hazard ratios for African-Americans versus Caucasians : disease recurrence = 1.1 , 95 % CI = 0.9 to 1.3 ; death = 1.1 , 95 % CI = 0.9 to 1.3 ) . Treatment-related toxicity differed between the African-American and Caucasian patients , with African-Americans experiencing statistically significantly lower rates of diarrhea ( P nausea ( P vomiting ( P = .01 ) , stomatitis ( P overall toxicity ( P = .005 ) . CONCLUSIONS In this study of patients with similar access to health care re sources and treatment with adjuvant chemotherapy , we found similar 5-year DFS and OS in African-Americans and Caucasians with stage II and III colon cancer . The two groups derived similar benefits from adjuvant chemotherapy . Moreover , African-Americans appeared to experience less treatment-related toxicity", "PURPOSE Concurrent chemoradiotherapy is st and ard treatment for patients with inoperable stage III non-small-cell lung cancer ( NSCLC ) . A phase II study by the Southwest Oncology Group using consolidation docetaxel after cisplatin ( P ) , etoposide ( E ) , and radiation ( XRT ) result ed in a median survival time ( MST ) of 26 months . This r and omized phase III trial evaluated whether consolidation docetaxel was responsible for this improved survival . PATIENTS AND METHODS Eligible patients had stage IIIA or IIIB NSCLC , baseline performance status of 0 to 1 , forced expiratory volume in 1 second > or= 1 L , and less than 5 % weight loss . Patients received P 50 mg/m(2 ) intravenously ( IV ) on days 1 , 8 , 29 , and 36 and E 50 mg/m(2 ) IV on days 1 - 5 and 29 - 33 concurrently with chest XRT to 59.40 Gy . Patients who did not experience progression were r and omly assigned to docetaxel 75 mg/m(2 ) IV every 21 days for three cycles versus observation . The primary end point was to compare overall survival ( Kaplan-Meier analysis ) . RESULTS On the basis of evidence of futility , a data and safety monitoring board recommended early termination after an analysis of the initial 203 patients . Patient characteristics ( n = 203 ) were as follows : 34 % female ; median age , 63 years ; 39.4 % stage IIIA ; and 60.6 % stage IIIB . One hundred forty-seven ( 72.4 % ) of 203 patients were r and omly assigned to docetaxel ( n = 73 ) or observation ( n = 74 ) . Grade 3 to 5 toxicities during docetaxel included febrile neutropenia ( 10.9 % ) and pneumonitis ( 9.6 % ) ; 28.8 % of patients were hospitalized during docetaxel ( v 8.1 % in observation arm ) , and 5.5 % died as a result of docetaxel . The MST for all patients ( n = 203 ) was 21.7 months ; MST was 21.2 months for docetaxel arm compared with 23.2 months for observation arm ( P = .883 ) . CONCLUSION Consolidation docetaxel after PE/XRT results in increased toxicities but does not further improve survival compared with PE/XRT alone in patients with stage III inoperable NSCLC", "BACKGROUND Intravenous bolus fluorouracil plus leucovorin is the st and ard adjuvant treatment for colon cancer . The oral fluoropyrimidine capecitabine is an established alternative to bolus fluorouracil plus leucovorin as first-line treatment for metastatic colorectal cancer . We evaluated capecitabine in the adjuvant setting . METHODS We r and omly assigned a total of 1987 patients with resected stage III colon cancer to receive either oral capecitabine ( 1004 patients ) or bolus fluorouracil plus leucovorin ( Mayo Clinic regimen ; 983 patients ) over a period of 24 weeks . The primary efficacy end point was at least equivalence in disease-free survival ; the primary safety end point was the incidence of grade 3 or 4 toxic effects due to fluoropyrimidines . RESULTS Disease-free survival in the capecitabine group was at least equivalent to that in the fluorouracil-plus-leucovorin group ( in the intention-to-treat analysis , P Capecitabine improved relapse-free survival ( hazard ratio , 0.86 ; 95 percent confidence interval , 0.74 to 0.99 ; P=0.04 ) and was associated with significantly fewer adverse events than fluorouracil plus leucovorin ( P capecitabine is an effective alternative to intravenous fluorouracil plus leucovorin in the adjuvant treatment of colon cancer", "PURPOSE We examined data from a large clinical trial to determine if chemotherapy dosing according to actual body weight places obese patients at greater risk of toxicity . PATIENTS AND METHODS Cancer and Leukemia Group B ( CALGB ) study 8541 , a r and omized study of schedule and dose of adjuvant cyclophosphamide , doxorubicin , and fluorouracil ( CAF ) for stage II breast cancer patients with positive regional lymph nodes , provided data on 1,435 women for analysis . Using body-mass index ( BMI ) , we classified a woman as obese if her BMI was > or = 27.3 kg/m2 ; doses were considered weight-based if within 5 % of values calculated using actual weight . Our primary analysis concerned toxicity risks during cycle 1 . RESULTS Among women who received weight-based doses of the most dose-intensive CAF regimen , 47 % of obese and 51 % of nonobese women experienced severe hematologic toxicity ( grade > or = 3 ) during cycle 1 ( P = .51 , two-tailed ) . The overall risk ratio ( obese v nonobese ) of treatment failure among women who received weight-based doses during cycle 1 was 1.02 ( 95 % confidence interval , 0.83 to 1.26 ) , stratified by treatment and adjusted for number of positive nodes , menopausal status , hormone receptor status , and tumor size . The overall adjusted failure risk ratio ( weight-based v reduced initial doses ) was 0.73 ( 95 % confidence interval , 0.53 to 1.00 ) among obese women . CONCLUSION Obese patients initially dosed ( within 5 % ) by actual weight did not experience excess cycle 1 toxicity or worse outcome compared with nonobese women dosed similarly . The data suggest that obese women who received reduced doses in cycle 1 experienced worse failure-free survival . We recommend that initial doses of CAF be computed according to actual body weight", "PURPOSE The combination of doxorubicin and cyclophosphamide ( AC ) is a st and ard adjuvant chemotherapy regimen . Studies of docetaxel and cyclophosphamide ( TC ) in metastatic breast cancer ( MBC ) showed promise in MBC . In 1997 , we initiated a r and omized adjuvant trial of TC compared with st and ard-dose AC with a primary end point of disease-free survival ( DFS ) . PATIENTS AND METHODS Patients were eligible if they had stage I to III operable invasive breast cancer with complete surgical excision of the primary tumor . Between June 1997 and December 1999 , 1,016 patients were r and omly assigned to four cycles of either st and ard-dose AC ( 60 and 600 mg/m2 , respectively ; n = 510 ) or TC ( 75 and 600 mg/m2 , respectively ; n = 506 ) , administered intravenously every 3 weeks as adjuvant chemotherapy . Radiation therapy ( as indicated ) and tamoxifen , for patients with hormone receptor-positive disease , were administered after completion of chemotherapy . RESULTS Both treatment groups ( TC and AC ) were well balanced with respect to major prognostic factors . Patients were observed through 2005 for a median of 5.5 years . At 5 years , DFS rate was significantly superior for TC compared with AC ( 86 % v 80 % , respectively ; hazard ratio [ HR ] = 0.67 ; 95 % CI , 0.50 to 0.94 ; P = .015 ) . Overall survival rates for TC and AC were 90 % and 87 % , respectively ( HR = 0.76 ; 95 % CI , 0.52 to 1.1 ; P = .13 ) . More myalgia , arthralgia , edema , and febrile neutropenia occurred on the TC arm ; more nausea and vomiting occurred on the AC arm as well as one incident of congestive heart failure . CONCLUSION At 5 years , TC was associated with a superior DFS and a different toxicity profile compared with AC ", "BACKGROUND A regimen of epirubicin , cisplatin , and infused fluorouracil ( ECF ) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma . We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer . METHODS We r and omly assigned patients with resectable adenocarcinoma of the stomach , esophagogastric junction , or lower esophagus to either perioperative chemotherapy and surgery ( 250 patients ) or surgery alone ( 253 patients ) . Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin ( 50 mg per square meter of body-surface area ) and cisplatin ( 60 mg per square meter ) on day 1 , and a continuous intravenous infusion of fluorouracil ( 200 mg per square meter per day ) for 21 days . The primary end point was overall survival . RESULTS ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer . Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group ( 46 percent and 45 percent , respectively ) , as were the numbers of deaths within 30 days after surgery . The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group . With a median follow-up of four years , 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died . As compared with the surgery group , the perioperative-chemotherapy group had a higher likelihood of overall survival ( hazard ratio for death , 0.75 ; 95 percent confidence interval , 0.60 to 0.93 ; P=0.009 ; five-year survival rate , 36 percent vs. 23 percent ) and of progression-free survival ( hazard ratio for progression , 0.66 ; 95 percent confidence interval , 0.53 to 0.81 ; P patients with operable gastric or lower esophageal adenocarcinomas , a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival . ( Current Controlled Trials number , IS RCT N93793971 [ controlled-trials.com ] . )", "PURPOSE The Southwest Oncology Group ( SWOG ) coordinated an Intergroup study with the participation of Radiation Therapy Oncology Group ( RTOG ) , and Eastern Cooperative Oncology Group ( ECOG ) . This r and omized phase III trial compared chemoradiotherapy versus radiotherapy alone in patients with nasopharyngeal cancers . MATERIAL S AND METHODS Radiotherapy was administered in both arms : 1.8- to 2.0-Gy/d fractions Monday to Friday for 35 to 39 fractions for a total dose of 70 Gy . The investigational arm received chemotherapy with cisplatin 100 mg/m2 on days 1 , 22 , and 43 during radiotherapy ; postradiotherapy , chemotherapy with cisplatin 80 mg/m2 on day 1 and fluorouracil 1,000 mg/m2/d on days 1 to 4 was administered every 4 weeks for three courses . Patients were stratified by tumor stage , nodal stage , performance status , and histology . RESULTS Of 193 patients registered , 147 ( 69 radiotherapy and 78 chemoradiotherapy ) were eligible for primary analysis for survival and toxicity . The median progression-free survival ( PFS ) time was 15 months for eligible patients on the radiotherapy arm and was not reached for the chemo-radiotherapy group . The 3-year PFS rate was 24 % versus 69 % , respectively ( P median survival time was 34 months for the radiotherapy group and not reached for the chemo-radiotherapy group , and the 3-year survival rate was 47 % versus 78 % , respectively ( P = .005 ) . One hundred eighty-five patients were included in a secondary analysis for survival . The 3-year survival rate for patients r and omized to radiotherapy was 46 % , and for the chemoradiotherapy group was 76 % ( P chemoradiotherapy is superior to radiotherapy alone for patients with advanced nasopharyngeal cancers with respect to PFS and overall survival", "BACKGROUND Chemoradiation became the st and ard of care for anal cancer after the ACT I trial . However , only two-thirds of patients achieved local control , with 5-year survival of 50 % ; therefore , better treatments are needed . We investigated whether replacing mitomycin with cisplatin in chemoradiation improves response , and whether maintenance chemotherapy after chemoradiation improves survival . METHODS In this 2 × 2 factorial trial , we enrolled patients with histologically confirmed squamous-cell carcinoma of the anus without metastatic disease from 59 centres in the UK . Patients were r and omly assigned to one of four groups , to receive either mitomycin ( 12 mg/m(2 ) on day 1 ) or cisplatin ( 60 mg/m(2 ) on days 1 and 29 ) , with fluorouracil ( 1000 mg/m(2 ) per day on days 1 - 4 and 29 - 32 ) and radiotherapy ( 50.4 Gy in 28 daily fractions ) ; with or without two courses of maintenance chemotherapy ( fluorouracil and cisplatin at weeks 11 and 14 ) . The r and om allocation was generated by computer and patients assigned by telephone . R and omisation was done by minimisation and stratified by tumour site , T and N stage , sex , age , and renal function . Neither patients nor investigators were masked to assignment . Primary endpoints were complete response at 26 weeks and acute toxic effects ( for chemoradiation ) , and progression-free survival ( for maintenance ) . The primary analyses were done by intention to treat . This study is registered at controlled-trials.com , number 26715889 . FINDINGS We enrolled 940 patients : 472 were assigned to mitomycin , of whom 246 were assigned to no maintenance , 226 to maintenance ; 468 were assigned to cisplatin , of whom 246 were assigned to no maintenance , 222 to maintenance . Median follow-up was 5.1 years ( IQR 3.9 - 6.9 ) . 391 of 432 ( 90.5 % ) patients in the mitomycin group versus 386 of 431 ( 89.6 % ) in the cisplatin group had a complete response at 26 weeks ( difference -0.9 % , 95 % CI -4.9 to 3.1 ; p=0.64 ) . Overall , toxic effects were similar in each group ( 334/472 [ 71 % ] for mitomycin vs 337/468 [ 72 % ] for cisplatin ) . The most common grade 3 - 4 toxic effects were skin ( 228/472 [ 48 % ] vs 222/468 [ 47 % ] ) , pain ( 122/472 [ 26 % ] vs 135/468 [ 29 % ] ) , haematological ( 124/472 [ 26 % ] vs 73/468 [ 16 % ] ) , and gastrointestinal ( 75/472 [ 16 % ] vs 85/468 [ 18 % ] ) . 3-year progression-free survival was 74 % ( 95 % CI 69 - 77 ; maintenance ) versus 73 % ( 95 % CI 68 - 77 ; no maintenance ; hazard ratio 0.95 , 95 % CI 0.75 - 1.21 ; p=0.70 ) . INTERPRETATION The results of our trial -- the largest in anal cancer to date --show that fluorouracil and mitomycin with 50.4 Gy radiotherapy in 28 daily fractions should remain st and ard practice in the UK . FUNDING Cancer Research UK", "BACKGROUND Despite aggressive local therapy , patients with locally advanced bladder cancer are at significant risk for metastases . We evaluated the ability of neoadjuvant chemotherapy to improve the outcome in patients with locally advanced bladder cancer who were treated with radical cystectomy . METHODS Patients were enrolled if they had muscle-invasive bladder cancer ( stage T2 to T4a ) and were to be treated with radical cystectomy . They were stratified according to age ( less than 65 years vs. 65 years or older ) and stage ( superficial muscle invasion vs. more extensive disease ) and were r and omly assigned to radical cystectomy alone or three cycles of methotrexate , vinblastine , doxorubicin , and cisplatin followed by radical cystectomy . RESULTS We enrolled 317 patients over an 11-year period , 10 of whom were found to be ineligible ; thus , 154 were assigned to receive surgery alone and 153 to receive combination therapy . According to an intention-to-treat analysis , the median survival among patients assigned to surgery alone was 46 months , as compared with 77 months among patients assigned to combination therapy ( P=0.06 by a two-sided stratified log-rank test ) . In both groups , improved survival was associated with the absence of residual cancer in the cystectomy specimen . Significantly more patients in the combination-therapy group had no residual disease than patients in the cystectomy group ( 38 percent vs. 15 percent , P cystectomy alone , the use of neoadjuvant methotrexate , vinblastine , doxorubicin , and cisplatin followed by radical cystectomy increases the likelihood of eliminating residual cancer in the cystectomy specimen and is associated with improved survival among patients with locally advanced bladder cancer", "PURPOSE This single centre , open labelled , r and omised non-inferiority trial compared concurrent chemoradiotherapy with carboplatin versus st and ard concurrent chemoradiotherapy with cisplatin in patients with locoregionally advanced nasopharyngeal cancer ( NPC ) . PATIENTS AND METHODS From August 1999 to December 2004 , 206 patients with locally advanced NPC were r and omised with 101 to cisplatin arm and 105 to carboplatin arm . Planned radiotherapy was the same in both groups . All the patients were evaluated for toxicity and survival according to the as-treated principle . RESULTS With a median follow-up of 26.3 months ( range 3 - 74.6 months ) , 59 % of patients in the cisplatin arm completed the planned concurrent chemoradiation treatment , compared to 73 % in the carboplatin arm . Forty-two percent of cisplatin patients completed the 3 cycles of adjuvant therapy compared to 70 % in the carboplatin group . There were more renal toxicity , leucopenia , and anaemia in the cisplatin group , and more thrombocytopenia in the carboplatin arm . The 3 year disease free survival rates were 63.4 % for the cisplatin group and 60.9 % for the carboplatin group ( p=0.9613 ) ( HR 0.70 , 95 % confidence interval ( CI ) : 0.50 - 0.98 ) . The 3 year overall survival rates were 77.7 % and 79.2 % for cisplatin and carboplatin groups , respectively ( p=0.9884 ) ( HR 0.83 , 95 % CI : 0.63 - 1.010 ) . CONCLUSION We concluded that the tolerability of carboplatin based regimen is better than that of the cisplatin regimen . Moreover , the treatment efficacy of carboplatin arm is not different from the st and ard regimen in the treatment of locoregional advanced stage NPC", "Meta‐ analysis data demonstrate a 5 % absolute survival benefit for neoadjuvant chemotherapy ( NAC ) using cisplatin‐based combination regimens in the radical treatment of muscle‐invasive bladder cancer ( MIBC ) . However , there are no r and omized , controlled trial data on the optimum regimen . Accelerated methotrexate , vinblastine , doxorubicin , and cisplatin ( AMVAC ) is a dose‐intense regimen that has the potential to minimize delays to definitive , potentially curative therapy . A retrospective analysis is presented of the efficacy and toxicity of AMVAC as NAC in patients with MIBC and its impact on the patient pathway" ]

[ "Background Shoulder pain is common in primary care , and has an unfavourable outcome in many patients . Information about predictors of shoulder pain related sick leave in workers is scarce and inconsistent . The objective was to develop a clinical prediction rule for calculating the risk of shoulder pain related sick leave for individual workers , during the 6 months following first consultation in general practice . Methods A prospect i ve cohort study with 6 months follow-up was conducted among 350 workers with a new episode of shoulder pain . Potential predictors included the results of a physical examination , sociodemographic variables , disease characteristics ( duration of symptoms , sick leave in the 2 months prior to consultation , pain intensity , disability , comorbidity ) , physical activity , physical work load , psychological factors , and the psychosocial work environment . The main outcome measure was sick leave during 6 months following first consultation in general practice . Results Response rate to the follow-up question naire at 6 months was 85 % . During the 6 months after first consultation 30 % ( 89/298 ) of the workers reported sick leave . 16 % ( 47 ) reported 10 days sick leave or more . Sick leave during this period was predicted in a multivariable model by a longer duration of sick leave prior to consultation , more shoulder pain , a perceived cause of strain or overuse during regular activities , and co-existing psychological complaints . The discriminative ability of the prediction model was satisfactory with an area under the curve of 0.70 ( 95 % CI 0.64–0.76 ) . Conclusion Although 30 % of all workers with shoulder pain reported sick leave during follow-up , the duration of sick leave was limited to a few days in most workers . We developed a prediction rule and a score chart that can be used by general practitioners and occupational health care providers to calculate the absolute risk of sick leave in individual workers with shoulder pain , which may help to identify workers who need additional attention . The performance and applicability of our model needs to be tested in other working population s with shoulder pain to enable valid and reliable use of the score chart in everyday practice", "This paper provides an up-to- date overview of the occurrence , diagnosis , risk factors , prognostic indicators and outcome of shoulder disorder ( SD ) , and of the validity and reproducibility of diagnostic classifications and diagnostic imaging techniques for SD . Furthermore , the available evidence on the effectiveness of non-steroidal anti-inflammatory drugs ( NSAIDs ) , corticosteroid injections and physiotherapy for SD is summarized on the basis of r and omized controlled trials with an acceptable quality of their methods . The annual incidence of SD is estimated at about 7 % , its 1-year period prevalence at about 51 % and its lifetime prevalence at about 10 % . While approximately 50 % of all patients with SD seek medical care , about 95 % are treated in primary health care . Of all new episodes of SD presenting to primary care , approximately 50 % seem to resolve within 6 months , while about 40 % seem to persist for up to 12 months . Several prognostic indicators for a favourable or a poor outcome of SD have been identified , but a comprehensive prognostic model is not available . While evidence for the prognostic validity of popular diagnostic classifications of SD is lacking , their reproducibility has been shown to be poor . The accuracy and clinical usefulness of diagnostic imaging techniques appear to be sufficiently verified for SD in secondary care , while their clinical usefulness in primary care and prognostic validity are not . NSAIDs and steroid injections for SD have been shown to be effective within 6 weeks , but their effect on long-term outcome remains unclear . There is very limited evidence for the effectiveness in SD of physiotherapy , including exercise therapy , ultrasound , electrotherapy , laser , mobilization and manipulation", "Measures of both generic and disease-specific health status are being developed and used with increasing frequency for the appraisal of musculoskeletal conditions . The purpose of this study was to compare prospect ively the validity of five question naires in the assessment of function of the shoulder . Ninety subjects who had various problems related to the shoulder agreed to enter the study . All of the subjects completed a question naire package that included the Shoulder Pain and Disability Index , the Simple Shoulder Test , the Subjective Shoulder Rating Scale , the Modified American Shoulder and Elbow Surgeons Shoulder Patient Self-Evaluation Form , and the Shoulder Severity Index as well as a measure of generic health status ( the acute version of the Short Form 36 [ SF-36 ] ) and two questions that asked the patient to rate the severity of the problem and his or her over-all health . Frequency distributions were created and compared among question naires . Spearman rank correlations were calculated to compare the question naires with each other and with other assessment s. One-way analysis of variance was used to determine the ability of the question naires to discriminate between self-rated severity of the problem and over-all health . The frequency distributions were similar among the five shoulder question naires , but those of the five shoulder question naires differed from that of the SF-36 . The correlations were good ( 0.73 ⩽ r ⩽ 0.80 ) among all of the five shoulder question naires except the Subjective Shoulder Rating Scale ; they were lower with the Subjective Shoulder Rating Scale and the physical function dimension of the SF-36 ( 0.12 ⩽ r ⩽ 0.60 ) . The shoulder question naires discriminated between levels of severity ( p levels of over-all health ( 0.10 ⩽ p ⩽ 0.86 ) . In this concurrent comparison of measures of shoulder-specific outcome in the same subjects , the shoulder question naires performed similarly , both in describing function of the shoulder and in discriminating between levels of severity . The shoulder question naires performed differently than the SF-36 , which confirms the need to use both disease-specific and generic health-status measures to evaluate patients who have a problem related to the shoulder", "The Shoulder Disability Question naire ( SDQ ) is a measure covering 16 items design ed to evaluate functional status limitation in patients with shoulder disorders . The responsiveness of the SDQ was evaluated for 180 patients with soft tissue shoulder disorders , without underlying systemic disorders . These patients participated in a r and omized placebo-controlled trial , in which ultrasound and electrotherapy appeared to be ineffective as adjuvants to st and ardized exercise therapy . At baseline and at 6-week follow-up , patients completed the SDQ and rated severity of shoulder pain and their chief complaint , while a research physiotherapist rated severity of symptoms and restriction of mobility . At the 6-week follow-up , patients also rated overall change since baseline . According to the calibrated responsiveness ratio ( CRR ) and the area under the receiver-operator characteristic curve ( AUC ) the SDQ discriminates accurately between self-rated clinical ly stable and improved subjects . The presented results suggest that the SDQ is as responsive as the compared outcome measures , and therefore is ready for use in clinical trials", "The vali date d , patient-reported Oxford shoulder score ( OSS ) was introduced around 10 years ago , primarily for the assessment of outcomes of shoulder surgery ( excluding shoulder stabilisation ) in r and omised trials . Its uptake has steadily increased in a number of countries and its use has also been extended . Recently a number of issues have been raised in relation to other related patient-reported outcome measures which were devised around the same time as the OSS . This included recommendations to change the scoring system . This paper review s issues concerning patient-reported outcome measures that apply to the OSS and makes some recommendations ( including changes to the scoring system ) as to how it should be used", "We developed a 12-item question naire for completion by patients having shoulder operations other than stabilisation . A prospect i ve study of 111 patients was undertaken before operation and at follow-up six months later . Each patient completed the new question naire and the SF36 form . Some filled in the Stanford Health Assessment Question naire ( HAQ ) . An orthopaedic surgeon assessed the Constant shoulder score . The single score derived from the question naire had a high internal consistency . Reproducibility , examined by test-retest reliability , was found to be satisfactory . The validity of the question naire was established by obtaining significant correlations in the expected direction with the Constant score and the relevant scales of the SF36 and the HAQ . Sensitivity to change was assessed by analysing the differences between the preoperative scores and those at follow-up . Changes in scores were compared with the patients ' responses to postoperative questions about their condition . The st and ardised effect size for the new question naire compared favourably with that for the SF36 and the HAQ . The new question naire was the most efficient in distinguishing patients who said that their shoulder was much better from all other patients . The shoulder question naire provides a measure of outcome for shoulder operations which is short , practical , reliable , valid and sensitive to clinical ly important changes", "Background Painful shoulders pose a substantial socioeconomic burden . A prospect i ve cost-of-illness study was performed to assess the costs associated with healthcare use and loss of productivity in patients with shoulder pain in primary health care in Sweden . Methods The study was performed in western Sweden , in a region with 24 000 inhabitants . Data were collected during six months from electronic patient records at three primary healthcare centres in two municipalities . All patients between 20 and 64 years of age who presented with shoulder pain to a general practitioner or a physiotherapist were included . Diagnostic codes were used for selection , and the cases were manually controlled . The cost for sick leave was calculated according to the human capital approach . Sensitivity analysis was used to explore uncertainty in various factors used in the model . Results 204 ( 103 women ) patients , mean age 48 ( SD 11 ) years , were registered . Half of the cases were closed within six weeks , whereas 32 patients ( 16 % ) remained in the system for more than six months . A fifth of the patients were responsible for 91 % of the total costs , and for 44 % of the healthcare costs . The mean healthcare cost per patient was € 326 ( SD 389 ) during six months . Physiotherapy treatments accounted for 60 % . The costs for sick leave contributed to 84 % of the total costs . The mean annual total cost was € 4139 per patient . Estimated costs for secondary care increased the total costs by one third . Conclusions The model applied in this study provides valuable information that can be used in cost evaluations . Costs for secondary care and particularly for sick leave have a major influence on total costs and interventions that can reduce long periods of sick leave are warranted", "The purpose of this study was to examine the psychometric properties of the American Shoulder and Elbow Surgeons St and ardized Shoulder Assessment Form ( ASES ) , patient self-report section . Patients with shoulder dysfunction ( n = 63 ) completed the ASES , The University of Pennsylvania Shoulder Score , and the Short Form-36 during the initial evaluation , 24 to 72 hours after the initial visit , and after 3 to 4 weeks of physical therapy . The test-retest reliability ( intraclass correlation coefficient[1-way r and om-effects ] , 0.84 ; 95 % CI lower limit , 0.75 ) and internal consistency ( Cronbach alpha , 0.86 ) values were acceptable . The st and ard error of the measure was 6.7 ASES points ( 90 % CI , 11.0 ) . Construct and discriminant validity was demonstrated . Responsiveness was demonstrated with a st and ardized response mean of 1.5 and an effect size of 1.4 . The minimal detectable change was 9.7 ASES points ( 90 % CI , 16 ) , and the minimal clinical ly important difference was 6.4 ASES points . The results indicate that the ASES is a reliable , valid , and responsive outcome tool", "A self-administered question naire was design ed to assess the severity of symptoms related to and the functional status of the shoulder . It includes domains of global assessment , pain , daily activities , recreational and athletic activities , work , satisfaction , and areas for improvement . Each domain is grade d separately and is weighted to arrive at the total score . The over-all scale and each domain were prospect ively tested for validity , reliability , and responsiveness to clinical change . One hundred patients who were seen for evaluation of the shoulder were enrolled in the study . The validity of the scale was demonstrated by moderate-to-high correlation of the domains and individual questions of the Shoulder Rating Question naire with those of the Arthritis Impact Measurement Scales 2 . Validity was supported further by significant correlation of the scores in each domain with the level of satisfaction in that domain and by significantly lower scores in domains that patients selected as areas important for improvement . The over-all scale and each domain were internally consistent ( Cronbach alpha , 0.71 to 0.90 ) . Reproducibility was evaluated by repeated administration of the question naire after a mean of three days to forty patients whose condition was clinical ly stable . Reproducibility of the over-all question naire and individual domains was excellent ( Spearman-Brown index , 0.94 to 0.98 ) . Individual questions were reproducible , with a weighted kappa value of more than 0.7 for each . Responsiveness was evaluated by comparison of the preoperative and postoperative scores of thirty patients who had a satisfactory result one year after an operation on the shoulder . The over-all Shoulder Rating Question naire and each domain were responsive to clinical change as demonstrated by favorable st and ardized response means ( range , 1.1 to 1.9 ) and indices of responsiveness ( range , 1.1 to 2.0 ) . Similar analysis performed for individual diagnostic groups supported the validity , reliability , and responsiveness of the question naire in each group . The self-administered shoulder question naire was found to be valid , reliable , and responsive to clinical change . These qualities should make it a useful instrument for the prospect i ve assessment of the outcome of treatment of disorders related to the shoulder", "OBJECTIVE --To develop and vali date a question naire to quantify disability associated with shoulder symptoms . METHODS --A set of questions relevant to shoulder symptoms from a general disability interview was developed and the question naire applied to a cross-sectional population survey and a prospect i ve study of general practice attenders . Subjects included adults who reported current shoulder pain in a population survey and patients from three general practice s who attended with shoulder symptoms during a six month period . The main outcome measures were : frequency of problems with daily living related to shoulder symptoms , total score on 22-item disability question naire , and measures of shoulder movement . RESULTS --A higher proportion ( 80 % ) of patients attending their general practitioner with shoulder symptoms had five or more disabilities compared with subjects reporting shoulder pain in a community survey ( 34 % ) . The ranked frequency with which each disability was reported was similar in the two groups , although sleep disturbance was the most common problem in consulters . Self-reported disability is correlated with measures of restricted shoulder movement . CONCLUSION --This disability question naire was simple to complete and should prove useful for both general practice and population -based studies of shoulder pain", "The patient-oriented measures , represented by self-administered question naire , have become an important aspect of clinical outcome assessment . To be used with different language groups and in different countries , question naires must be translated and adapted to new cultural characteristics and then vali date d by a widely accepted process to evaluate reliability and validity , fundamental characteristic for each measure . The aim of the study is to perform the cross-cultural adaptation and to assess the Italian version instrument reliability and validity . The study design is a cross-cultural adaptation and cross-sectional study of a sample of patients affected by shoulder disorder with a sub sample followed prospect ively for retest reliability . The American Shoulder and Elbow Surgeons St and ardized Shoulder Assessment Form was culturally adapted for Italian-speaking people , following the simplified Guillemin criteria . Reliability and validity were assessed in a cross-sectional study of 50 consecutive patients affected by shoulder disorder . A sub- sample of 20 patients was followed prospect ively for retest reliability . The results were compared with other vali date d patient-oriented measures . The ASES scales showed a high correlation with other patient-oriented measures , as hypothesized , and it also showed good values with regard to reproducibility , consistency and validity , to the original versions published in English . These findings suggest that the evaluation capacities of the Italian version of ASES are equivalent to those of English language version", "Background . Existing measures of self‐reported shoulder function fail to measure effectively the full range of shoulder functioning . The classic approach for improving the reliability of a scale is adding items , but a scale with a substantial number of items imposes a large response burden on participants . A more efficient approach is to use modern psychometric methods to construct an adaptive scale in which patients respond only to items that are targeted at their level of shoulder function . Objectives . We developed a Flexilevel Scale of Shoulder Function ( FLEX‐SF ) . This scale includes three testlets that target low , medium , and high shoulder function . Scores on the testlets were equated to a common mathematical metric . Design and Subjects . We developed an initial pool of 68 items . This pool was administered to 400 patients , and responses were calibrated using a rating scale model . Subsets of items were identified for an easy , medium difficulty , and hard testlet . Properties of the scale were evaluated in a 3‐month longitudinal study of 200 shoulder patients . Results . The FLEX‐SF exhibited high reliability at both the scale level ( intraclass correlation coefficient [ 3,1 ] = 0.90 ) and specific trait levels . The validity of the FLEX‐SF was supported by its internal and external responsiveness ( Guyatt responsiveness index = 1.12 ) and the pattern of its associations with other health status measures . Conclusions . The FLEX‐SF can be used as a primary endpoint in clinical trials even when there are relatively few people in each treatment group . The scale also has excellent properties for use in clinical setting s tracking individual changes over time", "Background Various shoulder outcome instruments have been used despite lack of information on their measurement properties ; reliability , responsiveness , and validity ; and correlation with health-related quality of life . Hypothesis Most shoulder outcome instruments have poor correlation with Short Form−36 , a general measure of health-related quality of life , and with each other . Study Design Cohort study ( diagnosis ) ; Level of evidence , 2 . Methods A consecutive group of 285 patients who had undergone shoulder surgery completed several shoulder outcome instruments — Short Form−36 ; University of California , Los Angeles shoulder score ; American Shoulder and Elbow Surgeons shoulder evaluation form ; Constant score ; Simple Shoulder Test ; Western Ontario Shoulder Instability Index ; and the rating sheet for Bankart repair ( Rowe score)—preoperatively and at 3 , 6 , 9 , and 12 months postoperatively . Internal consistency , st and ardized response mean , effect size , and Pearson correlation were used to evaluate reliability , responsiveness , and validity . Results The American Shoulder and Elbow Surgeons form , Simple Shoulder Test , and Western Ontario Shoulder Instability Index displayed good internal consistency . The University of California , Los Angeles shoulder score and American Shoulder and Elbow Surgeons form exhibited good responsiveness , whereas Short Form−36 showed the least responsiveness . Pearson correlation coefficients between the shoulder outcome instruments and Short Form−36 were less than excellent ( r ) . Pearson correlation coefficients between the outcome instruments were generally low except for the Constant score and University of California , Los Angeles shoulder score ( r = .673 , P reflect health-related quality of life well and poorly correlated with each other . This meant that the comparison of a given surgical result with different outcome instruments might be of little practical utility . Further prospect i ve and serial studies should be conducted to develop better shoulder outcome instruments that have significant reliability , responsiveness , validity , and correlation with health-related quality of life . A careful combination of outcome instruments might be necessary to compensate the current evaluation systems", "A shoulder pain and disability index ( SPADI ) was developed to measure the pain and disability associated with shoulder pathology . The SPADI is a self-administered index consisting of 13 items divided into two subscales : pain and disability . Thirty-seven male patients with shoulder pain were used in a study to examine the measurement characteristics of the SPADI . Test-retest reliability of the SPADI total and subscale scores ranged from 0.6377 to 0.6552 . Internal consistency ranged from 0.8604 to 0.9507 . SPADI total and subscale scores were highly negatively correlated with shoulder range of motion ( ROM ) supporting the criterion validity of the index . Principal components factor analysis with and without varimax rotation supported the construct validity of the total SPADI and its subscales . High negative correlations between changes in SPADI scores and changes in shoulder ROM indicated the SPADI detected changes in clinical status over short time intervals . The SPADI should prove useful for both clinical and research purpose" ]

[ "BACKGROUND Antidepressant-induced mania ( AIM ) has been described in bipolar disorder ( BD ) and has been associated with the short-allele of the serotonin transporter gene ( 5-HTT ) . We wished to investigate the frequency of and risk factors for AIM in pediatric patients with or at high risk for BD . METHODS Fifty-two children and adolescents ( 30 with BD and 22 with subthreshold manic symptoms , 15.1 + /- 3.4 years old ) , all with a parent with BD , were interviewed with their parents for manic/depressive symptoms occurring before and after past antidepressant treatment . The 47 subjects with serotonin reuptake inhibitor ( SSRI ) exposure were genotyped for the 5-HTT polymorphism . RESULTS Fifty percent of subjects were AIM + and 25.5 % had new onset of suicidal ideation . The AIM + and AIM - groups did not differ significantly in relation to allele ( p = .36 ) or genotype ( p = .53 ) frequencies of the 5-HTT polymorphism . The AIM + subjects were more likely to have more comorbidities ( 3.2 vs. 2.4 ; p = .02 ) and be BD type I ( p = .04 ) than AIM - subjects . CONCLUSIONS Youth with or at high risk for BD may be particularly vulnerable to SSRI AIM and thus should be monitored if given SSRIs . In this preliminary study , we did not find that the 5-HTT polymorphism significantly influenced vulnerability to AIM", "Fatty acid effects on colorectal cancer risk were examined in a national prospect i ve case-control study in Scotl and ( 1999 - 2006 ) , including 1,455 incident cases and 1,455 matched controls . Three conditional logistic regression models adjusted for energy ( residual method ) and for other risk factors were applied in the whole sample and were stratified by sex , cancer site , age , and tumor staging . Total and trans-monounsaturated fatty acids and palmitic , stearic , and oleic acids were dose-dependently associated with colorectal cancer risk , but these effects did not persist after further energy adjustment . Significant dose-dependent reductions in risk were associated with increased consumption of omega-3 polyunsaturated fatty acids ( highest vs. lowest quartile of intake : odds ratio = 0.63 , 95 % confidence interval : 0.50 , 0.80 ; p eicosapentaenoic ( odds ratio = 0.59 , 95 % confidence interval : 0.47 , 0.75 ; p docosahexaenoic ( odds ratio = 0.63 , 95 % confidence interval : 0.50 , 0.80 ; p < 0.0005 for trend ) acids . These associations persisted after including energy with the nutrient-energy-adjusted term or total fatty acid intake ( energy adjusted ) . The observed different effects of different types of fatty acids underline the importance of type of fat in the etiology and prevention of colorectal cancer", "This study investigated effects of PUFA and micronutrient supplementation on cognition in children with ADHD symptoms . In a r and omised controlled trial , 7 - 12-year-old children with symptoms 2 S.D. on Conners ' ADHD Index were given PUFA , PUFA+multivitamins/minerals ( MVM ) , or placebo for 15 weeks , and then all children were given PUFA+MVM for an additional 15 weeks . After 15 weeks there were improvements in a test of the ability to switch and control attention ( Creature Counting ) in the PUFA groups compared to placebo ( N=129 , p=0.002 ) . This improvement was also observed in the placebo group after taking PUFA from weeks 16 to 30 ( N=104 ) . There were no significant improvements in other cognitive measures , or with additional micronutrient supplementation . However , improvements in cognitive performance mediated previous parent-reported improvements in inattention , hyperactivity and impulsivity [ N. Sinn , J. Bryan , Effect of supplementation with polyunsaturated fatty acids and micronutrients on ADHD-related problems with attention and behaviour , J. Dev . Behav . Pediatr . 28 ( 2 ) ( 2007 ) 82 - 91 ] , suggestive of a common neurological mechanism for these symptoms", "Attention deficit/hyperactivity disorder ( ADHD ) , a common behavioural disorder in children , may be associated with comorbid physical and sleep complaints . Dietary intervention studies have shown convincing evidence of efficacy in reducing ADHD symptoms in children . In this pilot study , we investigated the effects of an elimination diet on physical and sleep complaints in children with ADHD . A group of 27 children ( 3.8–8.5 years old ) , who all met the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria for ADHD , were assigned r and omly to either a diet group ( 15/27 ) or a control group ( 12/27 ) . The diet group followed a 5-week elimination diet ; the control group adhered to their normal diet . Parents of both groups had to keep an extended diary and had to monitor the behaviour and the physical and sleep complaints of their child conscientiously . The primary endpoint was the clinical response , i.e. a decrease of physical and sleep complaints , at the end of the trial , based on parent ratings on a Physical Complaints Question naire . The number of physical and sleep complaints was significantly decreased in the diet group compared to the control group ( p : headaches or bellyaches , unusual thirst or unusual perspiration , and sleep complaints . The reduction of complaints seemed to occur independently of the behavioural changes ( p = 0.1 ) . However , the power of this comparison was low . A positive correlation existed between the reduction of physical and behavioural symptoms ( p children with or without an atopic constitution ( p = 0.7 ) . An elimination diet may be an effective instrument to reduce physical complaints in children with ADHD , but more research is needed to determine the effects of food on ( functional ) somatic symptoms in children with and without ADHD . This trial was registered as an International St and ard R and omised Controlled Trial , IS RCT N47247160", "Low dietary intakes of the n-3 long-chain PUFA ( LCPUFA ) EPA and DHA are thought to be associated with increased risk for a variety of adverse outcomes , including some psychiatric disorders . Evidence from observational and intervention studies for a role of n-3 LCPUFA in depression is mixed , with some support for a benefit of EPA and /or DHA in major depressive illness . The present study was a double-blind r and omised controlled trial that evaluated the effects of EPA+DHA supplementation ( 1.5 g/d ) on mood and cognitive function in mild to moderately depressed individuals . Of 218 participants who entered the trial , 190 completed the planned 12 weeks intervention . Compliance , confirmed by plasma fatty acid concentrations , was good , but there was no evidence of a difference between supplemented and placebo groups in the primary outcome - namely , the depression subscale of the Depression Anxiety and Stress Scales at 12 weeks . Mean depression score was 8.4 for the EPA+DHA group and 9.6 for the placebo group , with an adjusted difference of - 1.0 ( 95 % CI - 2.8 , 0.8 ; P = 0.27 ) . Other measures of mood , mental health and cognitive function , including Beck Depression Inventory score and attentional bias toward threat words , were similarly little affected by the intervention . In conclusion , substantially increasing EPA+DHA intake for 3 months was found not to have beneficial or harmful effects on mood in mild to moderate depression . Adding the present result to a meta- analysis of previous relevant r and omised controlled trial results confirmed an overall negligible benefit of n-3 LCPUFA supplementation for depressed mood", "Studies on formula-fed infants indicate a beneficial effect of dietary DHA on visual acuity . Cross-sectional studies have shown an association between breast-milk DHA levels and visual acuity in breast-fed infants . The objective in this study was to evaluate the biochemical and functional effects of fish oil ( FO ) supplements in lactating mothers . In this double-blinded r and omized trial , Danish mothers with habitual fish intake below the 50th percentile of the Danish National Birth Cohort were r and omized to microencapsulated FO [ 1.3 g/d long-chain n−3 FA ( n−3 LCPUFA ) ] or olive oil ( OO ) . The intervention started within a week after delivery and lasted 4 mon . Mothers with habitual high fish intake and their infants were included as a reference group . Ninety-seven infants completed the trial ( 44 OO-group , 53 FO-group ) and 47 reference infants were followed up . The primary outcome measures were : DHA content of milk sample s ( 0 , 2 , and 4 mon postnatal ) and of infant red blood cell ( RBC ) membranes ( 4 mon postnatal ) , and infant visual acuity ( measured by swept visual evoked potential at 2 and 4 mon of age ) . FO supplementation gave rise to a threefold increase in the DHA content of the 4-mon milk sample s ( P RBC reflected milk contents ( r=0.564 , P ) . Infant visual acuity was not significantly different in the r and omized groups but was positively associated at 4 mon with infant RBC-DHA ( P=0.004 , multiple regression ) . We concluded that maternal FO supplementation during lactation did not enhance visual acuity of the infants who completed the intervention . However , the results showed that infants with higher RBC levels of n−3 LCPUFA had a better visual acuity at 4 mon of age , suggesting that n−3 LCPUFA may influence visual maturation ", "BACKGROUND Regular consumption of n-3 fatty acids of marine origin can improve serum lipids and reduce cardiovascular risk . OBJECTIVE This study aim ed to determine whether eicosapentaenoic ( EPA ) and docosahexaenoic ( DHA ) acids have differential effects on serum lipids and lipoproteins , glucose , and insulin in humans . DESIGN In a double-blind , placebo-controlled trial of parallel design , 59 overweight , nonsmoking , mildly hyperlipidemic men were r and omly assigned to receive 4 g purified EPA , DHA , or olive oil ( placebo ) daily while continuing their usual diets for 6 wk . RESULTS Fifty-six men aged 48.8 + /- 1.1 y completed the study . Relative to those in the olive oil group , triacylglycerols fell by 0.45 + /- 0.15 mmol/L ( approximately 20 % ; P = 0.003 ) in the DHA group and by 0.37 + /- 0.14 mmol/L ( approximately 18 % ; P = 0.012 ) in the EPA group . Neither EPA nor DHA had any effect on total cholesterol . LDL , HDL , and HDL(2 ) cholesterol were not affected significantly by EPA , but HDL(3 ) cholesterol decreased significantly ( 6.7 % ; P = 0.032 ) . Although HDL cholesterol was not significantly increased by DHA ( 3 . 1 % ) , HDL(2 ) cholesterol increased by approximately 29 % ( P = 0.004 ) . DHA increased LDL cholesterol by 8 % ( P = 0.019 ) . Adjusted LDL particle size increased by 0.25 + /- 0.08 nm ( P = 0.002 ) with DHA but not with EPA . EPA supplementation increased plasma and platelet phospholipid EPA but reduced DHA . DHA supplementation increased DHA and EPA in plasma and platelet phospholipids . Both EPA and DHA increased fasting insulin significantly . EPA , but not DHA , tended to increase fasting glucose , but not significantly so . CONCLUSIONS EPA and DHA had differential effects on lipids , fatty acids , and glucose metabolism in overweight men with mild hyperlipidemia", "Patients with depression have been extensively reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids ( PUFAs ) , including significantly low eicosapentaenoic acid and docosahexaenoic acid in cell tissue contents ( red blood cell membrane , plasma , etc . ) and dietary intake . However , more evidence is needed to support its relation . In this study , we conducted an 8-week , double-blind , placebo-controlled trial , comparing omega-3 PUFAs ( 6.6 g/day ) [ corrected ] with placebo , on the top of the usual treatment , in 28 patients with major depressive disorder . Patients in the omega-3 PUFA group had a significantly decreased score on the 21-item Hamilton Rating Scale for Depression than those in the placebo group ( P omega-3 PUFAs could improve the short-term course of illness and were well tolerated in patients with major depressive disorder", "BACKGROUND Omega3 fatty acids may inhibit neuronal signal transduction pathways in a manner similar to that of lithium carbonate and valproate , 2 effective treatments for bipolar disorder . The present study was performed to examine whether omega3 fatty acids also exhibit mood-stabilizing properties in bipolar disorder . METHODS A 4-month , double-blind , placebo-controlled study , comparing omega3 fatty acids ( 9.6 g/d ) vs placebo ( olive oil ) , in addition to usual treatment , in 30 patients with bipolar disorder . RESULTS A Kaplan-Meier survival analysis of the cohort found that the omega3 fatty acid patient group had a significantly longer period of remission than the placebo group ( P = .002 ; Mantel-Cox ) . In addition , for nearly every other outcome measure , the omega3 fatty acid group performed better than the placebo group . CONCLUSION Omega3 fatty acids were well tolerated and improved the short-term course of illness in this preliminary study of patients with bipolar disorder", "Objective Recent observations showed that long chain omega 3 polyunsaturated fatty acids ( n-3 LCPUFA ) could represent a potential treatment for elderly depression . To determine if a n-3 LCPUFA containing supplement improves depressive symptoms , changes phospholipids acids profile and ameliorates Health related quality of life ( HRQoL ) in depressed elderly patients . Design Two-months , r and omized , double-blind , placebo-controlled trial . Setting Nursing home in Pavia , Italy . SubjectsForty-six depressed females , aged 66–95 years . Intervention22 depressed females were included in the intervention group ( n-3 group , that received 2.5 g/day of n-3 LCPUFA , with 1.67 grams of EPA and 0.83 grams of DHA ) , and 24 patients in the placebo group . The primary endpoint was the improvement of depressive symptoms as evaluated by Geriatric Depression Scale ( GDS ) . Secondary endpoints were the evaluation of modifications of erythrocyte membrane phospholipids fatty acid profile and of of HRQoL , by using the Short-Form 36-Item Health Survey ( SF-36 ) . All parameters were assessed before and after the treatment period of 8 weeks . Results The mean GDS at 2 months was significantly lowered only for the n-3 group . SF-36 physical and mental components were significantly increased in the intervention group . Compliance was good , as confirmed by erythrocyte membrane phospholipid FA concentrations , with significant increase of EPA and DHA in the intervention group . Conclusion The supplementation of n-3 LCPUFA in elderly female patients reduces the occurrence of depressive symptoms , improves phospholipids fatty acids profile and healthrelated quality of life ", "Purpose : To investigate the potential effect of dietary supplementation with omega-3 fatty acid on lipid composition of meibum , aqueous tear evaporation , and tear volume in patients with dry eye . Methods : In a pilot , prospect i ve , r and omized , double-masked study , patients with dry eye received a daily dose of fish oil , containing 450 mg of eicosapentaenoic acid , 300 mg of docosahexaenoic acid , and 1000 mg of flaxseed oil ( TheraTears Nutrition ; Advanced Vision Research , Woburn , MA ) for 90 days . There were 2 patient visits : baseline and final . At these visits , patients completed the ocular surface disease index to score subjective symptoms , and slit-lamp examinations , breakup time , corneal staining , Schirmer type I , fluorophotometry , evaporometry , and collection of meibomian gl and secretion sample s for lipid composition analysis were performed . Results : A total of 36 patients with dry eye completed the study . At the end of the study , 70 % of the patients became asymptomatic , whereas for the placebo group , 7 % of the symptomatic patients became asymptomatic . Schirmer testing and fluorophotometry suggested that the omega-3 supplement increased tear secretion . The lipid composition of the sample s collected from the omega-3 group was found to be very similar to that from the placebo group . No trends between groups were seen for other objective parameters . Conclusions : Dietary supplementation with omega-3 fatty acids in dry eye showed no significant effect in meibum lipid composition or aqueous tear evaporation rate . On the other h and , the average tear production and tear volume was increased in the omega-3 group as indicated by both Schirmer testing and fluorophotometry", "OBJECTIVES To compare the incidence and prevalence of bipolar disorder ( BD ) between adolescence and young adulthood ; to explore the stability and consequences of adolescent BD in young adulthood ; to determine the rate of switching from major depressive disorder ( MDD ) to BD ; and to evaluate the significance of subsyndromal BD ( SUB ) . METHODS A large , r and omly selected community sample ( n = 1,507 ) received diagnostic assessment s twice during adolescence , and a stratified subset ( n = 893 ) was assessed again at 24 years of age . In addition , direct interviews were conducted with all available first-degree relatives . Five mutually exclusive groups , based on diagnoses in adolescence , were compared : BD ( n = 17 ) , SUB ( n = 48 ) , MDD ( n = 275 ) , disruptive behavior disorder ( n = 49 ) , and no-disorder ( ND ) controls ( n = 307 ) . RESULTS Lifetime prevalence of BD was approximately 1 % during adolescence and 2 % , during young adulthood . Lifetime prevalence for SUB was approximately 5 % . Less than 1 % , of adolescents with MDD ' switched ' to BD by age 24 . Adolescents with BD had an elevated incidence of BD from 19 to 23 years , while adolescents with SUB exhibited elevated rates of MDD and anxiety disorders in young adulthood . BD and SUB groups both had elevated rates of antisocial symptoms and borderline personality symptoms . Compared to the ND group , adolescents with BD and SUB both showed significant impairment in psychosocial functioning and had higher mental-health treatment utilization at age 24 years of age . The relatives of adolescents with BD and SUB had elevated rates of MDD and anxiety disorders . The relatives of SUB prob and s had elevated BD , while the relatives of BD had elevated rates of SUB and borderline symptoms . CONCLUSIONS Adolescent BD showed significant continuity across developmental periods and was associated with adverse outcomes during young adulthood . Adolescent SUB was also associated with adverse outcomes in young adulthood , but was not associated with an increased incidence of BD . Due to high rates of comorbidity with other disorders , definitive conclusions regarding the specific clinical significance of SUB must await studies with larger numbers of ' pure ' SUB cases", "OBJECTIVE Data on outcome of juvenile onset bipolar disorder is limited . This study examined the course and outcome of bipolar disorder and assessed the rate and predictors of recovery and relapse in a sample of children and adolescents over a 4 - 5 year period . METHOD Twenty-five consecutively ascertained subjects ( 9 - 16 years ) with a diagnosis of mania ( mean duration at intake of 4.6 + /- 3.9 weeks ) , were comprehensively assessed at baseline and at 6-month intervals using the Diagnostic Interview for Children and Adolescents ( revised ) ( DICA-R ) , the Missouri Assessment for Genetic Interview in Children ( MAGIC ) , the Young 's Mania Rating Scale ( YMRS ) and the Children 's Global Assessment ( CGAS ) . The study phenotype required DSM-IV criteria of mania with elation and /or gr and iosity as a criterion to distinguish them from those with attention deficit hyperactivity disorder . Subjects received the st and ard treatment as prescribed by their primary treating team . RESULTS During the course of the study period , all 25 subjects ( 100 % ) recovered from the index episode . The mean time to recovery was 44 + /- 46 days . The mean duration of follow-up was 51.6 + /- 4.1 months . Sixteen subjects ( 64 % ) relapsed after a mean period of 18 + /- 16.4 months . A majority of the relapses ( 72.4 % ) were while the subjects were on treatment . CONCLUSIONS Acute juvenile onset mania has a high rate of recovery and low chronicity . The relapse rate was high and most of these occurred in the first 3 years despite aggressive prophylactic treatment . The effectiveness of currently used thymoleptics , in particular lithium , in the prophylaxis of juvenile bipolar disorder needs to be evaluated in controlled studies", "BACKGROUND Perinatal major depressive disorder ( MDD ) , including antenatal and postpartum depression , is common and has serious consequences . This study was design ed to investigate the feasibility , safety , and efficacy of omega-3 fatty acids for perinatal depression in addition to supportive psychotherapy . METHODS Perinatal women with MDD were r and omized to eicosapentaenoic ( EPA ) and docosahexaenoic acids ( DHA ) , 1.9g/day , or placebo for 8weeks . A manualized supportive psychotherapy was provided to all subjects . Symptoms were assessed with the Hamilton Rating Scale for Depression ( HAM-D ) and Edinburgh Postnatal Depression Scale ( EPDS ) biweekly . RESULTS Fifty-nine women enrolled ; N = 51 had two data collection points that allowed for evaluation of efficacy . Omega-3 fatty acids were well tolerated . Participants in both groups experienced significant decreases in EPDS and HAM-D scores ( p omega-3 fatty acids over placebo . Dietary omega-3 fatty acid intake was low among participants . LIMITATIONS The ability to detect an effect of omega-3 fatty acids may have been limited by sample size , study length , or dose . The benefits of supportive psychotherapy may have limited the ability to detect an effect of omega-3 fatty acids . CONCLUSIONS There was no significant difference between omega-3 fatty acids and placebo in this study in which all participants received supportive psychotherapy . The manualized supportive psychotherapy warrants further study . The low intake of dietary omega-3 fatty acids among participants is of concern , in consideration of the widely established health advantages in utero and in infants", "BACKGROUND Diagnosis of child mania has been contentious . OBJECTIVE To investigate natural history and prospect i ve validation of the existence and long-episode duration of mania in children . DESIGN Four-year prospect i ve longitudinal study of 86 subjects with intake episode mania who were all assessed at 6 , 12 , 18 , 24 , 36 , and 48 months . The phenotype was defined as DSM-IV bipolar I disorder ( manic or mixed ) with at least 1 cardinal symptom ( elation and /or gr and iosity ) to ensure differentiation from attention-deficit/hyperactivity disorder . Parent and child informants were separately interviewed , by highly experienced research nurses , using the Washington University in St Louis Kiddie Schedule for Affective Disorders and Schizophrenia ( WASH-U-KSADS ) . A Children 's Global Assessment Scale score of 60 or less was needed to establish definite impairment . Treatment was by subjects ' community practitioners . SETTING Research unit in a university medical school . PARTICIPANTS Subjects were obtained from psychiatric and pediatric sites by consecutive new case ascertainment , and their baseline age was 10.8 + /- 2.7 years . Onset of the baseline episode was 7.4 + /- 3.5 years . ( Data are given as mean + /- SD . ) MAIN OUTCOME MEASURES Episode duration , weeks ill , recovery/relapse rates , and outcome predictors . RESULTS Prospect i ve episode duration of manic diagnoses , using onset of mania as baseline date , was 79.2 + /- 66.7 consecutive weeks . Any bipolar disorder diagnosis occurred during 67.1 % + /- 28.5 % of total weeks , during the 209.4 + /- 3.3 weeks of follow-up . Subjects spent 56.9 % + /- 28.8 % of total weeks with mania or hypomania ( unipolar or mixed ) , and 38.7 % + /- 28.8 % of these were with mania . Major or minor depression and dysthymia ( unipolar or mixed ) occurred during 47.1 % + /- 30.4 % of total weeks . Polarity switches occurred 1.1 + /- 0.7 times per year . Low maternal warmth predicted faster relapse after recovery from mania ( chi(2 ) = 13.6 , P = .0002 ) , and psychosis predicted more weeks ill with mania or hypomania ( F(1,80 ) = 12.2 , P = .0008 ) . Pubertal status and sex were not predictive . ( Data are given as mean + /- SD . ) CONCLUSIONS These findings vali date the existence , long-episode duration , and chronicity of child mania . Differences from the natural history of adult bipolar disorder are discussed", "BACKGROUND Epidemiologic studies of fish consumption in relation to risk of stroke have yielded inconsistent results . OBJECTIVE In this study , we examined the association between fish consumption and stroke incidence in women . DESIGN We analyzed data from a population -based prospect i ve cohort of 34,670 women in the Swedish Mammography Cohort who were free of cardiovascular disease and cancer at baseline . Information on fish consumption was obtained by a self-administered question naire in 1997 . Incident cases of stroke were ascertained from the Swedish Hospital Discharge Registry . We used Cox proportional hazards regression to estimate relative risks ( RRs ) and 95 % CIs . RESULTS Over a mean follow-up of 10.4 y , we ascertained 1680 incident cases of stroke , including 1310 cerebral infa rct ions , 233 hemorrhagic strokes , and 137 unspecified strokes . Fish consumption was significantly inversely associated with risk of total stroke but not with cerebral infa rct ion or hemorrhagic stroke . Compared with women in the lowest quintile of fish consumption ( multivariable RR of total stroke for women in the highest quintile ( > 3.0 servings of fish/wk ) was 0.84 ( 95 % CI : 0.71 , 0.98 ; P for trend = 0.049 ) . Consumption of lean fish but not of other fish types was inversely associated with risk of stroke . The multivariable RR of total stroke was 0.67 ( 95 % CI : 0.49 , 0.93 ; P for trend = 0.07 ) for ≥3 servings of lean fish/wk compared with that for no consumption . CONCLUSION These results suggest that the consumption of fish , especially of lean fish , may reduce risk of stroke in women . This trial was registered at clinical trials.gov as NCT01127698", "CONTEXT Despite the high morbidity associated with bipolar disorder ( BP ) , few studies have prospect ively studied the course of this illness in youth . OBJECTIVE To assess the longitudinal course of BP spectrum disorders ( BP-I , BP-II , and not otherwise specified [ BP-NOS ] ) in children and adolescents . DESIGN Subjects were interviewed , on average , every 9 months for an average of 2 years using the Longitudinal Interval Follow-up Evaluation . SETTING Outpatient and inpatient units at 3 university centers . PARTICIPANTS Two hundred sixty-three children and adolescents ( mean age , 13 years ) with BP-I ( n = 152 ) , BP-II ( n = 19 ) , and BP-NOS ( n = 92 ) . MAIN OUTCOME MEASURES Rates of recovery and recurrence , weeks with syndromal or subsyndromal mood symptoms , changes in symptoms and polarity , and predictors of outcome . RESULTS Approximately 70 % of subjects with BP recovered from their index episode , and 50 % had at least 1 syndromal recurrence , particularly depressive episodes . Analyses of weekly mood symptoms showed that 60 % of the follow-up time , subjects had syndromal or subsyndromal symptoms with numerous changes in symptoms and shifts of polarity , and 3 % of the time , psychosis . Twenty percent of BP-II subjects converted to BP-I , and 25 % of BP-NOS subjects converted to BP-I or BP-II . Early-onset BP , BP-NOS , long duration of mood symptoms , low socioeconomic status , and psychosis were associated with poorer outcomes and rapid mood changes . Secondary analyses comparing BP-I youths with BP-I adults showed that youths significantly more time symptomatic and had more mixed/cycling episodes , mood symptom changes , and polarity switches . CONCLUSIONS Youths with BP spectrum disorders showed a continuum of BP symptom severity from subsyndromal to full syndromal with frequent mood fluctuations . Results of this study provide preliminary validation for BP-NOS", "INTRODUCTION Epidemiologic studies have suggested that consumption of cold water fish oils may have some protective function against depression . This proposition is supported by a series of biochemical and pharmacologic studies that have suggested that fatty acids may modulate neurotransmitter metabolism and cell signal trans-duction in humans and that abnormalities in fatty acid and eicosanoid metabolism may play a causal role in depression . Aware of the critical need for antidepression treatments that might not carry the risk of precipitating a manic episode in bipolar patients , we decided to conduct an open-label add-on trial of eicosapentaenoic acid ( EPA ) in bipolar depression . METHOD Twelve bipolar I out patients with depressive symptoms diagnosed by DSM-IV were treated with 1.5 to 2 g/day of the omega-3 fatty acid EPA for up to 6 months . The study was conducted between September 2001 and January 2003 . RESULTS Eight of the 10 patients who completed at least 1 month of follow-up achieved a 50 % or greater reduction in Hamilton Rating Scale for Depression scores within 1 month . No patients developed hypomania or manic symptoms . No significant side effects were reported . LIMITATIONS This study is limited both by the open-label design and by the small sample size . As in all previous reported studies , patients in this study were treated in an outpatient setting , so that the most severely depressed bipolar patients ( requiring hospitalization ) are not represented . CONCLUSIONS Although the ultimate utility of omega-3 fatty acids in bipolar depression is still an open question , we believe that these initial results are encouraging , especially for mild to moderate bipolar depression , and justify the continuing exploration of its use", "OBJECTIVE This study determined if augmentation of neuroleptics with 3 g/day of ethyl eicosapentaenoic acid ( EPA ) improves symptoms and cognition in patients with schizophrenia or schizoaffective disorder . METHOD Eighty-seven patients meeting criteria for schizophrenia or schizoaffective disorder who had residual symptoms despite neuroleptic treatment were r and omly assigned to receive either 3 g/day of ethyl EPA ( N=43 ) or placebo ( N=44 ) in a 16-week , double-blind supplementation trial . Assessment s were performed at baseline and at weeks 1 , 2 , 4 , 8 , 12 , and 16 ; a cognitive battery was administered at baseline and at week 16 . RESULTS No differences were found between groups in positive or negative symptoms , mood , cognition , or global impression ratings . Results were similar for the intention-to-treat ( N=87 ) and completer ( N=75 ) groups . CONCLUSIONS For schizophrenia patients treated with 3 g/day of ethyl EPA , improvement in residual symptoms and cognitive impairment was no greater than for schizophrenia patients treated with placebo", "OBJECTIVE The purpose of this study was to determine the effect of docosahexaenoic acid supplementation on plasma phospholipid docosahexaenoic acid content and indices of depression and information processing for women who breast-feed . STUDY DESIGN Mothers who planned to breast-feed their infants were assigned r and omly in a double-masked fashion to receive either docosahexaenoic acid ( approximately 200 mg/d ) or placebo for the first 4 months after the delivery . Major outcome variables included plasma phospholipid fatty acid patterns and scores on a self-rating question naire of current depression symptoms . A structured clinical interview of depression , scores on another self-rating question naire of depression symptoms , and a laboratory measure of information processing were obtained in subgroups of the total population . RESULTS Plasma phospholipid contents of docosahexaenoic acid at baseline were 3.15 + /- 0.78 and 3.31 + /- 0.70 ( mg/dL of total fatty acids ) in the docosahexaenoic acid and placebo groups , respectively . After 4 months , the plasma phospholipid docosahexaenoic acid content of the docosahexaenoic acid group was 8 % higher ( 3.40 + /- 0.97 mg/dL ) , whereas that of the placebo group was 31 % lower ( 2.27 + /- 0.87 mg/dL ) . Despite the higher plasma phospholipid docosahexaenoic acid content of the supplemented group after 4 months , there was no difference between groups in either self-rating or diagnostic measures of depression ; information processing scores of the two groups also did not differ . CONCLUSION Docosahexaenoic acid supplementation ( approximately 200 mg/d ) for 4 months after the delivery prevented the usual decline in plasma phospholipid docosahexaenoic acid content of women who breastfeed but did not influence self-ratings of depression , diagnostic measures of depression , or information processing", "OBJECTIVE Studies have reported that countries with high rates of fish oil consumption have low rates of depressive disorder . The authors studied a specific omega-3 fatty acid , the ethyl ester of eicosapentaenoic acid ( E-EPA ) , as an adjunct to treatment for depressive episodes occurring in patients with recurrent unipolar depressive disorder who were receiving maintenance antidepressant therapy . METHOD Twenty patients with a current diagnosis of major depressive disorder participated in a 4-week , parallel-group , double-blind addition of either placebo or E-EPA to ongoing antidepressant therapy . Seventeen of the patients were women , and three were men . RESULTS Highly significant benefits of the addition of the omega-3 fatty acid compared with placebo were found by week 3 of treatment . CONCLUSIONS It is not possible to distinguish whether E-EPA augments antidepressant action in the manner of lithium or has independent antidepressant properties of its own", "OBJECTIVE This study was an evaluation of the omega-3 fatty acid docosahexaenoic acid ( DHA ) for the treatment of major depression . METHOD Thirty-six depressed patients were r and omly assigned to receive DHA , 2 g/day , or placebo for 6 weeks . Response was defined a priori as a > or = 50 % reduction in the score on the Montgomery-Asberg Depression Rating Scale . Thirty-five participants were evaluable ; 18 received DHA , and 17 received placebo . RESULTS Response rates were 27.8 % in the DHA group and 23.5 % in the placebo group . The difference in response rates between groups did not reach statistical significance . CONCLUSIONS This trial failed to show a significant effect of DHA monotherapy in subjects with major depression", "BACKGROUND Epidemiological and clinical studies suggest that increased intake of eicosapentaenoic acid ( EPA ) alleviates unipolar depression . AIMS To examine the efficacy of EPA in treating depression in bipolar disorder . METHOD In a12-week , double-blind study individuals with bipolar depression were r and omly assigned to adjunctive treatment with placebo ( n=26 ) or with 1 g/day ( n=24 ) or 2 g/day ( n=25 ) of ethyl-EPA . Primary efficacy was assessed by the Hamilton Rating Scale for Depression ( HRSD ) , with changes in the Young Mania Rating Scale and Clinical Global Impression Scale ( CGI ) as secondary outcome measures . RESULTS There was no apparent benefit of 2 g over 1 g ethyl-EPA daily . Significant improvement was noted with ethyl-EPA treatment compared with placebo in the HRSD ( P=0.04 ) and the CGI ( P=0.004 ) scores . Both doses were well tolerated . CONCLUSIONS Adjunctive ethyl-EPA is an effective and well-tolerated intervention in bipolar depression", "OBJECTIVE Utilizing data from a previously characterized registry of subjects with bipolar illness , the authors examined age at onset of the first illness episode in cohorts of subjects born from 1900 through 1939 and from 1940 through 1959 . METHOD Demographic and clinical characteristics at the first full episode of bipolar disorder of subjects in a diagnostically vali date d voluntary bipolar disorder registry ( N=1,218 ) were review ed and subjected to statistical analyses . RESULTS The median age at onset of the first episode of bipolar illness was lower by 4.5 years in subjects born during or after 1940 ( median age=19 years ) , compared with subjects born before 1940 ( median age=23.5 years ) . The proportion of subjects with bipolar disorder presenting with a prepubertal onset was significantly higher in the later birth-year cohort than in the earlier birth-year cohort . More than 50 % of male and female subjects in both cohorts had a depressive episode as the first episode of bipolar illness . Subjects in each cohort who had a parent with major depression , bipolar disorder , or schizophrenia experienced their first episode nearly 4 to 5 years earlier than the other subjects in the cohort . CONCLUSIONS Prospect i ve epidemiological studies conducted with bipolar disorder subjects are needed to either affirm or refute these data on age at illness onset . If the results are affirmed , the early recognition of prepubertal bipolar disorder will be important , so that the condition can be treated with appropriate medications and medications that could potentially worsen the illness course can be avoided . Similarly , early recognition of bipolar illness is important , especially in women , to minimize use of antidepressant monotherapy for patients with bipolar illness . Among young people presenting with major depression as the first illness episode , a parental history of major depression , bipolar disorder , or psychosis may be a useful pointer to future bipolar disorder . Early recognition and appropriate treatment of bipolar illness may prevent the development of chronicity and serious functional impairment", "Objective : The aim of the study was to assess omega 3/6 fatty acids ( eye q ) in attention deficit hyperactivity disorder ( ADHD ) . Method : The study included a r and omized , 3-month , omega 3/6 placebo-controlled , one-way crossover trial with 75 children and adolescents ( 8—18 years ) , followed by 3 months with omega 3/6 for all . Investigator-rated ADHD Rating Scale — IV and Clinical Global Impression ( CGI ) scale were outcome measures . Results : A majority did not respond to omega 3/6 treatment . However , a subgroup of 26 % responded with more than 25 % reduction of ADHD symptoms and a drop of CGI scores to the near-normal range . After 6 months , 47 % of all showed such improvement . Responders tended to have ADHD inattentive subtype and comorbid neurodevelopmental disorders . Conclusion : A subgroup of children and adolescents with ADHD , characterized by inattention and associated neurodevelopmental disorders , treated with omega 3/6 fatty acids for 6 months responded with meaningful reduction of ADHD symptoms . ( J. of Att . Dis . 2009 ; 12(5 ) 394 - 401", "BACKGROUND The results of pilot trials suggest that omega-3 fatty acids may have efficacy in the treatment of mood symptoms in bipolar disorder . METHODS We conducted a 4-month , r and omized , placebo-controlled , adjunctive trial of ethyl-eicosapentanoate ( EPA ) 6 g/day in the treatment of bipolar depression and rapid cycling bipolar disorder . Subjects were receiving mood-stabilizing medications at therapeutic doses or plasma concentrations . The measures of efficacy were early study discontinuation , changes from baseline in depressive symptoms ( Inventory for Depressive Symptomology total score ) and in manic symptoms ( Young Mania Rating Scale total score ) , and manic exacerbations ( \" switches \" ) . We also measured side effects and bleeding time , a biomarker of drug action . RESULTS Overall , there were no significant differences on any outcome measure between the EPA and placebo groups . CONCLUSIONS This study did not find overall evidence of efficacy for adjunctive treatment with EPA 6 g/day in out patients with bipolar depression or rapid cycling bipolar disorder", "OBJECTIVE The authors hypothesized that changes in brain membrane composition result ing from omega-3 fatty acid administration in patients with bipolar disorder would result in greater membrane fluidity , as detected by reductions in T(2 ) values . METHOD Women with bipolar disorder ( N=12 ) received omega-3 fatty acids for 4 weeks . A cohort of bipolar subjects ( N=9 ) and a group without bipolar disorder ( N=12 ) did not receive omega-3 fatty acids . T(2 ) values were acquired at baseline and after 4 weeks . RESULTS Bipolar subjects who received omega-3 fatty acids had significant decreases in T(2 ) . There was a dose-dependent effect when the bipolar omega-3 fatty acid group was subdivided into high- and low-dose cohorts . CONCLUSIONS Omega-3 fatty acids lowered T(2 ) values , consistent with the hypothesis that the fluidity of cell membranes was altered . Further studies are needed to clarify the significance of alterations in brain physiology induced by omega-3 fatty acids , as reflected in T(2 ) values", "Converging evidence suggests that omega-3 polyunsaturated fatty acids have aetiological importance in depression . To determine the effect of adding fish oil to existing therapy in participants who were being treated for depression in a community setting , 77 participants were r and omly assigned to receive 8 g of either fish or olive oil per day in addition to their existing therapy . Fifty-nine ( 77 % ) participants completed 12 weeks of treatment . Dietary , biochemical and lifestyle factors were measured throughout the study . Mood was assessed using the Short Form Hamilton Depression Rating Scale ( HDRS-SF ) and the Beck Depression Inventory II . Sample size calculations were based on the HDRS-SF . Intention-to-treat and per protocol analyses were carried out using residual maximum likelihood . There was no evidence that fish oil improved mood when compared to the placebo oil , despite an increase in circulating omega-3 polyunsaturated fatty acids . However , mood improved significantly in both groups within the first 2 weeks of the study ( P depression in this setting", "Dietary deficiencies in essential omega-3 polyunsaturated fatty acids derived from fish are associated with depression and some fish oils may have therapeutic benefits . We aim ed to determine whether taking tuna fish oil confers any additional benefit to conventional outpatient treatment for major depression . A r and omized double-blind placebo-controlled four-month trial comparing tuna fish oil versus placebo was conducted on 83 out patients with major depression . Despite large reductions in depression there were no significant differences at any assessment time point between patients receiving fish oil compared to placebo . Red blood cell incorporation of fatty acids indicated good compliance with oil supplementation , although this sample was not initially deficient in omega-3s . This particular dose and type of fish oil conferred no additional benefit to conventional treatment of depression in this sample . Future studies could target participants with pre-existing omega-3 deficiency and appraise alternate enriched types and higher doses of omega-3 supplementation", "BACKGROUND In depressed patients , low blood levels of eicosapentaenoic acid are seen . We tested the antidepressive effect of ethyl-eicosapentaenoate in these patients . METHODS We included 70 patients with persistant depression despite ongoing treatment with an adequate dose of a st and ard antidepressant . Patients were r and omized on a double-blind basis to placebo or ethyl-eicosapentaenoate at dosages of 1 , 2 , or 4 g/d for 12 weeks in addition to unchanged background medication . Patients underwent assessment using the 17-item Hamilton Depression Rating Scale , the Montgomery-Asberg Depression Rating Scale , and the Beck Depression Inventory . RESULTS Forty-six ( 88 % ) of 52 patients receiving ethyl-eicosapentaenoate and 14 ( 78 % ) of 18 patients receiving placebo completed the 12-week study with no serious adverse events . The 1-g/d group showed a significantly better outcome than the placebo group on all 3 rating scales . In the intention-to-treat group , 5 ( 29 % ) of 17 patients receiving placebo and 9 ( 53 % ) of 17 patients receiving 1 g/d of ethyl-eicosapentaenoate achieved a 50 % reduction on the Hamilton Depression Rating Scale score . In the per- protocol group , the corresponding figures were 3 ( 25 % ) of 12 patients for placebo and 9 ( 69 % ) of 13 patients for the 1-g/d group . The 2-g/d group showed little evidence of efficacy , whereas the 4-g/d group showed nonsignificant trends toward improvement . All of the individual items on all 3 rating scales improved with the 1-g/d dosage of ethyl-eicosapentaenoate vs placebo , with strong beneficial effects on items rating depression , anxiety , sleep , lassitude , libido , and suicidality . CONCLUSION Treatment with ethyl-eicosapentaenoate at a dosage of 1 g/d was effective in treating depression in patients who remained depressed despite adequate st and ard therapy", "OBJECTIVE To determine whether docosahexaenoic acid ( DHA ) is related to visual and neural development in term breast-fed infants . DESIGN A prospect i ve study of 83 infants who were exclusively breast-fed for at least 3 months . We determined red blood cell and plasma fatty acids at 2 months , visual acuity at 2 , 4 , 6 , and 12 months , speech perception and an object search task at 9 months , Bayley 's mental development index and psychomotor development index at 6 and 12 months , and novelty pReference at 6 and 9 months . RESULTS The infant red blood cell phosphatidylethanolamine DHA was significantly related to visual acuity at 2 months of age ( r = 0.32 , P = .01 ) and 12 months of age ( r = 0.30 , P = .03 ) . The ability to discriminate nonnative retroflex and phonetic contrasts at 9 months of age was related to the plasma phospholipid DHA ( r = 0.48 , P DHA may influence the development of visual acuity and neural pathways associated with the developmental progression of language acquisition in term breast-fed infants . The extent to which our results can be attributed solely to DHA from maternal sources through breast milk or in gestation or other confounding factors remains to be determined", "OBJECTIVE Symptoms of bipolar disorder are increasingly recognized among children and adolescents , but little is known about the course of bipolar disorder among adults who experience childhood onset of symptoms . METHODS We examined prospect i ve outcomes during up to two years of naturalistic treatment among 3,658 adult bipolar I and II out patients participating in a multicenter clinical effectiveness study , the Systematic Treatment Enhancement Program for Bipolar Disorder ( STEP-BD ) . Age at illness onset was identified retrospectively by clinician assessment at study entry . RESULTS Compared to patients with onset of mood symptoms after age 18 years ( n = 1,187 ) , those with onset before age 13 years ( n = 1,068 ) experienced earlier recurrence of mood episodes after initial remission , fewer days of euthymia , and greater impairment in functioning and quality of life over the two-year follow-up . Outcomes for those with onset between age 13 and 18 years ( n = 1,403 ) were generally intermediate between these two groups . CONCLUSION Consistent with previous reports in smaller cohorts , adults with retrospectively obtained early-onset bipolar disorder appear to be at greater risk for recurrence , chronicity of mood symptoms , and functional impairment during prospect i ve observation", "Objective : Epidemiological , biological marker and treatment studies , as well as neuroscientific theories , indicate a possible link between omega-3 fatty acids and perinatal depression ( PND ) . Hence the aim of the present study was to assess whether omega-3 fatty acid treatment is superior to placebo in the treatment of PND . Method : A double-blind r and omized placebo-controlled trial was undertaken . Women with major depression during the perinatal period received either fish oil or placebo for six weeks . Changes in depression scores were recorded weekly . Results : A total of 26 subjects were recruited and there was no significant difference in depression scores between those receiving fish oil and those receiving the placebo . Conclusions : This is formally a negative study , suggesting that there is no benefit for omega-3 fatty acids over placebo in treating PND . The reason could be that the study was underpowered due to recruitment difficulties and therefore we suggest that it may be unwise to interpret this result as conclusive . Omega-3 is a natural product that is a safe and well-tolerated treatment . Further research is therefore needed in this area to establish whether omega-3 fatty acids are an effective treatment for PND", "OBJECTIVE To perform a double-blind , placebo-controlled , r and om assignment , parallel group , pharmacokinetically dosed study of lithium for adolescents with bipolar disorders ( BP ) and temporally secondary substance dependency disorders ( SDD ) . METHOD Subjects were 16.3 + /- 1.2 years old and were comprehensively assessed during a 6-week outpatient protocol that included r and om weekly urine collection for drug assays and r and om and weekly serum collection for lithium levels . RESULTS Using both intent-to-treat ( N = 25 ) and completer ( n = 21 ) analyses , there were significant differences on continuous and categorical measures between the active and placebo groups for both psychopathology measures and weekly r and om urine drug assays . The mean scheduled weekly serum lithium level of active responders was 0.9 mEq/L. Addiction to both alcohol and marijuana was the most frequent category of SDD . Mean age at onset of BP was 9.6 + /- 3.9 years and of SDD was 15.3 + /- 1.3 years . There were multigenerational mood disorders in 96 % and multigenerational SDD in 56 % of families . CONCLUSIONS Lithium treatment of BP with secondary SDD in adolescents was an efficacious treatment for both disorders . These results warrant replication with a long-term maintenance phase . The mean 6-year interval between the onset of BP and onset of SDD strongly argues for earliest recognition of BP", "OBJECTIVE This study evaluated the safety and effectiveness of divalproex sodium ( Depakote ) in the treatment of youths with bipolar disorder . METHOD Forty bipolar disorder patients aged 7 to 19 years , with a manic , hypomanic , or mixed episode , enrolled in an open-label study of divalproex ( 2 - 8 weeks ) , followed by a double-blind , placebo-controlled period ( 8 weeks ) . RESULTS Twenty-two subjects ( 61 % ) showed > or = 50 % improvement in Mania Rating Scale ( MRS ) scores during the open-label period . Significant ( all efficacy measures , including the MRS , Manic Syndrome Scale , Behavior and Ideation Scale , Brief Psychiatric Rating Scale , Clinical Global Impressions Severity scale , and Hamilton Rating Scale for Depression . Of the 23 subjects who discontinued the study during the open-label period , 6 ( 15 % ) discontinued for ineffectiveness , 6 ( 15 % ) for intolerance , 6 ( 15 % ) for noncompliance , and 6 ( 15 % ) for other reasons . Adverse events were generally mild or moderate in severity , with the most common being headache , nausea , vomiting , diarrhea , and somnolence . Laboratory data results were unremarkable . Too few subjects participated in the double-blind period for statistical analysis . CONCLUSION This study provides preliminary support for the safety and effectiveness of divalproex in the treatment of bipolar disorder in youths", "Objective : To compare therapeutic effects of eicosapentaenoic acid ( EPA ) , fluoxetine and a combination of them in major depression . Method : Sixty out patients with a diagnosis of major depressive disorder based on DSM-IV criteria and a score ≥15 in the 17-item Hamilton Depression Rating Scale ( HDRS ) were r and omly allocated to receive daily either 1000 mg EPA or 20 mg fluoxetine , or their combination for 8 weeks . Double dummy technique was used to double blind the study . Patients were assessed at 2 week intervals . Change in HDRS was the primary outcome measure . Results : Analysis of covariance for HDRS at week 8 across treatment groups was performed in 48 patients who completed at least 4 weeks of the study , with the last observation carried forward . Treatment , age of onset and baseline HDRS had a significant effect on HDRS at week 8 . EPA + fluoxetine combination was significantly better than fluoxetine or EPA alone from the fourth week of treatment . Fluoxetine and EPA appear to be equally effective in controlling depressive symptoms . Response rates ( ≥50 % decrease in baseline HDRS ) were 50 % , 56 % and 81 % in the fluoxetine , EPA and combination groups , respectively . Conclusions : In the present 8 week trial EPA and fluoxetine had equal therapeutic effects in major depressive disorder . EPA + fluoxetine combination was superior to either of them alone", "Essential fatty acids ( EFA ) are needed for normal sensory , cognitive , and motor function . The EFA blood profile seems to be different in children with attention-deficit/hyperactivity disorder ( ADHD ) as compared to matched controls . Previous open EFA supplementation trials were successful in demonstrating significant therapeutic effects in this population , whereas most of the r and omized controlled trials failed to show any benefit over placebo . The current r and omized , double-blind , placebo-controlled trial tested the influence of short-chain EFA supplementation on ADHD children , using parent and teacher question naires and a computerized continuous performance test . A total of 73 unmedicated children aged 7 - 13 years with a diagnosis of ADHD participated in the study ; 63 children completed the study . The EFA supplement contained 480 mg of linoleic acid and 120 mg of alpha-linolenic acid , and the placebo contained 1000 mg of vitamin C ( daily amounts ) ; both were given for a 7-week supplementation period . Analysis of variance for repeated measures revealed that both treatments ameliorated some of the symptoms , but no significant differences were found between the groups in any of the treatment effects" ]

[ "Background Patients with schizophrenia have lower longevity than the general population as a consequence of a combination of risk factors connected to the disease , lifestyle and the use of medications , which are related to weight gain . Methods A multicentric , r and omized , controlled-trial was conducted to test the efficacy of a 12-week group Lifestyle Wellness Program ( LWP ) . The program consists of a one-hour weekly session to discuss topics like dietary choices , lifestyle , physical activity and self-esteem with patients and their relatives . Patients were r and omized into two groups : st and ard care ( SC ) and st and ard care plus intervention ( LWP ) . Primary outcome was defined as the weight and body mass index ( BMI ) . Results 160 patients participated in the study ( 81 in the intervention group and 79 in the SC group ) . On an intent to treat analysis , after three months the patients in the intervention group presented a decrease of 0.48 kg ( CI 95 % -0.65 to 1.13 ) while the st and ard care group showed an increase of 0.48 kg ( CI 95 % 0.13 to 0.83 ; p=0.055 ) . At six-month follow-up , there was a significant weight decrease of −1.15 kg , ( CI 95 % -2.11 to 0.19 ) in the intervention group compared to a weight increase in the st and ard care group ( + 0.5 kg , CI 95 % -0.42–1.42 , p=0.017 ) . Conclusion In conclusion , this was a multicentric r and omized clinical trial with a lifestyle intervention for individuals with schizophrenia , where the intervention group maintained weight and presented a tendency to decrease weight after 6 months . It is reasonable to suppose that lifestyle interventions may be important long-term strategies to avoid the tendency of these individuals to increase weight . Clinical trials.gov", "BACKGROUND People with schizophrenia have significantly raised mortality but we do not know how these mortality patterns in the UK have changed since the 1990s . AIMS To measure the 25-year mortality of people with schizophrenia with particular focus on changes over time . METHOD Prospect i ve record linkage study of the mortality of a community cohort of 370 people with schizophrenia . RESULTS The cohort had an all-cause st and ardised mortality ratio of 289 ( 95 % CI 247 - 337 ) . Most deaths were from the common causes seen in the general population . Unnatural deaths were concentrated in the first 5 years of follow-up . There was an indication that cardiovascular mortality may have increased relative to the general population ( P = 0.053 ) over the course of the study . CONCLUSIONS People with schizophrenia have a mortality risk that is two to three times that of the general population . Most of the extra deaths are from natural causes . The apparent increase in cardiovascular mortality relative to the general population should be of concern to anyone with an interest in mental health", "Clozapine is associated with significant weight gain and metabolic disturbances . This multicentre , r and omized study comprised a double-blind , placebo-controlled treatment phase of 16 wk , and an open-label extension phase of 12 wk . Out patients who met DSM-IV-TR criteria for schizophrenia , who were not optimally controlled while on stable dosage of clozapine for > or =3 months and had experienced weight gain of > or = 2.5 kg while taking clozapine , were r and omized ( n=207 ) to aripiprazole at 5 - 15 mg/d or placebo , in addition to a stable dose of clozapine . The primary endpoint was mean change from baseline in body weight at week 16 ( last observation carried forward ) . Secondary endpoints included clinical efficacy , body mass index ( BMI ) and waist circumference . A statistically significant difference in weight loss was reported for aripiprazole vs. placebo ( -2.53 kg vs. -0.38 kg , respectively , difference=-2.15 kg , p Aripiprazole-treated patients also showed BMI ( median reduction 0.8 kg/m(2 ) ) and waist circumference reduction ( median reduction 2.0 cm ) vs. placebo ( no change in either parameter , p Aripiprazole-treated patients had significantly greater reductions in total and low-density lipoprotein ( LDL ) cholesterol . There were no significant differences in Positive and Negative Syndrome Scale total score changes between groups but Clinical Global Impression Improvement and Investigator 's Assessment Question naire scores favoured aripiprazole over placebo . Safety and tolerability were generally comparable between groups . Combining aripiprazole and clozapine result ed in significant weight , BMI and fasting cholesterol benefits to patients suboptimally treated with clozapine . Improvements may reduce metabolic risk factors associated with clozapine treatment", "Objective : Few interventions have been successful to prevent or reverse the medical complications associated with antipsychotic agents in the schizophrenia population . In particular , no single agent can correct multiple metabolic abnormalities such as insulin resistance , hyperlipidemia , inflammation , obesity , and fat distribution . We now report a r and omized placebo-controlled pilot study to examine the effects of ramelteon on obesity and metabolic disturbances among subjects with schizophrenia . Methods : A double-blind , placebo-controlled , 8-week pilot trial was conducted , adding ramelteon 8 mg/d to stable out patients with schizophrenia . Vital signs and anthropometric measurements , including height , weight , waist circumference , and body fat were assessed , and laboratory assays were tracked to monitor changes in metabolic markers . Results : Twenty-five subjects were r and omly assigned to treatment with study drug or placebo , and 20 subjects were included in the final analysis . Ramelteon did not improve anthropometric measurements , glucose metabolism , and inflammatory markers . There was , however , a significant decrease in total cholesterol and ratio of cholesterol to high-density lipoprotein in the ramelteon group . Although the st and ard anthropometric measures did not show significant change , the dual-energy x-ray absorptiometry scan showed a trend toward reduction in fat in the abdominal and trunk areas with a moderate effect size . Conclusions : Although ramelteon decreased cholesterol , treatment may have to be longer than 8 weeks and with a higher dose for maximal effect of ramelteon for body fat and lipid changes . Future studies are needed for patients with schizophrenia with a larger sample size to fully underst and ramelteon 's effects on abdominal adiposity and lipids", "Objectives Little is known about the prevalence of comorbidity rates in people with severe mental illness ( SMI ) in UK primary care . We calculated the prevalence of SMI by UK country , English region and deprivation quintile , antipsychotic and antidepressant medication prescription rates for people with SMI , and prevalence rates of common comorbidities in people with SMI compared with people without SMI . Design Retrospective cohort study from 2000 to 2012 . Setting 627 general practice s contributing to the Clinical Practice Research Data link , a UK primary care data base . Participants Each identified case ( 346 551 ) was matched for age , sex and general practice with 5 r and omly selected control cases ( 1 732 755 ) with no diagnosis of SMI in each yearly time point . Outcome measures Prevalence rates were calculated for 16 conditions . Results SMI rates were highest in Scotl and and in more deprived areas . Rates increased in Engl and , Wales and Northern Irel and over time , with the largest increase in Northern Irel and ( 0.48 % in 2000/2001 to 0.69 % in 2011/2012 ) . Annual prevalence rates of all conditions were higher in people with SMI compared with those without SMI . The discrepancy between the prevalence of those with and without SMI increased over time for most conditions . A greater increase in the mean number of additional conditions was observed in the SMI population over the study period ( 0.6 in 2000/2001 to 1.0 in 2011/2012 ) compared with those without SMI ( 0.5 in 2000/2001 to 0.6 in 2011/2012 ) . For both groups , most conditions were more prevalent in more deprived areas , whereas for the SMI group conditions such as hypothyroidism , chronic kidney disease and cancer were more prevalent in more affluent areas . Conclusions Our findings highlight the health inequalities faced by people with SMI . The provision of appropriate timely health prevention , promotion and monitoring activities to reduce these health inequalities are needed , especially in deprived areas", "Obesity and diabetes have caused problems for individuals with schizophrenia long before atypical antipsychotic agents . The prevalence of obesity , insulin resistance , impaired glucose tolerance , type 2 diabetes mellitus , dyslipidemia , and the Metabolic Syndrome has increased in people with schizophrenia as compared to the general population . Risk reduction studies for persons with obesity , diabetes , and cardiovascular disease indicate that cognitive/behavioral interventions that promote motivation and provide strategies to overcome the barriers in adherence to diet and activity modification are effective interventions for weight management and risk reduction . In the l and mark multi-center r and omized-controlled trial study , the Diabetes Prevention Project ( DPP ) , a cognitive/behavioral intervention , was more successful in producing weight loss and preventing diabetes than the drugs metformin , troglitazone or placebo . This pilot study examined the effectiveness of a cognitive/behavioral group intervention , modified after the DPP program , in individuals with schizophrenia or schizoaffective disorder taking atypical antipsychotics in a large urban public mental health system . Outcome measures included body weight , body mass index , waist-hip ratios , and fasting glucose levels . Both groups demonstrated elevated fasting glucose levels and were obese with a mean BMI of 33 . The group that received the cognitive/behavioral group intervention lost more weight than the treatment as usual group . The CB group participants lost an average of 5.4 lb or 2.9 % of body weight , and those in the control group lost 1.3 lb or 0.6 % body weight . The range of weight loss for the treatment group was from 1 to 20 lb . This pilot study has demonstrated that weight loss is possible with cognitive/behavioral interventions in a population with a psychotic disorder", "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", "CONTEXT Concerns about the safety and efficacy of diabetes interventions persist , in part because r and omized clinical trials ( RCTs ) have not measured their effect on patient-important outcomes , ie , death and quality of life ( morbidity , pain , function ) . OBJECTIVE To systematic ally determine the extent to which ongoing and future RCTs in diabetes will ascertain patient-important outcomes . DATA SOURCES On November 10 , 2007 , we search ed primary RCT registries Clinical Trials.gov ( http://www . clinical trials.gov ) , International St and ard R and omized Controlled Trial Number Register ( http://is rct n.org ) , and Australian New Zeal and Clinical Trials Registry ( http://www.anzctr.org.au ) . STUDY SELECTION We identified phase 2 through 4 RCTs enrolling patients with diabetes . Of 2019 RCTs , 1054 proved eligible . We r and omly sample d 50 % of the eligible RCTs ( 527 of 1054 ) and selected 436 registered since registration became m and atory ( 2004 ) . DATA EXTRACTION Pairs of review ers working independently collected study characteristics and determined the outcomes measured and their type ( physiological outcomes , surrogate outcomes thought to reflect an increased risk for patient-important outcomes , and patient-important outcomes ) . RESULTS Of the 436 registered RCTs included in this analysis , 24 ( 6 % ) had not started enrollment , 109 ( 25 % ) were actively enrolling , and 303 ( 69 % ) had completed enrollment . Primary outcomes were patient-important outcomes in only 78 of 436 RCTs ( 18 % ; 95 % confidence interval [ CI ] , 14%-22 % ) , physiological and laboratory outcomes in 69 of 436 ( 16 % ; 95 % CI , 13%-20 % ) , and surrogate outcomes in 268 of 436 ( 61 % ; 95 % CI , 57%-66 % ) . Patient-important outcomes were reported as primary or secondary outcomes in 201 of 436 ( 46 % ; 95 % CI , 41%-51 % ) . In multivariate analysis , large trials ( odds ratio [ OR ] , 1.10 ; 95 % CI , 1.02 - 1.19 for every additional 100 patients ) and trials of longer duration ( OR , 1.03 ; 95 % CI , 1.01 - 1.06 for every additional 30 days ) were more likely while parallel design RCTs ( OR , 0.15 ; 95 % CI , 0.05 - 0.44 ) and type 2 diabetes trials ( OR , 0.23 ; 95 % CI , 0.09 - 0.61 ) were less likely to assess patient-important outcomes as a primary outcome . CONCLUSION In this sample of registered ongoing RCTs in diabetes , only 18 % included patient-important outcomes as primary outcomes", "BACKGROUND Overweight and obesity are epidemic among persons with serious mental illness , yet weight-loss trials systematic ally exclude this vulnerable population . Lifestyle interventions require adaptation in this group because psychiatric symptoms and cognitive impairment are highly prevalent . Our objective was to determine the effectiveness of an 18-month tailored behavioral weight-loss intervention in adults with serious mental illness . METHODS We recruited overweight or obese adults from 10 community psychiatric rehabilitation outpatient programs and r and omly assigned them to an intervention or a control group . Participants in the intervention group received tailored group and individual weight-management sessions and group exercise sessions . Weight change was assessed at 6 , 12 , and 18 months . RESULTS Of 291 participants who underwent r and omization , 58.1 % had schizophrenia or a schizoaffective disorder , 22.0 % had bipolar disorder , and 12.0 % had major depression . At baseline , the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 36.3 , and the mean weight was 102.7 kg ( 225.9 lb ) . Data on weight at 18 months were obtained from 279 participants . Weight loss in the intervention group increased progressively over the 18-month study period and differed significantly from the control group at each follow-up visit . At 18 months , the mean between-group difference in weight ( change in intervention group minus change in control group ) was -3.2 kg ( -7.0 lb , P=0.002 ) ; 37.8 % of the participants in the intervention group lost 5 % or more of their initial weight , as compared with 22.7 % of those in the control group ( P=0.009 ) . There were no significant between-group differences in adverse events . CONCLUSIONS A behavioral weight-loss intervention significantly reduced weight over a period of 18 months in overweight and obese adults with serious mental illness . Given the epidemic of obesity and weight-related disease among persons with serious mental illness , our findings support implementation of targeted behavioral weight-loss interventions in this high-risk population . ( Funded by the National Institute of Mental Health ; ACHIEVE Clinical Trials.gov number , NCT00902694 . )", "PURPOSE We tested the feasibility and preliminary efficacy of a lifestyle intervention for middle-aged and older patients with schizophrenia and type-2 diabetes mellitus , using a r and omized pre-test , post-test control group design . METHOD Individuals with a diagnosis of schizophrenia or schizoaffective disorder over the age of 40 were r and omly assigned to 24-week Diabetes Awareness and Rehabilitation Training ( DART ; n=32 ) groups or Usual Care plus Information ( UCI ; n=32 ) comparison groups . Participants were recruited from board- and -care facilities and day treatment programs . Fifty-seven patients completed baseline and 6-month assessment s consisting of an interview , measures of body mass index , blood pressure , fasting blood chemistry , and accelerometry . A mixed-model analysis of variance was used to analyze the data . RESULTS A significant group x time interaction was found for body weight , with patients in the DART group losing a mean of 5 lb and those in the UCI gaining a mean 6 lb . Significant group x time interactions were also found for triglycerides , diabetes knowledge , diabetes self-efficacy , and self-reported physical activity , but not for fasting plasma glucose or glycosylated hemoglobin . CONCLUSIONS Group-based lifestyle interventions are feasible and produce positive health changes in middle-aged and older patients with schizophrenia and diabetes mellitus", "OBJECTIVE We sought to examine patients ' preferences regarding the design of diabetes trials . Specifically , do patients prefer trials to focus on patient-important outcomes ( vs. surrogate outcomes ) and provide practical/pragmatic answers ( vs. mechanistic/explanatory answers ) ? STUDY DESIGN AND SETTING We mailed a question naire to a stratified r and om sample of 4,796 patients with diabetes receiving care from 371 primary care clinicians in the US Midwest . Medical record review provided data on hemoglobin A1c ( HbA1c ) . Descriptive statistics , logistic regression , and multiple regression techniques were used for analysis . RESULTS We received completed surveys from 2,036 patients ( response rate of 42.5 % ) . On average , respondents were 65 years old , had 11 years of diabetes , and had excellent glycemic control ( HbA1c=7 % ) . Most patients ( > 75 % ) chose patient-important outcomes rather than HbA1c as their first choice for a trial primary outcome and preferred a practical trial design . Patients with poor glycemic control ( HbA1c>8.0 % ) were more likely to prefer HbA1c as a primary end point ( odds ratio : 1.5 ; 95 % confidence interval : 1.1 , 2.1 ) . CONCLUSION Individuals with diabetes report a strong preference for practical trials measuring the effect of treatments on patient-important outcomes . To our knowledge , this is the first report of patients endorsing key elements of the comparative effectiveness agenda" ]

[ "We recently conducted a prospect i ve , placebo‐controlled clinical study , where we could demonstrate , that a substitution of 200 μg sodium selenite for three months in patients with autoimmune thyroiditis reduced thyroid peroxidase antibody ( TPO‐Ab ) concentrations significantly . Forty‐seven patients from the initially 70 patients agreed to participate in a follow‐up cross‐over study for further six months . One group ( n = 13 ) , which initially received selenium continued to take 200 μg sodium selenite ( Se‐Se ) , one group stopped taking selenium ( Se‐0 ) ( n = 9 ) , another group which received placebo started to take 200 μg selenium ( n = 14 ) ( Plac‐Se ) and the last group was without selenium substitution ( Plac‐0 ) ( n = 11 ) . TPO‐Ab concentrations were measured at beginning and the end of the study . In the Se‐Se group , the TPO‐Ab concentrations further significantly p = 0.004 ) decreased from 625 ± 470 U/ml to 354 ± 321 U/ml , in the Se‐0 group the TPO‐Ab concentrations increased significantly p = 0.017 ) from 450 ± 335 to 708 ± 313 U/ml . In the placebo group , the TPO‐Ab concentrations in those patients who were followed without selenium substitution were unchanged ( 1351 ± 940 vs. 1724 ± 1112 U/ml , p = 0.555 ) . In contrast , the patients who received 200 μg sodium selenite after placebo , the TPO‐Ab concentrations decreased significantly ( p = 0.029 ) from 1182 ± 723 to 643 ± 477 U/ml", "CONTEXT Pregnant women who are positive for thyroid peroxidase antibodies [ TPOAb(+ ) ] are prone to develop postpartum thyroid dysfunction ( PPTD ) and permanent hypothyroidism . Selenium ( Se ) decreases thyroid inflammatory activity in patients with autoimmune thyroiditis . OBJECTIVE We examined whether Se supplementation , during and after pregnancy , influences the thyroidal autoimmune pattern and function . DESIGN This was a prospect i ve , r and omized , placebo-controlled study . SETTING The study was conducted in the Department of Obstetrics and Gynecology and Department of Endocrinology . PATIENTS A total of 2143 euthyroid pregnant women participated in the study ; 7.9 % were TPOAb(+ ) . INTERVENTIONS During pregnancy and the postpartum period , 77 TPOAb(+ ) women received selenomethionine 200 microg/d ( group S1 ) , 74 TPOAb(+ ) women received placebo ( group S0 ) , and 81 TPOAb(- ) age-matched women were the control group ( group C ) . MAIN OUTCOME MEASURES We measured the prevalence of PPTD and hypothyroidism . RESULTS PPTD and permanent hypothyroidism were significantly lower in group S1 compared with S0 ( 28.6 vs. 48.6 % , P Se supplementation during pregnancy and in the postpartum period reduced thyroid inflammatory activity and the incidence of hypothyroidism", "BACKGROUND Hashimoto 's thyroiditis ( HT ) is a common disease , and is the most prevalent cause of hypothyroidism . Symptoms and diseases associated with HT are considered to be caused by hypothyroidism . We hypothesized that higher antithyroperoxidase ( anti-TPO ) antibody levels would be associated with an increased symptom load and a decreased quality of life in a female euthyroid patient collective . METHODS In a prospect i ve cohort study 426 consecutive euthyroid female patients undergoing thyroid surgery for benign thyroid disease were included . Main outcome measures were preoperative anti-TPO levels , a symptom question naire and the SF-36 question naire , and lymphocytic infiltration of the thyroid tissue as evaluated by histology . RESULTS Histology revealed HT in 28/426 ( 6.6 % ) subjects . To maximize the sum of the predictive values , a cut-off point for anti-TPO of 121.0 IU/mL was calculated ( sensitivity 93.3 % [ 95 % confidence interval : 77.9%-99.0 % ] ; specificity 94.7 % [ 95 % confidence interval : 92.0%-96.7 % ] ) to predict the presence of histological signs of HT . The mean number of reported symptoms was significantly higher in patients with anti-TPO levels > 121.0 IU/mL than in the other group ( 6.7 ± 2.5 vs. 4.1 ± 2.8 ; p preoperative thyroid-stimulating hormone levels ( 1.7 ± 1.3 vs. 1.5 ± 1.4 μU/mL , respectively ; p = 0.155 ) . Chronic fatigue , dry hair , chronic irritability , chronic nervousness , a history of breast cancer and early miscarriage , and lower quality -of-life levels were significantly associated with anti-TPO levels exceeding the cut-off point ( p Women with HT suffer from a high symptom load . Hypothyroidism is only a contributing factor to the development of associated conditions", "UNLABELLED Selenium as an essential trace element is capable of exerting complex effects on the endocrine and immune system by its antioxidant capacity . The role of selenium is important because the level of free oxygen radicals is elevated in the physiological thyroid hormone synthesis . THE AIM OF STUDY was to determine whether selenium therapy can influence the level of antithyroid peroxidase and antithyroglobulin antibodies or whether there is a correlation between antioxidant capacity and the titer of autoantibodies . METHOD 132 patient with autoimmune thyroiditis were investigated in a prospect i ve , blind and placebo-controlled study . L-thyroxine substitution therapy was made in both groups and the level of TSH remained in the normal range . The selenium-treated group ( n = 70 patients , 68 female , mean age 41,4 + /- 9,5 year ) was compared with the placebo-treated group ( n = 62 patients , 61 female , mean age 42,7 + /- 8,3 year ) . Selenium therapy was continued by L-seleno-methionine ( per os 2 x 100 microg/day ) for one year . Determination of TSH , fT4 , fT3 and autoantibodies was carried out by chemiluminescence method . Total antioxidant capacity was determined by R and ox kit , the level of selenium in the sera by atomic absorption technique was measured . In the follow-up study , patients were controlled every third month and at the end of a one-year observation period . RESULTS The level of selenium in the untreated patients was significantly lower than in treated patients and controls . The fT3/fT4 ration proved to be higher in patients after selenium therapy . The titer of antithyroid antibodies ( mostly the antithyroid peroxidase ) significantly decreased at the end of the study . An inverse correlation was found between antioxidant capacity and the level of antithyroid peroxidase antibodies . The volume of thyroid gl and slightly diminished in treated patients . Side effects were not observed . CONCLUSIONS Selenium completed with L-thyroxine is a suitable therapy for patients with autoimmune thyroiditis", "In areas with severe selenium deficiency there is a higher incidence of thyroiditis due to a decreased activity of selenium-dependent glutathione peroxidase activity within thyroid cells . Selenium-dependent enzymes also have several modifying effects on the immune system . Therefore , even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases . We performed a blinded , placebo-controlled , prospect i ve study in female patients ( n = 70 ; mean age , 47.5 + /- 0.7 yr ) with autoimmune thyroiditis and thyroid peroxidase antibodies ( TPOAb ) and /or Tg antibodies ( TgAb ) above 350 IU/ml . The primary end point of the study was the change in TPOAb concentrations . Secondary end points were changes in TgAb , TSH , and free thyroid hormone levels as well as ultrasound pattern of the thyroid and quality of life estimation . Patients were r and omized into 2 age- and antibody (TPOAb)-matched groups ; 36 patients received 200 microg ( 2.53 micromol ) sodium selenite/d , orally , for 3 months , and 34 patients received placebo . All patients were substituted with L-T(4 ) to maintain TSH within the normal range . TPOAb , TgAb , TSH , and free thyroid hormones were determined by commercial assays . The echogenicity of the thyroid was monitored with high resolution ultrasound . The mean TPOAb concentration decreased significantly to 63.6 % ( P = 0.013 ) in the selenium group vs. 88 % ( P = 0.95 ) in the placebo group . A subgroup analysis of those patients with TPOAb greater than 1200 IU/ml revealed a mean 40 % reduction in the selenium-treated patients compared with a 10 % increase in TPOAb in the placebo group . TgAb concentrations were lower in the placebo group at the beginning of the study and significantly further decreased ( P = 0.018 ) , but were unchanged in the selenium group . Nine patients in the selenium-treated group had completely normalized antibody concentrations , in contrast to two patients in the placebo group ( by chi(2 ) test , P = 0.01 ) . Ultrasound of the thyroid showed normalized echogenicity in these patients . The mean TSH , free T(4 ) , and free T(3 ) levels were unchanged in both groups . We conclude that selenium substitution may improve the inflammatory activity in patients with autoimmune thyroiditis , especially in those with high activity . Whether this effect is specific for autoimmune thyroiditis or may also be effective in other endocrine autoimmune diseases has yet to be investigated", "OBJECTIVES The 36 item short form health survey ( SF-36 ) has proved to be of use in a variety of setting s where a short generic health measure of patient-assessed outcome is required . This measure can provide an eight dimension profile of health status , and two summary scores assessing physical function and mental well-being . The developers of the SF-36 in America have developed algorithms to yield the two summary component scores in a question naire containing only one-third of the original 36 items , the SF-12 . This paper documents the construction of the UK SF-12 summary measures from a large-scale data set from the UK in which the SF-36 , together with other questions on health and lifestyles , was sent to r and omly selected members of the population . Using these data we attempt here to replicate the findings of the SF-36 developers in the UK setting , and then to assess the use of SF-12 summary scores in a variety of clinical conditions . METHODS Factor analytical methods were used to derive the weights used to construct the physical and mental component scales from the SF-36 . Regression methods were used to weight the 12 items recommended by the developers to construct the SF-12 physical and mental component scores . This analysis was undertaken on a large community sample ( n = 9332 ) , and then the results of the SF-36 and SF-12 were compared across diverse patient groups ( Parkinson 's disease , congestive heart failure , sleep apnoea , benign prostatic hypertrophy ) . RESULTS Factor analysis of the SF-36 produced a two factor solution . The factor loadings were used to weight the physical component summary score ( PCS-36 ) and mental component summary score ( MCS-36 ) . Results gained from the use of these measures were compared with results gained from the PCS-12 and MCS-12 , and were found to be highly correlated ( PCS : rho = 0.94 , p SF-12 is able to produce the two summary scales originally developed from the SF-36 with considerable accuracy and yet with far less respondent burden . Consequently , the SF-12 may be an instrument of choice where a short generic measure providing summary information on physical and mental health status is required", "OBJECTIVE Selenium ( Se ) in the form of selenocysteine is an essential component of the family of the detoxifying enzymes glutathione peroxidase ( Gpx ) and of the iodothyronine selenodeiodinases that catalyse the extrathyroidal production of tri-iodothyronine ( T(3 ) ) . Thus , Se deficiency may seriously influence the generation of free radicals , the conversion of thyroxine ( T(4 ) ) to T(3 ) and the autoimmune process . Therefore , we performed a r and omised , placebo-controlled prospect i ve study to investigate the effects of Se treatment on patients with autoimmune thyroiditis ( AIT ) . DESIGN AND METHODS Sixty five patients aged 22 - 61 years ( median age 48 years ) with AIT were recruited into two groups . Group I ( Gr I ) ( n=34 ) was treated with selenomethionine ( Seme ) 200 microg , plus L-thyroxine ( LT(4 ) ) to maintain TSH levels between 0.3 - 2.0 mU/l , whereas group II ( Gr II ) ( n=31 ) received LT(4 ) plus placebo over a period of 6 months . Moreover , the pharmacokinetics of Seme were studied in 10 patients and eight volunteers at baseline and 2 h , 4 h , 6 h and 24 h after oral administration of a 200 microg tablet of Seme . Finally , Se levels were measured at the end of the study in some patients of both groups and their results were correlated with thyroid hormone levels . RESULTS In the pharmacokinetics study , basal serum concentration of Se ( 75+/-6 microg/l ) was within the reference range ( 70 - 125 microg/l ) , it promptly increased at 2 h , peaked at 4 h ( 147+/-17 microg/l ; P antibodies against thyroid peroxidase ( anti-TPO ) levels showed an overall decrease of 46 % at 3 months ( from 1875+/-1039 U/l to 1013+/-382 U/l ; P anti-TPO amounted to 21 % at 3 months and to 27 % at 6 months ( from 1758+/-917 U/l to 1284+/-410 U/l ; P against thyroglobulin levels between the groups . At the end of this study Se levels were found to be statistically significantly increased in Gr I ( n = 9/34 ) compared with Gr II ( n=11/31 ) ( 97+/-8.4 vs 79+/-8 ; P LT(4 ) in the treatment of AIT . The exact mechanism(s ) is not very well determined , it might enhance the activity of detoxifying enzymes and enforce the defense against oxidative stress", "The aim of this study is to investigate the long-term ( 9 months ) effects of variable doses ( 200/100 microg/day ) of L-selenomethionine on autoimmune thyroiditis ( AIT ) and the parameters affecting the success rate of this therapy . The present study was design ed in three steps : ( 1 ) 88 female patients with AIT ( mean age = 40.1 + /- 13.3 years ) were r and omized into two groups according to their initial serum TSH , thyroid peroxidase antibody ( TPOAb ) concentrations , and age . All the patients were receiving L-thyroxine to keep serum TSH 200 microg L-selenomethionine per day , orally for 3 months , and group C ( n = 40 , mean TPOAb = 770.3 + /- 406.2 IU/ml ) received placebo . ( 2 ) 40 volunteers of group S2 were r and omized into two age- and TPOAb-matched groups . Group S22 ( n = 20 ) went on taking L-selenomethionine 200 microg/day , while others ( group S21 ) lowered the dose to 100 microg/day . ( 3 ) 12 patients of group S22 ( group S222 ) went on taking L-selenomethionine 200 microg/day , while 12 patients of group S21 ( S212 ) increased the dose to 200 microg/day . Serum titers of TPOAb decreased significantly in group S2 ( 26.2 % , P 0.05 ) . TPOAb titers increased significantly in group S21 ( 38.1 % , P thyroglobulin antibody titers was only noted in group S2 ( 5.2 % , P L-selenomethionine substitution suppresses serum concentrations of TPOAb in patients with AIT , but suppression requires doses higher than 100 microg/day which is sufficient to maximize glutathione peroxidase activities . The suppression rate decreases with time", "CONTEXT No previous study determined monocyte- and lymphocyte-suppressing effects of levothyroxine and selenomethionine and assessed whether their coadministration is superior to treatment with only one of these drugs . OBJECTIVE Our objective was to compare the effect of levothyroxine and selenomethionine on monocyte and lymphocyte cytokine release and systemic inflammation in patients with Hashimoto 's thyroiditis . DESIGN , SETTING , PARTICIPANTS , AND INTERVENTION We conducted a r and omized clinical trial involving a group of 170 ambulatory euthyroid women with recently diagnosed and previously untreated Hashimoto 's thyroiditis and 41 matched healthy subjects . Participants were r and omized in a double-blind fashion to receive a 6-month treatment with levothyroxine , selenomethionine , levothyroxine plus selenomethionine , or placebo . One hundred sixty-five patients completed the study . MAIN OUTCOME MEASURES Monocyte and lymphocyte release of proinflammatory cytokines and plasma levels of C-reactive protein ( CRP ) were assessed . RESULTS Compared with the control subjects , monocytes and lymphocytes of Hashimoto 's thyroiditis patients released greater amounts of all cytokines studied . Levothyroxine reduced monocyte release of TNF-α , IL-1β , IL-6 , and monocyte chemoattractant protein-1 , whereas selenomethionine inhibited lymphocyte release of IL-2 , interferon-γ , and TNF-α , which was accompanied by a reduction in plasma CRP levels . The decrease in cytokine release and in plasma CRP levels was strongest when both drugs were given together . CONCLUSIONS Despite affecting different types of inflammatory cells , levothyroxine and selenomethionine exhibit a similar systemic antiinflammatory effect in euthyroid females with Hashimoto 's thyroiditis . This action , which correlates with a reduction in thyroid peroxidase antibody titers , may be associated with clinical benefits in the prevention and management of Hashimoto 's thyroiditis , particularly in subjects receiving both agents" ]

[ "BACKGROUND Adherence to evidence -based cardiovascular ( CV ) medications after an acute myocardial infa rct ion ( MI ) is low after the first 6 months . The use of fixed-dose combinations ( FDC ) has been shown to improve treatment adherence and risk factor control . However , no previous r and omized trial has analyzed the impact of a polypill strategy on adherence in post-MI patients . OBJECTIVES The cross-sectional FOCUS ( Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention ) study ( Phase 1 ) aim ed to eluci date factors that interfere with appropriate adherence to CV medications for secondary prevention after an acute MI . Additionally , 695 patients from Phase 1 were r and omized into a controlled trial ( Phase 2 ) to test the effect of a polypill ( containing aspirin 100 mg , simvastatin 40 mg , and ramipril 2.5 , 5 , or 10 mg ) compared with the 3 drugs given separately on adherence , blood pressure , and low-density lipoprotein cholesterol , as well as safety and tolerability over a period of 9 months of follow-up . METHODS In Phase 1 , a 5-country cohort of 2,118 patients was analyzed . Patients were r and omized to either the polypill or 3 drugs separately for Phase 2 . Primary endpoint was adherence to the treatment measured at the final visit by the self-reported Morisky-Green question naire ( MAQ ) and pill count ( patients had to meet both criteria for adherence at the in-person visit to be considered adherent ) . RESULTS In Phase 1 , overall CV medication adherence , defined as an MAQ score of 20 , was 45.5 % . In a multivariable regression model , the risk of being nonadherent ( MAQ adherence compared with the group receiving separate medications after 9 months of follow-up : 50.8 % versus 41 % ( p = 0.019 ; intention-to-treat population ) and 65.7 % versus 55.7 % ( p = 0.012 ; per protocol population ) when using the primary endpoint , attending the final visit with MAQ = 20 and high pill count ( 80 % to 110 % ) combined , to assess adherence . Adherence also was higher in the FDC group when measured by MAQ alone ( 68 % vs. 59 % , p = 0.049 ) . No treatment difference was found at follow-up in mean systolic blood pressure ( 129.6 mm Hg vs. 128.6 mm Hg ) , mean low-density lipoprotein cholesterol levels ( 89.9 mg/dl vs. 91.7 mg/dl ) , serious adverse events ( 23 vs. 21 ) , or death ( 1 , 0.3 % in each group ) . CONCLUSIONS For secondary prevention following acute MI , younger age , depression , and a complex drug treatment plan are associated with lower medication adherence . Meanwhile , adherence is increased in patients with higher insurance coverage levels and social support . Compared with the 3 drugs given separately , the use of a polypill strategy met the primary endpoint for adherence for secondary prevention following an acute MI . ( Fixed Dose Combination Drug [ Polypill ] for Secondary Cardiovascular Prevention [ FOCUS ] ; NCT01321255 )", "Background Adherence to preventive medication is often poor , and current interventions have had limited success . Purpose This study was conducted to pilot a r and omised controlled trial aim ed at increasing adherence to preventive medication in stroke survivors using a brief , personalised intervention . Methods Sixty-two stroke survivors were r and omly allocated to either a two-session intervention aim ed at increasing adherence via ( a ) introducing a plan linked to environmental cues ( implementation intentions ) to help establish a better medication-taking routine ( habit ) and ( b ) eliciting and modifying any mistaken patient beliefs regarding medication/stroke or a control group . Primary outcome was adherence to antihypertensive medication measured objective ly over 3 months using an electronic pill bottle . Results Fifty-eight people used the pill bottle and were analysed as allocated ; 54 completed treatment . The intervention result ed in 10 % more doses taken on schedule ( intervention , 97 % ; control , 87 % ; 95 % CI for difference ( 0.2 , 16.2 ) ; p = 0.048 ) . Conclusions A simple , brief intervention increased medication adherence in stroke survivors , over and above any effect of increased patient contact or mere measurement . ( http://controlled-trials.com , number IS RCT N38274953 .", "IMPORTANCE Most patients with cardiovascular disease ( CVD ) do not take recommended medications long-term . The use of fixed-dose combinations ( FDCs ) improves adherence in several clinical areas . Previous trials of cardiovascular FDCs have assessed short-term effects compared with placebo or no treatment . OBJECTIVE To assess whether FDC delivery of aspirin , statin , and 2 blood pressure-lowering agents vs usual care improves long-term adherence to indicated therapy and 2 major CVD risk factors , systolic blood pressure ( SBP ) and low-density lipoprotein cholesterol ( LDL-C ) . DESIGN , SETTING , AND PARTICIPANTS The UMPIRE trial , a r and omized , open-label , blinded-end-point trial among 2004 participants with established CVD or at risk of CVD enrolled July 2010-July 2011 in India and Europe . The trial follow-up concluded in July 2012 . INTERVENTIONS Participants were r and omly assigned ( 1:1 ) to an FDC-based strategy ( n=1002 ) containing either ( 1 ) 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril , and 50 mg atenolol or ( 2 ) 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril , and 12.5 mg hydrochlorothiazide or to usual care ( n=1002 ) . MAIN OUTCOMES AND MEASURES Adherence to medication ( defined as self-reported use of antiplatelet , statin , and ≥2 BP-lowering medications ) and changes in SBP and LDL-C from baseline . RESULTS At baseline , mean BP was 137/78 mm Hg , LDL-C was 91.5 mg/dL , and 1233 ( 61.5 % ) of 2004 participants reported use of antiplatelet , statin , and 2 or more BP-lowering medications . Median follow-up was 15 months ( interquartile range , 12 - 18 months ) . The FDC group had improved adherence vs usual care ( 86 % vs 65 % ; relative risk [ RR ] of being adherent , 1.33 ; 95 % CI , 1.26 - 1.41 ; P reductions in SBP ( -2.6 mm Hg ; 95 % CI , -4.0 to -1.1 mm Hg ; P .001 ) and LDL-C ( -4.2 mg/dL ; 95 % CI , -6.6 to -1.9 mg/dL ; P 727 participants ( 36 % ) , adherence at the end of study was 77 % vs 23 % ( RR , 3.35 ; 95 % CI , 2.74 - 4.09 ; P .001 for interaction ) , SBP was reduced by 4.9 mm Hg ( 95 % CI 7.3 - 2.6 mm Hg ; P = .01 for interaction ) , and LDL-C was reduced by 6.7 mg/dL ( 95 % CI , 10.5 - 2.8 mg/dL ; P = .11 for interaction ) . There were no significant differences in serious adverse events or cardiovascular events ( 50 [ 5 % ] in the FDC group and 35 [ 3.5 % ] in the usual care group ; RR , 1.45 ; 95 % CI , 0.94 - 2.24 ; P=.09 ) between the groups . CONCLUSIONS AND RELEVANCE Among patients with or at high risk of CVD , use of an FDC strategy for blood pressure , cholesterol , and platelet control vs usual care result ed in significantly improved medication adherence at 15 months and statistically significant but small improvements in SBP and LDL-C. TRIAL REGISTRATION clinical trials.gov Identifier : NCT01057537", "Background — Eliminating out-of-pocket costs for patients after myocardial infa rct ion ( MI ) improves adherence to preventive therapies and reduces clinical events . Because adherence to medical therapy is low among patients treated with coronary artery bypass graft surgery ( CABG ) , we evaluated the impact of providing full prescription coverage to this patient subgroup . Methods and Results — The MI Free Rx Event and Economic Evaluation ( FREEE ) trial r and omly assigned 5855 patients with MI to full prescription coverage or usual formulary coverage for all statins , & bgr;-blockers , angiotensin-converting enzyme inhibitors , or angiotensin receptor blockers . We assessed the impact of full prescription coverage on adherence , clinical outcomes , and healthcare costs using adjusted models among the 1052 patients who underwent CABG at the index hospitalization and 4803 who did not . CABG patients were older and had more comorbid illness ( P & bgr;-blockers and statins but were less likely to receive angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy ( P rates of adherence to all preventative medications after CABG ( all P rate of major vascular events or revascularization for patients treated with CABG ( hazard ratio , 0.91 ; 95 % confidence interval , 0.66–1.25 ) or without CABG ( hazard ratio , 0.93 ; 95 % confidence interval , 0.82–1.06 ) , with no interaction noted ( Pint = NS ) . After CABG , full prescription coverage significantly reduced patient out-of-pocket spending for drugs ( P=0.001 ) without increasing overall health expenditures ( P = NS ) . Conclusions — Eliminating drug copayments after MI provides consistent benefits to patients treated with or without CABG , leading to increased medication adherence , trends toward improved clinical outcomes , and reduced patient out-of-pocket expenses", "BACKGROUND Although most cardiovascular disease occurs in low-income and middle-income countries , little is known about the use of effective secondary prevention medications in these communities . We aim ed to assess use of proven effective secondary preventive drugs ( antiplatelet drugs , β blockers , angiotensin-converting-enzyme [ ACE ] inhibitors or angiotensin-receptor blockers [ ARBs ] , and statins ) in individuals with a history of coronary heart disease or stroke . METHODS In the Prospect i ve Urban Rural Epidemiological ( PURE ) study , we recruited individuals aged 35 - 70 years from rural and urban communities in countries at various stages of economic development . We assessed rates of previous cardiovascular disease ( coronary heart disease or stroke ) and use of proven effective secondary preventive drugs and blood-pressure-lowering drugs with st and ardised question naires , which were completed by telephone interviews , household visits , or on patient 's presentation to clinics . We report estimates of drug use at national , community , and individual levels . FINDINGS We enrolled 153,996 adults from 628 urban and rural communities in countries with incomes classified as high ( three countries ) , upper-middle ( seven ) , lower-middle ( three ) , or low ( four ) between January , 2003 , and December , 2009 . 5650 participants had a self-reported coronary heart disease event ( median 5·0 years previously [ IQR 2·0 - 10·0 ] ) and 2292 had stroke ( 4·0 years previously [ 2·0 - 8·0 ] ) . Overall , few individuals with cardiovascular disease took antiplatelet drugs ( 25·3 % ) , β blockers ( 17·4 % ) , ACE inhibitors or ARBs ( 19·5 % ) , or statins ( 14·6 % ) . Use was highest in high-income countries ( antiplatelet drugs 62·0 % , β blockers 40·0 % , ACE inhibitors or ARBs 49·8 % , and statins 66·5 % ) , lowest in low-income countries ( 8·8 % , 9·7 % , 5·2 % , and 3·3 % , respectively ) , and decreased in line with reduction of country economic status ( p(trend) received no drugs in high-income countries ( 11·2 % ) , compared with 45·1 % in upper middle-income countries , 69·3 % in lower middle-income countries , and 80·2 % in low-income countries . Drug use was higher in urban than rural areas ( antiplatelet drugs 28·7 % urban vs 21·3 % rural , β blockers 23·5%vs 15·6 % , ACE inhibitors or ARBs 22·8%vs 15·5 % , and statins 19·9%vs 11·6 % ; all p affected rates of drug use more than did individual-level factors ( eg , age , sex , education , smoking status , body-mass index , and hypertension and diabetes statuses ) . INTERPRETATION Because use of secondary prevention medications is low worldwide-especially in low-income countries and rural areas - systematic approaches are needed to improve the long-term use of basic , inexpensive , and effective drugs . FUNDING Full funding sources listed at end of paper ( see Acknowledgments )", "Background Most individuals at high cardiovascular disease ( CVD ) risk worldwide do not receive any or optimal preventive drugs . We aim ed to determine whether fixed dose combinations of generic drugs ( ‘ polypills ’ ) would promote use of such medications . Methods We conducted a r and omized , open-label trial involving 623 participants from Australian general practice s. Participants had established CVD or an estimated five-year CVD risk of ≥15 % , with indications for antiplatelet , statin and ≥2 blood pressure lowering drugs ( ‘ combination treatment ’ ) . Participants r and omized to the ‘ polypill-based strategy ’ received a polypill containing aspirin 75 mg , simvastatin 40 mg , lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg . Participants r and omized to ‘ usual care ’ continued with separate medications and doses as prescribed by their doctor . Primary outcomes were self-reported combination treatment use , systolic blood pressure and total cholesterol . Results After a median of 18 months , the polypill-based strategy was associated with greater use of combination treatment ( 70 % vs. 47 % ; relative risk 1.49 , ( 95 % confidence interval ( CI ) 1.30 to 1.72 ) p without differences in systolic blood pressure ( −1.5 mmHg ( 95 % CI −4.0 to 1.0 ) p = 0.24 ) or total cholesterol ( 0.08 mmol/l ( 95 % CI −0.06 to 0.22 ) p = 0.26 ) . At study end , 17 % and 67 % of participants in polypill and usual care groups , respectively , were taking atorvastatin or rosuvastatin . Conclusion Provision of a polypill improved self-reported use of indicated preventive treatments . The lack of differences in blood pressure and cholesterol may reflect limited study power , although for cholesterol , improved statin use in the polypill group counter-balanced use of more potent statins with usual care", "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", "Lowering blood pressure ( BP ) in stroke survivors reduces the risk of recurrent stroke . We tested the hypothesis that a nurse-led nonpharmacologic intervention would lower the BP of participants in an intervention group compared with a control group . A total of 349 patients who had sustained acute stroke or transient ischemic attack were r and omly assigned to either usual care or to 4 home visits by a nurse . During the visits , the nurse measured and recorded BP and provided individually tailored counseling on a healthy lifestyle . A total of 303 patients completed the 1-year follow up . No change in systolic BP was noted in either the intervention group or the control group . Because of an increase in diastolic BP in the control group ( P = .03 ) , a difference in mean diastolic BP between the 2 groups was found at follow-up ( P = .007 ) . Mean BP at follow-up was 139/82 mm Hg in the intervention group and 142/86 mm Hg in the control group . Linear regression analysis demonstrated that BP at the point of discharge was the strongest predictor of BP 1 year later ( P proportion of patients on antihypertensive medication increased in the intervention group ( P = .002 ) . Patients were compliant with antihypertensive therapy , and 92 % of the hypertensive patients in the intervention group followed the advice to see a general practitioner ( GP ) for BP checkups . At follow-up , 187 patients ( 62 % ) were hypertensive , with no difference in the rate of hypertension seen between the groups . Our data indicate that home visits by nurses did not result in a lowering of BP . Patients complied with antihypertensive therapy and GP visits in the case of hypertension . Nonetheless , the majority of patients were hypertensive at the 1-year follow up", "BACKGROUND Hypercholesterolemia control status is lacking throughout the western world . OBJECTIVES To examine whether the treatment recommendations given to ischemic heart disease patients at hospital discharge are compatible with the guidelines of the Israeli medical societies and the U.S. National Cholesterol Education Program for coronary artery disease prevention ; and to study the effects of brief educational sessions on the adherence of physicians with the guidelines . METHODS We included consecutive IHD patients admitted to four central hospitals in Israel between 1998 and 2000 . The study was conducted in two phases . In phase 1 , we review ed discharge letters to document treatment recommendations given to each patient . In phase 2 we educated the practitioners by review ing the Israeli medical societies and the NCEP guidelines and the quality of their recommendations in phase 1 , after which we reevaluated the discharge letters . RESULTS The study included 2,994 patients : 627 in phase 1 and 2,367 in phase 2 . Of the patients who needed cholesterol-lowering according to their low density lipoprotein levels , 37.4 % were not prescribed such drugs at discharge ( under-treatment group ) . This proportion was reduced by education to 26.6 % ( P target LDL goal in phase 1 ( under-dosage group ) as compared to 60.2 % in phase 2 ( P = 0.23 ) . In phase 2 there was an increase in the percent of patients reaching LDL levels reaching ' LDL levels target LDL was 1.16 , with 95 % confidence interval of 0.95 - 1.43 ) . CONCLUSIONS Physician recommendations to IHD patients discharged from hospital were suboptimal . We documented a high proportion of under-treated and under-dosaged patients . Brief educational sessions have a beneficial effect on the usage of statins ; however , additional effort in guideline implementations is needed", "STUDY OBJECTIVES To evaluate the outcome of a hospital discharge statin drug therapy initiation protocol following coronary artery bypass graft ( CABG ) surgery . Our goal was to measure the percentage of patients receiving statin drugs at hospital discharge and at a post-hospital discharge assessment following the implementation of the statin drug therapy initiation protocol . We also evaluated low-density lipoprotein cholesterol ( LDL-C ) goal attainment ( ie , safety monitoring , and tolerability of the statin drug . DESIGN Single-center , observational study with a historical control group . SETTING University-affiliated health system with a comprehensive heart care program that included a 14-bed cardiac surgery ICU . Approximately 400 CABG procedures are performed annually . PATIENTS Patients who underwent CABG surgery were eligible for inclusion in the study . The exclusion criteria were as follows : contraindications to statin therapy ; refusal to take a statin drug ; refusal to give informed consent ; and age INTERVENTION A protocol was implemented to recommend treatment with a statin drug at hospital discharge in all post-CABG surgery patients if the presurgical LDL-C level was > 100 mg/dL or the patient was receiving a statin prior to hospital admission . The protocol also included a presurgical assessment of lipoprotein levels and hepatic function . All cardiac surgery staff were educated regarding the specifics of the protocol . RESULTS A total of 403 patients were included in the study . The historical control group ( 202 subjects ) and the intervention group ( 201 subjects ) were similar with respect to gender , age , and baseline lipoprotein levels . The follow-up assessment interval was approximately 6 months in both groups . Overall , patients were more likely to receive a statin at hospital discharge in the intervention group compared to the control group ( relative risk [ RR ] , 1.6 ; 95 % confidence interval [ CI ] , 1.3 to 2.0 ) . Attainment of the goal for LDL-C level was similar between the intervention and control groups in the overall sample . Patients who were not at their LDL-C goal at baseline were more likely to have a follow-up LDL-C level of rate of liver function assessment was similar in the control and intervention groups . No patients in either group experienced elevations of alanine aminotransferase levels that were more than three times the upper limit of normal , and no cases of muscle toxicity were noted . CONCLUSION The initiation of therapy with a statin drug at hospital discharge following CABG surgery was associated with increased utilization rates . The LDL-C goal attainment improved in patients who were not at their goal prior to surgery . However , the persistence of medication use declined within 6 months . Statin therapy initiation was well-tolerated in this cohort of patients", "BACKGROUND Adherence to medications that are prescribed after myocardial infa rct ion is poor . Eliminating out-of-pocket costs may increase adherence and improve outcomes . METHODS We enrolled patients discharged after myocardial infa rct ion and r and omly assigned their insurance-plan sponsors to full prescription coverage ( 1494 plan sponsors with 2845 patients ) or usual prescription coverage ( 1486 plan sponsors with 3010 patients ) for all statins , beta-blockers , angiotensin-converting-enzyme inhibitors , or angiotensin-receptor blockers . The primary outcome was the first major vascular event or revascularization . Secondary outcomes were rates of medication adherence , total major vascular events or revascularization , the first major vascular event , and health expenditures . RESULTS Rates of adherence ranged from 35.9 to 49.0 % in the usual-coverage group and were 4 to 6 percentage points higher in the full-coverage group ( P rates of total major vascular events or revascularization were significantly reduced in the full-coverage group ( 21.5 vs. 23.3 ; hazard ratio , 0.89 ; 95 % CI , 0.90 to 0.99 ; P=0.03 ) , as was the rate of the first major vascular event ( 11.0 vs. 12.8 ; hazard ratio , 0.86 ; 95 % CI , 0.74 to 0.99 ; P=0.03 ) . The elimination of copayments did not increase total spending ( $ 66,008 for the full-coverage group and $ 71,778 for the usual-coverage group ; relative spending , 0.89 ; 95 % CI , 0.50 to 1.56 ; P=0.68 ) . Patient costs were reduced for drugs and other services ( relative spending , 0.74 ; 95 % CI , 0.68 to 0.80 ; P rates of first major vascular events and decreased patient spending without increasing overall health costs . ( Funded by Aetna and the Commonwealth Fund ; MI FREEE Clinical Trials.gov number , NCT00566774 . )", "Summary Background : Statins are life saving drugs in cardiovascular practice . However , they still are underprescribed in many situations despite their well-established benefits . Adherence may be improved by increased comprehension of the patients . Methods : Patients enrolled into a previous survey were r and omized into two groups as those , who were informed comprehensively ( Group 1 ) and those not ( Group 2 ) . 202 patients , all of whom were on secondary prevention , were contacted after median 15 months of follow up and evaluated whether they continued the statins , and reached targets . Results : 102 out of 202 patients were those enrolled into Group 1 , and 100 of them were those enrolled into Group 2 . In Group 1 , 62.7 % of patients were on continuous statin therapy during period betweeen initial and secondary contact , whereas , only 46 % of patients in Group 2 were on continuous statin therapy ( p = 0.017 ) . Being well-informed about statin increased the likelihood of being on continuous statin therapy after median of 15 months by 1.977 folds . Concerning targets , 64.7 % of those in Group 1 reached the targets , whereas , 43 % of those in Group 2 reached the targets ( p = 0.002 ) . Being well-informed about statin increased the likelihood of having suggested targets by ATP III after median of 15 months by 2.430 folds . Conclusion : Providing patients with comprehensive knowledge about statins , even in patients , who were already on statin therapy , seems not only to improve adherence but also increase the percentage of those reaching targets", "This r and omized , controlled trial evaluated the impact of personalized follow-up on compliance rates in high-risk patients receiving combination lipid-lowering therapy over 2 years . A r and om sample of 30 patients 7 - 30 days after cardiac surgery had baseline fasting low-density lipoprotein levels higher than 130 mg/dl . All patients received lovastatin 20 mg/day and colestipol 5 g twice/day . Weekly telephone contact was made with each patient for 12 weeks . Short- and long-term compliance was assessed by pill and packet counts and refill records . Compliance and lipid profile results were significantly better in the intervention group ( p parameters except high-density lipoprotein . However , this effect was not apparent during the first 12 weeks of therapy . Short-term telephone follow-up favorably affected compliance and lipid profile results up to 2 years after start of therapy", "Proven strategies to reduce risk of stroke recurrence are under‐utilized . We sought to evaluate the impact of st and ardized stroke discharge orders on treatment practice s in a cluster‐r and omized trial" ]

[ "Small , single-center studies suggest that catheter ablation of atrial fibrillation ( AF ) can improve ventricular function and reduce symptoms in patients with left ventricular ( LV ) dysfunction . However , ablation has not been compared with a pharmacologic strategy for AF . The authors evaluated patients with AF and symptomatic LV dysfunction ( ejection fraction pulmonary vein isolation ( PVI ) . They compared these patients with a matched cohort treated medically for AF and LV dysfunction via a retrospective case-control method . Fifteen patients ( 14 men , 56+/-11 years , 10 [ 67 % ] paroxysmal AF ) with AF for 4+/-3 years underwent PVI . Baseline ejection fraction was 37%+/-6 % and New York Heart Association ( NYHA ) class was 2.0+/-1.0 . Fifteen controls ( 13 men , 63+/-14 years , 11 [ 73 % ] paroxysmal AF ) with AF for 5+/-4 years were treated medically for AF . Baseline ejection fraction was 34%+/-11 % and NYHA class was 2.0+/-0.7 . The groups were similar in all respects . During a follow-up of 16+/-13 months after complete PVI , ejection fraction improved ( P=.001 ) to 50%+/-13 % and normalized in 8 patients ( 53 % ) . NYHA class improved to 1.3+/-0.5 ( P=.01 ) . In the medically treated group , after follow-up of 16+/-12 months , no improvement in ejection fraction ( 36%+/-12 % ) or NYHA class ( 1.8+/-0.7 ) was seen . Compared with pharmacologic therapy , PVI significantly improved LV function and NYHA class in patients with AF and symptomatic LV dysfunction . These provocative findings provide potent rationale for a r and omized clinical trial comparing ablation with pharmacologic therapy", "OBJECTIVES Our aim was to identify shortcomings in the management of patients with both atrial fibrillation ( AF ) and heart failure ( HF ) . BACKGROUND AF and HF often coincide in cardiology practice , and they are known to worsen each other 's prognosis , but little is known about the quality of care of this combination . METHODS In the observational Euro Heart Survey on AF , 5,333 AF patients were enrolled in 182 centers across 35 European Society of Cardiology member countries in 2003 and 2004 . A follow-up survey was performed after 1 year . RESULTS At baseline , 1,816 patients ( 34 % ) had HF . Recommended therapy for HF with left ventricular systolic dysfunction ( LVSD ) with a beta-blocker and either an angiotensin-converting enzyme inhibitor ( ACEI ) or angiotensin II receptor blocker was prescribed in 40 % of HF patients , while 29 % received the recommended drug therapy for both LVSD-HF and AF , consisting of the combination of a beta-blocker , either ACEI or angiotensin II receptor blocker , and oral anticoagulation . Rate control was insufficient with 40 % of all HF patients with permanent AF having a heart rate risk for mortality ( 9.5 % vs. 3.3 % ; p ( progression of ) HF ( 24.8 % vs. 5.0 % ; p AF progression ( 35 % vs. 19 % ; p ACEI prescription was associated with improved survival during 1-year follow-up ( odds ratio : 0.51 [ 95 % confidence interval : 0.31 to 0.85 ] ; p = 0.011 ) . CONCLUSIONS The prescription rate of guideline -recommended drug therapy for AF and LVSD-HF is low . R and omized controlled trials targeting this highly prevalent subgroup with AF and HF are warranted", "OBJECTIVES We aim ed to determine the safety and efficacy of pulmonary vein isolation ( PVI ) in atrial fibrillation ( AF ) patients with impaired left ventricular ( LV ) systolic function . BACKGROUND To date , PVI has been performed primarily in patients with normal LV function . Yet , many AF patients have impaired LV systolic function . The outcomes of PVI in patients with impaired LV systolic function are unknown . METHODS We included 377 consecutive patients undergoing PVI between December 2000 and January 2003 . Ninety-four patients had impaired LV function ( ejection fraction [ EF ] The control group was the remaining 283 patients who had a normal EF . End points included AF recurrence and changes in EF and quality of life ( QoL ) . RESULTS Mean EF was 36 % in our study group , compared with 54 % in controls . After initial PVI , 73 % of patients with impaired EF and 87 % of patients with normal EF were free of AF recurrence at 14 + /- 6 months ( p = 0.03 ) . In the study group , there was a nonsignificant increase in EF of 4.6 % and significant improvement in QoL. Complication rates were low and included a 1 % risk of pulmonary vein stenosis . CONCLUSIONS Although the AF recurrence rate after initial PVI in impaired EF patients was higher than in normal EF subjects , nearly three-fourths of patients with impaired EF remained AF-free . Although our sample size was nonr and omized , our results suggest PVI may be a feasible therapeutic option in AF patients with impaired EF . R and omized studies with more patients and longer follow-up are warranted", "Objective To determine whether or not radiofrequency ablation ( RFA ) for persistent atrial fibrillation in patients with advanced heart failure leads to improvements in cardiac function . Setting Patients were recruited from heart failure outpatient clinics in Scotl and . Design and intervention Patients with advanced heart failure and severe left ventricular dysfunction were r and omised to RFA ( rhythm control ) or continued medical treatment ( rate control ) . Patients were followed up for a minimum of 6 months . Main outcome measure Change in left ventricular ejection fraction ( LVEF ) measured by cardiovascular MRI . Results 22 patients were r and omised to RFA and 19 to medical treatment . In the RFA group , 50 % of patients were in sinus rhythm at the end of the study ( compared with none in the medical treatment group ) . The increase in cardiovascular magnetic resonance ( CMR ) LVEF in the RFA group was 4.5±11.1 % compared with 2.8±6.7 % in the medical treatment group ( p=0.6 ) . The RFA group had a greater increase in radionuclide LVEF ( a prespecified secondary end point ) than patients in the medical treatment group ( + 8.2±12.0 % vs + 1.4±5.9 % ; p=0.032 ) . RFA did not improve N-terminal pro-B-type natriuretic peptide , 6 min walk distance or quality of life . The rate of serious complications related to RFA was 15 % . Conclusions RFA result ed in long-term restoration of sinus rhythm in only 50 % of patients . RFA did not improve CMR LVEF compared with a strategy of rate control . RFA did improve radionuclide LVEF but did not improve other secondary outcomes and was associated with a significant rate of serious complications . Clinical trials registration number NCT00292162", "The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience .", "AIMS Beneficial effects of atrial fibrillation ( AF ) ablation have been demonstrated in patients with congestive heart failure ( CHF ) and significantly impaired left ventricular ejection fraction ( LVEF ) . However , the impact of pulmonary vein isolation ( PVI ) on cardiac function in patients with paroxysmal AF and impaired LVEF remains under discussion . This study aim ed to evaluate the impact of PVI for paroxysmal AF on cardiac function in patients with impaired LVEF using cardiac magnetic resonance imaging ( CMRI ) . METHODS AND RESULTS A total number of 70 patients with paroxysmal AF and episodes scanned on a 1.5-T-CMRI before and 6 months after PVI during sinus rhythm . End-diastolic volume , end-systolic volume , and LVEF were determined by epicardial and endocardial measurements . Patients were categorized into two groups regarding cardiac function as assessed by CMRI : group 1 patients ( n = 18 ) with an LVEF 50 % ( group 2 , n = 52 ) . Group 1 patients demonstrated a significant lower success rate than patients of group 2 after a follow-up of 152 + /- 40 days ( 50 vs. 73 % , P cardiac function after AF ablation ( 41 + /- 6 vs. 51 + /- 12 % , P = 0.004 ) , whereas group 2 patients did not show significant differences ( 60 + /- 6 vs. 59 + /- 9 % , P = 0.22 ) after a 6 months follow-up . CONCLUSION Pulmonary vein isolation improves cardiac function in patients with paroxysmal AF and impaired LVEF . These data suggest that an impaired LV function can be partially attributed to AF with short-lasting paroxysms", "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 Electrical isolation of the pulmonary veins by catheter ablation is an emerging treatment modality for the treatment of atrial fibrillation ( AF ) and is increasingly used in patients with heart failure . METHODS The catheter ablation versus st and ard conventional treatment in patients with left ventricular dysfunction and atrial fibrillation trial ( CASTLE-AF ) is a r and omized evaluation of ablative treatment of atrial fibrillation in patients with left ventricular dysfunction . The primary endpoint is the composite of all-cause mortality or worsening of heart failure requiring unplanned hospitalization using a time to first event analysis . Secondary endpoints are all-cause mortality , cardiovascular mortality , cerebrovascular accidents , worsening of heart failure requiring unplanned hospitalization , unplanned hospitalization due to cardiovascular reason , all-cause hospitalization , quality of life , number of therapies ( shock and antitachycardia pacing ) delivered by the implantable cardioverter-defibrillator ( ICD ) , time to first ICD therapy , number of device-detected ventricular tachycardia and ventricular fibrillation episodes , AF burden , AF free interval , left ventricular function , exercise tolerance , and percentage of right ventricular pacing . CASTLE-AF will r and omize 420 patients for a minimum of 3 years at 48 sites in the United States , Europe , Australia , and South America", "INTRODUCTION Catheter ablation is potentially curative treatment for atrial fibrillation ( AF ) . However , complications are more frequent and more severe compared with other ablation procedures . We investigated the complication rate in 1,000 AF ablation procedures in a high-volume center and examined possible risk factors . METHODS AND RESULTS One thous and consecutive circumferential pulmonary vein radiofrequency ablations were performed for symptomatic , drug-refractory AF . Major complications were defined as the ones that were life threatening , caused permanent harm , and required intervention or prolonged hospitalization . Thirty-nine ( 3.9 % ) major periprocedural complications were observed . There was no death immediately associated with the procedure . However , there were 2 deaths ( 0.2 % ) of unclear cause , 14 days and 4 weeks after ablation . The most common complications were tamponade ( 1.3 % ) , treated mainly by percutaneous drainage , and vascular complications ( 1.1 % ) . There were also 4 thromboembolic events ( 0.4 % ) : 3 nonfatal strokes and one transient ischemic attack . Importantly , 2 cases ( 0.2 % ) of atrial-esophageal fistula and 2 cases ( 0.2 % ) of endocarditis were observed . Factors associated with an increased complication risk were age > or = 75 years ( hazard ratio 3.977 , P = 0.022 ) and congestive heart failure ( hazard ratio 5.174 , P = 0.001 ) . CONCLUSION AF ablation still has a considerable number of major complications that may be life threatening or may lead to severe residues . Atrial-esophageal fistula is still observed despite continuous systematic methods to prevent it . Stroke , tamponade , and vascular complications are the most frequent major complications . However , in most patients treatment can be conservative and results in complete recovery . Advanced age and congestive heart failure seem to be associated with an increased risk of complications", "BACKGROUND Pulmonary-vein isolation is increasingly being used to treat atrial fibrillation in patients with heart failure . METHODS In this prospect i ve , multicenter clinical trial , we r and omly assigned patients with symptomatic , drug-resistant atrial fibrillation , an ejection fraction of 40 % or less , and New York Heart Association class II or III heart failure to undergo either pulmonary-vein isolation or atrioventricular-node ablation with biventricular pacing . All patients completed the Minnesota Living with Heart Failure question naire ( scores range from 0 to 105 , with a higher score indicating a worse quality of life ) and underwent echocardiography and a 6-minute walk test ( the composite primary end point ) . Over a 6-month period , patients were monitored for both symptomatic and asymptomatic episodes of atrial fibrillation . RESULTS In all , 41 patients underwent pulmonary-vein isolation , and 40 underwent atrioventricular-node ablation with biventricular pacing ; none were lost to follow-up at 6 months . The composite primary end point favored the group that underwent pulmonary-vein isolation , with an improved question naire score at 6 months ( 60 , vs. 82 in the group that underwent atrioventricular-node ablation with biventricular pacing ; P 6-minute-walk distance ( 340 m vs. 297 m , P ejection fraction ( 35 % vs. 28 % , P underwent pulmonary-vein isolation , 88 % of patients receiving antiarrhythmic drugs and 71 % of those not receiving such drugs were free of atrial fibrillation at 6 months . In the group that underwent pulmonary-vein isolation , pulmonary-vein stenosis developed in two patients , pericardial effusion in one , and pulmonary edema in another ; in the group that underwent atrioventricular-node ablation with biventricular pacing , lead dislodgment was found in one patient and pneumothorax in another . CONCLUSIONS Pulmonary-vein isolation was superior to atrioventricular-node ablation with biventricular pacing in patients with heart failure who had drug-refractory atrial fibrillation . ( Clinical Trials.gov number , NCT00599976 .", "INTRODUCTION Congestive heart failure ( CHF ) and atrial fibrillation ( AF ) are frequently linked , and when associated produce additive deleterious effects . In this prospect i ve study , the effects of catheter ablation for AF in patients with impaired left ventricular ( LV ) function are presented . METHODS Baseline data and clinical outcome have been prospect ively collected in 105 consecutive patients who underwent pulmonary vein ablation for the control of AF . We evaluated 40 patients affected by LV dysfunction with ejection fraction (EF) and compared them to the remaining 65 patients with normal ventricular function in terms of changes in LV function , maintenance of sinus rhythm , and quality of life during follow-up . RESULTS After a mean follow-up of 14+/-2 months , 87 % of patients with impaired LV function and 92 % of patients with normal ventricular function were in sinus rhythm , with or without antiarrhythmic therapy ( P = NS ) . A significant improvement in LVEF and fractional shortening was documented in patients with CHF ( 33+/-2 % vs 47+/-3 % , and 19+/-4 % vs 30+/-3 % , P exercise capacity and quality of life documented better improvements in patients with CHF compared to patients without CHF . CONCLUSIONS Catheter ablation in patients with LV dysfunction is feasible , not associated with higher procedural complications , and provides a significant improvement in LV performance , symptoms , and quality of life during follow-up", "BACKGROUND Congestive heart failure and atrial fibrillation often coexist , and each adversely affects the other with respect to management and prognosis . We prospect ively evaluated the effect of catheter ablation for atrial fibrillation on left ventricular function in patients with heart failure . METHODS We studied 58 consecutive patients with congestive heart failure and a left ventricular ejection fraction of less than 45 percent who were undergoing catheter ablation for atrial fibrillation . We selected as controls 58 patients without congestive heart failure who were undergoing ablation for atrial fibrillation , matched according to age , sex , and classification of atrial fibrillation . We evaluated the patients ' left ventricular function and dimensions , symptom score , exercise capacity , and quality of life at baseline and at months 1 , 3 , 6 , and 12 . RESULTS After a mean ( + /-SD ) of 12+/-7 months , 78 percent of the patients with congestive heart failure and 84 percent of the controls remained in sinus rhythm ( P=0.34 ) ( 69 percent and 71 percent , respectively , were in sinus rhythm without the administration of antiarrhythmic drugs ) . The patients with congestive heart failure had significant improvement in left ventricular function ( increases in the ejection fraction and fractional shortening of 21+/-13 percent and 11+/-7 percent , respectively ; P left ventricular dimensions ( decreases in the diastolic and systolic diameters of 6+/-6 mm and 8+/-7 mm , respectively ; P=0.03 and P exercise capacity , symptoms , and quality of life . The ejection fraction improved significantly not only in patients without concurrent structural heart disease ( 24+/-10 percent , P catheter ablation without the use of drugs in patients with congestive heart failure and atrial fibrillation significantly improve cardiac function , symptoms , exercise capacity , and quality of life", "OBJECTIVES The aim of this multicenter study was to evaluate the safety of discontinuing oral anticoagulation therapy ( OAT ) after apparently successful pulmonary vein isolation . BACKGROUND Atrial fibrillation ( AF ) is associated with an increased risk of thromboembolic events ( TE ) and often requires OAT . Pulmonary vein isolation is considered an effective treatment for AF . METHODS We studied 3,355 patients , of whom 2,692 ( 79 % male , mean age 57 + /- 11 years ) discontinued OAT 3 to 6 months after ablation ( Off-OAT group ) and 663 ( 70 % male , mean age 59 + /- 11 years ) remained on OAT after this period ( On-OAT group ) . CHADS(2 ) ( congestive heart failure , hypertension , age [ 75 years and older ] , diabetes mellitus , and a history of stroke or transient ischemic attack ) risk scores of 1 and > or = 2 were recorded in 723 ( 27 % ) and 347 ( 13 % ) Off-OAT group patients and in 261 ( 39 % ) and 247 ( 37 % ) On-OAT group patients , respectively . RESULTS During follow-up ( mean 28 + /- 13 months vs. 24 + /- 15 months ) , 2 ( 0.07 % ) Off-OAT group patients and 3 ( 0.45 % ) On-OAT group patients had an ischemic stroke ( p = 0.06 ) . No other thromboembolic events occurred . No Off-OAT group patient with a CHADS(2 ) risk score of > or = 2 had an ischemic stroke . A major hemorrhage was observed in 1 ( 0.04 % ) Off-OAT group patient and 13 ( 2 % ) On-OAT group patients ( p risk-benefit ratio favored the suspension of OAT after successful AF ablation even in patients at moderate-high risk of TE . This conclusion needs to be confirmed by future large r and omized trials" ]

[ "Observational longitudinal research is particularly useful for assessing etiology and prognosis and for providing evidence for clinical decision making . However , there are no structured reporting requirements for studies of this design to assist authors , editors , and readers . The authors developed and tested a checklist of criteria related to threats to the internal and external validity of observational longitudinal studies . The checklist criteria concerned recruitment , data collection , biases , and data analysis and descriptive issues relevant to study rationale , study population , and generalizability . Two raters independently assessed 49 r and omly selected articles describing stroke research published from 1999 to 2003 in six journals : American Journal of Epidemiology , Journal of Epidemiology and Community Health , Stroke , Annals of Neurology , Archives of Physical Medicine and Rehabilitation , and American Journal of Physical Medicine and Rehabilitation . On average , 17 of the 33 checklist criteria were reported . Criteria describing the study design were better reported than those related to internal validity . No relation was found between study type ( etiologic or prognostic ) or word count and quality of reporting . A flow diagram for summarizing participant flow through a study was developed . Editors and authors should consider using a checklist and flow diagram when reporting on observational longitudinal research", "Background Walking and cycling to school are one source of regular physical activity . The aim of this two years observational study in pre-pubertal children was to evaluate if walking and cycling to school was associated with higher total amount of physical activity and larger gain in bone mineral content ( BMC ) and bone width than when going by car or bus . Methods 133 boys and 99 girls aged 7 - 9 years were recruited to the Malmö Prospect i ve Paediatric Osteoporosis Prevention ( POP ) study . BMC ( g ) was measured by dual X-ray absorptiometry ( DXA ) in total body , lumbar spine ( L2-L4 ) and femoral neck ( FN ) at baseline and after 24 months . Bone width was measured in L2-L4 and FN . Skeletal changes in the 57 boys and 48 girls who consistently walked or cycled to school were compared with the 24 boys and 17 girls who consistently went by bus or car . All children remained in Tanner stage I. Level of everyday physical activity was estimated by accelerometers worn for four consecutive days and question naires . Comparisons were made by independent student 's t-tests between means and Fisher 's exact tests . Analysis of covariance ( ANCOVA ) was used to adjust for group differences in age at baseline , duration of organized physical activity , annual changes in length and BMC or bone width if there were differences in these traits at baseline . Results After the adjustments , there were no differences in the annual changes in BMC or bone width when comparing girls or boys who walked or cycled to school with those who went by car or bus . Furthermore , there were no differences in the levels of everyday physical activity objective ly measured by accelerometers and all children reached above the by the United Kingdom Expert Consensus Group recommended level of 60 minutes moderate to vigorous physical activity per day . Conclusion A physical active transportation to school for two years is in pre-pubertal children not associated with a higher accrual of BMC or bone width than a passive mode of transportation , possibly due to the fact that the everyday physical activity in these pre-pubertal children , independent of the mode of school transportation , was high", "OBJECTIVE To prospect ively examine potential benefits of active commuting to school on measures of weight status and physical activity in a sample of youth . RESEARCH METHODS AND PROCEDURES A cohort of students from seven elementary schools was measured four times -- in the fall and spring of fourth grade ( N = 1083 ) and fifth grade ( N = 924 ) . Participants were classified as active ( walking , biking , or skateboarding to school almost every day for baseline analyses or at least 2 d/wk for analyses of consistent active commuting ) or non-active commuters to school . Accelerometers were used to measure physical activity . Height , weight , and skinfolds were objective ly assessed . RESULTS Boys who actively commuted to school had lower BMI ( p skinfolds ( p BMI change or overweight status . DISCUSSION Walking and cycling to school may contribute to preventing excessive weight gain , or leaner children may walk or cycle to school", "OBJECTIVE This study examined differences in ( 1 ) psychosocial correlates of physical activity and in ( 2 ) physical activity within different context s and sedentary behaviors between normal weight and overweight adolescents . It further explored whether the prediction of physical activity by the psychosocial correlates is different in normal weight and overweight adolescents . RESEARCH METHODS AND PROCEDURE A community sample of 6078 11 to 19 year olds from 38 secondary schools , which were r and omly selected throughout the country , completed a vali date d computerized question naire about physical activity , sedentary behaviors , and psychosocial correlates . Differences in mean scores on the psychosocial correlates and on the self-rated physical activity were analyzed between the normal weight ( n=5563 ) and the overweight ( n=515 , 8.5 % ) group . RESULTS This study showed that overweight adolescents do less intense physical activities ( p psychosocial correlates related to physical activity ( p strength of the associations between psychosocial variables and total physical activity were comparable in overweight and normal weight adolescents . More support from family and friends , more fun in physical activity , higher self-efficacy , the perception of more competition benefits , and the perception of less lack of interest were all associated with higher total levels of physical activity . The results suggest that no specific tailoring on psychosocial correlates of physical activity is necessary for overweight adolescents compared with normal weight ones . DISCUSSION Both overweight and normal weight adolescents can be approached by interventions focusing on the same psychosocial variables to increase physical activity", "PURPOSE This study was conducted to determine if fifth- grade students who walked or bicycled to school on a regular basis were more physically active than those that did not . METHODS The sample consists of 219 fifth- grade students ( 10.3 + /- 0.6 yr , 44 % male , 58 % minority ) from eight r and omly selected urban and suburban elementary schools . Students wore an Acti-Graph physical activity monitor during the same week that they completed a daily survey to report their mode of transportation to and from school . Students were categorized on the number of reported active commuting trips , to and from school , per week ( regular;>or=5 ( N=11 ) , irregular ; 1 - 4 ( N=25 ) , nonactive ; 0 ( N=183 ) ) . RESULTS Compared with both other groups , regular active commuters accumulated 3 % more minutes of moderate-to-vigorous physical activity ( MVPA ; P=0.04 ) during weekdays . This weekday difference was because of regular active commuters accumulating 8.5 % more minutes of MVPA both before and after school ( P physical activity was seen among groups during school or in the evening . Based on the mean number of minutes the students wore their monitors on weekdays ( 800 min.d ) , the 3 % difference translates into approximately 24 additional minutes of MVPA per day for the regular active commuters . CONCLUSION Walking to school was associated with approximately 24 additional minutes of MVPA per day in fifth- grade students . Additional observational and experimental research in larger , more diverse sample s is needed to further clarify the effects of active commuting to school on total daily physical activity and other health outcomes", "BACKGROUND & OBJECTIVE Overweight and obesity are important determinants of health leading to adverse metabolic changes and increase the risk of non communicable diseases . Following the increase in adult obesity , the proportion of overweight and obese children and adolescents has also been increasing . Hence , the present study was undertaken to study the magnitude of overweight/obesity and its correlates among school going children of Wardha city in central India and suggest interventions . METHODS The cross-sectional study was carried out in all the 31 middle-schools ( 5th to 7th st and ard ) and high-schools ( 8th to 10th st and ard ) of Wardha city . Probability proportionate to size of population technique ( PPS ) was used to decide the number of children to be studied from each school , each class and then each section . Systematic r and om sampling technique was used to select the children from each section . Pre- design ed and pre-tested question naire was used to elicit the information on family characteristics and individual characteristics . Height and weight was measured and BMI was calculated . Overweight and obesity was assessed by BMI for age . Student who had BMI for age > or=85th and were classified as overweight and BMI for age > or=95th percentile of reference population were classified as obese . RESULTS Overweight and obesity was found to be 3.1 per cent ( 95 % CI : 2.5 - 3.8 % ) and 1.2 per cent ( 95 % CI : 0.8 - 1.8 % ) respectively ; together constitute 4.3 per cent ( 95 % CI : 3.6 - 5.2 % ) for overweight/ obesity . Final model of the multivariate logistic regression showed that the important correlates of overweight/obesity were urban residence , father and /or mother involved in service/business , English medium school and child playing outdoor games for less than 30 min . INTERPRETATION & CONCLUSION The magnitude of overweight/obesity among school going children of Wardha city was found to be 4.3 per cent . Family characteristics play important role in predisposing the children to overweight/obesity and hence the interventions need to be directed towards the families", "BACKGROUND Availability of parks is associated with higher levels of physical activity among children and adolescents . Few studies examine actual park use and park-based physical activity in these population s. PURPOSE This study examined associations among individual , park , and neighborhood environmental characteristics and children 's and adolescent 's park-based physical activity . METHODS Data were collected in 2007 on 2712 children in 20 r and omly selected parks in Durham NC . The System for Observing Play and Recreation in Communities ( SOPARC ) provided measures of physical activity . Hierarchic regression analysis assessed associations among individual , park , and neighborhood environmental characteristics and children 's park-based physical activity . Data were analyzed in 2010 . RESULTS Of the 2712 children observed , 34.2 % and 13.2 % were engaged in walking or vigorous physical activity . Environmental features of parks were associated with activity levels whereas neighborhood characteristics were not . Physical activity was negatively associated with gender ( girls ) ( p=0.003 ) ; presence of a parent ( p nonparental adult ( p=0.006 ) ; and an interaction involving the 0 - 5 years age group and style of play ( p=0.017 ) . Higher level of physical activity was associated with presence of other active children ( p number of recreation facilities and formal activities ( p=0.004 ) . CONCLUSIONS These social factors and design features should be considered in order to stimulate higher levels of park-based physical activity among children and adolescents", "BACKGROUND Active school transport ( AST ) is a recommended strategy to promote physical activity ( PA ) and prevent overweight ( OW ) in school-aged children . In many developing countries , such as Colombia , this association has not been well characterized . OBJECTIVE To determine the association between AST and weight status in a representative sample of adolescents from Montería , Colombia . METHODS Participants were 546 adolescents ( 278 boys ) aged 11 to 18 years old from 14 r and omly selected schools in Montería , Colombia in 2008 . The PA module of the Global School Health Survey ( GSHS-2007 ) was used to determine the prevalence of AST . To identify OW , participants were classified according to CDC 2000 criteria ( BMI ≥ 85th percentile ) . Association between AST and OW was determined by binomial logistic regression . RESULTS Odds ratios adjusted for age , sex , location of school , compliance with PA , and screen time recommendations showed that adolescents who reported AST had a significantly lower likelihood to be OW compared with adolescents who reported nonactive transportation ( OR = 0.5 , 95 % CI 0.3 - 0.8 , P AST as a useful PA domain with potential implication s for overweight prevention , in rapidly developing setting s. Further epidemiologic and intervention studies addressing AST are needed in the region" ]

[ "In order to determine whether treatment of hyperlipidaemia with simvastatin impairs exercise stress responses and so may contribute to an excess of suicides and violent deaths , the effects of simvastatin 20 mg daily and placebo on exercise physiology were compared in 19 patients . After 6 weeks of treatment there was no evidence of reduced exercise capacity , or of reduced cortisol or catecholamine responses . It is concluded that treatment of hyperlipidaemia with an inhibitor of HMG-CoA reductase does not significantly modify stress responses , and so the explanation for a possible increase in non-cardiac mortality must be sought elsewhere", "Objective . The present study was design ed to evaluate the lipid-altering efficacy , safety , and tolerability of lovastatin treatment in adolescent girls with heterozygous familial hypercholesterolemia . Methods . A total of 54 postmenarchal girls , aged 10 to 17 years , were enrolled in a 24-week , double-blind , r and omized , placebo-controlled study . After a 4-week diet/placebo run-in period , patients were r and omized to 1 of 2 groups : ( 1 ) treatment with diet plus lovastatin 20 mg/day for 4 weeks , followed by diet plus lovastatin 40 mg/day for 20 weeks , or ( 2 ) diet plus placebo for 24 weeks . Results . Baseline values of lipids , lipoproteins , and apolipoproteins ( apo ) were comparable between treatment groups . Lovastatin treatment was efficacious at reducing low-density lipoprotein cholesterol by 23 % to 27 % , total cholesterol by 17 % to 22 % , and apo B by 20 % to 23 % at weeks 4 and 24 , respectively . Between-treatment group differences were not statistically significant for triglycerides , very-low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , or apo A-I. Lovastatin was generally safe and well tolerated . There were no clinical ly significant alterations in vital signs ( blood pressure and pulse rate ) , anthropomorphic measurements ( height , weight , and BMI ) , hormone levels ( luteinizing hormone , follicle-stimulating hormone , dehydroepi and rosterone sulfate , estradiol , and cortisol ) , menstrual cycle length , or tests of liver and muscle function . Conclusions . Lovastatin offers an efficacious and well-tolerated treatment option for improving lipid profiles in adolescent girls with familial hypercholesterolemia", "CONTEXT Heterozygous familial hypercholesterolemia ( HeFH ) is a common disorder associated with early coronary artery disease , especially in men . The age at which drug therapy should be started is still controversial , as is the use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) . OBJECTIVE To assess the lipid-lowering efficacy , biochemical safety , and effect on growth and sexual development of lovastatin in adolescent boys with HeFH . DESIGN One-year , double-blind , placebo-controlled , balanced , 2-period , 2-arm r and omized trial . In the first period ( 24 weeks ) , lovastatin was increased at 8 and 16 weeks and the dosage remained stable during the second period ( 24 weeks ) . The study was conducted between 1990 and 1994 . SETTING Fourteen pediatric outpatient clinics in the United States and Finl and . PATIENTS Boys aged 10 to 17 years with HeFH . Of 132 r and omized subjects ( 67 intervention , 65 placebo ) , 122 ( 63 intervention , 59 placebo ) and 110 ( 61 intervention , 49 placebo ) completed the first and second periods , respectively . INTERVENTION Lovastatin , starting at 10 mg/d , with a forced titration at 8 and 16 weeks to 20 and 40 mg/d , respectively , or placebo . MAIN OUTCOME MEASURES The primary efficacy outcome measure was low-density lipoprotein cholesterol ( LDL-C ) . Primary safety measures were growth and sexual development . RESULTS Compared with placebo , LDL-C levels of patients receiving lovastatin decreased significantly ( P Growth and sexual maturation assessed by Tanner staging and testicular volume were not significantly different between the lovastatin and placebo groups at 24 weeks ( P = .85 ) and 48 weeks ( P = .33 ) ; neither were serum hormone levels or biochemical parameters of nutrition . However , the study was underpowered to detect significant differences in safety parameters . Serum vitamin E levels were reduced with lovastatin treatment consistent with reductions in LDL-C , the major carrier of vitamin E in the circulation . CONCLUSIONS This study in adolescent boys with HeFH confirmed the LDL-C-reducing effectiveness of lovastatin . Comprehensive clinical and biochemical data on growth , hormonal , and nutritional status indicated no significant differences between lovastatin and placebo over 48 weeks , although further study is required", "Effects of cortisol on human mood during stress situations are still incompletely understood , although this topic has important clinical implication s. In this experiment , the mood of 44 healthy young women ( all oral contraceptive users ) was examined . A double-blind , r and omized , placebo-controlled time series paradigm was used . Subjects were treated with either 30-mg cortisol or placebo orally . Forty-five minutes later , subjects attended a psychosocial stress procedure ( Trier Social Stress Test ; TSST ; C. Kirschbaum , K. M. Pirke , & D. H. Hellhammer , 1993 ) . The course of the subjects ' mood as well as salivary cortisol and alpha-amylase levels were measured before and after the TSST . With regard to mood , it was found that the groups did not differ in mood before the TSST . After stress exposure , the subjective ratings of current mood state of cortisol-treated women were significantly less negative than that of placebo-treated subjects . These findings show that raising cortisol levels prior to acute stress has a protective effect on mood during stress situations . Results are discussed with regard to the context of specific adaptive effects of cortisol and the role of cortisol in posttraumatic stress disorder", "Statine reduzieren die Cholesterin- und Isoprenoid-de-novo-Biosynthese , darüber hinaus die rezeptorvermittelte Aufnahme von Cholesterin für die Steroidhormonsynthese . In der vorgelegten r and omisierten , placebo-kontrollierten Studie wurde der Effekt von Pravastatin ( 40 mg/Tag ) auf die Plasmakonzentrationen von Steroidhormonen und Gonadotropinen untersucht . Die Patienten ( n = 22 ; 15 Männer , 7 Frauen ) wurden mit Pravastatin 40 mg/Tag oder Placebo beh and elt . Die Konzentrationen des Gesamtcholesterins sowie des LDL-Cholesterins und der Steroidhormone Östradiol , Testosteron , Cortisol und Dehydroepi and rosteron-Sulfat ( DHEAS ) sowie der Gonadotropine FSH und LH wurden untersucht . Pravastatin führte zu einer signifikanten Reduktion der Serumkonzentration des Gesamtcholesterins und des LDL-Cholesterins . Signifikante Veränderungen von Östradiol , Testosteron , Cortisol oder DHEAS wurden nicht beobachtet . Kompensatorische Veränderungen von FSH oder LH f and en sich nicht . Es wird schlussgefolgert , dass die Pravastatin-Therapie , die zu einer signifikanten Reduktion des Gesamtcholesterins und des LDL-Cholesterins führte , in therapeutisch verwendeten Dosierungen keinen Einfluss auf die Steroidhormon- Synthese oder die Freisetzung von Gonadotropinen hat . Statins reduce cholesterol and isoprenoid de novo bio synthesis as well as receptormediated uptake of cholesterol for steroidogenesis . The present r and omized placebo-controlled trial investigated whether pravastatin ( 40 mg/day ) reduces the plasma concentrations of steroid hormones as well as of gonadotropins . Patients ( n = 22 ; 15 males , 7 females ) were treated with pravastatin ( 40 mg/day ) or placebo . Levels of total and LDL cholesterol , the steroid hormones estradiol , testosterone , cortisol and dehydroepi and rosterone sulphate ( DHEAS ) as well as FSH and LH were studied . Pravastatin led to a significant reduction of total cholesterol and LDL cholesterol . There was no significant change in estradiol , testosterone , cortisol or DHEAS plasma concentrations . There was no compensatory change in FSH or LH . It is concluded that pravastatin does not alter steroid hormones or gonadotropins in a clinical ly applicable dose , which significantly reduces total and LDL cholesterol", "In this open-label , balanced , r and omized , placebo-controlled , parallel study , healthy male volunteers were r and omly divided into two groups . Each group received either a single oral dose of rosuvastatin 20 mg or placebo . Estimations were done at predose on day 1 of dosing ( baseline ) and 24 h postdose after days 7 and 14 . Serum cortisol and serum lipid levels were estimated using enzyme-linked immunosorbent assay kits and serum mevalonic acid ( MVA ) levels were measured using vali date d liquid chromatography – t and em mass spectrometry method . Rosuvastatin produced a statistically significant ( P total cholesterol , low-density lipoprotein cholesterol , very low-density lipoprotein cholesterol , and triglycerides . However , the increase in high-density lipoprotein cholesterol and decrease in cortisol and MVA were not statistically significant when compared to the placebo-treated group . The study showed that rosuvastatin at a dose of 20 mg/day for a period of 14 days was very potent as cholesterol-lowering agent , without any significant change in serum cortisol level in the healthy Indian male population", "BACKGROUND The West of Scotl and Coronary Prevention Study was a r and omized clinical trial comparing pravastatin with placebo in men with hypercholesterolemia who did not have a history of myocardial infa rct ion , with an average follow-up of approximately 5 years . The combined outcome of death from definite coronary heart disease or definite nonfatal myocardial infa rct ion was reduced from 7.9 to 5.5 % ( P deaths , hospitalizations and deaths due to coronary events and stroke , and incident cancers and deaths from cancer were tracked with the use of a national computerized record-linkage system . The results were analyzed with time-to-event analyses and use of Cox proportional-hazards models . RESULTS Five years after the trial ended , 38.7 % of the original statin group and 35.2 % of the original placebo group were being treated with a statin . In the period approximately 10 years after completion of the trial , the risk of death from coronary heart disease or nonfatal myocardial infa rct ion was 10.3 % in the placebo group and 8.6 % in the pravastatin group ( P=0.02 ) ; over the entire follow-up period , the rate was 15.5 % in the placebo group and 11.8 % in the pravastatin group ( P combined rate of death from coronary heart disease and hospitalization for coronary events for both periods . The rate of death from cardiovascular causes was reduced ( P=0.01 ) , as was the rate of death from any cause ( P=0.03 ) , over the entire follow-up period . There were no excess deaths from noncardiovascular causes or excess fatal or incident cancers . CONCLUSIONS In this analysis , 5 years of treatment with pravastatin was associated with a significant reduction in coronary events for a subsequent 10 years in men with hypercholesterolemia who did not have a history of myocardial infa rct ion", "Objective —The intercellular adhesion molecule-1 ( ICAM-1/CD54 ) and its lig and , CD11a/CD18 , mediate endothelial adhesion of leukocytes and their consecutive transmigration . Anti-inflammatory effects of statins are considered to be exerted in part through inhibition of leukocyte – endothelial interactions . We investigated the in vivo effects of simvastatin treatment in hypercholesterolemic patients and the influence of various statins on expression of cellular adhesion molecules in vitro . Methods and Results —A total number of 107 hypercholesterolemic patients were treated with 20 mg ( n=52 ) or 40 mg ( n=55 ) of simvastatin daily . After 6 weeks of treatment , peripheral blood mononuclear cells ( P BMC s ) expressed lower amounts of CD54- , CD18- , and CD11a-mRNA compared with pretreatment values . Surface expression of CD54 and CD18/CD11a on CD14 + -monocytes also decreased significantly in both groups of patients . Moreover , simvastatin , atorvastatin , and cerivastatin were found to downregulate tumor necrosis factor (TNF)-&agr ;– induced expression of CD54 and CD18/CD11a in isolated P BMC s obtained from normal donors as well as TNF-&agr ;– dependent expression of these CAMs in cultured human umbilical vein endothelial cells ( HUVECs ) . Furthermore , all three statins were found to reduce the binding of P BMC s to TNF-&agr ;– stimulated HUVECs in vitro . Conclusions —Statin-induced inhibition of expression of CD54 and CD18/CD11a in P BMC s and HUVECs with consecutive loss of adhesive function may contribute to the anti-inflammatory effects of these drugs and some of their beneficial clinical activities", "Background —Statins may exert important pleiotropic effects , ie , improve endothelial function , independently of their impact on LDL cholesterol . In humans , however , pleiotropic effects of statins have never been unequivocally demonstrated because prolonged statin treatment always results in reduced LDL cholesterol levels . We therefore tested the hypothesis that similar reductions in LDL cholesterol with simvastatin and ezetimibe , a novel cholesterol absorption inhibitor , result in different effects on endothelial function . Methods and Results —Twenty patients with chronic heart failure were r and omized to 4 weeks of simvastatin ( 10 mg/d ) or ezetimibe ( 10 mg/d ) treatment . Flow-dependent dilation ( FDD ) of the radial artery was determined by high-resolution ultrasound before and after intra-arterial vitamin C to determine the portion of FDD inhibited by radicals ( ΔFDD-VC ) . Activity of extracellular superoxide dismutase , a major vascular antioxidant enzyme system , was determined after release from the endothelium by a heparin bolus injection . Endothelial progenitor cells were analyzed with an in vitro assay . Simvastatin and ezetimibe treatment reduced LDL cholesterol to a similar extent ( 15.6 % versus 15.4 % ; P = NS ) , whereas changes in mevalonate , the product of HMG-CoA-reductase , differed between groups ( Δmevalonate-simvastatin , −1.04±0.62 versus Δmevalonate-ezetimibe , 1.79±0.94 ng/mL ; P Importantly , FDD was markedly improved after simvastatin ( 10.5±0.6 % versus 5.1±0.7 % ; P after ezetimibe treatment ( 5.6±0.5 % versus 5.8±0.6 % ; P = NS ) . ΔFDD-VC was substantially reduced after simvastatin but not after ezetimibe treatment . Extracellular superoxide dismutase activity was increased by > 100 % ( P after simvastatin but not ezetimibe treatment . Simvastatin treatment increased the number of functionally active endothelial progenitor cells , whereas ezetimibe had no effect . Conclusions —Four weeks of simvastatin treatment improves endothelial function independently of LDL cholesterol lowering , at least in part by reducing oxidant stress . Simvastatin may thereby exert important pleiotropic effects in humans", "Epidemiological and clinical studies have suggested that powerful cholesterol lowering may have adverse effects on mood and psychological well-being . Inhibition of cholesterol bio synthesis by simvastatin ( a hydroxymethyl glutaryl coenzyme A reductase inhibitor ) may also reduce steroid hormone bio synthesis . To explore if mood changes are related with steroid hormone levels , we design ed a r and omized double-blind placebo-controlled crossover trial . The separate and combined effects of a Mediterranean-type diet intervention and treatment with simvastatin 20 mg/day PO for 12 weeks were studied in 120 hypercholesterolemic but otherwise healthy middle-aged men . Psychological functioning was assessed with question naires , and steroid hormone levels in blood were assayed radioimmunologically before and after the treatments . Simvastatin result ed in a statistically significant increase of depression and somatization without changes in the anxiety , hostility or aggression scores . Mood changes seemed to be unrelated with the statistically significant but clinical ly insignificant decline in serum testosterone levels and unrelated with the increase in serum dehydroepi and rosterone levels" ]

[ "Objective : To analyse the effects of smoking reduction and smoking cessation on incidence of myocardial infa rct ion after adjustment for established cardiovascular risk factors . Design : Prospect i ve cohort study with record linkage to mortality and hospital registers . The association of individual change in smoking with myocardial infa rct ion was examined in Cox proportional hazard analyses with continuous heavy smokers ( ⩾5 cigarettes/day ) as reference . Setting : Pooled data from three population studies conducted in Copenhagen , Denmark . Participants : 10 956 men and 8467 women with complete information on smoking habits at two examinations five to ten years apart were followed up from the second examination for a first hospital admission or death from myocardial infa rct ion . Mean duration of follow up was 13.8 years . Main results : A total of 643 participants who were heavy smokers at baseline reduced their daily tobacco consumption by at least 50 % without quitting between first and second examination , and 1379 participants stopped smoking . During follow up 1658 men and 521 women experienced a fatal or non-fatal myocardial infa rct ion . After adjustment for cardiovascular risk factors , people who stopped smoking had a decreased risk of myocardial infa rct ion , hazard ratio 0.71 ( 95 % confidence intervals 0.59 to 0.85 ) . Smoking reduction was not associated with reduced risk of myocardial infa rct ion , hazard ratio 1.15 ( 95 % confidence intervals 0.94 to 1.40 ) . These associations remained unchanged after controlling for baseline illness in different ways . Conclusions : Smoking cessation in healthy people reduces the risk of a subsequent myocardial infa rct ion , whereas this study provides no evidence of benefit from reduction in the amount smoked", "Extending a previous finding of an association between functional genetic variation in the mu-opioid receptor gene and response to nicotine replacement therapy , we explored the role of genetic variants in two genes encoding mu-opioid-receptor-interacting proteins , namely ARRB2 and HINT1 . Participants were 374 smokers treated for nicotine dependence with either transdermal nicotine or nicotine nasal spray for 8 weeks in an open-label r and omized trial . In a logistic regression model controlling for OPRM1 genotype , treatment type , and other covariates , we found no significant main effect of ARRB2 genotype on abstinence at either end of treatment or 6-month follow-up . Participants with the HINT1 TT genotype had significantly higher abstinence rates at 6-month follow-up , but this may not be a pharmacogenetic effect , given that the participants were drug free during this time . Haplotype analysis did not reveal any significant associations for either gene . We found an interaction of ARRB2 and OPRM1 genotype on abstinence at 6 months that approached significance ; however , interpretation of this finding is limited by the small number of participants with the minor alleles for both genes . Although these data do not provide support for the role of genetic variation in these mu-opioid-receptor-interacting proteins and smoking cessation , further exploration of opioid pathway genes in larger prospect i ve pharmacogenetic trials may be warranted", "We conducted gender-stratified analyses on a systems-based c and i date gene study of 53 regions involved in nicotinic response and the brain — reward pathway in two r and omized clinical trials of smoking cessation treatments ( placebo , bupropion , transdermal and nasal spray nicotine replacement therapy ) . We adjusted P-values for multiple correlated tests , and used a Bonferroni-corrected α-level of 5 × 10−4 to determine system-wide significance . Four single-nucleotide polymorphisms ( rs12021667 , rs12027267 , rs6702335 , rs12039988 ; r2>0.98 ) in erythrocyte membrane protein b and 4.1 ( EPB41 ) had a significant male-specific marginal association with smoking abstinence ( odds ratio (OR)=0.5 ; 95 % confidence interval ( CI ) : 0.3–0.6 ) at end of treatment ( adjusted P significant male-specific gene – treatment interaction at 6-month follow-up ( adjusted P=3.9 × 10−5 ) ; within males using nasal spray , rs806365 was associated with a decrease in odds of abstinence ( OR=0.04 ; 95 % CI : 0.01–0.2 ) . While the role of CNR1 in substance abuse has been well studied , we report EPB41 for the first time in the nicotine literature", "INTRODUCTION The α4β2 nicotinic receptor is of central importance in tobacco dependence , while the homomeric α7 receptor may also play a role . In this c and i date gene study , we examine the association between 8 single nucleotide polymorphisms ( SNPs ) in genes coding for nicotinic acetylcholine receptor subunits α4 ( rs1044396 , rs2273504 , rs2236196 , and rs2273502 ) , α7 ( rs2133965 and rs4779969 ) , and β2 ( rs2072660 and rs2072661 ) and smoking abstinence in a cohort of quitters enrolled in a clinical trial of behavioral support . METHODS Data were obtained from the \" Patch in Practice \" study , involving 925 smokers in the United Kingdom . All participants were given an 8-week course of 15 mg of transdermal nicotine replacement therapy and blood was taken for genotyping . RESULTS Logistic regression analyses assessed the association between each selected SNP and smoking abstinence at 4 , 12 , 26 , and 52 weeks . There were no statistically significant associations with smoking cessation success or nicotine intake assessed by plasma cotinine levels . However , rs2273502 was associated with a consistent ( though nonsignificant ) increase in the odds of abstinence . CONCLUSIONS There was no compelling evidence that these SNPs were associated with a reduced or higher chance of abstinence . However , rs2273502 may be worth investigating in future studies", "INTRODUCTION We previously reported evidence that the T allele of the dopamine type-2 receptor ( DRD2 ) rs1800497 polymorphism is associated with improved response to nicotine replacement therapy ( NRT ) relative to placebo and that this association may only be present in females . However , evidence of the poor replication validity of genetic association studies is growing , particularly among those that report subgroup analyses . We therefore attempted to replicate our previous finding of an association between the DRD2 rs1800497 genotype and response to NRT in a new , larger cohort , with greater statistical power . METHODS Participants were r and omly assigned to one of two levels of smoking cessation behavioral support ( usual care vs. weekly support ) . All participants received 8 weeks of 15-mg NRT transdermal patch . RESULTS The presence of one or more T alleles was associated with a slightly but not significantly lower likelihood of abstinence at 3 and 6 months . We found evidence of a genotype x sex interaction effect . However , stratified analyses indicated a main effect of genotype opposite to the effect reported previously , with females carrying one or more copies of the T allele less likely to be abstinent . DISCUSSION Our results do not support an association between the DRD2 rs1800497 ( Taq1A ) polymorphism and response to NRT , contrary to our previous study", "We investigated the association of the OPRM1 genotype with long-term smoking cessation and change in body mass index ( BMI ) following a smoking cessation attempt among smokers who attempted to quit using the nicotine replacement therapy ( NRT ) patch or placebo in a r and omized controlled trial , and were followed-up over an 8-year period following their initial cessation attempt . We also investigated possible sex differences in these relationships , given evidence for sex differences in smoking cessation and central opioid mechanisms , as well as some evidence for sex differences in response to NRT . Our results indicate that OPRM1 genotype may moderate the effect of transdermal nicotine patch compared to placebo during active treatment , with a benefit of active NRT treatment evident in the OPRM1 AA genotype group only and those carrying one or more copies of the G allele demonstrating no benefit of active NRT versus placebo patch . Our results also indicate a sex difference in change in BMI at 8-year follow-up following a smoking cessation attempt , with ex-smokers demonstrating an increase in BMI , and this increase being greater in female subjects than in male subjects . We did not observe any association of OPRM1 genotype with change in BMI , although there was a trend for genotype to influence the observed sex difference in change in BMI over time . Future studies should attempt to replicate these findings , and investigate the relationship between both short- and long-term weight gain and smoking cessation and investigate possible mechanisms that may underlie these processes . Future studies should also investigate the role of OPRM1 genotype and smoking cessation on other appetitive and reward behaviours such as alcohol consumption", "This r and omized , double-blinded , placebo-controlled trial examined genetic influences on treatment response to sustained-release bupropion for smoking cessation . Smokers of European ancestry ( N = 291 ) , who were r and omized to receive bupropion or placebo ( 12 weeks ) plus counseling , were genotyped for the dopamine D2 receptor ( DRD2-Taq1A ) , dopamine transporter ( SLC6A3 3 ' VNTR ) , and cytochrome P450 2B6 ( CYP2B6 1459 CT ) polymorphisms . Main outcome measures were cotinine-verified point prevalence of abstinence at end of treatment and at 2- , 6- , and 12-month follow-ups post quit date . Using generalized estimating equations , we found that bupropion , compared with placebo , was associated with significantly greater odds of abstinence at all time points ( all p values DRD2 x bupropion interaction ( B = 1.49 , SE = 0.59 , p = .012 ) [ corrected ] and a three-way DRD2 x bupropion x craving interaction on 6-month smoking cessation outcomes ( B = -0.45 , SE = 0.22 , p = .038 ) , such that smokers with the A2/A2 genotype demonstrated the greatest craving reduction and the highest abstinence rates with bupropion . Furthermore , there was a significant DRD2 x CYP2B6 interaction ( B = 1.43 , SE = 0.56 , p = .01 ) , such that individuals with the DRD2-Taq1 A2/A2 genotype demonstrated a higher odds of abstinence only if they possessed the CYP2B6 1459 T/T or C/T genotype . Because the sample size of this study was modest for pharmacogenetic investigations , the results should be interpreted with caution . Although these results require replication , the data suggest preliminarily that the DRD2-Taq1A polymorphism may influence treatment response to bupropion for smoking cessation and , further , that exploration of gene x gene and gene x craving interactions in future , larger studies may provide mechanistic insights into the complex pharmacodynamics of bupropion", "The A1 allele of the dopamine D2 receptor gene ( DRD2 ) is associated with a reduced number of dopamine binding sites in the brain and with the increased likelihood of substance abuse and addictive behavior . In a study of smokers enrolled in an open-label , r and omized effectiveness trial , we investigated whether variants in the DRD2 receptor gene are associated with smoking cessation outcomes following treatment with a combination of bupropion SR and behavioral counseling . Adherence to treatment and point-prevalent smoking status were assessed at 3 and 12 months , respectively , following a target quit date . Compared to women who carry both A2 alleles , women with at least one A1 allele were more likely to report having stopped taking bupropion due to medication side effects ( odds ratio (OR)=1.91 , 95 % confidence interval (CI)=1.01–3.60 ; P smoking ( OR=0.76 , 95 % CI=0.56–1.03 ; P men . In women , individual variability in responsiveness to bupropion-based treatment may be partially due to differences in genetic variants influencing dopamine receptor function", "We investigated the association of catechol O-methyltransferase ( COMT ) genotype with abstinence following a smoking cessation attempt among a large cohort of smokers who attempted to quit using either the nicotine transdermal patch or placebo and were followed up over an 8-year period following their initial cessation attempt . In addition , we examined the possible moderating influence of sex on any association . The genotype × treatment interaction effect at 12-week follow-up indicated a greater benefit of active nicotine replacement treatment compared with placebo on likelihood of abstinence in the COMT Met/Met genotype group ( 33 % versus 12 % ) , in comparison to the Met/Val + Val/Val group ( 22 % versus 16 % ) . Our results indicate that COMT genotype may moderate the effect of active transdermal nicotine patch compared with placebo , with reduced relative benefit of nicotine replacement therapy in individuals with Met/Val or Val/Val genotype . Our data follow an emerging pattern of results suggesting that genetic variation in the dopamine pathway may provide a future basis for tailored smoking cessation therapies , but indicate that different genes influencing various components of this pathway may have different effects on response to smoking cessation pharmacotherapy . ( Cancer Epidemiol Biomarkers Prev 2007;16(6):1065–9", "ABSTRACT To determine whether the functional mu-opioid receptor ( OPRM1 ) Asn40Asp variant predicts the comparative efficacy of different forms of NRT , we conducted a clinical trial of transdermal nicotine ( TN ) vs nicotine nasal spray ( NS ) in 320 smokers of European ancestry . Smokers carrying the OPRM1 Asp40 variant ( n=82 ) were significantly more likely than those homozygous for the Asn40 variant ( n=238 ) to be abstinent at the end of treatment , and reported less mood disturbance and weight gain . The genotype effect on treatment outcome was most pronounced among smokers receiving TN , particularly during the 21 mg dose phase . Smokers who carry the OPRM1 Asp40 variant are likely to have a favorable response to TN and may benefit from extended therapy with the 21 mg dose", " Smokers ( ⩾10 cigarettes per day , N=331 ) of European ancestry taking part in a double-blind placebo-controlled r and omized trial of 12 weeks of treatment with bupropion along with counseling for smoking cessation were genotyped for a variable number of t and em repeats polymorphism in exon III of the dopamine D4 receptor gene . Generalized estimating equations predicting point-prevalence abstinence at end of treatment and 2 , 6 and 12 months after the end of treatment indicated that bupropion ( vs placebo ) predicted increased odds of abstinence . The main effect of Genotype was not significant . A Genotype × Treatment interaction ( P=0.005 ) showed that bupropion predicted increased odds of abstinence in long-allele carriers ( odds ratios (OR)=1.31 , P whereas bupropion was not associated with abstinence among short-allele homozygotes ( OR=1.06 , P=0.23 ) . The Genotype × Treatment interaction remained when controlling for demographic and clinical covariates ( P=0.01 ) and in analyses predicting continuous abstinence ( P's⩽0.054 ) . Bupropion may be more efficacious for smokers who carry the long allele , which is relevant to personalized pharmacogenetic treatment approaches", "Background : Exposure to prenatal tobacco smoke ( PTS ) has been associated with a number of health outcomes in the offspring , including some childhood cancers . Lower levels of genomic DNA methylation have also been associated with several types of cancers . We investigated whether PTS was associated with global DNA methylation levels in the offspring . Methods : Our sample was drawn from a birth cohort of women born between 1959 and 1963 in New York City ( n = 90 ) . We measured methylation of repetitive elements ( Sat2 , Alu , LINE-1 ) from peripheral blood granulocytes . We combined prospect ively collected data on PTS with adult epidemiologic data and blood sample s collected in 2001 to 2007 ( mean age , 43 years ) . We used linear regression to assess the association between PTS and repetitive element methylation . Results : Thirty-six percent of mothers smoked during pregnancy . We observed an inverse association between PTS and Sat2 methylation . This inverse association remained even after adjustment for potential mediators including child environmental tobacco smoke exposure , birth size , postnatal weight and height changes , and adult smoking status and alcohol intake ( β = −0.22 , 95 % confidence interval = −0.40 to −0.03 for ever exposed to PTS vs. never exposed using models of log-transformed methylation levels ) . PTS exposure was not statistically significantly associated with LINE-1 or Alu methylation . Conclusions : PTS exposure , measured at the time of pregnancy and not retrospectively reported , was associated with a decrease in Sat2 methylation but not LINE-1 or Alu methylation . Impact : If replicated in larger studies , this study supports a persistent effect of PTS on DNA methylation levels , as measured by Sat2 , in adulthood . Cancer Epidemiol Biomarkers Prev ; 20(12 ) ; 2518–23 . © 2011 AACR", "Although the efficacy of pharmacotherapy for tobacco dependence has been previously demonstrated , there is substantial variability among individuals in treatment response . We performed a systems-based c and i date gene study of 1295 single nucleotide polymorphisms ( SNPs ) in 58 genes within the neuronal nicotinic receptor and dopamine systems to investigate their role in smoking cessation in a bupropion placebo-controlled r and omized clinical trial . Putative functional variants were supplemented with tagSNPs within each gene . We used global tests of main effects and treatment interactions , adjusting the P-values for multiple correlated tests . An SNP ( rs2072661 ) in the 3′ UTR region of the β2 nicotinic acetylcholine receptor subunit ( CHRNB2 ) has an impact on abstinence rates at the end of treatment ( adjusted P = 0.01 ) and after a 6-month follow-up period ( adjusted P = 0.0002 ) . This latter P-value is also significant with adjustment for the number of genes tested . Independent of treatment at 6-month follow-up , individuals carrying the minor allele have substantially decreased the odds of quitting ( OR = 0.31 ; 95 % CI 0.18–0.55 ) . Effect of estimates indicate that the treatment is more effective for individuals with the wild-type ( OR = 2.14 , 95 % CI 1.20–3.81 ) compared with individuals carrying the minor allele ( OR = 0.83 , 95 % CI 0.32–2.19 ) , although this difference is only suggestive ( P = 0.10 ) . Furthermore , this SNP demonstrated a role in the time to relapse ( P = 0.0002 ) and an impact on withdrawal symptoms at target quit date ( TQD ) ( P = 0.0009 ) . Overall , while our results indicate strong evidence for CHRNB2 in ability to quit smoking , these results require replication in an independent sample", "Abilities to successfully quit smoking display substantial evidence for heritability in classic and molecular genetic studies . Genomewide association ( GWA ) studies have demonstrated single-nucleotide polymorphisms ( SNPs ) and haplotypes that distinguish successful quitters from individuals who were unable to quit smoking in clinical trial participants and in community sample s. Many of the subjects in these clinical trial sample s were aided by nicotine replacement therapy ( NRT ) . We now report novel GWA results from participants in a clinical trial that sought dose/response relationships for “ precessation ” NRT . In this trial , 369 European-American smokers were r and omized to 21 or 42 mg NRT , initiated 2 wks before target quit date s. Ten-week continuous smoking abstinence was assessed on the basis of self-reports and carbon monoxide levels . SNP genotyping used Affymetrix 6.0 arrays . GWA results for smoking cessation success provided no P value that reached “ genome-wide ” significance . Compared with chance , these results do identify ( a ) more clustering of nominally positive results within small genomic regions , ( b ) more overlap between these genomic regions and those identified in six prior successful smoking cessation GWA studies and ( c ) sets of genes that fall into gene ontology categories that appear to be biologically relevant . The 1,000 SNPs with the strongest associations form a plausible Bayesian network ; no such network is formed by r and omly selected sets of SNPs . The data provide independent support , based on individual genotyping , for many loci previously nominated on the basis of data from genotyping in pooled DNA sample s. These results provide further support for the idea that aid for smoking cessation may be personalized on the basis of genetic predictors of outcome", "Pharmacogenetic clinical trials seek to identify genetic modifiers of treatment effects . When a trial has collected data on many potential genetic markers , a first step in analysis is to screen for evidence of pharmacogenetic effects by testing for treatment‐by‐marker interactions in a statistical model for the outcome of interest . This approach is potentially problematic because ( i ) individual significance tests can be overly sensitive , particularly when sample sizes are large ; and ( ii ) st and ard significance tests fail to distinguish between markers that are likely , on biological grounds , to have an effect , and those that are not . One way to address these concerns is to perform Bayesian hypothesis tests [ Berger ( 1985 ) Statistical decision theory and Bayesian analysis . New York : Springer ; Kass and Raftery ( 1995 ) J Am Stat Assoc 90:773–795 ] , which are typically more conservative than st and ard uncorrected frequentist tests , less conservative than multiplicity‐corrected tests , and make explicit use of relevant biological information through specification of the prior distribution . In this article we use a Bayesian testing approach to screen a panel of genetic markers recorded in a r and omized clinical trial of bupropion versus placebo for smoking cessation . From a panel of 59 single‐nucleotide polymorphisms ( SNPs ) located on 11 c and i date genes , we identify four SNPs ( one each on CHRNA5 and CHRNA2 and two on CHAT ) that appear to have pharmacogenetic relevance . Of these , the SNP on CHRNA5 is most robust to specification of the prior . An unadjusted frequentist test identifies seven SNPs , including these four , none of which remains significant upon correction for multiplicity . In a panel of 43 r and omly selected control SNPs , none is significant by either the Bayesian or the corrected frequentist test . © 2007 Wiley‐Liss ,", "Smokers of European ancestry ( n=720 ) who participated in a double-blind , r and omised , placebo-controlled trial of transdermal nicotine replacement therapy , were genotyped for two functional polymorphisms ( variable number of t and em repeats ( VNTR ) and a C to T transition at position –521 ( C-521 T ) ) in the dopamine D4 receptor gene ( DRD4 ) gene . Logistic regression models of abstinence at 12- and 26-week follow-ups were carried out separately for each polymorphism . For the DRD4 VNTR models , the main effect of treatment was significant at both 12-week ( P=0.001 ) and 26-week ( P=0.006 ) follow-ups , indicating an increased likelihood of successful cessation on active nicotine replacement therapy transdermal patch relative to placebo . The main effect of DRD4 VNTR genotype was associated with abstinence at 12-week follow-up ( P=0.034 ) , with possession of one or more copies of the long allele associated with reduced likelihood of cessation ( 17 vs 23 % ) , but this effect was not observed at 26-week follow-up . For the DRD4 C-521 T models , no main effect or interaction terms involving genotype were retained in the models at either 12- or 26-week follow-up . These data are consistent with observations from studies of the DRD2 gene that genetic variants related to relatively decreased dopaminergic tone in the mesocorticolimbic system are associated with increased risk for relapse to smoking following a cessation attempt", "Despite the efficacy of bupropion for smoking cessation , smokers exhibit variability in treatment outcome . The CYP2B6 gene has been implicated in bupropion kinetics and nicotine metabolism , and is a plausible c and i date for pharmacogenetic studies of treatment response . We investigated whether a functional genetic polymorphism in the CYP2B6 gene predicts smoking outcomes in a placebo-controlled r and omized trial . Four hundred and twenty-six smokers of European Caucasian ancestry provided blood sample s and received bupropion ( 300 mg/day for 10 weeks ) or placebo , plus counseling . Smoking status , abstinence symptoms and side-effects were recorded weekly , and smoking status was verified at the end of treatment and at 6-month follow-up . Smokers with a decreased activity variant of CYP2B6 reported greater increases in cravings for cigarettes following the target quit date and had higher relapse rates . These effects were modified by a significant gender x genotype x treatment interaction , suggesting that bupropion attenuated the effects of genotype among female smokers . We conclude that smokers with the CYP2B6 variant may be more vulnerable to abstinence symptoms and relapse . Bupropion may attenuate these effects , especially among females . Additional trials are warranted to confirm these results , as are studies to explore the neurobiological mechanisms . Such research could ultimately enable practitioners to select the optimal type and dose of medication for individual smokers", "This study examined the role of dopaminergic genes in prospect i ve smoking cessation and response to bupropion treatment in a placebo-controlled clinical trial . Smokers of European ancestry ( N=418 ) provided blood sample s for genetic analysis and received either bupropion or placebo ( 10 weeks ) plus counseling . Assessment s included the dopamine D2 receptor ( DRD2 ) genotype , dopamine transporter ( SLC6A3 ) genotype , demographic factors , and nicotine dependence . Smoking status was verified at the end of treatment ( EOT ) and at 6-month follow-up . The results provided evidence for a significant DRD2 * SLC6A3 interaction effect on prolonged smoking abstinence and time to relapse at EOT , independent of treatment condition . Such effects were no longer significant at 6-month follow-up , however . These results provide the first evidence from a prospect i ve clinical trial that genes that alter dopamine function may influence smoking cessation and relapse during the treatment phase", "BACKGROUND Although bupropion is efficacious for smoking cessation , only a minority of smokers are able to quit . Pharmacogenetic research may improve treatment outcomes through discovery of DNA sequences predictive of successful pharmacotherapy for subgroups of smokers . We investigated variants in the catechol-O-methyltransferase ( COMT ) gene in a smoking cessation trial of bupropion . METHODS A double-blind , placebo-controlled , 10-week trial of bupropion and counseling ( with a 6-month follow-up period ) was conducted at two university-based smoking cessation research programs . Abstinence was biochemically verified at the end of treatment and at 6 months after the target quit date . RESULTS At the end of the treatment phase , statistically significant interaction effects indicated that COMT haplotypes of two SNPs ( rs737865 and rs165599 ) predicted the efficacy of bupropion compared with placebo . This interaction effect was attenuated at 6-month follow-up . CONCLUSIONS COMT haplotypes at rs737865 and rs165599 may predict a favorable outcome for bupropion treatment for smoking cessation . European-American smokers with a G allele at both SNPs may not benefit from bupropion treatment . Small numbers of some COMT haplotypes limit interpretation of response . If study findings are confirmed in additional large studies , COMT genotyping could be applied to identify likely responders to bupropion treatment for smoking cessation ", "Although bupropion and nicotine replacement therapy ( NRT ) are efficacious tobacco dependence treatments , there is substantial interindividual variability in therapeutic response and most smokers relapse . Pharmacogenetics research may improve treatment outcomes by identifying genetic variants predictive of therapeutic response . We investigated the roles of two functional genetic variants in the dopamine D2 receptor ( DRD2 ) gene in response to pharmacotherapy for tobacco dependence among participants in two r and omized clinical trials with a 6-month follow-up period : a double-blind placebo-controlled trial of bupropion ( n=414 ) and an open label trial of transdermal nicotine vs nicotine nasal spray ( n=368 ) . At the end of the treatment phase , a statistically significant ( p=0.01 ) interaction between the DRD2 − 141C Ins/Del genotype and treatment indicated a more favorable response to bupropion among smokers homozygous for the Ins C allele compared to those carrying a Del C allele . By contrast , smokers carrying the Del C allele had statistically significantly ( p=0.006 ) higher quit rates on NRT compared to those homozygous for the Ins C allele , independent of NRT type . The C957 T variant was also associated ( p=0.03 ) with abstinence following NRT . These results suggest that bupropion may be the preferred pharmacologic treatment for smokers homozygous for the DRD2 − 141 Ins C allele , while NRT may be more beneficial for those who carry the Del C allele . Study findings require confirmation in additional larger sample s before they are applied in practice", "We analyzed pooled data from two comparable r and omized placebo-controlled clinical trials of bupropion pharmacotherapy for smoking cessation for which data on DRD2 Taq1A genotype were available . A total of 722 smokers across the two trials were r and omized to 10 weeks of sustained-release bupropion hydrochloride or placebo . General estimating equation analysis demonstrated a significant gene x drug interaction ( B = 0.87 , SE = 0.34 , p = .009 ) . Smokers with the A2/A2 genotype using bupropion were more than three times as likely , relative to placebo , to be abstinent at end of treatment ( 35.2 % vs. 15.1 % ; OR = 3.25 , 95 % CI 2.00 - 5.28 ) and at 6 months of follow-up ( 26.7 % vs. 12.2 % ; OR = 2.81 , 95 % CI 1.66 - 4.77 ) , which was attenuated by 12 months ( 16.3 % vs. 10.7 % ; OR = 1.70 , 95 % CI 0.95 - 3.05 ) . We found no significant benefit of bupropion relative to placebo on smoking cessation outcomes at any time point in participants with A1/A1 or A1/A2 genotypes . These data suggest that bupropion may be effective for smoking cessation only in a subgroup of smokers with the DRD2 Taq1 A2/A2 genotype", "AIMS We investigated whether variants in the serotonin transporter gene ( SLC6A4 ) influence smoking cessation rates using antidepressant therapy ( i.e. bupropion and nortriptyline ) . DESIGN Pharmacogenetic ( secondary ) analysis of a r and omized , placebo-controlled efficacy trial of bupropion and nortriptyline for smoking cessation . SETTING Single-centre study , Maastricht University , the Netherl and s. PARTICIPANTS A total of 214 of 255 ( 84 % ) current daily smokers participating in a r and omized controlled efficacy trial . MEASUREMENTS Subjects were genotyped for three functional variants in SLC6A4 ( 5-HTTLPR , STin2 , rs25531 ) . Primary outcome measures were prolonged abstinence from weeks 4 - 12 , 4 - 26 and 4 - 52 . Secondary outcome measures included 7-day point prevalence abstinence at weeks 4 , 12 , 26 and 52 . FINDINGS Carriers of the 5-HTTLPR high-activity L-variant had higher prolonged cessation rates with bupropion than placebo [ odds ratio ( OR ) = 1.44 , 95 % confidence interval ( CI ) = 1.01 - 2.05 , P = 0.04 ] . Combining the three variants result ed in increased prolonged cessation rates for both bupropion and nortriptyline among carriers of four to five high-activity variants ( bupropion : OR = 2.00 , 95 % CI = 1.21 - 3.29 , P = 0.01 ; nortriptyline : OR = 1.91 , 95 % CI = 1.02 - 3.56 , P = 0.04 ) . Similar results were found for point prevalence abstinence . CONCLUSIONS Bupropion and nortriptyline seem to be more effective in smoking cessation among SLC6A4 high-activity variant carriers , probably by blocking the increased serotonin transporter activity , thereby increasing serotonin levels . Prospect i ve studies have to assess if this can improve cessation rates when treatment is targeted at individuals based on their genotypes", "BACKGROUND CYP2B6 is the primary enzyme involved in bupropion ( Zyban ; GlaxoSmithKline , Research Triangle Park , North Carolina ) metabolism . Genetic polymorphisms in CYP2B6 , such as CYP2B6 * 6 , can alter bupropion metabolism and may affect bupropion treatment outcome . METHODS Subjects participated in a smoking cessation clinical trial of bupropion versus placebo . The main outcome was a 7-day point prevalence abstinence rate measured 10 weeks after the start of treatment ( i.e. , end of treatment ) and at the 6-month follow-up ; secondary outcomes were severity of adverse effects , withdrawal , and urge to smoke . Subjects were haplotyped for the CYP2B6 * 6 variants . RESULTS Among smokers in the CYP2B6 * 6 group ( CYP2B6 * 1/*6 or CYP2B6 * 6/*6 genotype , n = 147 , 45 % of the population ) , bupropion produced significantly higher abstinence rates than placebo at the end of treatment ( 32.5 % vs. 14.3 % , p = .01 ) and at the 6-month follow-up ( 31.2 % vs. 12.9 % , p = .008 ) . In contrast , bupropion was no more effective than placebo for smokers in the CYP2B6 * 1 group ( CYP2B6 * 1/*1 , n = 179 ) at the end of treatment ( 31.0 % vs. 31.6 % , p = .93 ) or at the 6-month follow-up ( 22.0 % vs. 21.5 % , p = .94 ) . There was a significant genotype by treatment interaction at the end of treatment ( odds ratio [ OR ] = 2.97 , confidence interval [ CI ] = 1.05 - 8.40 , p = .04 ) , which was similar at 6-month follow-up ( OR = 2.98 , CI = .98 - 9.06 , p = .05 ) . CONCLUSIONS These data suggest that smokers with the CYP2B6 * 6 genotype have a higher liability to relapse on placebo and that they may be good c and i date s for bupropion treatment for smoking cessation", "The ability to quit smoking is heritable , yet few genetic studies have investigated prospect i ve smoking cessation . We conducted a systems-based genetic association analysis in a sample of 472 treatment-seeking smokers of European ancestry after 8 weeks of transdermal nicotine therapy for smoking cessation . The genotyping panel included 169 single-nucleotide polymorphisms ( SNPs ) in 7 nicotinic acetylcholine receptor subunit genes and 4 genes in the endogenous cholinergic system . The primary outcome was smoking cessation ( biochemically confirmed ) at the end of treatment . SNPs clustered in the choline acetyltransferase ( ChAT ) gene were individually identified as nominally significant , and a 5-SNP haplotype ( block 6 ) in ChAT was found to be significantly associated with quitting success . Single SNPs in ChAT haplotype block 2 were also associated with pretreatment levels of nicotine dependence in this cohort . To replicate associations of SNPs in haplotype blocks 2 and 6 of ChAT with nicotine dependence in a non-treatment-seeking cohort , we used data from an independent community-based sample of 629 smokers representing 200 families of European ancestry . Significant SNP and haplotype associations were identified for multiple measures of nicotine dependence . Although the effect sizes in both cohorts are modest , converging data across cohorts and phenotypes suggest that ChAT may be involved in nicotine dependence and ability to quit smoking . Additional sequencing and characterization of ChAT may reveal functional variants that contribute to nicotine dependence and smoking cessation", "In this follow-up of a r and omized placebo-controlled clinical trial of nicotine replacement transdermal patch for smoking cessation , 741 smokers of European ancestry who were r and omized to receive active patch or placebo patch were genotyped for the serotonin transporter gene-linked polymorphic region . The study setting was a primary care research network in Oxfordshire , United Kingdom . The primary outcome measures were biochemically verified sustained abstinence from cigarette smoking at end of treatment and 24-week follow-up . The main effect of genotype was not associated with sustained abstinence from smoking at either end of treatment ( SL : p=.33 ; SS : p=.81 ) or 24-week follow-up ( SL : p=.05 ; SS : p=.21 ) , and we found no evidence for a genotypextreatment interaction effect . In summary , despite the theoretically important contribution of serotonin neurotransmission to smoking cessation , the serotonin transporter gene was not associated with treatment response to nicotine patch for smoking cessation in this primary care-based trial" ]

[ "BACKGROUND Depression is one of the most disabling diseases , and causes a significant burden both to the individual and to society . WHO data suggests that depression causes 6 % of the burden of all diseases in Europe in terms of disability adjusted life years ( DALYs ) . Yet , the knowledge of the economic impact of depression has been relatively little research ed in Europe . AIMS OF THE STUDY The present study aims at estimating the total cost of depression in Europe based on published epidemiologic and economic evidence . METHODS A model was developed to combine epidemiological and economic data on depression in Europe to estimate the cost . The model was populated with data collected from extensive literature review s of the epidemiology and economic burden of depression in Europe . The cost data was calculated as annual cost per patient , and epidemiologic data was reported as 12-month prevalence estimates . National and international statistics for the model were retrieved from the OECD and Eurostat data bases . The aggregated annual cost estimates were presented in Euro for 2004 . RESULTS In 28 countries with a population of 466 million , at least 21 million were affected by depression . The total annual cost of depression in Europe was estimated at Euro 118 billion in 2004 , which corresponds to a cost of Euro 253 per inhabitant . Direct costs alone totalled dollar 42 billion , comprised of outpatient care ( Euro 22 billion ) , drug cost ( Euro 9 billion ) and hospitalization ( Euro 10 billion ) . Indirect costs due to morbidity and mortality were estimated at Euro 76 billion . This makes depression the most costly brain disorder in Europe , accounting for 33 % of the total cost . The cost of depression corresponds to 1 % of the total economy of Europe ( GDP ) . DISCUSSION Our cost results are in good agreement with previous research findings . The cost estimates in the present study are based on model simulations for countries where no data was available . The predictability of our model is limited to the accuracy of the input data employed . As there is no earlier cost-of-illness study conducted on depression in Europe , it is , however , difficult to evaluate the validity of our results for individual countries and thus further research is needed . CONCLUSION The cost of depression poses a significant economic burden to European society . The simulation model employed shows good predictability of the cost of depression in Europe and is a novel approach to estimate the cost-of-illness in Europe . IMPLICATION S FOR HEALTH CARE PROVISION AND POLICIES : Health and social care policy and commissioning must be evidence -based . The empirical results from this study confirm previous findings , that depression is a major concern to the economic welfare in Europe which has consequences to both healthcare providers and policy makers . One important way to stop this explosion in cost is through increased research efforts in the field . Moreover , better detection , prevention , treatment and patient management are imperatives to reduce the burden of depression and its costs . Mental healthcare policies and better access to healthcare for mentally ill are other challenges to improve for Europe . IMPLICATION S FOR FURTHER RESEARCH This study has identified several research gaps which are of interest for future research . In order to better underst and the impact of depression to European society long-term prospect i ve epidemiology and cost-of-illness studies are needed . In particular data is lacking for Central European countries . On the basis of our findings , further economic evaluations of treatments for depression are necessary in order to ensure a cost-effective use of European healthcare budgets", "OBJECTIVE To assess the antidepressant efficacy of S-adenosyl methionine ( SAMe ) , a naturally occurring methyl donor , versus the selective serotonin reuptake inhibitor ( SSRI ) escitalopram and a placebo control ; and to determine whether serum histamine or carnitine levels modified treatment response . METHODS We examined a sub sample ( n=144 ) from one site of a two-site study of adults with diagnosed Major Depressive Disorder ( MDD ) , recruited from 4/13/05 to 12/22/09 , who consented to the additional blood draw for serum histamine and carnitine levels . After washout , eligible subjects were r and omized to SAMe ( 1600 - 3200mg/daily ) , escitalopram ( 10 - 20mg/daily ) , or matching placebo for 12 weeks of double-blind treatment ( titration at week 6 in non-response ) . RESULTS On the primary outcome of the Hamilton Depression Rating Scale ( HAMD-17 ) , a significant difference in improvement was observed between groups from baseline to week 12 ( p=0.039 ) . The effect size from baseline to endpoint was moderate to large for SAMe versus placebo ( d=0.74 ) . SAMe was superior to placebo from week 1 , and to escitalopram during weeks 2 , 4 , and 6 . No significant effect was found between escitalopram and placebo or SAMe . Response rates ( HAMD-17≥50 % reduction ) at endpoint were 45 % , 31 % , and 26 % for SAMe , escitalopram , and placebo , respectively ; while remission rates ( HAM-D≤7 ) were 34 % for SAMe ( p=0.003 ) , 23 % for escitalopram ( p=0.023 ) , and 6 % for placebo . No correlation between baseline histamine level and reduction of HAMD-17 score was found for either the SAMe or escitalopram groups . Baseline carnitine levels were also not found to moderate response to either treatment . LIMITATIONS While SAMe appears to be an effective antidepressant agent , the overall findings from the parent study ( which showed no significant difference between groups due to site differences ) must be taken into consideration . CONCLUSIONS These preliminary results provide encouraging evidence for the use of SAMe in the treatment of MDD . Histamine and carnitine serum level may not necessarily moderate response to SAMe", "OBJECTIVE To characterize the impact of S-adenosyl methionine ( SAMe ) on homocysteine and potential risk of adverse cardiovascular effects by examining plasma levels of SAMe , S-adenosyl homocysteine ( SAH ) , total homocysteine ( tHCY ) , methionine ( MET ) , and 5-methyltetrahydrofolate ( 5-MTHF ) in 35 of 73 patients from a 6-week r and omized double-blind , placebo-controlled trial of SAMe augmentation in serotonin reuptake inhibitor partial responders with DSM-IV major depressive disorder ( MDD ) , published in 2010 . METHOD Subjects were r and omized from June 4 , 2004 , until August 8 , 2008 , to adjunctive placebo or SAMe 800 - 1600 mg/d for 6 weeks . Primary outcome measures included changes in one-carbon cycle intermediates within each treatment arm ( by paired t test ) and between treatment arms ( by independent sample s t test ) . Univariate analysis of variance and Fisher Protected Least Significant Difference were carried out to compare posttreatment levels of each one-carbon cycle intermediate . Secondary outcome measures included associations between clinical improvement and change in plasma intermediate levels , examined by linear regression ( for change in Hamilton Depression Rating Scale scores ) and logistic regression ( for response or remission ) . RESULTS We found significant differences in pretreatment plasma levels of tHCY ( P = .03 ) between the SAMe and placebo arms . Following 6 weeks of treatment , plasma SAMe ( P = .002 ) and SAH ( P levels increased significantly in the SAMe arm ; no intermediates in the placebo group changed significantly . Posttreatment plasma SAMe ( P = .0035 ) , SAH ( P and tHCY ( P = .0016 ) levels differed significantly between the SAMe and placebo groups . No significant associations were found between plasma intermediate levels and clinical improvement , response , or remission . CONCLUSIONS Despite concerns about the impact that SAMe therapy may have on homocysteine levels and risk of adverse cardiovascular effects , the lack of significant increase in tHCY levels after treatment suggests that no toxic effects from SAMe should be expected . Our findings , however , have some significant limitations and should be interpreted with caution . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00093847", "Cerebrospinal fluid ( CSF ) S-adenosylmethionine ( SAM ) levels were significantly lower in severely depressed patients than in a neurological control group . The administration of SAM either intravenously or orally is associated with a significant rise of CSF SAM , indicating that it crosses the blood-brain barrier in humans . These observations provide a rational basis for the antidepressant effect of SAM , which has been confirmed in several countries . CSF SAM levels were low in a group of patients with Alzheimer 's dementia suggesting a possible disturbance of methylation in such patients and the need for trials of SAM treatment", "Background This study reports on clinical data from an 8-week open-label study of 20 HIV-seropositive individuals , diagnosed with Major Depressive Disorder ( DSM-IV ) , who were treated with SAM-e ( S-Adenosylmethionine ) . SAM-e may be a treatment alternative for the management of depression in a population reluctant to add another \" pill \" or another set of related side effects to an already complex highly active antiretroviral therapy ( HAART ) regimen . Methods The Hamilton Rating Scale for Depression ( HAM-D ) and the Beck Depression Inventory ( BDI ) were used to assess depressive symptomatology from 1,2,4,6 and 8 weeks after initiation of treatment with SAM-e . Results Data show a significant acute reduction in depressive symptomatology , as measured by both the HAM-D and the BDI instruments . Conclusions SAM-e has a rapid effect evident as soon as week 1 ( p depression symptom rating scores throughout the 8 week study", "We evaluated the predictive value of the thyrotropin ( TSH ) response to thyrotropin‐releasing hormone ( TRH ) in 32 depressed out patients completing a double‐blind placebo‐controlled trial of s‐adenosyl‐l‐methionine ( SAMe ) , which failed to show any significant difference between SAMe and placebo . Treatment response was defined as the change in Hamilton Rating Scale for Depression ( HRSD‐24 ) score between baseline and the end of the six‐week trial . Subjects with TSH response outside the normal range ( 7–25 uU/ml ) had a significantly greater response than patients with a normal response . There was also a significant correlation between absolute deviations from the mean TSH response ( 16 uU/ml ) and changes in HRSD‐24 scores", "S-adenosyl-L-methionine ( SAMe ) is a naturally occurring substance which is a major source of methyl groups in the brain and has been found in previous studies to be an effective antidepressant . The aim of this study was to assess the efficacy of oral SAMe in the treatment of depressed postmenopausal women in a 30-day double-blind placebo-controlled r and omized trial . During the course of the study , 80 women , between the ages of 45 and 59 , who were diagnosed as having DSM-III-R major depressive disorder or dysthymia between 6 and 36 months following either natural menopause or hysterectomy , underwent 1 week of single-blind placebo washout , followed by 30 days of double-blind treatment with either SAMe 1,600 mg/day or placebo . There was a significantly greater improvement in depressive symptoms in the group treated with SAMe compared to the placebo group from day 10 of the study . Side effects were mild and transient", "BACKGROUND S-Adenosyl-L-methionine ( SAMe ) , a natural compound , is the most important methyl donor in the central nervous system . In several clinical trials , SAMe showed antidepressant activity . OBJECTIVE Two multicenter studies were conducted in patients with a diagnosis of major depressive episode [ baseline score on the 21-item Hamilton Depression Rating Scale ( HAM-D ) > or=18 ] to confirm the efficacy and safety of SAMe in the treatment of major depression . In the first study ( MC3 ) , 1600 mg SAMe/d was given orally ; whereas , in the second study ( MC4 ) , 400 mg SAMe/d was given intramuscularly . In both studies , the effects of SAMe were compared with those of 150 mg imipramine/d given orally in a double-blind design . DESIGN In MC3 , 143 patients received oral SAMe and 138 patients received imipramine for 6 wk . In MC4 , 147 patients received SAMe intramuscularly and 148 patients received imipramine for 4 wk . In both studies the 2 main efficacy measures were the final HAM-D score and the percentage of responders to Clinical Global Impression at the endpoint . Secondary efficacy measures were the endpoint Montgomery-Asberg Depression Rating Scale scores and the percentage of responders , responders being those patients showing a decrease in HAM-D score of > or=50 % from baseline . RESULTS In both studies , the results of SAMe and imipramine treatment did not differ significantly for any efficacy measure . However , significantly fewer adverse events were observed in the patients treated with SAMe . CONCLUSIONS The antidepressive efficacy of 1600 mg SAMe/d orally and 400 mg SAMe/d intramuscularly is comparable with that of 150 mg imipramine/d orally , but SAMe is significantly better tolerated", "Background S-adenosyl-L-methionine ( SAMe ) , a safe , endogenous , pleiotropic methyl donor well known for its antidepressant role , has been assumed to have a possible role in increasing plasma levels of compounds known to be able to raise cardiovascular risk . Although the issue is still being debated , betaine ( trimethylglycine ) , a specific methyl donor involved in the homocysteine circuit , may be able to reduce such a risk and /or , by determining a sparing effect on endogenous SAMe , may be able to improve the clinical efficiency of SAMe itself . Indeed , preliminary results have shown clinical improvement determined by an add-on therapy with betaine administered along with SAMe , versus SAMe alone , to patients affected by mild/moderate depression . Aim To evaluate the safety and antidepressant role played by the association of SAMe plus betaine versus amitriptyline administered in untreated individuals with a recent diagnosis of mild depression . Methods This small , open-label , r and omized , observational study enrolled 64 individuals with a diagnosis of mild depression according to the Zung Self-Rating Depression Scale . After r and omization , they were treated with either Laroxyl ® ( amitriptyline , 75 mg/day ) or DDM Metile ® ( enteric-coated SAMe , 500 mg/day , plus betaine , 250 mg/day ) for 12 months . Assessment of clinical scores and tolerability was performed at T=0 and after 3 , 6 , and 12 months . Results After 3 months , both treatments showed a small and not statistically significant improvement . After 6 and 12 months , both treated groups demonstrated a more noticeable improved response , although the group treated with SAMe plus betaine showed better results in terms of score , number of individuals in remission , and side effects . Compliance was overlapping in both treatments . Conclusion The association of SAMe plus betaine seems to be a safe and effective tool to counteract mild depression and also when used as monotherapy in subjects with a recent diagnosis", "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", " Twenty subjects entered a double-blind placebo-controlled trial of SAM in depression . Prolactin concentrations were measured before and after 14 days ' treatment . There was a highly significant fall in prolactin concentrations in the SAM-treated group", "A double-blind clinical trial was carried out to evaluate the efficacy of S-adenosyl-L-methionine ( SAMe ) in speeding the onset of action of imipramine ( IMI ) . SAMe is a naturally occurring substance that has been shown to possess antidepressant activity with a rapid mode of onset and minimal side effects . Sixty-three out patients with moderate to severe depression were included in the study . After an initial 1-week placebo period , only 40 patients entered the active treatment phase . During the first 2 weeks of the trial , half of these patients received 200 mg/day of SAMe intramuscularly , while the other half received placebo . Simultaneously , oral IMI was administered to all patients at a fixed dose of 150 mg/day . The onset of clinical response was determined by evaluating patients every second day . By the end of week 2 , the parenteral treatment was suppressed and IMI was adjusted according to individual needs . Depressive symptoms decreased earlier in the patients who were receiving the SAMe-IMI combination than in those who were receiving the placebo-IMI combination", "The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas", "The objectives of the present report were : a ) to determine the spontaneous remission rate in depressed out patients who do not receive antidepressant medication ; b ) to develop a novel method for obtaining a control group that can be used to gauge the effectiveness of antidepressant medication in clinical practice ; and c ) to compare response rates from the present sample with outcomes of depressed patients in our practice who were treated with antidepressant medications . By using a naturalistic design , prospect i ve assessment s were made on all depressed out patients . Twenty-five patients who met full criteria for a major depressive episode ended up not taking antidepressant medication for a variety of reasons . \" Response \" rates to a no-treatment trial were determined with st and ard outcome criteria using the Clinical Global Impression-Improvement scale . Eight patients ( 32.0 % ) had a positive response , 5 patients ( 20.0 % ) had a partial response , and 12 patients ( 48.0 % ) were nonresponders to a no-treatment trial . These response rates were higher than expected , but significantly lower than what we had found in a cohort of depressed patients who underwent an antidepressant trial ( p = .02 ) . Likewise , treatment-resistant patients fared better on pharmacotherapy , though this difference was not statistically significant . These results suggest that the occurrence of spontaneous remissions may be common in clinical practice , and therefore the specific short-term benefits of antidepressant medication in clinical practice may frequently be overestimated . Despite the high rate of spontaneous remission in our sample , the present study allowed us to confirm the effectiveness of antidepressant medication in clinical practice using a novel method for obtaining a control comparison group", "S-adenosyl-L-methionine ( SAMe ) is a natural substance which constitutes the most important methyl donor in transmethylation reactions in the central nervous system . Several clinical trials have shown that SAMe possesses an antidepressant activity . This multicentre study was carried out to confirm both efficacy and safety of SAMe in the treatment of major depression . SAMe was given intramuscularly ( i.m . ) at a dose of 400 mg/d , double-blind , vs. 150 mg/d oral Imipramine ( IMI ) in patients with a diagnosis of major depressive episode , with a baseline score on the 21-item Hamilton Depression Rating Scale ( HAMD ) of > or=18 . A total of 146 patients received SAMe whereas 147 received IMI for a period of 4 wk . The two main efficacy measures were endpoint HAMD score and percentage of responders to Clinical Global Impression ( CGI ) at week 4 . Secondary efficacy measures were the final Montgomery-Asberg Depression Rating Scale ( MADRS ) scores and the response rate intended as a fall in HAMD scores of at least 50 % with respect to baseline . The analysis of safety and tolerability was conducted in all treated patients . SAMe and IMI did not differ significantly on any efficacy measure , either main or secondary . Adverse events were significantly less in patients treated with SAMe compared to those treated with IMI . These data show 400 mg/d i.m . SAMe to be comparable to 150 mg/d oral IMI in terms of antidepressive efficacy , but significantly better tolerated . These findings suggest interesting perspectives for the use of SAMe in depression", "The results of a r and omized clinical trial can be reported using relative and /or absolute estimators of treatment effect . These various measures convey different information , and the choice can influence the physician 's appreciation of the size of treatment effect and , subsequently , treatment decisions . We compare the estimators with respect to the clinical ly relevant information conveyed to physicians , and identify which clinical questions can and can not be answered directly by each . We also identify opportunities for misinterpretation when one estimator is substituted for another , or when an estimator is mislabeled . Clinical ly important questions are addressed most directly by reporting both relative and absolute effects using relative risk and its complement , relative risk reduction , and risk difference and its reciprocal , number needed to treat . This is true of estimates of treatment effect derived from a single trial and also from meta- analysis of a group of trials . Because the control group 's risk affects the numerical value of the odds ratio , the odds ratio can not substitute for the risk ratio in conveying clinical ly important information to physicians . This is especially important when large treatment effects are shown in trials carried out in population s at high baseline risk", "We report a pilot study of S-adenosyl-methionine ( SAM ) in 13 depressed patients with Parkinson 's disease . All patients had been previously treated with other antidepressant agents and had no significant benefit or had intolerable side effects . SAM was administered in doses of 800 to 3600 mg per day for a period of 10 weeks . Eleven patients completed the study , and 10 had at least a 50 % improvement on the 17-point Hamilton Depression Scale ( HDS ) . One patient did not improve . Two patients prematurely terminated participation in the study because of increased anxiety . One patient experienced mild nausea , and another two patients developed mild diarrhea , which resolved spontaneously . The mean HDS score before treatment was 27.09 + /- 6.04 ( mean + /- st and ard deviation ) and was 9.55 + /- 7.29 after SAM treatment ( p SAM is well tolerated and may be a safe and effective alternative to the antidepressant agents currently used in patients with Parkinson 's disease", "Introduction ‐ The relationship between plasma levels of S‐adenosylmethionine ( SAMe ) , an endogenous methyl donor , and clinical response were studied in patients with a DSM‐III‐R diagnosis of major depression . Material and methods ‐ A double‐blind r and omized protocol comparingoral SAMe with oral desipramine , involving a total of 26 patients , was employed . Results ‐At the end of the 4‐week trial , 62 % of the patients treated with SAMe and 50 % of the patients treated with desipramine had significantly improved . Regardless of the type of treatment , patients witha 50 % decrease in their Hamilton Depression Scale ( HAM‐D ) score showed a significant increase in plasma SAMe concentration . Conclusion ‐ The significant correlation between plasma SAMe levels and the degree of clinical improvement in depressed patients regardless of the type of treatment suggests that SAMe may play an important role in regulating mood ", "OBJECTIVE Despite the progressive increase in the number of antidepressants , many patients with major depressive disorder continue to be symptomatic . Clearly , there is an urgent need to develop better tolerated and more effective treatments for this disorder . The use of S-adenosyl methionine ( SAMe ) , a naturally occurring molecule that serves as a methyl donor in human cellular metabolism , as adjunctive treatment for antidepressant nonresponders with major depressive disorder represents one such effort toward novel pharmacotherapy development . METHOD Participants were 73 serotonin reuptake inhibitor ( SRI ) nonresponders with major depressive disorder enrolled in a 6-week , double-blind , r and omized trial of adjunctive oral SAMe ( target dose : 800 mg/twice daily ) . Patients continued to receive their SRI treatment at a stable dose throughout the 6-week trial . The primary outcome measure for the study was the response rates according to the 17-item Hamilton Depression Rating Scale ( HAM-D ) . RESULTS The HAM-D response and remission rates were higher for patients treated with adjunctive SAMe ( 36.1 % and 25.8 % , respectively ) than adjunctive placebo ( 17.6 % versus 11.7 % , respectively ) . The number needed to treat for response and remission was approximately one in six and one in seven , respectively . There was no statistically significant difference in the proportion of SAMe- versus placebo-treated patients who discontinued the trial for any reason ( 20.6 % versus 29.5 % , respectively ) , due to adverse events ( 5.1 % versus 8.8 % , respectively ) , or due to inefficacy ( 5.1 % versus 11.7 % , respectively ) . CONCLUSIONS These preliminary results suggest that SAMe can be an effective , well-tolerated , and safe adjunctive treatment strategy for SRI nonresponders with major depressive disorder and warrant replication", "Abstract SAMe is a methyl donor involved in methylation processes generally , including the Central Nervous System . Thirty depressed patients were studied in a double blind trial . The Hamilton Depression Rating Scale was used for symptom evaluation . The drug ( 45 mg i.m . daily ) appeared to have a rapid and beneficial effect mainly upon depressed mood , suicidal tendencies , retardation and performance . Improvement was observed in 80 % of the cases in 4–6 days . Studies are now in progress to clarify the biological mechanism involved in SAMe 's antidepressive action", "The antidepressant properties of S-adenosylmethionine , an endogenous methyl donor , were studied in in patients who met the DSM-III criteria for major depression . Nine patients given intravenous S-adenosylmethionine and nine given low oral doses of imipramine were compared in a double-blind design for 14 days . The S-adenosylmethionine produced superior results by the end of the first week of treatment . By the end of the second week , 66 % of the S-adenosylmethionine patients had a clinical ly significant improvement in depressive symptoms , compared to 22 % of the imipramine patients . Side effects appeared to be fewer with S-adenosylmethionine than with imipramine during the last 5 days of the study", "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", "S-Adenosyl methionine may well have an antidepressant action beyond a placebo effect but this is virtually confined to endogenous depression . This should be subjected to further study . Our own double-blind placebo-controlled study is still incomplete . The indications are that SAM specifically affects folate , dopamine , and serotonin metabolism as well as activating and switching brain mechanisms . This suggests exciting prospect s for further investigations . SAM is a nontoxic physiological metabolite virtually free of side effects", "Experimental work on the acute , chronic , and fetal toxicity of SAMe was carried out by Stramentinoli and his colleagues ( 19 ) . The intravenous LD50 in rats is more than 2000 mg/kg , or the equivalent of 140–150 g in a man of 70 kg . In man , on the other h and , clinical trials have revealed a definite action of the substance in the CNS with doses as little as 80/zg/kg ; the largest dose so far administered intravenously to humans is 0.5 g daily and has produced no visible side effects", "OBJECTIVE To examine the comparative antidepressant efficacy of S-adenosyl-L-methionine ( SAMe ) and escitalopram in a placebo-controlled , r and omized , double-blind clinical trial . METHOD One hundred eighty-nine out patients ( 49.7 % female , mean [ SD ] age = 45 [ 15 ] years ) with DSM-IV-diagnosed major depressive disorder ( MDD ) were recruited from April 13 , 2005 , to December 22 , 2009 , at the Massachusetts General Hospital and at Butler Hospital . Patients were r and omized for 12 weeks to SAMe 1,600 - 3,200 mg/d , escitalopram 10 - 20 mg/d , or placebo . Doses were escalated at 6 weeks in the event of nonresponse . The main outcome measure was the 17-item Hamilton Depression Rating Scale ( HDRS-17 ) . Tolerability was assessed by the Systematic Assessment for Treatment of Emergent Events-Specific Inquiry ( SAFTEE-SI ) . RESULTS All 3 treatment arms demonstrated a significant improvement of about 5 - 6 points in HDRS-17 scores ( P .05 for all ) . Response rates in the intent-to-treat sample were 36 % for SAMe , 34 % for escitalopram , and 30 % for placebo . Remission rates were 28 % for SAMe , 28 % for escitalopram , and 17 % for placebo . No comparisons between treatment groups attained significance ( P > .05 for all ) . Tolerability was good , with gastrointestinal side effects ( 19 % for stomach discomfort and 20 % for diarrhea ) as the most common in the SAMe arm . Significant differences were observed between treatment groups for dizziness , anorgasmia , diminished mental acuity , and hot flashes ( P SAMe or the st and ard treatment escitalopram for MDD . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00101452", "During open trials of intravenous and oral S-adenosyl methionine ( SAM ) and a placebo-controlled trial of intravenous SAM in 29 patients , 25 patients had SAM and four had placebo ( 27 courses of SAM , two of the patients receiving two trials a piece ) . Nine of 11 bipolar patients ( all SAM-treated ) switched into elevated mood state ( hypomania , mania and euphoria ) and two did not respond . Six endogenous unipolar patients improved and five did not . No non-endogenous patient or placebo patient responded for more than 14 days . No unipolar patient switched into elated mood . In eleven ( 38 % ) trials and nine ( 33 % ) patients there was a switch from depression to elation . Biochemical data from the cerebrospinal fluid of eight patients suggested that the role of the dopaminergic system should be further explored", "OBJECTIVE The aim of this study was to examine whether gender differences may have affected treatment response to S-adenosyl methionine ( SAMe ) in a recent failed r and omized clinical trial ( RCT ) for adults with major depressive disorder . METHODS Data from a 2-site , 12-week , double-blind RCT ( n=189 ) assessing the efficacy of SAMe vs. placebo and a comparator selective serotonin reuptake inhibitor ( escitalopram ) were subjected to post-hoc analyses to evaluate effects of patient gender on treatment response . RESULTS When assessing the efficacy outcomes within each gender separately , SAMe was superior to placebo among males ( n=51 ) , but not among females ( n=62 ) . Males showed a significant reduction of depression severity from baseline to study endpoint on the 17-item Hamilton Depression Rating Scale ( 4.3 point difference ; p=0.034 ; d=0.95 ) , while females did not show significant change . This finding emerged despite equivalence on baseline measures of depression severity between the gender groups . CONCLUSION RESULTS of this secondary data analysis suggest that gender might impact the antidepressant efficacy of SAMe , with greater therapeutic effect found in males . The underlying mechanism is still relatively unknown . Further work is needed to replicate this observation in independent sample s. Clinical trials.gov identifier : NCT00101452", "Methylation has been implicated in the etiology of psychiatric illness . Parenteral S-adenosylmethionine , a methyl group donor , has been shown to be an effective antidepressant . The authors studied the antidepressant effect of oral S-adenosylmethionine in a r and omized , double-blind , placebo-controlled trial for 15 in patients with major depression . The results suggest that oral S-adenosylmethionine is a safe , effective antidepressant with few side effects and a rapid onset of action . S-Adenosylmethionine induced mania in a patient with no history of mania . S-Adenosylmethionine may be useful for patients who can not tolerate tricyclic anti-depressants . These findings support a role for methylation in the pathophysiology of depression" ]

[ "BACKGROUND The management of emergency department ( ED ) patients with presumed recent-onset atrial fibrillation or flutter≤48h in duration varies widely . OBJECTIVE AND METHOD We conducted a prospect i ve study across three affiliated community EDs within a large integrated health care delivery system to describe the management of patients with recent-onset atrial fibrillation or flutter , to determine the safety and effectiveness of ED cardioversion , and to measure the incidence of thromboembolism 30 days after discharge . RESULTS We enrolled 206 patients with convenience sampling between June 2005 and November 2007 . Mean age was 64.0±14.4 years ( range 21 - 96 years ) . Patients were grouped for analysis into four categories based on whether cardioversion was 1 ) spontaneous in the ED ( 59 ; 28.6 % ) ; 2 ) attempted with electrical or pharmacological means ( 115 ; 56.3 % ) , with success in 110 ( 95.7 % ) ; 3 ) hoped for during a short stint of home observation ( 16 ; 7.8 % , 11 of which spontaneously converted to sinus rhythm within 24h ) ; or 4 ) contraindicated ( 16 ; 7.8 % ) . Of the entire group , 183 ( 88.8 % ) patients were discharged home . Adverse events requiring ED interventions were reported in 6 ( 2.9 % ; 95 % confidence interval [ CI ] 1.1 - 6.2 % ) patients , all of whom recovered . Two ( 1.0 % ; 95 % CI 0.1 - 3.5 % ) patients were found to have an embolic event on 30-day follow-up . CONCLUSIONS Our approach to ED patients with presumed recent-onset atrial fibrillation or flutter seems to be safe and effective , with a high rate of cardioversion and discharge to home coupled with a low ED adverse event and 30-day thromboembolic event rate", "OBJECTIVE Ibutilide is a type III antiarrhythmic agent approved for the pharmacologic conversion of atrial fibrillation ( AF ) and atrial flutter ( AFl ) . Previous studies conducted outside the ED setting have demonstrated conversion rates of 60 % to 80 % . This response has been highest in patients with recent-onset AF-AFl . These observations and the 4-hour half-life of ibutilide suggest that it may be an excellent drug with which to treat AF-AFl in the ED . The purpose of the study was to examine the efficacy and safety of ibutilide in terminating AF-AFl in patients who present to the ED with symptoms of less than 3 days ' duration , neither angina nor heart failure , and no comorbid conditions that require admission . METHODS Among 36 enrolled patients , the admission electrocardiogram demonstrated AF in 26 and AFl in 10 . Ibutilide 1 mg was administered intravenously for 10 minutes . If sinus rhythm was not present 10 minutes after the infusion concluded , a second infusion of 1 mg was given . Successful conversion was defined as restoration of sinus rhythm within 1 hour after the last dose of ibutilide . RESULTS Sixteen ( 61.5 % ) of 26 patients with AF and 9 ( 90 % ) of 10 patients with AFl converted to sinus rhythm ( overall conversion rate=69 % ) . The mean time to arrhythmia termination was 19+/-9 minutes . The mean stay in the ED was 16.2 hours . No significant complications occurred . CONCLUSION We conclude that ibutilide is an excellent therapy option for restoring sinus rhythm in the ED . Its use may obviate the need for admission , avoid the risks and inconveniences of general anesthesia to perform electrical cardioversion , and reduce the ED length of stay in selected patients with recent-onset atrial arrhythmias", "OBJECTIVES While the short-term ( electrical cardioversion for emergency department ( ED ) patients with atrial fibrillation or flutter have been established , the 30-day outcomes with respect to stroke , thromboembolic events , or death have not been investigated . METHODS A two-center cohort of consecutive ED patients undergoing cardioversion for atrial fibrillation or flutter between January 1 , 2000 , and September 30 , 2007 , was retrospectively investigated . This cohort was probabilistically linked with both a regional ED data base and the provincial health registry to determine which patients had a subsequent ED visit or hospital admission , stroke , or thromboembolic event or died within 30 days . In addition , trained review ers performed a detailed chart abstract ion on 150 r and omly selected patients , with emphasis on demographics , vital signs , medical treatment , and predefined adverse events . Hemodynamically unstable patients or those whose condition was the result of an underlying acute medical diagnosis were excluded . Data were analyzed by descriptive methods . RESULTS During the study period , 1,233 patients made 1,820 visits for atrial fibrillation or flutter to the ED . Of the 400 eligible patients undergoing direct-current cardioversion ( DCCV ) , no patients died , had a stroke , or had a thromboembolic event in the following 30 days ( 95 % confidence interval [ CI ] = 0.0 to 0.8 % for all outcomes ) . A total of 141 patients were included in the formal chart review , with five patients ( 3.5 % , 95 % CI = 0.5 % to 6.6 % ) failing cardioversion , six patients ( 4.3 % , 95 % CI = 0.9 % to 7.6 % ) having a minor adverse event that did not change disposition , and five patients ( 3.5 % , 95 % CI = 0.5 % to 6.6 % ) admitted to hospital at the index visit . CONCLUSIONS Cardioversion of patients with atrial fibrillation or flutter in the ED appears to have a very low rate of long-term complications", "STUDY OBJECTIVE Patients presenting to the emergency department with acute atrial fibrillation are traditionally admitted to hospital . The objective of this study was to review the success and safety of ED cardioversion and discharge of patients with acute atrial fibrillation . METHODS This health records survey included a cohort sample of consecutive patients presenting with acute atrial fibrillation to the ED of a university-affiliated tertiary hospital . Patients who were in unstable condition on presentation , who had a complicating cardiac diagnosis , or those with other medical or surgical conditions requiring admission were excluded from the study analysis . Patient visit information was entered into a data base that included demographics and clinical presentation , investigations , ED therapy , complications , consultations , disposition , and follow up . Patient visits were then categorized into the following groups : no ED intervention , spontaneous resolution , heart rate control , attempted chemical cardioversion , or electrical cardioversion . The data were analyzed using descriptive methods . RESULTS Of the 289 eligible patients seen during an 18-month period , 62 % ( 180 ) underwent attempted chemical cardioversion with a 50 % success rate and 28 % ( 80 ) had attempted electrical cardioversion with a 89 % success rate . Ninety-three percent of electrical cardioversions were performed by emergency physicians . There was an overall 6 % ( 19 ) complication rate , 95 % of which were regarded as minor . One patient had a complication caused by a rate control medication , which necessitated hospital admission . Ninety-seven percent ( 280 ) of the patients were discharged home directly from the ED . CONCLUSION Cardioversion and immediate discharge of patients who present to the ED with acute atrial fibrillation appears to be both safe and effective . This management approach should be prospect ively evaluated in multiple setting", "STUDY OBJECTIVE We sought to describe the feasibility of an emergency department observation unit ( EDOU ) treatment protocol for the management of uncomplicated acute-onset atrial fibrillation ( AAF ) . METHODS This descriptive case series took place at a major suburban , university-affiliated teaching hospital . Patients were prospect ively enrolled in an EDOU treatment protocol if they had uncomplicated AAF that failed initial ED attempts to convert to sinus rhythm . In the EDOU , patients underwent ECG monitoring , serial creatine kianse MB measurements , and further rate control with optional electrical cardioversion . Primary outcomes measured were EDOU rate of conversion to sinus rhythm , rate of discharge home , length of stay , positive diagnostic outcomes , complications of AAF , and 7-day return visits . RESULTS Sixty-seven patients were studied . Patients were symptomatic for a median of 4.0 hours , had mean initial ED pulse rates of 137+/-23 beats/min , and spent 4.7+/-2.2 hours in the ED before transfer to the EDOU . While in the EDOU , 55 ( 82 % ) patients converted to sinus rhythm . Five ( 7 % ) patients were admitted because of positive test results : 2 for myocardial infa rct ion , 2 for fever , and 1 for ventricular tachycardia . Twelve ( 18 % ) patients remained in atrial fibrillation , with 9 admitted and 3 discharged . Overall , 81 % of patients were discharged in 11.8+/-7.0 hours , and 19 % were admitted after 17.6+/-9.5 hours of observation . Three discharged patients returned within 7 days , 2 for uncomplicated recurrent AAF and 1 for chest pain subsequently found to be noncardiac in origin . There were no major complications attributable to the EDOU protocol . CONCLUSION Selected patients with AAF for whom initial ED management fails can subsequently be managed in an EDOU with a high short-term conversion and discharge rate", "There is wide variation in the management of patients with atrial fibrillation ( AF ) in the emergency department ( ED ) . We aim ed to derive and internally vali date the first prospect i ve , ED-based clinical decision aid to identify patients with AF at low risk for 30-day adverse events . We performed a prospect i ve cohort study at a university-affiliated tertiary-care ED . Patients were enrolled from June 9 , 2010 , to February 28 , 2013 , and followed for 30 days . We enrolled a convenience sample of patients in ED presenting with symptomatic AF . C and i date predictors were based on ED data available in the first 2 hours . The decision aid was derived using model approximation ( preconditioning ) followed by strong bootstrap internal validation . We used an ordinal outcome hierarchy defined as the incidence of the most severe adverse event within 30 days of the ED evaluation . Of 497 patients enrolled , stroke and AF-related death occurred in 13 ( 3 % ) and 4 ( age , triage vitals ( systolic blood pressure , temperature , respiratory rate , oxygen saturation , supplemental oxygen requirement ) , medical history ( heart failure , home sotalol use , previous percutaneous coronary intervention , electrical cardioversion , cardiac ablation , frequency of AF symptoms ) , and ED data ( 2 hours heart rate , chest radiograph results , hemoglobin , creatinine , and brain natriuretic peptide ) . The decision aid 's c-statistic in predicting any 30-day adverse event was 0.7 ( 95 % confidence interval 0.65 , 0.76 ) . In conclusion , in patients with AF in the ED , Atrial Fibrillation and Flutter Outcome Risk Determination provides the first evidence -based decision aid for identifying patients who are at low risk for 30-day adverse events and c and i date s for safe discharge", "STUDY OBJECTIVE An emergency department ( ED ) observation unit protocol for the management of acute onset atrial fibrillation is compared with routine hospital admission and management . METHODS Adult patients presenting to the ED with atrial fibrillation of less than 48 hours ' duration without hemodynamic instability or other comorbid conditions requiring hospitalization were enrolled . Participants were r and omized to either ED observation unit care or routine inpatient care . The ED observation unit protocol included pulse rate control , cardiac monitoring , re assessment , and electrical cardioversion if atrial fibrillation persisted . Patients who reverted to sinus rhythm were discharged with a cardiology follow-up within 3 days , whereas those still in atrial fibrillation were admitted . All cases were followed up for 6 months and adverse events recorded . RESULTS Of the 153 patients , 75 were r and omized to the ED observation unit and 78 to routine inhospital care . Eighty-five percent of ED observation unit patients converted to sinus rhythm versus 73 % in the routine care group ( difference 12 % ; 95 % confidence interval [ CI ] -1 % to 25 % ] ; P=.06 ) . The median length of stay was 10.1 versus 25.2 hours ( difference 15.1 hours ; 95 % CI 11.2 to 19.6 ; P inpatient admission . Eleven percent of the ED observation unit group had recurrence of atrial fibrillation during follow-up versus 10 % of the routine inpatient care group ( difference 1 % ; 95 % CI -9 % to 11 % ; P=.93 ) . There was no significant difference between the groups in the frequency of hospitalization or the number of tests , and the number of adverse events during follow-up was similar in the 2 groups . CONCLUSION An ED observation unit protocol that includes electrical cardioversion is a feasible alternative to routine hospital admission for acute onset of atrial fibrillation and results in a shorter initial length of stay", "Health care re source utilization is high for patients presenting with acute atrial fibrillation ( AF ) . The potential for treatment algorithms to safely reduce re source consumption in this setting has not been prospect ively evaluated . We design ed and implemented a practice guideline for the management of patients presenting to the emergency department ( ED ) with the primary diagnosis of AF , with emphasis on appropriate cardioversion , use of oral rate-controlling medications , and expedited referral to an outpatient AF clinic . We prospect ively collected clinical and re source utilization data on all such patients for 14 months before and after institution of the guideline . Institution of the guideline was associated with a decreased rate of hospital admission ( from 74 % to 38 % ) , with no differences in ED return visits or hospital readmission within 30 days . No strokes or deaths were observed . This large decrease in re source utilization during the intervention phase of the study translated to an average decrease in 30-day total direct health care costs of approximately $ 1,400 US dollars per patient . Our clinical and cost outcomes were minimally affected after statistical adjustment for baseline differences between study groups . We conclude that the implementation of our practice guideline was feasible , safe , and effective . Widespread adoption of such practice s may have large financial implication s for the health care system", "Objective : To compare the success rates and short-term complications of three treatment approaches , pharmacological and direct-current cardioversion ( DCC ) , or ‘ wait- and -watch ’ among stable atrial fibrillation ( AF ) patients in the emergency department ( ED ) . Methods : All AF-related ED admissions during a 1-year period were retrospectively review ed , and those meeting criteria of eligibility for immediate cardioversion , based on clinical stability , AF duration and adequacy of anticoagulation , were included . The propensity score approach generalized for the three groups was used to adjust for the observational non-r and omized study nature . Results : Among 374 eligible patients , the rate of successful cardioversion was higher in DCC than in pharmacological or wait- and -watch groups ( 78.2 , 59.2 and 37.9 % respectively , p discharged from ED ( 52.9 , 47.9 and 32.1 % , p DCC was 2.43 times more effective than pharmacological treatment in achieving sinus rhythm ( 95 % confidence interval = 1.36–4.33 , p = 0.003 ) . Rehospitalization within 14 days due to probable AF-treatment-related complications of home-discharged patients was 3.4 % . Conclusions : DCC was found to be the most effective treatment , with few short-term complications following conversion of stable AF patients to sinus rhythm in the ED", "Atrial fibrillation ( AF ) is one of the most frequent dysrhythmias in patients coming to emergency departments ( EDs ) , and pharmacological treatment is frequently performed . The aim of this r and omized placebo-controlled multicenter trial was to compare propafenone ( a class 1C antidysrhythmic agent ) , administered i.v . in the ED , with placebo in the treatment of recent-onset AF ( . We r and omly allocated 156 patients ( 88 males ; 68 females ) from 18 to 80 years old , with recent-onset AF , to receive i.v . propafenone ( 2 mg/kg for 10 min ) or the matching placebo . The patients were followed for 2 h. Exclusion criteria were the presence of one of the following : lack of informed consent , clinical evidence of heart failure , clinical hyperthyroidism , recent acute myocardial infa rct ion , atrioventricular block , cardiac valve dysfunction , a history of bronchial asthma , and current treatment with antidysrhythmic agents including digitalis . The two groups did not differ significantly in terms of sex , age , body weight , or estimated time elapsed since the beginning of atrial fibrillation . Conversion to sinus rhythm occurred in 13 of the 75 patients who received the placebo ( 17.3 % ) and in 57 of the 81 patients who were given propafenone ( 70.3 % ) . In conclusion , intravenous propafenone administration in the ED can be considered a safe and effective approach for converting AF to sinus rhythm", "STUDY OBJECTIVE To determine the relative effectiveness of a verapamil-quinidine sequential combination versus digoxin-quinidine in the emergency department treatment of paroxysmal atrial fibrillation ( PAF ) . METHOD This prospect i ve , double-blind , r and omized , controlled trial involved patients , aged 18 to 75 years , with new-onset ( Consenting patients were r and omly assigned to receive rapid digitalization ( 1.0 mg over 2 hours ) or i.v . verapamil ( sequential 5-mg boluses up to 20 mg ) . After ventricular rate was controlled ( quinidine ( 200 mg ) was initiated and repeated every 2 hours until conversion to normal sinus rhythm ( NSR ) occurred , until 1 g of quinidine was administered , or until adverse effects supervened . Heart rate , blood pressure , cardiac rhythm , time to conversion , and adverse effects were documented . RESULTS Forty-four patients received the study drugs . Three were withdrawn , leaving 19 in the verapamil-quinidine ( VER-Q ) group and 22 in the digoxin-quinidine ( DIG-Q ) group . Sixteen patients ( 84 % ) in the VER-Q group and 10 ( 45 % ) in the DIG-Q group converted to NSR within 6 hours ( P Mean time to conversion ( + /-SD ) was 185 + /- 146 minutes for VER-Q and 368 + /- 386 minutes for DIG-Q patients ( P = NS ) . Twelve VER-Q patients ( 63 % ) and 6 DIG-Q patients ( 27 % ) were discharged from the ED ( P Minor adverse effects were more common in the VER-Q group . No mortality or significant morbidity occurred . CONCLUSION The sequential combination of verapamil and quinidine , in the doses studied , is an effective treatment for PAF and is superior to digoxin-quinidine . Digoxin should no longer be considered the treatment of choice for uncomplicated PAF", "Management of atrial fibrillation ( AF ) in the emergency department ( ED ) is variable because of the absence of universally adopted treatment guidelines . To address potentially preventable hospital admissions and prolonged length of stay , an AF treatment pathway was co-developed by physicians from the cardiac electrophysiology service and the department of emergency medicine at our institution . The impact of this AF pathway on patient outcomes was evaluated with a prospect i ve , observational study conducted in a single tertiary care center from July 1 , 2013 , to June 30 , 2014 . The primary study outcome was the rate of hospital admission . The secondary outcomes were duration of ED visit and inpatient length of stay . The 94 patients treated according to the AF pathway during the study period were less likely to be admitted than the 265 patients who received routine care ( 16 % vs 80 % , p mean length of stay was shorter for patients treated according to the AF pathway ( 32 vs 85 hours , p = 0.002 ) . The time spent in the ED was longer for patients in the AF pathway ( 16 vs 85 hours , p multidisciplinary pathway for management of AF in the ED led to a significant reduction in the rate of hospital admission . Patients who were admitted after receiving care according to the AF pathway had a shorter length of stay . In conclusion , utilization of a multidisciplinary AF pathway result ed in a 5-fold reduction in admission rate and > 2-fold reduction length of stay for admitted patients", "Background Direct current cardioversion ( DCC ) has been shown to be effective for the management of atrial fibrillation ( AF ) in the emergency department ( ED ) . Pharmacological cardioversion was compared with a strategy including DCC on patients with uncomplicated , recent-onset ( managed in a short observation unit ( SOU ) . Methods A prospect i ve observational study was undertaken over a period of 13 months in two institutions . A DCC-centred protocol was applied to 171 AF cases in a hospital ( DCC-cohort ) and pharmacological cardioversion to 151 AF cases in another hospital ( P-cohort ) . Patients remaining in AF after 24 h were admitted . The outcomes were rate of discharge in sinus rhythm , length of stay in the ED-SOU , rate of hospitalisation and complications of treatment . Data collected were analysed according to Student t test and χ2 statistics . Results Discharge in sinus rhythm was achieved in 159/171 cases in the DCC-cohort and 77/151 cases in the P-cohort ( 93 % vs 51 % ; number needed to treat ( NNT ) 2.4 ; 95 % CI 2.0 to 3.1 , p mean length of stay was 7 + 7 h in the DCC-cohort and 9 + 6 h in the P-cohort ( p=0.43 ) . Eleven cases from the DCC-cohort and 67 from the P-cohort were admitted ( admission rate 6 % vs 44 % ; NNT 2.6 ; 95 % CI 2.2 to 3.5 , p short-term complications occurred in the DCC-cohort and five in the P-cohort ( 2 % vs 3 % , p=0.59 ) . Two strokes were registered in the DCC-cohort during 6-month follow-up ( p undefined ) . Conclusions Electrical cardioversion of recent-onset AF in the SOU is safe , effective and reduces hospitalisations . Further studies are needed to identify the most cost-effective strategy for the management of AF patients in emergency setting", "STUDY OBJECTIVE We assess an alternative accelerated clinical pathway approach to the management of patients with newly diagnosed or new-onset atrial fibrillation ( AF ) . METHODS A prospect i ve , r and omized pilot study of 2 AF disease-management strategies was conducted at a single university hospital . A traditional approach of hospital admission versus an accelerated emergency department-based strategy with low-molecular-weight heparin and early cardioversion to sinus rhythm was assessed in a cohort of patients with uncomplicated AF . The primary end points were length of stay and total actual direct costs . RESULTS Eighteen patients were r and omized over a 15-month period . The accelerated treatment strategy in the ED result ed in a substantial decrease in length of stay ( 2.1+/-2.3 versus mean cost reduction ( $ 1,706+/-$1,512 versus $ 879+/-$394 ; P = .15 ) . The clinical outcomes ( rate of sinus rhythm at discharge and follow-up and complications caused by AF ) related to AF were similar in the 2 groups . CONCLUSION A disease-management strategy for new , uncomplicated AF that uses an ED-outpatient treatment pathway results in a shorter length of stay at potentially lower cost . The results of this pilot study warrant further investigation", "OBJECTIVE Published data supporting the best practice for patients with atrial fibrillation ( AF ) presenting to the emergency department ( ED ) are limited . Our objective was to evaluate the impact of an AF clinical protocol initiated in the ED with early follow-up in a specialty AF outpatient clinic . METHODS This was a single-center prospect i ve study of all consented patients with AF who were discharged from the ED through the AF clinical pathway and were then seen in the AF clinic . The primary endpoint was the rate of 90-day hospitalization/ED visits . Secondary endpoints included adherence to established AF anticoagulation guidelines , rate of thromboembolic events , quality of life , and patient satisfaction . RESULTS One hundred consecutive patients were enrolled in the study . Within 90 days , 15 had ED visits and 4 were hospitalized , whereas none developed thromboembolic complications . There were significant increases in the Atrial Fibrillation Effect on QualiTy of life survey quality of life ( 67.3 ± 24.8 vs. 89.2 ± 15.7 ; P and patient satisfaction ( 66.4 ± 25.3 vs. 77.9 ± 22.8 ; P 29 patients with CHADS2 score ≥2 , 20 ( 69 % ) were discharged from the AF clinic with oral anticoagulation . CONCLUSIONS We describe a novel approach to the care of patients with AF presenting to the ED . Usage of the ED-initiated AF clinical pathway with early follow-up in a protocol -driven AF clinic was associated with low readmission rates , no thromboembolic complications at 90 days , improved quality of life , and high patient satisfaction ", "OBJECTIVES Acute atrial fibrillation and flutter are very common arrhythmias seen in emergency department ( ED ) patients , but there is no consensus for their optimal management . The objective of this study was to examine the efficacy and safety of intravenous ( IV ) procainamide for acute atrial fibrillation or flutter . METHODS This health records review included a consecutive cohort of ED patients with acute-onset atrial fibrillation or atrial flutter who received IV procainamide at one university hospital ED during a five-year period . The st and ard clinical protocol involved IV infusion of 1 g of procainamide over 60 minutes , followed by electrical cardioversion if necessary . A trained observer extracted data from the original clinical records . Outcome measurements included conversion to sinus rhythm , adverse events , and relapse up to seven days . RESULTS The 341 study patients had a mean age of 63.9 years ( SD + /- 15.5 years ) , and 56.6 % were male . The conversion rates were 52.2 % ( 95 % confidence interval = 47 % to 58 % ) for 316 atrial fibrillation cases and 28.0 % ( 95 % confidence interval = 13 % to 46 % ) for 25 atrial flutter cases . Mean dose given was 860.7 mg ( SD + /- 231.2 mg ) , and median time to conversion was 55 minutes . Adverse events occurred in 34 cases ( 10.0 % ) : hypotension , 8.5 % ; bradycardia , 0.6 % ; atrioventricular block , 0.6 % ; and ventricular tachycardia , 0.3 % . There were no cases of torsades de pointes , cerebrovascular accident , or death . Most patients ( 94.4 % ) were discharged home , but 2.9 % of patients returned with a recurrence of atrial fibrillation within seven days . CONCLUSIONS This study of acute atrial fibrillation or flutter patients treated in the ED with IV procainamide suggests that this treatment is safe and effective in this setting . Procainamide should be prospect ively compared with other ED strategies", "Safety and effectiveness are the goals in treating patients with arrhythmias . In an open prospect i ve study , we observed the efficacy and safety of up to 2 mg intravenous ibutilide , a new class III antiarrhythmic agent in haemodynamically stable patients presenting in the emergency department ( ED ) with symptoms of recent-onset ( Arrhythmia termination within 90 min , haemodynamic parameters and proarrhythmic effects were assessed . Non-responders to the ibutilide infusion underwent external electrical cardioversion . We included 51 patients . In 31 patients therapeutic intervention with intravenous ibutilide was successful within 90 min ( 61 % ) . In another seven patients conversion to sinus rhythm occurred after 90 min without any other intervention ( 14 % ) . Blood pressure remained stable and no relevant proarrhythmic effects were observed . The 13 patients who did not respond to ibutilide treatment underwent successful external electrical cardioversion . The overall conversion rate was 100 % . Forty-seven patients ( 92 % ) were discharged within a median of 9 h and managed as out patients . In conclusion , in haemodynamically stable patients with recent-onset atrial fibrillation/flutter intravenous ibutilide and external electrical cardioversion for conversion to sinus rhythm turned out to be effective and safe . The short duration of admission makes this strategy attractive for use in the ED", "Introduction : There is a trend towards accelerated management of acute atrial fibrillation ( AF ) in the emergency department ( ED ) . We report our experience with biphasic cardioversion of acute AF . Methods : This was a prospect i ve , descriptive study at a tertiary hospital ED over a 6 month period . Acute AF was defined as symptoms that had been present for biphasic cardioversion for acute AF in the ED were enrolled . Data collected included : patient demographics , past medical history , details of biphasic cardioversion , outcome , complications , disposition , and length of stay . Results : There were 34 attempts at cardioversion in 33 patients . The mean ( SD ) age was 56 ( 16 ) years and 21 patients ( 64 % ) were men . Biphasic cardioversion was successful in 31 attempts ( 91 % ) . In 24 attempts ( 71 % ) , 100 J was selected as the initial energy level . This was successful in 21 attempts ( 88 % ) . There were three minor complications related to sedation . The mean ( SD ) length of stay was 5.6 ( 2.8 ) hours in the ED and 15 ( 25 ) hours in the hospital . The three patients who failed to revert were older ( mean age 64 years ) , had underlying cardiovascular disease , and spent longer in hospital ( 50 v 12 hours , p = 0.01 ) . Telephone follow up was conducted with 32 patients ( 97 % ) at 3 months . Recurrence of AF occurred in 7 patients ( 22 % ) . Most patients ( 31 , 97 % ) were satisfied with the biphasic cardioversion . Conclusions : Biphasic cardioversion of acute AF is effective . The majority of patients can be managed as out patients , and there is very high patient satisfaction with this approach . An initial shock energy level of 100 J is usually effective", "BACKGROUND A st and ard approach to recent onset atrial fibrillation ( AF ) in the emergency department ( ED ) in the United States has not been established . PURPOSE The purpose of this prospect i ve clinical trial was to determine how an ED protocol emphasizing rhythm control for recent onset AF compared similar patients receiving st and ard therapy in the same facility . METHODS We enrolled consecutive patients presenting to our community hospital with recent onset AF into a protocol , which called for rhythm control with procainamide and if unsuccessful electrical cardioversion and discharge home . We compared this prospect i ve cohort with matched historical controls . Primary outcome was admission rate . We also compared ED conversion rates and lengths of stay ( LOS ) . We reported 30-day data on the study group including ED recidivism , recurrent AF , outpatient follow-up , and any important adverse events . RESULTS Fifty-four patients were enrolled in the study group with 4 being admitted compared with 30 of 50 in the historical control group . Ninety-four percent of the study group converted compared with 28 % in the historical control . Both hospital and ED LOS were significantly shorter for the study group . Six patients had recurrent AF , and 4 of those returned to the ED . CONCLUSION An ED protocol that uses rhythm control decreased hospital admission and LOS , and there were no adverse events at 30 days", "STUDY OBJECTIVE In the United States , nearly 70 % of emergency department ( ED ) visits for atrial fibrillation result in hospitalization . The incidence of serious 30-day adverse events after an ED evaluation for atrial fibrillation remains low . This study 's goal was to prospect ively vali date our previously reported Risk Estimator Decision Aid for Atrial Fibrillation ( RED-AF ) model for estimating a patient 's risk of experiencing a 30-day adverse event . METHODS This was a prospect i ve cohort study , which enrolled a convenience sample of ED patients presenting with atrial fibrillation . RED-AF , previously derived from a retrospective cohort of 832 patients , assigns points according to age , sex , coexisting disease ( eg , heart failure , hypertension , chronic obstructive pulmonary disease ) , smoking , home medications ( eg , β-blocker , diuretic ) , physical examination findings ( eg , dyspnea , palpitations , peripheral edema ) , and adequacy of ED ventricular rate control . Primary outcome was occurrence of greater than or equal to 1 atrial fibrillation-related adverse outcome ( ED visits , rehospitalization , cardiovascular complications , death ) within 30 days . We identified a clinical ly relevant threshold and measured RED-AF 's performance in this prospect i ve cohort , assessing its calibration , discrimination , and diagnostic accuracy . RESULTS The study enrolled 497 patients between June 2010 and February 2013 . Of these , 120 ( 24 % ) had greater than or equal to 1 adverse event within 30 days . A RED-AF score of 87 was identified as an optimal threshold , result ing in sensitivity and specificity of 96 % ( 95 % confidence interval [ CI ] 91 % to 98 % ) and 19 % ( 95 % CI 15 % to 23 % ) , respectively . Positive and negative predictive values were 27 % ( 95 % CI 23 % to 32 % ) and 93 % ( 95 % CI 85 % to 97 % ) , respectively . The c statistic for RED-AF was 0.65 ( 95 % CI 0.59 to 0.71 ) . CONCLUSION In this separate validation cohort , RED-AF performed moderately well and similar to the original derivation cohort for identifying the risk of short-term atrial fibrillation-related adverse events in ED patients receiving a diagnosis of atrial fibrillation" ]

[ "Of 22 r and omized trials of rehabilitation with exercise after myocardial infa rct ion ( MI ) , one trial had results that achieved conventional statistical significance . To determine whether or not these studies , in the aggregate , show a significant benefit of rehabilitation after myocardial infa rct ion , we performed an overview of all r and omized trials , involving 4,554 patients ; we evaluated total and cardiovascular mortality , sudden death , and fatal and nonfatal reinfa rct ion . For each endpoint , we calculated an odds ratio ( OR ) and 95 % confidence interval ( 95 % CI ) for the trials combined . After an average of 3 years of follow-up , the ORs were significantly lower in the rehabilitation than in the comparison group : specifically , total mortality ( OR = 0.80 [ 0.66 , 0.96 ] ) , cardiovascular mortality ( OR = 0.78 [ 0.63 , 0.96 ] ) , and fatal reinfa rct ion ( OR = 0.75 [ 0.59 , 0.95 ] ) . The OR for sudden death was significantly lower in the rehabilitation than in the comparison group at 1 year ( OR = 0.63 [ 0.41 , 0.97 ] ) . The data were compatible with a benefit at 2 ( OR = 0.76 [ 0.54 , 1.06 ] ) and 3 years ( OR = 0.92 [ 0.69 , 1.23 ] ) , but these findings were not statistically significant . For nonfatal reinfa rct ion , there were no significant differences between the two groups after 1 ( OR = 1.09 [ 0.76 , 1.57 ] ) , 2 ( OR = 1.10 [ 0.82 , 1.47 ] ) , or 3 years ( OR = 1.09 [ 0.88 , 1.34 ] ) of follow-up . The observed 20 % reduction in overall mortality reflects a decreased risk of cardiovascular mortality and fatal reinfa rct ion throughout at least 3 years and a reduction in sudden death during the 1st year after infa rct ion and possibly for 2 - 3 years . With respect to the independent effects of the physical exercise component of cardiac rehabilitation , the relatively small number of \" exercise only \" trials , combined with the possibility that they may have had a formal or informal nonexercise component precludes the possibility of reaching any definitive conclusion . To do so would require a r and omized trial of sufficient size to distinguish between no effect and the most plausible effect based on the results of this overview", "BACKGROUND Recent clinical trials have shown that modification of plasma lipoprotein concentrations can favorably alter progression of coronary atherosclerosis , but no data exist on the effects of a comprehensive program of risk reduction involving both changes in lifestyle and medications . This study tested the hypothesis that intensive multiple risk factor reduction over 4 years would significantly reduce the rate of progression of atherosclerosis in the coronary arteries of men and women compared with subjects r and omly assigned to the usual care of their physician . METHODS AND RESULTS Three hundred men ( n = 259 ) and women ( n = 41 ) ( mean age , 56 + /- 7.4 years ) with angiographically defined coronary atherosclerosis were r and omly assigned to usual care ( n = 155 ) or multifactor risk reduction ( n = 145 ) . Patients assigned to risk reduction were provided individualized programs involving a low-fat and -cholesterol diet , exercise , weight loss , smoking cessation , and medications to favorably alter lipoprotein profiles . Computer-assisted quantitative coronary arteriography was performed at baseline and after 4 years . The main angiographic outcome was the rate of change in the minimal diameter of diseased segments . All subjects underwent medical and risk factor evaluations at baseline and yearly for 4 years , and reasons for all hospitalizations and deaths were documented . Of the 300 subjects r and omized , 274 ( 91.3 % ) completed a follow-up arteriogram , and 246 ( 82 % ) had comparative measurements of segments with visible disease at baseline and follow-up . Intensive risk reduction result ed in highly significant improvements in various risk factors , including low-density lipoprotein cholesterol and apolipoprotein B ( both , 22 % ) , high-density lipoprotein cholesterol ( + 12 % ) , plasma triglycerides ( -20 % ) , body weight ( -4 % ) , exercise capacity ( + 20 % ) , and intake of dietary fat ( -24 % ) and cholesterol ( -40 % ) compared with relatively small changes in the usual-care group . No change was observed in lipoprotein(a ) in either group . The risk-reduction group showed a rate of narrowing of diseased coronary artery segments that was 47 % less than that for subjects in the usual-care group ( change in minimal diameter , -0.024 + /- 0.066 mm/y versus -0.045 + /- 0.073 mm/y ; P deaths occurred in each group . There were 25 hospitalizations in the risk-reduction group initiated by clinical cardiac events compared with 44 in the usual-care group ( rate ratio , 0.61 ; P = .05 ; 95 % confidence interval , 0.4 to 0.9 ) . CONCLUSIONS Intensive multifactor risk reduction conducted over 4 years favorably altered the rate of luminal narrowing in coronary arteries of men and women with coronary artery disease and decreased hospitalizations for clinical cardiac events", "Background Significant regression of coronary and femoral atherosclerotic lesions has been documented by angiographic studies using aggressive lipid-lowering treatment . This study tested the applicability and effects of intensive physical exercise and low-fat diet on coronary morphology and myocardial perfusion in nonselected patients with stable angina pectoris . Methods and Results Patients were recruited after routine coronary angiography for stable angina pectoris ; they were r and omized to an intervention group ( n = 56 ) and a control group on “ usual care ” ( n = 57 ) . Treatment comprised intensive physical exercise in group training sessions ( minimum , 2 hr/wk ) , daily home exercise periods ( 20 min/d ) , and low-fat , low-cholesterol diet ( American Heart Association recommendation , phase 3 ) . No lipid-lowering agents were prescribed . After 12 months of participation , repeat coronary angiography was performed ; relative and minimal diameter reductions of coronary lesions were measured by digital image processing . Change in myocardial perfusion was assessed by 201TI scintigraphy . In patients participating in the intervention group , body weight decreased by 5 % ( p total cholesterol by 10 % ( p triglycerides by 24 % ( p high density lipoproteins increased by 3 % ( p = NS ) . Physical work capacity improved by 23 % ( p myocardial oxygen consumption , as estimated from maximal rate-pressure product , by 10 % , ( p Stress-induced myocardial ischemia decreased concurrently , indicating improvement of myocardial perfusion . Based on minimal lesion diameter , progression of coronary lesions was noted in nine patients ( 23 % ) , no change in 18 patients ( 45 % ) , and regression in 13 patients ( 32 % ) . In the control group , metabolic and hemodynamic variables remained essentially unchanged , whereas progression of coronary lesions was noted in 25 patients ( 48 % ) , no change in 18 patients ( 35 % ) , and regression in nine patients ( 17 % ) . These changes were significantly different from the intervention group ( p physical exercise and low-fat diet , coronary artery disease progresses at a slower pace compared with a control group on usual care", "Background —Whether cardiac rehabilitation ( CR ) is effective in patients older than 75 years , who have been excluded from most trials , remains unclear . We enrolled patients 46 to 86 years old in a r and omized trial and assessed the effects of 2 months of post-myocardial infa rct ion ( MI ) CR on total work capacity ( TWC , in kilograms per meter ) and health-related quality of life ( HRQL ) . Methods and Results —Of 773 screened patients , 270 without cardiac failure , dementia , disability , or contraindications to exercise were r and omized to outpatient , hospital-based CR ( Hosp-CR ) , home-based CR ( Home-CR ) , or no CR within 3 predefined age groups ( middle-aged , 45 to 65 years ; old , 66 to 75 years ; and very old , > 75 years ) of 90 patients each . TWC and HRQL were determined with cycle ergometry and Sickness Impact Profile at baseline , after CR , and 6 and 12 months later . Within each age group , TWC improved with Hosp-CR and Home-CR and was unchanged with no CR . The improvement was similar in middle-aged and old persons but smaller , although still significant , in very old patients . TWC reverted toward baseline by 12 months with Hosp-CR but not with Home-CR . HRQL improved in middle-aged and old CR and control patients but only with CR in very old patients . Complications were similar across treatment and age groups . Costs were lower for Home-CR than for Hosp-CR . Conclusions —Post-MI Hosp-CR and Home-CR are similarly effective in the short term and improve TWC and HRQL in each age group . However , with lower costs and more prolonged positive effects , Home-CR may be the treatment of choice in low-risk older patients", "OBJECTIVE --To determine whether a group programme of light exercise could improve quality of life in patients after acute myocardial infa rct ion to the same extent as a high intensity exercise training programme . SETTING --Australian teaching hospital . PATIENTS --224 men from a consecutive series of 339 men under 70 admitted to a coronary care unit with transmural acute myocardial infa rct ion . INTERVENTION-- Patients were r and omly allocated in hospital to a group programme lasting eight weeks of either high intensity exercise training or light exercise . MAIN OUTCOME MEASURES --Physical working capacity based on metabolic equivalents achieved from treadmill exercise tests at entry , after 11 weeks , and after one year . Quality of life based on self report scores of anxiety , depression , denial , and wellbeing and interview assessment s of activities and psychosocial adjustment at entry , after four months , and after one year . RESULTS --The two groups were well matched at entry . At 11 weeks the mean results of treadmill testing were 10.7 ( 95 % confidence interval 10.20 to 11.20 ) metabolic equivalents for exercise training and 9.7 ( 9.26 to 10.14 ) for light exercise ( t = 2.85 , df = 181 , p = 0.005 ) . Apart from this small temporary benefit in mean physical working capacity , there were no significant differences between groups . Improvement in occupational adjustment score from baseline to four months was greater after exercise training than after light exercise , but at one year repeated measures analysis of variance showed no significant effects of treatment or interaction between treatment and time point . CONCLUSION --The effects on quality of life of a low cost programme of light exercise are similar to those obtained from a high intensity exercise training programme", "Background : The CardioFit internet-based expert system was design ed to promote physical activity in patients with coronary heart disease ( CHD ) who were not participating in cardiac rehabilitation . Design : This r and omized controlled trial compared CardioFit to usual care to assess its effects on physical activity following hospitalization for acute coronary syndromes . Methods : A total of 223 participants were recruited at the University of Ottawa Heart Institute or London Health Sciences Centre and r and omly assigned to either CardioFit ( n = 115 ) or usual care ( n = 108 ) . The CardioFit group received a personally tailored physical-activity plan upon discharge from the hospital and access to a secure website for activity planning and tracking . They completed five online tutorials over a 6-month period and were in email contact with an exercise specialist . Usual care consisted of physical activity guidance from an attending cardiologist . Physical activity was measured by pedometer and self-reported over a 7-day period , 6 and 12 months after r and omization . Results : The CardioFit internet-based physical activity expert system significantly increased objective ly measured ( p = 0.023 ) and self-reported physical activity ( p = 0.047 ) compared to usual care . Emotional ( p = 0.038 ) and physical ( p = 0.031 ) dimensions of heart disease health-related quality of life were also higher with CardioFit compared to usual care . Conclusions : Patients with CHD using an internet-based activity prescription with online coaching were more physically active at follow up than those receiving usual care . Use of the CardioFit program could extend the reach of rehabilitation and secondary -prevention services", "OBJECTIVE To evaluate the effectiveness of a home-based cardiac rehabilitation ( CR ) program on post-coronary arteries bypass graft patients . METHODS This is a r and omized study conducted in King Fahd Armed Forces Hospital , Jeddah , Kingdom of Saudi Arabia between June 2008 and January 2010 . Forty-nine participants were r and omized to either a control group ( st and ard hospital treatment , n=21 ) or an intervention group ( home-based CR , n=28 ) . Data were collected before hospital discharge ( baseline test ) and repeated 6 months after hospital discharge ( follow-up test ) . RESULTS There were no significant differences between the groups in the body mass index , hemodynamics , serum fasting lipid profile , and Quality of Life question naire ( QoL ) ( p>0.05 ) , with differences in physical function and Hospital Anxiety and Depression Scales ( HADS ) ( p health-related QoL and risk factors compared to the control group , with significant differences in fasting blood glucose , triglycerides , high density lipoprotein cholesterol , physical function , and both QoL and HADS question naires ( p QoL , HADS , body mass index , heart rate , high density lipoprotein cholesterol and physical function ( p heart rate , QoL and physical function ( p The home-based CR program improves health-related QoL and risk factor profiles for patients following coronary arteries bypass graft to greater extent than the st and ard hospital care", "The Women ’s Lifestyle Heart Trial was a small ( N=28 ) r and omized controlled trial to evaluate the effects of a comprehensive lifestyle self-management program ( very low-fat vegetarian diet , stress-management training , exercise , group support , and smoking cessation ) on reduction of cardiovascular risk factors in postmenopausal women with coronary heart disease ( CHD ) . Women assigned to the treatment condition ( Prime Time ) participated in a week-long retreat followed by twice-weekly 4-hour meetings . Endpoints were program adherence ; changes in lipid profiles , body mass , blood pressure , hypolipidemic and antihypertensive medications ; and quality of life . Risk factor and psychosocial evaluations were conducted at baseline and at 4 , 12 , and 24 months . Repeated measures analyses of covariance revealed that the dietary , stress management , and physical activity changes made by intervention women were dramatic and lasting . There were significantly greater improvements in the Prime Time condition compared to the usual care control group on body mass , angina symptoms , and quality of life , and a tendency for a greater reduction in blood pressure-lowering medications . Similar patterns were seen in lipids , blood pressure , and lipid-lowering medications , but did not reach significance . These results demonstrate that postmenopausal CHD women can make lasting lifestyle changes , and that these changes may reduce the need for cardiac medications and improve CHD risk factors and quality of life", "The effects of an exercise program started early after myocardial infraction and the added effects of an outpatient teaching-counseling program were studied . At r and om , 84 patients were allocated to a control group ( A ) , 88 patients to an exercise group ( B1 ) and 86 patients to an exercise and teaching-counseling group ( B2 ) . The same exercise program was prescribed for patients in groups B1 and B2 and was started about 4.5 days after myocardial infa rct ion and continued for 3 months . The outpatient teaching-counseling program consisted of eight group sessions pertaining to risk factor reduction and psychosocial adjustment to myocardial infraction . A low-level treadmill test and an exercise test were performed at 3 months and the exercise test was repeated at 6 months . The clinical , hemodynamic and electrocardiographic responses to these tests were not different among the three groups . However , by the end of 3 months , patients in group B1 and B2 reported walking greater distances than patients in group A. The incidence of morbidity and mortality was not different between the groups . No deleterious or beneficial physiologic effects of an exercise program either by itself or combined with a teaching-counseling program were demonstrated . Routine medical care and our interventions were equally effective in permitting the spontaneous hemodynamics improvements after myocardial infraction . More than 3 months after myocardial infa rct ion , the group as a whole manifested spontaneous recovery in the form of a significant decrease in resting heart rate ( p less than 0.001 ) and a significant increase in systolic and diastolic blood pressure at rest and with submaximal exercise ( p less than 0.001 ) . No further improvements were observed between 3 and 6 months", "BACKGROUND It was the aim of this study to assess the long-term effects of physical exercise and low-fat diet on the progression of coronary artery disease . At the beginning of the study , 113 male patients with coronary artery disease were r and omized to an intervention group ( n=56 ) or a control group ( n=57 ) ; 90 patients ( 80 % ) could be reevaluated after 6 years . METHODS AND RESULTS Patients in the intervention group ( n=40 ) showed a reduction in total serum cholesterol ( 6.03+/-1.03 versus 5.67+/-1.01 mmol/L ; P triglyceride levels ( 1.94+/-0.8 versus 1.6+/-0.89 mmol/L ; P body mass index ( 26+/-2 versus 27+/-2 kg/m2 ; P = NS ) , but results were not statistically different from the control group ( n=50 ) ( total serum cholesterol , 6.05+/-1.02 versus 5.79+/-0.88 mmol/L ; triglycerides , 2.25+/-1.28 versus 1.85+/-0.96 mmol/L [ both P = NS ] ; body mass index , 26+/-2 versus 28+/-3 kg/m2 [ P physical work capacity ( 166+/-59 versus 212+/-89 W ; P stenoses progressed at a significantly slower rate than in the control group ( P Energy expenditure during exercise was assessed in a subgroup ; patients with regression of coronary stenoses spent an average of 1784+/-384 kcal/wk ( approximately 4 hours of moderate aerobic exercise per week ) . Multivariate regression analysis identified only physical work capacity as independently contributing to angiographic changes . CONCLUSIONS After 6 years of multifactorial risk intervention , there is significant and persistent improvement in lipoprotein levels and physical work capacity , which results in a significant retardation of disease progression . These beneficial effects appear to be largely due to chronic physical exercise", "Background It is widely believed that cardiac rehabilitation following acute myocardial infa rct ion ( MI ) reduces mortality by approximately 20 % . This belief is based on systematic review s and meta-analyses of mostly small trials undertaken many years ago . Clinical management has been transformed in the past 30–40 years and the findings of historical trials may have little relevance now . Objectives The principal objective was to determine the effect of cardiac rehabilitation , as currently provided , on mortality , morbidity and health-related quality of life in patients following MI . The secondary objectives included seeking programmes that may be more effective and characteristics of patients who may benefit more . Design , setting , patients , outcome measures A multi-centre r and omised controlled trial in representative hospitals in Engl and and Wales compared 1813 patients referred to comprehensive cardiac rehabilitation programmes or discharged to ‘ usual care ’ ( without referral to rehabilitation ) . The primary outcome measure was all-cause mortality at 2 years . The secondary measures were morbidity , health service use , health-related quality of life , psychological general well-being and lifestyle cardiovascular risk factors at 1 year . Patient entry ran from 1997 to 2000 , follow-up of secondary outcomes to 2001 and of vital status to 2006 . A parallel study compared 331 patients in matched ‘ elective ’ rehabilitation and ‘ elective ’ usual care ( without rehabilitation ) hospitals . Results There were no significant differences between patients referred to rehabilitation and controls in mortality at 2 years ( RR 0.98 , 95 % CI 0.74 to 1.30 ) or after 7–9 years ( 0.99 , 95 % CI 0.85 to 1.15 ) , cardiac events , seven of eight domains of the health-related quality of life scale ( ‘ Short Form 36 ’ , SF36 ) or the psychological general well-being scale . Rehabilitation patients reported slightly less physical activity . No differences between groups were reported in perceived overall quality of cardiac aftercare . Data from the ‘ elective ’ hospitals comparison concurred with these findings . Conclusion In this trial , comprehensive rehabilitation following MI had no important effect on mortality , cardiac or psychological morbidity , risk factors , health-related quality of life or activity . This finding is consistent with systematic review s of all trials reported since 1983 . The value of cardiac rehabilitation as practised in the UK is open to question", "Coronary artery diseases ( CAD ) are main causes of morbidity and hospitalisation in western countries and CAD patients are at considerable risk of suffering further cardiac events . The development and evaluation of secondary prevention programmes therefore an important task . This thesis includes investigations on CAD patients admitted to a secondary prevention programme at Malmö University Hospital , Malmö , Sweden . Four weeks after discharge from the hospital , consecutive male and female patients aged 50 - 70 years with acute myocardial infa rct ion ( AMI ) or treated with coronary artery bypass grafting ( CABG ) surgery were r and omised to a hospital organised preventive intervention or to usual follow-up at their general practitioners . In the three studies using this r and omised design , 87 ( study II ) , 90 ( study IV ) , and 106 ( study V ) intervention patients were available for evaluation . In addition , without r and omisation , lipid levels at four weeks after the event was compared with levels estimated within 24 hours after onset of symptoms in 141 AMI patients ( study I ) , and quality of life ( QL ) were estimated by question naire at one month and at one year after the event in 266 AMI , 94 CABG , and 16 percutaneous transluminal coronary angioplasty ( PTCA ) patients ( study III ) . The prevention programme was effective in improving food habits but showed no impact on smoking habits or physical exercise in AMI patients ( study II ) . The intervention also did not show any significant improvement in working capacity in AMI and CABG patients . However , working capacity improved in both intervention and reference CABG patients , most probably due to improved coronary circulation from the surgery ( study IV ) . Cholesterol levels decreased significantly in AMI and CABG intervention patients as compared to the corresponding reference patients . This difference most likely was due to a higher frequency of lipid lowering drugs used in the intervention patients ( study V ) . The prevention programme also decreased body mass index significantly in AMI but not in CABG patients ( study V ) . In AMI patients receiving thrombolysis , cholesterol levels estimated within 24 hours after onset of symptoms and at four weeks after the event were virtually equal . In AMI patients not receiving thrombolysis , the lipid estimates from four weeks after the event were slightly , but significantly , above the within 24 hours from onset of symptoms estimates ( study I ) . One month after the event , both somatic and psychological aspects of QL were negatively affected in AMI and CABG patients compared to population controls . One year after the event , patients differed from controls mainly in somatic symptoms ( study III ) . Thus , the intervention programme was most successful in affecting lipid levels and food habits in AMI patients . QL was considerably affected in patients following an cardiac event , especially during the initial recovery phase . In addition , in patients receiving thrombolysis , cholesterol levels estimated four weeks after an AMI are reasonably valid estimates of baseline values and may be used to decide about lipid lowering interventions", "Background : Many studies have shown that individual lifestyle factors are associated with cardiovascular mortality and all-cause mortality . Observational studies of comprehensive programmes have reported risk reductions . The objectives were to assess the long-term all-cause mortality by diagnosis in patients referred to a lifestyle modification programme , aim ed at combating coronary heart disease and stroke . Methods : A r and omized trial with 325 patients referred to the centre between 1988 and 1989 for dyslipidemia , hypertension , type 2 diabetes and coronary heart disease ; 239 patients were r and omized to the programme , 86 r and omized to usual care . Cases were admitted to the centre in groups of 30 for a 4-week residential comprehensive activity , in total 114 full-time hours , focusing on food preferences and selection s , and physical exercise . The activities were repeated during a 4-day revisit to the centre 1 year and 5 years after the 4-week intervention . Controls were referred back to their doctors , mainly in primary care , for usual care . Main outcome measure was all-cause mortality during 11–12 and 18–19 years after intervention . Results : At follow-up 11–12 years after referral , the relative risk reduction ( RRR ) was 76 % with the intention-to-treat analysis among cases admitted for dyslipidemia ( hazards ratio 0.24 , confidence interval 0.06–0.89 , P = 0.033 ) . After 18–19 years , the RRR was 66 % ( hazards ratio 0.34 , confidence interval 0.13–0.88 , P = 0.026 ) . No RRR was found for the other three diagnoses . Conclusion : Patients admitted for dyslipidemia reached a real long-term RRR of all-cause mortality . They had by definition a need for this programme", "Background Recent advances in drug therapy question as to the additional impact behavioral interventions may have on the prognosis of patients with clinical ly stable coronary heart disease ( CHD ) . Purpose The aim of the study was to evaluate the effects of a multimodal , behavioral intervention on myocardial perfusion ( MP ) and cardiac events , compared to st and ardized cardiologic care , in patients with stable CHD . Methods Seventy-seven CHD patients ( age 54.2 ± 6.9 years , male 87 % ) were r and omly assigned to a behavioral intervention plus st and ardized cardiologic care ( INT , n = 39 ) or st and ardized cardiologic care alone ( CO , n = 38 ) . MP was assessed by 201Thallium MP-scintigrams ( SPECT ) at baseline , after 2 , 3 , and 7 years , respectively . Subsequent cardiac events ( MI , PCI , CABG ) were assessed using the cardiologists ’ charts . Results Sixty-five patients ( 84 % ) completed the study . In all patients , the course of MP was significantly better in INT analysis of variance ( ANOVA group × time p = 0.001 ) ; this was also true for patients without subsequent PCI/CABG ( ANOVA group × time p = 0.002 ) . Incidence of cardiac events was significantly associated with INT ( 6 vs. 14 ; log rank test p = .047 ) . Conclusion The study suggests additional long-term benefits of a behavioral intervention on myocardial perfusion and cardiac events in patients with stable CHD compared to st and ardized cardiologic care only", "BACKGROUND This study examined whether a supervised exercise program improved 19-year survival in 30- to 64-year-old male myocardial infa rct ion patients . METHODS AND RESULTS The men ( n=651 ) were participants in the National Exercise and Heart Disease Project , a 3-year multicenter r and omized clinical trial conducted in the United States ( 1976 - 1979 ) . The treatment group ( n=315 ) exercised for 8 weeks in a laboratory . Thereafter , they jogged , cycled , or swam in a gymnasium/pool setting guided by an individualized target heart rate . Participants in the control group ( n=319 ) were to maintain normal routines but not participate in any regular exercise program . Participants were followed up until their death or December 31 , 1995 . Cox proportional hazards analysis revealed the all-cause mortality risk estimates ( 95 % CIs ) in the exercise group compared with controls to be 0.69 ( 0.39 to 1.25 ) after an average follow-up of 3 years , 0.84 ( 0.55 to 1.28 ) after 5 years , 0.95 ( 0.71 to 1.29 ) after 10 years , 1.02 ( 0.79 to 1.32 ) after 15 years , and 1.09 ( 0.87 to 1 . 36 ) after 19 years . Cardiovascular disease ( CVD ) mortality risk estimates ( 95 % CI ) for the same follow-up periods were 0.73 ( 0.37 to 1.43 ) , 0.98 ( 0.60 to 1.61 ) , 1.21 ( 0.79 to 1.60 ) , 1.14 ( 0.84 to 1.54 ) , and 1.16 ( 0.88 to 1.52 ) . However , each 1-MET increase in work capacity from baseline to the end of the original trial result ed in consistent reductions in all-cause and CVD mortality risk at each follow-up period , regardless of initial work-capacity level . CONCLUSIONS These findings indicate exercise-program participation result ed in nonsignificantly reduced mortality risks early in the follow-up period . Benefits diminished as time since participation increased , which suggests that the protective mechanisms associated with the program may be short term . Contamination between groups over time could also explain the diminished effects , because increased work capacity provided survival benefits up to 19 years", "OBJECTIVE To examine and evaluate improvements in cardiorespiratory fitness , psychological wellbeing , quality of life , and vocational status in postmyocardial infa rct ion patients during and after a comprehensive 12 month exercise rehabilitation programme . SUBJECTS The sample population comprised 124 patients with a clinical diagnosis of myocardial infa rct ion ( 122 men and two women ) . INTERVENTIONS 62 patients were r and omly allocated to a regular weekly aerobic training programme , three times a week for 12 months , and compared with 62 matched controls who did not receive any formal exercise training . A five year follow up question naire/interview was subsequently conducted on this population to determine selected vocational/lifestyle changes . RESULTS Significant improvements in cardiorespiratory fitness ( p , psychological profiles ( p and quality of life scores ( p mortality , a larger percentage of the regular exercisers resumed full time employment and they returned to work earlier than the controls . Controls took lighter jobs , lost more time from work , and suffered more non-fatal reinfa rct ions ( p aerobic exercise training improves cardiorespiratory fitness , psychological status , and quality of life . The trained population also had a reduction in morbidity following myocardial infa rct ion , and significant improvement in vocational status over a five year follow up period", "A prospect i ve , r and omized , controlled clinical trial in patients with coronary artery disease ( CAD ) and a concurrent physical disability evaluated the effects of a home exercise training program on cardiovascular function and blood lipids . Eighty-eight men between the ages of 42 and 72 years ( mean 62 ) with documented CAD and a physical disability with functional use of > or = 2 extremities including 1 arm were r and omized to either a 6-month home exercise training program using wheelchair ergometry or to a control group that received usual and customary care . Both groups received dietary instructions and were requested to follow a fat-controlled diet . Exercise test variables with echocardiography and blood lipids were measured at baseline and at 6 months . The home exercise training group significantly improved both peak exercise left ventricular ejection fraction ( p = 0.007 ) and fractional shortening ( p = 0.01 ) between baseline to 6 months , whereas the control group showed no significant changes . Exercise training effects of decreased resting heart rate ( p = 0.03 ) and decreased peak rate pressure product ( p = 0.03 ) were also found in the treatment group . No exercise-related cardiac complications occurred . Both groups significantly ( p high-density lipoprotein cholesterol levels . These results indicate that physically disabled men with CAD can safely participate in a home exercise training program which may result in intrinsic cardiac benefits . The metabolic cost of activities of daily living imposed on this disabled population may also have a positive effect on high-density lipoprotein cholesterol levels", "Background Exercise improves the clinical outcome of patients with coronary artery disease ( CAD ) ; however , the ideal exercise duration for each patient remains unclear . Objective To investigate the effects of exercise duration on arterial elastic properties and antioxidant/pro-oxidant mechanisms in patients with CAD . Design , setting , patients , interventions Sixty male patients with CAD were r and omised into two groups , and underwent exercise for 30 min or 60 min in a crossover design with 2 weeks ' wash-out period . In all participants aortic and radial blood pressures ( BP ) and arterial elastic properties ( augmentation index (AIx)/pulse wave velocity ( PWV ) ) were determined at baseline and 24 h after exercise . Plasma malonyldialdehyde ( MDA ) and superoxide dismutase (SOD)1 and SOD2 levels were also measured . Results Exercise had no effect on aortic and radial BP ( p = NS for all ) . Walking for 30min improved AIx ( from 33.79±0.91 % to 31.73±0.86 % , p PWV ( from 9.26±0.95 m/s to 9.06± 0.21 m/s , p exercise for 60min had adverse effects on vascular stiffness ( for AIx : from 33.37± 0.93 % to 33.73± 1.05 % , p = NS and for PWV : from 9.25±0.19 m/s to 9.37±0.21 m/s , p Exercise for 60min was associated with a significant 20 % increase in MDA levels ( p . Exercise had no effects on SOD1 levels , however it significantly increased SOD2 levels after 30min ( from 2.26±0.22ng/mL to 2.36±0.18ng/mL , p Conclusion Shorter exercise duration was associated with favourable antioxidant and vascular effects , while longer exercise blunted these beneficial effects and was accompanied by adverse effects on vascular function , mainly in older coronary patients . Further studies are required to explore the hypothesis that a more individualised approach to the selection of the appropriate exercise programme should be considered for patients with CAD", "AIM To investigate efficacy of early and long term physical training ( PT ) of moderate intensity in conditions of practical health care in Russia in patients with ischemic heart disease ( IHD ) of able to work age - survivors of acute coronary events . MATERIAL AND METHODS Three hundred ninety two patients were enrolled in this study . They were r and omized into intervention group \" O \" ( n=197 ) and control group \" C \" ( n=195 ) . Inclusion period was 3- 8 weeks from onset of myocardial infa rct ion ( MI ) , unstable angina ( UA ) , or intervention on coronary arteries . Patients were followed up for 1 year and efficacy of intervention was assessed by results of laboratory ( levels of lipids ) , instrumental ( ECG , exercise test on veloergometer , echocardiography ) , and clinical examination . In the group \" O \" regimen of PT with work loads of moderate intensity ( 50 - 60 % of power achieved during exercise test ) was used . Duration of FT was 45 - 60 min , frequency - 3 times a week . All patients received st and ard therapy for IHD and a lipid lowering drug when indicated . RESULTS Proofs of efficacy of PT in the given contingent of patients were obtained . This was manifested by significant increase of physical working capacity : prolongation of exercise time ( + 31.7 % , p volume of work performed ( + 74.3 % , p efficiency of cardiac work according to results of exercise tests . All parameters were significantly different from those in the group \" C \" . Structural functional parameters of the heart also improved in the group \" O \" : left ventricular ( LV ) stroke volume increased 4.5 % ( p ejection fraction increased 7.2 % ( p diastolic LV volume decreased 2.5 % ( p systolic LV volume decreased 8.1 % ( p stroke volume and LV ejection fraction rose to a lesser degree - by 5.5 % ( p LV diastolic volume increased 2.3 % ( p systolic volume did not change , while left atrium increased 3.4 % ( p dynamics of these parameters were significant ( p lipid profile after 1 year showed no changes in patients of group \" C \" , while in group \" O \" it revealed significant ( 3.6 % ) lowering of total ( T ) cholesterol ( CH ) ( p high density lipoprotein ( HDL ) CH ( + 12.3 % , p Atherogeneity index TCH/HDLCH decreased 8.5 % in the group \" O \" ( p body mass index decreased 2.8 % ( p frequency of attacks of angina decreased 50.8 % ( p total number of cardiovascular events - 26 ( 14.8 % ) vs 47 ( 27 % ) , p number of cardiovascular catastrophes - 5 ( 3 % ) vs 15 ( 8.7 % ) , p number of days out of work because of exacerbation of IHD per 1 person/year - 2.4 vs 4.2 , p course and outcomes of the disease was registered compared with the group \" C \" . CONCLUSION The data obtained are indicative of sufficient efficacy of the used program of PT and feasibility of its application in practice of ambulatory rehabilitation of patients with IHD - survivors of acute coronary events . It also can be looked upon as a method of secondary prevention as results of the study showed its positive impact on risk factors and outcomes of the disease", "Background In cardiac rehabilitation , 40 - 60-min exercise training sessions are advised . However , because of the increasing coronary artery disease ( CAD ) prevalence and higher workload for cardiac rehabilitation centres , it remains unclear whether 40-min exercise training sessions are equally effective as 60-min exercise training sessions . Design Prospect i ve r and omized clinical trial . Methods One hundred and thirty-four CAD patients were included in a 7-week rehabilitation programme . All patients exercised 3 days per week , at a heart rate corresponding to 65 % of baseline peak oxygen uptake ( VO2peak ) . Patients were r and omized in two groups : 40 versus 60-min exercise training sessions . Changes of body anthropometrics , resting haemodynamics , exercise capacity and ventilatory threshold , blood plasma lipid profile and C-reactive protein level were assessed . Results As a result of rehabilitation , exercise capacity , ventilatory threshold , and blood plasma lipid profile improved significantly in the total population ( P 0.05 ) . Body weight and waist circumference decreased significantly in total population ( P CAD patients , 40-min exercise training sessions seem to be at least as effective for improving body anthropometrics , blood plasma lipid profile and exercise capacity , as compared with 60-min exercise training sessions . Eur J Cardiovasc Prev Rehabil 15:453 - 459 © 2008 The European Society of Cardiology", "INTRODUCTION AND OBJECTIVES Very little information is available on the effect of cardiac rehabilitation programs on long-term survival . The primary aim of this study was to assess the effect of a structured cardiac rehabilitation program on mortality in patients who had suffered acute myocardial infa rct ion . The secondary endpoint was the effect on morbidity . PATIENTS AND METHOD The study included 180 low-risk male patients aged under 65 years . Patients were r and omly assigned to one of 2 groups : 90 entered into a comprehensive cardiac rehabilitation program , and 90 served as a control group . The mean follow-up period was 10 years . RESULTS All-cause mortality was significantly lower in the intervention group : the 10-year survival rate was 91.8 % in the intervention group compared with 81.7 % in the control group ( P=.04 ) . There was also a decrease in cardiovascular mortality , though it was not statistically significant : the 10-year survival rate was 91.8 % in the intervention group compared with 83.8 % in the control group ( P=.10 ) . The incidence of non-fatal complications was lower in the intervention group ( 35.2 % vs 63.2 % , P=.03 ) , as was the incidence of unstable angina ( 15.7 % vs 33.9 % , P = .02 ) and cardiac heart failure ( 3.0 % vs 14.4 % , P=.02 ) , and the need for coronary intervention ( 8.4 % vs 22.9 % , P=.02 ) . CONCLUSIONS The application of a comprehensive cardiac rehabilitation program significantly decreased long-term mortality and morbidity in low-risk patients after acute myocardial infa rct ion", "AIMS In a multifactorial lifestyle behaviour programme , of 2 years duration , to study the maintenance of achieved behaviour and risk factor-related changes . METHODS AND RESULTS Out of a consecutive population of 151 patients treated with percutaneous transluminal angioplasty under 65 years of age , 87 were r and omly allocated to an intervention group ( n=46 ) or to a control group ( n=41 ) . The programme started with a 4 week residential stay , which was focused on health education and the achievement of behaviour change . During the first year of follow-up , a maintenance programme included regular contacts with a nurse , while no further rehabilitative efforts were offered during the second year . One patient died ( control ) . During the second year the proportion of hospitalized patients was lower in the intervention group ( 4 % vs 20%;P lifestyle dependent behaviours : diet ( index at 0 , 12 and 24 months ) : 10.5+/-3 . 4 , 12.9+/-2.5 and 12.4+/-2.6 in the intervention group ( I ) vs 10 . 1+/-3.2 , 10.7+/-3.0 and 11.8+/-3.2 in the control group (C);P exercise sessions per week : 2.5+/-2.3 , 4.5+/-1.9 and 4.4+/-2.1 ( I ) vs 3.1+/-2.2 , 3.5+/-2.3 and 3.7+/-2.7 (C);P smoking ; 18 % , 6 % and 9 % ( I ) vs 12 % , 21 % and 18 % (C);P exercise capacity ( 0 , 12 and 24 months ) : 156+/-42 , 174+/-49 and 165+/-47 W ( I ) vs 164+/-40 , 163+/-49 and 156+/-48 watts (C);P serum cholesterol levels at 0 and 24 months : 5 . 4+/-0.8 and 5.2+/-0.9 mmol . l(-1)(I ) vs 5.4+/-1.0 and 4.9+/-0.9 mmol . l(-1)(C ) ; ns , low density lipoprotein cholesterol level : 3.6+/-0.8 and 3.4+/-0.8 mmol . l(-1)(I ) vs 3.7+/-0.9 and 3.3+/-0.7 mmol . l(-1)(C ) ; ns , triglyceride level : 2.2+/-1.6 and 1.8+/-1.3 mmol . l(-1)(I ) vs 2.2+/-1.4 and 1.6+/-0.6 mmol . l(-1)(C ) ; ns , body mass index ( 0 , 12 and 24 months ) : 27.5+/-4.5 , 27.0+/-4.3 and 27.4+/- 4.5 kg . m(-2)(I ) vs 26.8+/-2.8 , 26.9+/-2.7 and 26.9+/- 3.2 kg . m(-2)(C ) ; ns , waist/hip ratio or blood pressure . The two groups did not differ in quality of life , or psychological factors . Return to work after 12 and 24 months was 74 % and 78 % ( I ) vs 68 % and 61 % ( C ) ; ns . CONCLUSION This rehabilitation programme influenced important lifestyle behaviour and reduced some , but not all , important risk", "Introduction Systematic review er authors intending to include all r and omized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data . Objective The objective of this paper is to provide systematic review er authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of r and omized trials . Methods This guide is based on a review of the Cochrane h and book and published method ological research . The guide deals with participants excluded from the analysis who were considered ‘ non-adherent to the protocol ’ but for whom data are available , and participants with missing data . Results Systematic review er authors should include data from ‘ non-adherent ’ participants excluded from the primary study authors ' analysis but for whom data are available . For missing , unavailable participant data , authors may conduct a complete case analysis ( excluding those with missing data ) as the primary analysis . Alternatively , they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data . When the primary analysis suggests important benefit , sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis . The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta- analysis . The proposed guide does not take into account the uncertainty associated with assumed events . Conclusions This guide proposes methods for h and ling participants excluded from analyses of r and omized trials . These methods can help in establishing the extent to which risk of bias impacts meta- analysis results", "OBJECTIVE To estimate the incremental effects on cost and quality of life of cardiac rehabilitation after an acute coronary syndrome . DESIGN Open r and omised controlled trial with 1 year 's follow-up . Analysis was on an intention-to-treat basis . SETTING Two tertiary hospitals in Sydney . INTERVENTION 18 sessions of comprehensive exercise-based outpatient cardiac rehabilitation or conventional care as provided by the treating doctor . PARTICIPANTS 113 patients aged 41 - 75 years who were self-caring and literate in English . Patients with uncompensated heart failure , uncontrolled arrhythmias , severe and symptomatic aortic stenosis or physical impairment were excluded . MAIN OUTCOME MEASURES Costs ( hospitalisations , medication use , outpatient visits , investigations , and personal expenses ) ; and measures of quality of life . Incremental cost per quality -adjusted life year ( QALY ) saved at 1 year ( this estimate combines within- study utility effects with reported 1-year risk of survival and treatment effects of rehabilitation on mortality ) . Sensitivity analyses around a base case estimate included alternative assumptions of no treatment effect on survival , 3 years of treatment effect on survival and variations in utility . RESULTS The estimated incremental cost per QALY saved for rehabilitation relative to st and ard care was 42,535 US dollars when modelling included the reported treatment effect on survival . This increased to 70,580 US dollars per QALY saved if treatment effect on survival was not included . The results were sensitive to variations in utility and ranged from 19,685 US dollars per QALY saved to rehabilitation not being cost-effective . CONCLUSIONS The effects on quality of life tend to reinforce treatment advantages on survival for patients having postdischarge rehabilitation after an acute coronary syndrome . The estimated base case incremental cost per QALY saved is consistent with those historically accepted by decision making authorities such as the Pharmaceutical Benefits Advisory Committee", "To evaluate the efficacy of exercise training for increasing functional capacity in the 6 months after clinical ly uncomplicated myocardial infa rct ion , 198 men 52 + /- 9 years of age participated in a training study . They were r and omly assigned to one of four exercise protocol s : 8 to 26 weeks of training at home ( group 1 , n = 66 ) or in a group program ( group 2 , n = 61 ) following treadmill testing performed 3 weeks after infa rct ion , treadmill testing at 3 weeks without subsequent training ( group 3 , n = 34 ) , and treadmill testing for the first time at 26 weeks ( control , n = 37 ) . At 26 weeks functional capacity was significantly higher in patients training at home or in a group program than that in patients without training or in control patients : 8.1 + /- 1.5 , 8.5 + /- 1.3 , 7.5 + /- 1.8 , and 7.0 + /- 1.7 METs , respectively ( p less than .05 and p less than .001 ) . No significant differences in functional capacity were noted between patients training at home and those in a group program . No training-related complications occurred . Home and group training are equally effective in increasing functional capacity of low-risk patients after myocardial infa rct ion", "Objective To compare home-based cardiac rehabilitation ( CR ) with usual care ( control group with no rehabilitation ) in elderly patients who declined participation in centre-based CR . Design R and omised clinical trial with 12 months follow-up and mortality data after 5.5 years ( mean follow-up 4½ years ) . Setting Rehabilitation unit , Department of Cardiology , Copenhagen , Denmark . Participants Elderly patients ≥65 years with coronary heart disease . Intervention A physiotherapist made home visits in order to develop an individualised exercise programme that could be performed at home and surrounding outdoor area . Risk factor intervention , medical adjustment , physical and psychological assessment s were offered at baseline and after 3 , 6 and 12 months . Main outcome measurements The primary outcome was 6 min walk test ( 6MWT ) . Secondary outcomes were blood pressure , body composition , cholesterol profile , cessation of smoking , health-related quality of life ( HRQoL ) , anxiety and depression . Results 40 patients participated . The study population was characterised by high age ( median age 77 years , range 65–92 years ) and high level of comorbidity . Patients receiving home-based CR had a significant increase in the primary outcome 6MWT of 33.5 m ( 95 % CI : 6.2 to 60.8 , p=0.02 ) at 3 months , whereas the usual care group did not significantly improve , but with no significant differences between the groups . At 12 months follow-up , there was a decline in 6MWT in both groups ; −55.2 m ( 95 % CI : 18.7 to 91.7 , p the usual care group . There were no significant differences in blood pressure , body composition , cholesterol profile , cessation of smoking or HRQoL after 3 , 6 and 12 months follow-up . Conclusions Participation in home-based CR improved exercise capacity among elderly patients with coronary heart disease , but there was no significant difference between the home intervention and the control group . In addition , no significant difference was found in the secondary outcomes . When intervention ceased , the initial increase in exercise capacity was rapidly lost", "OBJECTIVES This study assessed the effects of cardiac rehabilitation ( CR ) on survival in a large cohort of older coronary patients . BACKGROUND R and omized controlled trials and meta-analyses have shown that CR improves survival . However , trial participants have been predominantly middle-aged , low- or moderate-risk , white men . METHODS The population consisted of 601,099 U.S. Medicare beneficiaries who were hospitalized for coronary conditions or cardiac revascularization procedures . One- to 5-year mortality rates were examined in CR users and nonusers using Medicare cl aims and 3 analytic techniques : propensity-based matching , regression modeling , and instrumental variables . The first method used 70,040 matched pairs , and the other 2 techniques used the entire cohort . RESULTS Only 12.2 % of the cohort used CR , and those users averaged 24 sessions . Each technique showed significantly lower ( p 1- to 5-year mortality rates in CR users than nonusers . Five-year mortality relative reductions were 34 % in propensity-based matching , 26 % from regression modeling , and 21 % with instrumental variables . Mortality reductions extended to all demographic and clinical subgroups including patients with acute myocardial infa rct ions , those receiving revascularization procedures , and those with congestive heart failure . The CR users with 25 or more sessions were 19 % relatively less likely to die over 5 years than matched CR users with 24 or fewer sessions ( p Mortality rates were 21 % to 34 % lower in CR users than nonusers in this socioeconomically and clinical ly diverse , older population after extensive analyses to control for potential confounding . These results are of similar magnitude to those observed in published r and omized controlled trials and meta-analyses in younger , more selected population", "AIMS Cardiac rehabilitation including exercise training is of proven value in ischaemic heart disease . However , elderly patients frequently are not encouraged to participate in such programmes . This study evaluates the physiological effects and self-reported quality of life after an aerobic outpatient group-training programme in subjects above the age of 65 years . METHODS AND RESULTS A consecutive series of 101 patients ( males 80 % ) aged 65 - 84 ( mean 71 ) years recovering from an acute coronary event were r and omized to either a supervised out patient group-training programme ( n=50 ) or to a control group ( n=51 ) . The two groups were well balanced as regards clinical characteristics . The compliance in the training group was 87 % . Exercise tolerance increased in the trained group from 104 to 122 and 111 W after 3 and 12 months respectively . The corresponding values were 102 , 105 and 105 W among controls . Parameters , such as quality of life , self-estimated level of physical activity , fitness and well-being were grade d higher by the trained patients than those who served as controls on the two occasions of follow-up . CONCLUSIONS Aerobic group-training of elderly patients recovering from an acute coronary event beneficially influences physical fitness and several parameters expressing quality of life . Great care has to be taken to preserve the initial effects by continued training", "BACKGROUND High-intensity interval training has been shown to be superior to moderate continuous exercise training in improving exercise capacity and endothelial function in patients with coronary artery disease . The objective of this study was to evaluate this training model on in-stent restenosis following percutaneous coronary intervention for stable or unstable angina . METHODS AND RESULTS We prospect ively r and omized 40 patients after percutaneous coronary intervention with implantation of a bare metal stent ( n = 30 ) or drug eluting stent ( n = 32 ) to a 6-month supervised high-intensity interval exercise training program ( n = 20 ) or to a control group ( n = 20 ) . At six months , restenosis , measured as in-segment late luminal loss of the stented coronary area , was smaller in the training group 0.10 ( 0.52 ) mm compared to the control group 0.39 ( 0.38 ) mm ( P = .01 ) . Reduction of late luminal loss in the training group was consistent with both stent types . Peak oxygen uptake increased in the training and control group by 16.8 % and 7.8 % , respectively ( P Flow-mediated dilation improved 5.2 % ( 7.6 ) in the training group and decreased -0.1 % ( 8.1 ) in the control group ( P = .01 ) . Levels of high-sensitivity C-reactive protein decreased by -0.4 ( 1.1 ) mg/L in the training group and increased by 0.1 ( 1.2 ) mg/L in the control group ( P = .03 for trend ) . CONCLUSIONS Regular high-intensity interval exercise training was associated with a significant reduction in late luminal loss in the stented coronary segment . This effect was associated with increased aerobic capacity , improved endothelium function , and attenuated inflammation", "OBJECTIVE To evaluate the long-term effect of a cardiac rehabilitation and prevention program ( CRPP ) on quality of life ( QOL ) and its cost effectiveness . DESIGN Prospect i ve , r and omized controlled trial . SETTING University-affiliated outpatient cardiac rehabilitation and prevention center . PARTICIPANTS A total of 269 patients ( 76 % men ; mean age , 64+/-11 y ) with recent acute myocardial infa rct ion ( AMI ; n=193 ) or after elective percutaneous coronary intervention ( PCI ; n=76 ) were r and omized in a ratio of 2 to 1 . INTERVENTION Patients received either CRPP ( an 8-wk exercise and education class in phase 2 ) or conventional therapy without exercise program ( control group ) . They were followed until they had completed all 4 phases of the program ( ie , 2 y ) . MAIN OUTCOME MEASURES QOL assessment s , by using the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) and Symptoms Question naire , were performed at the end of each phase . Direct health care cost was calculated , whereas cost utility was estimated as money spent ( in US dollars ) per quality -adjusted life-year ( QALY ) gained . RESULTS In the CRPP group , 6 of the 8 SF-36 dimensions improved significantly by phase 2 and were maintained throughout the study period . Patients were less anxious and depressed , and felt more relaxed and contented . In the control group , none of the SF-36 dimensions were improved by phase 2 , and bodily pain was increased . In phase 4 , only 4 dimensions were improved . Symptoms were unchanged except for increased hostility score . There was a significant gain in net time trade-off in the CRPP group after phase 2 . The direct health care expenses in the CRPP and control groups were 15,292 dollars and 15,707 dollars per patient , respectively . Therefore , the cost utility calculated was 640 dollars saved per QALY gained . Savings attributable to CRPP were primarily explained by the lower rate ( 13 % vs 26 % of patients , chi2 test=3.9 , P patients with coronary heart disease , a short-course CRPP was highly cost effective in providing better QOL to patients with recent AMI or after elective PCI . In addition , the improvement of QOL was quick and sustained for at least 2 years after CRPP", "BACKGROUND Current guidelines broadly recommend comprehensive cardiac rehabilitation ( CCR ) , although evidence for this is still limited . We investigated the 12-month effect of hospital-based CCR versus usual care ( UC ) for a broadly defined group of cardiac patients within the modern therapeutic era of cardiology . METHODS We conducted a central ly r and omized single-center clinical trial with blinded assessment of the primary outcome : registry-based composite of total mortality , myocardial infa rct ion , or acute first-time readmission due to heart disease . Other outcomes were hospitalization , risk profile , and quality of life . The trial included 770 participants ( 20 - 94 years ) with congestive heart failure ( 12 % ) , ischemic heart disease ( 58 % ) , or high risk of ischemic heart disease ( 30 % ) . Comprehensive cardiac rehabilitation is composed of 6 weeks of intensive intervention and systematic follow-up for 10.5 months . RESULTS We r and omized 380 patients to CCR versus 390 to UC . R and omization was well balanced . The primary outcome occurred in 31 % of both groups ( relative risk 0.96 , 95 % confidence interval 0.78 - 1.26 ) . Compared with the UC group , CCR significantly reduced length of stay by 15 % ( 95 % confidence interval 1.1%-27.1 % , P = .04 ) , mean number of cardiac risk factors above target ( 4.5 vs 4.1 , P = .01 ) , patients with systolic blood pressure below target ( P = .003 ) , physically inactivity ( P = .01 ) , and unhealthy dietary habits ( P = .0003 ) . Short-Form-36 and Hospital Anxiety and Depression Scale did not differ significantly . CONCLUSION At 12 months , the CCR and UC groups did not differ regarding the primary composite outcome . Comprehensive cardiac rehabilitation significantly reduced length of hospital stay and improved cardiac risk factors", "IMPORTANCE Cardiovascular disease prevention , including lifestyle modification , is important but underutilized . Mobile health strategies could address this gap but lack evidence of therapeutic benefit . OBJECTIVE To examine the effect of a lifestyle-focused semipersonalized support program delivered by mobile phone text message on cardiovascular risk factors . DESIGN AND SETTING The Tobacco , Exercise and Diet Messages ( TEXT ME ) trial was a parallel-group , single-blind , r and omized clinical trial that recruited 710 patients ( mean age , 58 [ SD , 9.2 ] years ; 82 % men ; 53 % current smokers ) with proven coronary heart disease ( prior myocardial infa rct ion or proven angiographically ) between September 2011 and November 2013 from a large tertiary hospital in Sydney , Australia . INTERVENTIONS Patients in the intervention group ( n = 352 ) received 4 text messages per week for 6 months in addition to usual care . Text messages provided advice , motivational reminders , and support to change lifestyle behaviors . Patients in the control group ( n=358 ) received usual care . Messages for each participant were selected from a bank of messages according to baseline characteristics ( eg , smoking ) and delivered via an automated computerized message management system . The program was not interactive . MAIN OUTCOMES AND MEASURES The primary end point was low-density lipoprotein cholesterol ( LDL-C ) level at 6 months . Secondary end points included systolic blood pressure , body mass index ( BMI ) , physical activity , and smoking status . RESULTS At 6 months , levels of LDL-C were significantly lower in intervention participants , with concurrent reductions in systolic blood pressure and BMI , significant increases in physical activity , and a significant reduction in smoking . The majority reported the text messages to be useful ( 91 % ) , easy to underst and ( 97 % ) , and appropriate in frequency ( 86 % ) . [ table : see text ] . CONCLUSIONS AND RELEVANCE Among patients with coronary heart disease , the use of a lifestyle-focused text messaging service compared with usual care result ed in a modest improvement in LDL-C level and greater improvement in other cardiovascular disease risk factors . The duration of these effects and hence whether they result in improved clinical outcomes remain to be determined . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12611000161921", "BACKGROUND Although recent meta- analysis trials have shown that exercise training may improve survival after myocardial infa rct ion , the mechanism of this beneficial effect is still unknown . The purpose of this study was to detect possible interactions between exercise training and predictors of prognosis after a first myocardial infa rct ion . METHODS AND RESULTS Patients with uneventful clinical courses after a first myocardial infa rct ion were r and omly assigned to a 4-week training period ( 125 patients , group 1 ) or to a control group ( 131 patients , group 2 ) . Before r and omization , all patients underwent a symptom-limited exercise test ( 28 + /- 2 days after myocardial infa rct ion ) , 24-hour Holter monitoring , and coronary arteriography ( 31 + /- 3 days after the acute episode ) . After a mean follow-up period of 34.5 months , 18 patients had cardiac deaths ( 5 in group 1 and 13 in group 2 ) . Multivariate analysis by Cox regression model showed that ejection fraction was the only independent prognostic indicator ( P = .03 ) . Evidence existed of an interaction between ejection fraction and exercise training , showing an effect of physical training on survival that depended on the patient 's ejection fraction . Among patients with ejection fractions relative risk for an untrained patient was 8.63 times higher than for a trained patient ( P = .04 ) , whereas for ejection fractions > 40 % , the estimated risks for trained and untrained patients were similar . CONCLUSIONS These data show that exercise training may prolong survival in post-myocardial infa rct ion patients with depressed left ventricular function . A r and omized trial in such patients seems warranted", "CONTEXT The Lifestyle Heart Trial demonstrated that intensive lifestyle changes may lead to regression of coronary atherosclerosis after 1 year . OBJECTIVES To determine the feasibility of patients to sustain intensive lifestyle changes for a total of 5 years and the effects of these lifestyle changes ( without lipid-lowering drugs ) on coronary heart disease . DESIGN R and omized controlled trial conducted from 1986 to 1992 using a r and omized invitational design . PATIENTS Forty-eight patients with moderate to severe coronary heart disease were r and omized to an intensive lifestyle change group or to a usual-care control group , and 35 completed the 5-year follow-up quantitative coronary arteriography . SETTING Two tertiary care university medical centers . INTERVENTION Intensive lifestyle changes ( 10 % fat whole foods vegetarian diet , aerobic exercise , stress management training , smoking cessation , group psychosocial support ) for 5 years . MAIN OUTCOME MEASURES Adherence to intensive lifestyle changes , changes in coronary artery percent diameter stenosis , and cardiac events . RESULTS Experimental group patients ( 20 [ 71 % ] of 28 patients completed 5-year follow-up ) made and maintained comprehensive lifestyle changes for 5 years , whereas control group patients ( 15 [ 75 % ] of 20 patients completed 5-year follow-up ) made more moderate changes . In the experimental group , the average percent diameter stenosis at baseline decreased 1.75 absolute percentage points after 1 year ( a 4.5 % relative improvement ) and by 3.1 absolute percentage points after 5 years ( a 7.9 % relative improvement ) . In contrast , the average percent diameter stenosis in the control group increased by 2.3 percentage points after 1 year ( a 5.4 % relative worsening ) and by 11.8 percentage points after 5 years ( a 27.7 % relative worsening ) ( P=.001 between groups . Twenty-five cardiac events occurred in 28 experimental group patients vs 45 events in 20 control group patients during the 5-year follow-up ( risk ratio for any event for the control group , 2.47 [ 95 % confidence interval , 1.48 - 4.20 ] ) . CONCLUSIONS More regression of coronary atherosclerosis occurred after 5 years than after 1 year in the experimental group . In contrast , in the control group , coronary atherosclerosis continued to progress and more than twice as many cardiac events occurred", "The British Heart Foundation and the Chest , Heart and Stroke Association have allocated funds to develop cardiac rehabilitation programmes . We have recently completed and now evaluate an exercise-based rehabilitation course reinforced with advice about return to normal activity for 110 patients who had suffered acute myocardial infa rct ion . Patients admitted to the Plymouth cardiac care unit were r and omised into groups : a control group to receive st and ard hospital care , and a rehabilitation group who , in addition , received an exercise programme reinforced with advice . Patients were assessed at entry to the study and at intervals thereafter . Assessment was by question naire and objective tests consisting of a 12-minute walking test and weekly outpatient pedometry . In the rehabilitation group patients were able to walk further and faster , return to work earlier , undertake more housework , and resume normal sexual activity ; they were less short of breath and did not experience more angina . However , the rehabilitation course brought little benefit to the patients ' perception of well-being and their anxiety about health or their outlook on life . Exercise and advice are important components of a rehabilitation programme , but more attention needs to be given to the psychological aspects of recovery from a heart attack", "BACKGROUND Disease management programs in which drugs are prescribed by dietitians or nurses have been shown to improve the coronary risk factor profile in patients with coronary heart disease . However , those disease management programs in which drugs are not prescribed by allied health professionals have not improved coronary risk factor status . The objective of the Coaching patients On Achieving Cardiovascular Health ( COACH ) study was to determine whether dietitians or nurses who did not prescribe medications could coach patients with coronary heart disease to work with their physicians to achieve the target levels for their total cholesterol ( TC ) and other risk factors . METHODS Multicenter r and omized controlled trial in which 792 patients from 6 university teaching hospitals underwent a stratified r and omization by cardiac diagnosis within each hospital : 398 were assigned to usual care plus The COACH Program and 394 to usual care alone . Patients in The COACH Program group received regular personal coaching via telephone and mailings to achieve the target levels for their particular coronary risk factors . There was one coach per hospital . The primary outcome was the change in TC ( DeltaTC ) from baseline ( in hospital ) to 6 months after r and omization . Secondary outcomes included measurement of a wide range of physical , nutritional , and psychological factors . The analysis was performed by intention to treat . RESULTS The COACH Program achieved a significantly greater DeltaTC than usual care alone : the mean DeltaTC was 21 mg/dL ( 0.54 mmol/L ) ( 95 % confidence interval [ CI ] , 16 - 25 mg/dL [ 0.42 - 0.65 mmol/L ] ) in The COACH Program vs 7 mg/dL ( 0.18 mmol/L ) ( 95 % CI , 3 - 11 mg/dL [ 0.07 - 0.29 mmol/L ] ) in the usual care group ( P reduction in TC from baseline to 6 months after r and omization was 14 mg/dL ( 0.36 mmol/L ) ( 95 % CI , 8 - 20 mg/dL [ 0.20 - 0.52 mmol/L ] ) greater in The COACH Program group than in the usual care group . Coaching produced substantial improvements in most of the other coronary risk factors and in patient quality of life . CONCLUSIONS Coaching , delivered as The COACH Program , is a highly effective strategy in reducing TC and many other coronary risk factors in patients with coronary heart disease . Coaching has potential effectiveness in the whole area of chronic disease management", "Aims To investigate the effects of exercise training ( ET ) on left ventricular ( LV ) volumes , cardiopulmonary functional capacity and N-terminal pro-brain natriuretic peptide ( NT-proBNP ) levels in postinfa rct ion patients with moderate LV dysfunction . Methods Sixty-one postinfa rct ion patients were r and omized into two groups : group T [ n = 30 , LV ejection fraction ( EF ) 41.6 ± 11.3 % , mean ± SD ] entered a 6-month ET programme , whereas group C ( n = 31 , EF 42.0 ± 7.6 % , P = NS ) did not . NT-proBNP assay , Doppler-echocardiography and cardiopulmonary exercise test were performed upon enrolment and at sixth months . Results At sixth months , trained patients showed an improvement in workload ( + 26 % , P ) , Vo2peak ( + 31 % , P ( LVEDVI ; −9 % , P reduction in NT-proBNP ( −71 % , P changes in NT-proBNP and in LVEDVI ( r=0.858 , P ) . Baseline NT-proBNP correlated with changes in LVEDVI in both trained ( r=0.673 , P showed unfavourable LVEDVI dilation ( + 8 % , P in NT-proBNP ( −40 % , P month ET induced a favourable LV remodelling and a marked fall in NT-proBNP that could predict LV remodelling in postinfa rct ion patients with moderate LV dysfunction", "This study evaluated long-term effects of 12 weeks of supervised training , of at least 45 minutes duration with two sessions per week , on physical performance and psychological well-being after myocardial infa rct ion ( MI ) . Sixty-nine patients were r and omized to either an exercise or a nonexercise group . Maximum exercise capacity 6 weeks post-MI was inversely related to the acute peak aspartate aminotransferase values in serum , as an index of infa rct size . One year post-MI , the increase in level of fitness ( 10 % ) in the training group did not significantly exceed ( p = .10 ) that of the controls ( 2 % ) . No intergroup differences were registered in self-rated psychological well-being and physical scores or in the return to work rate . In the training group , but not in the controls , the change in perceived dyspnoea at leisure-time activities was positively related to the objective ly measured peak exercise capacity . We conclude that after MI only marginal improvements in physical performance are achieved 6 months after training is finished , with no long-term psychological benefits apparent versus a usual care program . The adaptive implication s of supervised conventional exercise programs post-MI are therefore question ed", "The aim of this study was to determine the long-term effects on myocardial infa rct ion ( MI ) patients of a six-month comprehensive rehabilitation programme ( CRP ) conducted by an interdisciplinary team regarding cardiac events , physical and psychological conditions , life habits , and cardiac health knowledge . The results of a multivariate analysis carried out five years after the MI showed that cardiac events and psychological condition were not significantly influenced by the CRP . However , it was found that the physical condition of the patients benefited from the CRP ; self-reported physical fitness ( p physical exercise test ( p CRP participation was linked to significant modifications of life habits ( diet change ; p cardiac health knowledge was significantly improved by participation in the CRP ( basic cardiac knowledge ; p CRPs have had positive long-term effects on physical condition , life habits and cardiac health knowledge . No such effects , however , were found regarding either cardiac events or psychological condition", "This investigation was design ed to determine the impact of a brief period of cardiac rehabilitation , initiated within 6 weeks of acute myocardial infa rct ion ( AMI ) , on both disease-specific and generic health-related quality of life , exercise tolerance and return to work after AMI . With a stratified , parallel group design , 201 low-risk patients with evidence of depression or anxiety , or both , after AMI , were r and omized to either an 8-week program of exercise conditioning and behavioral counseling or to conventional care . Although the differences were small , significantly greater improvement was seen in rehabilitation group patients at 8 weeks in the emotions dimension of a new disease-specific , health-related Quality of Life Question naire , in their state of anxiety and in exercise tolerance . All measures of health-related quality of life in both groups improved significantly over the 12-month follow-up period . However , the 95 % confidence intervals around differences between groups at the 12-month follow-up effectively excluded sustained , clinical ly important benefits of rehabilitation in disease-specific ( limitations , -2.70 , 1.40 ; emotions , -4.86 , 1.10 , where negative values favor conventional care and positive values favor rehabilitation ) and generic health-related quality of life ( time trade-off , -0.062 , 0.052 ; quality of well-being , -0.042 , 0.035 ) or in exercise tolerance ( -38.5 , 52.1 kpm/min ) ; also , return to work was similar in the 2 groups ( relative risk , 0.93 ; confidence interval , 0.71 , 1.64 ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "Objective : Few exercise trials have focused on patients with both type 2 diabetes and coronary artery disease . We investigated the effects of 1 year of exercise training on HbA1c and VO2peak in these patients . Methods : Patients with type 2 diabetes and coronary artery disease ( n = 137 ) were r and omised to combined exercise training or control group . HbA1c was measured at the beginning and end of the study . Changes in VO2peak , and also ventilatory threshold and time to exhaustion , were assessed by cardiopulmonary exercise testing . Results : No differences in changes between the r and omised groups were observed in HbA1c and VO2peak , whereas ventilatory threshold and time to exhaustion increased significantly in the exercise group compared with the controls ( p = 0.046 and p = 0.034 ) . In patients without previous acute myocardial infa rct ion and diabetes microvascular complications ( n = 46 ) , the exercise group did improve HbA1c and VO2peak compared with the controls ( p = 0.052 and p = 0.035 ) . Conclusion : No significant effects of exercise training on HbA1c or VO2peak were observed in patients with type 2 diabetes and coronary artery disease , although improvements were seen in patients without vascular complications beyond coronary artery disease , implying that the degree of vascular disease may influence exercise responses . Ventilatory threshold and time to exhaustion did increase significantly , indicating improved exercise performance despite the minor change in VO2peak", "Six weeks after acute myocardial infa rct ion , 303 men were r and omly divided into exercise and control groups . The exercise group attended the hospital gymnasium twice weekly for a three-month supervised exercise course . Both groups were exercise tested before and after the course and at subsequent follow-up . The exercise group increased their physical fitness greatly compared with the control group . Eight per cent of the exercise group died during the period of follow-up , compared with 14 per cent of the control group ; this difference is not significant . There was an apparent improvement in mortality in those with inferior MI who completed the exercise course , which was not seen in those with MI in other sites . For many patients after MI progressive exercise is safe , improves physical fitness and may reduce mortality for those after inferior MI", "BACKGROUND Cardiac rehabilitation ( CR ) is widely accepted as beneficial for patients with myocardial infa rct ion ( MI ) and coronary artery bypass graft ( CABG ) . A need exists to evaluate how different formats of delivery can best meet CR service dem and s. METHODS AND RESULTS Cardiac patients ( n = 60 ) were r and omly assigned to either a st and ard 10-week ( 30 sessions ) or a 4-week ( 20 sessions ) multifactorial rehabilitation program . Patients underwent exercise testing using the Bruce protocol before , immediately after , and then 6 months after CR . Patients also completed the SF-36 quality of life question naire and the Hospital Anxiety and Depression scale at each time point . Compared with pre-CR , exercise time and metabolic equivalents attained were significantly increased , and heart rate significantly decreased both immediately ( P energy , pain , and general health were reported after CR , and in energy and emotional and social well-being at 6 months after CR . No differences were seen between the groups . CONCLUSIONS Cardiac rehabilitation after MI and CABG significantly improved exercise capacity and general health and well-being . No significant differences were detected between groups undergoing a 10-week or 4-week course . These preliminary data suggest that shortened courses of CR may be beneficial to cardiac patients and such courses may also facilitate more widespread use of CR", "Table . SI Units Systematic modification of coronary risk factors is not integrated into the medical care provided to most of the more than 1 million patients treated annually in the United States for acute myocardial infa rct ion by percutaneous transluminal coronary angioplasty or coronary artery surgery . Most of such patients have lipoprotein abnormalities [ 1 ] , and nearly one half smoke [ 2 ] . These risk factors , which contribute to subsequent morbidity and mortality , remain highly prevalent after acute cardiac events . Failure to integrate comprehensive risk factor modification into the st and ard medical care provided to patients after acute cardiac events primarily reflects the lack of an organizational framework or system . This deficiency in re source allocation for preventive and rehabilitative aspects of care in turn reflects the predominant orientation of the U.S. health care system to the management of acute illness [ 3 ] . Several clinical research studies have shown the effectiveness of risk factor modification , especially treatment of lipoprotein abnormalities [ 4 - 7 ] , in achieving regression of coronary artery lesions and reducing the clinical consequences of coronary artery disease [ 6 , 7 ] . However , risk factor interventions shown to be effective in clinical trials may not prove equally effective in clinical practice because of a paucity of re sources , especially nonphysician personnel . The lack of effective management systems limits the expected reduction in morbidity and mortality and the corresponding reduction in medical care costs that motivates current efforts to orient the priorities of the American health care system toward preventive and rehabilitative care . This r and omized , controlled trial compared the effectiveness of a physician-directed , nurse-managed , home-based case-management system for coronary risk factor modification with that of usual medical care . Outcomes were measured in both groups immediately after the end of the first year after acute myocardial infa rct ion . The term case-management system has been used in various context s. As used here , it refers to a system in which a nurse case-manager , working with different health care specialists ( a psychiatrist , a cardiologist , a lipid specialist , a nutritionist , and a nurse coordinator ) , managed coronary risk factors . Methods Enrollment and Orientation Program nurses enlisted patients on hospital day 3 or as soon as their medical condition stabilized . Study participants gave written informed consent to be r and omly assigned to a treatment group . Immediately after r and omization , program nurses introduced patients to the special intervention with the aid of a videotape . Usual Care The 585 patients in our study were cared for by 215 internists and 34 cardiologists in the five participating medical centers who were organized into practice groups of 5 to 10 physicians each . Cardiology consultation was often provided during hospitalization , but primary responsibility for follow-up care was generally assumed by internists . The usual care offered by the Kaiser Permanente Medical Care Program included physician counseling on smoking cessation and nutritionist counseling on dietary change during hospitalization and physician-managed , lipid-lowering drug therapy after hospital discharge . Group outpatient smoking cessation programs were available for a $ 50 fee . Group exercise rehabilitation , not generally provided by the Kaiser Permanente Medical Care Program during this study , was available to patients at various community facilities at an average cost of $ 1800 to $ 2700 for 3 months ' participation . Special Intervention The behavioral interventions in our case-management system , which were offered to the 293 patients in the intervention group in addition to usual care , were derived from social learning theory [ 8 , 9 ] and modified for medical problems [ 10 ] . In this model , persons must learn how to monitor the health habits they seek to change , set attainable sub goals to motivate and direct their efforts , use feedback of progress in ways that promote health , and enlist incentives and social support to sustain the effort needed to succeed [ 8 , 9 ] . In the hospital , patients were instructed on how to complete self-reports [ status reports ] of smoking , dietary intake , and exercise . Scheduled interactions between case managers and patients after discharge took three forms : 1 ) nurse-initiated telephone contacts ; 2 ) computer-generated progress reports mailed to patients based on question naires completed by patients and mailed to the nurses ; and 3 ) visits to the program nurse for treadmill exercise testing , initiation of lipid-lowering drug therapy , if indicated , and a single counseling session after a smoking relapse . The maximum number of treatment contacts during the year , including outcome measurement at 6 and 12 months , was as follows : 14 nurse-initiated telephone contacts , 8 patient visits to the blood chemistry laboratory , and 4 patient visits to the nurse case manager . Smoking Intervention Smoking was defined as the use of cigarettes , cigars , cigarillos , pipe tobacco , or any other form of tobacco in the 6 months before admission . Forty-three percent of patients were smokers . Patients who had smoked during the 6 months before hospitalization received the same intensive smoking cessation intervention during hospitalization ; this intervention has been described previously [ 11 ] . Physicians used a written script that enabled them to provide st and ardized counseling in less than 2 minutes . The hospital-based smoking cessation counseling focused on relapse prevention . Nurses conducted a st and ardized smoking history to evaluate patients ' addiction to smoking . Patients ' reported self-efficacy or confidence to resist smoking in each of 28 potentially high-risk situations was measured ; patients were then counseled on how to manage the situations in which they reported less than 70 % confidence . Patients also received a relapse prevention manual and a relaxation audiotape . They were advised that the nurse would telephone them 48 hours and 1 week after hospital discharge and at monthly intervals for as long as 6 months . Patients who relapsed were offered one additional visit with the nurse for further counseling . Nicotine polacrilex or transdermal nicotine patches were reserved for highly addicted patients who relapsed after hospital discharge . Nutritional Counseling A computer-based expert system developed by the investigators was used to provide nutritional counseling on a National Cholesterol Education Program [ 12 ] Step 2 diet that was low in cholesterol and saturated fat . A food frequency question naire design ed by the investigators was scored using the Cholesterol and Saturated Fat Index developed by Connor and colleagues [ 13 ] . Calculations of cholesterol and saturated fat totals were based on weekly rather than daily average food intakes . Data from the food frequency question naires , mailed by patients to the Stanford coordinating center and entered into a microcomputer , were used to generate progress reports that characterized patients ' dietary patterns , prioritized dietary change goals , and provided guides for managing difficult situations by directing patients to relevant sections of a nutrition workbook entitled Good Eating for Good Health developed by the program nutritionist . Patients in the intervention group completed a food frequency question naire during hospitalization that described their eating habits in the previous month . Patients also completed food frequency question naires 6 , 11 , and 26 weeks after admission . Progress reports were mailed to patients within 48 to 72 hours after the food frequency question naires were received . Detailed strategies for maintenance of dietary change were incorporated into the 26-week progress report . Question naires to evaluate outcomes were also completed at 36 and 52 weeks . Lipid-Lowering Drug Therapy The therapeutic goal of a plasma low-density lipoprotein (LDL)-cholesterol value of 2.46 mmol/L ( 95 mg/dL ) adopted for this trial was based on the mean post-treatment level of LDL cholesterol found in patients in the study by Blankenhorn and colleagues [ 4 ] . Patients with mean plasma LDL cholesterol values ( based on measurements in two separate blood sample s drawn 75 and 90 days after infa rct ion ) that exceeded this value were given initial drug therapy according to the four algorithms shown in Table 1 . Patients unable to tolerate bile acid-binding resin or nicotinic acid because of comorbid conditions or potentially adverse interactions with these agents received lovastatin or gemfibrozil . During a visit 90 days after discharge , the nurses did a brief physical examination and obtained a history relevant to hyperlipidemia . They provided detailed counseling to patients regarding the rationale for lipid-lowering drug therapy and ways to maximize drug efficacy and minimize drug side effects , and they advised patients on the schedule of laboratory visits and nurse-initiated follow-up telephone contacts . Table 1 . Initial Drug Therapy * Changes in drug therapy at 120 , 150 , and 180 days , which were coordinated by nurse-initiated telephone contacts , were based on three types of responses to initial therapy : 1 ) if lipoprotein levels returned to normal , the effective drug therapy was continued ; 2 ) if the response was incomplete , the dose of the effective medication was increased or another drug was added , or both ; and 3 ) if comorbid conditions worsened or blood chemistry abnormalities or intolerable side effects occurred , drug dosage was reduced or the patient was switched to another agent or both . A physician lipid specialist and a Stanford-based senior nurse-coordinator provided telephone consultation to the case managers . Before initiating lipid-lowering drug therapy at 90 days and at each subsequent step , nurses review ed the patients ' blood chemistry and lipoprotein values and elicited any symptoms requiring a change in therapy . The", "Background — Although preventive drug therapy is a priority after acute coronary syndrome , less is known about adherence to behavioral recommendations . The aim of this study was to examine the influence of adherence to behavioral recommendations in the short term on risk of cardiovascular events . Methods and Results — The study population included 18 809 patients from 41 countries enrolled in the Organization to Assess Strategies in Acute Ischemic Syndromes ( OASIS ) 5 r and omized clinical trial . At the 30-day follow-up , patients reported adherence to diet , physical activity , and smoking cessation . Cardiovascular events ( myocardial infa rct ion , stroke , cardiovascular death ) and all-cause mortality were documented to 6 months . About one third of smokers persisted in smoking . Adherence to neither diet nor exercise recommendations was reported by 28.5 % , adherence to either diet or exercise by 41.6 % , and adherence to both by 29.9 % . In contrast , 96.1 % of subjects reported antiplatelet use , 78.9 % reported statin use , and 72.4 % reported angiotensin-converting enzyme/angiotensin receptor blocker use . Quitting smoking was associated with a decreased risk of myocardial infa rct ion compared with persistent smoking ( odds ratio , 0.57 ; 95 % confidence interval , 0.36 to 0.89 ) . Diet and exercise adherence was associated with a decreased risk of myocardial infa rct ion compared with nonadherence ( odds ratio , 0.52 ; 95 % confidence interval , 0.4 to 0.69 ) . Patients who reported persistent smoking and nonadherence to diet and exercise had a 3.8-fold ( 95 % confidence interval , 2.5 to 5.9 ) increased risk of myocardial infa rct ion/stroke/death compared with never smokers who modified diet and exercise . Conclusions — Adherence to behavioral advice ( diet , exercise , and smoking cessation ) after acute coronary syndrome was associated with a substantially lower risk of recurrent cardiovascular events . These findings suggest that behavioral modification should be given priority similar to other preventive medications immediately after acute coronary syndrome . Clinical Trial Registration Information— URL : http:// clinical trials.gov/ct2/show/NCT00139815 . Unique identifier : NCT00139815", " One hundred six postmyocardial infa rct ion subjects who either achieved a mean work load of less than seven mets on treadmill testing , who were rated as anxious and /or depressed , or who met both criteria , participated in a controlled study comparing the rehabilitation effectiveness of exercise therapy and group counseling . Each intervention lasted 12 weeks . Follow-up evaluations were scheduled at three months , six months and one year . Exercise substantially increased mean work capacity , decreased fatigue , lessened anxiety and depression , and promoted independence and sociability . Counseling substantially reduced depression and promoted a sense of friendliness , and decreased interpersonal friction as well as greater independence and sociability . The control group reported no substantial change on any measured factor . Neither counseling nor exercise had an effect on mortality though subjects in the exercise group reported fewer major cardiovascular sequelae", " Two hundred patients who had suffered an acute myocardial infa rct ion 4 - 6 weeks before entered a r and omised controlled trial of exercise treatment at a community sports centre supervised by a general practitioner . Eighty one per cent of the treatment group continued to exercise until they returned to work and 73 % completed three months ' exercise . There were no serious complications of the exercise course . The prevalence of angina pectoris fell by 10 % in the treatment group but rose by 60 % in the control group . The perceived energy level rose by significantly more in the treatment group than in the controls . The rise in predicted maximum oxygen uptake was significantly greater in the treatment group than in the control group as was the reduction in the double product ( a reflection of myocardial workload ) at peak exercise . Coronary rehabilitation in the community can be both safe and effective", "Patients are generally advised to return to full normal activities , including work , 6 to 8 weeks after acute myocardial infa rct ion ( AMI ) . We assessed the outcomes of early return to normal activities , including work at 2 weeks , after AMI in patients who were stratified to be at a low risk for future cardiac events . Patients were considered for r and omization before discharge if they had no angina , had left ventricular ejection fraction > 40 % , a negative result from a symptom-limited exercise stress test for ischemia ( 7 METs . Patients with left ventricular ejection fraction return to normal activities at 2 weeks and 70 patients to undergo st and ard cardiac rehabilitation and return to normal activities at 6 weeks after AMI . There were no deaths or heart failure in either group . There was no significant difference in the incidence of reinfa rct ion , revascularization , left ventricular function , lipids , body mass index , smoking , or exercise test results at 6 months . In conclusion , return to full normal activities , including work at 2 weeks , after AMI appears to be safe in patients who are stratified to a low-risk group . This should have significant medical and socioeconomic implication", "The effects of a rehabilitation programme one year after myocardial infa rct ion ( MI ) were investigated in 171 patients under 65 years of age . These patients were allocated at r and om to rehabilitation and control groups before discharge from hospital . The groups were comparable with regard to age , sex and clinical data . The programme included physical exercise , counselling of patients and relatives , and social measures over a 3-month period during the convalescent stage . One year after MI patients in the rehabilitation group showed lower systolic blood pressure at rest and lower diastolic pressure on submaximal exercise than controls . No differences were found with regard to mean work capacity , days off work , return to work , psychological status , and underst and ing of the illness . At 12 months all patients were less physically and socially active than before MI , they were more dependent on their relatives than before , and they had poor underst and ing of their illness", "The study was set up to evaluate the long-term effects on mortality of a comprehensive rehabilitation and secondary prevention programme lasting 3 years after acute myocardial infa rct ion . The study group consisted of 375 consecutive , non-selected patients under 65 years of age r and omly allocated to an intervention group ( 188 patients ) or a control group ( 187 patients ) . After 15 years follow-up significantly lower incidence of sudden death ( 16.5 % vs 28.9 % , P = 0.006 ) and coronary mortality ( 47.9 % vs 58.5 % , P = 0.04 ) were seen in the intervention group compared with controls . Total mortality was 64.4 % and 66.8 % , respectively ( ns ) . The incidence of cancer death was 16 in the intervention group and three in the controls . Cardiac failure , enlarged heart , New York Heart Association functional class II or more and membership in the control group were significantly associated with coronary mortality during the first 3 years , and after 3 years enlarged heart , diabetes and reinfa rct ion were associated with late coronary death . Thus , comprehensive multifactorial intervention after acute myocardial infa rct ion had favourable long-term effects on coronary mortality and sudden death but no effect on total mortality", "This study enrolled 651 men with myocardial infa rct ion in five participating centers in a r and omized 3 year clinical trial of the effects of prescribed supervised exercise . The subjects , aged to 30 to 64 years , were screened for eligibility 2 to 36 months after their qualifying myocardial infa rct ion . The men in the exercise group pursued intensive exercise in the laboratory for 8 weeks and then in a gymnasium for 34 months . The experience of the exercise group was more favorable than that of the control group in most of the comparisons made . The cumulative 3 year total mortality rate was 7.3 percent for the control group and 4.6 percent for the exercise group ; the 3 year rate for recurrent myocardial infa rct ion was 7.0 and 5.3 percent , respectively . Mortality rates in the two groups did not differ significantly , but the data were consistent with an assumption of substantial benefit from exercise . Adjustment for small differences in baseline variables by multivariate methods did not material ly alter the estimate of effect of exercise . Certain subgroups showed a greater benefit from exercise", "BACKGROUND Rehabilitation is an important part of the treatment of patients with ischemic heart disease . Therefore , many patients undergoing coronary artery bypass surgery ( CABS ) also participate in cardiac rehabilitation programs . This study was conducted to investigate whether rehabilitation influences quality of life and work status after CABS . METHODS Consecutive patients undergoing elective CABS were r and omly assigned to a rehabilitation group ( R , N = 119 ) and a hospital-treatment group ( H N = 109 ) . All patients received usual medical care . Group R participated in a rehabilitation program based on exercise and counseling . The follow-up time was 5 years . The measured domains of health-related quality of life were heart symptoms , functional class , exercise capacity , use of medication , depression , the patients ' perception of health , and overall life situation . The Nottingham Health Profile as a measure of perceived distress was used . RESULTS Symptoms , use of medication , exercise capacity , and depression scores did not differ between groups R and H. Five years after the CABS , the patients in group R reported less restriction in physical mobility on the Nottingham Health Profile than patients in group H ( P = 0.005 ) , and more patients in group R than in group H perceived their health ( P = 0.03 ) and overall life situation ( P = 0.02 ) as good . The increase in the proportion of subjects working was higher in group R than group H at 3 years after the CABS ( P = 0.02 ) , but not at other follow-up times . CONCLUSION A cardiac rehabilitation program in conjunction with usual medical care after CABS may induce a perception of improved health . The influence on return to work is limited", "Background Lifestyle measures of coronary heart disease ( CHD ) prevention have been overshadowed by the efficacy of drug treatments . This is particularly the case in the setting of secondary prevention where the benefits of lipid lowering , anti-platelet and anti-hypertensive drugs have been emphasised in numerous trials . Lifestyle measures address several CHD risk factors at once and are generally free of serious side effects . Objectives The objective of the present study was to determine whether a comprehensive programme of lifestyle modification could favourably influence dietary and exercise habits in addition to smoking cessation over two years . In addition , an attempt was made to evaluate if this programme could favourably influence the five-year CHD-risk in the male population included in the study . Design A total of 197 patients with proven coronary heart disease were included and r and omised to a lifestyle intervention programme or to usual care . Follow-up was after a period of two years . Methods Intervention comprised a low fat diet , regular exercise , smoking cessation , psychosocial support and education , delivered by nurses on the rationale for pharmacological and lifestyle measures . Usual care comprised follow-up in the routine outpatient clinic . Both groups were given the same comprehensive medication according to recent guidelines . Results Patients in the lifestyle intervention group reduced the intake of saturated fat , sugar and cholesterol ( P exercise level ( P stopped smoking ( P care group . A sub analysis of the influence of five-year CHD calculated risk in males result ed in a relative risk reduction of 22 % ( 95 % confidence intervals 9 - 35 ) . Although significant , this result must be interpreted with caution due to poor statistical power and reproducibility of the method . Conclusions In the presence of modern drug treatments for secondary cardiovascular disease prevention it remains possible through a favourable diet , exercise and smoking cessation to show an additional reduction in the five-year risk for CHD in males", "OBJECTIVE Heart rehabilitation programmes improve the quality of life of coronary patients and the prognosis of the illness . Implementing these therapeutic systems into practice would be easier if their economic efficiency was proven . MATERIAL AND METHODS The expenses created by 180 survivors of a myocardial infa rct ion have been studied at the first and sixth year after the acute episode . The survivors were divided , at r and om , into two groups of 90 . One of them ( RG ) underwent a rehabilitation programme ( physical training , psychological action and control guidelines of risk factors ) . The other ( CG ) served as a control . RESULTS The profits , analyzing the direct expenses ( readmissions to hospital ) were of 5,074,039 ptas . the first year ( CG : 19,901,578 ; RG : 14,827,539 ) , and of 17,451,910 ptas . at the end of the study ( CG : 54,370,249 ; RG : 36,918,339 ) . Better results were obtained when review ing the indirect expenses ( derived from return to work ) , since the profits were of 26,000,000 ptas . after the first year ( CG : 54,750,000 ; RG : 28,750,000 ) and of 209,750,000 at the sixth year ( CG : 438,000,000 ; RG : 228,250,000 ) . The saving per patient was of 272,437 ptas . during the first 12 months and of 2,415,220 at the end of the follow-up . CONCLUSIONS These results justify the fact that the Public Administration and private Insurance Providers are taking into account the adequacy of implementing these therapeutic systems into practice", "The effect of a three-phase multifactorial institution-based rehabilitation programme on coronary heart disease ( CHD ) risk factors was studied in an open r and omised trial comprising 228 patients undergoing coronary artery bypass surgery allocated into a rehabilitation ( R ) group ( n = 119 ) and a hospital ( H = control ) group ( n = 109 ) . Follow-up examinations were performed at 6 and 12 months . Serum total cholesterol and triglyceride levels decreased significantly in both groups during follow-up . These decreases were not significantly different between the R and H groups . Serum high density lipoprotein ( HDL ) cholesterol level increased significantly at 6 and 12 months in the R group , but not in the H group . The differences in the changes between the groups were not significant . The ratio of serum HDL cholesterol to total cholesterol increased significantly in the R group from the preoperative value of 0.154 to 0.179 ( P less than 0.001 ) at 6 months and to 0.180 ( P less than 0.001 ) at 12 months . In the H group these values were 0.152 , 0.166 ( P less than 0.001 ) and 0.168 ( P less than 0.001 ) , respectively . The significance of the differences in the changes between the groups were P = 0.01 at 6 months and 0.06 at 12 months . These differences were more obvious in patients aged 55 years or under . There was a significant decrease ( P = 0.005 ) in the proportion of smokers in the R group and a significant increase in the proportion of patients taking regular exercise in both groups as assessed by question naire . ( ABSTRACT TRUNCATED AT 250 WORDS", "This study focused on the effects of hospital supervision and type of prescribed home exercise in cardiac rehabilitation programs on aerobic fitness , anxiety , and depression . Men who had a myocardial infa rct ion were r and omly assigned to four exercise programs : The first program consisted of purely hospital-based exercise . The second and third programs combined hospital and home exercise , including either bicycling or walking at home . In the fourth program , patients were encouraged to exercise at home , but were given no specific guidance . Fifty-two patients finished the eight-week exercise program and 35 completed the psychologic question naires . At the end of the eight weeks , there were significant differences in the programs ' effects on aerobic fitness . Purely hospital-supervised exercise and the combination of hospital-supervised bicycling with home walking increased aerobic fitness more than completely unsupervised exercise . Furthermore , there were differences in the programs ' effects on manifest anxiety . The combination of home and hospital bicycling was less beneficial than home walking and hospital bicycling or even completely unsupervised exercise at home . The results indicate that the degree of hospital supervision and the type of prescribed home exercise are important design features which may affect the success of cardiac rehabilitation exercise programs . No effects of the different exercise programs on patients ' depression could be found . In general , a close relationship between aerobic fitness and anxiety or depression could not be demonstrated . Implication s of these findings for the design of cardiac rehabilitation exercise programs are discussed", "The Ontario Exercise-Heart Collaborative Study was a multicenter r and omized clinical trial of high Intensity exercise for the prevention of recurrent myocardial infa rct ion in men . The 4-year recurrence rate among 379 patients on a program of high intensity exercise did not differ significantly from that among 354 control patients on a program of light exercise , despite the greater reduction in heart rate in the former group . The relative odds of recurrence in the high intensity group were 1.09 , with 95 % confidence limits of 0.61 and 1.96", "PURPOSE The convalescent period after myocardial infa rct ion ( MI ) has been associated with a \" spontaneous \" improvement in functional aerobic capacity that may be because of normal recovery processes unrelated to formal exercise training . The purpose of this study was to determine whether the frequency of formal training sessions is an important variable affecting the magnitude of improvement in cardiorespiratory fitness during phase II cardiac rehabilitation . METHODS The effect of exercise training frequency on cardiorespiratory fitness was evaluated during a 5-week early ( phase II ) cardiac rehabilitation program in 50 low-risk , male patients recovering from acute MI . Baseline grade d treadmill tests to fatigue endpoints , with direct measurement of maximal oxygen uptake ( VO2max ) , were administered 4 weeks after MI . The subjects were then r and omly assigned to either a control group ( n = 12 ) and restricted to \" very light \" physical activity ( requiring home , or to one of three training groups which , in addition to very light home activity , performed moderately intense ( approximately 70 % of VO2max ) aerobic exercise for 30 to 35 minutes either once per week ( n = 13 ) , twice per week ( n = 13 ) , or three times per week ( n = 12 ) in the hospital-based phase II program . The four groups were similar in age , clinical status , and use of beta- and calcium channel blockers . RESULTS Submaximal and maximal cardiorespiratory responses were initially similar in all four groups . Each of the four groups demonstrated significant ( P maximal treadmill duration at follow-up . However , VO2max increased significantly only in the three training groups . The spontaneous improvement in treadmill duration in the control group , in the absence of formal exercise training , may simply reflect recovery from the acute cardiac event . Those training two and three sessions per week also showed significant , comparable decreases in submaximal exercise heart rate and rate-pressure product and similar increases in maximal treadmill duration and VO2max . CONCLUSIONS Results suggest that two exercise sessions per week is as effective as three per week for cardiorespiratory conditioning in the early weeks of phase II cardiac rehabilitation", "Abstract The purpose of the trial was to analyze whether supervised physical training could reduce death and nonfatal reinfa rct ion in a nonselected series of postinfa rct patients . All patients born in 1913 and later , who were hospitalized for a myocardial infa rct ion during 1968–1970 in Goteborg Sweden , were r and omized to a training group ( 158 patients ) and a control group ( 157 patients ) . Other treatment was exactly the same and st and ardized for the two groups . Twenty-seven percent were excluded from training . Training started 3 months after the infa rct and was scheduled for three times a week . The training group had higher physical working capacity after 1 yr than the control group . Blood pressure was lower , but there was no differences in blood lipids . During 4 yr of follow-up , 28 patients died in the training group and 35 in the control group . The numbers of nonfatal reinfa rcts were 25 and 28 , respectively . Within the training group patients adhering to the program had lower mortality than those who did not , but the former also had lower initially predicted risk of dying . A special analysis of patients who attended the training program in comparison to matched controls also showed a lower mortality . No differences in mortality between the training group and the control group were statistically significant , however", "Complex interventions are more than the sum of their parts , and interventions need to be better theorised to reflect this Many people think that st and ardisation and r and omised controlled trials go h and in h and . Having an intervention look the same as possible in different places is thought to be paramount . But this may be why some community interventions have had weak effects . We propose a radical departure from the way large scale interventions are typically conceptualised . This could liberate interventions to be responsive to local context and potentially more effective while still allowing meaningful evaluation in controlled design s. The key lies in looking past the simple elements of a system to embrace complex system functions and processes . The suitability of cluster r and omised trials for evaluating interventions directed at whole communities or organisations remains vexed.1 It need not be.2 Some health promotion advocates ( including the WHO European working group on health promotion evaluation ) believe r and omised controlled trials are inappropriate because of the perceived requirement for interventions in different sites to be st and ardised or look the same.1 3 4 They have ab and oned r and omised trials because they think context level adaptation , which is essential for interventions to work , is precluded by trial design s. An example of context level adaptation might be adjusting educational material s to suit various local learning styles and literacy levels . Lead thinkers in complex interventions , such as the UK 's Medical Research Council , also think that trials of complex interventions must “ consistently provide as close to the same intervention as possible ” by “ st and ardising the content and delivery of the intervention.”5 By contrast , however , they do not see this as a reason to reject r and omised controlled trials . These divergent views have led to problems on two fronts . Firstly , the field of health promotion is being turned away from r and omised", "OBJECTIVE This study evaluated the effects of a home-based rehabilitation program for Chinese patients with myocardial infa rct ion in terms of health-related quality of life and psychological status . METHODS This was a r and omized , controlled trial with data collected at 2 university-affiliated public general hospitals in Xian ( Shaanxi Province , People 's Republic of China ) . One hundred and sixty patients with a myocardial infa rct ion were r and omly assigned to either the interventional group ( a home-based cardiac rehabilitation program using a self-help manual ) or the control group ( usual care ) . Health-related quality of life ( generic , Chinese Short Form 36-Item Health Survey ; disease-specific , Chinese Myocardial Infa rct ion Dimensional Assessment Scale ) and psychological status ( the Chinese Hospital Anxiety and Depression Scale ) were measured at baseline , program completion ( 6 weeks ) , and 3 and 6 months after hospital discharge . RESULTS Significant differences were evident in the main outcomes when the home-based group was compared with the usual care group at 6 weeks , 3 months , and 6 months . The home-based group had significantly higher scores on 4 of the 8 domains of the Chinese Short Form 36-Item Health Survey and on 3 of the 7 dimensions of the Chinese Myocardial Infa rct ion Dimensional Assessment Scale , with significantly lower scores on the anxiety , but not the depression , subscale of the Chinese Hospital Anxiety and Depression Scale . CONCLUSIONS A simple , home-based cardiac rehabilitation program for patients with acute myocardial infa rct ion , using a self-help manual , improves health-related quality of life and reduces anxiety . It appears feasible and acceptable , and does not produce inferior outcomes compared with usualcare in China", "375 consecutive patients below 65 years who had an acute myocardial infa rct ion ( AMI ) took part in a r and omised rehabilitation and secondary prevention trial ( part of a W.H.O.-coordinated project ) design ed to study the effects of a multifactorial intervention programme on morbidity , mortality , return to work , & c. After three years ' follow-up the cumulative coronary mortality was significantly smaller in the intervention group than in the controls ( 18.6 % versus 29.4 % , p = 0.02 ) . This difference was mainly due to a reduction of sudden deaths in the intervention group ( 5.8 % versus 14.4 % , p less than 0.01 ) . The reduction was greatest during the first six months after AMI . 18.1 % in the intervention group and 11.2 % in the controls ( p less than 0.10 ) presented with non-fatal reinfa rct ions . The number of patients with new Q-QS findings at the end of the three years was , however , almost the same in both groups . The results suggest that organised aftercare during the first six months after AMI with special emphasis on optimum medical control and health education contributes significantly to a reduction in the number of sudden deaths" ]

[ "This week , a series of four articles considers the place of the r and omised controlled trial as we approach the second century of experience with the concept . Its basic principle is genuine uncertainty as to which treatment arm of the trial it would be in a patient 's best interests to enter . This is not necessarily an easy concept to transmit ,", "Abstract Objective : To determine whether locally developed guidelines on asthma and diabetes disseminated through practice based education improve quality of care in non-training , inner city general practice s. Design : R and omised controlled trial with each practice receiving one set of guidelines but providing data on the management of both conditions . Subjects:24 inner city , non-training general practice s. Setting : East London . Main outcome measures : Recording of key variables in patient records ( asthma : peak flow rate , review of inhaler technique , review of asthma symptoms , prophylaxis , occupation , and smoking habit ; diabetes : blood glucose concentration , glycaemic control , funduscopy , feet examination , weight , and smoking habit ) ; size of practice disease registers ; prescribing in asthma ; and use of structured consultation “ prompts . ” Results : In practice s receiving diabetes guidelines , significant improvements in recording were seen for all seven diabetes variables . Both groups of practice s showed improved recording of review of inhaler technique , smoking habit , and review of asthma symptoms . In practice s receiving asthma guidelines , further improvement was seen only in recording of review of inhaler technique and quality of prescribing in asthma . Sizes of disease registers were unchanged . The use of structured prompts was associated with improved recording of four of seven variables on diabetes and all six variables on asthma . Conclusions : Local guidelines disseminated via practice based education improve the management of diabetes and possibly of asthma in inner city , non-training practice s. The use of simple prompts may enhance this improvement", "Disease-specific st and ards for directing patient management are becoming increasingly important . These st and ards , however , are often not followed because they are not sufficiently integrated into the clinical care setting . In this study we describe the development and evaluation of a Computer-Assisted Management Protocol ( CAMP ) of care guidelines for diabetes mellitus . While other studies have shown improved compliance with rule-based reminders , the CAMP customizes disease-specific care guidelines to individual patients over time . We evaluated the effect of the CAMP on compliance with guidelines in a prospect i ve , r and omized controlled study . The study was performed at a family practice clinic where much of the patient record is maintained electronically on The Medical Record ( TMR ) . The management protocol was developed from st and ards published by the American Diabetes Association . Fifty-eight providers were r and omized to either receive or not receive the CAMP for diabetes . Compliance with st and ards was assessed by chart audits of all encounters with diabetic patients during the study interval . The following conclusion was made : the Computer-Assisted Management Protocol result ed in a statistically significant improvement in compliance with diabetes care st and ards", "A r and omized controlled trial was conducted to compare three forms of diabetes follow-up : ( 1 ) general practitioner care , ( 2 ) a system of care shared between the general practitioner ( GP ) and clinic and ( 3 ) conventional clinic care . Two hundred and six diabetic patients without significant diabetes-related or other medical complications were r and omized to one of these follow-up systems . Metabolic control and blood pressure improved significantly and equally in all three groups ( p final attendance rates were 72 % for shared care compared with only 35 % for GP care and 53 % for clinic care . Data collection rates for shared care were comparable with the clinic group for r and om blood glucose ( 88.9 % vs 95.1 % ) , weight ( 93.5 % vs 98.3 % ) , and blood pressure ( 94.8 % vs 92.7 % ) . Only in the case of glycosylated haemoglobin did shared care have poorer data collection ( 66.0 % vs 98.4 % ) . In all these parameters , except blood pressure , shared care out-performed the GP group . We conclude that with adequate support from and communication with hospital-based diabetes services , GPs are capable of providing care appropriate to the needs of uncomplicated diabetic patients", "OBJECTIVE A controlled trial with 15-month follow-up was conducted in two outpatient clinics to study the effects of using the problem-based learning technique to implement a diabetes clinical practice guideline . RESEARCH DESIGN AND METHODS A total of 144 patients with type 2 diabetes aged 25 - 65 years in two internal medicine outpatient clinics were enrolled in the study . African-Americans and Hispanics made up > 75 % of the patients . Doctors and staff in one of the clinics were trained in the use of a clinical practice guideline based on Staged Diabetes Management . A problem-based learning educational program was instituted to reach consensus on a stepped intensification scheme for glycemic control and to determine the st and ards of care used in the clinic . HbA1c was obtained at baseline and at 9 and 15 months after enrollment . RESULTS At 9 months , there was a mean -0.90 % within-subject change in HbA1c in the intervention group , with no significant changes in the control group . The 15-month mean within-subject change in HbA1c of -0.62 % in the intervention group was also significant . Among intervention patients , those with the poorest glycemic control at baseline realized the greatest benefit in improvement of HbA1c . The intervention group also exhibited significant changes in physician adherence with American Diabetes Association st and ards of care . CONCLUSIONS Clinical practice guidelines are an effective way of improving the processes and outcomes of care for patients with diabetes . Problem-based learning is a useful strategy to gain physician support for clinical practice guidelines . More intensive interventions are needed to maintain treatment gains", "Abstract Objectives : To evaluate integrated care for diabetes in clinical , psychosocial , and economic terms . Design : Pragmatic r and omised trial . Setting : Hospital diabetic clinic and three general practice groups in Grampian . Patients : 274 adult diabetic patients attending a hospital clinic and registered with one of three general practice s. Intervention - R and om allocation to conventional hospital clinic care or integrated care . Integrated care patients seen in general practice every three or four months and in the hospital clinic annually . General practitioners were given written guidelines for integrated care . Main outcome measures : Metabolic control , psychosocial status , knowledge of diabetes , beliefs about control of diabetes , satisfaction with treatment , disruption of normal activities , numbers of consultations and admissions , frequency of metabolic monitoring , costs to patients and NHS . Results - A higher proportion of patients defaulted from conventional care ( 14 ( 10 % ) ) than from integrated care ( 4 ( 3 % ) , 95 % confidence interval of difference 2 % to 13 % ) . After two years no significant differences were found between the groups in metabolic control , psychosocial status , knowledge , beliefs about control , satisfaction with treatment , unscheduled admissions , or disruption of normal activities . Integrated care was as effective for insulin dependent as non-insulin dependent patients . Patients in integrated care had more visits and higher frequencies of examination . Costs to patients were lower in integrated care ( mean pounds sterling 1.70 ) than in conventional care ( pounds sterling 8) . 88 % of patients who experienced integrated care wished to continue with it . Conclusions : This model of integrated care for diabetes was at least as effective as conventional hospital clinic care", "A diabetes protocol characterized by self-monitoring of blood glucose was introduced in four general practice s with the aim of making the frequency of consultations dependent on the metabolic regulation and emphasizing body weight reduction . The feasibility of the programme was investigated and the results after 1 year were compared with those of conventional care in four control practice s. In the experimental practice s , 13 patients switched from a medical specialist 's to a general practitioner 's supervision , 20 remained under supervision of their GP and 33 started self-monitoring . The self-monitoring rate , the consultation frequency according to protocol , the low number of dropouts and inadequate referrals and adherence to the therapeutic scheme showed that the protocol was feasible for both the GPs and the patients . At the initial assessment , the regulation of the diabetes was worse in patients of the experimental group , compared with those of the control group ( mean HbA1 9.7 % vs 8.9 % ; p less than 0.05 ) . On average , patients in the experimental group ( n = 56 ) lost 0.4 kg of body weight , whereas those in the control group ( n = 73 ) gained 0.1 kg ( n.s . ) . The mean change in HbA1 , adjusted for the initial value , was -0.4 % in the experimental and + 0.5 % in the control group ( p less than 0.05 ) . The results of the protocol can be attributed to a combination of greater participation of the patient , the individualized consultation frequency and the prescription of oral hypoglycaemic agents according to body weight development", "OBJECTIVE --To evaluate the effectiveness and acceptability of central ly organised prompting for coordinating community care of non-insulin dependent diabetic patients . DESIGN --R and omised single centre trial . Patients allocated to prompted care in the community or to continued attendance at hospital diabetic clinic ( controls ) . Median follow up two years . SETTING --Two hospital outpatient clinics , 38 general practice s , and 11 optometrists in the catchment area of a district general hospital in Islington . PATIENTS --181 patients attending hospital outpatient clinics . NULL HYPOTHESIS -- There is no difference in process of medical care measures and medical outcome between prompted community care and hospital clinic care . RESULTS --14 hospital patients failed to receive a single review in the clinic as compared with three patients in the prompted group ( chi 2 = 6.1 , df = 1 ; p = 0.013 ) . Follow up for retinal screening was better in prompted patients than in controls ; two prompted patients defaulted as against 12 controls ( chi 2 = 6.9 , df = 1 ; p = 0.008 ) . Three measures per patient yearly were more frequent in prompted patients : tests for albuminuria ( median 3.0 v 2.3 ; p = 0.03 ) , plasma glucose estimations ( 3.1 v 2.5 ; p = 0.003 ) , and glycated haemoglobin estimations ( 2.4 v 0.9 ; p Continuity of care was better in the prompted group ( 3.2 v 2.2 review s by each doctor seen ; p plasma glucose concentration , glycated haemoglobin value , numbers admitted to hospital for a diabetes related reason , and number of deaths . Question naires revealed a high level of patient , general practitioner , and optometrist satisfaction . CONCLUSIONS --Six monthly prompting of non-insulin treated diabetic patients for care by inner city general practitioners and by optometrists is effective and acceptable", "OBJECTIVE To evaluate the effectiveness of a cluster visit model led by a diabetes nurse educator for delivering outpatient care management to adult patients with poorly controlled diabetes . RESEARCH DESIGN AND METHODS This study involved a r and omized controlled trial among patients of Kaiser Permanente 's Pleasanton , CA , center who were aged 16 - 75 years and had either poor glycemic control ( HbA1c > 8.5 % ) or no HbA1c test performed during the previous year . Intervention subjects received multidisciplinary outpatient diabetes care management delivered by a diabetes nurse educator , a psychologist , a nutritionist , and a pharmacist in cluster visit setting s of 10 - 18 patients /month for 6 months . Outcomes included change ( from baseline ) in HbA1c levels ; self-reported changes in self-care practice s , self-efficacy , and satisfaction ; and utilization of inpatient and outpatient health care . RESULTS After the intervention , HbA1c levels declined by 1.3 % in the intervention subjects versus 0.2 % in the control subjects ( P self-care practice s and several measures of self-efficacy improved significantly in the intervention group . Satisfaction with the program was high . Both hospital ( P = 0.04 ) and outpatient ( P adults with diabetes improved glycemic control , self-efficacy , and patient satisfaction and result ed in a reduction in health care utilization after the program", "Patients who fail to show for scheduled visits or who fail to contact their provider when warning symptoms occur pose important problems for the primary care physician . A group of interventions was examined to determine the effectiveness in increasing the number of prescribed office visits in patients with diabetes mellitus . This group of interventions included mailed packets with information on how to use the clinic , providers ' names and phone numbers , after-hours phone numbers , a list of early warning signs , and a booklet on managing diabetes mellitus ; mailed appointment reminders ; and intense followup of visit failures for prompt rescheduling . Eight hundred fifty-nine patients on drug therapy for diabetes mellitus were stratified by risk of hospitalization and r and omly assigned within strata to control and intervention groups . The intervention group received all interventions . After 1 year , the intervention group averaged 12 % more total contacts than the control group ( 5.8 vs. 5.2 , P = 0.01 ) , due largely to an increase in kept scheduled visits ( 4.1 vs. 3.6 , P = 0.006 ) . These effects were greatest in those patients at higher risk of hospitalization . Also , visit failures were reduced only in high-risk patients . The effect of the interventions did not diminish during the year of study . This systematic and repetitive intervention appears effective in increasing prescribed office visits and is especially effective in patients requiring more frequent care", "The effects of a new integrated system of diabetes care with an enhanced role of the diabetes specialist nurse based in a purpose d design diabetes centre , on diabetes control , attendance and cancellation rates , and admission for diabetic emergencies have been review ed . Glycaemic control was examined in : ( a ) a cohort of 163 insulin-treated and 47 non-insulin treated diabetic subjects ( age studied prospect ively before and 3 years following the introduction of a new system of care ; ( b ) a second cohort of more elderly patients aged greater than 65 years studied for the 3 years after the change over ; ( c ) a cross-sectional study of the clinic population ( n = 700 ) the year before and 3 years after the changeover ; ( d ) a group of patients attending st and ard unaltered clinics in the same district ( n = 157 ) . Significant and sustained falls in HbA1 were observed in all groups of subjects attending the centre , with the means for those aged less than 65 falling from 11.9 + /- 2.3 % to 9.9 + /- 1.9 % and for those aged over 65 from a mean of 11.7 + /- 2.0 % to 10.3 + /- 2.3 % , 3 years later . The cross-sectional study provided similar results with a mean HbA1 of 12.2 + /- 3.0 % prior to changeover and 10.4 + /- 4.4 % , 3 years later . Smaller but significant changes were observed in patients continuing to attend the routine clinic ( from 12.2 + /- 2.3 % to 11.3 + /- 2.6 % ) over a similar period . Yearly admission rates for ketoacidosis and hypoglycaemia fell from 44 and 23 , to 33 and 5 per annum , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS", "BACKGROUND Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus ( IDDM ) . We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications . METHODS A total of 1441 patients with IDDM--726 with no retinopathy at base line ( the primary -prevention cohort ) and 715 with mild retinopathy ( the secondary -intervention cohort ) were r and omly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections . The patients were followed for a mean of 6.5 years , and the appearance and progression of retinopathy and other complications were assessed regularly . RESULTS In the primary -prevention cohort , intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent ( 95 percent confidence interval , 62 to 85 percent ) , as compared with conventional therapy . In the secondary -intervention cohort , intensive therapy slowed the progression of retinopathy by 54 percent ( 95 percent confidence interval , 39 to 66 percent ) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent ( 95 percent confidence interval , 14 to 67 percent ) . In the two cohorts combined , intensive therapy reduced the occurrence of microalbuminuria ( urinary albumin excretion of > or = 40 mg per 24 hours ) by 39 percent ( 95 percent confidence interval , 21 to 52 percent ) , that of albuminuria ( urinary albumin excretion of > or = 300 mg per 24 hours ) by 54 percent ( 95 percent confidence interval 19 to 74 percent ) , and that of clinical neuropathy by 60 percent ( 95 percent confidence interval , 38 to 74 percent ) . The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia . CONCLUSIONS Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy , nephropathy , and neuropathy in patients with IDDM", "PURPOSE Clinical guidelines are design ed to assist in the management of specific diseases ; however , these guidelines are often neglected in the delivery of care . The purpose of this study was to determine whether clinician use of an clinical practice guideline would increase in response to having , at the patient visit , a decision support system based on a practice guideline that generates a customized management protocol for the individual patient using data from the patient 's electronic medical record . SUBJECTS AND METHODS In a 6-month controlled trial at a primary care clinic , 58 primary care clinicians were r and omized to receive either a special encounter form with the computer-generated guideline recommendations or a st and ard encounter form . The effect of computer-generated advice on clinician behavior was measured as rate of compliance with guideline recommendations . Data from 30 clinicians were analyzed ; data from 28 clinicians were excluded because these clinicians did not meet predefined criteria for minimum exposure to diabetic patient care . RESULTS Availability of patient management recommendations generated by the decision support system result ed in a two-fold increase in clinician compliance with care guidelines for diabetes mellitus ( P = 0.01 ) . Median compliance for the group receiving the recommendations was 32.0 % versus 15.6 % for the control group . CONCLUSION Decision support based on a clinical practice guideline is an effective tool for assisting clinicians in the management of diabetic patients . This decision support system provides a model for how a clinical practice guideline can be integrated into the care process by computer to assist clinicians in managing a specific disease through helping them comply with care st and ards . Use of decision support systems based on clinical practice guidelines could ultimately improve the quality of medical care", "The purpose of this study was to evaluate the effrcacy of using a telecommunication system to assist in the outpatient management of pediatric patients with insulin- dependent diabetes . Metabolic control , patients ' psychosocial status , family functioning , perceived quality of life , patterns of parental/child responsibility for daily diabetes maintenance , and nursing time-on-task were evaluated . One hundred six pediatric patients ( mean age= 13.3 years ) were r and omly assigned to an experimental or control outpatient clinic for 1 year . Experimental subjects transmitted self-monitoring blood glucose data by modem to the hospital every 2 weeks . Transmitted data were review ed by nurse practitioners who telephoned subjects to discuss regimen adjustments . Control subjects received st and ard care with regimen adjustments made by physicians . There were no significant between-group differences for metabolic control , rates of hospitalization or emergency-room visits , psychological status , general family functioning , quality of life , or parent-child responsibility . A significant decrease was noted in nursing time-on-task for experimental subjects", "The efficacy of a treatment and teaching programme for non-insulin-treated Type 2 diabetic patients in general practice was evaluated in a prospect i ve , controlled study . In a rural area in southern Austria , 53 patients from seven general practice s participated in a structured programme ( intervention group ) and 55 patients from seven general practice s without the programme served as the control group . After 6 months the weight reduction in the intervention group was 2.6 kg ( 1.6 - 3.7 kg , p HbA1c between the groups was 0.92 % ( 0.23 - 1.61 % , p Systolic ( -16.6 mmHg ) and diastolic ( -11.1 mmHg ) blood pressure , serum triglycerides ( -0.63 mmol I-1 ) , and serum cholesterol ( -0.40 mmol I-1 ) were reduced significantly in the intervention group ( p number of patients with callus formation and poor nail care decreased significantly after participating in the teaching programme ( p reduction in body weight , metabolic control or in risk factors for diabetic foot complications were observed . Calculated health care costs per patient and year decreased in the intervention group ( -33 pounds ) and increased in the control group ( + 30 pounds ) mainly due to changes in prescription of oral hypoglycaemic agents in both groups . This programme may be an efficient and helpful model to increase overall quality of diabetes care according to the St Vincent Declaration", "OBJECTIVE To examine baseline renal screening practice s and the effect of nurse case management of patients with diabetes in a group model health maintenance organization ( HMO ) . RESEARCH DESIGN AND METHODS We performed both 1-year retrospective and 1-year prospect i ve studies of renal assessment practice s and ACE inhibitor usage in a cohort of 133 diabetic patients enrolled in a r and omized controlled trial of a diabetes nurse case management program in a group model HMO . In accordance with American Diabetes Association recommendations , urine dipstick and quantitative protein and microalbuminuria testing rates were calculated . RESULTS At baseline , 77 % of patients were screened for proteinuria with dipsticks or had quantitative urine testing . Of patients with negative dipstick findings , 30 % had appropriate quantitative protein or microalbumin follow-up at baseline . Baseline ACE inhibitor usage was associated with decreased follow-up testing ( relative risk = 0.47 ) . Nurse case management was associated with increased quantitative protein or or microalbumin testing and increased follow-up testing ( relative risk = 1.65 and 1.60 , respectively ) . CONCLUSIONS We found a higher degree of adherence to recommendations for renal testing than has been reported previously . Nurse case management intervention further increased renal screening rates . The inverse association between ACE inhibitor usage and microalbumin testing highlights a potentially ambiguous area of current clinical pathways", "Computerized reminder systems have been shown to be effective in improving physician compliance with preventive services guidelines . Very little has been published about the use of computerized reminders for preventive care in diabetes . We implemented a computer-generated reminder system for diabetes care guidelines in a r and omized controlled study in the outpatient clinics of 35 internal medicine residents at the University of Utah and Salt Lake Veterans Affairs Hospitals . After a six month study period , compliance with the recommended care significantly improved in both the intervention group that received patient-specific reminders about the guidelines ( 38.0 % at baseline , 54.9 % at follow-up ) and the control group that received a nonspecific report ( 34.6 % at baseline , 51.0 % at follow-up ) . There was no significant difference between the two groups . Both clinic sites showed similar improvement over baseline levels of compliance . Residents who completed encounter forms used by the system showed a significantly greater improvement in compliance than those who did not complete encounter forms ( 19.7 % vs. 7.6 % , p = 0.006 ) . The improvements in guideline compliance were seen in all areas of diabetes preventive care studied , and significant improvements were seen with recommended items from the medical history , physical exam , laboratory testing , referrals , and patient education . The use of encounter forms by the providers significantly improved documented compliance with the guidelines in almost all categories of preventive care . These results suggest that computerized reminder systems improve compliance with recommended care more by facilitating the documentation of clinical findings and the ordering of recommended procedures than by providing the clinician with patient-specific information about guideline compliance status . Further study is needed to underst and the implication s of these findings to the development of future computerized reminder systems for chronic diseases such as diabetes", "OBJECTIVE To assess the effect of additional training of practice nurses and general practitioners in patient centred care on the lifestyle and psychological and physiological status of patients with newly diagnosed type 2 diabetes . DESIGN Pragmatic parallel group design , with r and omisation between practice teams to routine care ( comparison group ) or routine care plus additional training ( intervention group ) ; analysis at one year , allowing for practice effects and stratifiers ; self reporting by patients on communication with practitioners , satisfaction with treatment , style of care , and lifestyle . SETTING 41 practice s ( 21 in intervention group , 20 in comparison group ) in a health region in southern Engl and . SUBJECTS 250/360 patients ( aged 30 - 70 years ) diagnosed with type 2 diabetes and completing follow up at one year ( 142 in intervention group , 108 in comparison group ) . INTERVENTION 1.5 days ' group training for the doctors and nurses-introducing evidence for and skills of patient centred care and a patient held booklet encouraging questions . MAIN OUTCOME MEASURES Quality of life , wellbeing , haemoglobin A1c and lipid concentrations , blood pressure , body mass index ( kg/m2 ) . RESULTS Compared with patients in the C group , those in the intervention group reported better communication with the doctors ( odds ratio 2.8 ; 95 % confidence interval 1.8 to 4.3 ) and greater treatment satisfaction ( 1.6 ; 1.1 to 2.5 ) and wellbeing ( difference in means ( d ) 2.8 ; 0.4 to 5.2 ) . However , their body mass index was significantly higher ( d=2.0 ; 0.3 to 3.8 ) , as were triglyceride concentrations ( d=0.4 mmol/l ; 0.07 to 0.73 mmol/l ) , whereas knowledge scores were lower ( d=-2.74 ; -0.23 to -5.25 ) . Differences in lifestyle and glycaemic control were not significant . CONCLUSIONS The findings suggest greater attention to the consultation process than to preventive care among trained practitioners ; those committed to achieving the benefits of patient centred consulting should not lose the focus on disease management", "The Diabetes Control and Complications Trial ( DCCT ) and the Kumamoto study [ 1 , 2 ] showed that near-normal glycemic control reduces the development and progression of microvascular and neuropathic complications by approximately 50 % in type 1 and type 2 diabetes mellitus . Additional analyses [ 3 - 5 ] indicate that therapy to achieve near normalization of blood glucose levels is cost-effective compared with other treatments . Thus , the American Diabetes Association has recommended that all persons with diabetes attempt to achieve near normalization of blood glucose levels [ 6 ] . This recommendation is not routinely followed in medical practice . In a 1989 national survey of physician practice behaviors in the United States , 64 % of physicians agreed that achieving target HbA1c values is very important but only 18 % reported that they ordered HbA1c tests every 2 to 3 months for patients with type 1 diabetes [ 7 ] . Although 98 % agreed that patient education improves glucose control , only 55 % reported that they routinely used a dietitian or a diabetes educator in patient care . Studies indicate that bringing clinical practice into line with scientific knowledge can be difficult . Methods used to achieve diabetes control in clinical trials are re source intensive . The American Diabetes Association currently recommends that patients with diabetes see their primary care physicians two to four times per year . Data from the National Health Interview Survey , a nationally representative survey [ 8 ] , indicate that most patients with diabetes are seen by nonspecialists and that 69 % of physician visits last less than 15 minutes . Algorithms for diabetes care exist but may be complex and difficult for physicians to follow , given patient load , diversity of patients seen , lack of information systems , and time constraints . Simple , low-cost methods of translating guidelines into clinical care are required . One solution may be to make greater use of personnel other than physicians . Nurse case management was an integral part of intensive therapy in the DCCT and has proven to be effective in reducing smoking and cholesterol levels after acute myocardial infa rct ion [ 3 , 9 ] . A nonr and omized study [ 10 ] of more than 700 patients with diabetes in a health maintenance organization suggests that nurse case management may be effective in improving metabolic control . Other studies [ 11 , 12 ] show a strong association between algorithm-directed nurse interventions and improved glycemic control . To our knowledge , no r and omized , controlled clinical trial of nurse case management in diabetes has yet been published . In a 12-month r and omized , controlled trial , we compared a nurse case management model of diabetes care with usual diabetes management in a primary care setting . Methods Patients Our study was approved by the institutional review board of the Prudential Center for Health Care Research , and all patients gave written informed consent . Participants were recruited from two of the largest clinics within the Jacksonville Health Care Group , which is the largest provider of primary care services for the Prudential HealthCare HMO plan of Jacksonville , Florida . The Jacksonville Health Care Group is a group of 43 primary care physicians who provide care in eight clinics to more than 75 000 Prudential HealthCare plan members . Potential study participants were identified through a data base used to support quality -improvement activities . Prudential HealthCare HMO members who had diabetes were included in the data base if they had visited a physician for diabetes ( International Classification of Diseases , 9th Revision , codes 250.0 to 250.9 ) , had had a hospital cl aim processed for diabetes , had been seen by the utilization management nurse , or had been referred to an ophthalmologist for a diabetic retinal examination . This data base is up date d regularly . A list with each member 's name , address , telephone number , medical record number , member identification number , age , sex , physician , and clinic was generated by merging the data from the data base with enrollment information . In addition , a list of members who may have had diabetes was created by using pharmacy data . Adult members with diabetes who were potential study participants each received a recruitment call and were invited to schedule an appointment with a research assistant to discuss participation in the study . We made a total of 14 calls at different times and on different days before coding a member as unavailable . After consent was given and the eligibility assessment was completed , baseline information was obtained and an HbA1c test was ordered if the result of one given within the previous 60 days was not available . Patients were ineligible for the study if they had a recent HbA1c value less than 7.0 % ; had uncontrolled hypertension ( blood pressure > 180/110 mm Hg ) ; had unstable angina ( class 4 ) ; had had a myocardial infa rct ion in the past 3 months ; had had two or more episodes of seizures ; had alcoholism or drug abuse documented in the chart ; had late-stage complications of diabetes or other chronic conditions , such as severe immunodeficiency or cirrhosis ; were pregnant or were planning to become pregnant in the next 12 months ; or were unable to perform self-management . Patients were r and omly assigned in blocks to either the nurse case management ( intervention ) group or the usual care group . R and omization was based on a 1:1 allocation ratio and a block size of three . Each block contained six patients , three in each study group . This r and omization scheme ensured that the desired allocation ratio-one intervention patient to one usual care patient-was maintained after sequential enrollment of every sixth patient . Outcome Measures Change in HbA1c value was the primary outcome measure . Decreased HbA1c values correlate directly with reduced risk for diabetes-related microvascular and neuropathic complications in type 1 and type 2 diabetes [ 1 , 3 ] . We also assessed health-related quality of life by using four generic questions developed by the Centers for Disease Control and Prevention for the Behavioral Risk Factor Surveillance System ( BRFSS ) [ 13 , 14 ] . These questions evaluate key conceptual domains of health-related quality of life : 1 ) patient-perceived general health status , 2 ) patient-perceived physical dysfunction during the previous 30 days , 3 ) patient-perceived mental dysfunction during the previous 30 days , and 4 ) patient-perceived functional incapacity during the previous 30 days for either mental or physical reasons . The BRFSS quality -of-life measures have been vali date d in a national sample of adults in the United States [ 15 ] . Patient-perceived health was found to be a good proxy indicator for chronic disease conditions . The other three domains further characterize general health functioning and quality of life [ 15 ] . In this analysis , we report findings related to the patient-perceived general health status domain . Intervention and Follow-up The nurse case manager was a registered nurse and a certified diabetes educator . She was trained to follow a set of detailed management algorithms under the direction of a board-certified family medicine physician and an endocrinologist who were responsible for all diabetes management decisions for patients in the intervention group but were not primary care providers for these patients . The algorithms were specific for type of diabetes and were developed by a multidisciplinary team on which endocrinology , family medicine , nursing , pharmacy , health services research , and epidemiology were represented . The algorithms progressively moved a patient toward improvement of glycemic control through adjustments in medication , meal planning , and reinforcement of exercise ( Figure 1 ) . Figure 1 . Algorithm for management of type 2 diabetes mellitus . Patients assigned to receive nurse case management met with the nurse for an initial assessment , were instructed about a blood glucose monitoring schedule , and returned for a follow-up visit 2 weeks later . The initial visit with the nurse averaged 45 minutes . At the 2-week follow-up visit , the nurse review ed the patient 's blood glucose log ; explained the algorithm step to which the patient had been assigned ; and used this information as the baseline for subsequent medication adjustments , meal planning , and exercise reinforcement . Patients receiving nurse case management were also referred to a 5-week , 12-hour diabetes education program that included individual counseling by a dietitian , individual counseling by an exercise therapist , and group diabetes education classes . Subsequent in-person follow-up visits occurred quarterly . Patients in the nurse case management group who were taking insulin received weekly follow-up telephone calls . After the nurse review ed the blood glucose log and discussed glucose values with the patient , medication regimens were adjusted as needed and meal planning and exercise were reinforced . Patients treated with oral agents or diet and exercise received follow-up telephone calls every 2 weeks . The nurse case manager met at least biweekly with the family medicine physician and the endocrinologist to review patient progress , medication adjustments , and other issues related to diabetes care . All medication adjustments or changes were communicated to the patients ' regular primary care physicians . Patients assigned to receive usual care were given blood glucose meters and strips , were encouraged to discuss enrollment in the diabetes education class with their physicians if they had not done so in the past year , and continued to receive diabetes care and follow-up from their primary care physicians . The 5-week diabetes education program is a st and ard , free-of-charge benefit for all HMO members with diabetes . All Jacksonville Health Care Group primary care physicians participate in an annual diabetes care seminar and undergo regular peer review of their adherence to published diabetes care st and ards . Tests to", "BACKGROUND While lower-extremity amputation ( LEA ) is a frequent complication of diabetes , effective strategies for the prevention of LEA in primary care setting s have not been extensively studied . METHODS This prospect i ve study of American Indians with diabetes in a rural primary care clinic was divided into three periods : the st and ard care period ( 1986 to 1989 ) , during which patients received foot care at the discretion of the primary care provider ; the public health period ( 1990 to 1993 ) , during which patients were screened for foot problems and high-risk individuals received foot care education and protective footwear ; and the Staged Diabetes Management ( SDM ) period ( 1994 to 1996 ) , during which comprehensive guidelines for diabetic foot management were adapted by the primary care clinicians to their practice s and were systematic ally implemented . RESULTS A total of 639 individuals contributed 4322 diabetic person-years during the three periods of observation . Patient sex distribution , mean age , and mean duration of diabetes were similar i the three periods . The average annual LEA incidence was 29/1000 diabetic person-years for the st and ard care period ( n = 42 ) , 21/1000 for the public health period ( n = 33 ) , and 15/1000 for the SDM period ( n = 20 ) , an overall 48 % reduction ( P = .016 ) . Overall , the incidence of a first amputation declined from 21/1000 to 6/1000 ( P practice guidelines by local primary care providers was associated with improved diabetic foot care outcomes . SDM has relevance to primary care organizations seeking to improve outcomes for patients with diabetes", "OBJECTIVE : To assess the effectiveness of a pharmaceutical care model on the management of non-insulin-dependent diabetes mellitus ( NIDDM ) in urban African-American patients . DESIGN : Eligible patients were r and omized to either a pharmacist intervention or control group and followed over a 4-month period . Patients in the intervention group received diabetes education , medication counseling , instructions on dietary regulation , exercise , and home blood glucose monitoring , and evaluation and adjustment of their hypoglycemic regimen . Patients in the control group continued to receive st and ard medical care provided by their physicians . SETTING : A university-affiliated internal medicine outpatient clinic . PARTICIPANTS : The study population consisted of urban African-American patients with NIDDM currently attending the clinic . MAIN OUTCOME MEASURES : Primary outcome measures included fasting plasma glucose and glycated hemoglobin concentrations . Secondary outcome endpoints included blood pressure , serum creatinine , creatinine clearance , microalbumin to creatinine ratio , total cholesterol , triglycerides , high-density lipoprotein , and low-density lipoprotein concentrations . Quality -of-life assessment s were performed in both groups at baseline and at the end of the study . RESULTS : Thirty-nine patients ( 17 intervention , 22 control ) completed the study . The intervention group consisted of 12 women and 5 men with a mean ± SD age of 59 ± 12 years , total body weight ( TBW ) of 93 ± 22 kg , body mass index ( BMI ) of 34 ± 7 kg/m2 , and duration of NIDDM 6.8 ± 6.5 years . The control group consisted of 15 women and 7 men with a mean age of 65 ± 12 years , TBW of 88 ± 19 kg , BMI of 33 ± 7 kg/m2 , and a duration of NIDDM of 6.2 ± 4.8 y. Significant improvement in glycated hemoglobin ( p = 0.003 ) and fasting plasma glucose ( p = 0.015 ) was achieved in the intervention group . No change in glycemia was observed in the control subjects . Statistically significant differences in the final glycated hemoglobin ( p = 0.003 ) and fasting plasma glucose ( p = 0.022 ) concentrations were noted between groups . No significant changes in blood pressure control , lipid profile , renal function parameters , weight , or quality -of-life measures were noted within or between groups . CONCLUSIONS : Our data demonstrate the effectiveness of pharmaceutical care in the reduction of hyperglycemia associated with NIDDM in a group of urban African-American patients", "AIMS To examine the scope for cardiovascular disease risk factor intervention among diabetic patients in Engl and was examined using data from the Health Surveys for Engl and 1991 - 94 . This evaluation included calculating the proportion who require lipid lowering therapy according to the St and ing Medical Advisory Committee ( SMAC ) guidelines . METHODS The Health Survey for Engl and is an annual , nationwide household-based in which anthropomorphic data , blood pressure , lipids and details of cardiovascular risk factors are collected from households after r and om stratification for geographical and socio-economic factors within a population sample of 39639 adults , 970 ( 2.3 % ) diabetic subjects were identified . RESULTS Overall , 51 % of those with diabetes had hypertension ( systolic blood pressure > or = 160 mmHg or a diastolic BP > or = 95 mmHg or being on antihypertensive therapy ) , 27 % were obese ( body mass index > or = 30 kg/m2 ) and 19 % were current smokers . One-third of those with hypertension were untreated and less than one-half of those on treatment had their hypertension controlled to below 160/ 95 mmHg . More than one-quarter had poor glycaemic control ( glycated Hb>11 % or an HbA1c>7.5 % ) . Of those aged lipid lowering therapy according to the SMAC guidelines and almost all ( 94 % ) of these were not on treatment . An analysis showed that , because the SMAC guidelines do not require high density lipoprotein ( HDL ) cholesterol to be measured , their use is likely to result in substantial underestimation of the need for lipid lowering , particularly in diabetic women . CONCLUSION In Engl and , among those with diabetes there is considerable unmet need for cardiovascular risk factor intervention , particularly for hypertension and raised cholesterol . With this baseline established , future improvements can be monitored", "We conducted a pilot r and omised trial of computerised templates for the management of asthma and diabetes in general practice in six general practice s in North London . Uptake of the guidelines by general practitioners and practice nurses was assessed using qualitative ( semi-structured interviews design ed to assess the users ' views ) and quantitative ( change in use of the template during the study period ) outcome measures . The practice nurses used the templates frequently but general practitioners rarely used them . Several reasons were offered for non-use of the templates , such as the length of the template and non-involvement in the care of asthma or diabetes . Despite this , however , health professionals were favourably disposed to the use of templates for general clinical care . Pilot investigations of computerised templates are best achieved by observational or quasi-experimental methods rather than a r and omised controlled trial . The use of both qualitative and quantitative methods in this study allowed exploration of the barriers to use of computers", "A functional interpretation of clinical pharmacy as an implementing mechanism for extending the objectives and responsibilities of clinical pharmacology in ambulatory patient care is presented . Evidence is given to support the effectiveness of the clinical pharmacist in assisting primary care physicians with the design of optimal drug regimens and evaluating and managing patients on chronic drug therapy . Opportunities for the clinical pharmacist to carry out long-term drug trials and participate in the design and execution of epidemiological drug studies are also discussed . The clinical pharmacist can make important contributions to ambulatory patient care in areas of drug treatment and evaluation by working in concert with primary care physicians and clinical pharmacologists", "To examine the effects of intensive patient and /or physician diabetes education on patient health outcomes , a controlled trial was conducted in which internal medicine residents and their 532 diabetic patients were r and omly assigned to : routine care ; patient education ; physician education ; or both patient and physician education . Patient outcome data were analyzed either by analysis of covariance on post intervention values ( 2-hour post-pr and ial plasma glucose [ PPG ] ; body weight [ BW ] ; blood pressure [ BP ] ; or analysis of variance conducted on change values ( fasting plasma glucose [ FPG ] and glycosylated hemoglobin [ A1Hgb ] ) . After patient education , significant improvements were observed in FPG , A1Hgb , BW , and systolic and diastolic BP . Physician education result ed in significant decreases in FPG , A1Hgb and BW . The combination of patient plus physician education result ed in the greatest improvements in patients ' health outcomes including FPG , A1Hgb , PPG , BW and diastolic BP . Adjusted systolic BPs were not significantly different in the two groups . While these physiologic improvements were statistically and probably clinical ly significant , hyperglycemia and obesity still persisted . Thus , achieving optimal patient outcomes for a chronic disease like diabetes mellitus may require a greater or more effective use of re sources than currently estimated", "OBJECTIVE To compare the quality of ambulatory diabetes care delivered by physicians in the diabetes clinic versus the general medicine clinic of a university-affiliated Veterans Administration medical center . RESEARCH DESIGN AND METHODS This is a retrospective study that involved the review of medical records against predetermined process-of-care criteria . A total of 112 patients with diabetes were r and omly selected , of whom 56 were cared for in the general medicine clinic and 56 in the diabetes clinic . The following main outcome measures were examined : 1 ) the compliance with individual criteria ; and 2 ) the proportion of patient visits in each clinic receiving minimally acceptable quality , defined as a blood pressure measurement , a record of type of hypoglycemic medication , a glycated hemoglobin measurement within the past year , a urinalysis within the past year , an ophthalmologist or optometrist eye examination within the past year or scheduled in the next six months , a record of change in therapeutic management , and a scheduled return visit . RESULTS The diabetes clinic performed significantly better than the general medicine clinic on the following criteria : a record of a patient 's self-monitoring of blood glucose levels ; a foot examination ; a comprehensive eye examination ; a glycated hemoglobin measurement ; and a referral for diabetic education . The proportion of patient visits meeting the minimally acceptable levels of quality was better in the diabetes clinic than the general medicine clinic ( 73 vs. 52 % , P = 0.02 ) . CONCLUSIONS Patients cared for by physicians in the diabetes clinic receive better quality of diabetes care than do patients cared for by physicians in the general medical clinic . If patient care is to be shifted from specialists to generalists , additional attention needs to be paid to ensure that generalists have the knowledge and system re sources necessary to deliver an acceptable quality of diabetes care", "Given that 14 million Americans have diabetes [ 1 ] , the common complications of this disorder , such as foot ulcers and lower extremity amputations , are of major concern to the medical community . Approximately 20 % of all diabetic patients hospitalized in the United States are admitted because of foot complications [ 2 , 3 ] . Furthermore , about 50 % of all nontraumatic amputations in the United States are done in patients with diabetes [ 1 , 4 ] . This proportion equates to about 55 000 amputations a year [ 1 ] or 59.7 amputations for every 10 000 persons with diabetes [ 5 ] . Patients who undergo an amputation are at greater risk for a second similar procedure on either the same or the other leg [ 6 , 7 ] . Yet , it has been estimated that about one half of the amputations in patients with diabetes , or about one fourth of the total amputations done in the United States , are preventable [ 1 , 4 ] . Recently , the focus has been on preventive strategies that minimize foot damage in diabetic patients and thereby reduce the rates of ulcers and amputations . These preventive strategies are based on two observations : first , that simple efforts on the part of the health care provider or patient can reduce the likelihood of subsequent amputation due to diabetes-associated foot disease [ 8 ] ; and second , that many of these simple procedures are not being systematic ally applied by health care providers or patients [ 9 ] . For example , studies indicate that physicians infrequently examine the feet of patients with diabetes [ 9 , 10 ] . Also , most patients with diabetes do not engage in simple foot-care assessment s to identify lesions requiring early treatment [ 11 ] . Preventive strategies are not systematic ally applied for several reasons : First , patients may not be aware of foot-care procedures or how to do them , or they may not believe that such procedures can make a difference ; second , podiatry and orthopedics services that could assist in foot salvage in diabetic patients may not be available ; and , finally , the health care system may make it difficult for patients or health care providers to examine the feet of patients with diabetes [ 10 ] . Several uncontrolled studies found that implementation of improved foot-care programs can significantly reduce lower extremity complications in patients with diabetes ; these studies showed a 44 % to 85 % reduction in the rate of lower extremity amputations [ 4 , 12 - 14 ] . A recent casecontrol study also supports the implementation of preventive strategies , such as foot care , use of protective footwear , and aggressive treatment of foot infection by patients or health care providers , to decrease the risk for lower extremity amputation [ 15 ] . The intervention in our study was design ed to reduce the prevalence of risk factors for lower extremity amputations in patients with noninsulin-dependent diabetes and involved the three major elements of a prevention program : the patient , health care providers , and the health care system . Specifically , we did a r and omized , controlled trial to determine whether a comprehensive foot-care intervention could improve patients ' knowledge and performance of appropriate foot care ; increase the number of referrals to specialty clinics such as the podiatry clinic ; increase the frequency of foot examinations by health care providers and the documentation of risk factors in the medical record ; and improve short-term patient outcomes such as skin and nail conditions known to be risk factors for ulcers and amputations . Methods Setting Our study , the design of which is summarized in Figure 1 , was done from April 1989 to March 1991 in the academic general medicine practice of the Regenstrief Health Center in Indianapolis , Indiana [ 16 ] . The practice is subdivided into four primary care teams ( labeled A , B , C , and D ) , each with its own nursing and clerical staff . Each team sees patients for eight half-day sessions per week , with each session staffed by one or two faculty internists and two to four housestaff . Teams A and C were r and omly assigned to the intervention group ; teams B and D were assigned to the control group . Previous studies in which this method of r and omization was used have shown no baseline interteam differences in patient characteristics and physician practice behavior and no effect of the team on the study outcome [ 16 - 19 ] . Figure 1 . Summary of the study design . Patient Identification and Recruitment The computerized Regenstrief Medical Record System [ 20 ] was used to identify approximately 3000 patients with noninsulin-dependent diabetes , as well as the date and time of their next appointment . Only patients with noninsulin-dependent diabetes who were seen at least two times in the preceding year by the same provider were included in the study . Additional criteria for inclusion were as follows : an age greater than 40 years ; a diagnosis of diabetes after 30 years of age ; a diagnosis of diabetes based on National Diabetes Data Group criteria [ 21 ] or the presence of disease requiring medication for the control of hyperglycemia ; an intention to obtain care at the general medicine practice for the next 2 years ; and a body weight that was either ideal or heavier than ideal . Exclusion criteria included pregnancy ; major psychiatric illness , including dementia ; terminal illness likely to cause death within 1 year ; renal failure ( serum creatinine > 440 mol/L ) ; previous bilateral amputations above or below the knee ; or an inability to provide any self-care . Patients of investigators involved in the protocol were also excluded from the study . Of the 728 eligible patients , 244 refused to participate , 89 enrolled in the study but failed to keep their appointments for assessment , and 395 were assessed by trained nurse-clinicians . Of the 395 patients assessed , 352 ( 89 % ) completed the study ; 43 patients ( 11 % ) did not complete the study for the following reasons : death ( 11 patients ) ; change of residence ( 15 patients ) ; illness ( 6 patients ) ; transportation problems ( 3 patients ) ; and miscellaneous reasons ( 8 patients ) . Patient Assessment Sample s for determining fasting plasma glucose , cholesterol , triglyceride , high-density lipoprotein , hemoglobin A1C , and C-peptide levels were obtained from enrolled patients and immediately transported to a certified laboratory for analysis . Patients gave a history and had a physical examination at study entry and approximately 1 year later ( mean , 11.8 1.5 months ) . These examinations focused on risk factors for amputation and were administered by two trained nurse-clinicians who were blinded to the patients ' experimental conditions . Foot-related data derived from the history and physical examination included the patient 's self-reported foot-care behaviors ; the quality of the patient 's examination of his or her feet ; the severity of any foot lesions ; and the presence of musculoskeletal abnormalities , dermatologic conditions , peripheral vascular disease , and peripheral neuropathy ( the neuropathy assessment included quantitative measures of pressure and temperature sensation ) . Patients were question ed about their regular foot-care routine and were asked to show how they examined their feet . During this self-examination , nurse-clinicians observed whether patients ' scrutinized the toenails , the soles of the feet , and the area between toes . Musculoskeletal and dermatologic abnormalities were assessed using st and ard definitions of findings such as callus , hammer toe , and Charcot foot [ 3 , 22 ] . The nurse-clinicians palpated the dorsalis pedis , posterior tibial , and femoral pulses bilaterally in their assessment for peripheral vascular disease . If a pulse was absent at any one of the six sites palpated , the assessment was considered abnormal . Foot lesions were rated for severity using the Seattle Wound Classification System [ 23 ] , which ranges from a grade of 1.1 ( absence of lesions ) to a grade of 10 ( entire foot or leg is gangrenous ) . In our study , a foot lesion was defined as any wound , with or without functional interruption of the protective cutaneous barrier , ranging from a superficial scratch to an ulcer involving the epidermis . A serious foot lesion was defined by a severity grade of at least 1.3 , which indicates a minor , nonulcerated lesion with clinical evidence of healing sufficient to close previous interruption of the cutaneous barrier [ 23 ] or a blister . Pressure and temperature sensations were measured using the 5.07-log ( 0.1 mg)-force Semmes-Weinstein monofilament and the thermal sensitivity testing apparatus , according to st and ard techniques [ 24 - 26 ] . Thermal sensitivity was considered abnormal if the patient had a value greater than 2 st and ard deviations from the mean value for a group of healthy persons without diabetes ( warm > 2.04 C ; cool > 1.58 C ) . Practice Patterns of Health Care Providers Immediately after each scheduled visit , study patients had a structured interview [ 10 ] with a research assistant , who asked about foot self-examination and foot-care education given by health care providers ( the primary care physician or nursing personnel ) . In addition , a chart audit was conducted by a nurse-clinician who was blinded to the patients ' experimental condition . Information abstract ed from the medical record included the physician 's documentation of the findings from the history and physical examination ; any referral to podiatry , orthopedics , or vascular surgery clinics ; and diagnostic-test ordering related to the evaluation and treatment of diabetes-associated foot problems . Intervention The intervention cohort was exposed to several risk-reduction strategies . The nurse-clinicians conducted the patient education session with one to four patients , covering appropriate foot-care behaviors and footwear , using a commercially available slide and audiotape presentation [ 27 ] and pamphlets [ 28 ] . Behavioral contracts regarding desired foot-care behaviors were negotiated with each patient . Follow-up was done by telephone 2 weeks after the education sessions to remind patients", "AIM Our objective was to evaluate the effect of training in a patient-centred intervention for GPs and practice nurses on outcomes for patients with Type II diabetes . METHODS We carried out a r and omized controlled trial within general practice s as the basis for r and omization and a before- and -after design for measures of patient outcome . A parallel process study examined the use of the method by professionals . The study was carried out in 29 general practice s in South Glamorgan who had participated for at least 2 years in a local scheme of audit and CME in relation to Type II diabetes care . The subjects were 252 Type II diabetic patients recruited by 15 experimental and 14 control practice s. The main outcome measures were changes in glycosylated haemoglobin , patient satisfaction with care and treatment , functional health status and professional ability to apply the intervention . RESULTS Professionals adopted the innovative method with enthusiasm , but after 2 years only 19 % continued to apply the method systematic ally . The trial was , therefore , unable to demonstrate significant biochemical or functional improvements . This highlights the need to underst and the factors associated with professional uptake and subsequent ability to sustain changes in behaviour . CONCLUSIONS The efficacy of this behavioural intervention remains unproved , despite its acceptability to professional staff . Detailed and prolonged development and testing of behavioural interventions is an essential first step before embarking on r and omized controlled trials which involve complex behavioural changes in professionals or patients", "Shortages in health care personnel have caused the expansion of nurses * duties . Physician acceptance of this augmented role for the nurse will depend in fact on appropriate studies . Extending the responsibilities of the nurse practitioner to active patient treatment is the basis of this report .", "OBJECTIVE To examine whether a telephone-delivered intervention ( TDI ) , design ed to improve glycemie control in patients with non-insulin-dependent diabetes mellitus ( N1DDM ) , improved coronary risk factors in high-risk patients . RESEARCH DESIGN AND METHODS This r and omized controlled trial involved 275 veterans with N1DDM followed in a general medical clinic . Intervention ( TDI ) patients were telephoned at least monthly by a nurse . Calls emphasized compliance with the medical regimen ( diet , medications , and exercise ) , encouraged behavioral changes , and facilitated referrals to a dietitian or smoking cessation clinic . Control patients received no such calls . Baseline and 12-month follow-up measurements included fasting lipid profiles , weight , smoking status ( self-reported ; cessation verified by measurement of exhaled CO ) , adherence to diet and exercise ( self-reported ) , appointments , and medications ( hospital computerized data base ) . RESULTS After 12 months , equal numbers of obese patients in the two groups reported adhering to a diabetic diet and exercising , although more obese TDI patients had seen a dietitian ( 30 vs. 7 % , P = 0.003 ) . Weight loss was not seen in either group ( —0.9 ± 5.3 vs. —0.1 ± 3.6 kg , P = 0.202 ) . Hyperlipidemic TDI patients were more likely to see a dietitian ( 31 vs. 6 % , P = 0.003 ) and receive lipid-lowering medications ( 22 vs. 9 % , P = 0.096 ) , but serum cholesterol reduction was similar between groups ( –11.7 ± 33.4 vs. –4.3 ± 32.7 mg/dl , P = 0.270 ) ; comparable results were seen for high-density lipoprotein , low-density lipoprotein , and triglyceride levels . More TDI group smokers reported quitting ( 26 vs. 0 % , P = 0.033 ) , but the difference was not significant for CO-verified abstention ( 10 vs. 0 % , P = 0.231 ) . CONCLUSIONS The TDI improved self-reported adherence to regimens that might reduce coronary risk , but had little effect on objective measures of risk", "OBJECTIVE To assess in diabetic patients with coronary heart disease ( CHD ) the effect of cholesterol lowering with simvastatin on mortality and the risk of CHD and other atherosclerotic events . RESEARCH DESIGN AND METHODS A post hoc subgroup analysis was carried out on data from 202 diabetic patients and 4,242 nondiabetic patients with previous myocardial infa rct ion or angina pectoris , serum total cholesterol 5.5–8.0 mmol/l , and serum triglycerides ≤ 2.5 mmol/l who were participating in the Sc and inavian Simvastatin Survival Study ( 4S ) . Participants in the 4S were r and omly assigned to double-blind treatment with simvastatin , 20 mg daily , with blinded dosage titration up to 40 mg daily , according to cholesterol response during the first 6–18 weeks , or placebo . Endpoints were 1 ) total mortality , 2 ) major CHD events ( CHD death or nonfatal myocardial infa rct ion ) , 3 ) other acute atherosclerotic events , 4 ) myocardial revascularization procedures . RESULTS Over the 5.4-year median follow-up period , simvastatin treatment produced mean changes in serum lipids in diabetic patients similar to those observed in nondiabetic patients . The relative risks ( RRs ) of main endpoints in simvastatin-treated diabetic patients were as follows : total mortality 0.57 ( 95 % CI , 0.30–1.08 ; P = 0.087 ) , major CHD events 0.45 ( 95 % CI , 0.27–0.74 ; P = 0.002 ) , and any atherosclerotic event 0.63 ( 95 % CI , 0.43–0.92 ; P = 0.018 ) . The corresponding RRs in nondiabetic patients were the following : 0.71 ( 95 % CI , 0.58–0.87 ; P = 0.001 ) , 0.68 ( 95 % CI , 0.60–0.77 ; P with simvastatin improves the prognosis of diabetic patients with CHD . The absolute clinical benefit achieved by cholesterol lowering may be greater in diabetic than in nondiabetic patients with CHD because diabetic patients have a higher absolute risk of recurrent CHD events and other atherosclerotic events", "A crossover r and omized controlled trial of cycles of quality assurance in 16 primary care ( 8 medical , 8 pediatric ) group practice s was conducted . Of four medical and four pediatric tasks important to patient outcome , two were r and omly assigned to experimental intervention ( a quality assurance cycle ) , and two were also measured and used as blinded controls for each medical or pediatric group practice . Task performance was measured in each group for 12 months prior to , 9 months during , and 9 months after the experimental intervention , using as a performance score the percentage of evaluation criteria failed of those applicable to a case . As a result of quality assurance intervention , quality of performance was significantly improved in two of the tasks ( P patient health ( low physician motivation ) had greater improvement in quality . Unimproved tasks were associated with the perceived need for delivery system changes beyond the immediate control of the individual practitioner", "OBJECTIVE To determine the effectiveness of different types of interventions in improving health professional performance and health outcomes . DATA SOURCES MEDLINE , SCI SEARCH , CINAHL and the Research and Development Re source Base in CME were search ed for trials of educational interventions in the health care professions published between 1970 and 1993 inclusive . STUDY SELECTION Studies were selected if they provided objective measurements of health professional performance or health outcomes and employed r and om or quasi-r and om allocation methods in their study design s to assign individual subjects or groups . Interventions included such activities as conferences , outreach visits , the use of local opinion leaders , audit and feedback , and reminder systems . DATA EXTRACTION Details extracted from the studies included the study design ; the unit of allocation ( e.g. , patient , provider , practice , hospital ) ; the characteristics of the targeted health care professionals , educational interventions and patients ( when appropriate ) ; and the main outcome measure . DATA SYNTHESIS The inclusion criteria were met by 102 trials . Areas of behaviour change included general patient management , preventive services , prescribing practice s , treatment of specific conditions such as hypertension or diabetes , and diagnostic service or hospital utilization . Dissemination-only strategies , such as conferences or the mailing of unsolicited material s , demonstrated little or no changes in health professional behaviour or health outcome when used alone . More complex interventions , such as the use of outreach visits or local opinion leaders , ranged from ineffective to highly effective but were most often moderately effective ( result ing in reductions of 20 % to 50 % in the incidence of inappropriate performance ) . CONCLUSION There are no \" magic bullets \" for improving the quality of health care , but there are a wide range of interventions available that , if used appropriately , could lead to important improvements in professional practice and patient outcomes", "This project tested the importance of enhanced information transfer of home monitoring results to health care providers . The study tested whether computer-assisted communication of medical information between the chronic care patient and the physician can result in health care benefit . The information tools were constructed/adapted as a test of this hypothesis for diabetes mellitus . Patients connected a glucometer to an intelligent modem weekly for six to nine months . Graphical and mathematical tools extracted and emphasized the information content of the home monitoring data arriving at the central site . Data smoothing , trend analysis , and calculation of quality control statistics were incorporated into a graphical time series oriented report that was used by the health care provider during an outpatient visit . The integrated home monitoring system was tested on 20 patients with diabetes in a double cross-over design over a 15-month period . A significant improvement in serum glucose control as measured by glycated hemoglobin was shown in the study group , but not in the control group", "OBJECTIVE To determine whether multiple mailed patient reminders can produce an increase in the rate of diabetic retinal examinations ( DRE ) over that seen with a single reminder . RESEARCH DESIGN AND METHODS All diabetic members > or = 18 years who were enrolled in a large network-based health maintenance organization ( HMO ) in California from August 1996 to July 1997 were identified using cl aims and pharmacy data bases . Members who had no record of DRE in the HMO 's cl aims data base were then r and omized into two groups . Both groups received mailed educational material s and a reminder to obtain the examination . Their physician groups also received a letter explaining the program , current guidelines for DRE , and a list of their diabetes patients with their DRE status . The single intervention group received no additional reminders . The multiple intervention group received additional reminders at 3 , 6 , and 9 months after baseline if they continued with no record of service , as determined from the cl aims data base . RESULTS The study cohort comprised 19,523 diabetic members , which were r and omized into single ( n = 9,614 ) and multiple ( n = 9,909 ) intervention groups . There was an increase in monthly DRE rates after the intervention in August 1996 for both intervention groups . After the second reminder was sent to the multiple intervention group , the percentage of diabetic members receiving DRE was higher than the single intervention group . Rates before and after the third intervention were not significantly different , nor were monthly differences found . There was a significant difference in overall annual DRE rates between the groups ( P = 0.023 ) . CONCLUSIONS Multiple patient reminders are more effective than single reminders in improving DRE rates in a managed care setting . However , the improvement noted was clinical ly small and appeared only after the second reminder ; no incremental improvement was seen with additional reminders . Re sources used for multiple reminders aim ed at diabetic retinopathy might better be spent on other approaches to reducing complications of diabetes" ]

[ "BACKGROUND Treatment with warfarin sodium is effective for stroke prevention in atrial fibrillation but many physicians hesitate to prescribe it to elderly patients presumably because of the associated risk for bleeding and the inconvenience of frequent blood tests for the patients . METHODS In the Second Copenhagen Atrial Fibrillation , Aspirin , and Anticoagulation ( AFASAK 2 ) Study , we studied the rate of bleeding events associated with the incidence of thromboembolic events in patients receiving warfarin sodium , 1.25 mg/d ; warfarin sodium , 1.25 mg/d , plus aspirin , 300 mg/d ; aspirin , 300 mg/d ; or adjusted-dose warfarin therapy aim ing at an international normalized ratio of the prothrombin time ratio ( INR ) of 2.0 to 3.0 . The study was scheduled for 6 years from May 1 , 1993 , but owing to evidence of inefficiency of low-intensity therapy plus aspirin from another study it was prematurely terminated on October 2 , 1996 . Minor and major bleeding events were recorded prospect ively . The rate of bleeding was calculated using the Kaplan-Meier method and risk factors were identified by the Cox proportional hazards model . RESULTS Of 677 included patients , 130 ( median age , 77 years ; range , 67 - 89 years ) experienced bleeding . One woman and 12 men experienced major bleeding . Four had intracranial bleeding : 2 cases were fatal and 2 were nonfatal . During treatment with mini-dose warfarin , warfarin plus aspirin , aspirin , and adjusted-dose warfarin , the annual rate of major bleeding was 0.8 % , 0.3 % , 1.4 % , and 1.1 % , respectively ( P = .20 ) . After 3 years of treatment the cumulative rate of any bleeding was 24.7 % , 24.4 % , 30.0 % , and 41.1 % ( P = .003 ) , respectively . Increasing INRvalue ( P myocardial infa rct ion ( P = .001 ) were independent risk factors for bleeding , whereas increasing age was not . CONCLUSIONS Fixed mini-dose warfarin and aspirin alone or in combination were associated with both minor and major bleeding . The small number of major bleeding events in patients receiving adjusted-dose warfarin therapy as compared with those receiving less intensive antithrombotic treatments and the finding of no significant influence of age on the risk for bleeding indicate that even elderly patients with atrial fibrillation tolerate adjusted-dose warfarin therapy ( INR , 2.0 - 3.0 )", "OBJECTIVE This study was performed to characterize the risk of stroke in elderly patients with recurrent intermittent atrial fibrillation ( AF ) . BACKGROUND Although intermittent AF is common , relatively little is known about the attendant risk of stroke . METHODS A longitudinal cohort study was performed comparing 460 participants with intermittent AF with 1,552 with sustained AF treated with aspirin in the Stroke Prevention in Atrial Fibrillation studies and followed for a mean of two years . Independent risk factors for ischemic stroke were identified by multivariate analysis . RESULTS Patients with intermittent AF were , on average , younger ( 66 vs. 70 years , p women ( 37 % vs. 26 % p heart failure ( 11 % vs. 21 % , p annualized rate of ischemic stroke was similar for those with intermittent ( 3.2 % ) and sustained AF ( 3.3 % ) . In patients with intermittent AF , independent predictors of ischemic stroke were advancing age ( relative risk [ RR ] = 2.1 per decade , p hypertension ( RR = 3.4 , p = 0.003 ) and prior stroke ( RR = 4.1 , p = 0.01 ) . Of those with intermittent AF predicted to be high risk ( 24 % ) , the observed stroke rate was 7.8 % per year ( 95 % confidence interval 4.5 to 14 ) . CONCLUSIONS In this large cohort of AF patients given aspirin , those with intermittent AF had stroke rates similar to patients with sustained AF and similar stroke risk factors . Many elderly patients with recurrent intermittent AF have substantial rates of stroke and likely benefit from anticoagulation . High-risk patients with intermittent AF can be identified using the same clinical criteria that apply to patients with sustained AF", "Background and Purpose Temporal trends in stroke incidence in Denmark have not been previously reported . The Copenhagen City Heart Study is a prospect i ve study based on a r and omly selected sample of an urban population of , initially , 19,698 participants followed since 1976 . Over a period of 12 years , we studied three important aspects of stroke incidence in 848 identified cases : temporal trends , dependence on age and sex , and comparison of responders and nonresponders . Methods The participants were invited to two health examinations at 5-year intervals . The participants who attended at least one of the two examinations are termed responders and those who attended none nonresponders . The cases of first-ever stroke were collected from responders , the National Patient Register , and the National Register of Deaths and were verified by study of hospital records and death certificates . Results For responders aged 35–64 years and ≥65 years , there were no significant changes in the weighted rates in four consecutive 3-year periods . There was a tendency toward decreasing rates among younger women , but not in older women or men . The age- and sex-adjusted rates per 1,000 ( based on the Danish population in 1982 ) in responders in the entire 12-year follow-up period were 1.61 in women , 2.67 in men , and 2.14 in both sexes combined . Stroke incidence rates increased exponentially with age in both sexes , with rates in men generally twice those in women , even in the ≥75 years of age group . Age-adjusted rates were higher in nonresponders than in responders . For women , this ratio was 1.7 ; for men , 1.1 . Conclusions The stroke incidence in Copenhagen is relatively high and has shown no decreasing tendency over the period 1976–1988", "BACKGROUND AND PURPOSE Nonvalvular atrial fibrillation ( AF ) is a strong , independent risk factor for stroke , but the absolute rate of stroke varies widely among AF patients , importantly influencing the potential benefit of antithrombotic prophylaxis . We explore factors associated with ischemic stroke in AF patients taking aspirin . METHODS We performed multivariate logistic regression analysis of 2012 participants given aspirin alone or in combination with low , inefficacious doses of warfarin in the Stroke Prevention in Atrial Fibrillation I-III trials followed for a mean of 2.0 years , during which 130 ischemic strokes were observed . RESULTS Age ( relative risk [RR]=1.8 per decade , P hypertension ( RR=2.0 , P systolic blood pressure > 160 mm Hg ( RR=2.3 , P prior stroke or transient ischemic attack ( RR=2.9 , P stroke risk . Regular consumption of > /=14 alcohol-containing drinks per week was associated with reduced stroke risk ( adjusted RR=0.4 , P=0.04 ) . Among SPAF III participants , estrogen hormone replacement therapy was associated with a higher risk of ischemic stroke ( adjusted RR=3.2 , P=0.007 ) . With the use of these variables , a risk stratification scheme for primary prevention separated participants into those with high ( 7.1%/y , 22 % of the cohort ) , moderate ( 2.6%/y , 37 % of the cohort ) , and low ( 0.9%/y , 41 % of the cohort ) rates of stroke . Ischemic strokes in low-risk participants were less often disabling ( P Patients with AF who have high and low rates of stroke during treatment with aspirin can be identified . However , validation of our risk stratification scheme is necessary before it can be applied with confidence to clinical management . Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF , but these findings require confirmation", "Abstract Objective : To determine whether trial efficacy of prophylaxis with warfarin for patients with atrial fibrillation at high risk of stroke translates into effectiveness in clinical practice . Design : Two year prospect i ve cohort study . Setting : District general hospital . Participants : 167 patients with atrial fibrillation and at high stroke risk who were eligible for anticoagulation Interventions : Long term anticoagulation with warfarin at adjusted doses to maintain an international normalised ratio of 2.0 - 3.0 Main outcome measures : Comparison of patient characteristics , comorbidity , anticoagulation control , stroke rate , and haemorrhagic complications with pooled data from five r and omised controlled trials . Results : Patients in the study group were seven years older ( 95 % confidence interval 4 to 10 ) and comprised 33 % more women than patients in the pooled trials . The international normalised ratio was in the target range for 61 % of the time ( range 37%-85 % ) , below for 26 % of the time ( range 8%-32 % ) , and above for 13 % of the time ( range 6%-26 % ) . The time that patients in the study group spent in the target range was significantly less than in the pooled analysis . The incidence of stroke in the study group ( 2.0 % per year , 0.7 % to 4.4 % ) was comparable to that of patients receiving warfarin in pooled studies ( 1.4 % , 0.8 % to 2.3 % ) . Per year the incidence of major ( 1.7 % v 1.6 % ) and minor ( 5.4 % v 9.2 % ) bleeding complications was also similar . Conclusion : Rates of stroke and major haemorrhage after anticoagulation in clinical practice were comparable to those obtained from pooled data from r and omised controlled studies for patients with atrial fibrillation at high risk of", "BACKGROUND The Stroke Prevention in Atrial Fibrillation II study compared warfarin vs aspirin for stroke prevention in atrial fibrillation . Bleeding complications importantly detracted from warfarin 's net effectiveness , particularly among older patients . OBJECTIVES To analyze bleeding complications according to assigned therapy . To identify risk factors for bleeding during anticoagulation . METHODS Eleven hundred patients ( mean age , 70 years ) were r and omized to 325 mg of aspirin daily ( enteric coated ) vs warfarin ( target prothrombin time ratio , 1.3 to 1.8 ; approximate international normalized ratio , 2.0 to 4.5 ) . Major hemorrhages were defined prospect ively . RESULTS The rate of major bleeding while receiving warfarin was 2.3 % per year ( 95 % confidence interval [ CI ] , 1.7 to 3.2 ) vs 1.1 % per year ( 95 % CI , 0.7 to 1.8 ) while receiving aspirin ( relative risk , 2.1 ; 95 % CI , 1.1 to 3.1 ; P = .02 ) . Intracranial hemorrhage occurred at 0.9 % per year ( 95 % CI , 0.5 to 1.5 ) with warfarin and 0.3 % per year ( 95 % CI , 0.1 to 0.8 ) with aspirin ( relative risk , 2.4 ; P = .08 ) . Age ( P = .006 ) , increasing number of prescribed medications ( P = .007 ) , and intensity of anticoagulation ( P = .02 ) were independent risks for bleeding at any site during anticoagulation . The rate of major hemorrhage was 1.7 % per year in patients aged 75 years or younger who received anticoagulation vs 4.2 % per year in older patients ( relative risk , 2.6 , P = .009 ) ; rates by age for intracranial bleeding were 0.6 % per year and 1.8 % per year , respectively ( P = .05 ) . CONCLUSION Advancing age and more intense anticoagulation increase the risk of major hemorrhage in patients given warfarin for stroke prevention", "OBJECTIVES To assess whether older age is independently associated with hemorrhage risk in patients with atrial fibrillation , whether or not they are taking warfarin therapy . DESIGN Cohort study . SETTING Integrated healthcare delivery system . Thirteen thous and five hundred fifty-nine adults with nonvalvular atrial fibrillation . MEASUREMENTS Patient data were collected from automated clinical and administrative data bases using previously vali date d search algorithms . Medical charts were review ed from patients hospitalized were for major hemorrhage ( intracranial , fatal , requiring > or=2 units of transfused blood , or involving a critical anatomic site ) . Age was categorized into four categories ( 60 , 60 - 69 , 70 - 79 , and > or=80 ) , and multivariable Poisson regression was used to assess whether major hemorrhage rates increased with age , stratified by warfarin use and adjusted for other clinical risk factors for hemorrhage . RESULTS A total of 170 major hemorrhages were identified during 15,300 person-years of warfarin therapy and 162 major hemorrhages during 15,530 person-years off warfarin therapy . Hemorrhage rates rose with older age , with an average increase in hemorrhage rate of 1.2 ( 95 % confidence interval ( CI ) 1.0 - 1.4 ) per older age category in patients taking warfarin and 1.5 ( 95 % CI=1.3 - 1.8 ) in those not taking warfarin . Intracranial hemorrhage rates were significantly higher in those aged 80 and older ( adjusted rate ratio=1.8 , 95 % CI=1.1 - 3.1 for those taking warfarin , adjusted rate ratio=4.7 , 95 % CI=2.4 - 9.2 for those not taking warfarin ) than in those younger than 80 . CONCLUSION Older age increases the risk of major hemorrhage , particularly intracranial hemorrhage , in patients with atrial fibrillation , whether or not they are taking warfarin . Hemorrhage rates were generally comparable with those reported in previous r and omized trials , indicating that carefully monitored warfarin therapy can be used with reasonable safety in older patients", "BACKGROUND AND PURPOSE The risk of major vascular events after an initial episode of cerebral ischemia in patients with nonrheumatic atrial fibrillation ( NRAF ) varies from 2 % to 15 % in the first year and is approximately 5 % yearly thereafter . Few studies have reported on risk factors that can be used to identify high-risk subgroups within this patient population . METHODS We studied the predictive value of several easily obtainable clinical characteristics in a group of 375 placebo-treated patients with NRAF and a recent episode of transient or nondisabling cerebral ischemia who were entered in a multicenter clinical trial . The mean follow-up was 1.6 years . RESULTS By means of multivariate modeling , six independent variables were identified : history of previous thromboembolism , ischemic heart disease , enlarged cardiothoracic ratio on chest roentgenogram , systolic blood pressure greater than 160 mm Hg at study entry , NRAF for more than 1 year , and presence of an ischemic lesion on CT scan . These variables could also be used to stratify patients in low- , medium- , and high-risk subgroups for the other two arms of the trial , those treated with anticoagulation and aspirin . Patients older than 75 years with three or more risk factors seemingly benefited less from both aspirin and anticoagulant treatment . CONCLUSIONS Easily obtainable patient characteristics are helpful in estimating the potential effect of adequate secondary prevention in patients with NRAF who recently suffered a transient ischemic attack or minor ischemic stroke", "CONTEXT Nonvalvular atrial fibrillation ( AF ) carries an increased risk for stroke , but absolute rates of stroke vary widely within the broad spectrum of AF patients . OBJECTIVE To prospect ively vali date a risk stratification scheme identifying patients with AF with low rates of stroke when given aspirin . DESIGN Prospect i ve cohort study with mean duration of follow-up of 2.0 years , conducted between 1993 and 1997 . SETTING Outpatient clinics affiliated with academic medical centers . PATIENTS Patients with AF categorized as \" low risk \" based on the absence of 4 prespecified thromboembolic risk factors : recent congestive heart failure or left ventricular fractional shortening of 25 % or less , previous thromboembolism , systolic blood pressure greater than 160 mm Hg , or female sex at age older than 75 years . INTERVENTION All participants given aspirin , 325 mg/d . MAIN OUTCOME MEASURES Ischemic stroke ( considered disabling when Rankin score was II or worse 1 - 3 months later ) and systemic embolism ( primary events ) . RESULTS Among 892 participants , the mean ( SD ) age was 67 ( 10 ) years , 78 % were men , and histories of hypertension , diabetes , and ischemic heart disease were present in 46 % , 13 % , and 16 % , respectively . The rate of primary events was 2.2 % per year ( 95 % confidence interval [ CI ] , 1.6%-3.0 % ) , of ischemic stroke was 2.0 % per year ( 95 % CI , 1.5%-2.8 % ) , and of disabling ischemic strokes was 0.8 % per year ( 95 % CI , 0.5%-1.3 % ) . Those with a history of hypertension had a higher rate of primary events ( 3.6 % per year ) than those with no history of hypertension ( 1.1 % per year ) ( P rate of disabling ischemic stroke was low in those with and without a history of hypertension ( 1.4 % per year and 0.5 % per year , respectively ) . The rate of major bleeding during aspirin therapy was 0.5 % per year . CONCLUSION Patients with AF who have relatively low rates of ischemic stroke , particularly disabling stroke , during treatment with aspirin can be reliably identified", "Oral anticoagulants ( OA ) are the drug of choice for stroke prevention in patients with non-rheumatic atrial fibrillation ( NRAF ) . This clear benefit/risk ratio comes from several r and omized clinical trials ( RCT ) in which highly selected patients were strictly monitored . The aim of this study was to ascertain whether the safety of OA was also obtained outside the setting of clinical trials in consecutive patients starting treatment and routinely followed at Italian anticoagulation clinics . A total of 433 patients with NRAF were enrolled in the ISCOAT study and followed up for a mean of 1.4 years . Two patients ( 0.3 % per year ) suffered from a complete non-fatal ischemic stroke , 8 patients ( 1.3 % per year ) died of thrombosis-related vascular death , and 11 patients ( 11 events , 1.8 % per year ) suffered from major bleedings ( 2 fatal ) . Major bleeding occurred more frequently in patients > 75 years of age ( 6 events , 5.1 % per year ) than in younger patients ( 5 events , 1.0 % per year ) . The cumulative incidence of major bleeding in patients over 75 years of age ( 10.8 % ; 95 % CI , 1.8 - 19.8 ) was significantly higher than in younger patients ( 2.8 % ; 95 % CI , 0.3 - 5.3 , p = 0.006 ) . Major primary bleeding unrelated to organic lesions ( 7 patients , 1 male and 6 females ) occurred in 5 elderly patients ( > 75 years old ) with a cumulative incidence ( 9.6 % ; 95 % CI 0.8 - 18.4 ) significantly higher than in younger patients ( 1.2 % ; 95 % CI , 0 - 3.0 , p = 0.0003 ) . Univariate analysis revealed a higher frequency of major primary bleeding in females , in diabetic patients and in in those who had suffered a previous thromboembolic event . Multivariate analysis revealed that only age grater than 75 years was independently related to major primary bleedings ( RR 6.6 ; 95 % CI 1.2 - 37 , p = 0.032 ) . Minor bleedings ( n = 27 ) were not more frequent in elderly patients ( 6 % vs 4 % per year , p = ns ) . Patients were kept at optimal intensity of treatment for 63 % of the time . These data confirm the efficacy of OA but identify elderly patients as a high risk group of major bleeding", "Context The appropriate level of warfarin anticoagulation in elderly patients with atrial fibrillation has been debated because of an age-associated increase in intracerebral hemorrhage . Contribution Patients with atrial fibrillation and intracerebral hemorrhage who were receiving anticoagulation were matched with similar patients who did not develop intracerebral hemorrhage . Although intracerebral hemorrhage was associated with increasing age ( especially > 85 years ) and increasing international normalized ratios ( INRs ) ( especially > 3.5 ) , the incidence of intracerebral hemorrhage was not statistically different in patients with INRs less than 2.0 and those with INRs between 2.0 and 3.0 . This was true even among those older than 75 years of age . Implication s Risk for intracerebral hemorrhage is not diminished in elderly patients with atrial fibrillation when anticoagulation is maintained below an INR of 2.0 . The Editors Intracranial hemorrhage is the most dangerous complication of warfarin anticoagulant therapy because of its high short-term risk for death and severe neurologic deficit ( 1 - 5 ) . Warfarin is extremely effective in reducing the risk for ischemic stroke associated with atrial fibrillation ( 6 , 7 ) . However , fear of hemorrhage may prompt some physicians to avoid prescribing anticoagulation ( 8) , especially in elderly patients , who appear to have a higher risk for hemorrhage ( 8 - 13 ) . Prominent recent guidelines recommend using lower-intensity anticoagulation for the primary prevention of stroke in patients older than 75 years of age who have atrial fibrillation ( 14 ) and suggest a target international normalized ratio ( INR ) range of 1.6 to 2.5 , despite evidence that the risk for ischemic stroke increases sharply at INRs less than 2.0 ( 15 , 16 ) . Previous studies have not thoroughly addressed the relationship of age and anticoagulation intensity to the risk for intracranial hemorrhage among patients with atrial fibrillation ( 1 , 2 ) . A study of 121 patients with warfarin-associated intracranial hemorrhage used the now-out date d prothrombin time ratio as a measure of anticoagulation intensity and did not specifically address risk in patients with atrial fibrillation ( 1 ) . Earlier studies also included patients receiving anticoagulation for mechanical valves , whose risk-to-benefit ratio is different from that of patients with atrial fibrillation ( 1 , 2 , 17 ) . As the number of individuals with atrial fibrillation increases ( 18 - 21 ) and as a greater proportion of older adults receive anticoagulant therapy ( 22 ) , more precise data are needed about the association of age , INR , and risk for intracranial hemorrhage . Intracranial hemorrhage , although critically important , is an uncommon complication among patients with atrial fibrillation who are receiving anticoagulation . As a result , r and omized trials and cohort studies have difficulty accumulating enough hemorrhage events to powerfully assess risk factors . To address these limitations , we performed a large casecontrol study to evaluate the relationship of increasing age and INR to the risk for intracranial hemorrhage among patients with nonvalvular atrial fibrillation . Methods Case- Patients We performed a casecontrol study comparing 2 groups : 1 ) case- patients with nonvalvular atrial fibrillation who developed intracranial hemorrhage while taking warfarin and 2 ) controls who were receiving anticoagulation for nonvalvular atrial fibrillation but did not develop intracranial hemorrhage . We found potential case- patients using the Partners HealthCare System Research Patient Data Registry , which can identify patients with specific International Classification of Diseases , Ninth Revision , Clinical Modification ( ICD-9-CM ) diagnoses by search ing the Massachusetts General Hospital billing system . We search ed for patients 18 years of age or older who had diagnoses of atrial fibrillation ( ICD-9-CM code 427.31 ) and intracranial hemorrhage ( ICD-9-CM codes 430 , 431 , 432.0 , 432.1 , 432.9 ) at any time from October 1993 to June 2002 . By 1993 , nearly all prothrombin time ratios at the hospital were reported as INRs . We review ed medical records to confirm whether patients were eligible , that is , whether they had intracranial hemorrhage documented by computed tomography or magnetic resonance imaging and documentation of warfarin therapy for atrial fibrillation at the time of the event . We excluded patients who were not taking warfarin at the time of hemorrhage ; those who were receiving anticoagulation for rheumatic heart disease , mitral stenosis , or mechanical valve placement ; those whose event was an ischemic stroke with hemorrhagic conversion ; or those in whom clinical factors may have led to hemorrhage independent of warfarin therapy . These factors included underlying anatomic brain abnormalities ( such as tumors or aneurysms ) , antecedent major head trauma ( skull fracture , trauma with loss of consciousness , motor vehicle injury , or neurosurgical procedures ) , or platelet count less than 50 109 cells/L. Starting in July 1994 , consecutive patients with intracerebral hemorrhage have been enrolled through the Massachusetts General Hospital emergency department as part of a longitudinal cohort study ( 23 ) . To vali date our automated search strategy , we compared our case-patient list with the list of patients identified through the cohort study and found that our search strategy missed only 4 patients with intracerebral hemorrhage . We obtained data on patient date of birth , sex , and ethnicity from computerized records . The type of hemorrhage ( intracerebral , subdural , subarachnoid , intraventricular , or epidural ) was determined through review of radiology reports . Data on presenting symptoms , history of minor head trauma , concomitant aspirin use , and disposition status were obtained from review of the admission medical record and were recorded on a st and ardized data collection form . We recorded the INR measurement obtained closest to the onset of symptoms . If an INR was not available or fresh frozen plasma or vitamin K was administered before the measurement , we considered INR data missing . We review ed medical charts for documentation of the following comorbid conditions : history of cerebrovascular disease ( defined as previous ischemic stroke or carotid artery disease ) , hypertension , congestive heart failure , coronary artery disease , diabetes mellitus , and cancer ( excluding nonmelanoma skin cancer ) . Controls Controls were sample d from patients managed by the Massachusetts General Hospital Anticoagulation Management Services clinic , which followed approximately 1000 patients receiving anticoagulation for atrial fibrillation at any given time during the study period . All patients who were followed in the anticoagulation clinic , received anticoagulation for atrial fibrillation , and had an INR measurement obtained in the same month and year as the given case date were assigned a r and om number . Six controls per case-patient were then r and omly selected . We matched case- patients to controls by INR date to account for any technical changes in INR testing that may have occurred over time . Because of this sampling method , an individual patient could potentially serve as a control for more than 1 case-patient ( 24 ) . Like case- patients , controls were 18 years of age or older ; were receiving anticoagulation for atrial fibrillation ; and had no documented rheumatic heart disease , mitral stenosis , or valve replacement . We sought data on potential confounders of the association of age , INR , and risk for intracranial hemorrhage , focusing on relevant comorbid conditions and combined use of aspirin with warfarin . We review ed available computerized discharge summaries , outpatient clinic notes , and medication lists from up to 2 years before the admission date . If combination warfarin and aspirin use was not documented , patients were considered to not be taking aspirin . Statistical Analysis Case- patients were categorized by type of hemorrhage : intracerebral , subdural , and other ( subarachnoid , intraventricular , or epidural ) . Clinical differences between types of hemorrhage were compared by using the KruskalWallis test for continuous variables ( age and INR ) and chi-square tests for categorical variables . We compared case- patients with controls by using multivariable conditional logistic regression , matching on INR date . Patient age was divided into 5-year intervals that were coded as indicator variables , and the odds of intracranial hemorrhage for each interval were compared with the odds of hemorrhage at a referent age of 70 to 74 years . The INR was divided into a set of ordered intervals that were coded as indicator variables . The relative odds for intracranial hemorrhage at each interval were calculated by using an INR of 2.0 to 3.0 as the referent category . In addition to age , INR , sex , and ethnicity , the following variables were included in the multivariable models to control for potential confounding effects of clinical factors and aspirin use : cerebrovascular disease , hypertension , congestive heart failure , coronary artery disease , diabetes mellitus , cancer , and concomitant aspirin use . If no records were available for review , comorbid conditions and aspirin use were coded as missing . We used multiple imputations for missing data on ethnicity , comorbid conditions , and aspirin use ( 25 ) . We tested for interactions between age and INR and comorbid conditions using 2-way interactions . None of the interaction terms were included in the model if they were not statistically significant when tested collectively . We tested the model 's goodness of fit using the HosmerLemeshow method ( 26 ) . Because the hospital 's anticoagulation clinic did not follow some case- patients before the event , and since factors relating to differences in outpatient care and monitoring could have confounded our analyses , we repeated these analyses in the subgroup of case- patients managed by the anticoagulation clinic . These restricted analyses", "OBJECTIVES To determine the most cost-effective method of screening for atrial fibrillation ( AF ) in the population aged 65 years and over , as well as its prevalence and incidence in this age group . Also to evaluate the relative cost-effectiveness of different methods of recording and interpreting the electrocardiogram ( ECG ) within a screening programme . DESIGN Multicentred r and omised controlled trial . Purpose fully selected general practice s were r and omly allocated to 25 intervention practice s and 25 control practice s. SETTING Fifty primary care centres across the West Midl and s , UK . PARTICIPANTS Patients aged 65 years and over . INTERVENTIONS GPs and practice nurses in the intervention practice s received education on the importance of AF detection and ECG interpretation . Patients in the intervention practice s were r and omly allocated to systematic ( n = 5000 ) or opportunistic screening ( n = 5000 ) . Prospect i ve identification of pre-existing risk factors for AF within the screened population enabled comparison between targeted screening of people at higher risk of AF and total population screening . MAIN OUTCOME MEASURES AF detection rates in systematic ally screened and opportunistically screened population s in the intervention practice s were compared with AF detection rate in 5000 patients in the control practice s. The screening period was 12 months . RESULTS Baseline prevalence of AF was 7.2 % , with a higher prevalence in males ( 7.8 % ) and patients aged 75 years and over ( 10.3 % ) . The control population demonstrated higher baseline prevalence ( 7.9 % ) than either the systematic ( 6.9 % ) or opportunistic ( 6.9 % ) intervention population . In the control population 47 new cases were detected ( incidence 1.04 % per year ) . In the opportunistic arm 243 patients without a baseline diagnosis of AF were found to have an irregular pulse , with 177 having an ECG , yielding 31 new cases ( incidence 0.69 % per year ) . A further 44 cases were detected outside the screening programme ( overall incidence 1.64 % per year ) . In the systematic arm 2357 patients had an ECG yielding 52 new cases ( incidence 1.1 % per year ) . Of these , 31 were detected by targeted screening and a further 21 by total population screening . A further 22 cases were detected outside the screening programme ( overall incidence 1.62 % per year ) . In terms of ECG interpretation , computerised decision support software ( CDSS ) gave a sensitivity of 87.3 % , a specificity of 99.1 % and a positive predictive value ( PPV ) of 89.5 % compared with the gold st and ard ( cardiologist reporting ) . GPs and practice nurses performed less well . The only difference in performance between intervention population s and controls was that practice nurses from the control arm performed less well than with intervention practice nurses on interpretation of limb-lead ( PPV 38.8 % versus 20.8 % ) and single-lead ( PPV 37.7 % versus 24.0 % ) ECGs . The within-trial economic evaluation results showed the lowest incremental cost to be for the opportunistic arm , with an incremental cost-effectiveness ratio of 337 pounds Sterling for each additional case detected compared to the control arm . Opportunistic screening dominated both more intensive screening strategies . Model-based analyses showed small differences in cost and quality -adjusted life-years for different methods and intensities of screening , but annual opportunistic screening result ed in the lowest number of ischaemic strokes and greatest proportion of cases of AF diagnosed . Probabilistic sensitivity results indicated that there was a probability of approximately 60 % that screening from the age of 65 years was cost-effective in both men and women . CONCLUSIONS The results of the study indicated that in terms of a screening programme for atrial fibrillation in patients 65 and over , the only strategy that improved on routine practice was opportunistic screening , model-based analyses indicated that there was a probability of approximately 60 % of annual opportunistic screening being cost effective . It is suggested that the following topics are worthy of further investigation : the effect of the implementation of a screening programme for AF on the uptake and maintenance of anticoagulation in patients aged 65 years and over ; an evaluation of the role of CDSS in the diagnosis of cardiac arrythmias ; the best method for routinely detecting paroxysmal AF ; ways of improving healthcare professionals ' performance in ECG interpretation ; development of a robust economic model to incorporate data on new therapeutic agents for use as thromboprophylactic agents for patients with AF , and an evaluation of the relative risk of stroke for patients with incident as opposed to prevalent AF", "OBJECTIVE The goal of this study was to investigate the complications and control of warfarin treatment in patients with nonvalvular atrial fibrillation ( NVAF ) newly referred to an outpatient anticoagulation clinic . METHODS This study included new patients with NVAF who were referred to an anticoagulation clinic for warfarin therapy over a recruitment period of 21 months . To reflect real-world clinical practice , patient selection for anticoagulation and patient management were left to the referring physicians , who were blinded to their patients ' participation in the study . Patients were interviewed in person at the first clinic visit and then by telephone every 4 to 6 weeks . They were question ed about any bleeding or thromboembolic events . RESULTS A total of 402 patients were included ( 100 % of all new referrals over 21 months ) . The mean ( SD ) age was 72.3 ( 10.3 ) years , and 224 ( 56 % ) patients were men . The mean ( SD ) international normalized ratio ( INR ) was 2.4 ( 0.31 ) . Patients were followed up for a mean ( SD ) of 19 ( 8.1 ) months ( range , 1.0 - 31.0 months ) . They spent a mean ( SD ) 66 % ( 18.3 ) of time in the target range of INR ( ie , 2.0 - 3.0 ) . Annual event rates were 1.7 % ( 95 % CI , 0.4%-3.0 % ) for major bleeding , 16.6 % ( 95 % CI , 13.0%-20.2 % ) for minor bleeding , 1.2 % ( 95 % CI , 0.1%-2.3 % ) for ischemic stroke , and 0.3 % ( 95 % CI , 0.2%-0.8 % ) for transient ischemic attacks . There were no cases of hemorrhagic stroke or fatal bleeding . Variability of INR and number of medications were identified as risk factors for bleeding ( P = 0.03 and P = 0.001 , respectively ) . There was no significant association between age and bleeding . CONCLUSIONS Based on this analysis , the risks of long-term oral anticoagulation therapy in an outpatient anticoagulation clinic appear to reflect the results of clinical trials . Rates of ischemic stroke , major bleeding , and anticoagulation control were comparable . There was no age-related risk of complications" ]

[ "BACKGROUND Several instruments can be used to identify patients with an unfavourable course of low back pain in general practice . However , it is unclear which instrument is the predictor of outcome . AIM To compare the predictive performance ( that is , calibration and discrimination ) of risk estimation by GPs with assessment s using the Orebro Musculoskeletal Pain Screening Question naire , the Low Back Pain Perception Scale ( LBPPS ) , and a prediction rule developed for this purpose . DESIGN OF STUDY A prospect i ve cohort study with 1-year follow-up . SETTING General practice in The Netherl and s. METHOD The outcome ' unfavourable course of low back pain ' was defined as having no clinical ly important improvement at minimally 50 % of the measurements at 6 , 13 , 26 , and 52 weeks . Logistic regression analyses were used to study associations between potential predictors and outcome . RESULTS In total , 60 GPs recruited 314 patients to the study ( 16 patients were excluded from analysis due to missing data on the course of low back pain ) . Over a third of patients ( 112/298 ) showed an unfavourable course of low back pain on follow-up . Risk estimation by GPs , the Orebro question naire , the LBPPS , and the prediction rule had discriminative ability ( area under the curve ) of 0.59 ( 95 % CI [ confidence intervals ] = 0.52 to 0.66 ) ; 0.61 ( 95 % CI = 0.54 to 0.67 ) ; 0.59 ( 95 % CI = 0.52 to 0.66 ) ; and 0.75 ( 95 % CI = 0.69 to 0.81 ) respectively . The prediction rule included history of low back pain , self-perceived risk to develop chronic low back pain , no solicitous responses of the patient 's partner ( as reported by the patient ) , frequent walking at work , and ' pain catastrophising ' . CONCLUSION Although the prediction rule performed best with regard to calibration and discrimination , it needs to be externally vali date d. Risk estimation by GPs performs as well as other instruments and , at present , seems to be the best available option", "Objective : Mental health problems often affect functioning to such an extent that they result in sick leave . The worldwide reported prevalence of mental health problems in the working population is 10%–18 % . In developed countries , mental health problems are one of the main grounds for receiving disability benefits . In up to 90 % of cases the cause is stress-related , and health-care utilisation is mainly restricted to primary care . The aim of this study was to assess the effectiveness of our Minimal Intervention for Stress-related mental disorders with Sick leave ( MISS ) in primary care , which is intended to reduce sick leave and prevent chronicity of symptoms . Design : Cluster-r and omised controlled educational trial . Setting : Primary health-care practice s in the Amsterdam area , The Netherl and s. Participants : A total of 433 patients ( MISS n = 227 , usual care [ UC ] n = 206 ) with sick leave and self-reported elevated level of distress . Interventions : Forty-six primary care physicians were r and omised to either receive training in the MISS or to provide UC . Eligible patients were screened by mail . Outcome Measures : The primary outcome measure was duration of sick leave until lasting full return to work . The secondary outcomes were levels of self-reported distress , depression , anxiety , and somatisation . Results : No superior effect of the MISS was found on duration of sick leave ( hazard ratio 1.06 , 95 % confidence interval 0.87–1.29 ) nor on severity of self-reported symptoms . Conclusions : We found no evidence that the MISS is more effective than UC in our study sample of distressed patients . Continuing research should focus on the potential beneficial effects of the MISS ; we need to investigate which elements of the intervention might be useful and which elements should be adjusted to make the MISS effective", "Study Design . R and omized controlled trial . Objectives . To investigate the effectiveness and costs of a mini-intervention , provided in addition to the usual care , and the incremental effect of a work site visit for patients with subacute disabling low back pain . Summary of Background Data . There is lack of data on cost-effectiveness of brief interventions for patients with prolonged low back pain . Methods . A total of 164 patients with subacute low back pain were r and omized to a mini-intervention group ( A ) , a work site visit group ( B ) , or a usual care group ( C ) . Groups A ( n = 56 ) and B ( n = 51 ) underwent one assessment by a physician plus a physiotherapist . Group B received a work site visit in addition . Group C served as controls ( n = 57 ) and was treated in municipal primary health care . All patients received a leaflet on back pain . Pain , disability , specific and generic health-related quality of life , satisfaction with care , days on sick leave , and use and costs of health care consumption were measured at 3- , 6- , and 12-month follow-ups . Results . During follow-up , fewer subjects had daily pain in Groups A and B than in Group C ( Group A vs. Group C , P = 0.002 ; Group B vs. Group C , P = 0.030 ) . In Group A , pain was less bothersome ( Group A vs. Group C , P = 0.032 ) and interfered less with daily life ( Group A vs. Group C , P = 0.040 ) than among controls . Average days on sick leave were 19 in Group A , 28 in Group B , and 41 in Group C ( Group A vs. Group C , P = 0.019 ) . Treatment satisfaction was better in the intervention groups than among the controls , and costs were lowest in the mini-intervention group . Conclusions . Mini-intervention reduced daily back pain symptoms and sickness absence , improved adaptation to pain and patient satisfaction among patients with subacute low back pain , without increasing health care costs . A work site visit did not increase effectiveness", "Background . The IMPaCT Back study ( IMplementation to improve Patient Care through Targeted treatment for Back pain ) is a quality improvement study which aims to investigate the effects of introducing and supporting a subgrouping for targeted treatment system for patients with low back pain ( LBP ) in primary care . This paper details the subgrouping for targeted treatment system and the clinical training and mentoring programmes aim ed at equipping clinicians to deliver it . The subgrouping and targeted treatment system . This system differs from ‘ one-size fits all ’ usual practice as it suggests that first contact health care practitioners should systematic ally allocate LBP patients to one of the three subgroups according to key modifiable prognostic indicators for chronicity . Patients in each subgroup ( those at low , medium or high risk of chronicity ) are then managed according to a targeted treatment system of increasing complexity . The subgrouping tools . Subgrouping tools help guide clinical decision-making about treatment and onward referral . Two subgrouping tools have been used in the IMPaCT Back study , a 9-item version used by participating physiotherapists and a 6-item version used by GPs . The targeted treatments . The targeted treatments include a minimal intervention delivered by GPs ( for those patients at low risk of poor outcome ) or referral to primary care physiotherapists who can apply physiotherapy approaches to addressing pain and disability ( for those at medium risk ) and additional cognitive-behavioural approaches to help address psychological and social obstacles to recovery ( for those at high risk ) . The training packages . Building on previous interventions for other pilot studies and r and omized trials , we have developed and delivered clinical training and support programmes for GPs and physiotherapists . Discussion . This paper describes in detail the IMPaCT Back study ’s subgrouping for targeted treatment system and the training and mentoring packages aim ed at equipping clinicians to deliver it , within the IMPaCT Back study . Study registration . IS RCT N55174281", "BACKGROUND Medically unexplained physical symptoms present one of the most common problems in modern medical practice but often prove difficult to manage . The central position of the GP in the care of patients with medically unexplained symptoms has been emphasized repeatedly , but little is known about the attitudes of GPs to this role . Underst and ing how GPs view these patients may inform the development of effective strategies for management . OBJECTIVE Our aim was to survey the attitudes of UK GPs towards medically unexplained symptoms ( MUS ) and somatization . METHODS A r and om sample of 400 GPs in the South Thames ( West ) region were surveyed using a postal question naire . Respondents ' attitudes toward the cause and management of MUS were recorded . RESULTS A total of 284 completed question naires were returned ( 22 returned incomplete ) , giving an adjusted response rate of 75 % . Although it was broadly felt that patients with MUS are difficult to manage , most GPs felt that patients with MUS should be managed in primary care . Providing reassurance , counselling and acting as a ' gatekeeper ' to prevent inappropriate investigations were considered important roles for GP management . A majority felt that patients with MUS have personality problems or psychiatric illness . Fewer than half of the respondents felt that there are effective treatments available for somatization . CONCLUSION GPs consider the management of patients with MUS to be an important part of their workload , but there is a perception that effective management strategies are lacking . Psychiatrists need to offer greater support and training for GPs in this area of health care", "Abstract Objective To compare the effects of a minimal intervention strategy aim ed at assessment and modification of psychosocial prognostic factors and usual care for treatment of (sub)acute low back pain in general practice . Design Cluster r and omised clinical trial . Setting 60 general practitioners in 41 general practice s. Participants 314 patients with non-specific low back pain of less than 12 weeks ' duration , recruited by their general practitioner . Interventions In the minimal intervention strategy group the general practitioner explored the presence of psychosocial prognostic factors , discussed these factors , set specific goals for reactivation , and provided an educational booklet . The consultation took about 20 minutes . Usual care was not st and ardised . Main outcome measures Functional disability ( Rol and -Morris disability question naire ) , perceived recovery , and sick leave because of low back pain assessed at baseline and after 6 , 13 , 26 , and 52 weeks . Results The dropout rate was 8 % in the minimal intervention strategy group and 9 % in the usual care group . Multilevel analyses showed no significant differences between the groups on any outcome measure during 12 months of follow-up in the whole group or in relevant subgroups ( patients with high scores on psychosocial measures at baseline or a history of frequent or prolonged low back pain ) . Conclusion This study provides no evidence that ( Dutch ) general practitioners should adopt our new treatment strategy aim ed at psychosocial prognostic factors in patients with (sub)acute low back pain . Further research should examine why our new strategy was not more effective than usual care", "Underst and ing the course of back pain is important for clinicians and research ers , but analyses of longitudinal data from multiple time points are lacking . A prospect i ve cohort study of consecutive back pain consulters from five general practice s in the United Kingdom was carried out between 2001 and 2003 to identify groups defined by their pain pathways . Patients were sent monthly question naires for a year . Longitudinal latent class analysis was performed by using pain intensity scores for 342 consulters . Analysis yielded four clusters representing different pathways of back pain . Cluster 1 ( \" persistent mild \" ; n = 122 ) patients had stable , low levels of pain . Patients in cluster 2 ( \" recovering \" ; n = 104 ) started with mild pain , progressing quickly to no pain . Cluster 3 ( \" severe chronic \" ; n = 71 ) patients had permanently high pain . For patients in cluster 4 ( \" fluctuating \" ; n = 45 ) , pain varied between mild and high levels . Distinctive patterns for each cluster were maintained throughout follow-up . Clusters showed statistically significant differences in disability , psychological status , and work absence ( p back pain patients . Identification of four distinct groups of patients improves underst and ing of the course of back pain and may provide a basis of classification for intervention", "OBJECTIVE To describe a new tool design ed to capture patients ' perception of their low back pain ( LBP ) episodes-the patient perception scale ( PPS ) and test its ability to predict episode outcomes . METHODS Thirty-two family physicians recruited 526 low back pain patients during an office visit . Physicians completed a short question naire at the index visit , which included both their assessment s of patients ' patient perception scale ( PPS-doc ) and contact information . Patients were then interviewed by telephone within 2 weeks after the index visit , with follow-up telephone contacts at 2 , 4 , 8 and 12 months . The patient perception scale as reported by the physician ( PPS-doc ) and patient ( PPS-pt ) , each constituent question , and different combinations were analyzed for their ability to predict patient outcomes . RESULTS Patients ' responses ( PPS-pt ) proved predictive for all outcome items . PPS-doc was much less predictive . Measures of patient centeredness did not perform well in this study . CONCLUSION By using a short scale based on the patient 's perception of pain ( PPS-pt ) , it is possible to predict adverse outcomes of a low back pain episode . The patient perception scale should be evaluated further and perhaps combined with other instruments for targeting care and chronicity prevention efforts in low back pain . PRACTICE IMPLICATION S The PPS-pt could potentially be used as part of the st and ard initial patient evaluation of new LBP patients , as a proxy for \" yellow flags \" ( markers of psychosocial risk ) where a positive score might be the equivalent to high-risk identification . The apparent advantage of this scale is its brevity and simplicity of administration . The separation , through this scale of pain episodes into simple and complex LBP might be a useful tool for helping direct re sources and avoiding chronicity", "Study Design . Population ‐based r and omized clinical trial . Objectives . To develop and test a model of management of subacute back pain , to prevent prolonged disability . Summary of Background Data . The present management of back pain seems inadequate , and development of innovative models has been urged . Methods . A model for the treatment of subacute work‐related back pain has been developed and evaluated in a population ‐based r and omized clinical trial . Workers ( n = 130 ) from eligible workplaces in the Sherbrooke area ( N = 31 ) , who had been absent from work for more than 4 weeks for back pain , were r and omized , based on their workplace , in one of four treatment groups : usual care , clinical intervention , occupational intervention , and full intervention ( a combination of the last two ) . The duration of absence from regular work and from any work was evaluated using survival analysis . Functional status and pain were compared at study entry and after 1 year of follow‐up . Results . The full intervention group returned to regular work 2.41 times faster than the usual care intervention group ( 95 % confidence interval 1.19‐4.89 ; P = 0.01 ) . The specific effect of the occupational intervention accounted for the most important part of this result , with a rate ratio of return to regular work of 1.91 ( 95 % confidence interval = 1.18‐3.10 ; P demonstrated either a statistically significant reduction or a trend toward reduction in the three intervention groups , compared with the trend in the usual care intervention group . Conclusions . Close association of occupational intervention with clinical care is of primary importance in impeding progression toward chronicity of low back pain", "RATIONALE Depression and anxiety are significant comorbid and potentially modifiable conditions in chronic obstructive pulmonary disease ( COPD ) , but their effects on exacerbations are not clear . OBJECTIVES To investigate the independent effect of depression and anxiety on the risk of COPD exacerbations and hospitalizations . METHODS A multicenter prospect i ve cohort study in 491 patients with stable COPD in China . Multivariate Poisson and linear regression analyses were used , respectively , to estimate adjusted incidence rate ratios ( IRRs ) and adjusted effects on duration of events . MEASUREMENTS AND MAIN RESULTS Depression and anxiety were measured using the Hospital Anxiety and Depression Scale ( HADS ) at baseline . Other measurements included sociodemographic , clinical , psychosocial , and treatment characteristics . Patients were then monitored monthly for 12 months to document the occurrence and characteristics of COPD exacerbations and hospitalizations . Exacerbation was determined using both symptom-based ( worsening of > or = 1 key symptom ) and event-based definitions ( > or = 1 symptom worsening plus > or = 1 change in regular medications ) . A total of 876 symptom-based and 450 event-based exacerbations were recorded , among which 183 led to hospitalization . Probable depression ( HADS depression score > or = 11 ) was associated with an increased risk of symptom-based exacerbations ( adjusted IRR , 1.51 ; 95 % confidence interval [ CI ] , 1.01 - 2.24 ) , event-based exacerbations ( adjusted IRR , 1.56 ; 95 % CI , 1.02 - 2.40 ) , and hospitalization ( adjusted IRR , 1.72 ; 95 % CI , 1.04 - 2.85 ) compared with nondepression ( score duration of event-based exacerbations was 1.92 ( 1.04 - 3.54 ) times longer for patients with probable anxiety ( HADS anxiety score > or = 11 ) than those with no anxiety ( score exacerbations and hospitalizations . Further studies are warranted to confirm this finding and to test the effectiveness of antidepressants and psychotherapies on reducing exacerbations and improving health re source utilizations", "OBJECTIVES The aim of this study is to underst and in depth the experience of the family physician faced with the patient that he perceives as ' difficult ' . This was done by means of the ' long interview ' as a method of qualitative research . METHOD We interviewed 15 r and omly selected Board-certified family physicians , with five or more years experience as specialists , employed in the northern district of the ' Clalit Health Services ' , the major sick fund in Israel . RESULTS The participants stated that the ' difficult ' patients are not those with difficult medical problems but rather those who are violent , dem and ing , aggressive , rude and who seek secondary gain . Patients with multiple non-specific complaints and those with psychosomatic problems are also difficult for the family physician . Appropriate use of patient-doctor communication skills and an effort to improve relations with the patient through empathy , tolerance and non-judgmental listening were suggested by the physicians as ways of making the difficult encounter easier . CONCLUSIONS Family physicians acknowledge their responsibility for the ' difficult ' patient , and seek innovative and creative ways to cope with the difficult medical encounter . The more experienced the doctor is , the less he perceives patients as ' difficult ' , as he learns to accept greater diversity of behaviours in his patients", "BACKGROUND Patients with musculoskeletal pain account for a large number of consultations in primary care . Improving our underst and ing of factors that make patients seek care could be of interest in decision making and prevention in the health care system . OBJECTIVES Our objectives were to examine if health anxiety , somatization and fear-avoidance beliefs were of importance for care-seeking with either back pain or upper extremity pain and to look at possible differences between the two groups . METHODS This is a prospect i ve study with a baseline question naire and 18 months follow-up . Using the International Classification for Primary Care ( ICPC ) , we identified care-seekers with either back pain or upper extremity pain among the potential patients of eight GPs . For analysis , we used Cox proportional hazards regression analysis . Analysis was stratified by gender . RESULTS We found that previous regional pain was a strong predictor of care-seeking . Somatization was associated with seeking care for back pain . Health anxiety was a predictor among women suffering from back pain . Only previous pain was a predictor of care-seeking for upper extremity pain . CONCLUSION The study implies that prevention of back pain and upper extremity pain requires different strategies and that gender and health anxieties should be taken into account", "Background Medically unexplained physical symptoms ( MUPS ) are common in general practice ( GP ) , and are even more problematic as they become persistent . The present study examines the relationship between persistent MUPS in general practice on the one h and and quality of life , social conditions , and coping on the other h and . Additionally , it is examined how patients with persistent MUPS evaluate the quality of GP-care . Methods Data were used from a representative survey of morbidity in Dutch general practice , in which data from the electronic medical records were extracted . A r and om sample of patients participated in an extensive health interview and completed self-reported measures on social isolation , coping and the quality of GP-care . Patients with persistent MUPS ( N = 192 ) were compared with general practice patients not meeting the criteria for persistent MUPS ( N = 7.314 ) , and with a group of patients that visited the GP in comparable rates for medical diagnoses ( N = 2.265 ) . Multiple logistic regression analyses were used to control for relevant socio-demographic variables and chronic diseases . Results After adjustment for demographics and chronic diseases , patients with persistent MUPS reported more psychological distress , more functional impairment , more social isolation , and they evaluated the quality of GP-care less positive than the other two patient groups . Although the majority of MUPS patients were positive about the quality of GP-care , they more often felt that they were not taken seriously or not involved in treatment decisions , and more often reported that the GP did not take sufficient time . The three groups did not differ with respect to the statement that the GP unnecessarily explains physical problems as psychological ones . ConclusionS trengthening MUPS patients ' social network and encouraging social activities may be a meaningful intervention in which the GP may play a stimulating role . To further improve MUPS patients ' satisfaction with GP-care , GPs may pay extra attention to taking sufficient time when treating MUPS patients , taking the problems seriously , and involving them in treatment decisions", "Guidelines portray low back pain ( LBP ) as a benign self‐limiting disease which should be managed mainly by primary care physicians . For the German health care system we analyze which factors are associated with receiving specialist care and how this affects treatment . This is a longitudinal prospect i ve cohort study . General practitioners recruited consecutive adult patients presenting with LBP . Data on physical function , on depression , and on utilization of health services were collected at the first consultation and at follow‐up telephone interviews for a period of 12 months . Logistic regression models were calculated to investigate predictors for specialist consultations and use of specific health care services . Large proportions ( 57 % ) of the 1342 patients were seeking additional specialist care . Although patients receiving specialist care had more often chronic LBP and a positive depression score , the association was weak . A total of 623 ( 46 % ) patients received some form of imaging , 654 ( 49 % ) physiotherapy and 417 ( 31 % ) massage . Consulting a specialist remained the strongest predictor for imaging and therapeutic interventions while disease‐related and socio‐demographic factors were less important . Our results suggest that the high use of specialist care in Germany is due to the absence of a functioning primary care gate keeping system for patient selection . The high dependence of health care service utilization on providers rather than clinical factors indicates an un systematic and probably inadequate management of LBP", "The aim of this paper is to assess whether patient-centred consultations are more effective than the usual style of consultations used by general practitioners with patients suffering from benign chronic musculoskeletal pain and fibromyalgia . It also seeks to evaluate the differential characteristics of these two clinical groups of symptoms . The study was design ed as a cluster r and omised and simple blind trial . Twenty general practitioners took part and 110 patients were recruited . Compared with patients who received the usual treatment from their family physician , those who received a patient-centred approach showed greater improvement after 1 year in terms of psychological distress ( anxiety ) and number of tender points , as well as showing positive trends in some important outcomes such as pain intensity . Significantly better results were observed in those patients suffering chronic pain than in those with fibromyalgia , particularly as regards associated symptoms , self-rated pain and physical mobility as measured by the Nottingham health profile", "BACKGROUND CONTEXT Low back pain ( LBP ) is a major public health problem , with a considerable impact on workers . PURPOSE To model the risk of LBP in the male general working population . STUDY DESIGN / SETTING Repeated cross-sectional surveys in a wide occupational setting . PATIENT SAMPLE A r and om sample of 2,161 men working in various occupations in a French region participated in a first survey in 2002 , and 1,313 of these ( 60.8 % ) participated in a second survey in 2007 . OUTCOME MEASURE The self-reported prevalence of LBP during the previous week in the second survey . METHODS Twenty-one biomechanical , organizational , psychosocial , and individual factors were assessed in the first survey . The association between these potential risk factors and the prevalence of later LBP ( in the second survey ) was studied , using multistep logistic regression models . RESULTS Three hundred ninety-four men reported LBP in the second survey ( prevalence 30.0 % ) . The final multivariate model highlighted four risk factors : frequent bending ( odds ratio [ OR ] , 1.45 , 95 % confidence interval [ CI ] , 1.07 - 1.97 for bending forward only ; and OR , 2.13 , 95 % CI , 1.52 - 3.00 for bending both forward and sideways ) , driving industrial vehicles ( OR , 1.35 ; 95 % CI , 1.00 - 1.81 ) , working more hours than officially planned ( OR , 1.38 ; 95 % CI , 1.05 - 1.81 ) , and reported low support from supervisors ( OR , 1.35 ; 95 % CI , 1.02 - 1.79 ) . CONCLUSIONS These results emphasize that biomechanical factors remain worth considering , even when psychosocial factors are taken into account , and provide a significant contribution to preventive strategies", "The aim of this prospect i ve cohort study was to identify modifiable protective factors of the progression of acute/subacute low back pain ( LBP ) to the persistent state at an early stage to reduce the socioeconomic burden of persistent LBP . Patients attending a health practitioner for acute/subacute LBP were assessed at baseline addressing occupational , personal and psychosocial factors , and followed up over 12 weeks . Pearson correlations were calculated between these baseline factors and the presence of nonpersistent LBP at 12-week follow-up . For those factors found to be significant , multivariate logistic regression analyses were performed . The final 3-predictor model included job satisfaction , mental health and social support . The accuracy of the model was 72 % , with 81 % of nonpersistent and 60 % of persistent LBP patients correctly identified . Further research is necessary to confirm the role of different types of social support regarding their prognostic influence on the development of persistent LBP", "& NA ; Psychosocial factors have been shown to play an important role in the development of chronic low back pain ( LBP ) . In our recently completed cluster‐r and omized trial we found , however , no evidence of an effect of our minimal intervention strategy ( MIS ) aim ed at psychosocial factors , over usual care ( UC ) in patients with (sub)acute LBP . To explore the reasons why , this paper presents an evaluation of the processes presumably underlying the effectiveness of MIS . General practitioner ( GP ) attitude was evaluated by the Pain Attitudes and Beliefs Scale and two additional questions . GP behaviour was evaluated by analysing treatment registration forms and patients ' responses to items regarding treatment content . Patients also scored items on satisfaction and compliance . Modification of psychosocial measures was evaluated by analysing changes after 6 and 52 weeks on the Fear Avoidance and Beliefs Question naire , the Coping Strategies Question naire and the 4‐Dimensional Symptom Question naire . A total of 60 GPs and 314 patients participated in the study . GPs in the MIS‐group adopted a less biomedical orientated attitude than in the UC‐group , but were only moderately successful in identification of psychosocial factors . Treatment contents as perceived by the patient and patient satisfaction differed significantly between both groups . Changes on psychosocial measures , however , did not differ between groups . The suboptimal identification of psychosocial factors in the MIS‐group and the absence of a relevant impact on psychosocial factors may explain why MIS was not more effective than UC ", "Context Exercise and advice are common treatments for patients with subacute low back pain , but their effectiveness is unclear . Contribution In this trial , 259 adults with subacute low back pain received 12 real or sham physiotherapist-directed exercise sessions and 3 real or sham advice sessions over 6 weeks . Compared with sham exercise and sham advice , patients who received real exercise and real advice had the most benefit at 6 weeks . However , only a small benefit on patient-reported function persisted at 12 months . Implication Compared with no exercise or advice , a combination of physiotherapist-directed exercise and advice seems to improve pain and function in the short term for patients with subacute low back pain . The Editors Back pain is 1 of the most frequent reasons for consultation with a general practitioner ( 1 , 2 ) . Most treatment guidelines provide advice for patients on managing acute or recent-onset low back pain but not chronic pain ( 3 ) . This reflects the view that acute low back pain is typically self-limited and that only a small proportion of persons develop chronic pain . However , a recent systematic review of the prognosis of acute low back pain ( 4 ) showed that this view is inaccurate : Pain and disability are typically ongoing , and recurrences are common . Thus , effective treatments for patients whose pain and disability persist beyond the acute phase are needed . We are interested in the subacute phase , which is the transition period from acute ( duration 3 months ) low back pain . All treatment guidelines ( 3 ) endorse advice as a treatment for subacute low back pain , and advice is the most frequently administered treatment in general practice ( 1 ) . Exercise is the most common treatment for low back pain ( 2 , 5 , 6 ) , and some guidelines recommend it for subacute low back pain ( 3 ) . However , a systematic review of treatment for subacute low back pain ( 7 ) concluded that no high- quality evidence exists for the efficacy of any intervention . To address this knowledge gap , we conducted a factorial r and omized , placebo-controlled trial of the effect of exercise , advice , or both on pain , function , and global perceived effect . Methods Setting The trial was conducted at 7 physiotherapy clinics in Australia and New Zeal and , of which 6 were in university teaching hospitals and 1 was in a primary care clinic . There were 16 physiotherapists . Each clinic had 1 to 5 therapists providing treatment . We enrolled participants from January 2001 to June 2003 . The study protocol was approved by the institutional review boards of the University of Sydney , Sydney , Australia , and of each clinic . Participants We sought persons between 18 and 80 years of age with nonspecific low back pain lasting for at least 6 weeks but no longer than 12 weeks . Participants were recruited by direct referral to the trial by a health care professional ( n= 1 ) , invitations to patients on hospital waiting lists for physiotherapy treatment of low back pain ( n= 73 ) , and advertisements in newspapers ( n= 185 ) . Exclusion criteria were spinal surgery in the past 12 months , pregnancy , nerve root compromise , confirmed or suspected serious spinal abnormality ( for example , infection , fracture , or the cauda equina syndrome ) , contraindications to exercise , and poor comprehension of the English language . We did not exclude participants who were receiving low back pain treatment other than spinal surgery . Potential participants who reported osteoarthritis ; spondylitis ; spondylolysis ; spondylolisthesis ; disc protrusion , herniation , or prolapse ; or spinal stenosis were eligible . We asked participants not to take other treatments for low back pain during the 6-week treatment phase . Written informed consent was obtained from all participants before they enrolled in the trial . R and omization and Interventions After completing the baseline assessment , we r and omly allocated participants to 1 of 4 intervention groups : exercise and advice , exercise and sham advice , sham exercise and advice , or sham exercise and sham advice . The allocation schedule was generated by using the r and om-number function in Microsoft Excel ( Microsoft , Inc. , Redmond , Washington ) , and the allocation codes were placed in sequentially numbered , sealed , opaque envelopes . At each site , the trial coordinator or the physiotherapist allocated participants to groups by opening the next numbered envelope . This process ensured that allocation was concealed from participants , referring medical practitioners , trial staff who determined eligibility , and the assessor of outcomes . The 12 exercise or sham exercise sessions were delivered over 6 weeks : 3 sessions per week in weeks 1 and 2 , 2 sessions per week in weeks 3 and 4 , and 1 session per week in weeks 5 and 6 . In weeks 1 , 2 , and 4 , participants also received advice or sham advice . Sham treatments were design ed to provide similar contact time with the treating clinician . The clinicians who provided the sham treatments were the same ones who provided the real treatments . Registered physiotherapists who received training from an experienced clinical psychologist delivered treatment . Treatment consistency was promoted at the initial staff meeting and at regular trial treatment meetings , and by providing a treatment manual to all treatment providers . To assess treatment validity , an investigator recorded and assessed sample treatment sessions . In addition , 1 investigator regularly visited each treatment site to monitor delivery of treatment . The comprehensive treatment manual is in the Appendix . Appendix . Treatment Manual Exercise The exercise program was based on the program described by Lindstrm and colleagues ( 8) . It included an individualized , progressive , submaximal program design ed to improve the abilities of participants to complete functional activities that they specified as being difficult to perform because of low back pain . Each participant undertook aerobic exercise ( for example , a walking or cycling program ) ; stretches ; functional activities ; activities to build speed , endurance , and coordination ; and trunk- and limb-strengthening exercises . Physiotherapists used principles of cognitive-behavioral therapy , including setting goals of progressively increasing difficulty , encouraging self-monitoring of progress , and promoting self-reinforcement ( 9 ) . Physiotherapists provided individualized home exercise programs , which they regularly review ed , and they encouraged continuation of the home program after the intervention finished . Sham Exercise The control for the exercise intervention consisted of sham pulsed ultrasonography ( 5 minutes ) and sham pulsed short-wave diathermy ( 20 minutes ) . The sham units were identical to active units ( for example , the on and off lights illuminated and the output dial moved ) except that they did not provide output . To optimize treatment credibility , physiotherapists followed the usual clinical routine for delivering these treatments . The active forms of these treatments delivered in pulsed mode do not produce heat ; thus , previous experience with the treatments would not unblind participants . Participants allocated to exercise did not receive the active forms of these treatments . Advice Advice sessions were based on the program by Indahl and colleagues ( 10 ) and aim ed to encourage a grade d return to normal activities . The physiotherapist explained the benign nature of low back pain , addressed any unhelpful beliefs about back pain , and emphasized that being overly careful and avoiding light activity would delay recovery . Sham Advice During sham advice sessions , participants were given the opportunity to talk about their low back pain and any other problems . The physiotherapist responded in a warm and empathic manner , displaying genuine interest in the participant , but did not give advice about the low back pain ( 11 ) . Participants were told that the trial included active and placebo physiotherapy treatments and that they would receive 2 treatments , but they were not told whether the interventions they received were active or sham . Outcomes and Measurements We determined participants ' perceptions of the effectiveness of treatment at the beginning of the trial and at 12 months . We assessed treatment adherence by the number of appointments attended , session duration , and amount of time the physiotherapist spent with each participant . Participants were asked not to seek other treatments during the 6-week treatment period . Participants who discontinued treatment were encouraged to return for follow-up . Immediately before r and omization , we obtained baseline measurements . We collected additional data on work status , medication use , side effects , adverse events , and number and type of co- interventions at 6 weeks , 3 months , and 12 months after r and omization . We chose primary and secondary outcomes a priori . The primary outcomes were pain , global perceived effect , and functional ability at 6 weeks and 12 months . Secondary outcomes were pain , global perceived effect , and functional ability at 3 months ; number of health care contacts during the past 6 weeks ( determined at 12 months ) ; and disability and depression at 6 weeks , 3 months , and 12 months . We rated pain as average pain over the past week on a scale of 0 ( no pain ) to 10 ( worst pain possible ) ( 12 ) . We measured functional ability by using the Patient-Specific Functional Scale ( score range , 0 [ can not perform activity ] to 10 [ can perform activity at preinjury level ] ) ( 13 ) . We measured global perceived effect of treatment on an 11-point scale , ranging from 5 ( vastly worse ) to 5 ( completely recovered ) , with 0 being no change . We measured disability with the Rol and Morris Disability Question naire ( score range , 0 to 24 ) ( 14 ) . We measured depression , anxiety , and stress by using the 21-item Depression Anxiety Stress Scales ( DASS-21 ) ( score range for each subscale , 0 to 42 ) ( 15 ) . These measures have acceptable psychometric properties and are widely used in", "OBJECTIVE To determine the prevalence of serious pathology in patients presenting to primary care setting s with acute low back pain , and to evaluate the diagnostic accuracy of recommended \" red flag \" screening questions . METHODS An inception cohort of 1,172 consecutive patients receiving primary care for acute low back pain was recruited from primary care clinics in Sydney , Australia . At the initial consultation , clinicians recorded responses to 25 red flag questions and then provided an initial diagnosis . The reference st and ard was a 12-month followup supplemented with a specialist review of a r and om sub sample of participants . RESULTS There were 11 cases ( 0.9 % ) of serious pathology , including 8 cases of fracture . Despite the low prevalence of serious pathology , most patients ( 80.4 % ) had at least 1 red flag ( median 2 , interquartile range 1 - 3 ) . Only 3 of the red flags for fracture recommended for use in clinical guidelines were informative : prolonged use of corticosteroids , age > 70 years , and significant trauma . Clinicians identified 5 of the 11 cases of serious pathology at the initial consultation and made 6 false-positive diagnoses . The status of a diagnostic prediction rule containing 4 features ( female sex , age > 70 years , significant trauma , and prolonged use of corticosteroids ) was moderately associated with the presence of fracture ( the area under the curve for the rule score was 0.834 [ 95 % confidence interval 0.654 - 1.014 ] ; P = 0.001 ) . CONCLUSION In patients presenting to a primary care provider with back pain , previously undiagnosed serious pathology is rare . The most common serious pathology observed was vertebral fracture . Approximately half of the cases of serious pathology were identified at the initial consultation . Some red flags have very high false-positive rates , indicating that , when used in isolation , they have little diagnostic value in the primary care setting", "OBJECTIVES Because musculoskeletal pain is the second most frequent reason for seeking health care , the aims of this study were to determine the value of psychosocial variables in evaluating risk for developing chronic back pain problems and to develop a screening methodology to identify patients likely to have a poor prognosis . STUDY DESIGN A prospect i ve study was conducted on consecutive patients with acute or subacute back pain , in which patients completed a screening question naire and were then followed up for 6 months to determine outcome . The primary outcome variable was accumulated sick leave . METHODS One hundred forty-two consecutive patients were asked to complete a question naire design ed for this study . This question naire contained 24 items concerning psychosocial aspects of the problem . Six months later , patients were contacted to complete outcome questions about accumulated sick leave . RESULTS A total of 97 % of the patients completed both question naires . Although patients , on average , improved greatly , 18 % had 1 - 30 days and 20 % had fewer than 30 days of sick leave during the follow-up period . Five variables were found to be the strongest predictors of sick leave outcome ( fear-avoidance work beliefs , perceived improvement , problems with work function , stress , and previous sick leave ) , correctly classifying 73 % of the patients as opposed to a chance rate of 33 % . A total score was evaluated as a means of judging risk and found to be strongly related to outcome . CONCLUSION Potent psychosocial risk factors associated with future sick absenteeism were identified . Because the total score was related to outcome , the instrument may have use in screening patients with acute or subacute spinal pain in clinical situations", "Introduction In an earlier study , Gatchel et al. ( J Occup Rehabil 13:1–9 , 2003 ) demonstrated that participants at high risk for developing chronic low back pain disability ( CLBPD ) , who received a biopsychosocial early intervention treatment program , displayed significantly more symptom improvement , as well as cost savings , relative to participants receiving st and ard care . The purpose of the present study was to exp and on these results by examining whether the addition of a work-transition component would further strengthen the effectiveness of this early intervention treatment . Methods Using an existing algorithm , participants were identified as being high-risk ( HR ) or low-risk ( LR ) for developing CLBPD . HR participants were then r and omly assigned to one of three groups : early intervention ( EI ) ; early intervention with work transition ( EI/WT ) ; or st and ard care ( SC ) . Participants provided information regarding pain , disability , work status , and psychosocial functioning at baseline , periodically during treatment , and again 1 year following completion of treatment . Results At 1-year follow-up , no significant differences were found between the EI and EI/WT groups in terms of occupational status , self-reports of pain and disability , coping ability or psychosocial functioning . However , significant differences in all these outcomes were found comparing these groups to st and ard care . Conclusion The addition of a work transition component to an early intervention program for the treatment of ALBP did not significantly contribute to improved work outcomes . However , results further support the effectiveness of early intervention for high-risk ALBP patients", "OBJECTIVE The objective of this study was to determine the effectiveness of a training to increase collaboration between general practitioners and occupational health physicians in the treatment of patients with low back pain ( LBP ) because more collaboration might improve a patient 's recovery and shorten sick leave . METHODS In a controlled trial , the intervention in one region was compared with usual care in a control region . Participating physicians enrolled patients with LBP on sick leave for 3 - 12 weeks . Patients filled out three question naires : at inclusion , at 3 months , and at 6 months . Information on sick leave was gathered from occupational health services . All analyses were performed on an intention-to-treat basis . RESULTS Fifty-six patients with LBP were enrolled in each region . There was little collaboration between physicians during the project . Patients in the intervention region returned to work significantly later ( P=.005 ) but were significantly more satisfied with their occupational health physician ( P=.01 ) . No differences were found between the intervention and control patients for pain , disability , quality of life , and medical consumption . CONCLUSION Our study does not show a positive effect of the training to increase collaboration between general practitioners and occupational health physicians . The training may not have improved collaboration enough to influence the prognosis of LBP", "BACKGROUND Better insight into frequent comorbidities in patients with chronic ( ≥ 3 months ) low back pain ( LBP ) may help general practitioners when planning comprehensive care for these patients . OBJECTIVE To prospect ively study the prevalence of psychological , social , musculoskeletal and somatoform disorders in patients presenting with chronic non-specific LBP to general practitioners , in comparison to a contrast group of patients consulting in the same setting . METHODS This case-control study is embedded in a historical cohort , based on a primary care practice -based research network . All the health problems presented by the patients were prospect ively coded according to the international classification of primary care between 1996 and 2013 . The prevalence of psychological , social , musculoskeletal and somatoform disorders presented by the adult patients from 1 year before the onset of chronic LBP to 2 years after onset was compared to that of matched patients consulting without LBP , using conditional logistic regressions . RESULTS The 1511 patients with chronic LBP more often presented musculoskeletal disorders than the contrast group during the year before the onset of LBP and during the second year after it , with odds ratios ( 95%confidence intervals ) of 1.39 ( 1.20 - 1.61 ) and 1.56 ( 1.35 - 1.81 ) , respectively . They did not more often present psychological , social or non-musculoskeletal somatoform disorders . CONCLUSIONS General practitioners should consider all the musculoskeletal symptoms when caring for patients with chronic LBP . Rather than systematic ally screening for specific psychological , social or somatoform disorders , they should consider with the patient how LBP and any type of potential comorbidity interfere with his/her daily functioning", "Low back pain is the fifth most common reason for all physician visits in the United States ( 1 , 2 ) . Approximately one quarter of U.S. adults reported having low back pain lasting at least 1 whole day in the past 3 months ( 2 ) , and 7.6 % reported at least 1 episode of severe acute low back pain ( see Glossary ) within a 1-year period ( 3 ) . Low back pain is also very costly : Total incremental direct health care costs attributable to low back pain in the U.S. were estimated at $ 26.3 billion in 1998 ( 4 ) . In addition , indirect costs related to days lost from work are substantial , with approximately 2 % of the U.S. work force compensated for back injuries each year ( 5 ) . Many patients have self-limited episodes of acute low back pain and do not seek medical care ( 3 ) . Among those who do seek medical care , pain , disability , and return to work typically improve rapidly in the first month ( 6 ) . However , up to one third of patients report persistent back pain of at least moderate intensity 1 year after an acute episode , and 1 in 5 report substantial limitations in activity ( 7 ) . Approximately 5 % of the people with back pain disability account for 75 % of the costs associated with low back pain ( 8) . Many options are available for evaluation and management of low back pain . However , there has been little consensus , either within or between specialties , on appropriate clinical evaluation ( 9 ) and management ( 10 ) of low back pain . Numerous studies show unexplained , large variations in use of diagnostic tests and treatments ( 11 , 12 ) . Despite wide variations in practice , patients seem to experience broadly similar outcomes , although costs of care can differ substantially among and within specialties ( 13 , 14 ) . The purpose of this guideline is to present the available evidence for evaluation and management of acute and chronic low back pain ( see Glossary ) in primary care setting s. The target audience for this guideline is all clinicians caring for patients with low ( lumbar ) back pain of any duration , either with or without leg pain . The target patient population is adults with acute and chronic low back pain not associated with major trauma . Children or adolescents with low back pain ; pregnant women ; and patients with low back pain from sources outside the back ( nonspinal low back pain ) , fibromyalgia or other myofascial pain syndromes , and thoracic or cervical back pain are not included . These recommendations are based on a systematic evidence review summarized in 2 background papers by Chou and colleagues in this issue ( 15 , 16 ) from an evidence report by the American Pain Society ( 17 ) . The evidence report ( 17 ) discusses the evidence for the evaluation , and the 2 background papers ( 15 , 16 ) summarize the evidence for management . Methods The literature search for this guideline included studies from MEDLINE ( 1966 through November 2006 ) , the Cochrane Data base of Systematic Review s , the Cochrane Central Register of Controlled Trials , and EMBASE . The literature search included all English- language articles reporting on r and omized , controlled trials of nonpregnant adults ( age > 18 years ) with low back pain ( alone or with leg pain ) of any duration that evaluated a target medication and reported at least 1 of the following outcomes : back-specific function , generic health status , pain , work disability , or patient satisfaction . The American College of Physicians ( ACP ) and the American Pain Society ( APS ) convened a multidisciplinary panel of experts to develop the key questions and scope used to guide the evidence report , review its results , and formulate recommendations . The background papers by Chou and colleagues ( 15 , 16 ) provide details about the methods used for the systematic evidence review . This guideline grade s its recommendations by using the ACP 's clinical practice guidelines grading system , adapted from the classification developed by the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) work group ( Appendix Table 1 ) ( 18 ) . The evidence in this guideline was first evaluated by the ACP/APS panel by using a system adopted from the U.S. Preventive Services Task Force for grading strength of evidence , estimating magnitude of benefits , and assigning summary ratings ( Appendix Tables 2 , 3 , and 4 ) ( 19 ) . The evidence was independently review ed by the ACP 's Clinical Efficacy Assessment Subcommittee . The ratings for individual low back pain interventions discussed in this guideline are summarized in Appendix Table 5 for acute low back pain ( 4 weeks ' duration ) . This guideline considered interventions to have proven benefits only when they were supported by at least fair- quality evidence and were associated with at least moderate benefits ( or small benefits but no significant harms , costs , or burdens ) . Figures 1 and 2 present an accompanying algorithm . Appendix Table 1 . The American College of Physicians Clinical Practice Guidelines Grading System Appendix Table 2 . Methods for Grading the Strength of the Overall Evidence for an Intervention Appendix Table 3 . Definitions for Estimating Magnitude of Effects Appendix Table 4 . Recommendations and Summary Ratings Appendix Table 5 . Level of Evidence and Summary Grade s for Noninvasive Interventions in Patients with Acute Low Back Pain Appendix Table 6 . Level of Evidence and Summary Grade s for Noninvasive Interventions in Patients with Chronic or Subacute Low Back Pain Figure 1 . Initial evaluation of low back pain ( LBP Figure 2 . Management of low back pain ( LBP Recommendations : Evaluation of Low Back Pain Recommendation 1 : Clinicians should conduct a focused history and physical examination to help place patients with low back pain into 1 of 3 broad categories : nonspecific low back pain , back pain potentially associated with radiculopathy or spinal stenosis , or back pain potentially associated with another specific spinal cause . The history should include assessment of psychosocial risk factors , which predict risk for chronic disabling back pain ( strong recommendation , moderate- quality evidence ) . More than 85 % of patients who present to primary care have low back pain that can not reliably be attributed to a specific disease or spinal abnormality ( nonspecific low back pain [ see Glossary ] ) ( 20 ) . Attempts to identify specific anatomical sources of low back pain in such patients have not been vali date d in rigorous studies , and classification schemes frequently conflict with one another ( 21 ) . Moreover , no evidence suggests that labeling most patients with low back pain by using specific anatomical diagnoses improves outcomes . In a minority of patients presenting for initial evaluation in a primary care setting , low back pain is caused by a specific disorder , such as cancer ( approximately 0.7 % of cases ) , compression fracture ( 4 % ) , or spinal infection ( 0.01 % ) ( 22 ) . Estimates for prevalence of ankylosing spondylitis in primary care patients range from 0.3 % ( 22 ) to 5 % ( 23 ) . Spinal stenosis ( see Glossary ) and symptomatic herniated disc ( see Glossary ) are present in about 3 % and 4 % of patients , respectively . The cauda equina syndrome ( see Glossary ) is most commonly associated with massive midline disc herniation but is rare , with an estimated prevalence of 0.04 % among patients with low back pain ( 24 ) . A practical approach to assessment is to do a focused history and physical examination to determine the likelihood of specific underlying conditions and measure the presence and level of neurologic involvement ( 24 , 25 ) . Such an approach facilitates classification of patients into 1 of 3 broad categories : nonspecific low back pain , back pain potentially associated with radiculopathy ( see Glossary ) or spinal stenosis ( suggested by the presence of sciatica [ see Glossary ] or pseudoclaudication ) , and back pain potentially associated with another specific spinal cause . The latter category includes the small proportion of patients with serious or progressive neurologic deficits or underlying conditions requiring prompt evaluation ( such as tumor , infection , or the cauda equina syndrome ) , as well as patients with other conditions that may respond to specific treatments ( such as ankylosing spondylitis or vertebral compression fracture ) . Diagnostic triage into 1 of these 3 categories helps guide subsequent decision making . Clinicians should inquire about the location of pain , frequency of symptoms , and duration of pain , as well as any history of previous symptoms , treatment , and response to treatment . The possibility of low back pain due to problems outside the back , such as pancreatitis , nephrolithiasis , or aortic aneurysm , or systemic illnesses , such as endocarditis or viral syndromes , should be considered . All patients should be evaluated for the presence of rapidly progressive or severe neurologic deficits , including motor deficits at more than 1 level , fecal incontinence , and bladder dysfunction . The most frequent finding in the cauda equina syndrome is urinary retention ( 90 % sensitivity ) ( 24 ) . In patients without urinary retention , the probability of the cauda equina syndrome is approximately 1 in 10000 . Clinicians should also ask about risk factors for cancer and infection . In a large , prospect i ve study from a primary care setting , a history of cancer ( positive likelihood ratio , 14.7 ) , unexplained weight loss ( positive likelihood ratio , 2.7 ) , failure to improve after 1 month ( positive likelihood ratio , 3.0 ) , and age older than 50 years ( positive likelihood ratio , 2.7 ) were each associated with a higher likelihood for cancer ( 26 ) . The posttest probability of cancer in patients presenting with back pain increases from approximately 0.7 % to 9 % in patients with a history of cancer ( not including nonmelanoma skin cancer ) . In patients with any 1 of the other 3 risk factors , the likelihood of cancer only increases to approximately 1.2 % ( 26 ) . Features predicting the presence of vertebral infection have not been well studied", "Long-term sickness absence and incapacity benefits ( disability pension ) rates have increased across industrialised countries . Effective measures are needed to support return to work . The recommendations of this guidance were informed by the most appropriate available evidence of effectiveness and cost-effectiveness . Public health evidence was provided by research using a variety of study design s that attempted to determine the outcome of a particular intervention by evaluating status before and after the intervention had been effected , and was not limited to r and omised control trials . Where the evidence base was depleted or underdeveloped , expert witnesses were called to give their opinion on the best available evidence and emerging interventions . The process enabled challenge and contestability from stakeholder groups at different points as the guidance was developed . Forty-five heterogeneous studies were included in the review of interventions to reduce long-term sickness absence and transitions from short-term to long-term absence ( mainly covering the former and also mainly examining musculoskeletal conditions ) . The analysis of evidence was restricted to descriptive synthesis . Three general themes emerged from an analysis of the studies that were more likely to report positive results : early interventions ; multidisciplinary approaches ; and interventions with a workplace component . Two further review s were undertaken , one on interventions to reduce the re-occurrence of sickness absence , which identified seven studies on lower back pain , and concluded that early intervention and direct workplace input are important factors . The final evidence review focused on six studies of interventions for those in receipt of incapacity benefit . The evidence was that work-focused interviews coupled with access to tailored support are effective and cost-effective interventions . Practitioners should consider the impact of interventions and management options on work ability for patients of working age . Work ability should be considered a key outcome for future intervention studies", "Study Design . Economic evaluation from a societal perspective conducted alongside a r and omized controlled trial with a follow-up of 52 weeks . Objective . To evaluate the cost effectiveness and cost utility of an intensive group training protocol compared with usual care physiotherapy in patients with nonspecific chronic low back pain . The intensive group training protocol combines exercise therapy , back school , and behavioral principles . Summary of Background Data . Two studies found a significant reduction in absenteeism for a grade d activity program in occupational health care . This program has not yet been evaluated in a primary care physiotherapy setting . Methods . Participating physical therapists in primary care recruited 114 patients with chronic nonspecific low back pain . Eligible patients were r and omized to either the protocol group or the guideline group . Outcome measures included functional status ( Rol and Morris Disability Question naire ) , pain intensity ( 11-point numerical rating scale ) , general perceived effect and quality of life ( EuroQol-5D ) . Cost data were measured with cost diaries and included direct and indirect costs related to low back pain . Results . After 52 weeks , the direct health care costs were significantly higher for patients in the protocol group , largely due to the costs of the intervention . The mean difference in total costs amounted to & OV0556 ; 233 ( 95 % confidence interval : & OV0556 ; −2.185 ; & OV0556 ; 2.764 ) . The cost-effectiveness planes indicated no significant differences in cost effectiveness between the 2 groups . Conclusion . The results of this economic evaluation showed no difference in total costs between the protocol group and the guideline group . The differences in effects were small and not statistically significant . At present , national implementation of the protocol is not recommended" ]

[ "PURPOSE To compare the efficacy of three different formulations containing Betamethasone Valerate versus placebo in the topical treatment of phimosis . As a secondary goal , we compared the outcomes after 30 and 60 days of treatment . MATERIAL S AND METHODS Two hundred twenty boys aged 3 to 10 years old with clinical diagnosis of phimosis were enrolled . Patients were r and omized to one of the following groups : Group 1 : Betamethasone Valerate 0.2 % plus Hyaluronidase ; Group 2 : Betamethasone Valerate 0.2 % ; Group 3 : Betamethasone Valerate 0.1 % or Group 4 : placebo . Parents were instructed to apply the formula twice a day for 60 days and follow-up evaluations were scheduled at 30 , 60 and 240 days after the first consultation . Success was defined as complete and easy foreskin retraction . RESULTS One hundred ninety-five patients were included at our final analysis . Group 1 ( N = 54 ) , 2 ( N = 51 ) and 3 ( N = 52 ) had similar success and improvement rates , all treatment groups had higher success rates than placebo ( N = 38 ) . After 60 days of treatment , total and partial response rates for Groups 1 , 2 and 3 were 54.8 % and 40.1 % , respectively , while placebo had a success rate of 29 % . Success and improvement rates were significantly better in 60 days when compared to 30 days . CONCLUSIONS Betamethasone Valerate 0.1 % , 0.2 % and 0.2 % in combination with Hyaluronidase had equally higher results than placebo in the treatment of phimosis in boys from three to ten years-old . Patients initially with partial or no response can reach complete response after 60 days of treatment", "Aim : Phimosis is a common paediatric urological disorder and often necessitates circumcision . We prospect ively evaluated local steroid therapy ( LST ) as the first choice therapy for such children", "Objectives Topical steroids have been advocated as an effective alternative treatment to circumcision in boys with phimosis . We evaluated the effectiveness of topical steroid therapy compared to a placebo neutral cream in 240 patients with phimosis . Methods A prospect i ve study was carried out over a 24-months period , on an out-patient basis on two groups of patients with phimosis . One-hundred twenty patients applied a steroid cream twice a day for 4 weeks , and another group of 120 pts used a placebo cream twice a day for 4 weeks . Patients were assigned to either group by a computer-generated r and om choice . Results All patients in our series completed the two treatment periods without interruption . At a median follow-up of 20 months ( 6–30 months ) therapeutic success was obtained in 43.75 % ( 99/240 ) of cases , independently of the protocol . In particular , therapeutic success was obtained in 65.8 % ( 79/120 ) of cases in the steroids group and in 16.6 % ( 20/120 ) of cases in the placebo group , the difference being statistically significant ( P topical steroids represent a good alternative to surgery in case of phimosis . Steroid therapy using monometasone furoate 0.1 % in our series gave better results that placebo with an overall efficacy of 65.8 % . In patients where a phimotic ring persist after steroid therapy , circumcision is m and atory", "OBJECTIVE Circumcision has been the traditional method of choice in the treatment of boys with phimosis . Recently , several published studies worldwide have focused their interest on more conservative approaches in management of this condition . These studies advocate the use of topical steroids in the phimotic foreskin . We aim ed to investigate the efficacy and safety of a medium potency corticosteroid in boys with different types of prepuce retractabilty . PATIENTS AND METHODS A prospect i ve study was performed involving boys referred to our hospital for possible phimosis between January 2004 and February 2008 . All were treated initially with fluticasone proprionate 0.05 % for a period of 4 - 8 weeks . Patients were reassessed after 6 months of follow up . RESULTS A total of 1185 boys with a diagnosis of phimosis were treated with fluticasone proprionate 0.05 % . Successful results were achieved in 1079 ( 91.1 % ) patients including boys with mild balanitis xerotica obliterans . No side effects were noticed . CONCLUSION Our results show that fluticasone proprionate 0.05 % , a mild potent corticosteroid , is effective and safe in the treatment of boys with different types of phimosis", "PURPOSE We report a prospect i ve r and omized study comparing the effects of highly potent and moderately potent topical steroids in treating pediatric phimosis . MATERIAL S AND METHODS A total of 70 boys 1 to 12 years old with phimosis were r and omly assigned to receive topical application of either betamethasone valerate 0.06 % ( a highly potent steroid ) or clobetasone butyrate 0.05 % ( a moderately potent steroid ) . Parents of the boys were instructed to retract the foreskin gently without causing pain , and to apply the topical steroids over the stenotic opening of the prepuce twice daily for 4 weeks , then for another 4 weeks if no improvement was achieved . Retractibility of the prepuce was grade d from 0 to 5 . Response to treatment was arbitrarily defined as improvement in the retractibility score of more than 2 points . RESULTS Mean treatment and followup periods were 4.3 and 19.1 weeks , respectively . The response rates in boys treated with betamethasone valerate and clobetasone butyrate were 81.3 % and 77.4 % , respectively ( p = 0.63 ) . Mean retractibility score decreased from 3.9 + /- 1.0 to 1.7 + /- 1.1 , and 4.2 + /- 1.0 to 1.9 + /- 1.0 in the betamethasone and clobetasone groups , respectively . Both steroids were effective in all age groups . Pretreatment retractibility score did not affect treatment outcomes . No adverse effect was encountered . CONCLUSIONS Highly potent and moderately potent topical steroids are of comparable effectiveness in treating phimosis . A less potent steroid may be considered first to decrease the risk of the potential adverse effects", "OBJECTIVE To further test the application of topical steroids in boys referred to a paediatric surgical practice with pathological , non-retractable foreskins diagnosed as phimosis . PATIENTS AND METHODS This prospect i ve study comprised two groups of 20 boys each ( mean age 4.1 years , range 3 - 6 ) diagnosed as having phimosis ; twice daily , a topical steroid ( 0.05 % betamethasone cream ) was applied on the narrowed preputial skin in the first group and a neutral cream ( Vaseline ) in the second ( control ) group . Patients were treated for 4 weeks and the retractability of the foreskin and any side-effects assessed . RESULTS Good retraction of the foreskin was achieved in 19 patients treated with betamethasone cream and the response was unsatisfactory in 16 patients from the control group ; these 16 boys and one 6-year-old boy treated with betamethasone were circumsized . There were no side-effects or problems after the application of either cream . CONCLUSION Treatment with 0.05 % betamethasone cream is a simple and safe method for the treatment of phimosis in boys older than 3 years . An early operation is necessary in cases of genuine phimosis when 1 month of treatment with topical steroids has failed . We strongly support the saying , \" The fortunate foreskin of an infant boy will usually be left well alone by everyone but its owner '", "PURPOSE Between 2 % and 5 % of uncircumcised boys have persistent or pathological phimosis . Traditional treatment is usually circumcision . Recently medical treatment with topical corticosteroids has become more popular . We evaluated the efficacy of the topical steroid triamcinolone compared to foreskin retraction with an emollient cream and verified the long-term success rate of these treatments . MATERIAL S AND METHODS We performed a double-blind , r and omized , placebo controlled study to compare 2-month twice daily treatment with emollient cream ( placebo group 1 ) vs 0.1 % triamcinolone ( experimental group 2 ) . Boys between ages 3 and 12 years with persistent or pathological phimosis were included in analysis . Study EXCLUSION criteria were previous treatment with topical corticosteroid , untreated balanitis and any known medical condition with immune system impairment . Patients were seen 2 , 4 and 12 months after treatment initiation . Success was defined as complete , easy foreskin retraction at 4 and 12 months . Statistical analysis was done using Fisher 's exact test . RESULTS We enrolled 63 patients , of whom 43 completed the study . Despite multiple attempts 20 patients had incomplete followup and were excluded from study . Placebo group 1 included 25 patients and triamcinolone group 2 included 21 . In group 1 the success rate was significantly lower than in group 2 ( 9 patients or 39 % vs 16 or 76 % , p = 0.0086 ) . At 2 months 5 and 16 nonresponders in groups 2 and 1 , respectively , were treated in nonblinded fashion with topical triamcinolone . In this subgroup 1 of 3 group 2 patients and 6 of 13 in group 1 achieved complete , easy retraction . Two and 1 patients were lost to followup in groups 1 and 2 , respectively . Circumcision was required in only 5 patients ( 11.6 % ) , including 4 ( 17.4 % ) initially in group 1 . No complications were noted in either group . CONCLUSIONS Triamcinolone is a highly effective and safe short-term treatment for persistent physiological or pathological phimosis . However , at long-term followup recurrence is frequent and not rare with triamcinolone and it may require re-treatment or circumcision", "The effect of hydrocortisone ( HC ) , the steroid of lowest potency , and physiotherapy ( PT ) on non-retractile physiologic phimosis ( PP ) and the reduction of subsequent recurrent UTI was evaluated in male infants with UTI . Seventy-eight male infants with febrile UTI and nonretractile PP were prospect ively r and omized into HC ( Plancol , n=39 ) and control ( Vaseline , n=39 ) groups . Topical application of HC as a thin film around the preputial margin twice a day for four weeks with PT was instructed . The response rate in the HC group was 89.7 % ( 35/39 ) , which was significantly higher than the rate ( 20.5 % ; 8/39 ) in the control group ( P response rate was much higher ( 96.1 % ) in the subgroup with PT than in the group without PT . Most of the response ( 88.5 % ) was observed within two weeks . During the following year , the recurrent rate of UTI was 7.1 % ( 2/28 ) in the infants with retractile prepuces , which was significantly less than than the rate ( 29.6 % ; 8/27 ) in infants with nonretractile prepuces ( P HC and PT for 2–4 weeks proved to be a simple , safe and effective treatment for nonretractile PP in infants with UTI , and this procedure was beneficial in reducing recurrent UTI", "OBJECTIVE To assess whether it is the steroid alone or the gentle physical retraction combined with ointment that is responsible for the excellent results observed with topical steroid treatment of unretractable foreskin . DESIGN Prospect i ve , r and omised , double-blind study . SETTING University hospital , Sweden . SUBJECTS 30 Boys r and omised to be treated with clobetasol propionate ( n = 15 ) or placebo ( n = 15 ) . INTERVENTIONS The boys were examined 1 , 2 and 6 months , respectively , after treatment . MAIN OUTCOME MEASURES Comparison between the effects of clobetasol propionate and placebo . RESULTS Two patients in the steroid group and one in the placebo group withdrew from the study . 10 Boys in the steroid group showed an improvement within 2 months . The remaining 3 boys had no effect and were circumcised . Histopathological examination showed lichen sclerosus et atrophicus . Seven boys in the placebo group improved . The 7 non-responders were prescribed clobetasol propionate ointment , and all 7 improved . CONCLUSION 17 of 27 boys referred with \" phimosis \" were successfully treated with an ointment and gentle traction . When clobetasol propionate was given the non-responders success rate was increased to 24/27 ( 89 % )", "PURPOSE We evaluate whether steroid application alone or retraction and hygiene are responsible for successful results in boys treated with topical steroids for phimosis . MATERIAL S AND METHODS A prospect i ve study was performed , which included a control group of 42 patients with phimosis seen at our outpatient department from January to June 1997 . During that time we trained the parent to retract and clean the foreskin only . From July 1997 to June 1998 topical steroid cream was prescribed in addition to retraction and hygiene in 276 boys with phimosis . All cases were divided into 3 subgroups of asymptomatic , symptomatic and buried penis . RESULTS The response rate was greater than 95 % in patients who received topical steroid treatment in addition to improved hygiene . Only 13 boys ( less than 5 % ) had no response to steroid treatment . Of the control patients 23 ( 55 % ) had no response to gentle retraction and personal hygiene . There was a significant difference ( p response rate between the study and control groups . However , the subgroup with a buried penis responded poorly to steroid , retraction and hygiene treatment . There was significant difference ( p response rate between the buried penis and other steroid groups but no significant difference ( p>0.05 ) in the control group . CONCLUSIONS Phimosis is a physiological condition in neonates due to natural adhesion between the foreskin and the glans . Chronic infection due to poor hygiene is responsible for most cases of childhood phimosis . Circumcision is the traditional treatment of choice for phimosis or unretractable foreskin , although it is not always desired by parents or surgeons . Topical steroid cream is an easy , safe and nonsurgical alternative for phimosis . However , boys with a buried penis are not good c and i date s for steroid treatment", "Phimosis has been defined as unretractable foreskin without adherences or a circular b and of tight prepuce preventing full retraction . We suggested a new treatment protocol combining betamethasone with stretching exercises to reduce the number of patients requiring surgery for phimosis . Between January 2003 and September 2004 , 247 boys aged 4 to 14 years ( mean 7.6 ) were included in this consecutive , prospect i ve , open study . Patients were treated with 0.05 % betamethasone cream applied to the distal aspect of the prepuce twice daily for the first 15 days , then once daily for 15 more days . Preputial gymnastics started 1 week after topical application of betamethasone . Ninety-six percent of patients receiving 1 or more cycles of betamethasone showed complete resolution of phimosis . There was a significant difference ( P response rate between the study and control groups . Only 10 boys in the study group had no response to steroid and stretching . Treatment with topical steroids , combined with stretching exercises , is a suitable alternative to surgical correction ( preputial plasty/circumcision )", "OBJECTIVE The objective of our study was to assess the efficacy of topical steroids in the treatment of phimosis and evaluate patients using the Diagnostic and Statistical Manual-III-Revised ( DSM-III-R ) test with the aim of eliminating castration anxiety of circumcision in the phallic period . METHODS One hundred and forty-nine children with phimosis who required circumcision were included the study . The average age of the children was 4.47 years . All children underwent the DSM-III-R test and their parents were question ed . Patients were separated r and omly into three groups . Group I comprised 51 children who would undergo circumcision ; group II comprised 50 children who would be treated with a topical corticosteroid ( 0.05 % bethamethasone cream ) twice daily for 1 month ; and group III comprised 48 children who would be treated with a topical placebo cream . On the 5th day of treatment , parents were told to retract the prepuce and were given hygiene routine instructions . Patients were seen immediately after treatment and again 2 months later . RESULTS In group II , 16 of the 50 children had non-retractable prepuce . Forty-two cases of phimosis were corrected after treatment . Eight patients received further monthly treatment and five benefited from the second course of treatment . In group III , 17 of the 48 patients had non-retractable prepuce and four had satisfactory results . Forty-four patients received placebo treatment for another month and eventually , 40 children underwent circumcision in this group . DSM-III-R test results showed a significant shift to anxiety in the circumcision group . The were no significant differences in the other groups . CONCLUSION Topical steroids for the treatment of phimosis is a highly effective treatment alternative to surgery . It avoids or delays circumcision and can be practised during the phallic period to decrease castration anxiety . The treatment is suitable for patients from any religious or cultural background", "Objective To evaluate the treatment of phimosis using topical steroid . Material and methods This was a follow-up study after a prospect i ve , r and omized , double-blind study . A total of 137 boys with phimosis were r and omly assigned to either betamethasone treatment or placebo for 4 weeks , with application of the cream twice daily . Non-responders to treatment were offered steroid treatment for a further 4 weeks . All patients were invited to a follow-up examination after 18 months . Results The mean pre-treatment phimosis grade s in the steroid and control groups were 5.08±0.66 and 4.97±0.70 , respectively . At the 4-week follow-up , 49 boys ( 74 % ) in the steroid group were cured , compared to only 31 ( 44 % ) in the control group . Fourteen boys were circumcised after another 4 weeks of treatment ; 43 of the remaining 57 boys ( 17 in the steroid group ; 40 in the control group ) had been cured . After a total of 92 boys took part in the 18-month follow-up study : 79 had been cured and 13 had suffered a relapse . Twenty-six patients did not took part in the follow-up investigation . No side-effects were noted . Conclusions When treatment is necessary for phimosis , we recommend application of topical steroid as first-line treatment because surgery can then be avoided in 85 % of cases . This first r and omized , double-blind , follow-up study shows that the treatment effect persists for at least 18 months" ]

[ "Abstract Purpose It was our hypothesis that patient-specific instrumentation ( PSI ) can improve the accuracy of the rotational alignment in TKA based on the concept of the system and on the potential to clearly identify pre-operatively during planning the classical anatomical l and marks that serve as references to set-up the rotation both for the femur and tibia . Material s and methods In this prospect i ve comparative r and omized study , 40 patients ( 20 in each group ) operated in our institution between September 2012 and January 2013 by the 2 senior authors were included . R and omization of patients into one of the two groups was done by the Hospital Informatics Department with the use of a systematic sampling method . All patients received the same cemented high-flex mobile bearing TKA . In the PSI group , implant position was compared to the planed position using previously vali date d dedicated software . The position of the implants ( frontal and sagittal ) was compared in the 2 groups on st and ard X-rays , and the rotational position was analysed on post-operative CT-scan . Results 90 % of the patients add tibial rotation where the variations were much higher . Mean HKA was 179 ° ( 171–185 ) in the PSI group with 4 outliers ( 2 varus : 171 ° and 172 ° :184 ° and 185 ° ) and 178.3 ° with 2 outliers ( 171 ° and 176 ° ) in the control group . No difference was observed between the two groups concerning the frontal and sagittal position of the implants on the ML and AP X-rays . No significant difference of femoral rotation was observed between the two groups with a mean of 0.4 ° in the PSI group and 0.2 ° in the control group ( p : n.s ) . Mean tibial rotation was 8 ° of internal rotation in the PSI group and 15 ° of internal rotation in the st and ard group ( p : n.s ) . Conclusion Based on our results , we were unable to confirm our hypothesis as PSI can not improve rotation in TKA . More work needs to be done to more clearly define the place of PSI in TKA , to keep on improving the accuracy of the system and to better define the individual targets in TKA in terms of frontal , sagittal and rotational positioning of the implant for each patient . Level of evidence Prospect i ve comparative r and omized study , Level II", "Background Recently , patient-specific guides ( PSGs ) have been introduced , cl aim ing a significant improvement in accuracy and reproducibility of component positioning in TKA . Despite intensive marketing by the manufacturers , this cl aim has not yet been confirmed in a controlled prospect i ve trial . Questions / purpose sWe ( 1 ) compared three-planar component alignment and overall coronal mechanical alignment between PSG and conventional instrumentation and ( 2 ) logged the need for applying changes in the suggested position of the PSG . Methods In this r and omized controlled trial , we enrolled 128 patients . In the PSG cohort , surgical navigation was used as an intraoperative control . When the suggested cut deviated more than 3 ° from target , the use of PSG was ab and oned and marked as an outlier . When cranial-caudal position or size was adapted , the PSG was marked as modified . All patients underwent long-leg st and ing radiography and CT scan . Deviation of more than 3 ° from the target in any plane was defined as an outlier . Results The PSG and conventional cohorts showed similar numbers of outliers in overall coronal alignment ( 25 % versus 28 % ; p = 0.69 ) , femoral coronal alignment ( 7 % versus 14 % ) ( p = 0.24 ) , and femoral axial alignment ( 23 % versus 17 % ; p = 0.50 ) . There were more outliers in tibial coronal ( 15 % versus 3 % ; p = 0.03 ) and sagittal 21 % versus 3 % ; p = 0.002 ) alignment in the PSG group than in the conventional group . PSGs were ab and oned in 14 patients ( 22 % ) and modified in 18 ( 28 % ) . Conclusions PSGs do not improve accuracy in TKA and , in our experience , were somewhat impractical in that the procedure needed to be either modified or ab and oned with some frequency . Level of Evidence Level I , therapeutic study . See instructions for authors for a complete description of levels of evidence", "BACKGROUND Patient-specific femoral and tibial cutting blocks produced with use of data from preoperative computed tomography ( CT ) or magnetic resonance imaging ( MRI ) scans have been employed recently to optimize component alignment in total knee arthroplasty . We report the results of a r and omized controlled trial in which CT scans were used to compare postoperative component alignment between patients treated with custom instruments and those managed with traditional instruments . METHODS The in-hospital data and early clinical outcomes , including Knee Society scores , were determined in a r and omized clinical trial of forty-seven patients who had undergone a total of forty-eight primary total knee arthroplasties with patient-specific instruments ( twenty-two knees ) or st and ard instruments ( twenty-six knees ) . Orientation of the implants was compared by using three-dimensional CT data . RESULTS No significant differences were found between the study and control groups with respect to any clinical outcome after a minimum of six months of follow-up . The patient-specific tibial cutting block was ab and oned in favor of a st and ard external alignment jig in seven of the twenty-two study knees because of possible malalignment . A detailed analysis of intent-to-treat and per- protocol groups of study and control knees did not show any significant improvement in component alignment , including femoral component rotation in the axial plane , in the patients treated with the custom instruments . The percentage of outliers -- defined as less than -3 ° or more than 3 ° from the correct orientation of the tibial slope -- was significantly higher in the group treated with use of patient-specific blocks than it was in the control group , in both the intent-to-treat ( 32 % versus 8 % , p = 0.032 ) and the per- protocol ( 47 % versus 6 % , p = 0.0008 ) analysis . CONCLUSIONS There were no significant improvements in clinical outcomes or knee component alignment in patients treated with patient-specific cutting blocks as compared with those treated with st and ard instruments . The group treated with patient-specific cutting blocks had a significantly higher prevalence of malalignment in terms of tibial component slope than the knees treated with st and ard instruments ", "Background Patient-specific instrumentation potentially improves surgical precision and decreases operative time in total knee arthroplasty ( TKA ) but there is little supporting data to confirm this presumption . Questions / purpose sWe asked whether patient-specific instrumentation would require infrequent intraoperative changes to replicate a single surgeon ’s preferences during TKA and whether patient-specific instrumentation guides would fit securely . Methods We prospect ively evaluated the plan and surgery in 60 patients treated with 66 TKAs performed with patient-specific instrumentation and recorded any changes . A subset of six postoperative radiographic changes to the femoral and tibial components ( implant size , coronal and sagittal alignment ) was analyzed to determine if surgeon intervention was beneficial . Each guide was evaluated to determine fit . We compared patient demographics and implant sizing in the patient-specific instrumentation group with a control group in which traditional instrumentation was used . Results We recorded 161 intraoperative changes in 66 knee arthroplasties ( 2.4 changes/knee ) performed with patient-specific instrumentation . The predetermined implant size was changed intraoperatively in 77 % of femurs and 53 % of tibias . We identified a subset of 95 intraoperative changes that could be radiographically evaluated to determine if our changes were an improvement or detriment to reaching goal alignment . Eighty-two of the 95 changes ( 86 % ) made by the surgeon were an improvement to the recommended alignment or size of patient-specific instrumentation . The guide did not fit securely on eight femurs ( 12 % ) and three tibias ( 5 % ) . Tourniquet time and blood loss were not improved with patient-specific instrumentation . Conclusions We caution surgeons against blind acceptance of patient-specific instrumentation technology without supportive data .Level of Evidence Level III , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence", "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", "The primary purpose of this prospect i ve , r and omized study was to determine if patient-specific instrumentation ( PSI ) for total knee arthroplasty ( TKA ) shortened surgical time . Secondarily the number of instrument trays and alignment were also compared to cases performed with traditional instrumentation ( TI ) . Fifty-two cases ( 26 per group ) were r and omized and videotaped to measure the length of surgery , as well as each individual surgical step . Component alignment and mechanical axis was measured radiographically for each patient . Total surgical time was over 4 minutes shorter for patients in the TI group ( 57.4 minutes vs. 61.8 minutes ; P instrument trays were used in the TI group ( 7.3 vs. 2.5 ; P difference in mechanical alignment between groups on postoperative long alignment radiographs ( P=0.77 ) . In conclusion , PSI did not shorten surgical time or improve alignment compared with TI in this prospect i ve , r and omized trial , but did reduce the required number of trays", "Patient specific instrumentation ( PSI ) was developed to increase total knee arthroplasty ( TKA ) accuracy and efficiency . The study purpose was to compare immediate post-operative mechanical alignment , achieved using PSI , with conventional and computer assisted surgery ( CAS ) instruments in high volume TKA practice s. This prospect i ve , multicenter , non-r and omized study accrued 66 TKA patients using PSI . A computed tomography ( CT ) based algorithm was used to develop the surgical plan . Sixty-two percent were females , 99 % were diagnosed with osteoarthritis , average age at surgery was 66 years , and 33 was the average body mass index . A historical control group was utilized that underwent TKA using conventional instruments ( n=86 ) or CAS ( n=81 ) , by the same set of surgeons . Postoperative mechanical alignment was comparable across the groups . Operative time mean and variance were significant", "Abstract Purpose The aim of this study was to investigate the post-operative radiological outcomes of patient-specific instrumentation ( PSI ) surgery versus conventional total knee arthroplasty ( TKA ) . Methods Sixty patients scheduled for a primary TKA were prospect ively divided into PSI or conventional technique . Coronal and sagittal radiographic long limb films were taken post-operatively . The accepted values for normal alignment were 180 ° ± 3 ° for hip-knee-ankle angle ; 90 ° ± 3 ° for coronal femoral component angle or coronal tibia component angle ; 0 ° to 3 ° flexion for sagittal femoral component angle and 0 ° to 7 ° posterior slope for sagittal tibia component angle . Results For hip-knee-ankle angle , there were 21 % more outliers in the PSI group compared to the conventional group ( p = 0.045 ) . Most of these outliers had valgus deformity in the PSI group and varus deformity in the conventional group ( p = 0.045 ) . For implant placement , there was no difference in the proportion of outliers between the two groups . There was also no difference in the duration of surgery . Conclusions This study showed that PSI surgery is associated with a larger proportion of outliers for lower limb alignment . PSI surgery as an alternative to conventional TKA is not advisable . Level of evidence II", "UNLABELLED Patient-specific cutting guides ( PSCG ) are an extension of preoperative planning for total knee arthroplasty ( TKA ) . We wanted to evaluate their contribution to postoperative lower limb alignment . This study involved primary TKA cases being performed with PSCG between 10/05/2010 and 05/03/2013 and then followed prospect ively . The analysis involved the PSCG usage and postoperative measurement of the patient 's HKA , medial distal femoral joint angle ( MDFA ) and medial proximal tibia joint angle ( MPTA ) . Of the 104 eligible cases , 68 were included ; 11 of these cases were not performed completely with the PSCG as initially planned . Thus we compared these 11 cases with the 57 where PSCG were used . The preoperative HKA in the included cases was 175.8 ° ± 7.8 ; the postoperative angles on average were 179.2 ° ± 2.9 for the HKA , 89.9 ° ± 1.6 for the MDFA and 89.0 ° ± 2.3 for the MPTA . The average postoperative deviation from the target values was 2.22 ° ± 2.14 for the HKA angle , 1.07 ° ± 1.15 for the MDFA and 1.66 ° ± 1.90 for the MPTA . There were no significant differences between the two groups in any of the measurements . The lower limb alignment goal was achieved in 50 cases ( 73 % ) , with 41 of these achieved with PSCG ( 82 % ) . Of the 18 cases where the target was not achieved , PSCG were used 16 times ( 88 % ) . In this study cohort , lower limb alignment was not significantly closer to an HKA of 180 ° or achieved more often with the use of PSCG versus st and ard instrumentation . Since the results of the two groups can be superimposed , we found no evidence that use of PSCG improves postoperative lower limb alignment . LEVEL OF EVIDENCE IV . STUDY TYPE Cohort", "Purpose The aim of this study was to compare radiological results of total knee arthroplasties ( TKAs ) performed with patient-specific computed tomography (CT)-based instrumentation and conventional technique . The main study hypothesis was that CT-based patient-specific instrumentation ( PSI ) increases the accuracy of TKA . Methods A prospect i ve , r and omized controlled trial was carried out between January and December 2011 . A group of 112 patients who met the inclusion and exclusion criteria were enrolled in this study and r and omly assigned to an experimental or control group . The experimental group comprised 52 patients operated on with the aid of the Signature ™ CT-based implant positioning system . The control group consisted of 60 patients operated on using conventional instrumentation . The radiographic evaluation of implant positioning and overall coronal alignment was performed 12 months after the surgery by using st and ing anteroposterior radiographs of the entire lower limb and st and ard lateral radiographs . Results Of the 112 patients initially enrolled for the study , 95 were included in the subsequent analyses . There were no statistically significant differences between groups in respect to coronal and sagittal component positioning and overall coronal alignment , except for frontal tibial component positioning . For this parameter , better results were obtained in the control group , with borderline statistical significance . Conclusions Our study did not reveal superiority of the CT-based PSI system over conventional instrumentation . Further high- quality investigations of patient-specific systems are absolutely indispensable to assess their utility for TKA . In our opinion , the surgeon applying PSI technology is required to have advanced knowledge and considerable experience with the conventional method", "The purpose of the current prospect i ve , r and omized study was to compare the value of a new mechanically aligned patient-matched instrument system for total knee arthroplasty ( TKA ) ( Visionaire ; Smith & Nephew , Inc , Memphis , Tenn ) ( VIS ) to that of st and ard TKA surgical instrumentation ( STD ) . Twenty-nine primary TKA patients were enrolled and completed surgery ( 15 VIS and 14 STD ) . Postoperatively , mechanical alignment was significantly closer to neutral zero in the VIS group ( 1.7 ° vs 2.8 ° ; P = .03 ) . Furthermore , the VIS group demonstrated significant reductions in duration of hospital stay , operative time , incision length , and number of used instrument trays ( P < .05 ) . Although additional research is underway to confirm these preliminary results , this evidence suggests that patient-matched instrumentation may support repeatable improvements in surgical accuracy and hospital efficiency", "Abstract Purpose The purpose of the study was to evaluate the accuracy of the planning of the patient-specific pin guides in total knee arthroplasty ( TKA ) . This planning was performed primarily by a technician of the company and offered to the surgeon . All parameters of the implantation can either be modified or accepted by the surgeon . The hypothesis was that the plan needs preoperative intervention by the surgeon . Methods A prospect i ve study in 50 patients was carried out . All patients received the same posterior-stabilised implant with patient-specific instrumentation . All surgical parameters ( coronal , sagittal , rotational alignment , femoral and tibial resection levels and implant sizes ) were checked by the orthopaedic surgeon and changed if necessary . Results Preoperatively , the femoral size was changed in 8 patients ( 16 % ) , the femoral flexion in 23 patients ( 46 % ) , the femoral shift in 34 patients ( 68 % ) , the tibial size in 24 patients ( 48 % ) and the tibial rotation in all patients . The epicondylar axis was accepted in 47 patients ( 94 % ) in the technician plan . Mean planning time was 8 ± 4 min . Intraoperatively , the femoral anterior – posterior size was in 50 patients ( 100 % ) the same as in the surgeon and in 42 patients ( 84 % ) the same as in the technician plan ( p = 0.003 ) . The tibial component implanted was in 42 patients ( 84 % ) the same as in the surgeon and in 19 patients ( 38 % ) the same as in the technician plan ( p A femoral distal recut was necessary in 31 patients ( 62 % ) and a change of the tibial proximal cut in 17 patients ( 34 % ) during surgery . Intraoperatively , no changes of the femoral and tibial alignment , the femoral anterior – posterior size , the femoral flexion , the femoral shift , the femoral and tibial rotation were necessary . Postoperatively , the coronal mechanical overall axis was within ±3 ° in 47 patients ( 94 % ) with a maximum deviation of 5.6 ° . Conclusions Significant changes of the technician plan were necessary to get an accurate preoperative plan . Intraoperative changes were significant less compared to the surgeon than to the technician plan . No major changes ( alignment , femoral anterior – posterior size and rotation ) of the surgeon plan were necessary . Surgeons using patient-specific pin guides in TKA may verify the default plan provided by the technician . A blind reply on the technician plan may be not recommended . Level of evidence Therapeutic study , Level III", "Abstract Objective To determine whether poor reporting of methods in r and omised controlled trials reflects on poor methods . Design Observational study . Setting Reports of r and omised controlled trials conducted by the Radiation Therapy Oncology Group since its establishment in 1968 . Participants The Radiation Therapy Oncology Group . Outcome measures Content of reports compared with the design features described in the protocol s for all r and omised controlled trials . Results The method ological quality of 56 r and omised controlled trials was better than reported . Adequate allocation concealment was achieved in all trials but reported in only 42 % of papers . An intention to treat analysis was done in 83 % of trials but reported in only 69 % of papers . The sample size calculation was performed in 76 % of the studies , but reported in only 16 % of papers . End points were clearly defined and α and βerrors were prespecified in 76 % and 74 % of the trials , respectively , but only reported in 10 % of the papers . The one exception was the description of drop outs , where the frequency of reporting was similar to that contained in the original statistical files of the Radiation Therapy Oncology Group . Conclusions The reporting of method ological aspects of r and omised controlled trials does not necessarily reflect the conduct of the trial . Review ing research protocol s and contacting trialists for more information may improve quality assessment", "BACKGROUND Robotic-assisted total hip replacement has become a common method of implantation , especially in Europe . It frequently has been postulated that robotic reaming would result in an improved clinical outcome due to the better fit of the prosthesis , but that has never been demonstrated in a prospect i ve study , to our knowledge . The purpose of this study was to compare robotic-assisted implantation of a total hip replacement with conventional manual implantation . METHODS One hundred and fifty-four patients scheduled for total hip replacement were r and omly assigned to undergo either conventional manual implantation of an S-ROM prosthesis ( eighty patients ) or robotic-assisted implantation of such a prosthesis ( seventy-four patients ) . The five-axis ROBODOC was used for the robotic-assisted procedures . Preoperatively as well as at three , six , twelve , and twenty-four months after surgery , the scores according to the Harris and Merle d'Aubigné systems and the Mayo clinical score were determined . Radiographs made at these intervals were analyzed for evidence of loosening , prosthetic alignment , and heterotopic ossification . RESULTS Thirteen ( 18 % ) of the seventy-four attempted robotic implantations had to be converted to manual implantations as a result of failure of the system . The duration of the robotic procedures was longer than that of the manual procedures ( mean and st and ard deviation,107.1 + /- 29.1 compared with 82.4 + /- 23.4 minutes , p Limb-length e quality ( mean discrepancy , 0.18 + /- 0.30 compared with 0.96 + /- 0.93 cm , p varus-valgus orientation of the stem ( mean angle between the femur and the shaft of the prosthesis , 0.34 degrees + /- 0.67 degrees compared with 0.84 degrees + /- 1.23 degrees , p robotic procedures . At six months , slightly more heterotopic ossification was seen in the group treated with robotic implantation . The group treated with robotic implantation had a better Mayo clinical score at six and twelve months and a better Harris score at twelve months ; however , by twenty-four months , no difference was found between the groups with regard to any of the three scores . Dislocation was more frequent in the group treated with robotic implantation : it occurred in eleven of the sixty-one patients in that group compared with three of eighty in the other group ( p . Recurrent dislocation and pronounced limping were indications for revision surgery in eight of the sixty-one patients treated with robotic implantation compared with none of the seventy-eight ( excluding two with revision for infection ) treated with manual insertion ( p Rupture of the gluteus medius tendon was observed during all of the revision operations . CONCLUSIONS The robotic-assisted technology had advantages in terms of preoperative planning and the accuracy of the intraoperative procedure . Disadvantages were the high revision rate ; the amount of muscle damage , which we believe was responsible for the higher dislocation rate ; and the longer duration of surgery . This technology must be further developed before its widespread usage can be justified", "Patient-specific cutting guides ( PSCGs ) are design ed to improve the accuracy of alignment of total knee replacement ( TKR ) . We compared the accuracy of limb alignment and component positioning after TKR performed using PSCGs or conventional instrumentation . A total of 80 patients were r and omised to undergo TKR with either of the different forms of instrumentation , and radiological outcomes and peri-operative factors such as operating time were assessed . No significant difference was observed between the groups in terms of tibiofemoral angle or femoral component alignment . Although the tibial component in the PSCGs group was measurably closer to neutral alignment than in the conventional group , the size of the difference was very small ( 89.8 ° ( sd 1.2 ) vs 90.5 ° ( sd 1.6 ) ; p = 0.030 ) . This new technology slightly shortened the bone-cutting time by a mean of 3.6 minutes ( p and the operating time by a mean 5.1 minutes ( p = 0.019 ) , without tangible differences in post-operative blood loss ( p = 0.528 ) or need for blood transfusion ( p = 0.789 ) . This study demonstrated that both PSCGs and conventional instrumentation restore limb alignment and place the components with the similar accuracy . The minimal advantages of PSCGs in terms of consistency of alignment or operative time are unlikely to be clinical ly relevant", "Background Patient-specific CT-based instrumentation may reduce implant malpositioning and improve alignment in TKA . However , it is not known whether this innovation is an advance that benefits patients . Questions / purpose sWe evaluated ( 1 ) the precision of patient-specific TKA by comparing the incidence of outliers in postoperative alignment between TKAs using patient-specific instruments and TKAs using conventional instruments , and ( 2 ) the reliability of patient-specific instruments by intraoperatively investigating whether the surgery could be completed with patient-specific instruments alone . Methods In this r and omized controlled trial , we compared patient-specific TKA instruments from one manufacturer ( n = 50 ) with conventional TKA instruments ( n = 50 ) . Postoperative hip-knee-ankle angles , femoral component rotation , and coronal and sagittal alignments of each component were measured . The validity of the patient-specific instrument was examined using cross-checking procedures with conventional instruments during the surgeries . When the procedure could not be completed accurately with patient-specific instruments , the procedure was converted to TKA using conventional instruments , and the frequency of this occurrence was tallied . Results Outliers in the hip-knee-ankle angle were comparable between groups ( 12 % in the patient-specific instrument group and 10 % in the conventional instrument group ) . Other parameters such as sagittal alignment and femoral component rotation did not differ in terms of outliers . Patient-specific guides were ab and oned in eight knees ( 16 % ) during the surgery because of malrotation of the femoral components and decreased slope of the tibia . Conclusions Accuracy was comparable between TKAs done with patient-specific instruments and those done with conventional instruments . However , the patient-specific instrument procedures had to be aborted frequently , incurring expenses that did not benefit patients .Level of Evidence Level II , therapeutic study . See Instructions for Authors for a complete description of levels of evidence" ]

[ " Objectives To evaluate the effect of association of tamsulosin/tadalafil taken daily compared with tamsulosin/placebo in the lower urinary tract with urodynamic study ( UDS ) . Methods All patients underwent baseline UDS before r and omization to tamsulosin 0.4 mg/tadalafil 5 mg ( Group 1 ; n = 20 ) or tamsulosin 0.4 mg/placebo ( Group 2 ; n = 20 ) once daily for 30 days . End-of- study UDS were performed on completion of the treatment period . The primary end point was to demonstrate changes in urodynamic variables in the voiding phase , detrusor pressure at maximum flow ( PdetQmax ) , and maximum flow rate ( Qmax ) , from baseline to week four . Results The primary outcome measure of this clinical trial , PdetQmax , showed a significant reduction in tamsulosin/tadalafil group ( 13 ± 17.0 ) compared to tamsulosin/placebo ( −1.2 ± 14.35 ) group ( P = 0.03 ) . Qmax increased in both groups , tamsulosin/tadalafil ( 1.0 ± 2.4 ) and tamsulosin/placebo ( 1.4 ± 2.4 ) , but the difference was not significant between treatment groups ( P = 0.65 ) . Total IPSS , storage , and voiding sub-score improved significantly in tamsulosin/tadalafil compared with tamsulosin/placebo group . Conclusions The association of tamsulosin/tadalafil reduces detrusor pressure at maximum flow without changing the maximum flow rate during micturition and significantly improves lower urinary tract symptoms compared with the isolated use of tamsulosin", "This prospect i ve study evaluated the safety of tadalafil 5 mg taken once a day in terms of hypotensive side effects and whether it improves lower urinary tract symptoms ( LUTS ) and restores sexual function in patients with erectile dysfunction who are receiving concomitant α-blocker ( AB ) therapy for benign prostatic hyperplasia ( BPH ) . A total of 158 LUTS/BPH patients receiving AB therapy for ≥3 months were given tadalafil 5 mg once a day . Before treatment with tadalafil ( V1 ) , and 4 weeks ( V2 ) and 12 weeks ( V3 ) after starting tadalafil , blood pressure , heart rate , International Prostate Symptom Score ( IPSS ) , maximal urine flow rate ( Qmax ) , postvoiding residual urine volume , and International Index of Erectile Function ( IIEF-5 ) score were measured . Of the 158 LUTS/BPH patients , a total of 119 completed the trial . Blood pressure ( systolic and diastolic ) and heart rate did not change . IPSS and IIEF-5 scores improved significantly , but Qmax and postvoiding residual urine volume did not ; however , in the 39 men with a low baseline Qmax ( ≤10 mL/s ) , Qmax rose significantly from 7.97 ± 1.44 mL/s ( baseline ) to 8.91 ± 1.60 mL/s ( V3 ; P = .012 ) . The remaining patients ( baseline Qmax > 10 mL/s ) did not change . At V2 and V3 , adverse side effects were observed in 10 men ( 7.30 % ) and 6 men ( 5.04 % ) , respectively . Facial flushing was the most common adverse side effect ( 6 men at V2 and 4 men at V3 ) , followed by headache ( 2 men each at V2 and V3 ) and dizziness ( 2 men at V2 ) . Two patients dropped out of the study because of adverse side effects . In conclusion , tadalafil 5 mg once a day in combination with AB appeared to have few adverse effects on hypotensive events and can improve LUTS and restore sexual function ", "Summary Aims / objectives : In the BESIDE study , combination therapy ( antimuscarinic [ solifenacin ] and β3‐adrenoceptor agonist [ mirabegron ] ) improved efficacy over solifenacin monotherapy without exacerbating anticholinergic side effects in overactive bladder ( OAB ) patients ; however , a potential synergistic effect on the cardiovascular ( CV ) system requires investigation . Methods OAB patients remaining incontinent despite daily solifenacin 5 mg during 4‐week single‐blind run‐in , were r and omised 1:1:1 to double‐blind daily combination ( solifenacin 5 mg/mirabegron 25 mg , increasing to 50 mg after week 4 ) , solifenacin 5 or 10 mg for 12 weeks . CV safety assessment s included frequency of CV‐related treatment‐emergent adverse events ( TEAEs ) , change from baseline in vital signs ( systolic blood pressure [ SBP ] , diastolic blood pressure [ DBP ] , pulse rate ) and electrocardiogram ( ECG ) parameters . Results The frequency of hypertension , tachycardia and ECG QT prolongation , respectively , was low and comparable across combination ( 1.1 % , 0.3 % , 0.1 % ) , solifenacin 5 mg ( 0.7 % , 0.1 % , 0.1 % ) , and solifenacin 10 mg groups ( 0.8 % , 0 % , 0.1 % ) . Adjusted mean ( SE ) change from baseline to end of treatment ( EoT ) in SBP , DBP , and pulse rate with combination ( 0.07 mm Hg [ 0.38 ] , −0.35 mm Hg [ 0.26 ] , 0.47 bpm [ 0.28 ] ) , solifenacin 5 mg ( −0.93 mm Hg [ 0.38 ] , −0.45 mm Hg [ 0.26 ] , 0.43 bpm [ 0.28 ] ) and solifenacin 10 mg ( −1.28 mm Hg [ 0.38 ] , −0.48 mm Hg [ 0.26 ] , 0.27 bpm [ 0.28 ] ) was generally comparable , with the exception of a mean treatment difference of ~1 mm Hg in SBP between combination and solifenacin monotherapy ; SBP was unchanged with combination and decreased with solifenacin monotherapy . Mean changes from baseline to EoT in ECG parameters were generally similar across treatment groups , except for QT interval corrected using Fridericia 's formula , which was higher with solifenacin 10 mg ( 3.30 mseconds ) vs. combination ( 0.49 mseconds ) and solifenacin 5 mg ( 0.77 mseconds ) . Conclusion The comparable frequency of CV‐related TEAEs , changes in vital signs and ECG parameters indicates no synergistic effect on CV safety outcomes when mirabegron and solifenacin are combined", "PURPOSE We examined the effects of doxazosin , finasteride and combination therapy among men with benign prostatic hyperplasia on quality of life assessed with MOS-SF-36 ( Medical Outcomes Study Short-Form 36 ) and 2 disease specific instruments ( BII , benign prostatic hyperplasia Impact Index and I-PSS-QoL , International Prostate Symptom Score-QoL ) during 4 years . MATERIAL S AND METHODS The MTOPS ( Medical Therapy of Prostatic Symptoms ) study was a multicenter , r and omized , double-blind , placebo controlled clinical trial with a primary outcome of time to benign prostatic hyperplasia progression . Change in quality of life was a secondary outcome . A total of 2,872 men enrolled in the MTOPS study who had 3 baseline quality of life measures and at least 1 followup measure by any of the quality of life instruments were analyzed . RESULTS Compared with men assigned to placebo , men assigned to doxazosin and combination experienced a statistically significant improvement in the BII at year 4 . Men assigned to each of the drug groups also experienced a significant improvement in the I-PSS-QoL compared with those assigned to placebo . Considering longitudinal changes during 4 years , a significant improvement in BII and I-PSS-QoL scores was observed in men assigned to the drug groups compared with those assigned to placebo . However , there were no significant differences for the MOS-SF-36 subscales and summary scores when drug groups were compared with the placebo group . CONCLUSIONS The quality of life of men treated with doxazosin , finasteride , and the drugs combined generally improved when assessed with the BII and the I-PSS-QoL compared with those treated with placebo . Quality of life did not show improvement when measured by the MOS-SF-36", "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 )", "Objectives The aim of this study was to compare outcomes using two preference-based measures of health status ( EQ-5D-5L and OAB-5D ) in patients with overactive bladder ( OAB ) treated with solifenacin plus mirabegron or solifenacin monotherapy in the BESIDE trial . Methods Patients with OAB who remained incontinent after 4 weeks ’ treatment with solifenacin 5 mg were r and omized 1:1:1 to combination treatment ( solifenacin 5 mg plus mirabegron [ 25 mg for the first 4 weeks/50 mg for the last 8 weeks ] ) , solifenacin 5 mg , or solifenacin 10 mg . EQ-5D-5L and OAB-q were administered at baseline , weeks 4 , 8 , 12 , and end of treatment ( EoT ) . OAB-5D scores were derived from OAB-q results . Responder analysis was carried out using several definitions of minimally important difference . Results A total of 2054 patients received one or more doses of study treatment ( combination , n = 694 ; solifenacin 5 mg , n = 684 ; solifenacin 10 mg , n = 676 ) . EQ-5D-5L Index mean score changes ( from baseline to EoT ) were greater with combination ( 0.059 ) than with solifenacin 5 mg ( 0.040 ) and 10 mg ( 0.044 ) monotherapy , but the differences were not statistically significant . A significantly greater improvement was observed for combination on OAB-5D ( 0.107 vs 0.085 for 5 mg , and 0.087 for 10 mg ; p ≤ 0.01 ) . The dimensions most improved overall were anxiety/depression , pain/discomfort , and usual activities on EQ-5D-5L , and urge , urine loss , and coping on OAB-5D . The proportion of responders was significantly greater with combination compared with monotherapy using OAB-5D only . Conclusions Improvements were observed in all study arms on both the EQ-5D-5L and OAB-5D , although only the OAB-5D showed a statistically significant benefit for combination versus solifenacin monotherapy . Combining generic and condition-specific preference-based health status measures allowed for assessment of dimensions that were particularly relevant to this patient population , while permitting comparison with outcomes from other studies , treatments , and population s via EQ-5D", "Twenty-nine postmenopausal women with slight to severe stress urinary incontinence and estrogen deficiency symptoms in the urogenital tract were treated with estriol , p.o . 4 mg once daily , and either phenylpropanolamine ( PPA ) , p.o . 50 mg twice daily , or placebo for periods of 6 weeks according to a r and omized double-blind crossover schedule . At urodynamic recordings the maximum urethral closure pressure increased by 22 % with combined treatment ( p less than 0.001 ) and an additional effect of PPA to estriol was shown ( p = 0.022 ) . The pressure transmission ratio increased , by about 15 % , with both treatments ( p less than 0.07 ) . The number of leakage episodes was reduced by 28 % with combined treatment ( p = 0.007 ) , but not with estriol alone ( p = 0.08 ) . Both combined treatment and estriol alone reduced significantly ( p less than 0.01 ) the urinary incontinence complaints . Twelve women ( 43 % ) preferred combined treatment , while 7 ( 25 % ) preferred estriol alone . In women with initially slight to very severe urine loss , combined treatment reduced also ( p = 0.02 ) the amount of urine loss , measured at a st and ardized physical stress test . Signs of estrogen deficiency in vulva , vagina and urethra were reduced , 75 % ( p less than 0.001 ) or 65 % ( p = 0.001 ) with estriol given in combination with PPA or alone . Maturation index of both urethral and vaginal epithelium displayed significant changes . It is concluded that the combined treatment , PPA + estriol , by affecting both the muscular and mucosal factor of the urethra , is more effective than estriol alone for treatment of female stress urinary incontinence in the postmenopausal ages", "Purpose This large dose-ranging study explored the benefits of different combinations of mirabegron and solifenacin on health-related quality of life ( HRQoL ) , based on patient-reported outcomes ( PROs ) , and patients ( ‘ responders ’ ) achieving clinical ly meaningful improvements in efficacy and HRQoL. Methods SYMPHONY ( NCT01340027 ) was a Phase II , placebo- and monotherapy-controlled , dose-ranging , 12-week trial . Adult patients with overactive bladder ( OAB ) for ≥3 months were r and omized to 1 of 12 groups : 6 combination ( solifenacin 2.5/5/10 mg + mirabegron 25/50 mg ) , 5 monotherapy ( solifenacin 2.5/5/10 mg , or mirabegron 25/50 mg ) , or placebo . Change from baseline to end of treatment was assessed , versus placebo and solifenacin 5 mg in : PROs ( OAB-q [ Symptom Bother/total HRQoL ] and Patient Perception of Bladder Condition score ) , and responders achieving minimally important differences ( MIDs ) in PROs and predetermined clinical ly meaningful improvements in efficacy ( e.g. Full Analysis Set included 1278 patients . Combination therapy of solifenacin 5/10 mg + mirabegron 25/50 mg significantly improved PROs versus solifenacin 5 mg and placebo , and significantly more responders achieved MIDs in PROs and efficacy . Micturition frequency normalization was approximately twofold greater with 10 + 25 mg ( OR 2.06 [ 95 % CI 1.11 , 3.84 ; p = 0.023 ] ) and 5 + 50 mg ( OR 1.91 [ 95 % CI 1.14 , 3.21 ; p = 0.015 ] ) versus solifenacin 5 mg . Conclusion Combining mirabegron 25/50 mg and solifenacin 5/10 mg improves objective and subjective efficacy outcomes compared with placebo or solifenacin 5 mg", "To evaluate the potential of solifenacin 5 mg combined with mirabegron 25 or 50 mg to deliver superior efficacy compared with monotherapy , with acceptable tolerability , in the general overactive bladder ( OAB ) population with urinary incontinence ( UI )", "BACKGROUND Storage symptoms are particularly bothersome in men with lower urinary tract symptoms ( LUTS ) but may not be adequately treated by α-blocker monotherapy . OBJECTIVE To assess the efficacy and safety of a fixed-dose combination ( FDC ) of solifenacin and an oral controlled absorption system ( OCAS ) formulation of tamsulosin compared with placebo and compared with tamsulosin OCAS ( TOCAS ) monotherapy in men with moderate to severe storage symptoms and voiding symptoms . DESIGN , SETTING , AND PARTICIPANTS A double-blind 12-wk phase 3 study in 1334 men with storage and voiding LUTS : total International Prostate Symptom Score ( IPSS ) ≥ 13 , maximum urinary flow rate ( Qmax ) 4.0 - 12.0 ml/s , two or more urgency episodes per 24 h of Patient Perception of Intensity of Urgency Scale grade 3 or 4 , and eight or more micturitions per 24h . INTERVENTION Patients were r and omised to placebo , TOCAS 0.4 mg , FDC solifenacin 6 mg plus TOCAS 0.4 mg , or FDC solifenacin 9 mg plus TOCAS 0.4 mg . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary efficacy end points were ( 1 ) total IPSS and ( 2 ) Total Urgency and Frequency Score ( TUFS ) . An FDC met the success criteria if it demonstrated superiority compared with placebo and noninferiority compared with TOCAS for total IPSS , as well as superiority compared with TOCAS for TUFS . RESULTS AND LIMITATIONS Reductions in total IPSS and TUFS were observed with both solifenacin 6 mg plus TOCAS ( -7.0 and -8.1 , respectively ) and solifenacin 9 mg plus TOCAS ( -6.5 and -7.6 , respectively ) compared with TOCAS ( -6.2 and -6.7 , respectively ) and placebo ( -5.4 and -4.4 , respectively ) . Solifenacin 6 mg plus TOCAS met all prespecified success criteria for both primary end points , while solifenacin 9 mg plus TOCAS met success criteria compared with placebo but not compared with TOCAS . Both FDCs improved quality of life ( QoL ) measures and were well tolerated , with low incidences of acute urinary retention . CONCLUSIONS The FDC of solifenacin 6 mg plus TOCAS significantly improved storage and voiding symptoms , as well as QoL parameters , compared with placebo . This FDC also improved storage symptoms and QoL compared with TOCAS alone in men with moderate to severe storage symptoms and voiding symptoms , and it was well tolerated", "BACKGROUND Alpha blockers are prescribed to manage lower urinary tract symptoms ( LUTS ) associated with benign prostatic hyperplasia ( BPH ) . Antimuscarinics are prescribed to treat overactive bladder ( OAB ) . OBJECTIVE To investigate the safety of a combination of solifenacin ( SOLI ) and tamsulosin oral controlled absorption system ( TOCAS ) in men with LUTS and bladder outlet obstruction ( BOO ) . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , parallel-group , placebo-controlled study in men aged > 45 yr with LUTS and BOO for ≥3 mo , total International Prostate Symptom Score ( IPSS ) ≥8 , BOO index ≥20 , maximum urinary flow rate ( Q(max ) ) ≤12 ml/s , and voided volume ≥120 ml . INTERVENTIONS Once-daily coadministration of TOCAS 0.4 mg plus SOLI 6 mg , TOCAS 0.4 mg plus SOLI 9 mg , or placebo for 12 wk . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary ( safety ) measurements : Q(max ) and detrusor pressure at Q(max ) ( P(det)Q(max ) ) . Other safety assessment s included postvoid residual ( PVR ) volume . Secondary end points included bladder contractile index ( BCI ) score and percent bladder voiding efficiency ( BVE ) . An analysis of covariance model compared each TOCAS plus SOLI combination with placebo . RESULTS AND LIMITATIONS Both active treatment groups were noninferior to placebo at end of treatment ( EOT ) for P(det)Q(max ) and Q(max ) . Mean change from baseline PVR was significantly higher at all time points for TOCAS 0.4 mg plus SOLI 6 mg , and at weeks 2 , 12 , and EOT for TOCAS 0.4 mg plus SOLI 9 mg versus placebo . Both treatment groups were similar to placebo for BCI and BVE . Urinary retention was seen in only one patient receiving TOCAS 0.4 mg plus SOLI 6 mg . Limitations of the study were that prostate size and prostate-specific antigen level were not measured . CONCLUSIONS TOCAS 0.4 mg plus SOLI 6 mg or 9 mg was noninferior to placebo at EOT for P(det)Q(max ) and Q(max ) in men with LUTS and BOO , and there was no clinical or statistical evidence of increased risk of urinary retention", "BACKGROUND No authors have investigated whether the administration of local oestrogens in addition to antimuscarinics could have a synergistic effect in the therapy of overactive bladder ( OAB ) . OBJECTIVES To compare the efficacy of antimuscarinics alone versus antimuscarinics in combination with local oestrogens for OAB ; to verify whether risk factors for lower antimuscarinic efficacy can be overcome by the concomitant use of local oestrogens . DESIGN , SETTING , AND PARTICIPANTS Some 229 postmenopausal women with symptomatic urodynamically proven detrusor overactivity were prospect ively enrolled at a tertiary level urogynaecology centre and divided into two groups . INTERVENTION Women in group 1 ( n=129 ) were prescribed tolterodine extended release ( ER ) 4 mg once daily ; women in group 2 ( n=100 ) were prescribed both tolterodine ER 4 mg and concomitant oestriol cream application once daily . MEASUREMENTS All women underwent clinical evaluation and urodynamics in accordance with the Good Urodynamic Practice s Guidelines . After 12 wk of treatment the two groups were compared in terms of subjective efficacy for OAB symptom improvement using a three-point scale . Nonresponders were compared to the patients who improved or were cured in order to identify risk factors for resistance to therapy . RESULTS AND LIMITATIONS There was no significant difference between the two groups in terms of efficacy of therapy : 80.6 % in group 1 versus 82 % in group 2 ( p=0.86 ) . Patients with urodynamically proven detrusor overactivity ( DO ) occurring during provocative manoeuvres and patients with coital incontinence during orgasm reported a higher failure rate both in the overall study population and in group 2 . A possible limitation of the study is the nonr and omised design . CONCLUSIONS No synergistic effect of local oestrogens and antimuscarinics in the treatment of OAB was found . Antimuscarinic treatment has lower cure rates in women with symptomatic DO complaining of incontinence at orgasm or in patients with DO following provocative manoeuvres . The association of local oestrogens does not influence the role of the two mentioned risk factors", "CONTEXT Menopausal hormone therapy has long been credited with many benefits beyond the indications of relieving hot flashes , night sweats , and vaginal dryness , and it is often prescribed to treat urinary incontinence ( UI ) . OBJECTIVE To assess the effects of menopausal hormone therapy on the incidence and severity of symptoms of stress , urge , and mixed UI in healthy postmenopausal women . DESIGN , SETTING , AND PARTICIPANTS Women 's Health Initiative multicenter double-blind , placebo-controlled , r and omized clinical trials of menopausal hormone therapy in 27,347 postmenopausal women aged 50 to 79 years enrolled between 1993 and 1998 , for whom UI symptoms were known in 23,296 participants at baseline and 1 year . INTERVENTIONS Women were r and omized based on hysterectomy status to active treatment or placebo in either the estrogen plus progestin ( E + P ) or estrogen alone trials . The E + P hormones were 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate ( CEE + MPA ) ; estrogen alone consisted of 0.625 mg/d of conjugated equine estrogen ( CEE ) . There were 8506 participants who received CEE + MPA ( 8102 who received placebo ) and 5310 who received CEE alone ( 5429 who received placebo ) . MAIN OUTCOME MEASURES Incident UI at 1 year among women without UI at baseline and severity of UI at 1 year among women who had UI at baseline . RESULTS Menopausal hormone therapy increased the incidence of all types of UI at 1 year among women who were continent at baseline . The risk was highest for stress UI ( CEE + MPA : relative risk [ RR ] , 1.87 [ 95 % confidence interval { CI } , 1.61 - 2.18 ] ; CEE alone : RR , 2.15 [ 95 % CI , 1.77 - 2.62 ] ) , followed by mixed UI ( CEE + MPA : RR , 1.49 [ 95 % CI , 1.10 - 2.01 ] ; CEE alone : RR , 1.79 [ 95 % CI , 1.26 - 2.53 ] ) . The combination of CEE + MPA had no significant effect on developing urge UI ( RR , 1.15 ; 95 % CI , 0.99 - 1.34 ) , but CEE alone increased the risk ( RR , 1.32 ; 95 % CI , 1.10 - 1.58 ) . Among women experiencing UI at baseline , frequency worsened in both trials ( CEE + MPA : RR , 1.38 [ 95 % CI , 1.28 - 1.49 ] ; CEE alone : RR , 1.47 [ 95 % CI , 1.35 - 1.61 ] ) . Amount of UI worsened at 1 year in both trials ( CEE + MPA : RR , 1.20 [ 95 % CI , 1.06 - 1.36 ] ; CEE alone : RR , 1.59 [ 95 % CI , 1.39 - 1.82 ] ) . Women receiving menopausal hormone therapy were more likely to report that UI limited their daily activities ( CEE + MPA : RR , 1.18 [ 95 % CI , 1.06 - 1.32 ] ; CEE alone : RR , 1.29 [ 95 % CI , 1.15 - 1.45 ] ) and bothered or disturbed them ( CEE + MPA : RR , 1.22 [ 95 % CI , 1.13 - 1.32 ] ; CEE alone : RR , 1.50 [ 95 % CI , 1.37 - 1.65 ] ) at 1 year . CONCLUSIONS Conjugated equine estrogen alone and CEE + MPA increased the risk of UI among continent women and worsened the characteristics of UI among symptomatic women after 1 year . Conjugated equine estrogen with or without progestin should not be prescribed for the prevention or relief of UI", "BACKGROUND Combining the β3-adrenoceptor agonist mirabegron and the antimuscarinic ( AM ) agent solifenacin may improve efficacy in the treatment of overactive bladder ( OAB ) while reducing the AM side effects . OBJECTIVE The primary objective was to evaluate the efficacy of combinations of solifenacin/mirabegron compared with solifenacin 5 mg monotherapy . The secondary objective was to explore the dose-response relationship and the safety/tolerability compared with placebo and monotherapy . DESIGN , SETTING , AND PARTICIPANTS A phase 2 , factorial design , r and omised , double-blind , parallel-group , placebo- and monotherapy-controlled trial , conducted at 141 sites in 20 European countries . Male and female patients were aged ≥18 yr with symptoms of OAB for ≥3 mo . INTERVENTION A total of 1306 patients ( 66.4 % female ) were r and omised to 12 wk of treatment in 1 of 12 groups : 6 combination groups ( solifenacin 2.5 , 5 , or 10 mg plus mirabegron 25 or 50 mg ) , 5 monotherapy groups ( solifenacin 2.5 , 5 , or 10 mg , or mirabegron 25 or 50 mg ) , or placebo . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Change from baseline to end of treatment in mean volume voided per micturition ( MVV ) ( primary end point ) and mean numbers of micturitions per 24 h , incontinence episodes per 24 h , and urgency episodes per 24 h were analysed using an analysis of covariance model . Safety assessment s included treatment-emergent adverse events ( TEAEs ) , blood pressure , pulse rate , postvoid residual ( PVR ) volume , and laboratory and electrocardiography ( ECG ) parameters . RESULTS AND LIMITATIONS Compared with solifenacin 5 mg monotherapy , all combinations with solifenacin 5 or 10 mg significantly improved MVV , with adjusted differences ranging from 18.0 ml ( 95 % confidence interval [ CI ] , 5.4 - 30.0 ) to 26.3 ml ( 95 % CI , 12.0 - 41.0 ) . Three combination groups significantly reduced micturition frequency compared with solifenacin 5 mg , ranging from -0.80 ( 95 % CI , -1.39 to -0.22 ) to -0.98 ( 95 % CI , -1.68 to -0.27 ) . Five of six combinations significantly reduced urgency episodes compared with solifenacin 5 mg , ranging from -0.98 ( 95 % CI , -1.78 , to -0.18 ) to -1.37 ( 95 % CI , -2.03 to -0.70 ) . No dose-related trends in TEAEs , blood pressure , pulse rate , PVR volume , or laboratory or ECG parameters were observed between combination and monotherapy groups , although the incidence of constipation was slightly increased with combination therapy . CONCLUSIONS Combination therapy with solifenacin/mirabegron significantly improved MVV , micturition frequency , and urgency compared with solifenacin 5 mg monotherapy . All combinations were well tolerated , with no important additional safety findings compared with monotherapy or placebo . PATIENT SUMMARY To improve treatment of overactive bladder ( OAB ) , mirabegron/solifenacin in combination was compared with each drug alone and placebo . Combination therapy improved OAB symptoms and had similar safety and acceptability . TRIAL REGISTRATION Clinical trials.gov : NCT01340027", "Purpose The purpose of the study is to evaluate the clinical efficacy of initial combined therapy of an alpha-blocker and anticholinergic agent compared with the alpha-blocker alone in patients with benign prostatic hyperplasia ( BPH ) with overactive bladder ( OAB ) . Methods Hundred and fifty-six BPH patients with International Prostate Symptom Score ( IPSS ) of over 14 ( voiding sub-score ≥8 and storage sub-score ≥6 ) were prospect ively included in Korea . Group 1 ( n = 69 ) was the patients who were treated with Tamsulosin 0.2 mg daily alone for 4 weeks and after 8 weeks they were treated with tamsulosin 0.2 mg and solifenacin 5.0 mg daily combination . Group 2 ( n = 70 ) was the patients who were treated initially with tamsulosin 0.2 mg and solifenacin 5.0 mg combination for 12 weeks . Detailed question naires were used to assess treatment satisfaction at 4th week and at 12th week of treatment in 2 groups . Results Baseline characteristics were not different between the 2 groups . In the 4th week , there was no difference between the 2 groups with regard to IPSS total score and voiding symptom score , although the IPSS storage symptom score was significantly lower in the Group 2 [ −2.0 ( 0.2 ) △ 23.8 vs. −3.0 ( 0.2 ) △ 35.7 ] ( P in storage indices such as IPSS storage symptom score , OABSS , and urgency symptoms compared with baseline in each group ( P with alpha-blocker and anticholinergic agent helped to improve storage symptoms and quality -of-life scores earlier for patients with lower urinary tract symptoms related to BPH and OAB symptoms", "Objective : To increase the safety and effectiveness of treatments for overactive bladder ( OAB ) with moderate symptoms in elderly patients . Patients and Methods : Patients were examined at the Urodynamic Department of the Regional Diagnostic Center ( Vladivostok , Russian Federation ) from September 1 , 2012 to December 31 , 2012 . The assignment of patients [ n = 177 , average age 69 . 4 years , 98 women ( 55.4 % ) and 79 men ( 44.6 % ) ] was r and om and blind in this placebo-controlled study . Patients were distributed into subgroups according to the method of treatment as follows : group А1 : n = 57 , trospium 30 mg/day + solifenacin 10 mg/day ; group А2 : n = 61 , trospium 15 mg/day + solifenacin 5 mg/day ; group А3 : n = 59 , placebo . All patients underwent a urodynamic examination in accordance with international st and ards before and 2 months after treatment . ICIQ-SF question naires recommended by the International Continence Society ( ICS ) and bladder diaries were used to evaluate the clinical results . The clinical severity of the OAB symptoms and the effectiveness of the treatment were evaluated based on the frequency of episodes of incontinence ( EI ) per day . Three or fewer EI per day were considered moderate dysfunction of the lower urinary tract . Results : Groups of elderly patients with moderate symptoms of OAB who were treated with st and ard- and low-dose trospium and solifenacin demonstrated a significant increase in the median values of reflex volume , bladder capacity , and detrusor compliance and a decrease in the frequency of urination and urinary urgencies . The frequency of EI in both of the main groups decreased by almost 2-fold in comparison to the initial data and reached the following values : group А1 : 1.27 ( -1.08 ) , p ≤ 0.05 ; group A2 : 1.49 ( -1.18 ) , p ≤ 0.05 . The correlation with the decrease in the frequency of EI in these groups was r = 0.85 ( p ≤ 0.01 ) . The percentage of patients with a significant decrease ( EI ≥1.0 ) among those treated with st and ard- and low-dose trospium and solifenacin increased synchronously , prompting us to suppose the absence of a direct correlation between medicine dose and therapeutic effect for moderate OAB symptoms . Conclusion : The combination of low-dose trospium and solifenacin provides good clinical and urodynamic effects in elderly patients with moderate symptoms of OAB . Combination of these drugs in st and ard doses for such patients is excessive", "OBJECTIVE To compare the safety and efficacy of combined therapy using sildenafil and tamsulosin for management of acute urinary retention ( AUR ) with tamsulosin alone in patients with benign prostate hyperplasia ( BPH ) . MATERIAL S AND METHODS 101 patients were enrolled in a r and omized placebo-controlled study from June 2009 to April 2012 . Patients presenting with an initial episode of spontaneous AUR underwent urethral catheterization and then prospect ively r and omized to receive tamsulosin 0.4 mg plus sildenafil 50 mg in group A and tamsulosin 0.4 mg plus placebo in group B for three days . Urethral catheter was removed three days after medical treatment and patient 's ability to void assessed at the day after catheter removal and seven days later . Patients who voided successfully were followed at least for three months . RESULTS Mean age of patients was 59.64 ± 3.84 years in group A and 60.56 ± 4.12 years in group B ( p value = 0.92 ) . Mean prostate volume and mean residual urine were comparable between both groups ( p value = 0.74 and 0.42 , respectively ) . Fifteen patients in group A ( success rate : 70 % ) and nineteen patients in group B ( success rate : 62.7 % ) had failed trial without catheter ( TWOC ) at 7th day following AUR ( p value = 0.3 ) . No significant difference was noted between both groups regarding the rate of repeated AUR at one month and three month follow-up period ( p = 0.07 and p = 0.45 , respectively ) . CONCLUSION It seems that combination therapy by using 5-phosphodiesterase inhibitor and tamsulosin has no significant advantages to improve urinary retention versus tamsulosin alone", "To examine the safety and efficacy of mirabegron as ‘ add‐on ’ therapy to solifenacin in patients with overactive bladder ( OAB )", "INTRODUCTION Lower urinary tract symptoms ( LUTS ) associated with benign prostatic hyperplasia ( BPH ) and erectile dysfunction are common disorders of advancing age . AIM To evaluate the efficacy and safety of tamsulosin and tadalafil in patients with LUTS due to BPH . METHODS In this prospect i ve r and omized study , 133 men complaining of LUTS due to BPH were included . Forty-five patients received tamsulosin 0.4 mg/day alone ( Group A ) , 44 patients received tadalafil 10 mg/day ( Group B ) , and combination therapy ( tamsulosin and tadalafil both ) was instituted in 44 patients ( Group C ) . After a 2-week medication free run-in period , they were evaluated for International Prostatic Symptom Score ( IPSS ) , International Index of Erectile Function score ( IIEF5 ) , quality of life ( IPSS QoL ) , maximum urinary flow rate ( Qmax ) , post-void residual urine ( PVR ) volume , and safety parameters before and at 3 months of treatment . MAIN OUTCOME MEASURES There were primary ( IPSS , IPSS QoL index , Qmax , and PVR ) and secondary ( erectile function [ EF ] domain scores from IIEF5 ) efficacy end points . Safety assessment included laboratory tests and patient 's reporting of adverse event . RESULTS A significant improvement in IPSS score was observed in all the 3 groups A , B , and C ( -50.90 % , P IIEF5 score increased significantly in these three groups ( + 39.28 % , P increase in Qmax and decrease in PVR were also observed ( 33.99 % , P QoL scores improved significantly ( -73.35 % , P P , respectively ) . Side effects were dyspepsia , heartburn , headache , flushing , myalgia , and backache . Adverse effect dropout was 3.7 % . No participant experienced any severe or serious adverse events . CONCLUSIONS In patients with LUTS due to BPH , tamsulosin and tadalafil alone or in combination cause a significant improvement in patients with LUTS . Their EF also improves with these medications . The improvement is better with combination therapy compared with single agent alone", "OBJECTIVE The purpose of our study was to evaluate the effect of alfuzosin and tadalafil as combination therapy compared with each monotherapy , in patients with lower urinary tract symptoms ( LUTS ) due to benign prostatic hyperplasia ( BPH ) . METHODS Men over the age of 50 years with LUTS secondary to BPH and an International Prostate Symptom Score ( IPSS ) 8 or higher , were r and omized to receive 10 mg alfuzosin ( n = 25 ) , 10 mg tadalafil ( n = 25 ) or the combination of both the drugs ( n = 25 ) once daily for 3 months . Symptoms were assessed at baseline , 6 weeks and 3 months . The primary endpoint was the change in IPSS from the baseline . Secondary endpoints were changes in IPSS storage and voiding subscores , peak urinary flow rate , residual urine volume , IPSS quality of life score and erectile domain score . RESULTS There were significant improvements in all IPSS scores , peak urinary flow rate and IPSS quality of life score from baseline at both 6 weeks and 3 months in all the three groups ( P IPSS scores and reducing post-void residual urine volume ( P to alfuzosin regarding improvement in maximum urine flow rate ( P = 0.22 ) , similar to tadalafil in improvement on erectile function ( P = 0.22 ) and better than each monotherapy in improving the IPSS quality of life ( P ≤ 0.015 ) . CONCLUSION Alfuzosin and tadalafil combination therapy provides greater symptomatic improvement as compared to either monotherapy in men with LUTS due to BPH", "Purpose To evaluate how much the improvement of lower urinary tract symptoms ( LUTS ) affects sexual function and which storage symptoms or voiding symptoms have the greatest effect on sexual function . Material s and Methods A total of 187 patients were enrolled in this study . Patients were r and omly assigned to receive either tamsulosin 0.2 mg ( group A ) or tamsulosin 0.2 mg and solifenacin 5 mg ( group B ) . At 4 weeks and 12 weeks , the LUTS and sexual function of the patients were evaluated by use of the International Index of Erectile Function-5 ( IIEF5 ) , International Prostate Symptom Score ( IPSS ) , Overactive Bladder Symptom Score ( OABSS ) question naire , uroflowmetry , and bladder scan . Results Both groups A and B showed statistically significant improvements in IPSS , OABSS , and quality of life ( QoL ) . Group A showed improved maximum flow rate , mean flow rate , and residual urine volume by time . Group B did not show an improvement in flow rate or residual urine volume but total voiding volume increased with time . The IIEF5 score was not improved in either group . In group A , the IIEF5 score dropped from 13.66±4.97 to 11.93±6.14 after 12 weeks ( p=0.072 ) . Group B showed a decline in the IIEF5 score from 13.19±5.91 to 12.45±6.38 ( p=0.299 ) . Although group B showed a relatively smaller decrease in the IIEF5 score , the difference between the two groups was not significant ( p=0.696 ) . Conclusions Tamsulosin monotherapy and combination therapy with solifenacin did not improve erectile function despite improvements in voiding symptoms and QoL. The improvement in storage symptoms did not affect erectile function", "BACKGROUND The BESIDE study demonstrated that combination therapy ( mirabegron and solifenacin 5 mg ) improved overactive bladder symptoms versus solifenacin 5 mg or 10 mg , and was well tolerated . OBJECTIVE To ensure efficacy and safety is maintained in older patients ( > 65 yr ) , who usually experience greater symptom severity and comorbidities , a prespecified sub analysis stratified by age group was conducted . DESIGN , SETTING , AND PARTICIPANTS Patients remaining incontinent ( ≥1 episode during 3-d diary ) following 4-wk single-blind daily solifenacin 5 mg were r and omized 1:1:1 to a daily double-blind combination ( solifenacin 5 mg and mirabegron 25 mg , increased to 50 mg at wk 4 ) , solifenacin 5 mg or 10 mg for 12 wk . Four cohorts stratified by age ( . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Efficacy assessment s : change from baseline to end of treatment in average daily incontinence ( primary ) and micturition frequency ( key secondary ) , number of incontinence episodes during the 3-d diary ( key secondary ) , and change from baseline in average daily urgency and urgency incontinence episodes . Safety included treatment-emergent adverse events and vital signs . RESULTS AND LIMITATIONS Full analysis set included 2110 patients : 30.9 % aged ≥65 yr and 8.9 % aged ≥75 yr . At the end of treatment , daily , and 3-d incontinence daily micturitions , urgency , and urgency incontinence , were improved in each treatment group and age group ; the largest reductions were observed with combination in each age cohort . There were no notable differences in vital signs or the incidence of treatment-emergent adverse events between treatment and age groups , with the exception of dry mouth , which was highest with solifenacin 10 mg . CONCLUSIONS Efficacy and safety in the overall population is maintained in older ( ≥65 yr ) and elderly ( ≥75 yr ) patients treated with a combination of solifenacin and mirabegron , or solifenacin monotherapy ; irrespective of age , combination was associated with the greatest improvement in overactive bladder symptoms . PATIENT SUMMARY This study investigated the effectiveness and safety of a combination of two different treatments ( mirabegron 50 mg and solifenacin 5 mg ) or solifenacin ( 5 mg or 10 mg ) alone in patients aged overactive bladder . Symptoms of overactive bladder , such as the urgent need to visit the toilet , incontinence , and frequent urination , were improved with all treatments regardless of the patient 's age , but combination treatment demonstrated the greatest benefit , and was well tolerated", "OBJECTIVE To evaluate the effects of add-on treatment with an anticholinergic ( imidafenacin ) on persistent overactive bladder ( OAB ) symptoms despite α-blocker ( tamsulosin ) treatment in patients with benign prostatic hyperplasia ( BPH ) . METHODS Patients with BPH ≥50 years old , with urinary urgency at least once per week and total OAB symptom score ( OABSS ) ≥3 points after ≥8-week treatment with tamsulosin were enrolled in a multicenter , open-label study ( not double-blinded ) . Patients were r and omized to receive tamsulosin ( 0.2 mg/day ) alone or tamsulosin ( 0.2 mg/day ) + imidafenacin ( 0.1 mg 2 times a day ) . Primary endpoint was 12-week change in OABSS ; secondary endpoints were changes in OABSS , International Prostate Symptom Score ( IPSS ) , micturition time chart ( MTC ) , hours of undisturbed sleep ( HUS ) , and quality of life ( IPSS-QOL and BPH impact index [ BII ] ) . For statistical analysis , a mixed-effects model and t test were used . RESULTS In total , 308 men were enrolled . The change from baseline to 12 weeks in total OABSS was significantly greater with add-on imidafenacin than tamsulosin alone ( 2.11 , 95 % confidence interval [ CI ] 1.47 - 2.74 , P ) . Improvements in frequencies of daytime urination , nighttime urination , urinary urgency , urgency incontinence , IPSS , HUS , IPSS-QOL , and BII , were significantly greater from 4 weeks through 12 weeks in the imidafenacin group . Between-group difference in postvoid residual volume at 12 weeks was not significant ( -1.74 mL , 95 % CI -8.19 to 4.72 ) , and no events of urinary retention were reported . CONCLUSION Combined tamsulosin and imidafenacin treatment is effective and safe in patients with BPH with persistent OAB symptoms after tamsulosin monotherapy . Furthermore the combination treatment improved the QOL in BPH patients with OAB", "AIMS To assess the efficacy and safety of pregabalin alone or in combination with tolterodine extended release ( ER ) in subjects with idiopathic OAB . METHODS This 26-week , multicenter , r and omized , double-blind , placebo-controlled , three-period crossover study enrolled women aged ≥ 18 years that were diagnosed with OAB and reported ≥ 8 micturitions/24 hr and ≥ 4 urgency episodes/week on 5-day bladder diary at baseline . Subjects were r and omized to 1 of 10 treatment sequences and received three of five treatments , each for 4 weeks with 4-week washout periods : st and ard-dose pregabalin/tolterodine ER ( 150 mg twice daily [BID]/4 mg once daily [ QD ] , n=102 ) , pregabalin alone ( 150 mg BID , n=105 ) , tolterodine ER alone ( 4 mg QD , n=104 ) , low-dose pregabalin/tolterodine ER ( 75 mg BID/2 mg QD , n=105 ) , and placebo ( n=103 ) . Subjects completed 5-day diaries at the end of treatment and washout periods . The primary endpoint was change from baseline to week 4 in mean voided volume ( MVV ) per micturition . The primary comparison was st and ard-dose pregabalin/tolterodine ER versus tolterodine ER alone ; secondary comparisons were pregabalin alone versus tolterodine ER alone and versus placebo . RESULTS Baseline-adjusted changes in MVV were significantly greater after treatment with st and ard-dose pregabalin/tolterodine ER ( 39.5 ml ) versus tolterodine ER alone ( 15.5 ml ; P with pregabalin alone ( 27.4 ml ) versus tolterodine ER alone ( P=0.005 ) and placebo ( 11.9 ml ; P=0.0006 ) . Treatments were generally well tolerated ; discontinuation rates due to adverse events were 4 % , 2 % , 5 % , 0 % , and 1 % with st and ard- and low-dose pregabalin/tolterodine ER , pregabalin , tolterodine ER , and placebo , respectively . CONCLUSIONS Pregabalin , alone or with tolterodine ER may offer an alternative treatment option for idiopathic OAB in women", "Lower urinary tract symptoms ( LUTS ) and erectile dysfunction ( ED ) are frequently encountered in ageing males . We compared the efficacy of alfuzosin 10 mg alone or in combination with sildenafil 50 mg in the treatment of LUTS due to benign prostatic hyperplasia . One hundred male patients older than 45 years were r and omized to two groups containing 50 patients each ; one group receiving alfuzosin 10 mg and the other group alfuzosin 10 mg combined with sildenafil 50 mg . International Prostate Symptom Score ( IPSS ) , quality of life ( QoL ) , maximum flow rate ( Qmax ) , prostate volume and post‐void residual urine were evaluated . The mean age was 60.2 ± 17.8 . Mean data of evaluated parameters in both groups at the end of 3rd month compared with baseline values are given respective order as ; 5.1 ( 26.8 % ) and 5.8 ( 28.2 % ) points decreases in IPSS ; 1.6 ( 41.1 % ) and 1.8 ( 45 % ) points decreases in QoL ; and 3.4 ( 29.6 % ) and 3.4 ( 33 % ) points increases in Qmax . The outcomes of our study can not be interpreted in such a way to report that alpha blocker‐PDE5 inhibitor combination has a better efficacy than alpha blocker treatment alone in patients with LUTS", "OBJECTIVES To report the secondary analyses of treatment satisfaction and clinical ly meaningful improvements in a r and omized study comparing coadministration of tadalafil 5 mg with finasteride 5 mg versus finasteride alone in men with prostatic enlargement secondary to benign prostatic hyperplasia . METHODS An international , r and omized , double-blind , parallel study was carried out in men aged ≥45 years who were 5-alpha reductase inhibitor naïve , and had an International Prostate Symptom Score ≥13 and prostate volume ≥30 mL ; 350 men received placebo/finasteride and 345 received tadalafil/finasteride over 26 weeks . Treatment satisfaction was assessed per protocol using the Treatment Satisfaction Scale-Benign Prostatic Hyperplasia . Responder cut-offs , analyzed post-hoc were total International Prostate Symptom Score improvement ≥3 points or ≥25 % from r and omization . RESULTS Baseline patient characteristics were generally comparable between responders and non-responders . The proportion of patients with an International Prostate Symptom Score improvement ≥3 points with tadalafil/finasteride and placebo/finasteride , respectively , at week 4 was 57.0 % and 47.9 % ( OR 1.45 , 95 % confidence interval 1.07 - 1.97 ) , at week 12 was 68.8 % and 60.7 % ( OR 1.48 , 95 % confidence interval 1.07 - 2.05 ) and at week 26 was 71.4 % and 70.2 % ( OR 1.14 , 95 % confidence interval 0.81 - 1.61 ) ; for IPSS change ≥25 % , the corresponding proportions were 44.8 % and 32.9 % ( OR 1.66 , 95 % confidence interval 1.21 - 2.28 ) , 55.5 % and 51.9 % ( OR 1.18 , 95 % confidence interval 0.87 - 1.62 ) , and 62.0 % and 58.3 % ( OR 1.23 , 95 % confidence interval 0.89 - 1.70 ) . Treatment satisfaction at week 26 was significantly greater with tadalafil/finasteride versus placebo/finasteride for total treatment satisfaction scale score ( P=0.031 ) and satisfaction with efficacy subscore ( P = 0.025 ) ; scores were not significantly different between treatments for satisfaction with dosing or side-effects ( both P ≥ 0.371 ) . CONCLUSIONS Tadalafil/finasteride results in significantly more patients achieving early clinical meaningful improvements in symptoms , and in greater treatment satisfaction versus placebo/finasteride", "Introduction : In Korea , increasing attention has recently been given to the use of phytotherapeutic agents to alleviate the symptoms of BPH . Serenoa repens has been shown to have an equivalent efficacy to Finasteride or Tamsulosin in the treatment of BPH in previous studies . The present study was design ed to compare the efficacy and safety of Serenoa repens plus tamsulosin with tamsulosin only over 12 months in men with LUTS secondary to BPH . Material s and Methods : One hundred forty men with symptomatic BPH ( IPSS ≥10 ) were recruited in our hospital for a 12-month , open-label , r and omized trial . Patients were r and omly assigned to either tamsulosin 0.2 mg/day plus Serenoa repens 320 mg/day ( n = 60 ) or tamsulosin 0.2 mg/day only ( n = 60 ) . Prostate volume and PSA were measured at baseline and at end-point , whereas total IPSS , and its storage and voiding subscores , LUTS-related QoL , Qmax , and PVR were evaluated at baseline and later every 6 months . Results : Total 103 patients were finally available : 50 in the TAM + SR group and 53 in the TAM group . At 12 months , total IPSS decreased by 5.8 with TAM + SR and 5.5 with TAM ( p = 0.693 ) ; the storage symptoms improved significantly more with TAM + SR ( -1.7 vs. -0.8 with TAM , p = 0.024 ) . This benefit with regard to storage symptom in the TAM + SR group lasts at 12 months ( -1.9 vs. -0.9 , p = 0.024 ) . The changes of voiding subscore , LUTS-related QoL , Qmax , PVR , PSA , and prostate volume showed no significant differences between the TAM + SR and TAM groups . During the treatment period , 8 patients ( 16.9 % ) with TAM and 10 ( 20 % ) with TAM + SR had drug-related adverse reactions , which included ejaculatory disorders , postural hypotension , dizziness , headache , gastro-intestinal disorders , rhinitis , fatigue and asthenia . Conclusions : The combination treatment of Serenoa repens and tamsulosin was shown to be more effective than tamsulosin monotherapy in reducing storage symptoms in BPH patients after 6 months and up to 12 months of treatment", "Abstract Purpose To evaluate the efficacy and safety of adding a low-dose oral desmopressin to tamsulosin therapy for treatment of nocturia in patients with benign prostatic hyperplasia ( BPH ) . Methods Eligible patients with BPH and nocturia ≥2/night were r and omly allocated to two treatment groups ; the first of which received 3-month treatment scheme of daily oral dose of tamsulosin OCAS 0.4 mg and desmopressin MELT 60 mcg ( D/T group ) , while the second one received tamsulosin OCAS 0.4 mg only ( T group ) . Patients were followed on monthly basis and changes in the parameters from baseline to 3 months after treatment were assessed on I-PSS/QoL question naire , 7-day voiding diary , urinalysis , serum sodium , abdominal ultrasonography and uroflowmetry . Results A total of 248 patients were included within the study ; 123 patients in the combined D/T group and 125 patients in T group . The frequencies of night voids decreased by 64.3 % in D/T group compared to 44.6 % in T group . The first sleep period , significantly increased from 82.1 to 160.0 min and from 83.2 to 123.8 min in D/T and T group , respectively ; and significant differences between both groups were observed at the end of study ( p were significantly improved with no statistical difference between both groups . No serious adverse effects were reported in both groups . Conclusion The addition of low-dose oral desmopressin therapy to an α-blocker tamsulosin provides effective treatment for nocturia in patients with LUTS/BPH", "Alpha-blockers and 5-alpha-reductase inhibitors are medical therapies that are being used as alternatives to surgical interventions to relieve symptoms of benign prostatic hyperplasia ( BPH ) . Taken as monotherapy , alpha-blockers and 5-alpha-reductase inhibitors have each been shown to provide relief from BPH symptoms . Treatment with finasteride over 4 years has been shown to reduce both BPH symptoms and the likelihood of acute urinary retention and the need for surgery . Direct comparison of the alpha-blocker terazosin with finasteride has been done , but only for a period of 1 year . The Medical Therapy of Prostatic Symptoms ( MTOPS ) trial is a multicenter , r and omized , placebo-controlled , double-masked clinical trial design ed to evaluate the long-term efficacy of the alpha-blocker doxazosin and the 5-alpha-reductase inhibitor finasteride , whether taken as a monotherapy or in combination , in preventing or delaying the progression of BPH . We describe in this paper the design of the MTOPS trial , the concept of BPH progression , the definition and methods of determining the primary outcome events and the proposed statistical analysis methods . A unique feature of MTOPS is the inclusion of prostate biopsies on a subgroup of r and omized participants . Volunteers among r and omized participants are to undergo a biopsy of the prostate at predetermined time points during the trial . Studies that will be conducted using the tissue specimens collected in MTOPS can potentially provide information at the molecular level on the natural history of BPH among medically treated and untreated men with moderate to severe symptoms of BPH", "OBJECTIVE To examine the effects of oral estrogen/progestin on incontinence and related lower urinary tract conditions among female nursing home ( NH ) residents . DESIGN R and omized placebo-controlled trial . SETTING Five NHs . PARTICIPANTS Thirty-two incontinent female residents of average age 88 . MEASUREMENTS Subjects were r and omized to receive either oral estrogen ( 0.625 mg ) combined with progesterone ( 2.5 mg ) or placebo , daily for 6 months . Measures of incontinence severity , the clinical appearance of the vagina , vaginal and urethral cytology , and urine and vaginal cultures were made at baseline , 3 months , and 6 months . In addition to active drug or placebo , all subjects received regular toileting assistance ( prompted voiding ) by trained research aides during 3-day data - collection periods to compensate for mobility and cognitive impairments . RESULTS At 3 and 6 months there were no significant differences between the groups in the severity of incontinence , the prevalence of bacteriuria , or the results of vaginal cultures . Several clinical findings associated with atrophic vaginitis improved more in the active than the placebo group and vaginal pH and vaginal and urethral cytology exhibited a partial estrogenic effect . CONCLUSIONS Our results must be interpreted with caution because of the size and the select nature of our subject sample . Up to 6 months of oral estrogen had only a partial estrogenic effect on vaginal and urethral epithelium and no clinical effects in this patient population . We believe that future studies of estrogen for urinary incontinence in frail NH residents should utilize a topical preparation and consider targeting urinary tract infection as an additional outcome measure", "Objective : To evaluate the efficacy and safety of fesoterodine extended-release ( ER ) plus tamsulosin in men with lower urinary tract symptoms ( LUTS ) associated with benign prostatic hyperplasia ( BPH ) . Patients and Methods : Men aged ≥50 years , with LUTS , prostate volume ≤60 ml and International Prostate Symptom Score ( IPSS ) ≥13 were enrolled in this study . 173 consecutive patients were treated initially with tamsulosin ( 0.4 mg ) for 1 week . At the second visit , 47 patients out of the sample of 173 who were still experiencing inconvenient LUTS were r and omized into two groups . The first group received a therapy with tamsulosin and fesoterodine combination ( group 1 , n = 24 ) while the second continued the therapy with the single administration of tamsulosin ( group 2 , n = 23 ) for an additional 4-week period . Results : There was no statistically significant difference in age , prostate volume , Qmax , and postvoid residual urine between the two groups . A statistical significance appeared in the combination group regarding the storage and the total IPSS values among the second and third visits ( 10.5 ± 1.4 to 8.5 ± 1.3 and 16.1 ± 1.8 to 13.7 ± 1.5 respectively ) . Conclusion : Regarding bothersome LUTS and storage symptoms , fesoterodine ER and tamsulosin combination was significantly more effective than the single administration of tamsulosin", " BACKGROUND Phytotherapy has been used to treat patients with lower urinary tract symptoms ( LUTS ) . We evaluated the efficacy and tolerability of combination therapy between Serenoa Repens ( SeR ) , Lycopene ( Ly ) , and Selenium ( Se ) + tamsulosin versus single therapies . METHODS PROCOMB trial ( IS RCT N78639965 ) was a r and omized double-blinded , double-dummy multicenter study of 225 patients between 55 and 80 years old , PSA ≤ 4 ng/ml , IPSS ≥12 , prostate volume ≤60 cc , Qmax ≤15 ml/sec , postvoid residual urine ( PVR ) A ( SeR-Se-Ly ) , group B ( tamsulosin 0.4 mg ) , group C ( SeR-Se-Ly + tamsulosin 0.4 mg ) . The primary endpoints of the study were the reduction of IPSS , PVR , and increase of Qmax in group C versus monotherapy groups . RESULTS The decrease for combination therapy was significantly greater versus group A ( P PVR from baseline to 6 months . A greater decrease in IPSS was observed for Group C versus group A ( P increase in Qmax versus group B ( P the changes of IPSS and Qmax were greater for Group C versus monotherapies ( each comparison for IPSS ( each comparison P CONCLUSION SeR-Se-Ly + tamsulosin therapy is more effective than single therapies in improving IPSS and increasing Qmax in patients with LUTS", "BACKGROUND Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder ( OAB ) and is often difficult to treat with antimuscarinic monotherapy . OBJECTIVE To evaluate the efficacy and the safety and tolerability of combination ( solifenacin 5 mg and mirabegron 50 mg ) versus solifenacin 5 or 10 mg in OAB patients remaining incontinent after 4 wk of solifenacin 5 mg . DESIGN , SETTING , AND PARTICIPANTS OAB patients remaining incontinent despite daily solifenacin 5 mg during 4-wk single-blind run-in were r and omised 1:1:1 to double-blind daily combination or solifenacin 5 or 10 mg for 12 wk . Patients receiving the combination were initiated on mirabegron 25 mg increasing to 50 mg after week 4 . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was a change from baseline to end of treatment ( EOT ) in the mean number of incontinence episodes per 24h ( stratified rank analysis of covariance [ ANCOVA ] ) . Key secondary end points were a change from baseline to EOT in the mean number of micturitions per 24h ( ANCOVA ) and number of incontinence episodes noted in a 3-d diary at EOT ( mixed-effects Poisson regression ) . A trial ( BESIDE ) comparing combination treatment ( solifenacin plus mirabegron ) with one treatment alone ( solifenacin ) tested the superiority of combination versus solifenacin 5 mg , noninferiority ( and potential superiority ) of combination versus solifenacin 10 mg ( key secondary end points ) , and the safety and tolerability of combination therapy versus solifenacin monotherapy . RESULTS AND LIMITATIONS A total of 2174 patients were r and omised to combination ( n=727 ) , solifenacin 5 mg ( n=728 ) , or solifenacin 10 mg ( n=719 ) . At EOT , combination was superior to solifenacin 5 mg , with significant improvements in daily incontinence ( p=0.001 ) , daily micturitions ( p , and incontinence noted in a 3-d diary ( p=0.014 ) . Combination was noninferior to solifenacin 10 mg for key secondary end points and superior to solifenacin 10 mg for improving daily micturitions . All treatments were well tolerated . CONCLUSIONS Adding mirabegron 50 mg to solifenacin 5 mg further improved OAB symptoms versus solifenacin 5 or 10 mg , and it was well tolerated in OAB patients remaining incontinent after initial solifenacin 5 mg . PATIENT SUMMARY In this 12-wk study , overactive bladder patients who remained incontinent despite initial solifenacin 5 mg treatment received additional treatment with mirabegron 50 mg . Combining mirabegron 50 mg with solifenacin 5 mg was superior to solifenacin 5 mg alone in improving symptoms of incontinence and frequent urination , and it was well tolerated . TRIAL REGISTRATION Clinical Trials.gov NCT01908829", "OBJECTIVE Estimate the prevalence of urinary incontinence ( UI ) , overactive bladder ( OAB ) , and other lower urinary tract symptoms ( LUTS ) among men and women in five countries using the 2002 International Continence Society ( ICS ) definitions . METHODS This population -based , cross-sectional survey was conducted between April and December 2005 in Canada , Germany , Italy , Sweden , and the United Kingdom using computer-assisted telephone interviews . A r and om sample of men and women aged > /= 18 yr residing in the five countries and who were representative of the general population s in these countries was selected . Using 2002 ICS definitions , the prevalence estimates of storage , voiding , and postmicturition LUTS were calculated . Data were stratified by country , age cohort , and gender . RESULTS A total of 19,165 individuals agreed to participate ; 64.3 % reported at least one LUTS . Nocturia was the most prevalent LUTS ( men , 48.6 % ; women , 54.5 % ) . The prevalence of storage LUTS ( men , 51.3 % ; women , 59.2 % ) was greater than that for voiding ( men , 25.7 % ; women , 19.5 % ) and postmicturition ( men , 16.9 % ; women , 14.2 % ) symptoms combined . The overall prevalence of OAB was 11.8 % ; rates were similar in men and women and increased with age . OAB was more prevalent than all types of UI combined ( 9.4 % ) . CONCLUSIONS The EPIC study is the largest population -based survey to assess prevalence rates of OAB , UI , and other LUTS in five countries . To date , this is the first study to evaluate these symptoms simultaneously using the 2002 ICS definitions . The results indicate that these symptoms are highly prevalent in the countries surveyed", "AIMS To evaluate patient-reported outcomes ( PROs ) of combinations of solifenacin and mirabegron compared with solifenacin and mirabegron monotherapy and with placebo in patients with overactive bladder ( OAB ) from the SYNERGY trial . METHODS Following a 4-week placebo run-in , period patients ( ≥18 years ) with OAB were r and omized 2:2:1:1:1:1 to receive solifenacin 5 mg + mirabegron 25 mg ( combination 5 + 25 mg ) , solifenacin 5 mg + mirabegron 50 mg , ( combination 5 + 50 mg ) , solifenacin 5 mg , mirabegron 25 mg , mirabegron 50 mg or placebo for 12 weeks , followed by a 2-week washout period . At each visit , PROs related to quality of life , symptom bother , and treatment satisfaction were assessed , including OAB-q Symptom Bother score , health-related quality of life ( HRQOL ) Total score , treatment satisfaction-visual analogue scale ( TS-VAS ) , and patient perception of bladder condition ( PPBC ) question naires . RESULTS Overall , 3527 patients were r and omized into the study , with 3494 receiving double-blind treatment . At end of treatment ( EoT ) , both combination groups showed greater improvements in OAB-q Symptom Bother score compared with the monotherapy groups ( nominal P in HRQOL Total scores were observed in the combination groups versus monotherapy groups ( P ≤ 0.002 ) . For both combination groups , the OAB-q Symptom Bother score responder rates at EoT were statistically significantly higher versus mirabegron monotherapy ( P for many HRQOL parameters , including OAB-q Symptom Bother score , HRQOL Total score , and PPBC ", "Abstract Purpose To evaluate the efficacy and safety of imidafenacin ( IM ) , a novel short half-life anticholinergic , as add-on therapy for male LUTS with nocturia and nocturnal polyuria . Material s and methods This multicenter , prospect i ve , r and omized , open-labelled study was conducted and involved men who had frequency , urgency , and nocturia despite receiving a stable dose of α1-blocker for ≥1 month . Subjects were r and omised to control ( α1-blocker alone ) , IM twice/day ( α1-blocker + 0.1 mg imidafenacin twice daily ) , or IM nightly ( α1-blocker plus 0.1 mg imidafenacin nightly ) group ; the treatment period was 8 weeks . Primary endpoints included improvements in night-time frequency and Nocturia Quality of Life Question naire ( N-QOL ) scores . Secondary endpoints included changes from the baseline in frequency volume chart variables , and post-void residual volume . Results and limitations Compared with the controls , IM twice/day and IM nightly patients had a significantly lower night-time frequency ( changes from baseline : 0.1 ± 0.8 in control , −0.6 ± 0.9 in IM twice/day , and −0.4 ± 1.0 in IM nightly , p = 0.5227 , 0.0006 and 0.0143 , respectively ) . The hours of undisturbed sleep and N-QOL score were significantly improved in IM twice/day group , though not IM nightly group . Nocturnal urine volume was significantly reduced in IM nightly group , although total urine volume remained unchanged . Conclusions A short half-life anticholinergic is suggested to be safe and effective as an add-on therapy for residual nocturia in patients with male LUTS receiving α1-blocker treatment . Anticholinergic administration nightly could reduce the nocturnal urine volume", "PURPOSE To evaluate the long term efficacy and safety of the use of propiverine and terazosine combination in patients with LUTS and DO by a placebo controlled study . MATERIAL S AND METHODS One hundred patients were enrolled in the study . They were r and omized into two groups ( each group consisted of 50 patients ) . Terazosine and placebo were administered to the patients in Group 1 and terazosine plus propiverine HCL was administered to Group 2 . The patients were evaluated by international prostate symptom score ( IPSS ) , the first four questions of IPSS ( IPSS4 ) , the 8th question of IPSS ( quality of life-QoL ) , overactive bladder symptom score question naire ( OAB-q V8 ) , PSA test , urodynamic studies , post voiding residue ( PVR ) . All patients were followed for one year and were reassessed for comparison . RESULTS IPSS , IPSS4 , OAB symptoms , QoL score , PVR , and Qmax scores of the groups did not differ . After one year treatment , there was significant improvement in IPSS , IPSS4 , OAB symptoms , QoL and Qmax values in Group 2 . No significant improvement was noted for the same parameters in Group 1 . CONCLUSION This is the first study to show long term safety and efficacy of anticholinergic therapy for patients with LUTS . In patients with OAB or DO , long term anticholinergic treatment may be regarded as a treatment option", "PURPOSE To revise the 2003 version of the American Urological Association 's ( AUA ) Guideline on the management of benign prostatic hyperplasia ( BPH ) . MATERIAL S AND METHODS From MEDLINE ® search es of English language publications ( January 1999 through February 2008 ) using relevant MeSH terms , articles concerning the management of the index patient , a male ≥45 years of age who is consulting a healthcare provider for lower urinary tract symptoms ( LUTS ) were identified . Qualitative analysis of the evidence was performed . Selected studies were stratified by design , comparator , follow-up interval , and intensity of intervention , and meta-analyses ( quantitative synthesis ) of outcomes of r and omized controlled trials were planned . Guideline statements were drafted by an appointed expert Panel based on the evidence . RESULTS The studies varied as to patient selection ; r and omization ; blinding mechanism ; run-in periods ; patient demographics , comorbidities , prostate characteristics and symptoms ; drug doses ; other intervention characteristics ; comparators ; rigor and intervals of follow-up ; trial duration and timing ; suspected lack of applicability to current US practice ; and techniques of outcomes measurement . These variations affected the quality of the evidence review ed making formal meta- analysis impractical or futile . Instead , the Panel and extractors review ed the data in a systematic fashion and without statistical rigor . Diagnosis and treatment algorithms were adopted from the 2005 International Consultation of Urologic Diseases . Guideline statements concerning pharmacotherapies , watchful waiting , surgical options and minimally invasive procedures were either up date d or newly drafted , peer review ed and approved by AUA Board of Directors . CONCLUSIONS New pharmacotherapies and technologies have emerged which have impacted treatment algorithms . The management of LUTS/BPH continues to evolve", "Thirty-six postmenopausal women with objective ly verified stress incontinence were treated with oral estriol ( Triovex , 2 mg x 1 ) and phenylpropanolamine ( Kontexin , 50 mg x 2 ) alone and in combination . After an initial four-week single-blind period with phenylpropanolamine ( PPA ) , either estriol or estriol and PPA were given r and omly in four-week periods , in a crossover design . PPA and estriol in combination as well as PPA alone , raised the intraurethral pressure and significantly reduced the urinary loss by 35 per cent in a st and ardized physical strain test . In women with an initial low urethral pressure estriol also induced pressure increase . The leakage episodes and the assessed leakage amounts were significantly reduced by both estriol and PPA given separately as single treatment ( 28 % ) or when given as combined therapy ( 40 % ) . Most of the women preferred the combined treatment to either drug alone . Additive but no synergistic effects are indicated", "PURPOSE We evaluated the efficacy and safety of add-on treatment with a β3-adrenoceptor agonist ( mirabegron ) for overactive bladder symptoms remaining after α1-blocker ( tamsulosin ) treatment in men with benign prostatic obstruction . MATERIAL S AND METHODS Patients with benign prostatic obstruction with urinary urgency at least once per week and a total OABSS of 3 or more points after 8 or more weeks of treatment with tamsulosin were enrolled in the study . They were r and omly allocated to receive 0.2 mg tamsulosin daily or 0.2 mg tamsulosin and 50 mg mirabegron daily for 8 weeks . The primary end point was change in total OABSS . Safety assessment s included change in post-void residual urine volume and adverse events . RESULTS From January 2012 through September 2013 a total of 94 patients were r and omized . Of these patients 76 completed the protocol treatment . In the full analysis set the change in total OABSS during the treatment period was significantly greater in the combination group than in the monotherapy group ( -2.21 vs -0.87 , p=0.012 ) . The changes in scores for urinary urgency , daytime frequency , International Prostate Symptom Score storage symptom subscore and quality of life index at 8 weeks were significantly greater in the combination group . The change in post-void residual urine volume was significantly greater in the combination group . Although 6 patients experienced adverse events in the combination group , urinary retention was observed in only 1 patient . CONCLUSIONS Combined tamsulosin and mirabegron treatment is effective and safe for patients with benign prostatic obstruction who have overactive bladder symptoms after tamsulosin monotherapy", "Purpose A cost minimisation analysis compares the costs of different interventions ’ to ascertain the least expensive over time . We compared different prostate targeted drug treatments with TURP to identify the optimal cost saving duration of a medical therapy for symptomatic benign prostatic enlargement ( BPE ) . Methods The Evolution registry is a prospect i ve , multicentre registry , conducted by the European Association of Urology Research Foundation ( EAUrf ) for 24 months in 5 European countries . Evolution was design ed to register the management of symptomatic BPE in clinical practice setting s in 5 European countries . Direct cost evaluation associated with prostate targeted medical therapies and TURP was also recorded and analysed . Results In total , 1838 men were enrolled with 1246 evaluable at 24 months . Medical therapies were more cost saving than TURP for treatment duration s ranging from 2.9 to 70.4 years . Cost saving depended on both medication class and individual country assessed . Daily tamsulosin monotherapy was more cost saving than TURP for ≤ 13.9 years in Germany compared to ≤ 32.7 years in Italy . Daily finasteride monotherapy was more cost saving for ≤ 5.9 years in France compared to ≤ 36.9 years in Spain . Combination therapy was more cost saving for ≤ 5.9 years for Italian patients versus ≤ 13.8 years in Germany . Conclusions BPE medical management was more cost saving than TURP for different specific treatment duration s. Information from this study will allow clinicians to convey medical and surgical costs over time , to both patients and payors alike , when considering BPE treatment", "OBJECTIVE To investigate the treatment outcome of discontinuing 1 medication from 2-year combination therapy for male benign prostatic hyperplasia/lower urinary tract symptoms . MATERIAL S AND METHODS Patients with International Prostate Symptom Score ≥ 8 , total prostatic volume ( TPV ) > 30 mL , and maximum flow rate ( Qmax ) the 5α-reductase inhibitor ( 5ARI ) discontinue ( DC-5ARI ) or α-blocker discontinue ( DC-α-blocker ) group . All patients received combination therapy with dutasteride ( 0.5 mg QD ) and doxazosin ( 4 mg QD ) for 2 years and then discontinued either one drug for 12 months . The primary endpoint was the occurrence of resuming medication . The secondary endpoints were the net parameters changed or the need of transurethral resection of the prostate ( TURP ) . RESULTS A total of 117 patients in DC-5ARI and 113 in DC-α-blocker group completed the study . The baseline TPV and Qmax were similar between groups before combination therapy . Resumption of combination therapy was significantly more in DC-5ARI than DC-α-blocker group ( 51.3 % vs 31.0 % ; P = .005 ) . The mean duration from discontinuing to resuming medication was 5.0 ± 4.4 months in DC-α-blocker and 7.8 ± 3.8 months in DC-5ARI group ( P The TPV progression ( 29.1 % vs 8.0 % ; P the need for TURP ( 14.5 % vs 7.1 % ; P = .043 ) were significantly higher in DC-5ARI than DC-α-blocker group . Patients with larger TPV ( 45.8 ± 18.1 mL ) had significantly greater need for resuming 5ARI than smaller TPV ( 36.3 ± 16.9 mL ; P = .007 ) , and a lower Qmax might predict resuming α-blocker . CONCLUSION After a 2-year combination therapy , discontinuation of either one drug induced benign prostatic hyperplasia progression in either group . Greater risk of resuming medication and needing TURP were noted in patients who discontinued 5ARI ", "OBJECTIVE To evaluate the clinical response and adverse events ( AEs ) of solifenacin ( SOL ) or mirabegron ( MIR ) in benign prostatic hyperplasia patients with persistent overactive bladder ( OAB ) symptoms after dutasteride ( DUT ) treatment . METHODS Fifty cases with residual OAB symptom score ( OABSS ) ≥ 5 and OABSS Q3 ≥ 2 after at least 6 months treatment of DUT were included in this study . Patients were administered 5 mg/d of SOL ( N = 25 ) or 50 mg/d of MIR ( N = 25 ) , and International Prostate Symptom Score ( IPSS ) and OABSS were prospect ively collected at 4 and 12 weeks . The safety was evaluated by changes in postvoided residual urine volume and the incidence of AEs . RESULTS After DUT administration , the mean prostate volume , IPSS , and OABSS were 39.0 mL , 17.6 , and 8.1 , respectively . SOL 5 mg significantly reduced the IPSS , OABSS , and OABSS Q3 at 4 and at 12 weeks ( -3.1 , -2.7 , -1.3 ; P the SOL treatment owing to AEs . All patients could continue the 12 weeks of MIR treatment , and MIR 50 mg reduced IPSS and OABSS at 4 weeks and reduced IPSS , OABSS , and the OABSS Q3 ( -3.0 , -2.5 , -0.9 ; P weeks . Postvoided residual urine volume increased by ≥ 100 mL after treatment in 2 cases in the SOL group but not in any patient in the MIR group . CONCLUSION Additional SOL or MIR might result in amelioration of the persistent OAB symptom after DUT treatment in patients with an enlarged prostate", "INTRODUCTION Safety and efficacy of tamsulosin and vardenafil are well established : however , there is no report regarding combined therapy with these drugs for lower urinary tract symptoms ( LUTSs ) secondary to benign prostatic hyperplasia ( BPH ) . AIM To compare the safety and efficacy of tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus vardenafil 10 mg/day in patients with LUTS/BPH in a r and omized trial with 12-week follow-up . METHODS We conducted a r and omized , double-blind , placebo-controlled study on 60 men with persistent storage LUTS after 2-week run-in with tamsulosin . MAIN OUTCOME MEASURES International Prostate Symptom Score ( IPSS ) , IPSS-bother , International Index of Erectile Function , Version 5 ( IIEF-5 ) and Over Active Bladder question naire ( OAB-q ) scores , uroflowmetry data ( Qmax , Qave ) , and postvoiding residual urine were recorded after run-in ( baseline ) , and 2 and 12 weeks after treatment . Differences between vardenafil and placebo at different times were calculated with unpaired sample s t-test . Between-group differences in change from baseline to 2 and 12 weeks were evaluated with analysis of variance . RESULTS We found a between-group significant difference from baseline to 12 weeks in the following : ( i ) Qmax ( placebo : + 0.07 , vardenafil : + 2.56 , P = 0.034 ) ; ( ii ) Qave ( placebo : -0.15 , vardenafil : + 1.02 , P = 0.031 ) ; ( iii ) irritative-IPSS subscores ( placebo : -1.67 , vardenafil : -3.11 , P = 0.039 ) ; and ( iv ) IIEF ( placebo : + 0.06 , vardenafil : + 2.61 , P = 0.030 ) . No patient reported any serious ( grade ≥ 2 ) adverse event ( AE ) . There were no differences in the incidence of common , treatment-related AEs between men undergoing combined therapy or tamsulosin alone . CONCLUSIONS The combination of tamsulosin and vardenafil for 12 weeks was well tolerated and more effective to improve both LUTS and erectile function , as compared with tamsulosin alone . Further studies are needed to assess the role of combined therapy of phosphodiesterase type 5 inhibitors and alpha blockers in treating LUTS/BPH", "PURPOSE Medical treatment for men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia is 5α-reductase inhibitor monotherapy or coadministration with an α-blocker . We assessed the effects of tadalafil 5 mg coadministered with finasteride 5 mg during 26 weeks on lower urinary tract symptoms and sexual symptoms . MATERIAL S AND METHODS In an international , r and omized , double-blind , parallel study of men 45 years old or older who were 5α-reductase inhibitor naïve and had an I-PSS ( International Prostate Symptom Score ) of 13 or greater and prostate volume 30 ml or greater , 350 were treated with placebo/finasteride and 345 received tadalafil/finasteride for 26 weeks . Changes in lower urinary tract symptoms secondary to benign prostatic hyperplasia were assessed with the I-PSS , erectile dysfunction improvements were assessed with the IIEF-EF ( International Index of Erectile Function-Erectile Function ) in sexually active men and safety was assessed by evaluating adverse events . RESULTS Least squares mean changes from baseline in I-PSS after 4 , 12 and 26 weeks of tadalafil/finasteride coadministration were -4.0 , -5.2 and -5.5 , respectively . Corresponding values for placebo/finasteride coadministration were -2.3 , -3.8 and -4.5 ( p ≤ 0.022 at all visits favoring tadalafil/finasteride coadministration ) . I-PSS subscores ( storage and voiding ) and quality of life index were also numerically improved with tadalafil/finasteride coadministration . Least squares mean changes from baseline in IIEF-EF with tadalafil/finasteride coadministration were 3.7 after 4 weeks , and 4.7 after 12 and 26 weeks . Corresponding values for placebo/finasteride coadministration were -1.1 , 0.6 and -0.0 ( p favoring tadalafil/finasteride coadministration ) . Tadalafil/finasteride coadministration was well tolerated and most adverse events were mild/moderate . CONCLUSIONS The coadministration of tadalafil/finasteride provides early improvement in lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement . Tadalafil/finasteride coadministration also improves erectile function in men who have comorbid erectile dysfunction", "BACKGROUND Short-term trials have demonstrated the efficacy and safety of combination therapy using antimuscarinics and α-blockers in men with lower urinary tract symptoms ( LUTS ) . The Study of Solifenacin Succinate and Tamsulosin Hydrochloride OCAS ( oral controlled absorption system ) in Males with Lower Urinary Tract Symptoms ( NEPTUNE ) II is the first long-term study using solifenacin ( Soli ) and the oral controlled absorption system formulation of tamsulosin ( TOCAS ) . OBJECTIVE To evaluate long-term ( up to 52 wk ) safety and efficacy of flexible dosing of two fixed-dose combinations ( FDC ) of Soli plus TOCAS in men with moderate to severe storage symptoms and voiding symptoms . DESIGN , SETTING , AND PARTICIPANTS Patients with both storage and voiding LUTS , maximum urinary flow rate of 4.0 - 12.0 ml/s , prostate size the 40-wk , open-label NEPTUNE II study . INTERVENTION FDC of Soli 6 mg plus TOCAS 0.4 mg , or Soli 9 mg plus TOCAS 0.4 mg ; patients could switch between doses in NEPTUNE II . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Safety and efficacy data from NEPTUNE and NEPTUNE II were combined to cover a 52-wk period . Primary efficacy end points were total International Prostate Symptom Score ( IPSS ) and total urgency and frequency score ( TUFS ) ; secondary end points included IPSS storage and voiding subscores , micturition diary variables , and quality of life parameters . RESULTS In all , 1066 men completed NEPTUNE and received one dose or more of study medication in NEPTUNE II . Treatment-emergent adverse events were reported in 499 ( 46.8 % ) patients who participated in NEPTUNE II ; most were mild or moderate . Urinary retention occurred in 13 of 1208 ( 1.1 % ) patients receiving one or more FDCs in NEPTUNE and /or NEPTUNE II ; 8 ( 0.7 % ) required catheterisation ( acute urinary retention [ AUR ] ) . Reductions in total IPSS and TUFS during NEPTUNE were maintained for up to 52 wk of FDC treatment , with mean reductions of 9.0 ( st and ard deviation [ SD ] : 5.7 ) and 10.1 ( SD : 9.2 ) , respectively , from baseline to end of treatment . Clinical ly relevant improvements were also observed for secondary efficacy end points . CONCLUSIONS Long-term treatment with FDC Soli plus TOCAS was well tolerated and efficacious in men with storage and voiding LUTS , with a low incidence of AUR . PATIENT SUMMARY Treatment with solifenacin plus tamsulosin in a fixed-dose combination tablet was well tolerated by men with lower urinary tract symptoms . Improvements in symptoms were achieved after 4 wk of treatment , with further improvements at week 16 maintained for up to 52 wk throughout the study" ]

[ "BACKGROUND AND OBJECTIVES : Little is known about chronic neuromotor disability ( CND ) including cerebral palsy and motor impairments after acquired brain injury in children surviving early complex cardiac surgery ( CCS ) . We sought to determine the frequency and presentation of CND in this population while exploring potentially modifiable acute care predictors . METHODS : This prospect i ve follow-up study included 549 children after CCS requiring cardiopulmonary bypass at ≤6 weeks of age . Groups included those with only 1 CCS , mostly biventricular CHD , and those with > 1 CCS , predominantly single ventricle defects . At 4.5 years of age , 420 ( 94.6 % ) children received multidisciplinary assessment . Frequency of CND is given as percentage of assessed survivors . Predictors of CND were analyzed using multiple logistic regression analysis . RESULTS : CND occurred in 6 % ( 95 % confidence interval [ CI ] 3.7%–8.2 % ) of 4.5-year survivors ; for 1 CCS , 4.2 % ( CI 2.3%–6.1 % ) and > 1 , 9.8 % ( CI 7%–12.6 % ) . CND presentation showed : hemiparesis , 72 % ; spasticity , 80 % ; ambulation , 72 % ; intellectual disability , 44 % ; autism , 16 % ; epilepsy , 12 % ; permanent vision and hearing impairment , 12 % and 8 % , respectively . Overall , 32 % of presumed causative events happened before first CCS . Independent odds ratio for CND are age ( days ) at first CCS , 1.08 ( CI 1.04–1.12 ; P 1 CCS , 3.57 ( CI 1.48–8.9 ; P = .005 ) . CONCLUSIONS : CND is not uncommon among CCS survivors . The frequency of associated disabilities characterized in this study informs pediatricians caring for this vulnerable population . Shortening the waiting period and reducing preoperative plasma lactate levels at first CCS may assist in reducing the frequency of CND", "BACKGROUND It is not known whether developmental and neurological outcomes in the preschool period differ depending on whether the predominant vital organ support strategy used in infant heart surgery was total circulatory arrest ( CA ) or low-flow cardiopulmonary bypass . METHODS AND RESULTS Infants with D-transposition of the great arteries who underwent an arterial-switch operation were r and omly assigned to a support method consisting predominantly of CA or low-flow cardiopulmonary bypass . Developmental and neurological status were evaluated blindly at 4 years of age in 158 of 163 eligible children ( 97 % ) . Neither IQ scores nor overall neurological status were significantly associated with either treatment group or duration of CA . The CA group scored lower on tests of motor function ( gross motor , P=0.01 ; fine motor , P=0.03 ) and had more severe speech abnormalities ( oromotor apraxia , P=0.007 ) . Seizures in the perioperative period , detected either clinical ly or by continuous electroencephalographic monitoring , were associated with lower mean IQ scores ( 12.6 and 7.7 points , respectively ) and increased risk of neurological abnormalities ( odds ratios , 8.4 and 5.6 , respectively ) . The performance of the full cohort was below expectations in several domains , including IQ , expressive language , visual-motor integration , motor function , and oromotor control . CONCLUSIONS Use of CA to support vital organs during open heart surgery in infancy is associated , at the age of 4 years , with worse motor coordination and planning but not with lower IQ or with worse overall neurological status", "Background : It is unknown whether intraoperative hyperglycemia in infants is associated with worse neurodevelopmental outcomes after low-flow cardiopulmonary bypass ( LF ) , deep hypothermic circulatory arrest ( CA ) , or both . Methods : In a data base review of a prospect i ve trial of 171 infants undergoing arterial switch for D-transposition of the great arteries who were r and omly assigned to predominately LF or CA , glucose was measured after induction ( T1 ) , 5 min after cardiopulmonary bypass onset ( T2 ) , at the onset of CA or LF ( T3 ) , 5 min after CPB resumption ( T4 ) , at rewarming to 32 ° C ( T5 ) , 10 min after cardiopulmonary bypass weaning ( T6 ) , and 90 min after CA or LF ( T7 ) . Outcomes included seizures , electroencephalographic findings , and neurodevelopmental evaluation at 1 , 4 , and 8 yr . Results : Glucose concentrations were affected by support strategy and age at surgery . Lower glucose in the entire group at T6–T7 tended to predict electroencephalographic seizures ( P = 0.06 and P = 0.007 ) but was not related to clinical seizures . Within the predominantly CA group , higher glucose did not correlate with worse outcomes . Rather , it was associated with more rapid electroencephalographic normalization of “ close burst ” and “ relative continuous ” activity at all times except T2 ( P ≤ 0.03 ) , a finding more pronounced in infants aged 7 days old or younger . Intraoperative serum glucose concentrations were unrelated to neurodevelopmental outcomes at ages 1 , 4 , and 8 yr . Conclusions : Low glucose after cardiopulmonary bypass tended to relate to electroencephalographic seizures and slower electroencephalogram recovery , independent of CA duration . High glucose concentrations were not associated with worse neurodevelopmental outcomes . Avoiding hypoglycemia may be preferable to restricting glucose in infants undergoing heart surgery", "Objective . Studies of developmental outcomes in children with congenital heart disease ( CHD ) frequently use assessment s conducted in infancy as primary endpoints . Whether test scores of CHD patients in infancy are predictive of status at school age has not been evaluated , however . Methods . In the Boston Circulatory Arrest Study , 135 children with D-transposition of the great arteries repaired by arterial switch operation were administered the Bayley Scales of Infant Development and the Fagan Test of Infant Intelligence at 1 year of age and the Wechsler Intelligence Scale for Children , Third Edition and the Wechsler Individual Achievement Test at 8 years . Results . Although most 1-year test scores were significantly associated with 8-year test scores , the amounts of shared variance were modest ( low scores at 8 years ( ≤85 ) had had scores > 84 at 1 year . Conclusion . This pattern suggests that although test scores at 1 year are modestly associated with test scores at 8 years , many children who are at risk for poor late outcomes will not be identified on the basis of 1-year test scores . Long-term follow-up of children with CHD is necessary to draw inferences about the developmental sequelae of preoperative , intraoperative , and postoperative factors", "BACKGROUND Deep hypothermia with either total circulatory arrest or low-flow cardiopulmonary bypass is used to support vital organs during heart surgery in infants . We compared the developmental and neurologic sequelae of these two strategies one year after surgery . METHODS Infants with D-transposition of the great arteries who underwent an arterial-switch operation were r and omly assigned to a method of support consisting predominantly of circulatory arrest or a method consisting predominantly of low-flow bypass . Developmental and neurologic evaluations and magnetic resonance imaging ( MRI ) were performed at one year of age . RESULTS Of the 171 patients enrolled in the study , 155 were evaluated . After adjustment for the presence or absence of a ventricular septal defect , the infants assigned to circulatory arrest , as compared with those assigned to low-flow bypass , had a lower mean score on the Psychomotor Development Index of the Bayley Scales of Infant Development ( a 6.5-point deficit , P = 0.01 ) and a higher proportion had scores = 80 ( i.e. , 2 SD or more below the population mean ) ( 27 percent vs. 12 percent , P = 0.02 ) . The score on the Psychomotor Development Index was inversely related to the duration of circulatory arrest ( P = 0.02 ) . The risk of neurologic abnormalities increased with the duration of circulatory arrest ( P = 0.04 ) . The method of support was not associated with the prevalence of abnormalities on MRI scans of the brain , scores on the Mental Development Index of the Bayley Scale , or scores on a test of visual-recognition memory . Perioperative electroencephalographic seizure activity was associated with lower scores on the Psychomotor Development Index ( P = 0.002 ) and an increased likelihood of abnormalities on MRI scans of the brain ( P delayed motor development and neurologic abnormalities at the age of one year than is surgery with low-flow bypass as the predominant support strategy", "BACKGROUND Truncus arteriosus ( TA ) is an uncommon congenital cardiac lesion that portends an exceedingly poor prognosis if not repaired . The objective of this study was to assess the clinical and developmental outcomes in a prospect i ve cohort of patients who underwent TA repair . METHODS All patients who underwent a TA repair between 1996 and 2012 were included . Follow-up clinical , neurologic , and developmental data were obtained from the Western Canadian Complex Pediatric Therapies Follow-up Program data base . Functional developmental outcomes were assessed at 21.1 ± 2.5 months of age with the Adaptive Behavior Assessment System-II , General Adaptive Composite ( GAC ) score . Survival and outcomes were compared between those with and without chromosomal abnormalities ( CA ) . Survival and freedom from reintervention were assessed by Kaplan-Meier analysis . RESULTS The study comprised 36 infants ( 19 male ) . CA was identified in 13 , with 22q11.2 deletion in 10 patients . Patients underwent TA repair at a median age of 10 days ; 5 patients underwent concomitant interrupted arch repair . There were 8 deaths , 2 of which occurred in the hospital . The 5-year survival was 79.4 % . Survival was similar between those with and without CA . At 5 years , freedom from reoperation was 77.2 % . The mean GAC was higher in the patients without CA ( 93.6 ± 12.8 vs 76.1 ± 13.1 , p = 0.0016 ) . CONCLUSIONS Patients with surgically repaired TA continue to have significant postoperative mortality . Reoperation and cardiac catheterization are eventualities for a quarter of patients in the first 5 years of life . Functional developmental outcome in patients without CA is good , although it is significantly impaired in those with CA", "Objectives Neonates with single ventricle congenital heart disease are at risk for structural cerebral abnormalities . Little is known about the further evolution of cerebral abnormalities until Fontan procedure . Methods Between August 2012 and July 2015 , we conducted a prospect i ve cross-sectional two centre study using cerebral magnetic resonance imaging ( MRI ) and neuro-developmental outcome assessed by the Bayley-III . Forty-seven children ( 31 male ) were evaluated at a mean age of 25.9 ± 3.4 months with hypoplastic left heart syndrome ( 25 ) or other single ventricle ( 22 ) . Results Cerebral MRI was abnormal in 17 patients ( 36.2 % ) including liquor space enlargements ( 10 ) , small grey ( 9 ) and minimal white ( 5 ) matter injuries . Eight of 17 individuals had combined lesions . Median ( range ) cognitive composite score ( CCS ) ( 100 , 65 - 120 ) and motor composite score ( MCS ) ( 97 , 55 - 124 ) were comparable to the reference data , while language composite score ( LCS ) ( 97 , 68 - 124 ) was significantly lower ( P = 0.040 ) . Liquor space enlargement was associated with poorer performance on all Bayley-III subscores ( CCS : P = 0.02 ; LCS : P = 0.002 ; MCS : P = 0.013 ) . The number of re-operations [ odds ratio ( OR ) 2.2 , 95 % confidence interval ( CI ) 1.1 - 4.3 ] ( P = 0.03 ) and re- interventions ( OR 2.1 , 95 % CI 1.1 - 3.8 ) ( P = 0.03 ) was associated with a higher rate of overall MRI abnormalities . Conclusions Cerebral MRI abnormalities occur in more than one third of children with single ventricle , while the neuro-developmental status is less severely affected before Fontan procedure . Liquor space enlargement is the predominant MRI finding associated with poorer neuro-developmental status , warranting further studies to determine aetiology and further evolution until school-age", "Objectives To estimate the prevalence of childhood permanent hearing loss ( PHL ) after early cardiac surgery . Study design This prospect i ve observational ( 1996‐2015 ) study after complex cardiac surgery with cardiopulmonary bypass at ≤6 weeks of life reports audiology follow‐up by registered pediatric‐experienced audiologists at 6‐8 months postsurgery , age 2 years , and as required throughout and thereafter to complete diagnoses . PHL at any frequency ( 500‐4000 Hz ) is defined as responses of > 25‐decibel hearing level in either ear . PHL was evaluated by type ( conductive or sensorineural ) , pattern ( flat or sloping ) , and severity ( mild to profound ) . Results Survival rate was 83.4 % ( 706 of 841 children ) with a 97.9 % follow‐up rate ( 691 children ) ; 41 children had PHL , 5.9 % ( 95 % CI 4.3 % , 8.0 % ) . By cardiac defect , prevalence was biventricular , 4.0 % ( 95%CI 2.5 % , 6.1 % ) ; single ventricle , 10.8 % ( 95%CI 6.8 % , 16.1 % ) . Eighty‐seven ( 12.6 % ) of 691 had syndromes/genetic abnormalities with known association with PHL ; of these , 17 ( 41.5 % ) had PHL . Of 41 children , 4 had permanent conductive , moderate to severe loss ( 1 bilateral ) ; 37 had moderate to profound sensorineural loss ( 29 bilateral with 20 sloping and 9 flat ) , 6 with cochlear implant done or recommended . Conclusions Infants surviving complex cardiac surgery are at high risk for PHL . Over 40 % with PHL have known syndromes/genetic abnormalities , but others do not have easily identifiable risk indicators . Early cardiac surgery should be considered a risk indicator for PHL ", "OBJECTIVES Despite recent advances in the treatment of children with univentricular heart , their neurodevelopmental outcome remains a major concern . METHODS This prospect i ve follow-up study evaluated the neurodevelopmental outcome of 23 patients with hypoplastic left heart syndrome , 14 with other forms of univentricular heart , and 46 healthy control subjects at a median age of 12.2 months . The Griffiths Developmental Scale and Alberta Infant Motor Scale served for developmental evaluation . RESULTS The mean Griffiths developmental quotient of children with hypoplastic left heart syndrome was significantly less ( 91.6 ) than that of control children ( 106.8 , P gross motor domain ( P = .001 ) but not in overall development ( 100.6 ) . Alberta Infant Motor Scale scores were significantly lower in children with hypoplastic left heart syndrome ( 37.5 , P seizure ( P = .002 ) , and the highest plasma lactate level after the bidirectional Glenn operation ( P = .045 ) were significantly associated with the developmental quotient . CONCLUSIONS At age 1 year , the level of development of children with univentricular heart was significantly lower than for control subjects only in motor skills , whereas children with hypoplastic left heart syndrome had a more widespread developmental delay . The diagnosis , a clinical seizure history , and increased plasma lactate levels after the bidirectional Glenn operation emerged as risk factors", "OBJECTIVES The purpose of this study was to investigate early markers of risk for neurobehavioral compromise in survivors with congenital heart disease ( CHD ) . METHODS Pregnant women in whom a fetal CHD had been diagnosed before 24 weeks ' gestational age ( GA ) were enrolled in this prospect i ve pilot study for serial Doppler ultrasound assessment of the fetal middle cerebral artery ( MCA ) and umbilical arteries . The cerebral-to-placental resistance ratio ( CPR ) and MCA pulsatility index ( PI ) Z-scores for GA were calculated . After birth , subjects underwent high-density ( 128-lead ) electroencephalography ( EEG ) , and beta frequency ( 12 - 24 Hz ) b and EEG power , a measure of local neural synchrony , was analyzed . Neurodevelopment was assessed at 18 months with the Bayley Scales of Infant Development (BSID)-III . RESULTS Thirteen subjects were enrolled : four with hypoplastic left heart syndrome ( HLHS ) , four with transposition of the great arteries ( TGA ) and five with tetralogy of Fallot ( TOF ) . Compared with subjects with normal CPR , those with CPR mean BSID cognitive scores ( 91.4 ± 4.8 vs. 99.2 ± 3.8 , P = 0.008 ) . Fetal MCA-PI Z-score also correlated with BSID cognitive score ( r = 0.589 , P = 0.03 ) as did neonatal EEG left frontal polar ( r = 0.58 , P = 0.037 ) and left frontal ( r = 0.77 , P = 0.002 ) beta power . Furthermore , fetal Doppler measures were associated with EEG power : fetuses with CPR beta power as newborns than did fetuses with normal CPR , and fetal MCA-PI Z-score correlated with neonatal EEG left frontal polar ( r = 0.596 , P = 0.04 ) and left frontal ( r = 0.598 , P = 0.04 ) beta power . CONCLUSION In fetuses with HLHS , TGA and TOF , abnormal cerebrovascular resistance predicts decreased neonatal EEG left frontal beta power and lower 18-month cognitive development scores", "Background Developmental and language outcomes at 2 years of age of children who had arterial switch operation ( ASO ) for transposition of the great arteries 2004–2010 are described . Methods In this prospect i ve cohort study , 91/98 ( 93 % ) children who underwent ASO were assessed at 2 years of age with the Bayley Scales of Infant & Toddler Development—3rd Edition . Outcomes were compared by patient and perioperative variables using bivariate and multivariate regression analyses to identify predictors of language delay . Results Infants without ventricular septal defect ( VSD ) ( n = 60 ) were more likely to be outborn ( 73 vs 58 % , p = 0.038 ) , require septostomy ( 80 vs 58 % , p = 0.026 ) , have a shorter cross clamp time ( min ) ( 62.7 vs 73.0 , p = 0.019 ) , and a lower day 1 post-operative plasma lactate ( mmol/L ) ( 3.9 vs 4.8 , p = 0.010 ) . There were no differences in cognitive , motor and language outcomes based on presence of a VSD . Language delay ( lower Language Composite Scores ( −20.2 , 95 % CI −32.3 to −9.1 ) . Conclusions Outcomes at 2 years of age in children who undergo ASO are comparable to the normative sample with the exception of language . There is a risk of language delay for which maternal education and cross-clamp duration are predictors . These findings suggest that focused post-operative early language interventions could be considered", "to test early nutritional interventions and prospect i ve observational cohorts . RCTs are generally accepted as method ologically the best approach for informing health policy . They can equalise unknown as well as known confounding factors and so can demonstrate causation ; they permit estimation of effect size and so can be used to assess likely", "BACKGROUND By decreasing preoperative morbidity , prenatal diagnosis could improve neurodevelopmental outcomes in infants with critical congenital heart disease . We explored the impact of prenatal diagnosis on perinatal and perioperative variables and on outcomes at 1 year of age . METHODS We analyzed a data base of children enrolled in prospect i ve studies on surgical support techniques from 1988 to 2000 . Selection criteria included a diagnosis of D-transposition of the great arteries with intact ventricular septum or ventricular septal defect , no extracardiac congenital anomalies , birth weight > 2.3 kg , and repair by arterial switch procedure . RESULTS Of 346 patients at enrollment , 25 had a prenatal diagnosis , and 321 did not . Children with prenatal diagnosis , compared with those without , had a lower likelihood of birth by spontaneous labor , lower birth weights , lower Apgar 5 scores , a higher rate of preoperative endotracheal intubation , and surgery at a younger age . They tended to have a lower incidence of fetal distress during labor . At 1 year of age , 272 patients were tested with the Psychomotor Development Index and Mental Development Index of the Bayley Scales . Mean z scores were similar in those with and without prenatal diagnosis for both Psychomotor Development Index ( -0.92 + /- 0.93 vs -0.88 + /- 1.05 ) and Mental Development Index ( -0.29 + /- 1.13 vs -0.41 + /- 0.93 ) . CONCLUSIONS Infants with D-transposition of the great arteries with and without prenatal diagnosis differed with respect to perinatal and perioperative variables , but their development at 1 year of age was similar . Future studies should include a greater number of children with prenatal diagnosis and a variety of congenital heart lesions", "BACKGROUND : Despite increasing survival , patients with hypoplastic left heart syndrome ( HLHS ) and other forms of functionally univentricular heart defects ( UVHs ) remain at increased risk of long-term neurodevelopmental deficits . METHODS : A nationwide sample of 23 patients with HLHS , 13 with UVH , and 40 controls were followed prospect ively until the age of 5 years , when neurologic , neuropsychological , and motor examinations and brain MRI were performed . RESULTS : The median full-scale IQ was significantly lower in patients with HLHS ( 97 , P Major neurodevelopmental impairment was found in 26 % of the patients with HLHS and 23 % of those with UVH , and minor neurologic dysfunction was found in 43 % and 46 % , respectively . MRI revealed abnormalities , mostly ischemic changes of different degrees , in 82 % of the patients with HLHS and in 56 % of those with UVH . Prominent changes were significantly associated with neurodevelopmental findings and parental reports of adaptive behavior . In linear regression , significant risk factors for a worse outcome were a history of clinical seizures in connection with the primary operation , a lower diameter of the neonatal ascending aorta , and several pre- , peri- , and postoperative factors related to the primary and bidirectional Glenn operations . CONCLUSIONS : Although median cognitive performance was within the normal range , neurodevelopmental and brain MRI abnormalities were found in the majority of the patients with UVH , and especially in those with HLHS , at preschool age . Both a narrowed ascending aorta and operation-related factors contributed to these findings", "Background We aim ed to determine whether sepsis is associated with neurocognitive outcomes 4.5 years after congenital heart disease surgery in early infancy . Methods and Results A secondary analysis from a prospect i ve inception cohort included all children having congenital heart disease surgery done at ≤6 weeks of age with cardiopulmonary bypass at the Western Canadian referral center from 1996 to 2009 . Follow-up at the referral center determined the primary outcomes at 4.5 years with full-scale , performance , and verbal intelligence quotients on the Wechsler Preschool and Primary Scale of Intelligence . Perioperative variables were collected prospect ively , and confirmation of blood culture – positive sepsis was done retrospectively . Multiple linear regression models for neurocognitive outcomes and multiple Cox proportional hazards regression for mortality were determined . Sepsis occurred in 97 of 502 patients ( 19 % ) overall and in 76 of 396 survivors ( 19 % ) with 4.5-year follow-up . By 4.5 years , there were 91 ( 18 % ) deaths , and 396 of 411 survivors ( 96 % ) had follow-up completed . Extracorporeal membrane oxygenation was associated with worse scores on all neurocognitive outcomes on multivariable regression ; the association between extracorporeal membrane oxygenation and full-scale intelligence quotient had a regression coefficient of −13.6 ( 95 % CI −21.3 to −5.9 ; P = 0.001 ) . Sepsis perioperatively was associated with performance and verbal intelligence quotients , with a trend for full-scale intelligence quotient ( P = 0.058 ) on multivariable regression . The regression coefficient for sepsis was strongest for performance intelligence quotient ( −5.31 ; 95 % CI −9.84 to −0.78 ; P = 0.022 ) . Sepsis was not but extracorporeal membrane oxygenation was associated with mortality by 4.5 years . Conclusions Perioperative sepsis and extracorporeal membrane oxygenation were associated with adverse neurocognitive outcomes on multivariable regression . Quality improvement to prevent sepsis has the potential to improve long-term neurocognitive outcomes in infants after surgery for congenital heart disease", "BACKGROUND The outcome of infants who have transient seizures after open heart surgery has not been studied . Using the data base of the Boston Circulatory Arrest Study involving 171 children with D-transposition of the great arteries , we explored the relationship between early postoperative clinical and EEG seizures and neurodevelopmental outcomes at ages 1 and 2 1/2 years . METHODS AND RESULTS At 1 year , children returned for developmental and neurological evaluations and MRI . Parent-completed developmental question naires were collected at 2 1/2 years of age . At 1 year , children with early postoperative seizures had lower Psychomotor Development Index ( motor function ) scores ( clinical seizures : 12.9 mean difference [ MD ] ; 95 % confidence interval [ CI ] , 2.2 to 23.6 ; P=.02 ; EEG seizures : 13.3 MD ; 95 % CI , 6.8 to 19.7 ; P Mental Developmental Index scores of children with clinical or EEG seizures were also lower , but the differences were not statistically significant . Infants with seizures were more likely to have an abnormal neurological examination ( clinical seizures : 78 % versus 31 % ; P=.008 ; EEG seizures : 58 % versus 34 % ; P=.04 ) . Children with EEG seizures were more likely to have MRI abnormalities ( 43 % versus 13 % , P=.002 ) . At age 2 1/2 , children with EEG seizures had lower scores in several areas of function . CONCLUSIONS In infants undergoing the arterial switch operation for correction of D-transposition of the great arteries , transient postoperative clinical and EEG seizures were associated with worse neurodevelopmental outcomes at ages 1 and 2 1/2 years as well as neurological and MRI abnormalities at 1 year of age . The occurrence of such seizures may provide an early sign of brain injury with neurological and developmental sequelae", "A r and omized clinical trial was conducted to compare the early development of children with d-transposition of the great arteries ( N=171 ) repaired by an arterial switch operation that used either predominantly total circulatory arrest or predominantly continuous low-flow cardiopulmonary bypass . The children assigned to the circulatory arrest group scored lower than those assigned to low-flow bypass on the Bayley Scales of Infant Development at 1 year of age . Responses to parental question naires completed when the children were 2.5 years old indicated that the children in the circulatory arrest group , especially those with a ventricular septal defect , also manifested poorer expressive language and were considered to display more internalizing and externalizing problem behaviors . The use of circulatory arrest to protect vital organs during open heart surgery might place children at increased risk of early developmental difficulties , especially in the domains of motor and language function", "Background — The Norwood procedure for stage 1 palliation of hypoplastic left heart syndrome is performed with either the modified Blalock-Taussig ( MBTS ) or the right ventricle – to – pulmonary artery ( RVPA ) shunt . In our institution , surgical practice changed from use of the MBTS to use of the RVPA shunt in 2002 . We analyzed survival and mental and psychomotor outcomes of the 2 consecutive surgical eras . Methods and Results — Between September 1996 and July 2005 , 94 neonates with hypoplastic left heart syndrome underwent the Norwood procedure . Patients were recruited as neonates and followed up prospect ively . Health , mental , and psychomotor outcomes ( Bayley Scales of Infant Development-II ) were assessed at 2 years . The study subjects were from the Norwood-MBTS era ( n=62 ; 1996 to 2002 ) or the Norwood-RVPA era ( n=32 ; 2002 to 2005 ) . In the MBTS era , early and 2-year mortality rates were 23 % ( 14/62 ) and 52 % ( 32/62 ) ; the mean ( SD ) mental and psychomotor developmental indices were 79 ( 18 ) and 67 ( 19 ) . In the RVPA era , early and 2-year mortality rates were 6 % ( 2/32 ) and 19 % ( 6/32 ) ; the mean ( SD ) mental and psychomotor developmental indices were 85 ( 18 ) and 78 ( 18 ) . The 2-year mortality rate ( P=0.002 ) and the psychomotor developmental index ( P=0.029 ) were improved in the more recent surgical era . On multivariable Cox regression analysis , postoperative highest serum lactate independently predicted 2-year mortality in the MBTS and RVPA eras . Conclusions — Analysis of 2 consecutive surgical eras of hypoplastic left heart syndrome patients undergoing the Norwood procedure showed a significant improvement in 2-year survival and psychomotor development in the more recent era . Adverse neurodevelopmental outcome in this patient population remains a concern", "& NA ; We investigated the prevalence of neurological abnormalities and learning problems in a population cohort of children with dextro‐transposition of the great arteries ( d‐TGA ) born between January 1 , 1981 and July 1 , 1990 . Fifty‐seven of the 60 survivors and 35 siblings in the control group underwent neurodevelopmental assessment s. As compared with population norms , children with d‐TGA were more likely to have abnormal neurological examination findings , learning disabilities , and behavioral disorders . There was no significant difference in IQ or frequency of abnormal neurological examination results between children undergoing atrial as compared with arterial switch procedures . Compared with their siblings , the children with d‐TGA had more neurological findings and learning disabilities . The siblings of children with d‐TGA had more learning problems than expected . The findings suggest that ongoing surveillance is indicated for children surviving d‐TGA . Furthermore , a familial tendency for learning differences should to be taken into consideration when neurodevelopmental outcomes of various perioperative parameters are examined", "OBJECTIVES Neonates with hypoplastic left heart syndrome ( HLHS ) are at risk of high mortality and neurodevelopmental morbidity . As an alternative to Norwood-type stage I palliation , the hybrid procedure has been developed . It consists of bilateral pulmonary artery b and ing , catheter-based stenting of the arterial duct and balloon atrioseptostomy and delays open-heart surgery . Thus , it may be associated with a better outcome . The aim of this study was to determine the mortality and neurodevelopmental outcome in patients with HLHS and other univentricular heart ( UVH ) defects treated with hybrid or Norwood procedures . METHODS Thirty-one children ( 18 males ) with HLHS and other UVH defects undergoing Norwood or hybrid procedure between 2004 and 2008 were consecutively enrolled . Mortality and neurodevelopmental outcome at 1 year of age were determined . RESULTS One-year mortality was 36 % ( 31 % in the hybrid vs. 39 % in the Norwood group , P=0.71 ) . Predictors of mortality were lower birth weight ( P=0.02 ) , older age at first procedure ( P=0.02 ) and smaller size of ascending aorta ( P=0.05 ) . Overall , median psychomotor development index ( PDI ) and mental development index ( MDI ) of the Bayley Scales of Infant Development II were lower than the norm of 100 [ PDI 57 ( 49 - 99 ) , P surgical treatment on neurodevelopmental outcome was found . Predictors of impaired motor outcome were length of hospital stay ( LOHS ) ( P=0.01 ) , lower body weight at second procedure ( P=0.004 ) and female sex ( P=0.01 ) . Predictors of impaired cognitive outcome were longer mechanical ventilation time ( P=0.03 ) , intensive care unit stay ( P=0.04 ) and LOHS ( P Mortality at 1 year of age is comparable between patients undergoing hybrid and Norwood procedures . Early neurodevelopmental outcome is significantly impaired in patients with both HLHS and other UVH defects . Multicentre r and omized studies are needed to determine the long-term neurodevelopmental outcome of children treated with the hybrid procedure", "Background — We report neuropsychological and structural brain imaging assessment s in children 16 years of age with d-transposition of the great arteries who underwent the arterial switch operation as infants . Children were r and omly assigned to a vital organ support method , deep hypothermia with either total circulatory arrest or continuous low-flow cardiopulmonary bypass . Methods and Results — Of 159 eligible adolescents , 139 ( 87 % ) participated . Academic achievement , memory , executive functions , visual-spatial skills , attention , and social cognition were assessed . Few significant treatment group differences were found . The occurrence of seizures in the postoperative period was the medical variable most consistently related to worse outcomes . The scores of both treatment groups tended to be lower than those of the test normative population s , with substantial proportions scoring ≥1 SDs below the expected mean . Although the test scores of most adolescents in this trial cohort are in the average range , a substantial proportion have received remedial academic or behavioral services ( 65 % ) . Magnetic resonance imaging abnormalities were more frequent in the d-transposition of the great arteries group ( 33 % ) than in a referent group ( 4 % ) . Conclusions — Adolescents with d-transposition of the great arteries who have undergone the arterial switch operation are at increased neurodevelopmental risk . These data suggest that children with congenital heart disease may benefit from ongoing surveillance to identify emerging difficulties . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00000470", "BACKGROUND Expectations for outcomes after the neonatal arterial switch operation ( ASO ) continue to change . This cohort study describes neurodevelopmental outcomes at age 12 months after neonatal ASO , and analyzes both modifiable and nonmodifiable factors for association with adverse outcomes . METHODS Patients who underwent an ASO ( n=30 ) were enrolled in a prospect i ve outcome study , with comprehensive clinical data collection during the first 12 months of life . Brain magnetic resonance imaging was done preoperatively and 7 days postoperatively , and the Bayley Scales of Infant Development III was performed at age 12 months . RESULTS Ten of 30 patients ( 33 % ) had preoperative magnetic resonance imaging injury ; 13 of 30 patients ( 43 % ) had new postoperative magnetic resonance imaging injury . Twenty patients ( 67 % ) had Bayley Scales of Infant Development III : Cognitive Composite st and ard score mean was 104.8±15.0 , Language Composite st and ard score median was 90.0 ( 25th to 75th percentile , 83 to 94 ) , and Motor Composite st and ard score mean was 92.3±14.2 . Best subsets multivariable analysis found associations between lower preoperative and intraoperative cerebral oxygen saturation , preoperative magnetic resonance imaging brain injury , total bypass time , and total midazolam dose and lower Bayley Scales of Infant Development III scores at age 12 months . CONCLUSIONS At 12 months after ASO , neurodevelopmental outcome means were within normal population ranges . The new associations reported in this study between potentially modifiable perioperative factors and outcomes require investigations in larger patient cohorts . Beyond survival , which was 100 % in this cohort , factors influencing quality of life including neurodevelopmental outcomes should be routinely investigated in studies of ASO patients", "BACKGROUND It is important to identify early predictors of functional limitations in children after congenital heart surgery to optimise their independence as they prepare for school . The purpose of this study is to determine potentially modifiable predictor variables of functional abilities in pre-school children who underwent complex cardiac surgery at 6 weeks of age or earlier . METHODS This prospect i ve inception cohort study comprised a sample of 165 survivors ( 63 % boys ) who had complex cardiac surgery ( 75 % biventricular repairs ) at Stollery Children 's Hospital , Edmonton , Alberta . We excluded children with chromosomal abnormalities . When children were 4 - 5 years of age , the parents completed the Adaptive Behavioral Assessment System II . Regression analysis was used to assess the association between multiple risk factors and each of the four continuous composite scores . RESULTS The mean scores for the practical domain and general adaptive composite score of the Adaptive Behavioural Assessment System were lower than the conceptual and social domains , with 13.3 % of the children having a delay in the practical domain . There was a significant association between the general adaptive ( p=0.003 ; 0.012 ) , conceptual ( p=0.0004 ; 0.042 ) , social ( p=0.0007 ; 0.028 ) , and the practical ( p=0.046 ; 0.003 ) domain composite scores with the mother 's education and preoperative plasma lactate , respectively . CONCLUSION Maternal education may be a marker for the social context of children , and warrants societal attention to improve functional outcomes . Preoperative lactate as a potentially modifiable variable may warrant increased attention to early diagnosis and aggressive resuscitation of young infants with congenital heart disease", "OBJECTIVES Our goal was to determine which of the two major methods of vital organ support used in infant cardiac surgery , total circulatory arrest and low-flow cardiopulmonary bypass , results in better neurodevelopmental outcomes at school age . METHODS In a single-center trial , infants with dextrotransposition of the great arteries underwent the arterial switch operation after r and om assignment to either total circulatory arrest or low-flow cardiopulmonary bypass . Developmental , neurologic , and speech outcomes were assessed at 8 years of age in 155 of 160 eligible children ( 97 % ) . RESULTS Treatment groups did not differ in terms of most outcomes , including neurologic status , Full-Scale or Performance IQ score , academic achievement , memory , problem solving , and visual-motor integration . Children assigned to total circulatory arrest performed worse on tests of motor function including manual dexterity with the nondominant h and ( P = .003 ) , apraxia of speech ( P = .01 ) , visual-motor tracking ( P = .01 ) , and phonologic awareness ( P = .003 ) . Assignment to low-flow cardiopulmonary bypass was associated with a more impulsive response style on a continuous performance test of vigilance ( P worse behavior as rated by teachers ( P = .05 ) . Although mean scores on most outcomes were within normal limits , neurodevelopmental status in the cohort as a whole was below expectation in many respects , including academic achievement , fine motor function , visual-spatial skills , working memory , hypothesis generating and testing , sustained attention , and higher-order language skills . CONCLUSIONS Use of total circulatory arrest to support vital organs during heart surgery in infancy is generally associated with greater functional deficits than is use of low-flow cardiopulmonary bypass , although both strategies are associated with increased risk of neurodevelopmental vulnerabilities", "BACKGROUND Preoperative brain injury is common in neonates with complex congenital heart disease . Increasing evidence suggests a complex interaction of prenatal and postnatal risk factors for development of brain white matter injury , called periventricular leukomalacia ( PVL ) , in neonates with complex congenital heart disease . To date , there remains a limited underst and ing of the risk factors contributing to preoperative PVL in hypoplastic left heart syndrome ( HLHS ) . METHODS Neonates with HLHS or HLHS variants from 3 prospect i ve magnetic resonance imaging studies ( 2003 - 2010 ) were selected for this cohort . Preoperative brain magnetic resonance imaging was performed the morning of the surgery . Stepwise multilogistic regression of patient characteristics , mode of delivery ( cesarean section vs vaginal ) , time of diagnosis ( prenatal vs postnatal ) , HLHS subtypes , brain total maturation score , time to surgery , individual averaged daily preoperative blood gases , and complete blood cell count values was used to determine significant associations . RESULTS A total of 57 neonates with HLHS were born at 38.7 ± 2.3 weeks ; 86 % ( 49/57 ) had a prenatal diagnosis , with 31 % ( 18/57 ) delivered by cesarean section . HLHS with aortic atresia ( AA ) was common in this cohort , 71 % ( 41/57 ) . Preoperative PVL was identified in 19 % ( 11/57 ) . Male patients with AA ( P = .004 ) were at higher risk for PVL . Lower total brain maturation score was also identified as a strong predictor for preoperative PVL ( P = .005 ) . CONCLUSIONS In neonates with HLHS , nonmodifiable patient-related factors , including male sex with AA ( lack of ante grade blood flow ) and lower total brain maturation score , placed neonates at the greatest risk for preoperative white matter injury", "BACKGROUND Red blood cell transfusions may or may not improve oxygen delivery to the tissues . Some studies suggest transfusion might contribute to adverse outcomes . This study investigated the association between hemoglobin concentration and transfusion with outcome in cyanotic neonates undergoing Norwood operations . METHODS Infants 6 weeks old or younger with hypoplastic left heart syndrome undergoing staged Norwood operations between September 1996 and July 2005 were included . Demographics and preoperative , operative , and postoperative variables were collected prospect ively . Hemoglobin concentration , transfusion , fluid balance , and chest tube losses were collected retrospectively . The association of variables with outcomes , including early and 2-year mortality , mental and psychomotor developmental indices at 18 to 24 months of age , and ventilator days were determined by univariate and multiple regression analyses . RESULTS Ninety-four patients had Norwood operations . Excluded were 10 requiring postoperative extracorporeal life support and 2 with chromosomal abnormalities . By multiple regression analysis , only a higher nadir hemoglobin on days 2 to 5 postoperatively was associated with higher early mortality ( odds ratio , 2.09 ; 95 % confidence interval [ CI ] , 1.14 to 3.87 ; p = 0.018 ) , and the highest preoperative dopamine dose and highest epinephrine dose on day 2 to 5 postoperatively were associated with 2-year mortality ; however , neither hemoglobin concentration nor number of transfusions were associated with mental or psychomotor developmental indices . The number of transfusions on day 2 to 5 postoperatively was associated with ventilator days in multiple variable analysis ( effect size , 1.85 ; 95 % CI , 0.33 to 3.36 ; p = 0.018 ) . CONCLUSIONS This single-center cohort study found transfusion was not associated with improved outcomes in neonates undergoing Norwood operations", "OBJECTIVE We studied brain structure abnormalities in adolescents and young adults who had undergone the neonatal arterial switch operation for transposition of the great arteries and related them to the neurologic and psycho-intellectual outcomes . METHODS In a prospect i ve longitudinal study , 60 unselected adolescents and young adults who had undergone surgery with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass were re-evaluated at a mean age of 16.9±1.7 years to determine their clinical neurologic status , intellectual development , and psychological condition . The results were related to population norms and anatomic structural abnormalities assessed by brain magnetic resonance imaging , with consideration of the risk factors in the preoperative and perioperative periods . RESULTS Neurologic impairment was more frequent ( 10 % ) than in the normal population . Although the average full-scale , verbal , and performance intelligence quotients were not reduced , scores>2 st and ard deviations less than the expected mean were increased . Above average scores were found for analytical thinking , but the orthography testing results were reduced . The self-rated psychological condition was better than expected . Magnetic resonance imaging demonstrated moderate or severe structural brain abnormalities in 32 % of the patients . Periventricular leukomalacia was detected in > 50 % ; its severity correlated with the grade of neurologic impairment , which correlated significantly with reduced intelligence , analytical thinking , and orthography . Preoperative acidosis and hypoxia were the only independent patient-related risk factors for neurologic dysfunction , reduced intelligence , periventricular leukomalacia , and reduced brain volume . CONCLUSIONS Despite encouraging overall neurodevelopmental outcomes , a significant minority had performances below the expected level , emphasizing the need for ongoing surveillance . Considering the high frequency of structural brain abnormalities , prospect i ve long-term studies are needed to define their prognostic value with respect to the neuropsychological outcomes in childhood and adolescence", "ABSTRACT . This study was part of a r and omized clinical trial comparing the central nervous system effects of the two vital organ‐support methods used in infant cardiac surgery : total circulatory arrest and low‐flow cardiopulmonary bypass . The extent to which visual‐spatial deficits are ( 1 ) associated with surgical and perioperative variables , ( 2 ) attributable to visual‐perceptual , motor control , or metacognitive deficits , and ( 3 ) associated with adaptive difficulties at home or school was evaluated . The subjects were 155 8‐year‐old children with D‐transposition of the great arteries who underwent the arterial switch operation before 3 months of age . As part of a comprehensive evaluation , the Rey‐Osterrieth Complex Figure ( ROCF ) was administered . ROCF copy productions were classified as having a Basal Organization Level of 1 ( low ) or 2 or greater . A five‐category clinical rating was also assigned . More than half of the children in the cohort ( 52 % ) had copy productions scored at Level 1 , more than twice the expected frequency . The risk of having a low score was not associated with vital organ support method or other surgical variables . On the basis of comparisons of the relative fits of nested logistic regression models , poor visual‐perceptual abilities were more predictive of having a Level 1 score than either motor control or metacognitive deficits . Children with poor copy production scores had lower mathematics scores , but not lower reading scores or poorer parent and teacher ratings of adaptive competence . The percentage of children receiving remedial school services was associated with ROCF clinical rating , ranging from 58 % in the worst category to 8 % in the best category . Visual‐spatial deficits are common among children after infant heart surgery and seem to reflect visual‐perceptual rather than motor control or metacognitive deficits . In addition , these deficits do not seem to be clearly associated with the intraoperative methods or postoperative events evaluated . J Dev Behav Pediatr 24:169‐179 , 2003 . Index terms : congenital heart disease , visual‐spatial skills , transposition of the great arteries , Rey‐Osterrieth Complex Figure", "OBJECTIVE Small head circumferences and white matter injury in the form of periventricular leukomalacia have been observed in population s of infants with severe forms of congenital heart defects . This study tests the hypothesis that congenital heart defects delay in utero structural brain development . METHODS Full-term infants with hypoplastic left heart syndrome or transposition of the great arteries were prospect ively evaluated with preoperative brain magnetic resonance imaging . Patients with independent risk factors for abnormal brain development ( shock , end-organ injury , or intrauterine growth retardation ) were excluded . Outcome measures included head circumferences and the total maturation score on magnetic resonance imaging . Total maturation score is a previously vali date d semiquantitative anatomic scoring system used to assess whole brain maturity . The total maturation score evaluates 4 parameters of maturity : ( 1 ) myelination , ( 2 ) cortical infolding , ( 3 ) involution of glial cell migration b and s , and ( 4 ) presence of germinal matrix tissue . RESULTS The study cohort included 29 neonates with hypoplastic left heart syndrome and 13 neonates with transposition of the great arteries at a mean gestational age of 38.9 + /- 1.1 weeks . Mean head circumference was 1 st and ard deviation below normal . The mean total maturation score for the cohort was 10.15 + /- 0.94 , significantly lower than reported normative data in infants without congenital heart defects , corresponding to a delay of 1 month in structural brain development . CONCLUSION Before surgery , term infants with hypoplastic left heart syndrome and transposition of the great arteries have brains that are smaller and structurally less mature than expected . This delay in brain development may foster susceptibility to periventricular leukomalacia in the preoperative , intraoperative , and postoperative periods", "OBJECTIVES Despite the technical advantages of total circulatory arrest for vital organ support during infant heart surgery , many centers have moved away from its use because of the demonstrated effects of circulatory arrest of long duration on neurodevelopmental outcomes . Our goal was to determine the functional form of the association between duration of circulatory arrest and risk of neurodevelopmental dysfunction . METHODS From 1988 to 1992 , in a single-center trial , infants with d-transposition of the great arteries underwent the arterial switch operation after r and om assignment to circulatory arrest or low-flow bypass . The alpha-stat method was used , and hematocrit on bypass was maintained at 20 % . Developmental , neurologic , and speech outcomes were assessed at 8 years of age in 155 of 160 eligible children ( 97 % ) . Outcomes selected for analysis were Full-Scale , Verbal , and Performance IQ , Reading and Mathematics Composite , time to complete the Grooved Pegboard ( dominant h and ) , and the Mayo Test for Apraxia . RESULTS Nonparametric regression and piecewise linear models indicated that neurodevelopmental outcomes were generally not adversely affected unless the duration of circulatory arrest exceeded a threshold of 41 minutes ( 95 % 1-sided lower confidence limit of 32 minutes ) . CONCLUSIONS We found that the effect of duration of total circulatory arrest on later neurodevelopmental outcomes is nonlinear , with little influence at shorter duration s and with steadily worsening outcomes after longer duration s of circulatory arrest . Because the effects of duration of circulatory arrest may vary according to diagnosis , age at surgery , and other bypass and perioperative variables , this study can not ascertain a universally \" safe \" duration of total circulatory arrest", "BACKGROUND There has been increasing recognition of adverse neurodevelopmental sequelae in some children after repair of congenital heart defects . Even among children with the same cardiac defect , significant interindividual variation exists in developmental outcome . Polymorphisms of apolipoprotein E have been identified as a risk factor for worse neurologic recovery after central nervous system injury . METHODS A single-institution prospect i ve study of patients cardiopulmonary bypass for repair of congenital heart defects was undertaken to evaluate the association between apolipoprotein E genotype and postoperative neurodevelopmental dysfunction . Developmental outcomes were evaluated at 1 year of age by using the Bayley Scales of Infant Development . RESULTS One-year evaluation was performed in 244 patients . After adjustment for preoperative and postoperative covariates-including gestational age , age at operation , sex , race , socioeconomic status , cardiac defect , and use of deep hypothermic circulatory arrest-the apolipoprotein E epsilon2 allele was associated with a worse neurologic outcome as assessed by the Psychomotor Developmental Index of the Bayley Scales of Infant Development ( P = .036 ) . Patients with the apolipoprotein E epsilon2 allele had approximately a 7-point decrease in the Psychomotor Developmental Index . CONCLUSIONS Apolipoprotein E epsilon2 allele carriers had significantly lower Psychomotor Development Index scores at 1 year of age after infant cardiac surgery . The effect was independent of ethnicity , socioeconomic status , cardiac defect , and use of deep hypothermic circulatory arrest . An effect of the apolipoprotein E epsilon4 allele was not detected . Genetic polymorphisms that decrease neuroresiliency and impair neuronal repair after central nervous system injury are important risk factors for neurodevelopmental dysfunction after infant cardiac surgery", "While the trajectory of self-esteem from adolescence to adulthood varies from person to person , little research has examined how differences in early developmental processes might affect these pathways . This study examined how early motor skill development interacted with preterm birth status to predict self-esteem from adolescence through the early 30s . We addressed this using the oldest known , prospect ively followed cohort of extremely low birth weight ( Motor skills were measured using a performance-based assessment at age 8 and a retrospective self-report , and self-esteem was reported during three follow-up periods ( age 12 - 16 , age 22 - 26 , and age 29 - 36 ) . We found that birth weight status moderated the association between early motor skills and self-esteem . Stable over three decades , the self-esteem of normal birth weight participants was sensitive to early motor skills such that those with poorer motor functioning manifested lower self-esteem , while those with better motor skills manifested higher self-esteem . Conversely , differences in motor skill development did not affect the self-esteem from adolescence to adulthood in individuals born at extremely low birth weight . Early motor skill development may exert differential effects on self-esteem , depending on whether one is born at term or prematurely", "IMPORTANCE There are no well-established noninvasive biomarkers for identifying patients at risk for poor outcome after surgery for congenital heart disease . Few studies have assessed prognostic accuracy of cerebral tissue oxygenation index ( cTOI ) measured by near infrared spectroscopy ( NIRS ) . OBJECTIVE To assess the utility of noninvasive NIRS monitoring as a predictor of outcomes after neonatal cardiac surgery through measurement of cTOI . To examine the utility of noninvasive NIRS monitoring in combination with lactate concentration and inotropic score in prediction of outcomes after neonatal cardiac surgery . DESIGN Prospect i ve longitudinal cohort study . SETTING Operating room and cardiac intensive care unit , Children 's National Heart Institute . PARTICIPANTS Seventy-five patients with complex congenital heart disease undergoing surgical repair within first month of life . EXPOSURE Cerebral TOI , blood lactate , and inotropic scores were measured preoperative , intraoperative and up to 24 hours postoperative . MAIN OUTCOME MEASURES Postoperative mortality and neurodevelopmental outcome assessed by the Bayley Scales of Infant Development ( BSID II ) . Mental and motor scores were obtained at 6 , 15 , and 21 months . Good outcome was defined as survival and BSID mental and motor scores ≥70 points . Poor outcome was defined as death or BSID scores of 75 patients prospect ively followed including 40 patients with single ventricle and 35 with two ventricles . Four patients died before discharge and ten died within 21 months . Seven patients were lost to follow-up . Among survivors with follow-up ( n = 54 ) , BSID was abnormal in 25 ( 46 % ) . Patients with poor outcome ( n = 39 ) had lower mean cTOI 60 minutes off-CPB ( 48 % vs. 58 % , P = .003 ) and 24 hours postoperative ( 49 % vs. 59 % , P higher lactate ( 8.2 vs. 5.0 mmol/L , P = .005 ) and higher inotropic scores ( 10 vs. 6 , P = .02 ) at 24 hours postoperative . ROC analysis indicated that cTOI had moderate predictive accuracy of outcome ( AUC = 0.751 , P predictive accuracy was improved using both cTOI and lactate at 24 hours postoperative ( AUC = 0.813 , 95 % CI : 0.705 - 0.921 , P 7.4 mmol/L , respectively ( sensitivity = 95 % ) . CONCLUSION Cerebral TOI combined with lactate at 24 hours postoperative are accurate non-invasive predictive biomarkers of patient survival and neurodevelopmental outcome in neonates with CHD undergoing cardiac surgery", "OBJECTIVES / AIM To determine whether sedation/analgesia drugs used before , during , and after infant cardiac surgery are associated with neurocognitive and functional outcomes . BACKGROUND Some animal models suggest neurotoxic effects of anesthetic drugs on the developing brain ; however , potential human effects are unknown . Whether these results can be extrapolated to humans is unknown . METHODS / MATERIAL S Prospect i ve follow-up project of all infants ≤6 weeks old having surgery for congenital heart disease between 04/03 and 12/06 . Demographic , perioperative , and sedation/analgesia variables were collected . Outcomes at kindergarten age were Wechsler Preschool and Primary Scale of Intelligence-III , Beery-Buktenica Developmental Test of Visual Motor Integration ( VMI-V ) , and General Adaptive Composite ( GAC ) of the Adaptive Behavior Assessment System-II . Multivariable linear regression was used to identify predictor variables . RESULTS From 135 infants who underwent heart surgery , 19 died , 17 were excluded , 8 were lost to follow-up , leaving 91 children for analysis . Multiple linear regression found days on chloral hydrate [ 3.5 ( 3.7 ) days ] was associated with lower performance intelligence quotient ( PIQ ) ( Effect size -1.03 ; 95 % CI -1.96 , -0.10 ; P = 0.03 ) , and cumulative dose [ 54.2 ( 60.3 ) mg·kg(-1 ) ] of benzodiazepines was associated with lower VMI scores ( Effect size -0.07 ; 95 % CI -0.12 , -0.01 ; P = 0.026 ) . No other associations were found between sedation/analgesia variables and full-scale IQ , PIQ , Verbal IQ , VMI , or GAC . CONCLUSION Assessment of this cohort at kindergarten age found a small statistically significant association between days on chloral hydrate and PIQ , and benzodiazepine cumulative dose and lower VMI . No other association between sedation/analgesia drugs and outcomes was found", "Uncertainty exists regarding the degree to which infants with congenitally malformed hearts are at risk of behavioural disorders in childhood . Data was collected as part of a r and omized clinical trial involving 155 children with surgically corrected transposition ( concordant atrioventricular and ventriculo-arterial connections or alignments ) . As infants , they underwent the arterial switch operation , involving deep hypothermia with predominantly total circulatory arrest or predominantly low-flow continuous cardiopulmonary bypass as the method of providing support to the vital organs . Parents completed the Child Behavior Checklist when the patients were aged 4 and 8 years , and the Connors ' Parent Rating Scale at the age of 8 years . When the children were aged 8 , teachers completed the Teacher 's Report Form and the Connors ' Teacher Rating Scale . In the cohort as a whole , the frequencies of behavioural problems identified by both parents and teachers were elevated , particularly on the scales for competence of the Child Behavior Checklist , and the Adaptive scales of the Teacher 's Report Form . Approximately 1 in 5 patients had scores for Total Problem Behavior in the range of clinical concern on both the Child Behavior Checklist and the Teacher 's Report Form . Few differences were found , however , according to the method of operative treatment . Postoperative seizures were associated with social and attention problems . Children experiencing academic problems at the age of 8 showed a larger increase in behavioural problems between the ages of 4 and 8 than did children making adequate academic progress . Children with congenitally malformed hearts who underwent reparative surgery in infancy using a strategy of severe haemodilution and alpha stat are at increased risk of behavioural problems in middle childhood", "OBJECTIVE The purpose of this study was to describe social-emotional outcomes and the relationship with neurodevelopmental outcomes in a cohort of 2-year-old children who underwent surgery for congenital heart disease ( CHD ) in infancy , and explore the relationship between the outcomes and parental and surgical factors . DESIGN A two-center prospect i ve cross-sectional cohort study . PATIENTS A cohort of 105 2-year-olds who underwent surgery in infancy for severe CHD MEASURES : Social-emotional and neurodevelopment was evaluated with the Infant and Toddler Social and Emotional Assessment tool ( ITSEA ) , and the Bayley Scales of Infant Toddler Development , Third Edition . RESULTS Neurodevelopment was delayed in the CHD cohort with significantly worse results compared to published Australian-based norms in all domains ( P Cognitive ( P Language ( P Social-emotional outcome was similar to Australian norms in all domains but better than the American based norms in the Internalizing domain ( P maternal education was associated to better neurodevelopmental outcome in all domains and better scores in the internalizing and externalizing domains of the ITSEA . There was a moderate correlation ( r = 0.43 , P Language and social-emotional competence . Motor development was influenced by the need for a significant cardiac reoperation . CONCLUSIONS The influences of social factors may be underestimated in the outcome of children with CHD . Language development in those with CHD may be improved with intervention targeting social-emotional competence ; further research is needed in this area", "Objective Historical cohort studies have reported adverse neurodevelopment following cardiac surgery during early infancy . Advances in surgical techniques and perioperative care have coincided with updating of neurodevelopmental assessment tools . We aim ed to determine perioperative risk factors for impaired neurodevelopment at 2 years following surgery for congenital heart disease ( CHD ) in early infancy . Design and patients We undertook a prospect i ve longitudinal study of 153 full-term infants undergoing surgery for CHD before 2 months of age . Infants were excluded if they had a genetic syndrome associated with neurodevelopmental impairment . Outcome measures Predefined perioperative parameters were recorded and infants were classified according to cardiac anatomy . At 2 years , survivors were assessed using the Bayley Scales of Infant Development-III . Results At 2 years , 130 children ( 98 % of survivors ) were assessed . Mean cognitive , language and motor scores were 93.4±13.6 , 93.6±16.1 and 96.8±12.5 respectively ( 100±15 norm ) . Twenty ( 13 % ) died and 12 ( 9 % ) survivors had severe impairment ( score , mostly language ( 8 % ) . The lowest scores were in infants born with single ventricle physiology with obstruction to the pulmonary circulation who required a neonatal systemic-to-pulmonary artery shunt . Additional risk factors for impairment included reduced gestational age , postoperative elevation of lactate or S100B and repeat cardiac surgery . Conclusions In the modern era of infant cardiac surgery and perioperative care , children continue to demonstrate neurodevelopmental delays . The use of up date d assessment tools has revealed early language dysfunction and relative sparing of motor function . Ongoing follow-up is critical in this high-risk population ", "OBJECTIVES / AIM To determine whether sedation/analgesia drugs used before , during , and after infant cardiac surgery are associated with neurodevelopmental outcome . BACKGROUND Animal models suggest detrimental effects of anesthetic drugs on the developing brain . Whether these results can be extrapolated to human neonates is unclear . METHODS / MATERIAL S This is a prospect i ve follow-up project conducted in Western Canada . In all infants ≤6 weeks of age having surgery for congenital heart disease between April 2003 and December 2006 , demographic and perioperative variables were collected prospect ively . Sedation/analgesia variables were collected retrospectively . For each drug class ( inhalationals , opioids , benzodiazepines , ketamine , and chloral hydrate ) , we calculated the cumulative dose received during hospitalization , average dose received per day , and cumulative number of days the patient received the drug . The outcomes at 18 - 24 months were as follows : General Adaptive Composite and motor scaled scores of the Adaptive Behavior Assessment System , significant mental , motor , and vocabulary delay . Multivariable logistic and linear regression was used to analyze the data . RESULTS One hundred and thirty-five neonates underwent open heart surgery ; 19 died , 16 had chromosomal abnormality , and five were lost to follow up , leaving 95 survivors for analysis . Multiple linear regression analysis found no evidence of an association between sedation/analgesia variables and ABAS-GAC score or motor scale score . Multiple logistic regression analysis found no evidence of an association between sedation/analgesia variables and significant mental , motor , or vocabulary delay . CONCLUSION We found no evidence of an association between dose and duration of sedation/analgesia drugs during the operative and perioperative period and adverse neurodevelopmental outcomes", "BACKGROUND In this study we report magnetic resonance imaging ( MRI ) brain injury and 12-month neurodevelopmental outcomes when regional cerebral perfusion ( RCP ) is used for neonatal aortic arch reconstruction . METHODS Fifty-seven neonates receiving RCP during aortic arch reconstruction were enrolled in a prospect i ve outcome study . RCP flows were determined by near-infrared spectroscopy and transcranial Doppler monitoring . Brain MRI was performed preoperatively and 7 days postoperatively . Bayley Scales of Infant Development III was performed at 12 months . RESULTS Mean RCP time was 71 ± 28 minutes ( range , 5 to 121 minutes ) and mean flow was 56.6 ± 10.6 mL/kg/min . New postoperative MRI brain injury was seen in 40 % of patients . For 35 RCP patients at age 12 months , mean Bayley Scales III Composite st and ard scores were : Cognitive , 100.1 ± 14.6 ( range , 75 to 125 ) ; Language , 87.2 ± 15.0 ( range , 62 to 132 ) ; and Motor , 87.9 ± 16.8 ( range , 58 to 121 ) . Increasing duration of RCP was not associated with adverse neurodevelopmental outcomes . CONCLUSIONS Neonatal aortic arch repair with RCP using a neuromonitoring strategy results in 12-month cognitive outcomes that are at reference population norms . Language and motor outcomes are lower than the reference population norms by 0.8 to 0.9 st and ard deviations . The neurodevelopmental outcomes in this RCP cohort demonstrate that this technique is effective and safe in supporting the brain during neonatal aortic arch reconstruction", "UNLABELLED Controversy exists regarding the integrity of the nervous system in the newborn with a congenital heart defect who must undergo corrective or palliative open heart surgery . Neurodevelopmental sequelae have been primarily attributed to surgical procedures without st and ardized evaluation of the preoperative neurologic status . OBJECTIVE To determine whether newborns with congenital heart defects demonstrate abnormalities in neurobehavioral status before surgery . STUDY DESIGN In this prospect i ve study , a st and ardized neonatal neurobehavioral assessment and a neurologic examination were conducted independently in a consecutive series of 56 neonates referred to our hospital for investigation of open heart surgery . RESULTS Neurobehavioral and neurologic abnormalities were documented in greater than half of the cohort and included hypotonia , hypertonia , jitteriness , motor asymmetries , and absent suck . Poor state regulation ( 62 % ) and feeding difficulties ( 34 % ) also were commonly observed . Furthermore , 3 subjects had seizures , 35.7 % were microcephalic , and 12.5 % were macrocephalic . The overall likelihood of neurobehavioral abnormalities was not enhanced by indicators of cardiorespiratory compromise . Interestingly , newborns with acyanotic congenital heart defects were more likely to demonstrate neurologic compromise than were those with cyanotic defects . CONCLUSIONS Findings suggest that the prevalence of neurobehavioral abnormalities before surgery in newborns with congenital heart defects has been underappreciated and would indicate that factors other than intraoperative procedures should be considered in the genesis of brain injury in this population .congenital heart defects , neurologic examination , newborn", "OBJECTIVES To assess the effect of prenatal diagnosis of congenital heart disease on neurocognitive outcomes in children with d-transposition of the great arteries ( TGA ) after surgical correction . STUDY DESIGN A prospect i ve study of children born with a TGA between 2003 and 2005 and aged 4 to 6 years was conducted . General intelligence , language , executive functions , and social cognition scores and preoperative , intraoperative , and postoperative factors were evaluated according to time of TGA diagnosis . Neurocognitive data were also compared with a control group . RESULTS Forty-five eligible patients ( 67 % male ) were examined ; 29 had a prenatal diagnosis of TGA and 16 did not . All children were comparable in age , sex , and demographic variables . Diagnostic groups did not differ in preoperative , intraoperative , and postoperative variables . Preoperative acidosis was more frequent in the postnatal group ( 18 % versus 3 % ) . All patients had normal IQ scores , language , and verbal working memory . However , neurocognitive deficits were more prevalent and more severe in children with a postnatal-TGA . Prenatal diagnosis was associated with better outcomes in executive functions . CONCLUSIONS Prenatal diagnosis of TGA is associated with better neurocognitive outcomes . Time of diagnosis may influence the development of early complex cognitive skills such as executive functions", "BACKGROUND : The newest measure of neurodevelopmental outcomes , the Bayley Scales of Infant and Toddler Development , 3rd Edition ( Bayley-III ) , gives higher-than-expected scores for preterm infants ; results after cardiac surgery are unknown . OBJECTIVES : The goal of this study was to report Bayley-III scores after cardiac surgery and compare the results with those of the Bayley Scales of Infant Development , 2nd Edition ( BSID-II ) on a subset of the same children . METHODS : In this prospect i ve , inception cohort , neurodevelopmental outcome study after complex cardiac surgery in infants from 2004 to 2007 , the Bayley-III was given to 110 survivors ( 68 % boys ) at a mean age of 21 months ( SD : 4 months ) . Analysis of variance was used to compare intergroup differences . Results for both test editions on the same 25 children were compared by using paired- sample s statistics . RESULTS : Mean ( SD ) Bayley-III mean composite scores ( CSs ) for 110 children were as follows : cognitive , 95.9 ( 14.1 ) ; language , 90.8 ( 18.1 ) ; and motor , 93.7 ( 14.2 ) , differentiating selected cardiac surgery groups . The average difference in mean CSs was 7.4 points higher than BSID-II scores for a previous cohort from this site and 7.2 points higher than a systematic review report . Direct comparison of BSID-II and Bayley-III revealed an average difference in mean CSs of 6.1 points , similar to normative results . Mean cognitive CSs increased by 10.0 ( P language by 1.4 ( P = .526 ) , and motor by 6.9 points ( P = .009 ) . CONCLUSIONS : Research ers should be careful attributing higher Bayley-III scores to changes in acute care . At-risk children who previously qualified for early developmental intervention may no longer do so . School-age longitudinal studies are needed to determine the accuracy of early developmental estimates using the Bayley-III", "OBJECTIVES To determine neonatal global and regional brain volumes in infants with congenital heart disease ( CHD ) in comparison with healthy controls and to determine brain growth . STUDY DESIGN Prospect i ve cohort study in infants undergoing open-heart surgery for complex CHD . Global and regional volumetric measurements on preoperative cerebral magnetic resonance imaging were manually segmented in children without overt brain lesions . RESULTS Preoperative brain volumetry of 19 patients demonstrates reduction in total and regional brain volumes , without any specific regional predilection compared with 19 healthy control infants ( total brain volume reduction : 21 % , regional brain volume reduction 8%-28 % , all P Infants with CHD undergoing bypass surgery have smaller brain volumes prior to surgery without a specific regional predilection . This suggests a fetal origin of reduced brain growth", "OBJECTIVE To assess neurodevelopment in children with hypoplastic left heart syndrome ( HLHS ) or other types of functionally single ventricle ( univentricular heart , UVH ) and to estimate the effect of possible clinical predictors on outcome . STUDY DESIGN A total of 22 patients with HLHS and 14 with UVH , surviving after palliative surgery performed in the same center , and 42 healthy control subjects were examined at a median age of 30.2 months neurologically and according to the Bayley Scales of Infant Development in a population based prospect i ve neurodevelopmental follow-up study . RESULTS The mean Mental Developmental Index was significantly lower ( 89.9 ) in patients with HLHS than in control subjects ( 105.5 , P mean Psychomotor Developmental Index in patients with HLHS ( 80.7 , P mean Mental Developmental Index lags behind control subjects . Psychomotor Developmental Index is impaired in patients with both HLHS and UVH . Routine neurodevelopmental follow-up is recommended for this seriously ill patient group", "BACKGROUND Preterm children have problems with mathematics but knowledge about the predictors of specific mathematic abilities in preterm population s is scarce . AIMS This study investigated neurodevelopmental pathways to children 's general and specific mathematic abilities across the full gestational age range . STUDY DESIGN Prospect i ve geographically defined longitudinal investigation in Germany . SUBJECTS 947 children across the full gestational age range ( 23 - 41 weeks ) . Outcome measures . At 8 years , children 's cognitive and mathematic abilities were measured and residuals of a regression predicting mathematic scores by IQ were used to identify specific mathematic abilities . RESULTS Neurodevelopmental cascade models revealed that adverse effects of preterm birth on mathematic abilities were mediated by neonatal risk . Specific mathematic abilities were uniquely predicted by the duration of hospitalization and ventilation . CONCLUSIONS Prolonged neonatal medical treatment and , in particular , mechanical ventilation may lead to specific impairments in mathematic tasks . These findings have implication s for the mode of respiratory support in neonates , routine follow-up and intervention planning as well as research about brain reorganization after preterm birth", "OBJECTIVES Neonates undergoing complex congenital heart surgery have a significant incidence of neurologic problems . Erythropoietin has antiapoptotic , antiexcitatory , and anti-inflammatory properties to prevent neuronal cell death in animal models , and improves neurodevelopmental outcomes in full-term neonates with hypoxic ischemic encephalopathy . We design ed a prospect i ve phase I/II trial of erythropoietin neuroprotection in neonatal cardiac surgery to assess safety and indicate efficacy . METHODS Neonates undergoing surgery for D-transposition of the great vessels , hypoplastic left heart syndrome , or aortic arch reconstruction were r and omized to 3 perioperative doses of erythropoietin or placebo . Neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development III was performed at age 12 months . RESULTS Fifty-nine patients received the study drug . Safety profile , including magnetic resonance imaging brain injury , clinical events , and death , was not different between groups . Three patients in each group died . Forty-two patients ( 22 in the erythropoietin group and 20 in the placebo group ; 79 % of survivors ) returned for 12-month follow-up . In the group receiving erythropoietin , mean Cognitive Scale scores were 101.1 ± 13.6 , Language Scale scores were 88.5 ± 12.8 , and Motor Scale scores were 89.9 ± 12.3 . In the group receiving placebo , Cognitive Scale scores were 106.3 ± 10.8 ( P = .19 ) , Language Scores were 92.4 ± 12.4 ( P = .33 ) , and Motor Scale scores were 92.6 ± 14.1 ( P = .51 ) . CONCLUSIONS Safety profile for erythropoietin administration was not different than placebo . Neurodevelopmental outcomes were not different between groups ; however , this pilot study was not powered to definitively address this outcome . Lessons learned suggest optimized study design features for a larger prospect i ve trial to definitively address the utility of erythropoietin for neuroprotection in this population", "OBJECTIVE To test the hypothesis that postoperative length of stay ( LOS ) after infant heart surgery might be an easily measured surrogate marker for various events that culminate in later adverse cognitive outcome . METHODS Among 160 eligible patients with D-transposition of the great arteries undergoing reparative surgery in infancy , 155 ( 97 % ) were reevaluated at age 8 years with IQ and achievement testing . We explored whether LOS quartiles were associated with these outcomes when adjusting for perioperative and sociodemographic variables . RESULTS Longer cardiac intensive care unit ( CICU ) LOS quartiles were associated at age 8 years with lower full-scale IQ ( P=.02 ) , lower verbal IQ ( P=.02 ) , and with tendencies toward lower performance IQ ( P=.08 ) and math achievement ( P=.08 ) in adjusted models . Compared with patients in the first quartile of CICU LOS , those in the fourth quartile had mean scores for full-scale IQ that were lower by 7.2 points ( P=.01 ) ; verbal IQ , 7.3 points ( P=.02 ) ; performance IQ , 5.8 points ( P=.05 ) ; and math achievement , 6.0 points ( P=.07 ) . Analyses on hospital LOS quartile were similar . CONCLUSIONS Longer postoperative LOS is associated with worse later cognitive function , even when adjusted for perioperative events , perfusion times , and sociodemographic variables . Further research is necessary to determine the mechanisms underlying this relation", "BACKGROUND Previous research on developmental outcomes of infants with congenital heart disease ( CHD ) has shown delays in both cognitive and motor skills . AIMS To describe outcomes on the Bayley Scales of Infant and Toddler Development , 3rd edition ( Bayley-III ) for infants with CHD and to compare those findings to published results for similar sample s of infants assessed on the 2nd edition of the Bayley Scales ( BSID-II ) . STUDY DESIGN Prospect i ve cohort . PARTICIPANTS AND OUTCOME MEASURES Of 50 infants with CHD who participated in this longitudinal study ( 2006 - 2008 ) at the Royal Children 's Hospital in Melbourne , Australia , 47 were assessed on the Bayley-III ( median age=24.5 months ) , administered by a psychologist or neonatologist . Although neither assessor was blind to the CHD diagnosis , they were unaware of results of previous developmental assessment s conducted in this longitudinal study . RESULTS For the Bayley-III cognitive composite score , 17.0 % of infants showed mild delays ( 1 - 2 SD below the mean ) , 2.1 % had moderate delays ( 2 - 3 SD below the mean ) , and none had severe delays ( greater than 3 SD below the mean ) . Motor composite scores showed mild delays in 10.9 % of infants and moderate delays in 2.2 % ; none had severe motor delays . These findings differ from study results using the BSID-II in similar infants . CONCLUSIONS The Bayley-III may underestimate developmental delay in 2-year-old children with CHD when compared to results of similar children tested at 12 - 36 months of age on the BSID-II", "Background : Neonates with congenital heart disease ( CHD ) are at high risk of punctate white matter injury ( WMI ) and impaired brain development . We hypothesized that WMI in CHD neonates occurs in a characteristic distribution that shares topology with preterm WMI and that lower birth gestational age ( GA ) is associated with larger WMI volume . Objective : ( 1 ) To quantitatively assess the volume and location of WMI in CHD neonates across three centres . ( 2 ) To compare the volume and spatial distribution of WMI between term CHD neonates and preterm neonates using lesion mapping . Methods : In 216 term born CHD neonates from three prospect i ve cohorts ( mean birth GA : 39 weeks ) , WMI was identified in 86 neonates ( UBC : 29 ; UCSF : 43 ; UCZ : 14 ) on pre‐ and /or post‐operative T1 weighted MRI . WMI was manually segmented and volumes were calculated . A st and ard brain template was generated . Probabilistic WMI maps ( total , pre‐ and post‐operative ) were developed in this common space . Using these maps , WMI in the term CHD neonates was compared with that in preterm neonates : 58 at early‐in‐life ( mean postmenstrual age at scan 32.2 weeks ) ; 41 at term‐equivalent age ( mean postmenstrual age at scan 40.1 weeks ) . Results : The total WMI volumes of CHD neonates across centres did not differ ( p = 0.068 ) : UBC ( median = 84.6 mm3 , IQR = 26–174.7 mm3 ) ; UCSF ( median = 104 mm3 , IQR = 44–243 mm3 ) ; UCZ ( median = 121 mm3 , IQR = 68–200.8 mm3 ) . The spatial distribution of WMI in CHD neonates showed strong concordance across centres with predilection for anterior and posterior rather than central lesions . Predominance of anterior lesions was apparent on the post‐operative WMI map relative to the pre‐operative map . Lower GA at birth predicted an increasing volume of WMI across the full cohort ( 41.1 mm3 increase of WMI per week decrease in gestational age ; 95 % CI 11.5–70.8 ; p = 0.007 ) , when accounting for centre and heart lesion . While WMI in term CHD and preterm neonates occurs most commonly in the intermediate zone/outer subventricular zone there is a paucity of central lesions in the CHD neonates relative to preterms . Conclusions : WMI in term neonates with CHD occurs in a characteristic topology . The spatial distribution of WMI in term neonates with CHD reflects the expected maturation of pre‐oligodendrocytes such that the central regions are less vulnerable than in the preterm neonates . HighlightsWe quantitatively assess the volume and location of WMI in term CHD neonates . WMI in term CHD neonates occurs in a characteristic topology . WMI distribution reflects regional variability in pre‐oligodendrocyte maturation . Term CHD neonates exhibit less central WMI relative to that of preterm newborns . Younger birth GA predicts greater WMI volume independent of other risk", "BACKGROUND Neurodevelopmental outcome after neonatal arterial switch operation for complete transposition of the great arteries is an important topic needing prospect i ve assessment . METHODS A group of 33 unselected children ( 3.0 to 4.6 years ) operated on as neonates with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass and a control group of 32 age-matched healthy children ( 3.0 to 4.8 years ) underwent evaluation of socioeconomic and clinical neurological status and a st and ardized test comprising all areas of child development . Results of patients were related to those of the control group , to population norms , and to preoperative , perioperative , and postoperative cerebral risk factors . RESULTS Clinical neurological status was normal in 26 patients ( 78.8 % ) and reduced in 7 ( 21.2 % ) . Complete developmental score and the subscores for motor function , visual perception , learning and memory , cognitive function , language , and socioemotional functions were not different compared to population norms . Compared to the patients , the children of the control group scored higher on tests of complete development , cognition , and language , but also on socioeconomic status . Complete developmental score and the scores for motor , cognitive , and language functions were weakly inversely related to the duration of circulatory arrest , but not to the duration of bypass . Cerebral risk factors such as serum levels of the neuron-specific enolase , perinatal acidosis , perinatal asphyxia , peri- and postoperative cardiocirculatory insufficiency , or clinical seizures were not correlated to the test results . CONCLUSIONS Neonatal arterial switch operation with combined circulatory arrest and low flow bypass is associated with neurological impairment , but not with reduced development as assessed by formal testing of motor , cognitive , language , and behavioral functions . Perioperative serum level of the neuron-specific enolase is not a valid marker for later developmental impairment", "BACKGROUND Early identification of infants with CHD at heightened risk of developmental delays can inform surveillance priorities . This study investigated pre-operative and post-operative neuromotor performance in infants undergoing open-heart surgery , and their developmental status at 6 months of age , to identify risk factors and inform care pathways . METHODS Infants undergoing open-heart surgery before 4 months of age were recruited into a prospect i ve cohort study . Neuromotor performance was assessed pre-operatively and post-operatively using the Test of Infant Motor Performance and Prechtl 's Assessment of General Movements . Development was assessed at 6 months of age using the Ages and Stages Question naire third edition . Pre-operative and post-operative General Movements performance was compared using McNemar 's test and test of infant motor performance z-scores using Wilcoxon 's signed rank test . Risk factors for delayed development at 6 months were explored using logistic regression . RESULTS Sixty infants were included in this study . In the 23 ( 38 % ) infants . A total of 60 infants were recruited . In the 23 ( 38 % ) infants assessed pre-operatively , there was no significant difference between pre- and post-operative performance on the GMs ( p=0.63 ) or TIMP ( p=0.28 ) . At discharge , 15 ( 26 % ) infants presented with abnormal GMs , and the median TIMP z-score was -0.93 ( IQR : -1.4 to -0.69 ) . At 6 months , 28 ( 52.8 % ) infants presented with gross motor delay on the ASQ-3 , significantly negatively associated with gestational age ( p=0.03 ) , length of hospital stay ( p=0.04 ) and discharge TIMP score ( p=0.01 ) . CONCLUSIONS Post-operative assessment using the GMs and TIMP may be useful to identify infants requiring individualised care and targeted developmental follow-up . Long-term developmental surveillance beyond 6 months of age is recommended" ]

[ "Electroencephalography (EEG)-neurofeedback has been shown to offer therapeutic benefits to patients with attention-deficit/hyperactivity disorder ( ADHD ) in several , mostly uncontrolled studies . This pilot study is design ed to test the feasibility and safety of using a double-blind placebo feedback-controlled design and to explore the initial efficacy of individualized EEG-neurofeedback training in children with ADHD . Fourteen children ( 8–15 years ) with ADHD defined according to the DSM-IV-TR criteria were r and omly allocated to 30 sessions of EEG-neurofeedback ( n = 8) or placebo feedback ( n = 6 ) . Safety measures ( adverse events and sleep problems ) , ADHD symptoms and global improvement were monitored . With respect to feasibility , all children completed the study and attended all study visits and training sessions . No significant adverse effects or sleep problems were reported . Regarding the expectancy , 75 % of children and their parent(s ) in the active neurofeedback group and 50 % of children and their parent(s ) in the placebo feedback group thought they received placebo feedback training . Analyses revealed significant improvements of ADHD symptoms over time , but changes were similar for both groups . This pilot study shows that it is feasible to conduct a rigorous placebo-controlled trial to investigate the efficacy of neurofeedback training in children with ADHD . However , a double-blind design may not be feasible since using automatic adjusted reward thresholds may not work as effective as manually adjusted reward thresholds . Additionally , implementation of active learning strategies may be an important factor for the efficacy of EEG-neurofeedback training . Based on the results of this pilot study , changes are made in the design of the ongoing study", "The efficacy of group parent training was assessed in improving compliance and time on task in preschoolers with attention-deficit disorder with hyperactivity . Positive effects were obtained on measures of child compliance , but not on measures of attention . Parental compliance-management skills and overall style of interaction were also positively affected . The use of parent training for early intervention with ADDH children is discussed", "This study evaluates the effectiveness of cognitive behavioral therapy ( CBT ) in improving the home behavior of children with attention deficit hyperactivity disorder ( ADHD ) . Twenty-five boys ( age 7 to 13 ) with a diagnosis of ADHD were r and omized to a CBT or supportive therapy control group . Outcome measures included parent and teacher ratings of the child on the Behavior Problem Checklist-Attention Problem Subscale ( BPC-AP ) , and the Self-Control Rating Scale ( SCRS ) , parent ratings on the Modified Werry Weiss Activity Scale , and child ratings on the Piers Harris Self-Concept Scale and Matching Familiar Figures Task . Data were analyzed using a two-way analysis of variance for main effects . A significant improvement favoring CBT was found on the Werry Weiss Scale , which measures the parent 's perception of the child 's hyperactivity in the home , and the child 's rating of his/her self-esteem on the Piers Harris Self-Concept Scale . Other outcome measures did not demonstrate statistical differences . This research provides support for the use of CBT in children with ADHD . CBT was found to improve the parent 's perception of the child 's hyperactivity in the home as well as the child 's self-esteem", "Methods : Various developmental problems including attention-deficit/hyperactivity disorder ( ADHD ) have been linked to biological deficiencies in polyunsaturated fatty acids ( PUFAs ) . Additionally , there is evidence that symptoms may be reduced with PUFA supplementation . This study investigated effects of supplementation with PUFAs on symptoms typically associated with ADHD . Because nutrients work synergistically , additional effects of micronutrient supplementation were also investigated . A total of 132 Australian children aged 7 to 12 years with scores ≥2 SD above the population average on the Conners ADHD Index participated in a r and omized , placebo-controlled , double-blind intervention over 15 weeks , taking PUFAs alone , PUFAs + micronutrients , or placebo . Due to unreturned question naires , data were only available for 104 children . Results : Significant medium to strong positive treatment effects were found on parent ratings of core ADHD symptoms , inattention , hyperactivity/impulsivity , on the Conners Parent Rating Scale ( CPRS ) in both PUFA treatment groups compared with the placebo group ; no additional effects were found with the micronutrients . After a one-way crossover to active supplements in all groups for a further 15 weeks , these results were replicated in the placebo group , and the treatment groups continued to show significant improvements on CPRS core symptoms . No significant effects were found on Conners Teacher Rating Scales . Conclusion : These results add to preliminary findings that ADHD-related problems with inattention , hyperactivity , and impulsivity might respond to treatment with PUFAs and that improvements may continue with supplementation extending to 30 weeks", "Neurofeedback treatment has been demonstrated to reduce inattention , impulsivity and hyperactivity in children with attention deficit/hyperactivity disorder ( ADHD ) . However , previous studies did not adequately control confounding variables or did not employ a r and omized reinforcer-controlled design . This study addresses those method ological shortcomings by comparing the effects of the following two matched biofeedback training variants on the primary symptoms of ADHD : EEG neurofeedback ( NF ) aim ing at theta/beta ratio reduction and EMG biofeedback ( BF ) aim ing at forehead muscle relaxation . Thirty-five children with ADHD ( 26 boys , 9 girls ; 6–14 years old ) were r and omly assigned to either the therapy group ( NF ; n = 18 ) or the control group ( BF ; n = 17 ) . Treatment for both groups consisted of 30 sessions . Pre- and post-treatment assessment consisted of psychophysiological measures , behavioural rating scales completed by parents and teachers , as well as psychometric measures . Training effectively reduced theta/beta ratios and EMG levels in the NF and BF groups , respectively . Parents reported significant reductions in primary ADHD symptoms , and inattention improvements in the NF group were higher compared to the control intervention ( BF , dcorr = −.94 ) . NF training also improved attention and reaction times on the psychometric measures . The results indicate that NF effectively reduced inattention symptoms on parent rating scales and reaction time in neuropsychological tests . However , regarding hyperactivity and impulsivity symptoms , the results imply that non-specific factors , such as behavioural contingencies , self-efficacy , structured learning environment and feed-forward processes , may also contribute to the positive behavioural effects induced by neurofeedback training", "This pilot study evaluated the effects of supplementation with PUFA on blood FA composition and behavior in children with Attention-Deficit/Hyperactivity Disorder (AD/HD)-like symptoms also reporting thirst and skin problems . Fifty children were r and omized to treatment groups receiving either a PUFA supplement providing a daily dose of 480 mg DHA , 80 mg EPA , 40 mg arachidonic acid ( AA ) , 96 mg GLA , and 24 mg α-tocopheryl acetate , or an olive oil placebo for 4 mon of doubleblind parallel treatment . Supplementation with the PUFA led to a substantial increase in the proportions of EPA , DHA , and α-tocopherol in the plasma phospholipids and red blood cell ( RBC ) total lipids , but an increase was noted in the plasma phospholipid proportions of 18∶3n-3 with olive oil as well . Significant improvements in multiple but outcomes ( as rated by parents ) were noted in both groups , but a clear benefit from PUFA supplementation for all behaviors characteristic of AD/HD was not observed . For most outcomes , improvement of the PUFA group was consistently nominally better than that of the olive oil group ; but the treatment difference was significantly , by secondary intent-to-treat analysis on only 2 out of 16 outcome measures : conduct problems rated by parents ( −42.7 vs. −9.9 % , n=47 , P=0.05 ) , and attention symptoms rated by teachers ( −14.8 vs. + 3.4 % , n=47 , P=0.03 ) . PUFA supplementation led to a greater number of participants showing improvement in oppositional defiant behavior from a clinical to a non clinical range compared with olive oil supplementation ( 8 out of 12 vs. 3 out of 11 , n=33 , P=0.02 ) . Also , significant correlations were observed when comparing the magnitude of change between increasing proportions of EPA in the RBC and decreasing disruptive behavior as assessed by the Abbreviated Symptom Question naire ( ASQ ) for parents ( r=−0.38 , n=31 , P ) , and for EPA and DHA in the RBC and the teachers ' Disruptive Behavior Disorders ( DBD ) Rating Scale for Attention ( r=−0.49 , n=24 , P increase in α-tocopherol concentrations in the RBC and a decrease in scores for all four subscales of the teacher 's DBD ( Hyperactivity , r=−0.45 ; Attention , r=−0.60 ; Conduct , r=−0.41 ; Oppositional/Defiant Disorder , r=−0.54 ; n=24 , P as well as the ASQ for teachers ( r=−0.51 , n=24 , P both n−3 FA and vitamin E in children with behavioral disorders", "Thirty-one children , selected for marked inattention and overactivity , were studied in a double-blind , placebo-controlled crossover study of essential fatty acid ( EFA ) supplementation . Subjects received the active treatment and placebo conditions for 4 weeks each and were assessed on a variety of cognitive , motor , and st and ardized rating scale measures . EFA supplementation ( evening primrose oil ; Efamol ® ) result ed in significantly lower levels of palmitoleic acid ( a nonessential fatty acid ) and higher concentrations of dihomogammalinolenic acid , an EFA previously found to be deficient in some hyperactive children . Supplementation was also associated with significant changes on two performance tasks and with significant improvement to parent ratings on the subscales design ated as Attention Problem and Motor Excess of the Revised Behavior Problem Checklist . However , a variety of eight other psychomotor performance tests and two st and ardized teacher rating scales failed to indicate treatment effects . When the experimentwise probability level was set at.05 , only 2 of 42 variables showed treatment effects . Baseline EFA concentrations appeared to be unrelated to treatment response . It was concluded that EFA supplementation , as employed here , produces minimal or no improvements in hyperactive children selected without regard to baseline EFA concentrations", "Utilizing a double-blind , placebo design , the effects of a high ( 0.8 mg/kg ) and a low ( 0.4 mg/kg ) dose of methylpheni date alone and in combination with behavioral parent training plus child self-control instruction were evaluated with 96 attention deficit hyperactivity disorder children . No evidence of the superiority of the combined conditions relative to medication alone was found . Some limited support was found for the hypothesis that the effects of a high dose of psychostimulant medication could be achieved by combining the low dose with a behavioral intervention . The importance of the latter finding is highlighted by the fact that both the benefits and untoward effects of the psychostimulants appear to increase with the dose", "Few studies have examined whether attention can be improved with training , even though attention difficulties adversely affect academic achievement . The present study was a r and omized-controlled trial evaluating the impact of Computerized Attention Training ( CAT ) and Computer Assisted Instruction ( CAI ) on attention and academic performance in 77 inattentive first grade rs . Students receiving either intervention were more likely than controls to show a moderate decline in teacher rated attention problems in first grade . Students receiving CAI also showed gains in reading fluency and in teacher ratings of academic performance . Intervention effects for attention were absent by second grade largely because attention problems declined in all groups . However , post hoc analyses indicated potential longer-term benefits for children with 6 or more inattentive symptoms at baseline . Persistent attention problems were associated with poorer academic performance in multiple domains . Results provide initial evidence that CAT and CAI can improve children ’s attention in the classroom - and support additional studies to determine whether more clinical ly significant benefits are attainable", "Nine hyperactive male subjects , selected on the basis of showing a favorable \" response \" to the Feingold diet in an earlier study , were maintained on a strict elimination ( Feingold ) diet for 11 weeks , and were given multiple trials of placebo and challenge food material s. Parental and teacher ratings , classroom behavior observations , and neuropsychological test scores obtained during baseline , placebo , and challenge conditions , in general , were not found to be adversely affected by the artificial color challenge material s. As expected , comparable data gathered on a matched control group showed them to receive substantially better ratings than the hyperactive subjects on the majority of the comparison measures employed . Possible explanations for the discrepancy between the dramatic clinical -anecdotal reports that have been given and the much more equivocal findings from formal experimental projects are presented", "OBJECTIVE To evaluate two different parent-based therapies for preschool attention-deficit/hyperactivity disorder ( ADHD ) in a community sample . METHOD Three-year-old children displaying a preschool equivalent of ADHD ( n = 78 ) were r and omly assigned to either a parent training ( PT ; n = 30 ) , a parent counseling and support ( PCO&S ; n = 28 ) , or a waiting-list control group ( n = 20 ) . The PT group received coaching in child management techniques . The PC&S group received nondirective support and counseling . Measures of child symptoms and mothers ' well-being were taken before and after intervention and at 15 weeks follow-up . RESULTS ADHD symptoms were reduced ( F2,74 = 11.64 ; p mothers ' sense of well-being was increased by PT relative to both other groups ( F2,74 = 10.32 ; p ly significant improvement ( chi 2 = 4.08 ; p = .048 ) . CONCLUSIONS PT is a valuable treatment for preschool ADHD . PC&S had little effect on children 's behavior . Constructive training in parenting strategies is an important element in the success of parent-based interventions . Psychostimulants are not a necessary component of effective treatment for many children with preschool ADHD", "There is accumulating evidence that computerised cognitive training of inhibitory control and /or working memory can lead to behavioural improvement in children with AD/HD . Using a r and omised waitlist control design , the present study examined the effects of combined working memory and inhibitory control training , with and without passive attention monitoring via EEG , for children with and without AD/HD . One hundred and twenty-eight children ( 60 children with AD/HD , 68 without AD/HD ) were r and omly allocated to one of three training conditions ( waitlist ; working memory and inhibitory control with attention monitoring ; working memory and inhibitory control without attention monitoring ) and completed with pre- and post-training assessment s of overt behaviour ( from 2 sources ) , trained and untrained cognitive task performance , and resting EEG activity . The two active training conditions completed 25 sessions of training at home over a 4- 5-week period . Results showed significant improvements in overt behaviour for children with AD/HD in both training conditions compared to the waitlist condition as rated by a parent and other adult . Post-training improvements in the areas of spatial working memory , ignoring distracting stimuli , and sustained attention were reported for children with AD/HD . Children without AD/HD showed behavioural improvements after training . The improvements for both groups were maintained over the 6-week period following training . The passive attention monitoring via EEG had a minor effect on training outcomes . Overall , the results suggest that combined WM/IC training can result in improved behavioural control for children with and without AD/HD", "Two functional magnetic resonance imaging ( fMRI ) experiments were undertaken to measure the effect of neurofeedback training ( NFT ) , in AD/HD children , on the neural substrates of selective attention and response inhibition . Twenty unmedicated AD/HD children participated to these experiments . Fifteen children were r and omly assigned to the Experimental ( EXP ) group whereas the other five children were r and omly assigned to the Control ( CON ) group . Only subjects in the EXP group underwent NFT . EXP subjects were trained to enhance the amplitude of the SMR ( 12–15 Hz ) and beta 1 activity ( 15–18 Hz ) , and decrease the amplitude of theta activity ( 4–7 Hz ) . Subjects from both groups were scanned one week before the beginning of NFT ( Time 1 ) and 1 week after the end of NFT ( Time 2 ) , while they performed a “ Counting Stroop ” task ( Experiment 1 ) and a Go/No-Go task ( Experiment 2 ) . At Time 1 , in both groups , the Counting Stroop task was associated with significant activation in the left superior parietal lobule . For the Go/No-Go task , no significant activity was detected in the EXP and CON groups . At Time 2 , in both groups , the Counting Stroop task was associated with significant activation of the left superior parietal lobule . This time , however , there were significant loci of activation , in the EXP group , in the right ACC , left cau date nucleus , and left substantia nigra . No such activation loci were seen in CON subjects . For the Go/No-Go task , significant loci of activation were noted , in the EXP group , in the right ventrolateral prefrontal cortex , right ACcd , left thalamus , left cau date nucleus , and left substantia nigra . No significant activation of these brain regions was measured in CON subjects . These results suggest that NFT has the capacity to functionally normalize the brain systems mediating selective attention and response inhibition in AD/HD children", "There are no empirically supported psychosocial treatments for adolescents with attention-deficit hyperactivity disorder ( ADHD ) . This study examined the treatment benefits of the Challenging Horizons Program ( CHP ) , a psychosocial treatment program design ed to address the impairment and symptoms associated with this disorder in young adolescents . In addition to evaluating social and academic functioning outcomes , two critical questions from previous studies pertaining to the timing , duration , and family involvement in treatment were addressed . Forty-nine students recruited in two cohorts were r and omly assigned to receive either the CHP or a community care condition . Outcomes suggested that students who received the CHP improved compared to students in the control condition on measures of symptoms and impairment . Implication s related to timing , duration , and family involvement are reported , as well as recommendations for future studies", "BACKGROUND Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder ( ADHD ) , but no longer-term ( i.e. , > 4 months ) investigations have compared these 2 treatments or their combination . METHODS A group of 579 children with ADHD Combined Type , aged 7 to 9.9 years , were assigned to 14 months of medication management ( titration followed by monthly visits ) ; intensive behavioral treatment ( parent , school , and child components , with therapist involvement gradually reduced over time ) ; the two combined ; or st and ard community care ( treatments by community providers ) . Outcomes were assessed in multiple domains before and during treatment and at treatment end point ( with the combined treatment and medication management groups continuing medication at all assessment points ) . Data were analyzed through intent-to-treat r and om-effects regression procedures . RESULTS All 4 groups showed sizable reductions in symptoms over time , with significant differences among them in degrees of change . For most ADHD symptoms , children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care . Combined and medication management treatments did not differ significantly on any direct comparisons , but in several instances ( oppositional/aggressive symptoms , internalizing symptoms , teacher-rated social skills , parent-child relations , and reading achievement ) combined treatment proved superior to intensive behavioral treatment and /or community care while medication management did not . Study medication strategies were superior to community care treatments , despite the fact that two thirds of community-treated subjects received medication during the study period . CONCLUSIONS For ADHD symptoms , our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication . Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms , but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes", "In a Latin-square double-crossover with r and om assignment to sequence , 18 boys , aged 6 - 12 years , with attention-deficit hyperactivity disorder received 1 month each of placebo , D-amphetamine , and Efamol ( evening primrose oil containing gamma-linolenic acid , with vitamin E as preservative ) . Parents ' ratings were noncontributory . Teachers ' ratings showed a trend of Efamol effect between placebo and D-amphetamine . The trend reached significance ( p less than 0.05 ) only on Conners Hyperactivity Factor . Dosage may be crucial ; 8 Efamol capsules per day were used in this study . Heuristic data scrutiny suggested possible interaction ( sequence effect ) . Further study with a different design and dose is suggested . This study does not establish Efamol as an effective treatment", " 76 selected overactive children were treated with an oligoantigenic diet , 62 improved , and a normal range of behaviour was achieved in 21 of these . Other symptoms , such as headaches , abdominal pain , and fits , also often improved . 28 of the children who improved completed a double-blind , crossover , placebo-controlled trial in which foods thought to provoke symptoms were reintroduced . Symptoms returned or were exacerbated much more often when patients were on active material than on placebo . 48 foods were incriminated . Artificial colorants and preservatives were the commonest provoking substances , but no child was sensitive to these alone", "Teacher ratings , objective classroom and laboratory observational data , attention-concentration , and other psychological measures obtained on 36 school-age , hyperactive boys under experimental and control diet conditions yielded no support for the Feingold hypothesis . Parental ratings revealed positive behavioral changes for the experimental diet ; however , they seemed primarily attributable to one diet sequence . Parents ' behavioral ratings on ten hyperactive , preschool boys indicated a positive response to the experimental diet ; again , laboratory observations showed no diet effect", "The efficacy of the Incredible Years parent and child training programs is established in children diagnosed with oppositional defiant disorder but not among young children whose primary diagnosis is attention-deficit/hyperactivity disorder ( ADHD ) . We conducted a r and omized control trial evaluating the combined parent and child program interventions among 99 children diagnosed with ADHD ( ages 4–6 ) . Mother reported significant treatment effects for appropriate and harsh discipline , use of physical punishment , and monitoring , whereas fathers reported no significant parenting changes . Independent observations revealed treatment effects for mothers ' praise and coaching , mothers ' critical statements , and child total deviant behaviors . Both mothers and fathers reported treatment effects for children 's externalizing , hyperactivity , inattentive and oppositional behaviors , and emotion regulation and social competence . There were also significant treatment effects for children 's emotion vocabulary and problem-solving ability . At school teachers reported treatment effects for externalizing behaviors and peer observations indicated improvements in treated children 's social competence", "OBJECTIVE To study the efficacy and safety of phosphatidylserine ( PS ) containing Omega3 long-chain polyunsaturated fatty acids attached to its backbone ( PS-Omega3 ) in reducing attention-deficit/ hyperactivity disorder ( ADHD ) symptoms in children . METHOD A 15-week , double-blind , placebo-controlled phase followed by an open-label extension of additional 15 weeks . Two hundred ADHD children were r and omized to receive either PS-Omega3 or placebo , out of them , 150 children continued into the extension . Efficacy was assessed using Conners ' parent and teacher rating scales ( CRS-P , T ) , Strengths and Difficulties Question naire ( SDQ ) , and Child Health Question naire ( CHQ ) . Safety evaluation included adverse events monitoring . RESULTS The key finding of the double-blind phase was the significant reduction in the Global : Restless/impulsive subscale of CRS-P and the significant improvement in Parent impact-emotional ( PE ) subscale of the CHQ , both in the PS-Omega3 group . Exploratory subgroup analysis of children with a more pronounced hyperactive/impulsive behavior , as well as mood and behavior-dysregulation , revealed a significant reduction in the ADHD-Index and hyperactive components . Data from the open-label extension indicated sustained efficacy for children who continued to receive PS-Omega3 . Children that switched to PS-Omega3 treatment from placebo showed a significant reduction in subscales scores of both CRS-P and the CRS-T , as compare to baseline scores . The treatment was well tolerated . CONCLUSIONS The results of this 30-week study suggest that PS-Omega3 may reduce ADHD symptoms in children . Preliminary analysis suggests that this treatment may be especially effective in a subgroup of hyperactive-impulsive , emotionally and behaviorally-dysregulated ADHD 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", "BACKGROUND For children with attention deficit/hyperactivity disorder ( ADHD ) , a reduction of inattention , impulsivity and hyperactivity by neurofeedback ( NF ) has been reported in several studies . But so far , unspecific training effects have not been adequately controlled for and /or studies do not provide sufficient statistical power . To overcome these method ological shortcomings we evaluated the clinical efficacy of neurofeedback in children with ADHD in a multisite r and omised controlled study using a computerised attention skills training as a control condition . METHODS 102 children with ADHD , aged 8 to 12 years , participated in the study . Children performed either 36 sessions of NF training or a computerised attention skills training within two blocks of about four weeks each ( r and omised group assignment ) . The combined NF treatment consisted of one block of theta/beta training and one block of slow cortical potential ( SCP ) training . Pre-training , intermediate and post-training assessment encompassed several behaviour rating scales ( e.g. , the German ADHD rating scale , FBB-HKS ) completed by parents and teachers . Evaluation ( ' placebo ' ) scales were applied to control for parental expectations and satisfaction with the treatment . RESULTS For parent and teacher ratings , improvements in the NF group were superior to those of the control group . For the parent-rated FBB-HKS total score ( primary outcome measure ) , the effect size was .60 . Comparable effects were obtained for the two NF protocol s ( theta/beta training , SCP training ) . Parental attitude towards the treatment did not differ between NF and control group . CONCLUSIONS Superiority of the combined NF training indicates clinical efficacy of NF in children with ADHD . Future studies should further address the specificity of effects and how to optimise the benefit of NF as treatment module for ADHD", "Seventy-eight children , referred to a diet clinic because of hyperactive behaviour , were placed on a ' few foods ' elimination diet . Fifty nine improved in behaviour during this open trial . For 19 of these children it was possible to disguise foods or additives , or both , that reliably provoked behavioural problems by mixing them with other tolerated foods and to test their effect in a placebo controlled double blind challenge protocol . The results of a crossover trial on these 19 children showed a significant effect for the provoking foods to worsen ratings of behaviour and to impair psychological test performance . This study shows that observations of change in behaviour associated with diet made by parents and other people with a role in the child 's care can be reproduced using double blind methodology and objective assessment s. Clinicians should give weight to the accounts of parents and consider this treatment in selected children with a suggestive medical history", "BACKGROUND Learned self-control of slow cortical potentials ( SCPs ) may lead to behavioral improvement in attention-deficit/hyperactivity disorder ( ADHD ) . Hence , training effects should also be reflected at the neurophysiological level . METHODS Thirteen children with ADHD , aged 7 - 13 years , performed 25 SCP training sessions within 3 weeks . Before and after training , the German ADHD rating scale was completed by parents , and event-related potentials were recorded in a cued continuous performance test ( CPT ) . For a waiting-list group of nine children with ADHD , the same testing was applied . RESULTS ADHD symptomatology was reduced by approximately 25 % after SCP training . Moreover , a decrease of impulsivity errors and an increase of the contingent negative variation were observed in the CPT task . CONCLUSIONS This study provides first evidence for both positive behavioral and specific neurophysiological effects of SCP training in children with ADHD", "BACKGROUND The effectiveness of parent training ( PT ) when delivered as part of specialist tier-two services for preschool AD/HD children has been recently demonstrated . AIMS To assess the effectiveness of the same PT programme when delivered as part of routine primary care by non-specialist nurses . METHOD A sample of 89 3-year-old children with preschool AD/HD took part in a controlled trial of an eight-week ( one hour a week ) , health visitor delivered , PT package . Children , allocated r and omly to PT ( n = 59 ) and waiting list control ( WLC ; n = 30 ) groups , were compared . RESULTS PT did not reduce AD/HD symptoms . Maternal well-being decreased in both PT and WLC groups . CONCLUSIONS While PT is an effective intervention for preschool AD/HD when delivered in specialized setting s , these benefits do not appear to generalize when programme are delivered as part of routine primary care by non-specialist nurses", "BACKGROUND The effects of a restricted elimination diet in children with attention-deficit hyperactivity disorder ( ADHD ) have mainly been investigated in selected subgroups of patients . We aim ed to investigate whether there is a connection between diet and behaviour in an unselected group of children . METHODS The Impact of Nutrition on Children with ADHD ( INCA ) study was a r and omised controlled trial that consisted of an open-label phase with masked measurements followed by a double-blind crossover phase . Patients in the Netherl and s and Belgium were enrolled via announcements in medical health centres and through media announcements . R and omisation in both phases was individually done by r and om sampling . In the open-label phase ( first phase ) , children aged 4 - 8 years who were diagnosed with ADHD were r and omly assigned to 5 weeks of a restricted elimination diet ( diet group ) or to instructions for a healthy diet ( control group ) . Thereafter , the clinical responders ( those with an improvement of at least 40 % on the ADHD rating scale [ ARS ] ) from the diet group proceeded with a 4-week double-blind crossover food challenge phase ( second phase ) , in which high-IgG or low-IgG foods ( classified on the basis of every child 's individual IgG blood test results ) were added to the diet . During the first phase , only the assessing paediatrician was masked to group allocation . During the second phase ( challenge phase ) , all persons involved were masked to challenge allocation . Primary endpoints were the change in ARS score between baseline and the end of the first phase ( masked paediatrician ) and between the end of the first phase and the second phase ( double-blind ) , and the abbreviated Conners ' scale ( ACS ) score ( unmasked ) between the same timepoints . Secondary endpoints included food-specific IgG levels at baseline related to the behaviour of the diet group responders after IgG-based food challenges . The primary analyses were intention to treat for the first phase and per protocol for the second phase . INCA is registered as an International St and ard R and omised Controlled Trial , number IS RCT N 76063113 . FINDINGS Between Nov 4 , 2008 , and Sept 29 , 2009 , 100 children were enrolled and r and omly assigned to the control group ( n=50 ) or the diet group ( n=50 ) . Between baseline and the end of the first phase , the difference between the diet group and the control group in the mean ARS total score was 23·7 ( 95 % CI 18·6 - 28·8 ; p the mean ACS score between the same timepoints was 11·8 ( 95 % CI 9·2 - 14·5 ; p score increased in clinical responders after the challenge by 20·8 ( 95 % CI 14·3 - 27·3 ; p ACS score increased by 11·6 ( 7·7 - 15·4 ; p foods , relapse of ADHD symptoms occurred in 19 of 30 ( 63 % ) children , independent of the IgG blood levels . There were no harms or adverse events reported in both phases . INTERPRETATION A strictly supervised restricted elimination diet is a valuable instrument to assess whether ADHD is induced by food . The prescription of diets on the basis of IgG blood tests should be discouraged . FUNDING Foundation of Child and Behaviour , Foundation Nuts Ohra , Foundation for Children 's Welfare Stamps Netherl and s , and the KF Hein Foundation", "BACKGROUND Our objective was to estimate the lifetime prevalence of psychopathology in a sample of youth with and without attention deficit hyperactivity disorder ( ADHD ) through young adulthood using contemporaneous diagnostic and analytic techniques . METHOD We conducted a case-control , 10-year prospect i ve study of ADHD youth . At baseline , we assessed consecutively referred male , Caucasian children with ( n=140 ) and without ( n=120 ) DSM-III-R ADHD , aged 6 - 18 years , ascertained from psychiatric and pediatric sources to allow for generalizability of results . At the 10-year follow-up , 112 ( 80 % ) and 105 ( 88 % ) of the ADHD and control children , respectively , were reassessed ( mean age 22 years ) . We created the following categories of psychiatric disorders : Major Psychopathology ( mood disorders and psychosis ) , Anxiety Disorders , Antisocial Disorders ( conduct , oppositional-defiant , and antisocial personality disorder ) , Developmental Disorders ( elimination , language , and tics disorder ) , and Substance Dependence Disorders ( alcohol , drug , and nicotine dependence ) , as measured by blinded structured diagnostic interview . RESULTS The lifetime prevalence for all categories of psychopathology were significantly greater in ADHD young adults compared to controls , with hazard ratios and 95 % confidence intervals of 6.1 ( 3.5 - 10.7 ) , 2.2 ( 1.5 - 3.2 ) , 5.9 ( 3.9 - 8.8 ) , 2.5 ( 1.7 - 3.6 ) , and 2.0 ( 1.3 - 3.0 ) , respectively , for the categories described above . CONCLUSIONS By their young adult years , ADHD youth were at high risk for a wide range of adverse psychiatric outcomes including markedly elevated rates of antisocial , addictive , mood and anxiety disorders . These prospect i ve findings provide further evidence for the high morbidity associated with ADHD across the life-cycle and stress the importance of early recognition of this disorder for prevention and intervention strategies", "A crossover ‘ placebo’-controlled , double-blind design was used to examine the effectiveness of an oligoantigenic diet in 49 children with hyperactive/disruptive behavior disorder . Effects of diet were compared with those yielded by stimulant medication ( methylpheni date ) . The study was conducted in an inpatient unit at the Department of Child and Adolescent Psychiatry , Central Institute of Mental Health , Mannheim . Change in behavior was measured in st and ardized situations by trained raters , including behavior assessment when testing with CPT and PAT , during a free play situation , and at school . Twelve children ( 24 % ) showed significant behavioral improvement in two behavior ratings during diet relative to control diet conditions . Methylpheni date used in 36 children yielded more responders ( 44 % ) than diet . The amount of positive changes in behavior in those who received both treatments was about the same . Although only effective in a minority of children , dietary treatment can not be neglected as a possible access to treating hyperactive/disruptive children and merits further investigation", "The aim of this study is to assess the efficacy of a restricted elimination diet in reducing symptoms in an unselected group of children with Attention deficit/hyperactivity disorder ( ADHD ) . Dietary studies have already shown evidence of efficacy in selected subgroups . Twenty-seven children ( mean age 6.2 ) who all met the DSM-IV criteria for ADHD , were assigned r and omly to either an intervention group ( 15/27 ) or a waiting-list control group ( 12/27 ) . Primary endpoint was the clinical response , i.e. a decrease in the symptom scores by 50 % or more , at week 9 based on parent and teacher ratings on the abbreviated ten-item Conners Scale and the ADHD-DSM-IV Rating Scale . The intention-to-treat analysis showed that the number of clinical responders in the intervention group was significantly larger than that in the control group [ parent ratings 11/15 ( 73 % ) versus 0/12 ( 0 % ) ; teacher ratings , 7/10 ( 70 % ) versus 0/7 ( 0 % ) ] . The Number of ADHD criteria on the ADHD Rating Scale showed an effect size of 2.1 ( cohen ’s d ) and a scale reduction of 69.4 % . Comorbid symptoms of oppositional defiant disorder also showed a significantly greater decrease in the intervention group than it did in the control group ( cohens ’s d 1.1 , scale reduction 45.3 % ) . A strictly supervised elimination diet may be a valuable instrument in testing young children with ADHD on whether dietary factors may contribute to the manifestation of the disorder and may have a beneficial effect on the children ’s behaviour", "OBJECTIVE To assess the value of search ing for unpublished data by exploring the extent to which Cochrane review s include unpublished data and by evaluating the quality of unpublished trials . STUDY DESIGN AND SETTING We screened all 2,462 completed Cochrane review s published since 2000 in the Cochrane Data base of Systematic Review s Issue 3 , 2006 . In a r and om sample ( n=61 ) of 292 review s , including unpublished trials , we studied all 116 references . RESULTS Unpublished trials make up 8.8 % of all included trials in our sample . Thirty-eight percent of the \" unpublished \" trials have in fact been published . Allocation concealment was \" unclear \" or not adequate in 54.3 % and 61.3 % reported blinding . In 47.2 % reported withdrawal rates were > 20 % . Trials that were eventually published had larger mean population sizes ( P-value , 0.02 ) . Of the reported sponsors , 87.3 % were drug companies . Method ological quality and publication bias are mentioned in half of the review s and explored in a third . Quality ratings did not have consequences for pooling , because 82.8 % was included in the forest plots . CONCLUSIONS A minority of Cochrane review s include \" unpublished trials \" and many of these are eventually published . Truly unpublished studies have poor or unclear method ological quality . Therefore , it may be better to invest in regular updating of review s , rather than in extensive search ing for unpublished data", "Children were included in this challenge study if according to parental report ( 1 ) the child 's hyperactive behavior had been noticeably improved for at least 3 mo . as a result of adherence to the Feingold diet and ( 2 ) dietary violations such as those used in the study were reported to have a noticeable negative effect . Evaluations of 14 objective measures in a double-blind , cross-over design yielded no significant differences between diet infraction and noninfraction conditions . In addition to question ing the stated efficacy of the diet , findings suggest that one should not depend solely on parental report when evaluating a dietary effect and should also weigh potential negative effect of adherence to the diet", "OBJECTIVE To determine whether docosahexaenoic acid ( DHA ) supplementation for 4 months decreases the symptoms of attention-deficit/hyperactivity disorder ( ADHD ) . STUDY DESIGN Sixty-three 6- to-12-year-old children with ADHD , all receiving effective maintenance therapy with stimulant medication , were assigned r and omly , in a double-blind fashion , to receive DHA supplementation ( 345 mg/d ) or placebo for 4 months . Outcome variables included plasma phospholipid fatty acid patterns , scores on laboratory measures of inattention and impulsivity ( Test of Variables of Attention , Children 's Color Trails test ) while not taking stimulant medication , and scores on parental behavioral rating scales ( Child Behavior Checklist , Conners ' Rating Scale ) . Differences between groups after 4 months of DHA supplementation or placebo administration were determined by analysis of variance , controlling for age , baseline value of each outcome variable , ethnicity , and ADHD subtype . RESULTS Plasma phospholipid DHA content of the DHA-supplemented group was 2.6-fold higher at the end of the study than that of the placebo group ( 4.85 + /- 1.35 vs 1.86 + /- 0.87 mol % of total fatty acids ; P objective or subjective measure of ADHD symptoms . CONCLUSION A 4-month period of DHA supplementation ( 345 mg/d ) does not decrease symptoms of ADHD", "BACKGROUND Although several clinical trials have evaluated the impact of n-3 polyunsaturated fatty acid ( PUFA ) on patients with attention-deficit hyperactivity disorder ( ADHD ) , changes in plasma PUFA composition were not always assessed following n-3 supplementation . Furthermore , no reports are available on the efficacy of n-3 PUFA in Canadian youth with ADHD . OBJECTIVES To determine fatty acid ( FA ) composition , and the efficacy and safety of n-3 PUFA supplementation on ADHD clinical symptoms in French Canadian primary school children . PATIENTS AND METHODS The Strengths and Weaknesses in ADHD and Normal Behaviors ( SWAN ) and Conners ' question naires were used to assess changes in ADHD symptoms in 37 children ( only 26 children completed the study from zero to 16 weeks ) . They were divided into two groups ( A and B ) , and participated in a 16-week , double-blind , one-way , crossover r and omized study . In the first phase , group A received the n-3 PUFA supplement and group B received n-6 PUFA ( sunflower oil ) as a placebo . During the second phase , group B received the active n-3 PUFA supplement that was continued in group A. FA composition and lipid profile were assessed during the phases of the study . RESULTS FA differences between groups were observed in the 26 patients . Supplementation with n-3 PUFA result ed in significant increases in eicosapentaenoic and docosahexaenoic acids in group A , while group B was enriched with alpha-linolenic , gamma-linolenic and homo-gamma-linolenic acids . The n-3 PUFA supplement was tolerated without any adverse effects . A statistically significant improvement in symptoms was noted based on the parent version of the Conners ' question naire from baseline to the end of phase 1 , and this amelioration continued from phases 1 to 2 , although the latter changes from phases 1 and 2 were not statistically significant in any of the subscales except for the subscale measuring inattention in group B. The improvement was greater in patients from group A in phase 1 and in patients from group B in phase 2 . A subgroup of eight patients ( four in each group ) displayed a statistically significant clinical improvement following the administration of the n-3 PUFA supplement , particularly for the inattention and global Diagnostic and Statistical Manual of Mental Disorders , Fourth edition , total Conners ' subscales . CONCLUSIONS A subgroup of children with ADHD who used n-3 PUFA supplements achieved and maintained symptom control . The data of the present study also supported n-3 PUFA safety and tolerability , but limited changes were noted in the FA profile in French Canadians with ADHD", "Two variants of a behavioral family intervention ( BFI ) program known as Triple P were compared using 87 preschoolers with co-occurring disruptive behavior and attentional/hyperactive difficulties . Families were r and omly allocated to enhanced BFI ( EBFI ) , st and ard BFI ( SBFI ) , or a waitlist ( WL ) control group . At postintervention both BFI programs were associated with significantly lower levels of parent-reported child behavior problems , lower levels of dysfunctional parenting , and greater parental competence than the WL condition . The EBFI condition was also associated with significantly less observed child negative behavior in comparison to the WL . The gains achieved at postintervention were maintained at 1-year follow-up . Contrary to predictions , the enhanced program was not shown to be superior to the st and ard program using any of the outcome measures at either postintervention or follow-up . Each of the programs produced significant reductions in children 's co-occurring disruptive behavior and attentional/hyperactive difficulties with 80 % of the children showing clinical ly reliable improvement in observed negative behavior from preintervention to follow-up", "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", "Objective : The aim of the study was to assess omega 3/6 fatty acids ( eye q ) in attention deficit hyperactivity disorder ( ADHD ) . Method : The study included a r and omized , 3-month , omega 3/6 placebo-controlled , one-way crossover trial with 75 children and adolescents ( 8—18 years ) , followed by 3 months with omega 3/6 for all . Investigator-rated ADHD Rating Scale — IV and Clinical Global Impression ( CGI ) scale were outcome measures . Results : A majority did not respond to omega 3/6 treatment . However , a subgroup of 26 % responded with more than 25 % reduction of ADHD symptoms and a drop of CGI scores to the near-normal range . After 6 months , 47 % of all showed such improvement . Responders tended to have ADHD inattentive subtype and comorbid neurodevelopmental disorders . Conclusion : A subgroup of children and adolescents with ADHD , characterized by inattention and associated neurodevelopmental disorders , treated with omega 3/6 fatty acids for 6 months responded with meaningful reduction of ADHD symptoms . ( J. of Att . Dis . 2009 ; 12(5 ) 394 - 401", "OBJECTIVE To investigate the effectiveness of behavioral parent training ( BPT ) as adjunct to routine clinical care ( RCC ) . METHOD After a first phase of RCC , 94 children with attention-deficit/hyperactivity disorder ( ADHD ) ages 4 - 12 , all referred to a Dutch outpatient mental health clinic , were r and omly assigned to 5 months of BPT plus concurrent RCC ( n = 47 ) or to 5 months of RCC ( n = 47 ) alone . BPT consisted of 12 sessions in group format ; RCC included family support and pharmacotherapy when appropriate . Exclusionary criteria were minimized , and children with and without medication could participate . Parent-reported behavioral problems , ADHD symptoms , internalizing problems , and parenting stress were assessed before and after treatment . Follow-up assessment of the BPT + RCC group was completed 25 weeks post-BPT intervention . Repeated- measures analyses of variance were carried out on an intention-to-treat basis . RESULTS Both groups showed improvements over time on all measures . BPT + RCC was superior to RCC alone in reducing behavioral ( p = .017 ) and internalizing ( p = .042 ) problems . No outcome differences were found in ADHD symptoms ( p = .161 ) and parenting stress ( p = .643 ) . These results were equal for children with and without medication . Children allocated to RCC alone received more polypharmaceutical treatment . CONCLUSIONS Adjunctive BPT enhances the effectiveness of routine treatment of children with ADHD , particularly in decreasing behavioral and internalizing problems , but not in reducing ADHD symptoms or parenting stress . Furthermore , adjunctive BPT may limit the prescription of polypharmaceutical treatment", "In a test of Feingold 's hypothesis that food additives trigger the hyperactive response , 26 hyperactive children were r and omly assigned to treatment conditions whereby they were given active or placebo medications in combination with challenge cookies with artificial food colors or control cookies without the additives . The children were crossed over into each of the four treatment conditions and experimental procedures were employed , including double-blind assessment s through the completion of behavior checklists , by teachers and parents . Stimulant medications were clearly more effective than diet in reducing hyperactive behavior . The parent ratings indicate strong drug effects and inconclusive diet effects . Drug effects are marked in teacher ratings as well . However , when the children were receiving placebos , their hyperactive behaviors in the classroom were greater when eating cookies with artificial colors than when eating cookies without artificial colors . According to the ratings , approximately seven children were no longer hyperactive . There is evidence to suggest that the behavior of three to eight children was diet-responsive , depending on the criteria used . There is evidence , particularly in teacher ratings , in support of Feingold 's hypothesis if it is modified . Further research is required to specify which subtypes of hyperactive children respond to a diet free of artificial food colors", "Objective . This study examined the efficacy of 2 computer-based training systems to teach children with attention deficit/hyperactivity disorder ( ADHD ) to attend more effectively . Design / methods . A total of 41 children with ADHD from 2 middle schools were r and omly assigned to receive 2 sessions a week at school of either neurofeedback ( NF ) or attention training through a st and ard computer format ( SCF ) , either immediately or after a 6-month wait ( waitlist control group ) . Parents , children , and teachers completed question naires pre- and postintervention . Results . Primary parents in the NF condition reported significant ( P Conners ’s Rating Scales — Revised ( CRS-R ) and Behavior Assessment Scales for Children ( BASC ) subscales ; and in the SCF condition , they reported significant ( P the CRS-R Inattention scale and ADHD index , the BASC Attention Problems Scale , and on the Behavioral Rating Inventory of Executive Functioning ( BRIEF ) . Conclusion . This r and omized control trial provides preliminary evidence of the effectiveness of computer-based interventions for ADHD and supports the feasibility of offering them in a school setting", "Essential fatty acids ( EFA ) are needed for normal sensory , cognitive , and motor function . The EFA blood profile seems to be different in children with attention-deficit/hyperactivity disorder ( ADHD ) as compared to matched controls . Previous open EFA supplementation trials were successful in demonstrating significant therapeutic effects in this population , whereas most of the r and omized controlled trials failed to show any benefit over placebo . The current r and omized , double-blind , placebo-controlled trial tested the influence of short-chain EFA supplementation on ADHD children , using parent and teacher question naires and a computerized continuous performance test . A total of 73 unmedicated children aged 7 - 13 years with a diagnosis of ADHD participated in the study ; 63 children completed the study . The EFA supplement contained 480 mg of linoleic acid and 120 mg of alpha-linolenic acid , and the placebo contained 1000 mg of vitamin C ( daily amounts ) ; both were given for a 7-week supplementation period . Analysis of variance for repeated measures revealed that both treatments ameliorated some of the symptoms , but no significant differences were found between the groups in any of the treatment effects" ]

[ "Objectives This study aim ed to test the hypothesis that there is no difference in the survival rates of molars treated according to the conventional restorative treatment ( CRT ) using amalgam , atraumatic restorative treatment ( ART ) using high-viscosity glass ionomer , and ultraconservative treatment ( UCT ) protocol after 3.5 years . Material s and methods Cavitated primary molars were treated according to CRT , ART , and UCT ( small cavities were restored with ART and medium/large cavities were daily cleaned with toothpaste/toothbrush under supervision ) . Molar extraction s result ing from toothache , sepsis , or pulp exposure were failures . The Kaplan – Meier method was used to estimate the survival curves . Results The numbers of treated teeth , among the 302 6–7-year-old children , were 341 ( CRT ) , 244 ( ART ) , and 281 ( for UCT group : 109 small ART , 166 open cavities , and 6 combinations ) . Protocol groups were similar at baseline regarding gender and mean decayed missing filled tooth score , but not regarding age and type of surface . The numbers of molars extracted were 22 ( CRT ) , 16 ( ART ) , and 26 ( UCT ) . Fistulae were most often recorded . After 3.5 years , the cumulative survival rate ± st and ard error for all molars treated was 90.9 ± 2.0 % with CRT , 90.4 ± 2.4 % with ART , and 88.6 ± 1.9 % with UCT ( p = 0.13 ) . Only a type of surface effect was observed over the 3.5-year period : survival rates for molars were higher for single- than for multiple-surface cavities . Conclusion There was no difference in the cumulative survival rates of primary molars treated according to the CRT , ART , and UCT protocol s over a 3.5-year period . Clinical relevance Keeping cavities in primary molars biofilm-free might be another treatment option alongside restoring such cavities through conventional and ART protocol", "OBJECTIVES To assess and compare the cumulative survival rate of amalgam and atraumatic restorative treatment ( ART ) restorations in primary molars over 3 years . METHODS 280 children aged 6 - 7 years old were enrolled in a cluster r and omized controlled clinical trial using a parallel group design covering two treatment groups : conventional restorative treatment with amalgam ( CRT ) and atraumatic restorative treatment ( ART ) using a high-viscosity glass-ionomer ( HVGIC ) Ketac Molar Easymix . Three pedodontists placed 750 restorations ( 364 amalgam and 386 ART in 126 and 154 children , respectively ) which were evaluated at 0.5 , 1 , 2 and 3 years . The proportional hazard rate regression model with frailty correction , ANOVA and Wald tests , and the Jackknife procedure were applied in analysing the data . RESULTS The cumulative survival rates over 3 years for all , single- and multiple-surface CRT/amalgam restorations ( 72.6 % , 93.4 % , 64.7 % , respectively ) were no different from those of comparable ART/HVGIC restorations ( 66.8 % ; 90.1 % and 56.4 % , respectively ) ( p=0.10 ) . Single-surface restorations had higher survival rates than multiple-surface restorations for the both treatment procedures ( p failed because of mechanical reasons ( 94.8 % ) than of secondary caries ( 5.2 % ) . No difference in reasons for restoration failures between all types of amalgam and ART/HVGIC restorations were observed ( p=0.24 ) . SIGNIFICANCE The high-viscosity glass-ionomer used in this study in conjunction with the ART is a viable option for restoring carious dentin lesions in single surfaces in vital primary molars", "The aim of the present clinical study was an in vivo evaluation of an improved conventional glass ionomer cement Ketac Molar ( ESPE ) , compared to a polyacid modified composite resin , Dyract ( Dentsply/De Trey ) , used in primary molars . Fifty-three Ketac Molar and fifty-two Dyract restorations were placed in box-only preparations in primary molars . The application time for the chemically cured Ketac Molar , was longer compared to the light-cured Dyract . In comparing the material s , no differences were found , comparing both material s regarding secondary caries , marginal adaptation , wear and fracture toughness . One case of recurrent caries adjacent to a Ketac Molar restoration and two cases in the Dyract group were reported . Two Ketac Molar restorations and one Dyract showed bulk fracture at the time of evaluation . At the twelve-month evaluation , no difference between the investigated material s was registered , which indicates that Ketac Molar can be used as a proximal restoration in the primary dentition . It should be emphasized , however , that one-year data should not be extrapolated to indicate the long-term success of restorations", "BACKGROUND As the world population ages , the requirement for cost-effective methods of treating chronic disease conditions increases . In terms of oral health , there is a rapidly increasing number of dentate elderly with a high burden of maintenance . Population surveys indicate that older individuals are keeping their teeth for longer and are a higher caries risk group . Atraumatic Restorative Treatment ( ART ) could be suitable for patients in nursing homes or house-bound elderly , but very little research has been done on its use in adults . OBJECTIVES To compare the cost-effectiveness of ART and a conventional technique ( CT ) for restoring carious lesions as part of a preventive and restorative programme for older adults . METHODS In this r and omized clinical trial , 82 patients with carious lesions were r and omly allocated to receive either ART or conventional restorations . Treatment costs were measured based on treatment time , material s and labour . For the ART group , the cost of care provided by a dentist was also compared to the cost of having a hygienist to provide treatment . Effectiveness was measured using percentage of restorations that survived after a year . RESULTS Eighty-two patients received 260 restorations , that is , 128 ART and 132 conventional restorations . 91.1 % of the restorations were on one surface only . After a year , 252 restorations were assessed in 80 patients . The average cost for ART and conventional restorations was € 16.86 and € 28.71 respectively ; the restoration survival percentages were 91.1 % and 97.7 % , respectively . This result ed in a cost-effectiveness ratio of 0.18 ( ART ) and 0.29 ( CT ) . When the cost of a hygienist to provide ART was inserted in the analysis , the result ing ratio was 0.14 . CONCLUSIONS Atraumatic restorative treatment was found to be a more cost-effective alternative to treat older adults after 1 year , compared to conventional restorations , especially in out of surgery facilities and using alternative workforce such as hygienists . Atraumatic restorative treatment can be a useful tool to provide dental care for frail and fearful individuals who might not access dental treatment routinely", "BACKGROUND Laboratory studies show diverse behaviour of different br and s of glass-ionomer cements ( GIC ) . AIM This study investigated the clinical performance [ survival rate ( SR ) ] of three GIC br and s applied to proximal atraumatic restorative treatment ( ART ) restorations . Additionally , the SR of the tooth was evaluated . DESIGN Proximal cavities of 262 primary molars were restored . The patients had been r and omly allocated to two operators and three GIC br and s : Fuji IX , Hi-Dense , and Maxxion R. Restorations were evaluated after 1 , 6 , 12 , 18 , 24 , 30 , and 36 months . Failed restorations were , if possible , repaired or replaced . Linear regression analyses were used to evaluate the effect of GIC br and , operator , and surface of restoration . Kaplan-Meier survival analysis and log-rank test were performed for both restoration survival and tooth survival ( α = 5 % ) . RESULTS After 3 years , 82.4 % of the restorations were evaluated . The SR of the restorations was 24.4 % , and there was no difference among GIC br and s ( log-rank test , P = 0.6 ) . In the first 18 months , a significant operator effect and significantly higher failures in distal surfaces were found . The SR of the tooth was 81.7 % . CONCLUSIONS The SR of proximal ART restorations was relatively low when compared with the SR of the tooth . There are no differences in the performance among the GIC br and s used in the study", "This study compared the survival of restorations produced through the atraumatic restorative treatment ( ART ) approach using glass-ionomer with those produced through the traditional approach using amalgam ( MTA ) in deciduous dentitions over a period of 3 years . Using a parallel group design , 835 grade 1 children , aged 6–7 years , participated . A total of 482 children were treated through the ART and 353 children through the MTA approach . Eight dentists produced a total of 1,891 single- and multiple-surface restorations . After 3 years , 22.1 % of the restorations were lost for evaluation . There was a statistically significant difference in the combined survival of all single- and multiple-surface restorations between the two approaches in favour of the ART approach ( p = 0.04 ) . The study revealed a 3-year cumulative survival percentage of single-surface ART and MTA restorations of 86.1 and 79.6 % , respectively . The difference was statistically significant ( p = 0.03 ) . The main reasons for both single-surface ART and MTA restorations to fail was ‘ restoration missing ’ followed by ‘ gross marginal defect ’ . The 3-year cumulative survival percentages of multiple-surface ART and MTA restorations were 48.7 and 42.9 % , respectively . The difference was not statistically significant ( p > 0.05 ) . The 3-year survival percentages of single- and multiple- surface ART and MTA restorations varied widely amongst the 8 operators with an operator effect ( p = 0.001 ) for multiple-surface MTA restorations . It can be concluded that the ART approach using glass-ionomer yielded better results in treating dentinal lesions in deciduous teeth than did the traditional approach using amalgam after 3 years . It is recommended to select the ART approach to complement the other activities of the school oral health programme", "BACKGROUND The authors evaluated the 24-month performance of a packable resin-based composite/dentin bonding system and a high-viscosity glass ionomer cement ( GIC ) in restorations placed in primary molars with the atraumatic restorative treatment ( ART ) approach . METHODS Three dentists placed 419 restorations in 219 children aged 6 through 10 years who had bilateral matched pairs of carious posterior Class I and II primary teeth . They used a split-mouth design to place the two material s , which were assigned r and omly to contralateral sides . The authors evaluated the restorations according to U.S. Public Health Service Ryge criteria . RESULTS After 24 months , 96.7 percent of the Class I GIC restorations and 91 percent of the resin-based composite restorations survived , while the success rates for the Class II restorations were 76.1 percent and 82 percent for the GIC and resin-based composite restorations , respectively . The survival rate of the Class II resin-based composite restorations was 5.9 percent higher than that of the GIC restorations at the 24-month evaluation , but this difference was not statistically significant . However , the study results showed a statistically significant difference in survival rates between Class I and II restorations for both material s. CONCLUSION AND CLINICAL IMPLICATION S The two-year clinical performance of both material s was satisfactory for the restoration of Class I and II primary molars using the ART approach", "OBJECTIVES The aims of this study are to assess the feasibility of the Atraumatic Restorative Treatment ( ART ) approach in primary teeth and to compare the ART approach with traditional amalgam restorations in primary molars . METHODS This study was conducted in a paediatric dentistry clinic in Kuwait between April 1999 and December 2001 . The ART and amalgam restorations were placed r and omly on comparable pairs of primary molars , if available . In addition , the ART approach was used for other primary teeth that had no pulpal involvement and no perceived pain before treatment . The restorations were assessed by both the ART evaluation criteria and USPHS criteria in August-September 2000 and in August-December 2001 . The mean follow-up period for the restorations was 8.3 months in the first assessment ( 2000 ) and 22 months in the second assessment ( 2001 ) . The assessment was possible for 35 children ( mean age = 5.7 years ) , 18 of whom had comparable pairs ( n = 35 pairs ) of restorations in their primary molars . In addition , 48 other ART restorations were assessed in 2000 and 42 in 2001 . RESULTS In a 2-year follow-up , 89.6 % of all ART restorations were considered successful . The failure rate of the comparable pairs of ART and amalgam restorations was 5.7 % . There was no significant difference in success rate between ART and amalgam techniques . CONCLUSIONS Based on a 2-year follow-up evaluation , the class I ART restorations seemed to have a high success rate , indicating the appropriateness of the ART approach in primary teeth", "Objectives The aims of this study were to compare 2-year cumulative survival rates of amalgam and atraumatic restorative treatment ( ART ) restorations in primary molars and to investigate the determinants of the survival rate of restorations . Material s and methods A controlled clinical trial using a parallel group design was carried out on 258 children aged 6–7 years old , allocated to two treatment groups : conventional restorative treatment using amalgam and ART using high-viscosity glass ionomer . A total of 364 amalgam restorations and 386 ART restorations were placed by three pedodontists in 126 and 158 children , respectively , and were evaluated after 0.5 , 1 , and 2 years . Restorations were placed in vital primary molars with neither pain nor signs of pulp involvement . The survival analysis was conducted using the proportional hazard rate regression model with frailty correction . Results The 2-year cumulative survival rates for all amalgam ( 77.3 % ) and ART ( 73.5 % ) restorations were not statistically significantly different , but there was an effect of “ type of surface ” ( single/multiple ) and “ cavity filling time ” on the survival rates . Both amalgam and ART single-surface restorations had higher survival rates than multiple-surface restorations of the same material . Secondary caries was responsible for 36 and 38 % of failures in amalgam and ART restorations , respectively . Mean time for restoring all type of cavities with amalgam and ART restorations was 13.6 and 13.7 min , respectively . Conclusions Amalgam and ART restorations presented similar survival rates over a 2-year period for all , single-surface , and multiple-surface restorations . Clinical relevance In the cause of finding alternatives to amalgam , ART restorations using high-viscosity glass ionomer might be a suitable option for managing cavitated dentine carious lesions in vital primary molars" ]

[ "OBJECTIVE We evaluated the association between mothers ' use of multivitamin supplements and their infants ' risk for omphalocele , a congenital anomaly of the abdominal wall . Omphalocele can occur in certain multiple congenital anomaly patterns with neural tube defects , for which a protective effect of multivitamins with folic acid has been demonstrated . METHODS We used data from a population -based case-control study of infants born from 1968 - 1980 to mothers residing in metropolitan Atlanta . Case-infants with nonsyndromic omphalocele ( n = 72 ) were actively ascertained from multiple sources . Control-infants ( n = 3029 ) , without birth defects , were selected from birth certificates by stratified r and om sampling . RESULTS Compared with no use in the periconceptional period , periconceptional use of multivitamin supplements ( regular use from 3 months before pregnancy through the first trimester of pregnancy ) was associated with an odds ratio for nonsyndromic omphalocele of 0.4 ( 95 % confidence interval [ CI ] : 0.2 - 1.0 ) . For the subset comprising omphalocele alone or with selected midline defects ( neural tube defects , hypospadias , and bladder/cloacal exstrophy ) , the odds ratio was 0.3 ( 95 % CI : 0.1 - 0.9 ) . These estimates were similar when the reference group also included women who began using multivitamins late in pregnancy ( during the second or third month of pregnancy ) . The small number of participants limited the precision of subgroup analyses and translated into wide confidence intervals that included unity . CONCLUSIONS Periconceptional multivitamin use was associated with a 60 % reduction in the risk for nonsyndromic omphalocele . These findings await replication from additional studies to confirm the findings , generate more precise estimates , and detail possible mechanisms of actions", "The hypothesis was tested that the additional dietary uptake of n-3 fatty acids , in particular of DHA and 5-methyltetrahydrofolate ( 5-MTHF ) , during the second half of pregnancy would influence proliferation and apoptosis in the full-term human placenta . The diets of pregnant women from Spain ( n 55 ) were supplemented with modified fish oil and /or 5-MTHF or placebo , and assigned in a r and om , double-blind manner to one of the four groups . Immunohistochemistry and immunoblotting were used to detect placental proliferation and apoptosis with monoclonal antibodies for key proteins that reflected the extent of both processes : proliferation cell nuclear antigen ( PCNA ) , p53 , cytokeratin 18 neoepitope . The PCNA level in the fish oil/5-MTHF-treated group was higher by 66 % ( P levels of p53 and cytokeratin 18 neoepitope were unaffected by treatment . PCNA expression was altered only in the trophoblast compartment ( placebo 11.1 ( se 0.5 ) % v. combination 21.5 ( se 1.2 ) % ; P proportion of nuclei stained in endothelial and other stromal cells was similar in the placebo and combined treatment groups . No correlation was found between fish oil or 5-MTHF supplementation and the levels of the proteins . The present data suggest that supplementation with fish oil and /or 5-MTHF had no effect on the parameters reflecting placental proliferation and apoptosis . A defined combination of DHA and 5-MTHF may , however , affect placental proliferation", "One third of the Indian babies are of low birth weight ( birth size in a prospect i ve study of 797 rural Indian women , focusing on macronutrient intakes , dietary quality and micronutrient status . Maternal intakes ( 24-h recall and food frequency question naire ) and erythrocyte folate , serum ferritin and vitamin C concentrations were measured at 18 + /- 2 and 28 + /- 2 wk gestation . Mothers were short ( 151.9 + /- 5.1 cm ) and underweight ( 41.7 + /- 5.1 kg ) and had low energy and protein intakes at 18 wk ( 7.4 + /- 2.1 MJ and 45.4 + /- 14.1 g ) and 28 wk ( 7.0 + /- 2.0 MJ and 43.5 + /- 13.5 g ) of gestation . Mean birth weight and length of term babies were also low ( 2665 + /- 358 g and 47.8 + /- 2.0 cm , respectively ) . Energy and protein intakes were not associated with birth size , but higher fat intake at wk 18 was associated with neonatal length ( P birth weight ( P triceps skinfold thickness ( P birth size was strongly associated with the consumption of milk at wk 18 ( P green leafy vegetables ( P Erythrocyte folate at 28 wk gestation was positively associated with birth weight ( P between size at birth and maternal energy and protein intake but strong associations with folate status and with intakes of foods rich in micronutrients suggest that micronutrients may be important limiting factors for fetal growth in this undernourished community", "Higher folate needs are present during pregnancy , which may lead to tissular deficiency in the mother and to depleted newborn folate reserves . The aim of this work was to assess the prevalence of folate deficiency and to establish the rates of serum and red cell folate in two groups of mothers and newborn infants , one receiving only iron and the other iron and folate during pregnancy . The rates of serum and red cell folate found at the end of pregnancy were significantly higher in the group which received folate ; however , the percentage of cases with tissular folate deficiency was low in both groups , with no significant difference ( 3.8 % and 1.3 % , respectively ) . These findings , along with the lack of effect of supplemental folate on erythropoiesis , pose some questions on the usefulness of supplemental folate during pregnancy in our country", "BACKGROUND The risk of recurrent neural-tube defects is decreased in women who take folic acid or multivitamins containing such during the periconceptional period . The extent to which folic acid supplementation can reduce the first occurrence of defects is not known . METHODS We conducted a r and omized , controlled trial of periconceptional multivitamin supplementation to test the efficacy of this treatment in reducing the incidence of a first occurrence of neural-tube defects . Women planning a pregnancy ( in most cases their first ) were r and omly assigned to receive a single tablet of a vitamin supplement ( containing 12 vitamins , including 0.8 mg of folic acid ; 4 minerals ; and 3 trace elements ) or a trace-element supplement ( containing copper , manganese , zinc , and a very low dose of vitamin C ) daily for at least one month before conception and until the date of the second missed menstrual period or later . RESULTS Pregnancy was confirmed in 4753 women . The outcome of the pregnancy ( whether the fetus or infant had a neural-tube defect or congenital malformation ) was known in 2104 women who received the vitamin supplement and in 2052 who received the trace-element supplement . Congenital malformations were significantly more prevalent in the group receiving the trace-element supplement than in the vitamin-supplement group ( 22.9 per 1000 vs. 13.3 per 1000 , P = 0.02 ) . There were six cases of neural-tube defects in the group receiving the trace-element supplement , as compared with none in the vitamin-supplement group ( P = 0.029 ) . The prevalence of cleft lip with or without cleft palate was not reduced by periconceptional vitamin supplementation . CONCLUSIONS Periconceptional vitamin use decreases the incidence of a first occurrence of neural-tube defects", "A r and omised double-blind prevention trial with a factorial design was conducted at 33 centres in seven countries to determine whether supplementation with folic acid ( one of the vitamins in the B group ) or a mixture of seven other vitamins ( A , D , B1,B2,B6,C and nicotinamide ) around the time of conception can prevent neural tube defects ( anencephaly , spina bifida , encephalocele ) . A total of 1817 women at high risk of having a pregnancy with a neural tube defect , because of a previous affected pregnancy , were allocated at r and om to one of four groups -- namely , folic acid , other vitamins , both , or neither . 1195 had a completed pregnancy in which the fetus or infant was known to have or not have a neural tube defect ; 27 of these had a known neural tube defect , 6 in the folic acid groups and 21 in the two other groups , a 72 % protective effect ( relative risk 0.28 , 95 % confidence interval 0.12 - 0.71 ) . The other vitamins showed no significant protective effect ( relative risk 0.80 , 95 % Cl 0.32 - 1.72 ) . There was no demonstrable harm from the folic acid supplementation , though the ability of the study to detect rare or slight adverse effects was limited . Folic acid supplementation starting before pregnancy can now be firmly recommended for all women who have had an affected pregnancy , and public health measures should be taken to ensure that the diet of all women who may bear children contains an adequate amount of folic acid", "BACKGROUND Zinc and folate are important for fetal growth . However , the relationship between the dietary intake of these nutrients and pregnancy outcome is not settled . METHODS A prospect i ve study was conducted to ascertain the relationship between maternal dietary zinc and folate intake ( n = 1398 ) , serum zinc and folate levels ( n = 289 ) , and infant birthweight . Twenty-four hour recalls were used to measure energy , zinc , folate and other nutrient intakes at 18 and 30 weeks of gestation . Subjects in the study were offered daily folic acid ( 1.0 mg ) and iron ( 60 mg as ferrous sulfate ) at enrollment . RESULTS Maternal zinc nutriture as assessed by serum and dietary intake was not associated with birthweight or length of gestation . There was a small but significant positive association between maternal folate intake and adjusted infant birthweight ( beta = 0.05 , p = 0.03 ) . The indirect measures of maternal nutritional status including maternal pre-pregnancy weight ( beta = 8.0 , p = 0.0001 ) and weight gain during pregnancy ( beta = 18.1 , p = 0.0001 ) were stronger predictors of adjusted infant birthweight as compared to energy intake and intake of zinc and folate . An increase of 320 , 290 , and 48 g in infant birthweight was associated with the 90th-10th percentile difference for pre-pregnancy weight , weight gain during pregnancy , and folate intake respectively . CONCLUSION These results indicate that pre-pregnancy weight and weight gain during pregnancy are both strong predictors of infant birthweight . Folate intake , although significantly associated with birthweight , was a weak predictor while maternal intake of zinc and other nutrients was not associated with birthweight", "BACKGROUND Adolescents are more likely than adults to consume energy-dense , micronutrient-poor diets and to experience adverse pregnancy outcomes . OBJECTIVES The objectives were to assess micronutrient intake and blood biomarkers prospect ively in pregnant adolescents recruited to the About Teenage Eating ( ATE ) Study and to determine associations with pregnancy outcome . DESIGN Pregnant adolescents ( n = 500 ) were recruited from 2 UK inner city population s. Dietary intake was assessed with three 24-h dietary recalls , and micronutrient status was assessed by measurement of third trimester blood biomarkers . Pregnancy outcomes included small-for-gestational age ( SGA ) birth and preterm delivery . RESULTS Median iron and folate intakes were lower than UK and US recommended amounts . Folate and vitamin B-12 status were lower in smokers , despite no differences in dietary intake . Serum folate was serum total homocysteine ( tHcy ) was elevated ( > 10 micromol/L ) in 20 % of subjects . Fifty-two percent of the subjects had iron deficiency anemia , and 30 % had serum 25-hydroxyvitamin D concentrations SGA birth was higher in subjects with poorer folate status ( red blood cell folate , P = 0.003 ; serum folate , P = 0.02 ; tHcy , P = 0.01 ; simple regression ) and those with low folate intakes , regardless of the inclusion ( P = 0.021 ) or exclusion ( P = 0.049 ) of intake from supplements ( simple regression ) . Adjustment for confounding variables confirmed the independence of these associations . The risk of SGA birth was also higher in subjects with low food iron intake ( P = 0.049 ) , but not when intake included iron from supplements ( P = 0.21 ) . The risk of SGA birth was lower in subjects with iron deficiency anemia ( P = 0.002 ) . CONCLUSION Poor micronutrient intake and status increase the risk of SGA births in pregnant adolescents", "We investigated whether a woman 's periconceptional use of a multivitamin containing folic acid was associated with a reduced risk for delivering offspring with a conotruncal heart defect or a limb deficiency . Data were derived from a population -based case-control study of fetuses and liveborn infants with conotruncal or limb defects among a 1987 - 88 cohort of births in California . Telephone interviews were conducted with mothers of 207 ( 87.0 % of eligible ) conotruncal cases , 178 ( 82.0 % ) limb defect cases , and of 481 ( 76.2 % ) r and omly selected liveborn nonmalformed control infants . Reduced risks were observed for maternal use of multivitamins containing folic acid from one month before until two months after conception . Odds ratios and 95 % confidence intervals for any compared to no multivitamin use were 0.70 ( 0.46 - 1.1 ) for conotruncal defects and 0.64 ( 0.41 - 1.0 ) for limb defects . Controlling for maternal race/ethnicity , age , education , gravidity , alcohol use , and cigarette use result ed in a further reduction to the odds ratio for conotruncal defects , 0.53 ( 0.34 - 0.85 ) , but not for limb defects . Among non-vitamin using women , consumption of cereal containing folic acid was also associated with reduced risk for both defects . Women who take multivitamins have 30 - 35 % lower risk of delivering offspring with either conotruncal or limb defects . This association may not be attributable to folic acid specifically , but may be a consequence of other multivitamin components , or some unknown behaviors that highly correlate with regular use of a multivitamin . However , should the association prove causal , it offers an important opportunity for preventing thous and s of serious birth defects", "Folic acid administered to pregnant Bantu , whose diet is low in folate , was associated with a significant reduction in the incidence of prematurity . No such effect could be demonstrated in White patients subsisting on an average Western diet . This suggests that folate deficiency may contribute to the “ pregnancy wastage ” in population s whose dietary folate intake is low , and is a further indication for folic acid supplementation during pregnancy in these groups" ]

[ "Supplementation with n-3 polyunsaturated fatty acids ( PUFA ) for 6 weeks did not alter plasma leptin concentrations in male smokers . Changes in dietary intake of saturated fatty acids ( FA ) correlated positively , whereas changes in the intake of PUFA correlated negatively to changes in plasma leptin levels . A 3-week n-3 PUFA-enriched diet , as compared with a 3-week lard-enriched diet , induced lower plasma leptin concentration and reduced leptin mRNA expression in rat epididymal adipose tissue . In the human trophoblast cell line ( BeWo ) , n-3 PUFA had a dose- and time-dependent effect on leptin expression . One mM of eicosapentaenoic acid or docosahexaenoic acid ( DHA ) reduced leptin expression by 71 % and 78 % , respectively , as compared with control , after 72 h. There was no effect on expression of the signal transducing form of the leptin receptor . In BeWo cells transfected with the human leptin promoter , we found that n-3 PUFA reduced leptin promoter activity ; in contrast saturated and monounsaturated FA had no effect on leptin promoter activity . The transcription factors peroxysomal proliferator activated receptor gamma and sterol regulatory element binding protein-1 mRNAs were reduced after incubation with n-3 PUFA , whereas the expression of CCAAT/enhancer binding protein alpha was unchanged . DHA-reduced leptin expression was abolished in BeWo cells grown in cholesterol-free medium . In conclusion , n-3 FA decreased leptin gene expression both in vivo and in vitro . The direct effects of PUFA on leptin promoter activity indicate a specific regulatory action of FA on leptin expression", "BACKGROUND Information is lacking on the potential effect of n-3 polyunsaturated fatty acids ( PUFAs ) on the adipose tissue of patients with type 2 diabetes . OBJECTIVE We evaluated whether n-3 PUFAs have additional effects on adiposity , insulin sensitivity , adipose tissue function ( production of adipokines and inflammatory and atherogenic factors ) , and gene expression in type 2 diabetes . DESIGN Twenty-seven women with type 2 diabetes without hypertriglyceridemia were r and omly allocated in a double-blind parallel design to 2 mo of 3 g/d of either fish oil ( 1.8 g n-3 PUFAs ) or placebo ( paraffin oil ) . RESULTS Although body weight and energy intake measured by use of a food diary were unchanged , total fat mass ( P subcutaneous adipocyte diameter ( P Insulin sensitivity was not significantly different between the 2 groups ( measured by homeostasis model assessment in all patients and by euglycemic-hyperinsulinemic clamp in a subgroup of 5 patients per group ) . By contrast , atherogenic risk factors , including plasma triacylglycerol ( P ratio of triacylglycerol to HDL cholesterol ( atherogenic index , P plasma plasminogen activator inhibitor-1 ( P inflammation-related genes was reduced in subcutaneous adipose tissue after the fish oil , but not the placebo , treatment . CONCLUSIONS A moderate dose of n-3 PUFAs for 2 mo reduced adiposity and atherogenic markers without deterioration of insulin sensitivity in subjects with type 2 diabetes . Some adipose tissue inflammation-related genes were also reduced . These beneficial effects could be linked to morphologic and inflammatory changes in adipose tissue . This trial was registered at clinical trials.gov as NCT0037", "The study was design ed to evaluate the chronic regulation of plasma leptin by dietary ( n-3 ) polyunsaturated fatty acids ( PUFA ) in insulin-resistant , sucrose-fed rats . Male Sprague-Dawley rats were r and omly assigned to consume for 3 or 6 wk a diet containing 57.5 % ( g/100 g ) sucrose and 14 % lipids as either fish oil ( SF ) or control oils ( SC ) . After 3 and 6 wk of consuming the SF diet , plasma leptin was 70 % ( P plasma leptin was adjusted by total fat mass , as measured by dual-energy X-ray absorptiometry . Despite high leptin levels , food intake of rats fed the SF diet was greater than in SC-fed rats without any difference in body weight or total fat mass . After 3 wk , accumulated leptin in epididymal and retroperitoneal adipose tissue was higher in the SF-fed rats than in the SC-fed rats . However , after 6 wk , tissue leptin in the SF-fed rats did not differ from that of the SC-fed rats . The SF diet increased adipose tissue glucose transporter-4 protein quantity and prevented the sucrose-induced elevations in plasma triglycerides and free fatty acids . When all SC- and SF-fed rats ( both diets and feeding duration s ) were considered , plasma leptin levels were positively correlated with body weight ( r = 0.5 , P plasma leptin at a given time could be inappropriately high for a given fat mass in insulin-sensitive rats fed ( n-3 ) PUFA ", "Introduction There is evidence that n-3 polyunsaturated fatty acids ( n-3 PUFAs ) exert beneficial effects to improve type 2 diabetes mellitus ( T2DM ) , but its complications remain poorly understood . Hypoadiponectinemia is one of the important mechanisms responsible for T2DM which necessitates developing novel therapeutic strategies . We aim ed to determine the effect of n-3 PUFA supplementation on circulating adiponectin and mRNA expression of adiponectin receptors ( AdipoR1 , AdipoR2 ) and Sirt-1 in T2DM patients . Material and methods A r and omized , double-blind , placebo-controlled trial of 10-week follow-up of n-3 PUFAs ( 2.7 g/day ) vs. placebo in T2DM patients ( n = 88 ) was conducted . In detail , T2DM patients ( n = 44 ) were treated with n-3 PUFAs and the remainder received placebo . Anthropometric and metabolic characteristics were assessed in all participants . Circulating level of adiponectin and mRNA expression of AdipoR1 , AdipoR2 and Sirt-1 were measured in peripheral blood mononuclear cells ( P BMC ) using real-time polymerase chain reaction before and after the intervention . Results It was found that n-3 PUFAs increased AdipoR1 gene expression ( fold change = 1.321 in n-3 PUFAs vs. 1.037 in placebo ) and AdipoR2 mRNA ( fold change = 1.338 in n-3 PUFAs vs. 1.034 in placebo ) . No significant changes were observed for Sirt-1 expression . The serum level of adiponectin significantly ( p = 0.035 ) increased in n-3 PUFAs ( 5.09 to 5.58 μg/ml ) but remained unchanged in the placebo group . Conclusions Daily supplementation with n-3 PUFAs ( 2.7 g ) was effective to significantly improve gene expression of AdipoR1 and AdipoR2 and the serum level of adiponectin in T2DM patients . Therefore , n-3 PUFAs might emerge as an adjuvant for current antidiabetic therapies . However , confirmatory long-term studies are required", "BACKGROUND : Visfatin is an adipocytokine which is secreted from adipose tissue and can affect on the diabetes inflammatory reaction and also serum lipids level . On the other h and , Omega-3 can also prevent formation of insulin resistance . In the present study , the effect of Omega-3 on the serum visfatin concentration was evaluated . METHODS : 71 women with type II diabetes were r and omly assigned to the group that took Omega-3 capsules or control group with placebo capsules . In the first step , study subjects filled a question naire collecting their age , height , weight , waist circumference , and hip circumference . Also their blood sample s were taken for blood tests . In the second step , the intervention was done for 8 weeks and in the third step the aforementioned were collected again . In the blood sample s visfatin and lipid profiles ( low density lipoprotein [ LDL ] , high density lipoprotein [ HDL ] , triglyceride [ TG ] , and cholesterol ) , glucose and HbA1c were measured . RESULTS : There was no significant difference in serum visfatin level between Omega-3 and placebo groups before the intervention ( p = 0.14 ) , while after the intervention , the mean serum visfatin level in the Omega-3 group was significantly higher ( p serum visfatin level before and after the intervention in both groups was significant ( p visfatin level following consuming Omega-3 fats but according to controversial issues on insulin-like function of visfatin , the effects of Omega-3 on diabetes should be studied more in further studies", "Objectives —Fish oil rich in n-3 polyunsaturated fatty acids ( PUFAs ) or n-3 PUFAs have been shown to reduce the incidence of coronary heart disease . Here we investigated the effect of highly purified eicosapentaenoic acid ( EPA ) on production of adiponectin , the only established antiatherogenic and antiinflammatory adipocytokine , in rodent models of obesity and human obese subjects . Methods and Results —We demonstrated that EPA increases adiponectin secretion in genetically obese ob/ob mice and high-fat diet – induced obese mice . In the in vitro coculture of adipocytes and macrophages , EPA reversed the coculture-induced decrease in adiponectin secretion at least in part through downregulation of tumor necrosis factor-&agr ; in macrophages . We also showed significant increase in plasma adiponectin concentrations in human obese subjects after a 3-month treatment with EPA ( 1.8 g daily ) . Multivariate regression analysis revealed that EPA treatment is the only independent determinant of plasma adiponectin concentrations . Conclusion —This study demonstrates that EPA increases adiponectin secretion in rodent models of obesity and human obese subjects , possibly through the improvement of the inflammatory changes in obese adipose tissue . Because EPA has reduced the risk of major coronary events in a large-scale , prospect i ve , r and omized clinical trial , this study provides important insight into its therapeutic implication in obesity-related metabolic sequelae", "Recent evidence suggests that omega-3 polyunsaturated fatty acids [ n-3 PUFAs : eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) ] , improve insulin sensitivity in humans . In a double-blind , placebo-controlled , r and omized , crossover study , we investigated the effects of EPA/DHA on paraoxonase-1 activity as well as fasting and postpr and ial levels of circulating adiponectin and leptin in 34 subjects with type 2 diabetes mellitus who received daily for 6 weeks either 2 g purified EPA/DHA or olive oil ( placebo ) , separated by a 6 weeks washout . At the end of each treatment , measurements were performed in fasting state and 2 , 4 , and 6 h following a st and ardized high-fat meal ( 600 kcal ) . No significant differences in fasting and postpr and ial circulating adiponectin , leptin , and paraoxonase-1 activity were seen between n-3 PUFAs and placebo . Our data do not support an insulin sensitizing effect of n-3 PUFAs by means of influencing circulating adipocytokines in this population . Clinical Trial Register Number : NCT00328536", "Background Energy restriction affects circulating leptin and ghrelin concentrations . The aim of this study To investigate whether seafood consumption affects fasting leptin and ghrelin concentrations in addition to weight loss . Methods In this 8-week dietary intervention , subjects ( 324 Icel and ic , Spanish and Irish subjects , 20–40 years , BMI 27.5–32.5 kg/m2 ) were r and omized to energy-restricted diets ( −30 % ) of identical macronutrient composition but different amount of seafood : control ( no seafood ) ; lean fish ( 150 g cod , three times per week ) ; fatty fish ( 150 g salmon , three times per week ) ; EPA&DHA [ daily docosahexaenoic (DHA)/eicosapentaenoic acid ( EPA ) capsules ] . Anthropometric data , ghrelin , leptin , and insulin were measured at baseline and endpoint . Linear models investigated the effects of seafood on fasting leptin , ghrelin and insulin . Results Body weight ( −5.2 ± 3.0 kg ) , leptin ( −34.8 % ) and insulin ( −13.5 % ) decreased , while ghrelin increased ( 5.6 % ) ( all P endpoint insulin was significantly lower in the EPA&DHA group ( −16.4 % , P = 0.025 ) compared to control , endpoint leptin in men was lower in the salmon group ( −22.9 % , P = 0.026 ) , and the EPA&DHA group tended to have higher endpoint ghrelin ( 5.6 % , P = 0.060 ) , an effect seen only in women indicated by a significant gender × EPA&DHA interaction . Weight loss explained the effects of fatty seafood on leptin and ghrelin , but not insulin . Conclusions Consumption of fatty seafood can modulate fasting insulin , ghrelin and leptin during an 8-week intervention . Effects are partly gender specific and are partly explained by weight loss . Consumption of lean fish does not affect circulating hormones in comparison to control . The most consistent effect on circulating hormones is mediated by weight loss", "AIM The aim of this study was to evaluate the significance of endothelial cell-derived microparticles ( EDMP ) , angiopoietin-2 ( Ang-2 ) and adiponectin in hyperlipidemic patients with and without type 2 diabetes mellitus , and to compare the two for the effects of eicosapentaenoic acid ( EPA ) on these markers . METHODS One hundred and twenty-six hyperlipidemic patients with and without type 2 diabetes mellitus received EPA 1,800 mg daily , and 50 of the patients were non-diabetic . RESULTS EDMP and Ang-2 levels prior to treatment were higher in diabetic patients than in non-diabetic patients , whereas adiponectin levels were lower in diabetics . When diabetic patients were classified into two groups on the basis of Ang-2 levels , the levels of all markers remained unchanged in those without a high Ang-2 level after EPA treatment . In contrast , all markers except for adiponectin were decreased significantly in diabetic patients with high Ang-2 levels after 6 months of EPA treatment . These diabetic patients with high Ang-2 levels displayed a more significant increase in adiponectin levels after EPA treatment than those who did not . CONCLUSION These results suggest that EPA possesses an adiponectin-dependent anti-atherosclerotic effect and may be beneficial for the prevention of vascular complications in diabetic patients with high Ang-2 levels", "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", "Objective : To determine the effects of dietary consumption of milled flaxseed or flaxseed oil on glycemic control , n-3 fatty acid status , anthropometrics , and adipokines in individuals with type 2 diabetes . Design : Thirty-four participants were r and omized into a parallel , controlled trial . Subjects : The participants were adults with type 2 diabetes ( age 52.4 ± 1.5 years , body mass index 32.4 ± 1.0 kg/m2 , n = 17 men and 17 women ) . Interventions : Participants consumed a selection of bakery products containing no flax ( control group [ CTL ] , n = 9 ) , milled flaxseed ( FXS , n = 13 ; 32 g/d ) , or flaxseed oil ( FXO , n = 12 ; 13 g/d ) daily for 12 weeks . The FXS and FXO groups received equivalent amounts of alpha-linolenic acid ( ALA ; 7.4 g/day ) . Measures of Outcome : The primary outcome measures were fasting plasma hemoglobin A1c , glucose , insulin , and phospholipid fatty acid composition . The secondary outcome measures were fasting circulating leptin and adiponectin , as well as body weight , body mass index , and waist circumference . Dietary intake assessment and calculations for homeostasis model assessment for insulin resistance and quantified insulin sensitivity check were also completed . Results : The FXS and FXO groups had increases in plasma phospholipid n-3 fatty acids ( ALA , eicosapentaenoic acid [ EPA ] , or decosapentaenoic acid [ DPA ] , but not docosahexaenoic acid ) , and the FXO group had more EPA and DPA in plasma phospholipids compared to the FXS group . All groups had similar caloric intakes ; however , the CTL group experienced a 4 % weight gain compared to baseline ( p including glycemic control , were unchanged by dietary treatment . Conclusions : Milled FXS and FXO intake does not affect glycemic control in adults with well-controlled type 2 diabetes . Possible prevention of weight gain by flax consumption warrants further investigation", "Objective This prospect i ve study evaluates the effect of insulin sensitizers , pioglitazone ( PGZ ) and metformin ( MET ) on plasma adiponectin and leptin levels in subjects newly diagnosed with type 2 diabetes mellitus ( T2DM )", "Background : The aims of this research were to investigate ( 1 ) the impact of docosahexaenoic acid (DHA)-rich fish oil supplementation on body composition , plasma adiponectin level , and peroxisome proliferator-activated receptor γ ( PPARγ ) gene expression , and ( 2 ) whether the effect of DHA-rich fish oil supplementation on the aforementioned variables is modulated by PPARγ Pro12Ala polymorphism . Methods : We genotyped PPARγ Pro12Ala polymorphism in subjects with type 2 diabetes mellitus ( T2DM ) . Ala carriers and non-Ala carriers were r and omly assigned to DHA-rich fish oil or placebo intake for 8 weeks . Results : Glycemic control was not affected by the intervention . The supplementation with DHA-rich fish oil decreased waist circumference ( p , body fat mass ( p = 0.01 ) , body fat percent ( p = 0.04 ) , and visceral fat rating ( p = 0.02 ) as well as trunk fat mass ( p = 0.04 ) . Weight , body mass index , fat-free mass , adiponectin level , and PPARγ gene expression changes showed no significant difference . No gene-diet interaction was found on body composition , adiponectin level , and PPARγ gene expression . Conclusions : DHA-rich fish oil supplementation favorably modulated body composition in patients with T2DM and could be useful to reduce visceral obesity . However , the PPARγ Pro12Ala polymorphism did not influence the changes in the desired variables", "Fatty acids ( FA ) can impair glucose metabolism to a varying degree depending on time of exposure and also of type of FA . Here we tested for acute effects of marine n-3 FA on insulin sensitivity , insulin secretion , energy metabolism , and oxidative stress . This was a r and omized , double-blind , crossover study in 11 subjects with type 2 diabetes mellitus . A 4-hour lipid infusion ( Intralipid [ Fresenius Kabi , Halden , Norway ] , total of 384 mL ) was compared with a similar lipid infusion partly replaced by Omegaven ( Fresenius Kabi ) that contributed a median of 0.1 g fish oil per kilogram body weight , amounting to 0.04 g/kg of marine n-3 FA . Insulin sensitivity was assessed by isoglycemic hyperinsulinemic clamps ; insulin secretion ( measured after the clamps ) , by C-peptide glucagon tests ; and energy metabolism , by indirect calorimetry . Infusion of Omegaven increased the proportion of n-3 FA in plasma nonesterified fatty acids ( NEFA ) compared with Intralipid alone ( 20:5n-3 : median , 1.5 % [ interquartile range , 0.6 % ] vs -0.2 % [ 0.2 % ] , P = .001 ; 22:6n-3 : 0.8 % [ 0.4 % ] vs -0.7 % [ 0.2 % ] , P = .001 ) . However , glucose utilization was not affected ; neither was insulin secretion or total energy production ( P = .966 , .210 , and .423 , respectively , for the differences between the lipid clamps ) . Omegaven tended to lower oxidation of fat ( P = .062 ) compared with Intralipid only , correlating with the rise in individual n-3 NEFA ( r = 0.627 , P = .039 ) . The effects of clamping on phospholipid FA composition , leptin , adiponectin , or F(2)-isoprostane concentrations were not affected by Omegaven . Enrichment of NEFA with n-3 FA during a 4-hour infusion of Intralipid failed to affect insulin sensitivity , insulin secretion , or markers of oxidative stress in subjects with type 2 diabetes mellitus", "BACKGROUND Low adiponectin levels are discussed as risk factor for cardiovascular events . This is of special importance in individuals with type 2 diabetes ( T2DM ) because they are at higher risk for cardiovascular diseases . The present study aim ed to investigate the effect of two plant oils rich in polyunsaturated fatty acids ( PUFA ) , with different content of omega-3 fatty acids , on adiponectin levels , glucose and lipid metabolism in T2DM individuals treated either with insulin or oral anti-diabetics ( OAD ) . METHODS Ninety-two subjects with T2DM [ 34 treated with insulin ( T2DM-Ins ) and 58 treated with OAD ( T2DM-OAD ) ] participated in this r and omised , double-blind , parallel intervention study . Individuals received either 9 g of nut oil ( n-3:n-6 ratio : 1.3 : 6.1 ) or mixed oil ( n-3:n-6 ratio : 0.6 : 5.7 ) per day for 10 weeks . The fatty acid profile , tocopherol , adiponectin levels and parameters regarding glucose and lipid metabolism were assessed at baseline , during and after the intervention . RESULTS Compliance was confirmed by significant increases in γ-tocopherol and PUFA in both oil groups . An increase in adiponectin levels in T2DM-Ins participants ( + 6.84 % in nut oil and + 4.47 % in mixed oil group after 10 weeks compared to baseline ) was observed , albeit not significantly different from T2DM-OAD individuals ( P = 0.051 ) . Lipid and glucose metabolism were not affected by the intervention . CONCLUSIONS The present study provides evidence that a small and easy change in dietary behaviour towards better fat quality moderately increases adiponectin levels in T2DM-Ins subjects , independently of the administered plant oil", "To investigate the relative role of the adiponectin and leptin in the insulin resistance ( IR ) and obesity we studied plasma levels of these adipocytokines in obese and insulin resistant postmenopausal ( PM ) females with type 2 diabetes ( DM2 ) during 6 months of Metformin therapy . We recruited 26 PM women , between the ages of 50 and 67 ( 59,7+/-8,1 years ) . These women had a BMI of 36,6+/-1,8 kg/m2 . After baseline measurements Metformin therapy has been initiated ( 1700+/-2550 mg per day ) . Duration of therapy was 6 months . The results of investigations of adipocytokines after Metformin 6 months therapy shown that circulating adiponectin levels were significantly increased ( 19,1+/-6,0 vs. 16,1+/-3,9 ng/ml , p=0,008 ) together with significant reduction of BMI ( 35,9+/-1,9 vs. 36,6+/-1,8 kg/m2 , p=0,005 ) and IR ( 3,05+/-0,89 vs. 3,96+/-0,70 , p adiponectin levels positively correlated with the magnitude of BMI reduction ( r=0,4784 , p=0,013 ) and IR reduction ( r=0,5779 , p=0,002 ) . Any significant correlation did not observed between changes of leptin levels and BMI , leptin levels and IR . In summary , our data suggest that hypoadiponectinemia in PM may be explained by only IR because the amelioration of whole-body insulin action by 6-month Metformin therapy leads to increase of plasma adiponectin levels ; leptin levels did not significantly change after 6-month Metformin therapy", "OBJECTIVE ω-3 Polyunsaturated α-linolenic acid ( ALA ) supplementation has not been studied in the setting of adiponectin levels and insulin sensitivity ( IS ) improvements in patients with type 2 diabetes mellitus ( T2DM ) by hyperinsulinemic-euglycemic clamp ( HEC ) . The aim of this study was to examine the influence of ω-3 ALA on IS and adiponectin . METHODS We conducted a r and omized study in patients with T2DM and assessed IS using HEC . Twenty patients with T2DM were included and r and omly assigned to receive 3 g/d of ALA or placebo for 60 d , in a double-blind design . The assessment of IS by HEC was performed at baseline and after 60 d in all patients ; blood sample s were taken for the measurement of serum lipids , glucose , insulin , adiponectin , and cytokines . The primary outcome variables were an increase of both glucose infusion rate ( GIR ) in steady state and glucose metabolization ( M ) by HEC . The secondary outcomes were an increase in adiponectin levels and a decrease in fasting plasma glucose , glycated hemoglobin , homeostasis model assessment -estimated insulin resistance ( HOMA-IR ) index , lipids and cytokines . The study was conducted at an academic medical center . RESULTS The ALA group improved IS corrected for fat-free mass ( M/FFM ; P = 0.04 ) . Both groups showed increased adiponectin after 60 d ( P = 0.01 ) , however , the increase for the ALA group was greater ( P = 0.04 ) . In the ALA group , adiponectin was positively correlated with GIR ( r = 0.76 ; P = 0.01 ) and M/FFM ( r = 0.62 ; P = 0.06 ) , and negatively correlated with HOMA-IR ( r = -0.61 ; P = 0.03 ) . CONCLUSION ω-3 ALA supplementation improved glucose homeostasis and was associated with an increase in adiponectin . Improvement in the overall metabolic profile with ω-3 ALA suggests a potential clinical utility for this agent and requires further investigation" ]

[ "Background — MRI-detected brain lesions are common after left atrial catheter ablation for symptomatic atrial fibrillation . The clinical relevance of these acute ischemic lesions is not fully understood , but ablation-related cerebral injury could contribute to cognitive dysfunction . Methods and Results — In the prospect i ve Mesh Ablator versus Cryoballoon Pulmonary Vein Ablation of Symptomatic Paroxysmal Atrial Fibrillation ( MACPAF ) study , serial 3-T brain MRIs and neuropsychological assessment were performed to analyze the rate of ablation-related brain lesions and their effect on cognitive function . Thirty-seven patients with paroxysmal atrial fibrillation ( median age , 63.0 [ interquartile range , 57–68 ] years ; 41 % female ; median CHA2DS2VASc score 2 [ interquartile range , 1–3 ] ) underwent 41 ablation procedures according to study criteria . None of these patients had overt neurological deficits after ablation . High-resolution diffusion-weighted imaging , performed within 48 hours after ablation , showed that new brain lesions ( range , 1–17 ) were present in 16 ( 43.2 % ) patients after 18 ( 43.9 % ) left atrial catheter ablation procedures . Follow-up MRI at 6 months ( median , 6.5 ; interquartile range , 6–7 ) revealed that 7 ( 12.5 % ) of the 56 total acute brain lesions after ablation formed a persistent glial scar in 5 ( 31.3 % ) patients . Large diffusion-weighted imaging lesions and a corresponding fluid-attenuated inversion recovery lesion 48 hours after ablation predicted lesion persistence on 6-month follow-up . Neither persistent brain lesions nor the ablation procedure itself had a significant effect on attention or executive functions , short-term memory , or verbal and nonverbal learning after 6 months . Conclusions — Ablation-related acute ischemic brain lesions persist to some extent but do not cause cognitive impairment 6 months after the ablation procedure . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01061931", "BACKGROUND Asymptomatic cerebral lesions ( ACL ) may occur during atrial fibrillation ( AF ) ablation . We sought to compare the ACL incidence between 3 contemporary technologies : ( 1 ) irrigated radiofrequency current ( RFC ) , ( 2 ) the single big cryoballoon ( CB ) , and ( 3 ) the endoscopic laser-balloon ( LB ) in a prospect i ve r and omized pilot study . METHODS AND RESULTS Ninety-nine patients were treated in 3 groups . Diffusion weighted MRI was acquired pre- ( n = 20 ) and 24 - 48 h postablation ( n = 99 ) . After ablation , new ACL were detected in 22 % of patients without significant differences between groups ( RFC 8/33 ; CB 6/33 ; LB 8/33 ; P = 0.8 ) . The presence of hypertension was identified as the only independent predictor of ACL by univariate regression analysis . During LB ablation , more ablation lesions ( 140 ± 19 vs 119 ± 18 ; P = 0.007 ) were applied during longer procedures ( 166 ± 36 vs 143 ± 32 min ; P = 0.05 ) in patients with ACL . Univariate analysis revealed that a higher number of ablation lesions predicted ACL ( P = 0.02 ) . CONCLUSION In this prospect i ve , r and omized , single-center pilot study , ablation technology did not influence the occurrence of ACL during AF ablation", "INTRODUCTION There are limited comparative data on catheter ablation of atrial fibrillation ( CAAF ) using the second-generation cryoballoon ( CB-2 ) versus point-by-point radiofrequency ( RF ) . This study examines the acute/long-term CAAF outcomes using these 2 strategies . METHODS AND RESULTS In this multicenter , retrospective , nonr and omized analysis , procedural and clinical outcomes of 1,196 patients ( 76 % with paroxysmal AF ) undergoing CAAF using CB-2 ( n = 773 ) and open-irrigated , non-force sensing RF ( n = 423 ) were evaluated . Pulmonary vein isolation was achieved in 98 % with CB-2 and 99 % with RF ( P = 0.168 ) . CB-2 was associated with shorter ablation time ( 40 ± 14 min vs. 66 ± 26 min ; P and procedure time ( 145 ± 49 minutes vs. 188 ± 42 minutes ; P greater fluoroscopic utilization ( 29 ± 13 minutes vs. 23 ± 14 minutes ; P transient ( 7.6 % vs. 0 % ; P persistent ( 1.2 % vs. 0 % ; P = 0.026 ) phrenic nerve palsy occurred exclusively with CB-2 , other adverse event rates were similar between CB-2 ( 1.6 % ) and RF ( 2.6 % ) ; P = 0.207 . However , freedom from AF/atrial flutter/tachycardia at 12 months following a single procedure without antiarrhythmic therapy was greater with CB-2 ( 76.6 % ) versus RF ( 60.4 % ) ; P patients with paroxysmal AF ( P Additionally , CB-2 was associated with reduced long-term need for antiarrhythmic therapy ( 16.7 % vs. 22.0 % ; P = 0.024 ) and repeat ablations ( 14.6 % vs. 24.1 % ; P CB-2 coupled with RF as occasionally required was associated with greater freedom from atrial arrhythmias at 12 months following a single procedure without antiarrhythmic therapy when compared to open-irrigated , non-force sensing RF , alone", "BACKGROUND Contact force ( CF ) monitoring could be useful in accomplishing circumferential pulmonary vein ( PV ) isolation ( CPVI ) for atrial fibrillation ( AF ) . OBJECTIVE The purpose of this study was to compare procedure parameters and outcomes between CF-guided and non-guided CPVI . METHODS Thirty-eight consecutive AF patients ( mean age 60 ± 11 years , 28 paroxysmal AF ) undergoing CPVI were r and omized to non-CF-guided ( n = 19 ) and CF-guided ( n = 19 ) groups . CPVI was performed with the ThermoCool SmartTouch catheter in both groups . The end-point was bidirectional block between the left atrium ( LA ) and PV . In the CF group , CF was kept between 10 and 20 g during CPVI , whereas in the non-CF group , all CF information was blanked . Radiofrequency energy at 30 W in the anterior and 25 W in the posterior LA wall was applied for 20 - 25 seconds at each point . RESULTS CPVI was successfully accomplished without any major complications in both groups . Mean CF in the non-CF and CF groups were 5.9 ± 4.5 g and 11.1 ± 4.3 g , respectively , for left-side CPVI , and 9.8 ± 6.6 g and 12.1 ± 4.8 g , respectively , for right-side CPVI ( both P The procedure and fluoroscopy times for CPVI in the non-CF and CF groups were 96 ± 39 minutes and 59 ± 16 minutes , respectively ( P respectively . Total number of residual conduction gaps was 6.3 ± 3.0 in the non-CF group and 2.8 ± 1.9 in the CF group ( P free from any atrial tachyarrhythmias ( P = .34 ) . CONCLUSION CF-guided CPVI is effective in reducing procedure time and additional touch-up ablation and may improve long-term outcome ", "Background — There is a lack of data on the comparative efficacy and procedural safety of open irrigated radiofrequency ( RF ) and cryoballoon catheter ( CB ) ablation for pulmonary vein isolation in patients with paroxysmal atrial fibrillation . Methods and Results — In a prospect i ve , noninferiority study , 315 patients were r and omly assigned to RF ( n=159 ) or CB ( n=156 ) ablation . The primary end point was freedom from atrial arrhythmia with absence of persistent complications . Patients were largely comparable between groups with more vascular disease in the RF group ( 8.2 % versus 2.6 % for CB ; P=0.028 ) . The primary end point at 12 months was achieved by 70.7 % with RF and 73.6 % with CB ( multiple procedure success ) , including 31 redo procedures in each group ( 19.5 % of RF versus 19.9 % of CB ; P=0.933 ) . For the intention-to-treat population , noninferiority of CB was revealed for the predefined inferiority margin ( risk difference , 0.029 ; 95 % confidence interval , −0.074 to 0.132 ; P Rates at 6 months were 63.1 % and 64.1 % for the RF and CB groups ( single procedure success ) , and noninferiority was confirmed ( risk difference , 0.010 ; 95 % confidence interval , −0.097 to 0.116 ; P=0.002 ) . Periprocedural complications for the index procedure were more frequent in the CB group ( 5.0 % RF , 12.2 % CB ; P=0.022 ) with a significant difference in phrenic nerve palsies ( 0 % RF , 5.8 % CB ; P=0.002 ) . Conclusion — This large , prospect i ve , r and omized , controlled study demonstrates noninferiority of CB ablation versus RF ablation for treating patients with paroxysmal atrial fibrillation . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00774566", "AIMS Catheter ablation of the pulmonary veins ( PVs ) is a promising therapeutic approach for symptomatic atrial fibrillation ( AF ) . The prospect i ve r and omized single-centre study ' Mesh Ablator versus Cryoballoon Pulmonary Vein Ablation of Symptomatic Paroxysmal Atrial Fibrillation ' ( MACPAF ; clinical trials.gov NCT01061931 ) compared the efficacy and safety of two balloon-based PV ablation systems . METHODS AND RESULTS Thirty-two patients underwent PV ablation for symptomatic paroxysmal AF using the A rct ic Front ® or the HD Mesh Ablator ® catheter according to study protocol . The primary endpoint was complete PV isolation ( PVI ) at the end of the ablation procedure , determined by exit block after achieving entrance block . Long-term follow-up data are not included in this publication . Patients ' mean age was 61.7 ± 8.9 years , 43.2 % were female , and median CHA₂DS₂-VASc score was 2.0 . In the intention-to-treat analysis , the rate of the primary endpoint was 56.5 % in patients r and omized to the A rct ic Front ® and 9.5 % in patients r and omized to the HD Mesh Ablator ® catheter ( P = 0.001 ) . In the per- protocol analysis , complete PVI was achieved in 13 ( 76.5 % ) of 17 A rct ic Front ® patients but in none of the 15 HD Mesh Ablator ® patients ( P major and two minor complications in each study arm but no clinical ly evident stroke . Post-procedural AF recurrence was detected within hospital stay in two ( 11.8 % ) A rct ic Front ® patients and in seven ( 46.7 % ) HD Mesh Ablator ® patients ( P = 0.049 ) . CONCLUSION The MACPAF study revealed a superiority of the A rct ic Front ® catheter concerning complete PVI . Owing to the insufficient efficacy of the HD Mesh Ablator ® catheter , the safety board decided to stop MACPAF prematurely", "BACKGROUND Catheter ablation is an established treatment for atrial fibrillation ( AF ) . Cryoballoon ablation ( CBA ) has emerged as an alternative to radiofrequency ablation ( RFA ) . However , there are few data comparing these modalities for treatment of paroxysmal AF ( pAF ) in the U.S. POPULATION The purpose of this study was to compare procedural times , safety , and efficacy of CBA against RFA . METHODS A single-center prospect i ve cohort study evaluated patients who underwent catheter ablation for pAF using CBA or RFA between January 1 , 2010 and October 31 , 2013 . Patients with prior ablation and those without rhythm follow-up for at least 3 months were excluded . The primary end point was freedom from AF , atrial flutter , and atrial tachycardia ( FFAF ) > 30 seconds after a 3-month blanking period without requirement for antiarrhythmic drugs . We also compared rates of successful pulmonary vein isolation ( PVI ) , fluoroscopy and procedure times , and major complication rates . RESULTS A total of 201 patients were included ( CBA = 101 , RFA = 100 ) . The rate of successful PVI was 99.3 % in CBA versus 97.4 % in RFA ( P = 0.08 ) . Procedure times were shorter with CBA ( 192.9 ± 44.0 minutes vs 283.7 ± 78.0 minutes , P total fluoroscopy times ( 46.0 ± 22.4 minutes vs 73.0 ± 30.1 minutes , P 0.001 ) . Overall complication rates were equivalent ; however , fewer cardiac perforations occurred with CBA ( 0 % vs 4 % , P = 0.042 ) . The 1-year FFAF rates were 60.3 % for CBA and 61.1 % for RFA ( log rank P = 0.93 ) . CONCLUSION CBA was associated with equivalent 1-year FFAF rate as RFA for pAF . Procedure and fluoroscopy times were shorter for CBA and fewer cardiac perforations occurred", "AIMS Cerebral embolism is a possible serious complication during catheter ablation of atrial fibrillation ( AF ) . The purpose of this prospect i ve pilot study was to analyse the incidence and possible impact of cryo ablation on cerebral lesions and possible differences to radiofrequency ( RF ) ablation during pulmonary vein isolation ( PVI ) . METHODS AND RESULTS Pulmonary vein isolation was performed in 89 patients , either with the cryoballoon technique ( n = 45 ) or with RF ablation ( n = 44 ) . Phenprocoumon was stopped 3 days before intervention and replaced by subcutaneous low-molecular-weight heparin . During the catheter procedure , an infusion of unfractionated heparin was maintained to achieve an activated clotting time ( ACT ) of > 300 s. Cerebral magnetic resonance imaging scans were performed 1 day before and after PVI , and at 3-month follow-up . Chronic lesions were observed in 11 patients ( 12.3 % ) before PVI without statistically significant difference between the two groups . None of the patients had neurological symptoms during or following the procedure . Seven patients ( 7.9 % ) developed acute lesions 1 day after PVI , without statistically significant difference between the group treated by cryoenergy ( 8.9 % ) and RF ablation ( 6.8 % ) . Patients with acute lesions were significantly older compared with those without acute cerebral lesions . No additional cerebral lesions during follow-up were observed . CONCLUSION A considerable portion of patients with AF but without any neurological symptoms had chronic cerebral lesions before PVI . Additional acute lesions could be added after the procedure . Both ablation techniques showed additional cerebral acute lesions with no neurological symptoms after PVI", "Background To prevent atrial fibrillation ( AF ) recurrence after catheter ablation , pulmonary venous isolation ( PVI ) at an antral level is more effective than segmental ostial ablation . Cryoablation around the pulmonary venous ( PV ) ostia for AF therapy is potentially safer compared to radiofrequency ablation ( RFA ) . The aim of this study was to investigate the efficacy of a strategy using a large cryoablation balloon to perform antral cryoablation with ‘ touch-up ’ ostial cryoablation for PVI in patients with paroxysmal and persistent AF . Methods Paroxysmal and persistent AF patients undergoing their first left atrial ablation were recruited . After cryoballoon therapy , each PV was assessed for isolation and if necessary , treated with focal ostial cryoablation until PVI was achieved . Follow-up with Holter monitoring was performed . Clinical outcomes of the cryoablation protocol were compared , with consecutive patients undergoing PVI by RFA . Results 124 consecutive patients underwent cryoablation . 77 % of paroxysmal and 48 % of persistent AF subjects were free from AF at 12 months after a single procedure . Over the same time period , 53 consecutive paroxysmal AF subjects underwent PVI with RFA and at 12 months , 72 % were free from AF at 12 months ( p = NS ) . There were too few persistent AF subjects ( n=8 ) undergoing solely PVI by RFA as a comparison group . Procedural and fluoroscopic times during cryoablation were significantly shorter than RFA . Conclusions PV isolation can be achieved in less than 2 h by a simple cryoablation protocol with excellent results after a single intervention , particularly for paroxysmal AF", "Background . There are little comparative data on catheter ablation of paroxysmal atrial fibrillation ( AF ) using the contact force radiofrequency ( CF-RF ) catheter versus the second-generation cryoballoon ( CB2 ) . Methods and results . This is a single center , retrospective , nonr and omized study of 98 patients with symptomatic , drug-refractory paroxysmal AF who underwent their first PVI ablation using either the CB2 ( n = 40 ) or CF-RF ( n = 58 ) . The mean age was 60 years with 63 % men , a mean LA size of 42 mm . The procedure duration ( 74 ± 17 versus 120 ± 49 minutes p CB2 group ; the fluoroscopy time ( 14 ± 17 versus 16 ± 5 minutes , p = 0.45 ) was similar . Complete PVI was achieved in 96 % of patients with RF-CF and 98 % with CB2 . Phrenic nerve palsies ( 2 transient and 1 persistent ) occurred exclusively in the CB2 group and 1 severe , nonlethal complication ( pericardial tamponade ) occurred in the CF-RF group . At 24-month follow-up , the success rate , defined as freedom from AF/atrial tachycardia ( AT ) after a single procedure without antiarrhythmic drug , was comparable in CF-RF group and CB2 group ( 65.5 % versus 67 % , resp . , log rank p = 0.54 ) . Conclusion . Both the CB2 and the RF-CF ablation appeared safe ; the success rate at 2 years was comparable between both technologies", "Summary Background Evidence from animal and human studies suggests that cryoablation might be associated with a lesser inflammatory response and activation of coagulation compared with radiofrequency ablation . The study was aim ed at comparing the effect of cryoballoon and radiofrequency catheter ablation of paroxysmal atrial fibrillation on markers of myocardial damage , inflammation , and activation of coagulation . Methods Forty-one patients received either cryoballoon ( n = 23 ) or radiofrequency ( n = 18 ) ablation of atrial fibrillation . We measured troponin I , high-sensitivity CRP , and interleukin 6 at baseline from the cubital vein , and from the right and left atrium before and after ablation , and from the cubital vein the following day . Prothrombin fragments 1 + 2 , soluble P‑selectin , and D‑dimer were measured before and after ablation from both atria . Results We observed higher troponin I release in the cryoballoon than in the radiofrequency group ( 7.01 mcg/l ( interquartile range [ IQR ] : 5.30–9.09 ) vs 2.32 mcg/l ( IQR : 1.45–2.98 ) , p The levels of inflammatory markers ( high-sensitivity CRP and interleukin 6 ) in the two groups were comparable , as were the levels of markers of coagulation activation . Procedure duration , fluoroscopy times , and mid-term success ( 23 months , IQR 7–32 ) of the two groups were also comparable . Conclusions Cryoballoon ablation of atrial fibrillation causes more significant myocardial damage , that is , more extensive ablation lesions , compared with radiofrequency catheter ablation . However , no major differences between these two ablation techniques with regard to the inflammatory response and activation of the coagulation system were observed", "BACKGROUND Radiofrequency ( RF ) ablation procedures for atrial fibrillation ( AF ) are associated with potential risks of thromboembolism , which may be minimized by the use of cryoablation that preserves the integrity of endocardium . The objective of this study was to compare the thrombogenic potential of transvenous cryoablation versus RF ablation during pulmonary vein ( PV ) isolation . METHODS AND RESULTS Thirty consecutive patients with paroxysmal AF were r and omized to undergo segmental PV isolation procedure using 4-mm tip RF ablation ( n = 15 ) or cryoablation ( CryoCor , San Diego , CA , USA ) ( n = 15 ) . Blood sample s were drawn after sheath insertion ( baseline ) , after transseptal puncture , before ablation ( after heparin administration ) , and after isolation of a superior PV . Activation of coagulation was measured with plasma levels of prothrombin fragment 1 + 2 ( F1 + 2 ) and thrombin-antithrombin III complex ( TAT ) , and platelets by plasma level of beta-thromboglobulin ( beta-TG ) and flow cytometric enumerating of P-selectin (CD62)-positive platelets . In both groups , the plasma level of beta-TG , F1 + 2 , and TAT were elevated after sheath insertion . The percentage changes in plasma level of beta-TG , F1 + 2 , and TAT and CD41/62-positive platelets from baseline after transseptal puncture and before ablation were similar ( P > 0.05 ) . However , the percentage changes in CD62-positive platelets from baseline were significantly higher in patients treated with RF ablation ( 82 + /- 20 % ) than with cryoablation ( 22 + /- 14 % , P = 0.02 ) , although their plasma levels of beta-TG , F1 + 2 , and TAT were not different ( P > 0.05 ) . CONCLUSIONS Significant platelet and coagulation activations were observed during PV ablation procedures , and heparin administration only prevented activation of coagulation but not platelets . Persistent platelets activation was observed during RF energy application , but not during cryoablation", "BACKGROUND Although radiofrequency ( RF ) and cryoballoon ( CB ) based technologies for pulmonary vein isolation ( PVI ) have both individually been demonstrated to be effective and safe for the treatment of paroxysmal AF , head-to-head comparisons are lacking . The purpose of this study was to compare the outcome of cryoballoon versus radiofrequency ablation in patients with paroxysmal atrial fibrillation undergoing pulmonary vein isolation . METHODS Out of a prospect i ve registry of 327 patients undergoing PVI , 208 patients ( age 58±11 years , ejection fraction 59±6 % , left atrial size 39±6 mm ) with paroxysmal AF were identified . The presented data set was obtained by 1:1 propensity score matching and contained 142 patients undergoing CB-PVI or RF-PVI in conjunction with a 3D mapping system , respectively . We compared single procedure efficacy of the two methods using a Cox proportional hazards model . RESULTS After a mean follow-up of 28 months and a single procedure , AF recurred in 37 of 71 ( 52 % ) in the CB-PVI group and in 31 of 71 patients ( 44 % ) in the RF-PVI group ( HR [ 95 % CI]=1.19 [ 0.74 , 1.92 ] , p=0.48 ) . Recurrence of AF for PVI using solely the CB was observed in 23 of 51 ( 45 % ) patients and in 23 of 51 ( 45 % ) patients in the corresponding RF-PVI group ( HR [ 95 % CI]=0.93 [ 0.52 , 1.66 ] , p=0.81 ) . Complication rate was not different between the groups . CONCLUSION A propensity score matched comparison between CB-PVI and RF-PVI using a 3D-mapping system for AF ablation showed similar long-term success rates", "BACKGROUND Inflammation plays a prominent role in the etiology of the early recurrence of atrial fibrillation ( ERAF ) . We prospect ively compared the proportion of ERAF and time-course patterns of biomarkers between radiofrequency ( RF ) and cryoballoon ( CB ) ablation . METHODS AND RESULTS We enrolled 82 consecutive paroxysmal AF patients undergoing pulmonary vein ( PV ) isolation , performed with either a 28-mm 2nd-generation CB and 3-min freeze technique or point-by-point RF ablation . Each group had 41 patients . In the RF group , all PVs were successfully isolated with 28.9 ± 6.5 min of RF delivery . In the CB group , a mean of 5.3 ± 1.4 applications/patient was delivered . The proportion of ERAF was similar between the groups . The time-course patterns significantly differed between the groups for high-sensitivity C-reactive protein ( hs-CRP ) value ( P=0.006 ) and myocardial injury markers ( P Greater myocardial injury was observed in the CB than in the RF group ( P peak hs-CRP value was comparable between the groups . The 2-day post-procedure hs-CRP value was the sole factor correlating with ERAF as identified by the multivariable analysis ( hazard ratio 1.697 ; 95 % confidence interval , 1.005 - 2.865 ; P=0.048 ) in the RF , but not the CB group . CONCLUSIONS The proportion of ERAF was comparable after RF and 2nd-generation CB ablation . Despite CB ablation exhibiting greater myocardial injury than RF ablation , the inflammatory responses were comparable between the groups . The inflammatory response extent predicted ERAF post-RF ablation but not post-CB ablation", "INTRODUCTION Ablation of pulmonary veins ( PV ) is an established therapeutic option for patients with symptomatic drug-refractory paroxysmal atrial fibrillation ( AF ) . Radiofrequency ( RF ) is currently the most widespread energy source for PV ablation . Cryothermal energy applied with a cryoballoon technique as an alternative has recently evolved . METHODS AND RESULTS In a case-control setting , we compared 20 patients with paroxysmal AF who underwent their first PV ablation with the cryoballoon technique to 20 matched patients with conventional RF ablation . In the case of persistent electrical potentials after cryoballoon ablation , it was combined with ablation with a conventional cryocatheter . All patients performed daily event recording for 3 months after ablation procedure . Ablation parameters and success rate after 3 and 6 months were compared . In the cryoballoon group , the overall success rate was 55 % ( 50 % in the cryoballoon only group [ 14 patients ] and 66 % in the combination group [ 6 patients ] ) , as opposed to the RF group with 45 % . AF episode burden was lower after cryoballoon ablation . There was no significant difference between cryoballoon and RF ablation regarding procedure parameters . In the cryoballoon group , 3 phrenic nerve palsies occurred using the 23 mm balloon that resolved spontaneously . CONCLUSION PV ablation with the cryoballoon technique is feasible and seems to have a similar success rate in comparison to RF ablation . Procedure- and fluoroscopy duration are not longer than in conventional RF ablation", "AIM Catheter ablation of paroxysmal atrial fibrillation ( PAF ) is associated with an important risk of early and late recurrence , necessitating repeat ablation procedures . The aim of this prospect i ve r and omized patient-blind study was to compare the efficacy and safety of cryoballoon ( Cryo ) versus radiofrequency ( RF ) ablation of PAF after failed initial RF ablation procedure . METHODS Patients with a history of symptomatic PAF after a previous failed first RF ablation procedure were eligible for this study . Patients were r and omized to Cryo or RF redo ablation . The primary endpoint of the study was recurrence of atrial tachyarrhythmia , including AF and left atrial flutter/tachycardia , after a second ablation procedure at 1 year of follow-up . All patients were implanted with a cardiac monitor ( Reveal XT , Medtronic ) to continuously track the cardiac rhythm . Patients with an AF burden ( AF% ) ≤ 0.5 % were considered AF-free ( Responders ) , while those with an AF% > 0.5 % were classified as patients with AF recurrences ( non-Responders ) . RESULTS Eighty patients with AF recurrences after a first RF pulmonary vein isolation ( PVI ) were r and omized to Cryo ( N = 40 ) or to RF ( N = 40 ) . Electrical potentials were recorded in 77 mapped PVs ( 1.9 ± 0.8 per patient ) in Cryo Group and 72 PVs ( 1.7 ± 0.8 per patient ) in RF Group ( P = 0.62 ) , all of which were targeted . In Cryo group , 68 ( 88 % ) of the 77 PVs were re-isolated using only Cryo technique ; the remaining 9 PVs were re-isolated using RF . In RF group , all 72 PVs were successfully re-isolated ( P = 0.003 vs Cryo ) . By intention-to-treat , 23 ( 58 % ) RF patients were AF-free vs 17 ( 43 % ) Cryo patients on no antiarrhythmic drugs at 1 year ( P = 0.06 ) . Three patients had temporary phrenic nerve paralysis in the Cryo group ; the RF group had no complications . Of the 29 patients who had only Cryo PVI without any RF ablation , 11 ( 38 % ) were AF-free vs 20 ( 59 % ) of the 34 patients who had RF only ( P = 0.021 ) . CONCLUSION When patients require a redo pulmonary vein isolation ablation procedure for recurrent PAF , RF appears to be the preferred energy source relative to Cryo", "INTRODUCTION Catheter ablation of paroxysmal AF using the Cryoballoon ( CRYO ) has yielded similar success rates to conventional wide encirclement using radiofrequency catheter ablation ( RFCA ) , but r and omized data are lacking . Pilot data suggested a high success rate with a combined approach ( COMBINED ) using wide encirclement with RFCA followed by 2 CRYO applications to each vein . We compared these 3 strategies in a r and omized controlled trial . METHODS AND RESULTS Patients undergoing first time paroxysmal AF ablation were r and omized to RFCA , CRYO , or COMBINED . Patients were followed up at 3 , 6 , and 12 months with 7 days of ambulatory ECG monitoring . Success was defined as freedom from arrhythmia without antiarrhythmic drugs after a single procedure . A total of 237 patients were r and omized . Success at 1 year was achieved in 47 % in the RFCA group , 67 % in the CRYO group , and 76 % in the COMBINED group ( P RFCA vs. CRYO , P Procedure time was 211 ( IQR 174 - 256 ) minutes for RFCA compared to 167 ( 136 - 202 ) minutes for CRYO and 278 ( 243 - 327 ) minutes for COMBINED ( P CRYO and results in a higher single procedure success rate than conventional point by point RFCA . The COMBINED approach was not superior to CRYO alone", "BACKGROUND Catheter ablation is used extensively with curative intention in atrial fibrillation . Radiofrequency ablation has long been a st and ard of care , while cryoballoon technology has emerged as a feasible approach with promising results . Prospect i ve multicenter registry data referring to both ablation technologies in AF ablation therapy are lacking . METHODS Between January 2007 and August 2011 , a total of 3,775 consecutive patients with symptomatic paroxysmal AF who underwent PV ablation in their respective centers were enrolled . The cohort was divided into 2 groups according to the ablation energy source used : cryoballoon ablation ( group 1 , n = 905 [ 24.0 % ] , median age 63 years , 64.3 % men ) and RF ablation ( group 2 , n = 2870 [ 76.0 % ] , median age 63 years , 62.7 % men ) . Comorbidities and baseline clinical characteristics were similar in both groups . RESULTS Acute success rate was similar in both groups ( 97.5 % in cryo vs 97.6 % in RF ; P = 0.81 ) . Procedure times were similar , ablation and fluoroscopy times were higher in cryoballoon when compared to RF ablation . Overall complication rate was similar in cryo- ( 4.6 % ) and RF-ablation ( 4.6 % ; P = 1.0 ) . Phrenic nerve palsy was more often in cryo versus RF ablation ( 2.1 % in cryo vs 0.0 % in RF ; P Other complications were more common in RF compared to cryoablation ( 4.6 % in RF vs 2.7 % in cryo ; P RF ablation is the most widespread ablation method in Germany , but use of cryoballoon increased significantly . Procedure times were similar , but ablation and fluoroscopy times were longer in cryoballoon ablation . No significant differences were found in terms of acute success and overall complication rate", "BACKGROUND Atrial fibrillation ( AF ) is the most common sustained cardiac arrhythmia imposing substantial morbidity and mortality . Catheter-based pulmonary vein isolation ( PVI ) using radiofrequency current ( RFC ) has become a st and ard treatment for drug-resistant and symptomatic paroxysmal AF ( PAF ) . In recent years , the cryoballoon-based technique is increasingly used as a promising alternative with a short learning curve . METHODS The FIRE AND ICE trial is a prospect i ve , r and omized , controlled , open , blinded outcome assessment , noninferiority trial comparing cryoballoon- , and RFC-based PVI . Patients with drug-resistant PAF will be r and omized in a 1:1 matrix in multiple European centers . The primary hypothesis is that cryoballoon ablation is not inferior to RFC ablation using 3-dimensional mapping with respect to clinical efficacy . The primary endpoint is defined as the time to first documented clinical failure , including : ( 1 ) recurrence of AF ; ( 2 ) atrial flutter or atrial tachycardia ; ( 3 ) prescription of class I or III antiarrhythmic drugs ; or ( 4 ) re-ablation , whichever comes first , following a blanking period of 3 months after the index ablation procedure . The primary safety endpoint is a composite of death , stroke/transient ischemic attack , cardiac arrhythmias ( apart from AF recurrence ) causally related to the therapeutic intervention , and procedure-related serious adverse events . CONCLUSION The FIRE AND ICE trial compares 2 different technologies to perform catheter ablation of PAF with respect to efficacy and safety . It aims at providing objective data to guide selection and usage of ablation catheters in the treatment of AF", "INTRODUCTION The additional benefit of contact force ( CF ) technology during pulmonary vein isolation ( PVI ) for paroxysmal atrial fibrillation ( AF ) to improve mid-term clinical outcome is unclear . METHODS AND RESULTS Eligible patients with symptomatic paroxysmal AF were enrolled in this prospect i ve trial , comparing circular antral catheter ablation ( guided by Carto 3 System , Biosense Webster ) using either a new open-irrigated CF catheter ( SmartTouch Thermocool , Biosense Webster ) ( CF group ) or a non-CF open-irrigated catheter ( EZ Steer Thermocool , Biosense Webster ) ( control group ) . Overall , 30 patients were enrolled in each group , with a st and ardized 12-month follow-up , free of antiarrhythmic therapy . Demographic , cardiovascular and anatomic characteristics were similar in both groups . Though complete PVI was eventually achieved in all cases in both groups , success using an exclusive anatomic approach was 80.0 % in CF group versus 36.7 % in control group ( P fluoroscopy exposure ( P radiofrequency time ( P = 0.01 ) . The incidence rates of AF recurrence were 10.5 % ( 95 % CI , 1.38 - 22.4 ) in the CF group , and 35.9 % ( 95 % CI , 12.4 - 59.4 ) in the control group ( log rank test , P = 0.04 ) . After adjustment on potential confounders , the use of CF catheter was found to be associated with a lower AF recurrence ( OR 0.18 , 95 % CI 0.04 - 0.94 , P = 0.04 ) . CONCLUSION Our findings suggest a potential benefit of real-time CF sensing technology , in reducing AF recurrence during the first year after PVI", "AIMS In the setting of paroxysmal atrial fibrillation ( AF ) , there are no available data comparing the mid-term outcome of patients undergoing pulmonary vein isolation ( PVI ) catheter ablation using contact-force (CF)-guided radiofrequency ( RF ) vs. second-generation balloon cryotherapy . METHODS AND RESULTS Prospect i ve single-centre evaluation , carried out from March 2011 to February 2013 , comparing CF radiofrequency ( Thermocool ( ® ) SmartTouch ™ , Biosense Webster , Inc. ) ( CF group ) with cryoballoon ablation ( A rct ic Front Advance ™ 28 mm cryoballoon , Medtronic , Inc. ) ( CB group ) , in regards to procedural safety and efficacy , as well as recurrence at 12 months . Overall , 150 consecutive patients were enrolled ( 75 in each group ) . The characteristics of patients of both the groups were similar ( 61.2 ± 9.9 years , women 25.3 % , mean AF duration 4.1 ± 4.0 years , mean CHA2DS2-VASc score 1.4 ± 1.3 , mean HAS-BLED 1.4 ± 0.6 ) . Duration of the procedure was significantly lower in the CF group ( 110.7 ± 32.5 vs. 134.5 ± 48.3 min , P = 0.001 ) , with a lower duration of fluoroscopy ( 21.5 ± 8.5 vs. 25.3 ± 9.9 min , P = 0.017 ) and X-ray exposure ( 4748 ± 2411 cGy cm² vs. 7734 ± 5361 cGy cm² , P = 0.001 ) . In contrast , no significant difference was found regarding significant procedural complication ( 2.7 vs. 1.3 % in CF and CB groups , respectively ; P = 0.56 ) , and PVI was eventually achieved in all cases . At 12 months , AF recurrence occurred in 11 patients ( 14.7 % ) in the CB group and in 9 patients ( 12.0 % ) in the CF group ( HR = 1.20 95 % CI 0.50 - 2.90 ; log rank P = 0.682 ) . CONCLUSIONS Our preliminary findings suggest that CF-guided radiofrequency and cryotherapy present very similar performances in the setting of paroxysmal AF catheter ablation", "AIMS Atrial fibrillation ( AF ) ablation is increasingly being performed in electrophysiology laboratories . Pericardial effusion ( PE ) is certainly one of the most frequently observed complications during AF ablation . The aim of our study was to investigate the incidence and outcome of PE following cryothermal energy balloon ablation ( CBA ) in comparison with conventional circumferential pulmonary vein isolation with a focal radiofrequency ( RF ) catheter . METHODS AND RESULTS A total of 133 consecutive patients ( 105 males ) with paroxysmal AF were included in this study . Forty-six patients ( 36 males ) underwent CBA ( A rct ic Front , Medtronic , USA ) and 87 ( 69 males ) point-by-point RF ablation guided by electroanatomical mapping ( Carto , Biosense Webster , Diamond Bar , CA , USA ) . Ablation was performed under general anaesthesia with both techniques . All patients underwent a 2D transthoracic echocardiogram within 24 h before and after the procedure as routinely performed in our centre . Pericardial effusion was detected in 19 ( 14.2 % ) of 133 patients . Sixteen patients presented mild effusion , one moderate effusion , and two pericardial tamponades . There was no significant difference in the incidence of PE between the cryoballoon and the RF group ( 11 vs. 16 % ) . A longer procedural time , coronary artery disease , and arterial hypertension were found to be independent predictors of PE during AF ablation . CONCLUSION Pericardial effusion occurred in a similar proportion following CBA and RF ablation for AF . Pericardial effusion was mostly mild and asymptomatic , with benign clinical outcome not requiring additional hospitalization days", "BACKGROUND Results from r and omized trials design ed to compare cryoenergy with radiofrequency for pulmonary vein ( PV ) isolation are lacking . OBJECTIVE To compare the efficacy of a simplified strategy for PV cryoablation ( group C ) vs PV isolation with open-irrigated radiofrequency catheters ( group R ) . METHODS Fifty patients with paroxysmal atrial fibrillation ( AF ) and 4 independent PVs received a Reveal XT implantable cardiac monitor and were r and omized to group C or group R. In group C , PV ablation was done with a single A rct ic Front balloon ( 23 or 28 mm ) per patient and two 300-second applications per PV . No further applications were delivered to close residual conduction gaps . In group R , bidirectional PV conduction block was pursued with Lasso and Navistar ThermoCool catheters and the CARTO system . The primary end point was the proportion of patients remaining free from AF recurrences ≥2 minutes without taking antiarrhythmic drugs 12 months after ablation . RESULTS The primary end point was met by 12 ( 48 % ) patients in group C and 25 ( 68 % ) patients in group R ( odds ratio 0.43 ; P = .05 ) . This difference disappeared after adjustment for acute procedural outcome . In patients for whom all 4 PVs were blocked at the end of the procedure , there was no difference between group C and group R in the primary end point ( 67 % vs 68 % ; P = .94 ) . CONCLUSIONS The efficacy of the simplified strategy for PV cryoablation tested in this study is inferior to PV isolation using open-irrigated radiofrequency catheters with electrophysiological and electroanatomical guidance . Complete PV conduction block is critical to the success of AF ablation", "BACKGROUND Catheter ablation is less successful for persistent atrial fibrillation than for paroxysmal atrial fibrillation . Guidelines suggest that adjuvant substrate modification in addition to pulmonary-vein isolation is required in persistent atrial fibrillation . METHODS We r and omly assigned 589 patients with persistent atrial fibrillation in a 1:4:4 ratio to ablation with pulmonary-vein isolation alone ( 67 patients ) , pulmonary-vein isolation plus ablation of electrograms showing complex fractionated activity ( 263 patients ) , or pulmonary-vein isolation plus additional linear ablation across the left atrial roof and mitral valve isthmus ( 259 patients ) . The duration of follow-up was 18 months . The primary end point was freedom from any documented recurrence of atrial fibrillation lasting longer than 30 seconds after a single ablation procedure . RESULTS Procedure time was significantly shorter for pulmonary-vein isolation alone than for the other two procedures ( P pulmonary-vein isolation alone were free from recurrent atrial fibrillation , as compared with 49 % of patients assigned to pulmonary-vein isolation plus complex electrogram ablation and 46 % of patients assigned to pulmonary-vein isolation plus linear ablation ( P=0.15 ) . There were also no significant differences among the three groups for the secondary end points , including freedom from atrial fibrillation after two ablation procedures and freedom from any atrial arrhythmia . Complications included tamponade ( three patients ) , stroke or transient ischemic attack ( three patients ) , and atrioesophageal fistula ( one patient ) . CONCLUSIONS Among patients with persistent atrial fibrillation , we found no reduction in the rate of recurrent atrial fibrillation when either linear ablation or ablation of complex fractionated electrograms was performed in addition to pulmonary-vein isolation . ( Funded by St. Jude Medical ; Clinical Trials.gov number , NCT01203748 . )", "BACKGROUND Experimental data suggest that use of cryoablation in pulmonary vein isolation ( PVI ) is associated with less cell damage and less thrombus formation compared to radiofrequency ( RF ) energy . OBJECTIVE The purpose of this study was to test the hypothesis that cryoablation significantly reduces markers of cell damage , platelet activation , and inflammation in patients undergoing PVI for treatment of atrial fibrillation ( AF ) . METHODS Sixty patients with symptomatic drug-resistant AF ( age 56 ± 9 years , 48 males , 38 with paroxysmal AF ) were r and omly assigned to undergo PVI using either an open irrigated-tip RF catheter or a cryoballoon . Markers of cell damage ( high-sensitive troponin T [ hs-TnT ] , microparticles ) , platelet activation ( platelet reactivity by aggregometry , expression of platelet surface proteins P-selectin and activated glycoprotein [ GP ] IIb/IIIa ) , and inflammatory response ( high-sensitive C-reactive protein [ hs-CRP ] ) were determined before and up to 48 hours after the procedure . RESULTS PVI result ed in a significant rise in hs-TnT , microparticles , markers of platelet activation , and hs-CRP over time , with distinct temporal patterns for each parameter . However , after Bonferroni correction for repeated measurements , no significant differences were noted in these parameters between patients treated with cryoablation or RF energy . Procedural time was significantly shorter in patients treated with cryoballoon ( 177 ± 30 minutes vs 200 ± 46 minutes , P = .03 ) , with no differences in fluoroscopic time , periprocedural complications , or success rate . CONCLUSION Cryoablation and RF energy result in a comparable rise of markers of cell damage , platelet activation and inflammatory response . The data do not support the concept of an improved safety profile for cryoablation in PVI", "Aim Cryoballoon ablation ( Cryoballoon ) has emerged as a new alternative for the treatment of symptomatic drug-refractory atrial fibrillation ( AF ) . Whether the results of Cryoballoon are more reproducible than those of radiofrequency ( RF ) ablation remains to be proved . Methods and results A total of 860 consecutive patients undergoing a first ablation procedure for paroxysmal AF ( 467 treated with RF and 393 treated with Cryoballoon ) were selected from a prospect i ve multicentre survey of AF ablation ( FrenchAF ) . Radiofrequency and Cryoballoon were compared regarding mid-term efficacy and safety . During a median follow-up of 14 months ( interquartile range 8–23 ) , patients treated with Cryoballoon displayed similar rates of freedom from atrial arrhythmia relapse in centres performing this technique ( 68–80 % at 18 months ) . However , in centres performing RF , a greater heterogeneity in procedural results was observed ( 46–79 % were free from atrial arrhythmia relapse at 18 months ) . On multivariate analysis , Cryoballoon ( HR = 0.47 , 95 % CI 0.35–0.65 , P AF ablation caseload ( HR = 0.87 per every 100 AF ablation procedures per year ; 95 % CI 0.80–0.96 , P = 0.003 ) were independent predictors of procedural success . However , on sensitivity analysis , according to the ablation method , annual AF ablation caseload predicted only sinus rhythm maintenance in the subgroup of patients treated with RF . Analysis of interoperator results with Cryoballoon and RF confirmed lower reproducibility of RF , but suggested that besides caseload , other operator-related factors may play a role . Conclusion Cryoballoon seems to be less operator-dependent and more reproducible than RF in the setting of paroxysmal AF ablation", "BACKGROUND Current guidelines recommend pulmonary-vein isolation by means of catheter ablation as treatment for drug-refractory paroxysmal atrial fibrillation . Radiofrequency ablation is the most common method , and cryoballoon ablation is the second most frequently used technology . METHODS We conducted a multicenter , r and omized trial to determine whether cryoballoon ablation was noninferior to radiofrequency ablation in symptomatic patients with drug-refractory paroxysmal atrial fibrillation . The primary efficacy end point in a time-to-event analysis was the first documented clinical failure ( recurrence of atrial fibrillation , occurrence of atrial flutter or atrial tachycardia , use of antiarrhythmic drugs , or repeat ablation ) following a 90-day period after the index ablation . The noninferiority margin was prespecified as a hazard ratio of 1.43 . The primary safety end point was a composite of death , cerebrovascular events , or serious treatment-related adverse events . RESULTS A total of 762 patients underwent r and omization ( 378 assigned to cryoballoon ablation and 384 assigned to radiofrequency ablation ) . The mean duration of follow-up was 1.5 years . The primary efficacy end point occurred in 138 patients in the cryoballoon group and in 143 in the radiofrequency group ( 1-year Kaplan-Meier event rate estimates , 34.6 % and 35.9 % , respectively ; hazard ratio , 0.96 ; 95 % confidence interval [ CI ] , 0.76 to 1.22 ; P primary safety end point occurred in 40 patients in the cryoballoon group and in 51 patients in the radiofrequency group ( 1-year Kaplan-Meier event rate estimates , 10.2 % and 12.8 % , respectively ; hazard ratio , 0.78 ; 95 % CI , 0.52 to 1.18 ; P=0.24 ) . CONCLUSIONS In this r and omized trial , cryoballoon ablation was noninferior to radiofrequency ablation with respect to efficacy for the treatment of patients with drug-refractory paroxysmal atrial fibrillation , and there was no significant difference between the two methods with regard to overall safety . ( Funded by Medtronic ; FIRE AND ICE Clinical Trials.gov number , NCT01490814 . )" ]

[ "CONTEXT Recent guidelines for treatment of overweight and obesity include recommendations for risk stratification by disease conditions and cardiovascular disease ( CVD ) risk factors , but the role of physical inactivity is not prominent in these recommendations . OBJECTIVE To quantify the influence of low cardiorespiratory fitness , an objective marker of physical inactivity , on CVD and all-cause mortality in normal-weight , overweight , and obese men and compare low fitness with other mortality predictors . DESIGN Prospect i ve observational data from the Aerobics Center Longitudinal Study . SETTING Preventive medicine clinic in Dallas , Tex . PARTICIPANTS A total of 25714 adult men ( average age , 43.8 years [ SD , 10.1 years ] ) who received a medical examination during 1970 to 1993 , with mortality follow-up to December 31 , 1994 . MAIN OUTCOME MEASURES Cardiovascular disease and all-cause mortality based on mortality predictors ( baseline CVD , type 2 diabetes mellitus , high serum cholesterol level , hypertension , current cigarette smoking , and low cardiorespiratory fitness ) stratified by body mass index . RESULTS During the study period , there were 1025 deaths ( 439 due to CVD ) during 258781 man-years of follow-up . Overweight and obese men with baseline CVD or CVD risk factors were at higher risk for all-cause and CVD mortality compared with normal-weight men without these predictors . Using normal-weight men without CVD as the referent , the strongest predictor of CVD death in obese men was baseline CVD ( age- and examination year-adjusted relative risk [ RR ] , 14.0 ; 95 % confidence interval [ CI ] , 9.4 - 20.8 ) ; RRs for obese men with diabetes mellitus , high cholesterol , hypertension , smoking , and low fitness were similar and ranged from 4.4 ( 95 % CI , 2.7 - 7.1 ) for smoking to 5.0 ( 95 % CI , 3.6 - 7.0 ) for low fitness . Relative risks for all-cause mortality in obese men ranged from 2.3 ( 95 % CI , 1.7 - 2.9 ) for men with hypertension to 4.7 ( 95 % CI , 3.6 - 6.1 ) for those with CVD at baseline . Relative risk for all-cause mortality in obese men with low fitness was 3.1 ( 95 % CI , 2.5 - 3.8 ) and in obese men with diabetes mellitus 3.1 ( 95 % CI , 2.3 - 4.2 ) and as slightly higher than the RRs for obese men who smoked or had high cholesterol levels . Low fitness was an independent predictor of mortality in all body mass index groups after adjustment for other mortality predictors . Approximately 50 % ( n = 1674 ) of obese men had low fitness , which led to a population -attributable risk of 39 % for CVD mortality and 44 % for all-cause mortality . Baseline CVD had population attributable risks of 51 % and 27 % for CVD and all-cause mortality , respectively . CONCLUSIONS In this analysis , low cardiorespiratory fitness was a strong and independent predictor of CVD and all-cause mortality and of comparable importance with that of diabetes mellitus and other CVD risk factors", "BACKGROUND The proportion of overweight adolescents has increased , but the behavioral risk factors for overweight youth are not well understood . OBJECTIVE To examine how diet , physical activity , and sedentary behaviors relate to overweight status in adolescents . DESIGN AND SETTING Baseline data from the Patient-Centered Assessment and Counseling for Exercise Plus Nutrition Project , a r and omized controlled trial of adolescents to determine the effects of a clinic-based intervention on physical activity and dietary behaviors . PARTICIPANTS A total of 878 adolescents aged 11 to 15 years , 42 % of whom were from minority background s. MAIN OUTCOME MEASURE Centers for Disease Control and Prevention body mass index-for-age percentiles divided into 2 categories : normal weight ( or=85th percentile ) . RESULTS Overall , 45.7 % of the sample was classified as AR + O with a body mass index for age at the 85th percentile or higher . More girls from minority background s ( 54.8 % ) were AR + O compared with non-Hispanic white girls ( 42 % ) ( chi(2)(1 ) = 7.6 ; P = .006 ) . Bivariate analyses indicated that girls and boys in the AR + O group did fewer minutes per day of vigorous physical activity , consumed fewer total kilojoules per day , and had fewer total grams of fiber per day than those in the normal-weight group . Boys in the AR + O group also did fewer minutes per day of moderate physical activity and watched more minutes per day of television on nonschool days than normal-weight boys . Final multivariate models indicated that independent of socioeconomic status ( as assessed by household education level ) , girls had a greater risk of being AR + O if they were Hispanic or from another minority background ( odds ratio [ OR ] = 1.65 ; 95 % confidence interval [ CI ] , 1.09 - 2.49 ) and a reduced risk of being AR + O as minutes per day of vigorous physical activity increased ( OR = 0.93 ; 95 % CI , 0.89 - 0.97 ) . A low level of vigorous physical activity was the only significant risk factor for boys being AR + O ( OR = 0.92 ; 95 % CI , 0.89 - 0.95 ) . Analyses based on meeting behavioral guidelines supported these findings and showed that failing to meet the 60 min/d moderate to vigorous physical activity guideline was associated with overweight status for both girls and boys . In addition , boys who failed to meet sedentary behavior and dietary fiber guidelines were more likely to be overweight . CONCLUSIONS Of the 7 dietary and physical activity variables examined in this cross-sectional study , insufficient vigorous physical activity was the only risk factor for higher body mass index for adolescent boys and girls . Prospect i ve studies are needed to clarify the relative importance of dietary and physical activity behaviors on overweight in adolescence", "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", "Type 2 diabetes is a common disease in industrialized countries . It is a major cause of cardiovascular disease and all-cause mortality ( 1 - 6 ) , and its prevalence has increased continuously over the past few decades ( 1 ) . The American Diabetes Association currently defines impaired fasting glucose as a fasting plasma glucose level from 6.1 to 6.9 mmol/L ( 110 to 125 mg/dL ) and type 2 diabetes as a fasting plasma glucose level of 7.0 mmol/L ( 126 mg/dL ) or more ( 1 ) . Data from several prospect i ve studies show an inverse association between physical activity and diabetes ( 7 - 13 ) . However , these studies are limited by the use of self-reporting of physical activity and presence of type 2 diabetes ( 7 - 12 ) . Self-reporting of physical activity tends to be imprecise , and type 2 diabetes is undiagnosed in about 50 % of the prevalent cases ( 14 ) . This leads to misclassification on both exposure and outcome measures ( 15 ) . These limitations may result in underestimation of the true association between sedentary habits and risk for type 2 diabetes . Impaired fasting glucose is a strong predictor of type 2 diabetes , cardiovascular disease , and other diabetic complications ( 6 , 16 - 18 ) . The underlying cause of impaired fasting glucose is unknown , and no prospect i ve study of the association between physical activity and impaired fasting glucose has been published . We examined the relation of cardiorespiratory fitness , objective ly determined by a maximal exercise test on a treadmill , to the incidence of impaired fasting glucose and type 2 diabetes . Cases of impaired fasting glucose and diabetes at baseline and follow-up were determined by using the American Diabetes Association 's current guidelines ( 1 ) . Methods Patients In our population -based prospect i ve study , we included 8633 men 30 to 79 years of age at baseline ( mean , 43.5 years ) who completed at least two medical evaluations at the Cooper Clinic in Dallas , Texas , from 1970 to 1995 . Patients come to the Cooper Clinic for preventive medical examinations and health promotion counseling . Many are sent by their employers for these services , some are referred by their personal physicians , and others are self-referred . More than 97 % of the patients are white , and most are employed in executive or professional occupations . More than 75 % are college graduates . Although study participants came from middle and upper socioeconomic strata , they were similar to other well-characterized population -based cohorts in terms of blood pressure , cholesterol level , body weight , and cardiorespiratory fitness ( 19 ) . The study was review ed and approved annually by the institutional review board at the Cooper Institute for Aerobics Research . Additional details of the study methods and population characteristics of the cohort have been published elsewhere ( 20 , 21 ) . Because clinical or sub clinical heart disease and other conditions associated with type 2 diabetes may alter the level of physical activity and thus cardiorespiratory fitness , we excluded men with an abnormal resting or exercise electrocardiogram or a history of heart attack , stroke , or cancer at the baseline clinical examination ( n=2350 ) . The baseline evaluation was performed after participants gave written informed consent for the initial medical examination and registration in the follow-up study . Examinations were done after patients had fasted for at least 12 hours and included personal and family health histories , a question naire on demographic characteristics and health habits , a physical examination , an exercise test , anthropometric measurement , electrocardiography , blood chemistry analyses , and blood pressure measurement . Technicians who followed a st and ard manual of operations administered all procedures . Impaired fasting glucose and type 2 diabetes were diagnosed according to American Diabetes Association criteria that define impaired fasting glucose as a fasting plasma glucose level of 6.1 to 6.9 mmol/L ( 110 mg/dL to 125 mg/dL ) and diabetes as a fasting plasma glucose level of 7.0 mmol/L ( 126 mg/dL ) or more ( 1 ) . Patients who did not meet these criteria but who reported a history of diabetes or current therapy with oral antidiabetic agents or insulin were also considered to have diabetes . We excluded patients who had diabetes at baseline according to any of these criteria ( n=377 ) . Cardiorespiratory fitness was assessed with a maximal exercise test that followed a modified Balke protocol ( 22 ) . Details of treadmill speed and elevation have been described elsewhere ( 20 , 21 ) . Briefly , the test began with the patient walking on a horizontal treadmill at 88 m/min . After the first minute , the elevation increased to 2 % ; the elevation then increased 1 % each minute up to 25 minutes . For the few patients who were still able to continue , the elevation was held constant after 25 minutes and the speed was increased by 5.4 m/min until the patient reached volitional fatigue . Use of this protocol for the exercise test correlates highly ( r=0.92 ) with measured maximal oxygen uptake ( 23 ) . All patients in our study achieved at least 85 % of their age-predicted maximal heart rate ; average maximal heart rates ( SD ) in each age group were 186 11 beats/min for patients 30 to 39 years of age , 179 12 beats/min for those 40 to 49 years of age , 172 13 beats/min for those 50 to 59 years of age , and 162 17 beats/min for those 60 years of age or older . Average maximal heart rates in each age group exceeded the age-predicted rate ( 220 beats/min age in years ) , which indicates that the exercise test can be considered maximal performance . We defined level of fitness by total time on the treadmill at the baseline examination , as in our previous studies ( 20 , 21 ) . Treadmill times were placed in frequency distributions for specific age groups ( 30 to 39 , 40 to 49 , 50 to 59 , or 60 or more years of age ) . The least fit 20 % of the participants in each age group were classified as low fitness , the next 40 % as moderate fitness , and the remaining 40 % as high fitness . The respective cut-points for total treadmill time in the low- , moderate- , and high-fitness groups were 945 seconds or less , 946 to 1259 seconds , and 1260 seconds or more for patients 30 to 39 years of age ; 849 seconds or less , 850 to 1020 seconds , and 1021 seconds or more for patients 40 to 49 years of age ; 750 seconds or less , 751 to 1035 seconds , and 1036 seconds or more for patients 50 to 59 years of age ; and 644 seconds or less , 645 to 953 seconds , and 954 seconds or more for patients 60 years of age or older . These cut-points at the 20th and 60th percentiles to define fitness levels were used in previous studies ( 20 , 21 ) and were selected before analysis for our investigation . However , we calculated these cut-points with patients in the current study , from which unhealthy persons were excluded . Therefore , they differ somewhat from the cut-points derived from the entire cohort of the Aerobics Center Longitudinal Study ( 21 ) . For some analyses , such as the models that included change in fitness from baseline to follow-up , cardiorespiratory fitness was expressed as maximal metabolic units ( metabolic equivalents [ METs ] , calculated as the working metabolic rate/resting metabolic rate ; 1 MET is equivalent to an oxygen uptake of 3.5 mL1 kg1 ) achieved on the exercise test . In other analyses , time on the treadmill was used as a continuous variable . Serum sample s were analyzed by using automated techniques in a laboratory that participates in the Centers for Disease Control and Prevention Lipid St and ardization Program . Blood pressure was measured by using auscultatory methods with a mercury sphygmomanometer . We defined high blood pressure as systolic blood pressure of at least 140 mm Hg , diastolic blood pressure of at least 90 mm Hg , or a history of hypertension . Height and weight were measured with a st and ard physician 's scale and stadiometer , and body mass index was calculated as weight in kg/height in m2 . Waist circumference was measured with a st and ard anthropometric tape . Statistical Analysis We used SAS statistical software for data analyses ( 24 ) . The incidence of impaired fasting glucose was calculated for men with normal fasting glucose at baseline , and the incidence of diabetes was based on data from all 8633 patients . For analyses with impaired fasting glucose as the outcome , we excluded 1122 men who had impaired fasting glucose at baseline and an additional 69 men who had normal fasting plasma glucose at baseline but developed diabetes during follow-up . Rates of impaired fasting glucose or diabetes were calculated by dividing the number of incident cases during the study period by the number of person-years over the same period . We defined the study period as the interval between the baseline examination and the last follow-up visit . We used logistic regression to estimate the association between dependent variables and independent variables after adjustment for possible confounding factors . We used general linear models to study the cross-sectional association of fitness level and parental history of diabetes ( 24 , 25 ) . To account for the possible cohort effect of baseline year , we examined the relation between incident cases and baseline year and found no association . We used tests for ordinal linear trend to evaluate the possible relation of higher treadmill time with risk for impaired fasting glucose or diabetes after dividing the sample into the three fitness groups . All P values are two-sided , and those less than 0.05 were considered statistically significant . Role of the Funding Source The funding agencies did not participate in the collection , analysis , or interpretation of data presented in this report or in the decision to su bmi t the manuscript for publication . Results During an average follow-up of 6.1 4.8 years ( range , 1 to 24.8 years ) that included 52 588 person-years , 593 men developed impaired fasting glucose and 149 developed diabetes . Of the men with incident diabetes , 139 ( 93 % ) were not aware of", "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" ]

[ "OBJECTIVE The authors examined the efficacy of intramuscular flunitrazepam compared with intramuscular haloperidol for the immediate control of agitated or aggressive behavior in acutely psychotic patients . METHOD Twenty-eight actively psychotic in patients , aged 20 - 60 years , who were under treatment with neuroleptic agents were selected for the study . Each was r and omly assigned on a double-blind basis to receive either 5 mg i.m . of haloperidol ( N=13 ) or 1 mg i.m . of flunitrazepam ( N=15 ) during an aggressive event . Verbal and physical aggression was measured over time with the Overt Aggression Scale . Patients were also rated with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale . RESULTS Both flunitrazepam and haloperidol exhibited acute antiaggressive activity . This beneficial effect , as assessed by the Overt Aggression Scale , was obtained within 30 minutes . CONCLUSIONS Intramuscular flunitrazepam may serve as a convenient , rapid , safe , and effective adjunct to neuroleptics in reducing aggressive behavior in emergency psychiatric setting", "Although paramedics and emergency department ( ED ) personnel are routinely required to assess the mental states of patients they are attempting to treat , no structured and easily administered tool has been vali date d for their use . The objective of this study was to determine whether a quantitative Brief Mental Status Examination ( BMSE ) can serve as such a tool . The six-item BMSE was administered to 100 ED patients for whom an assessment of mental status was warranted . The st and ard assessment of mental status ( normal , mildly impaired , or severely impaired ) and competence to refuse emergency care were provided by the attending physician . The usefulness and ease of administration of the BMSE were rated by the physicians and nurses administering it . We found that BMSE scores correlated significantly with physicians ' assessment s of patients ' mental status and competence to refuse care . Using physician assessment as a st and ard , the BMSE had a sensitivity of 72 % and a specificity of 95 % in identifying severely impaired individuals . Examiners ' ratings of ease of administration were closely related to the degree of impairment found . Finally , examiners rated the BMSE as useful in 98 % of cases . We conclude from these preliminary results that the BMSE , upon further testing , may prove to be a valid and useful tool for assessing the mental states of emergency patients in both prehospital and ED setting ", "Abstract Background Kraepelin ’s partial interpretation of agitated depression as a mixed state of “ manic-depressive insanity ” ( including the current concept of bipolar disorder ) has recently been the focus of much research . This paper tested whether , how , and to what extent both psychomotor symptoms , agitation and retardation in depression are related to bipolarity and anxiety . Method The prospect i ve Zurich Study assessed psychiatric and somatic syndromes in a community sample of young adults ( N = 591 ) ( aged 20 at first interview ) by six interviews over 20 years ( 1979–1999 ) . Psychomotor symptoms of agitation and retardation were assessed by professional interviewers from age 22 to 40 ( five interviews ) on the basis of the observed and reported behaviour within the interview section on depression . Psychiatric diagnoses were strictly operationalised and , in the case of bipolar-II disorder , were broader than proposed by DSM-IV-TR and ICD-10 . As indicators of bipolarity , the association with bipolar disorder , a family history of mania/hypomania/cyclothymia , together with hypomanic and cyclothymic temperament as assessed by the general behavior inventory ( GBI ) [ 15 ] , and mood lability ( an element of cyclothymic temperament ) were used . Results Agitated and retarded depressive states were equally associated with the indicators of bipolarity and with anxiety . Longitudinally , agitation and retardation were significantly associated with each other ( OR = 1.8 , 95 % CI = 1.0–3.2 ) , and this combined group of major depressives showed stronger associations with bipolarity , with both hypomanic/cyclothymic and depressive temperamental traits , and with anxiety . Among agitated , non-retarded depressives , unipolar mood disorder was even twice as common as bipolar mood disorder . Conclusion Combined agitated and retarded major depressive states are more often bipolar than unipolar , but , in general , agitated depression ( with or without retardation ) is not more frequently bipolar than retarded depression ( with or without agitation ) , and pure agitated depression is even much less frequently bipolar than unipolar . The findings do not support the hypothesis that agitated depressive syndromes are mixed states . Limitations The results are limited to a population up to the age of 40 ; bipolar-I disorders could not be analysed ( small N )", "Objective Published research on agitation is limited by the difficulty in generalizing findings from trials using moderately agitated , carefully selected patients treated with single agents . More specifically , there are few comparative studies examining common intramuscular ( IM ) regimens ( ie , haloperidol with or without benzodiazepines ) with IM atypical antipsychotics . Therefore , we conducted a retrospective chart review to compare IM olanzapine and haloperidol in a “ real-world ” population with agitation . Method We performed a retrospective evaluation of charts from 146 consecutive emergency department patients who received either IM haloperidol or IM olanzapine for agitation . We used a clinical ly oriented proxy marker of efficacy — the necessity for additional medication intervention for agitation (AMI)—as our primary outcome measure . Results Additional medication intervention for agitation was required by 43 % ( 13/30 ) patients when haloperidol was given alone and by 18 % ( 13/72 ) when haloperidol was given with a benzodiazepine . In the case of olanzapine , AMI was required by 29 % ( 6/21 ) of patients receiving olanzapine alone and by 18 % ( 2/11 ) of patients given olanzapine plus a benzodiazepine . A significant percentage of patients had clinical characteristics ( nonpsychiatric triage complaint , drug/alcohol use , severe agitation ) that differ from more selective sample s. Conclusions Overall , these finding suggest that in a naturalistic emergency department setting , haloperidol monotherapy is less effective — at least in requiring AMI — than olanzapine with or without a benzodiazepine or haloperidol plus a benzodiazepine . Moreover , these later 3 regimens seemed comparable . Prospect i ve studies examining the treatment of real-world agitation , including head-to-head comparisons of the haloperidol-benzodiazepine combination with newer IM antipsychotics , are needed", "Abstract : Quetiapine ( QTP ) combined with lithium ( Li ) or divalproex ( DVP ) for the treatment of mania was evaluated in 2 double-blind , placebo-controlled studies . Patients were r and omized to 3 or 6 weeks of treatment with QTP plus Li/DVP or placebo ( PBO ) plus Li/DVP . Quetiapine was dosed up to 800 mg/d ; Li was dosed to achieve serum concentrations of 0.7 - 1.0 mEq/L and DVP to 50 - 100 μg/mL. A total of 402 patients were r and omized : 197 to QTP + Li/DVP and 205 to PBO + Li/DVP . The mean quetiapine dose in responders was 492 ( ±204 ) mg/d . Improvement in the Young Mania Rating Scale ( YMRS ) at day 21 in the QTP + Li/DVP group ( −15.29 ) was statistically superior to the PBO + Li/DVP group ( −12.19 ) ( P achieved a response ( ≥50 % decrease in the YMRS ) at day 21 ( QTP + Li/DVP , 55.7 % ; PBO + Li/DVP , 41.6%;P scores by day 21 were also significantly greater in QTP + Li/DVP-treated patients ( −1.59 ) versus PBO + Li/DVP ( −1.19 ) ( P . Common adverse events ( ≥5 % and twice that in the PBO + Li/DVP group ) in the QTP + Li/DVP group were somnolence , dry mouth , and asthenia . Quetiapine combined with Li/DVP was not associated with extrapyramidal symptoms ( including akathisia ) or emergent depression . More QTP + Li/DVP-treated patients completed the trial , and there was no difference in discontinuation rates due to adverse events between the two groups . Quetiapine , in combination with lithium or divalproex , is well tolerated and has superior efficacy to lithium or divalproex alone in the treatment of bipolar mania", "Background Conventional antipsychotics augmented with benzodiazepines have been the st and ard acute treatment for psychiatric emergencies for more than 50 years . The inability of patients to give informed consent limits r and omised , controlled studies . This observational study on immediate therapy for aggression and impulse control in acutely agitated patients ( IMPULSE ) evaluated the short-term effectiveness and tolerability of atypical and typical antipsychotic medications ( AP ) in a non-interventional setting . Methods This was a comparative , non-r and omised , prospect i ve , open-label , observational study . Treatment over the first 5 days was classified according to whether any olanzapine , risperidone , or haloperidol was included or not . Documentations ( PANSS-excited component , CGI-aggression , CGI-suicidality , tranquilisation score ) were at baseline ( day 1 ) and days 2–6 after start of AP . Results During the short treatment-period , PANSS-EC and CGI-aggression scores improved in all cohorts . 68.7 % of patients treated with olanzapine , 72.2 % of patients treated with risperidone , and 83.3 % of patients treated with haloperidol received concomitant benzodiazepines ( haloperidol vs. non-haloperidol : p olanzapine ( 73.8 % ) were fully alert according to a tranquilisation score and active at day 2 than patients treated with risperidone ( 57.1 % ) or haloperidol ( 58.0 % ) . Conclusion Current medication practice s for immediate aggression control are effective with positive results present within a few days . In this study , concomitant benzodiazepine use was significantly more frequent in patients receiving haloperidol", "OBJECTIVE Aggressive patients are not uncommon in acute inpatient behavioral health units of general hospitals . Prior research identifies various predictors associated with aggressive inpatient behavior . This prospect i ve observational study examines the demographic and clinical characteristics of aggressive in patients and the routine medications these patients were receiving at discharge . METHOD Thirty-six adults diagnosed with a DSM-IV mental disorder who met 2 of 6 established inclusion criteria for high violence risk and a Clinical Global Impressions-Severity of Illness ( CGI-S ) scale score ≥ 4 were observed for a maximum of 28 days on the 23-bed case mix acute behavioral health unit of St Luke 's University Hospital , Bethlehem , Pennsylvania , from January 2012 to May 2013 . Primary outcome measures were the Modified Overt Aggression Scale ( MOAS ) and CGI-S ; secondary measures were symptom outcome measures and demographic and clinical characteristics data . Analysis was conducted using repeated measures methodology . RESULTS Younger males with a history of previous violence , psychiatric admissions , and symptoms of severe agitation were more at risk for aggressive behavior . Positive psychotic symptoms , a diagnosis of bipolar disorder , substance use , and comorbid personality disorders also increased risk . Significant improvements from baseline to last visit were observed for the CGI-S and MOAS ( P the MOAS and CGI-S at last visit ( P symptom of agitation was significantly correlated to MOAS scores at both baseline and last visit ( P both severity of illness and level of aggression ", "This r and omized , parallel-group , open study investigated the efficacy and safety of risperidone oral solution ( RIS-OS ) in combination with clonazepam and intramuscular haloperidol for the treatment of acute agitation in patients with schizophrenia , and the study explored the possibility of decreasing the efficacy of an acute 6-week treatment by switching intramuscular haloperidol injection to RIS-OS . Two hundred and five agitation-exhibiting schizophrenic in patients at six hospitals were originally included in the study . The 47-day trial consisted of 5 days ( session I ) of receiving either oral treatment ( RIS-OS plus clonazepam ) or intramuscular treatment ( intramuscular haloperidol ) and a 42-day ( session II ) period of either withdrawing from clonazepam or shifting from intramuscular haloperidol to a RIS-OS period . The primary efficacy outcome was measured as the change in the Positive and Negative Syndrome Scale-Excited Component ( PANSS-EC ) in session I and the change in the PANSS in session II . Safety was assessed by the frequency of the adverse events . Mean PANSS-EC improvement was significant after 5 days of treatment in both groups ( P>0.05 ) and was similar between the two treatment groups ( P ’ PANSS-EC scores improved or remained stable during the drawback/shift treatment period . Efficacy was not significantly different between the two treatment groups after the 6-week treatment ( P>0.05 ) . However , combination treatment exhibited greater efficacy , and adverse events , especially extrapyramidal symptoms , were lower with the oral treatment than with the intramuscular treatment in session I. These results show that RIS-OS in combination with clonazepam is an effective treatment , comparable with intramuscular haloperidol , and is well-tolerated for acute agitation in patients with schizophrenia", "Background Psychomotor agitation can be associated with a wide range of medical conditions . Although clinical practice advocates the use of several drugs for the management of psychomotor agitation , there are still very few controlled studies comparing the profiles of action and the adverse effects of different drugs that induce tranquilization . Objectives The purpose of this study was to compare the efficacy and safety of 4 low-dose pharmacological interventions used to control psychomotor agitation guided by the clinical response . Methods Using a r and omized , rated-blind design , 100 agitated patients were assigned to receive 1 of 4 treatments : haloperidol ( 2.5 mg ) + promethazine ( 25 mg ) ( HLP + PMZ ) , haloperidol ( 2.5 mg ) + midazolam ( 7.5 mg ) ( HLP + MID ) , ziprasidone ( 10 mg ) ( ZIP ) , or olanzapine ( 10 mg ) ( OLP ) . Patients were evaluated just before the intervention and after 30 , 60 , and 90 minutes , using the Agitation-Calmness Evaluating Scale . Adverse effects were assessed within 24 hours after the intervention , using selected items from the UKU Scale ( Ugvalg Klinisk Undersgelser Side Effect Scale ) . According to the clinical indication , medication could be repeated twice after the first injection . Data were analyzed using general linear model with repeated measures and logistic regression . Results All treatment options promoted a reduction in agitation , without causing excessive sedation , although a lower reduction in agitation was observed with HLP + PMZ and ZIP compared with HLP + MID and OLZ . The need for an additional dose of medication was observed in 22 patients , and only 8 remained agitated during the entire 90-minute period . A higher risk for the development of extrapyramidal symptoms within the following 24 hours was observed with HLP + PMZ . Discussion Low doses of haloperidol combined with midazolam can be as effective as olanzapine in reducing psychomotor agitation without increasing the risk of extrapyramidal effects . Because of the higher risk for the occurrence of extrapyramidal symptoms , the combination of haloperidol with promethazine should be considered a second-line treatment option", "BACKGROUND The relationship between psychomotor agitation in unipolar depression and mood-switching from depression to manic , hypomanic and mixed states has been controversial . We investigated the future risk of initial mood-switching as a function of psychomotor agitation in unipolar depression . METHODS We identified 189 participants diagnosed with major depressive disorder ( MDD ) . We divided all patients with MDD into two categories ( 1 ) agitated patients ( n=74 ) , and ( 2 ) non-agitated patients ( n=115 ) . These groups were prospect ively followed and compared by time to mood-switching . Kaplan-Meier survival curves , log-rank test for trend for survivor functions , and Cox proportional hazard ratio estimates for a multivariate model were conducted to examine the risk of mood-switching by psychomotor agitation . RESULTS During follow-up , mood-switching occurred in 20.3 % of the agitated patients and 7.0 % of the non-agitated patients . In the Kaplan-Meier survival estimates for time to incidence of mood-switching with agitated or non-agitated patients , the cumulative probability of developing mood-switching for agitated patients was higher than those for non-agitated patients ( log-rank test : χ(2)=7.148 , df=1 , p=0.008 ) . Survival analysis was also performed using Cox proportional hazards regression within a multivariate model . The agitation remained significantly associated with incidence of mood-switching ( HR=2.98 , 95 % CI : 1.18 - 7.51 ) . LIMITATIONS We did not make a clear distinction between antidepressant-induced mood-switching and spontaneous switching . CONCLUSIONS The main finding demonstrated that MDD patients with agitation were nearly threefold as likely to experience mood-switching , suggesting that psychomotor agitation in MDD may be related to an indicator of bipolarity", "OBJECTIVE Evaluate the efficacy and tolerability of quetiapine ( QTP ) combined with lithium ( Li ) or divalproex ( DVP ) in the treatment of acute mania . METHODS Patients were r and omized to 21 days of double-blind treatment with QTP plus Li/DVP , or placebo ( PBO ) plus Li/DVP . QTP was rapidly dosed up to a maximum of 800 mg/day ; Li was dosed to 0.7 - 1.0 mEq/L ; or DVP to 50 - 100 microg/mL. RESULTS Fifty-six of 91 ( 61.5 % ) individuals in the QTP + Li/DVP group compared with 49 of 100 ( 49 % ) taking PBO + Li/DVP completed the study . A significantly greater mean reduction in total Young Mania Rating Scale ( YMRS ) score was observed at end-point in patients receiving QTP + Li/DVP compared with those in the PBO + Li/DVP group ( -13.76 versus -9.93 ; p = 0.021 ) . The response rate ( > or = 50 % YMRS improvement ) was significantly higher in the QTP + Li/DVP group than in PBO + Li/DVP-treated patients ( 54.3 % versus 32.6 % ; p = 0.005 ) , as was the proportion of patients achieving clinical remission ( YMRS + Li/DVP also had a significantly greater improvement in Clinical Global Impressions-Bipolar ( CGI-BP ) Severity of Illness scores ( -1.38 versus -0.78 ; p = 0.001 ) . The mean last-week dose of QTP was 584 mg/day in patients meeting response criteria . Common adverse events ( at least 10 % and twice the rate of Li/DVP ) in the QTP + Li/DVP group included somnolence , dry mouth , asthenia , and postural hypotension . CONCLUSIONS Quetiapine combined with either Li or DVP has superior efficacy compared with Li or DVP monotherapy for treating patients with bipolar mania . Combination therapy was well-tolerated and most adverse events were mild , withdrawal because of adverse events being only 5 % compared with 6 % on Li or DVP monotherapy", "OBJECTIVE To evaluate the efficacy and tolerability of quetiapine monotherapy versus placebo for the treatment of mania associated with bipolar disorder . METHOD In an international , multicenter , double-blind , parallel-group , 12-week study , patients with a DSM-IV diagnosis of bipolar I disorder ( manic episode ) were r and omly assigned to treatment with quetiapine ( flexibly dosed up to 800 mg/day ) , placebo , or lithium . The primary efficacy measure was change from baseline in Young Mania Rating Scale ( YMRS ) score at day 21 . Data were gathered from April 2001 to May 2002 . RESULTS More patients in the quetiapine ( 72/107 ) and lithium ( 67/98 ) groups completed the study compared with the placebo group ( 35/97 ) . Improvement ( reduction ) in YMRS score was significantly greater for quetiapine than placebo at day 7 ( -8.03 vs. -4.89 ; p quetiapine patients compared with placebo patients fulfilled YMRS response criteria at day 21 ( 53.3 % vs. 27.4 % ; p Quetiapine was also superior to placebo in efficacy at day 21 and day 84 by all secondary measures . Lithium-treated patients improved significantly compared with placebo patients and similarly to quetiapine-treated patients on the primary efficacy measure . The most common adverse events for quetiapine were dry mouth , somnolence , and weight gain , while lithium was associated with tremor and insomnia . The quetiapine and placebo groups had similar , low levels of extrapyramidal symptom-related adverse events . CONCLUSIONS Quetiapine demonstrated superior efficacy to placebo in patients with bipolar mania and was well tolerated", "STUDY OBJECTIVE We determine whether droperidol , midazolam , or the combination is more effective for intramuscular sedation in violent and acute behavioral disturbance in the emergency department ( ED ) . METHODS We conducted a blinded r and omized controlled trial of intramuscular sedation for violent and acute behavioral disturbance , comparing droperidol ( 10 mg ) , midazolam ( 10 mg ) , and droperidol ( 5 mg)/midazolam ( 5 mg ) . Inclusion criteria were patients requiring physical restraint and parenteral sedation . The primary outcome was the duration of the violent and acute behavioral disturbance , defined as the time security staff were required . Secondary outcomes included time until additional sedation was administered , staff and patient injuries , further episodes of violent and acute behavioral disturbance , and drug-related adverse effects . RESULTS From 223 ED patients with violent and acute behavioral disturbance , 91 patients were included ; 33 received droperidol , 29 received midazolam , and 29 received the combination . There was no difference in the median duration of the violent and acute behavioral disturbance : 20 minutes ( interquartile range [ IQR ] 11 to 37 min ) for droperidol , 24 minutes ( IQR 13 to 35 minutes ) for midazolam , and 25 minutes ( IQR 15 to 38 minutes ) for the combination . Additional sedation was required in 11 ( 33 % ; 95 % confidence interval [ CI ] 19 % to 52 % ) droperidol patients , 18 ( 62 % ; 95 % CI 42 % to 79 % ) midazolam patients , and 12 ( 41 % ; 95 % CI 24 % to 61 % ) in the combination group . The hazard ratio for additional sedation in the midazolam versus droperidol group was 2.31 ( 95 % credible interval 1.01 to 4.71 ) ; for the combination versus droperidol , 1.18 ( 95 % credible interval 0.46 to 2.50 ) . Patient and staff injuries and number of further episodes of violent and acute behavioral disturbance did not differ between groups . There were two adverse effects for droperidol ( 6 % ; 95 % CI 1 % to 22 % ) , 8 for midazolam ( 28 % ; 95 % CI 13 % to 47 % ) , and 2 for the combination ( 7 % ; 95 % CI 1 % to 24 % ) . An abnormal QT occurred in 2 of 31 ( 6 % ; 95 % CI 1 % to 23 % ) droperidol patients , which was not different from the other groups . CONCLUSION Intramuscular droperidol and midazolam result ed in a similar duration of violent and acute behavioral disturbance , but more additional sedation was required with midazolam . Midazolam caused more adverse effects because of oversedation , and there was no evidence of QT prolongation associated with droperidol compared with midazolam", "Objectives : Psychotic agitation of psychiatric patients is a common manifestation that needs emergent management . Traditionally , parenteral or intramuscular injection of antipsychotics was conducted for treatment of psychotic agitation . Considering that the rapidly absorbed form of risperidone ( risperidone orodispersible tablet ) could be used for the agitated patient , comparison of oral risperidone and intramuscular haloperidol was performed in emergency treatment of psychotic agitation in this study . Methods : 124 patients with psychotic agitation were recruited at the emergency room or inpatient ward . They were r and omly assigned to either the group of oral risperidone or intramuscular haloperidol . Efficacy of both treatments was measured and compared using the 5-item acute agitation cluster from the Positive and Negative Syndrome Scale-Excited Component ( PANSS-EC ) and the Clinical Global Impression-Severity of Illness Scale ( CGI-S ) . Tolerability and safety were also compared between the two groups . Results : The PANSS-EC and CGI-S scores were significantly decreased over time in both treatment groups without any significant group difference and time by group interaction effect ( F = 459.7 , p no serious adverse events in both groups . Conclusion : For the emergency treatment of psychotic agitation , risperidone orodispersible tablet was as effective and tolerable as intramuscular administration of haloperidol . Therefore , we might choose oral medication instead of intramuscular injection for treatment of patients with acute psychotic agitation", "OBJECTIVE While the efficacy of antipsychotic medications for the treatment of psychosis is generally established , the speed of onset of antipsychotic action remains controversial . The objective of this study was to evaluate the early response ( within the first 24 h ) in psychosis with ziprasidone IM treatment , and to determine whether this early effect is distinct from a reduction in agitation symptoms . METHODS In a 24-h , double-blind study , hospitalized patients with psychotic disorder and acute agitation were r and omized to treatment with fixed doses of IM ziprasidone : 2 mg ( N=38 ) or 20 mg ( N=41 ) . Efficacy assessment s were based on the PANSS positive subscale and PANSS early psychosis factor score ( conceptual disorganization , hallucinatory behavior , and unusual thought content ) at 4 and 24 h. RESULTS Ziprasidone IM demonstrated a significant dose-related effect ( 20 mg vs. 2 mg ) on both the PANSS early psychosis factor score and the PANSS positive subscale at the first post-baseline time point ( 4 h ) , and at 24 h ( all p ziprasidone IM on early psychosis at 24 h ( p agitation symptoms . CONCLUSIONS These findings suggest , in addition to an early reduction in acute agitation , ziprasidone IM may be associated with a more rapid improvement in psychotic symptoms than previously reported , thus lending further support to the emergent hypothesis of early psychosis improvement in antipsychotic treatment", "Background Olanzapine rapid-acting intramuscular ( IM ) injection is an atypical antipsychotic drug already used overseas and recently approved in Japan . The objective of this study was to confirm the efficacy of rapid-acting IM olanzapine 10 mg was greater than IM placebo in patients with exacerbation of schizophrenia with acute psychotic agitation by comparing changes from baseline to 2 hours after the first IM injection , as measured by the Positive and Negative Syndrome Scale-Excited Component ( PANSS-EC ) total score . Methods We conducted a placebo-controlled , r and omized , double-blind , parallel-group study in Japanese patients diagnosed with schizophrenia according to the diagnostic criteria specified in the DSM-IV-TR . Patients were r and omized to 2 treatment groups : IM olanzapine ( 10 mg ) or IM placebo . The primary efficacy outcome was the change in PANSS-EC from baseline to 2 hours after the first IM injection . Treatment groups were compared with an analysis of variance model which included treatment and site as factors . During the 24-hour treatment period , safety was assessed by clinical examination and laboratory investigations , electrocardiograms , extrapyramidal symptoms scales , and recording spontaneously reported adverse events . Results Of the 91 r and omized patients , 90 patients ( 45 IM olanzapine-group ; 45 IM placebo-group ) were in the full analysis set . The mean change of PANSS-EC total score from baseline to 2 hours after the first IM injection ( mean±st and ard deviation ) was −9.2±4.5 for the IM olanzapine group and −2.8±5.6 for the IM placebo group . The difference between treatment groups was statistically significant ( p no deaths , serious adverse events , treatment-emergent adverse events ( TEAEs ) leading to discontinuation , severe TEAEs , or instances of oversedation in this study . There were no statistically significant differences between treatment groups in the proportion of patients with potentially clinical ly significant changes in laboratory tests , vital signs ( blood pressure and pulse rate ) , electrocardiograms , and treatment-emergent extrapyramidal symptoms . Conclusion The efficacy of IM olanzapine 10 mg in patients with exacerbation of schizophrenia with acute psychotic agitation was greater than IM placebo in the primary efficacy measure , PANSS-EC . Intramuscular olanzapine 10 mg was shown to be generally safe and tolerable , and could be a new option for treatment of schizophrenia in Japan . Trial Registration", "BACKGROUND There is a need for a rapid-acting , non-injection , acute treatment for agitation . AIMS To evaluate inhaled loxapine for acute treatment of agitation in schizophrenia . METHOD This phase III , r and omised , double-blind , placebo-controlled , parallel-group study ( Clinical Trials.gov number NCT00628589 ) enrolled 344 individuals who received one , two or three doses of inhaled loxapine ( 5 or 10 mg ) or a placebo . Lorazepam rescue was permitted after dose two . The primary efficacy end-point was change from baseline in Positive and Negative Syndrome Scale-Excited Component ( PANSS-EC ) 2 h after dose one . The key secondary end-point was Clinical Global Impression-Improvement scale ( CGI-I ) score 2 h after dose one . RESULTS Inhaled loxapine ( 5 and 10 mg ) significantly reduced agitation compared with placebo as assessed by primary and key secondary end-points . Reduced PANSS-EC score was evident 10 min after dose one with both 5 and 10 mg doses . Inhaled loxapine was well tolerated , and the most common adverse events were known effects of loxapine or minor oral effects common with inhaled medications . CONCLUSIONS Inhaled loxapine provided a rapid , well-tolerated acute treatment for agitation in people with schizophrenia", "Background Agitated or violent patients constitute 10 % of all emergency psychiatric treatment . Management guidelines , the preferred treatment of clinicians and clinical practice all differ . Systematic review s show that all relevant studies are small and none are likely to have adequate power to show true differences between treatments . Worldwide , current treatment is not based on evidence from r and omised trials . In Brazil , the combination haloperidol-promethazine is frequently used , but no studies involving this mix exist . Methods TREC-Rio ( Tranquilização Rápida-Ensaio Clínico [ Translation : Rapid Tranquillisation- Clinical Trial ] ) will compare midazolam with haloperidol-promethazine mix for treatment of agitated patients in emergency psychiatric rooms of Rio de Janeiro , Brazil . TREC-Rio is a r and omised , controlled , pragmatic and open study . Primary measure of outcome is tranquillisation at 20 minutes but effects on other measures of morbidity will also be assessed . TREC-Rio will involve the collaboration of as many health care professionals based in four psychiatric emergency rooms of Rio as possible . Because the design of this trial does not substantially complicate clinical management , and in several aspects simplifies it , the study can be large , and treatments used in everyday practice can be evaluated", "OBJECTIVE This r and omized controlled trial studied whether seclusion and restraint could be prevented in the psychiatric care of persons with schizophrenia without an increase of violence . METHODS Over the course of a year , 13 wards of a secured national psychiatric hospital in Finl and received information about seclusion and restraint prevention . Four high-security wards ( N=88 beds ) for men with psychotic illness were then stratified by coercion rates and r and omly assigned to two equal groups . In the intervention wards , staff , patients , and doctors were trained for six months in applying six core strategies to prevent seclusion-restraint ; six months of supervised intervention followed . Poisson 's regression analyses compared monthly incidence rate ratios ( IRRs ) of coercion and violence ( per 100 patient-days ) . RESULTS The proportion of patient-days with seclusion , restraint , or room observation declined from 30 % to 15 % for intervention wards ( IRR=.88 , 95 % confidence interval [CI]=.86-.90 , p Seclusion-restraint time decreased from 110 to 56 hours per 100 patient-days for intervention wards ( IRR=.85 , CI=.78-.92 , p Incidence of violence decreased from 1.1 % to .4 % for the intervention wards and from .1 % to .0 % for control wards . Between-groups differences were significant for seclusion-restraint-observation days ( p=.001 ) and seclusion-restraint time ( p=.001 ) but not for violence ( p=.91 ) . CONCLUSIONS Seclusion and restraint were prevented without an increase of violence in wards for men with schizophrenia and violent behavior . A similar reduction may also be feasible under less extreme circumstances", "Rapid tranquilization is a routinely practice d method of calming agitated psychotic patients by use of neuroleptics , benzodiazepines , or both in combination . Although several studies have examined the efficacy of the three approaches , none have compared these treatments in a prospect i ve , r and omized , double-blind , multicenter trial . Ninety-eight psychotic , agitated , and aggressive patients ( 73 men and 25 women ) were prospect ively enrolled during an 18-month period in emergency departments in five university or general hospitals . Patients were r and omly assigned to receive intramuscular injections of lorazepam ( 2 mg ) , haloperidol ( 5 mg ) , or both in combination . Patients in each treatment group received 1 to 6 injections of the same study drug within 12 hours , based on clinical need . They were evaluated hourly after the first injection until at least 12 hours after the last . Efficacy was assessed on the Agitated Behavior Scale ( ABS ) , a modified Brief Psychiatric Rating Scale ( MBPRS ) , Clinical Global impressions ( CGI ) scale , and an Alertness Scale . Effective symptom reduction was achieved in each treatment group with significant ( P ABS ( hour 1 ) and MBPRS ( hours 2 and 3 ) suggest that tranquilization was most rapid in patients receiving the combination treatment . Study event incidence ( side effects ) did not differ significantly between treatment groups , although patients receiving haloperidol alone tended to have more extrapyramidal system symptoms . The superior results produced by the combination treatment support the use of lorazepam plus haloperidol as the treatment of choice for acute psychotic agitation", "BACKGROUND Few double-blind trials have examined the efficacy of a combination of a mood stabiliser and an atypical antipsychotic in acute mania . AIMS To determine the efficacy of risperidone in combination with a mood stabiliser in acute mania . METHOD Patients taking a mood stabiliser were r and omised to 3 weeks ' treatment with risperidone ( n=75 ) or placebo ( n=76 ) . RESULTS Young Mania Rating Scale ( YMRS ) scores improved rapidly with significantly greater reductions at week 1 in the risperidone group compared with the placebo group . At end-point YMRS scores decreased by 14.5 and 10.3 points in the risperidone and placebo groups , respectively . Significant improvements v. placebo ( P YMRS scores in the risperidone group than in the placebo group . Incidence of adverse events was similar in both groups . CONCLUSIONS Risperidone is superior to placebo when used in combination with lithium or divalproex in acute mania", "AIMS The aim of this study was to identify predictors of completed suicide in a wide sample of psychiatric in patients receiving retrospective and prospect i ve DSM-IV diagnoses . METHODS We followed up 4441 severe psychiatric patients who were hospitalized for some time during a 35-year period in a private hospital setting . We collected sociodemographic , clinical and temperamental data . RESULTS Ninety-six patients from the sample committed suicide . There were no sex differences in suicide completion and no differences between major psychiatric disorders , but people who had been hospitalized for anxiety disorders did not commit suicide and people with bipolar disorders were more likely to commit suicide than people with unipolar major depression . Shorter-term treatment with lithium and anticonvulsants , longer-term treatment with antidepressants , history of suicide attempts , suicidal thinking , and single status positively predicted completed suicide . Suicide tended to occur after a mean period of about 14 years of duration of disease . Patients ' symptoms during the period preceding suicide were assessed through interviewing patients ' physicians or family members . Symptoms occurring in > 10 % of cases were , in decreasing order , inner tension , racing/crowded thoughts , aggressive behavior , guilt , psychomotor agitation , persecutory ideation , anxiety , and hallucinations . Surprisingly , cyclothymic temperament was less associated with completed suicide as compared to other temperaments . CONCLUSIONS Suicide is likely to occur in a milieu of agitation , mixed anxiety and depression , and psychosis . Longer-term mood stabilizer treatment may reduce the rate of completed suicide", "Patients presenting to the emergency department with acute agitation frequently require physical and chemical restraint . To determine the efficacy of lorazepam vs. droperidol , we conducted a prospect i ve , r and omized study of violently agitated patients requiring chemical restraint . Patients were r and omized to receive either lorazepam or droperidol i.v . A six-point sedation scale was used . Sedation scores were recorded at time 0 , 5 , 10 , 15 , 30 , and 60 min . Vital signs were compared at time 0 and at 60 min . Repeat dosages of each drug could be given at 30 min . Toxicology screen , ethanol and creatinine phosphokinase levels were obtained . A total of 202 patients were evaluated . One hundred patients received lorazepam and 102 patients received droperidol . Agitation was attributed to methamphetamine toxicity in 146 patients ( 72 % ) , cocaine toxicity in 28 ( 14 % ) , psychiatric illness in 20 ( 10 % ) , and ethanol withdrawal in 8 ( 4 % ) . Ethanol intoxication was present in 98 patients ( 49 % ) . Both drugs had similar sedation profiles at 5 min . Patients receiving droperidol had significantly lower sedation scores at times 10 , 15 , 30 , and 60 than lorazepam . More repeat doses of lorazepam were given ( 40 ) than droperidol ( 8) at 30 min . We conclude that droperidol produces a more rapid and better sedation than lorazepam at the doses used in this study in agitated patients requiring chemical restraint . Lorazepam is more likely to require repeat dosing than droperidol . Methamphetamine toxicity was present in the majority of patients in this study", "Introduction : The purpose of this study was to compare efficacy and safety among intramuscular olanzapine , intramuscular haloperidol , orally disintegrating olanzapine tablets , and oral risperidone solution for agitated patients with psychosis during the first 24 hours of treatment in an acute care psychiatric ward . Methods : Forty-two in patients from an acute care psychiatric ward of a medical center in central Taiwan were enrolled . They were r and omly assigned to 1 of the 4 treatment groups ( 10-mg intramuscular olanzapine , 10-mg olanzapine oral disintegrating tablet , 3-mg oral risperidone solution , or 7.5-mg intramuscular haloperidol ) . Agitation was measured by using the excited component of the Positive and Negative Syndrome Scale ( PANSS-EC ) , the Agitation-Calmness Evaluation Scale , and the Clinical Global Impression-Severity Scale during the first 24 hours . Results : There were significant differences in the PANSS-EC total scores for the 4 intervention groups at 15 , 30 , 45 , 60 , 75 , and 90 minutes after the initiation of treatment . More significant differences were found early in the treatment . In the post hoc analysis , the patients who received intramuscular olanzapine or orally disintegrating olanzapine tablets showed significantly greater improvement in PANSS-EC scores than did patients who received intramuscular haloperidol at points 15 , 30 , 45 , 60 , 75 , and 90 minutes after injection . Conclusions : These findings suggest that intramuscular olanzapine , orally disintegrating olanzapine tablets , and oral risperidone solution are as effective treatments as intramuscular haloperidol for patients with acute agitation . Intramuscular olanzapine and disintegrating olanzapine tablets are more effective than intramuscular haloperidol in the early phase of the intervention . There is no significant difference in effectiveness among intramuscular olanzapine , orally disintegrating olanzapine tablets , and oral risperidone solution", "Abstract Intramuscular ( IM ) antipsychotics are preferred for efficient control of agitation symptoms . Previous studies have demonstrated that IM ziprasidone is efficacious and safe for treatment of agitation in schizophrenia . However , clinicians now recognize that racial differences may contribute to altered therapeutic response and tolerability . This study compared the efficacy and tolerability of IM ziprasidone versus IM haloperidol for the management of agitation in Chinese subjects with schizophrenia . Subjects with acute schizophrenia were r and omized to either ziprasidone ( n = 189 , 10 to 20 mg as required up to a maximum of 40 mg/d ) or haloperidol ( n = 187 , 5 mg every 4 to 8 hours to a maximum of 20 mg/d ) for 3 days . Psychiatric assessment s and adverse events were assessed at baseline , 2 , 4 , 24 , 48 , and 72 hours . In the ziprasidone group , 2.1 % of subjects discontinued versus 3.7 % in the haloperidol group . The least squares mean change ( SE ) from baseline to 72 hours in Brief Psychiatry Rating Scale total score was −17.32 ( 0.7 ) for ziprasidone ( n = 167 ) and −18.44 ( 0.7 ) for haloperidol ( n = 152 ) , with a 95 % confidence interval treatment difference of −0.7 to 2.9 . Fewer subjects experienced adverse events after ziprasidone ( n = 54 , 28.6 % ) than haloperidol ( n = 116 , 62.0 % ) , with a notably higher incidence of extrapyramidal symptoms in the haloperidol group ( n = 69 , 36.9 % ) compared to the ziprasidone group ( n = 4 , 2.1 % ) . For controlling agitation in schizophrenia in this Chinese study , ziprasidone had a favorable tolerability profile and comparable efficacy and safety compared to haloperidol", "BACKGROUND The MacArthur Violence Risk Assessment Study ( MacVRAS ) in the USA provided strong evidence to support an actuarial approach in community violence risk assessment . AIMS To examine the predictive accuracy of the MacVRAS measures , in addition to structured professional judgement , in a UK sample of patients discharged from in-patient care in the north-west of Engl and . METHOD A prospect i ve study of 112 participants assessed pre-discharge and followed up at 24 weeks post-discharge . Pre-discharge measures were compared with prevalence of violent behaviour to determine predictive validity of risk factors . RESULTS Historical measures of risk and measures of psychopathy , impulsiveness and anger were highly predictive of community violence . The more dynamic clinical and risk management factors derived from structured professional judgement ( rated at discharge ) added significant incremental validity to the historical factors in predicting community violence . CONCLUSIONS Although static measures of risk relating to past history and personality make an important contribution to assessment of violence risk , consideration of current dynamic factors relating to illness and risk management significantly improves predictive accuracy", "OBJECTIVES New treatment options for dementia and its behavioral disturbances have become available since publication of The Expert Consensus Guidelines on the Treatment of Agitation in Older Persons with Dementia in 1998 . While only 2 cholinesterase inhibitors , donepezil and tacrine , were available in 1998 , 3 new cognitive-enhancing agents have been introduced since that time as well as several new atypical antipsychotics and antidepressants . However , there are still limited data from controlled studies to guide clinicians in choosing among these agents and sequencing and combining treatments . We therefore conducted a new survey study of expert opinion on the treatment of cognitive impairment and behavioral disturbances associated with dementia . METHODS Based on a literature review , a 61- question survey was developed with 1,225 options . Most options were scored using a modified version of the R AND 9-point scale for rating appropriateness of medical decisions . For other options , the experts were asked to write in answers . The survey was sent to 50 North American experts on dementia , 100 % of whom completed it . In analyzing responses to items rated on the 9-point scale , consensus was defined as a nonr and om distribution of scores by chi-square \" goodness-of-fit \" test . Based on the 95 % confidence interval around the mean , we assigned a categorical rank ( first line/preferred , second line/alternate , third line/usually inappropriate ) to each option . Guidelines indicating preferred treatment strategies were then developed for selected clinical situations . RESULTS For patients at risk for dementia , the experts recommended control of hypertension and diabetes . They also recommended aspirin and would consider a lipid-lowering agent in patients at risk for vascular dementia . Cholinesterase inhibitors were an option for patients with mild cognitive impairment ( i.e. , at risk for Alzheimer 's dementia [ AD ] ) . To slow cognitive impairment in mild/moderate AD , the experts recommended a cholinesterase inhibitor alone or combined with vitamin E. Donepezil and galantamine were the preferred cholinesterase inhibitors . The experts recommended combining a cholinesterase inhibitor with a N-methyl-D-aspartate ( NMDA ) antagonist ( e.g. , memantine ) if a patient with mild/moderate dementia has an inadequate response to monotherapy . Control of hypertension and diabetes was the treatment of choice , in patients with mild/moderate vascular or mixed AD/vascular dementia , with aspirin another first-line option . Cholinesterase inhibitors were also a first-line option for mild/moderate mixed AD/vascular dementia . Among nonpharmacological interventions for mild/moderate dementia , the experts recommended caregiver education , supportive therapy for caregivers , referral to day treatment , exercise programs , and respite care . For moderate/severe AD or mixed AD/vascular dementia , the experts recommended combining an NMDA antagonist with a cholinesterase inhibitor . For moderate/severe vascular or mixed AD/vascular dementia , they recommended control of hypertension and diabetes . The experts ' ratings underscore the importance of nonpharmacological strategies aim ed at reducing caregiver burden in more severe dementia . Management of agitation and other behavioral disturbances was another focus of this study . The experts recommended using an atypical antipsychotic for agitation associated with delirium , psychosis , aggression , or anger . They would also consider divalproex to manage anger with a risk of physical aggression . Selective serotonin reuptake inhibitors were recommended for the treatment of depression or anxiety in patients with dementia . Benzodiazepines or atypical antipsychotics were viewed as short-term options for acute anxiety . Trazodone was recommended for insomnia . The experts also gave recommendations concerning dosage levels , duration of treatment , and choice of medications for patients with different complicating conditions . CONCLUSIONS The experts reached high levels of consensus on key steps in treating dementia and associated behavioral disturbances . Within the limits of expert opinion and with the expectation that new research data will take precedence , these guidelines may provide direction for clinicians offering care to patients with dementia", "Introduction This double-blind , placebo-controlled study investigated the efficacy and safety of intramuscular ( IM ) aripiprazole and IM haloperidol for the treatment of acute agitation in patients with schizophrenia or schizoaffective disorder . Material s and methods Four-hundred and forty-eight patients were r and omized ( 2:2:1 ratio ) to IM aripiprazole 9.75 mg , IM haloperidol 6.5 mg , or IM placebo . Patients could receive up to three injections over the first 24 h , with second and third injections administered ≥2 and ≥4 h , respectively , after the first if deemed clinical ly necessary . Primary efficacy measure was mean change in Positive and Negative Syndrome Scale Excited Component ( PEC ) score from baseline to 2 h. Results Mean improvement in PEC at 2 h was significantly greater for IM aripiprazole ( −7.27 ) vs placebo ( −4.78 ; p All secondary efficacy measures showed significantly greater improvements at 2 h for IM aripiprazole and IM haloperidol over placebo . Mean number of injections/patient and percentage of patients requiring benzodiazepines were significantly lower for IM aripiprazole vs placebo ( p tolerated . Extrapyramidal symptom-related adverse events were similar for aripiprazole ( 1.7 % ) and placebo ( 2.3 % ) and lower than with haloperidol ( 12.6 % ) . Conclusion These results show that IM aripiprazole is an effective treatment , comparable to IM haloperidol , and well-tolerated for acute agitation in patients with schizophrenia", "In a controlled study , inpatient violence was measured during placebo , high-potency ( haloperidol ) and low-potency ( chlorpromazine or clozapine ) neuroleptics . Some patients had a marked increase in violent behavior with the moderately high-dose haloperidol , but not with low-potency neuroleptics . The authors discuss reasons for the increased violence with haloperidol , including akathisia and drug-induced behavioral toxicity", "OBJECTIVE To compare the effectiveness of intramuscular olanzapine , ziprasidone , haloperidol plus promethazine , haloperidol plus midazolam and haloperidol alone as the first medication(s ) used to treat patients with agitation and aggressive behavior . METHOD One hundred fifty patients with agitation caused by psychotic or bipolar disorder were r and omly assigned under double-blind conditions to receive olanzapine , ziprasidone , haloperidol plus midazolam , haloperidol plus promethazine or haloperidol alone . The Overt Agitation Severity Scale , Overt Aggression Scale and Ramsay Sedation Scale were applied within 12 hours after the first dosage . RESULTS All medications produced a calming effect within one hour of administration , but only olanzapine and haloperidol reduced agitation by less than 10 points , and only olanzapine reduced aggression by less than four points in the first hour . After twelve hours , only patients treated with haloperidol plus midazolam had high levels of agitation and aggression and also more side effects . Ziprasidone , olanzapine and haloperidol alone had more stable results for agitation control , while ziprasidone , haloperidol plus promethazine and olanzapine had stable results for aggression control . CONCLUSION Olanzapine , ziprasidone , haloperidol plus promethazine , haloperidol plus midazolam and haloperidol were effective in controlling agitation and aggression caused by mental illness over 12 hours . Although all the drugs had advantages and disadvantages , haloperidol plus midazolam was associated with the worst results in all the observed parameters", "OBJECTIVES To compare the efficacy of sedation , need for rescue sedation , rates of respiratory depression , and complications of droperidol , ziprasidone , and midazolam when used for the treatment of emergency department ( ED ) patients requiring sedation for acute undifferentiated agitation . METHODS A prospect i ve , r and omized , double-blind trial of agitated ED patients requiring emergent sedation was performed . Patients were r and omized to receive droperidol 5 mg , ziprasidone 20 mg , or midazolam 5 mg intramuscularly . Interval measurements were made at 0 , 15 , 30 , 45 , 60 , and 120 minutes and included Altered Mental Status Scale ( AMS ) scores , oxygen saturations , and end-tidal carbon dioxide levels . RESULTS A total of 144 patients were enrolled ; 50 patients received droperidol , 46 received ziprasidone , and 48 received midazolam . Adequate sedation ( mean AMS score midazolam ( mean AMS score , -0.81 ) and 30 minutes for patients receiving droperidol ( mean AMS score , -1.3 ) and ziprasidone ( mean AMS score , -0.74 ) . Rescue medication for sedation was necessary in 38 of 144 patients ( droperidol , 5 of 50 ; ziprasidone , 9 of 46 ; midazolam , 24 of 48 ; p cardiac dysrhythmias were identified in any treatment group . Respiratory depression that clinical ly required treatment with supplemental oxygen occurred in 21 of 144 patients ( droperidol , 4 of 50 ; ziprasidone , 7 of 46 ; midazolam , 10 of 48 ; p = 0.20 ) . No patients required endotracheal intubation . CONCLUSIONS Acutely agitated ED patients se date d with droperidol or ziprasidone required rescue medications to achieve adequate sedation less frequently than those se date d with midazolam . The onset of adequate sedation is delayed with ziprasidone , relative to the other agents", "OBJECTIVE This multicenter , r and omized , double-blind , placebo-controlled study evaluated the efficacy and safety of intramuscular ( IM ) aripiprazole in patients with acute agitation with a DSM-IV diagnosis of schizophrenia , schizoaffective disorder , or schizo-phreniform disorder . METHOD Patients were r and omly assigned to IM aripiprazole 1 mg , 5.25 mg , 9.75 mg , or 15 mg ; IM haloperidol 7.5 mg ; or placebo and observed for 24 hours . The primary efficacy measure was mean change in the Positive and Negative Syndrome Scale-Excited Component ( PEC ) score from baseline to 2 hours after initial dosing . Secondary measures included the Agitation-Calmness Evaluation Scale ( ACES ) score . The study was carried out at 50 centers worldwide between April 2002 and January 2003 . RESULTS A total of 357 patients were r and omly assigned to treatment . Intramuscular aripiprazole 5.25 mg , 9.75 mg , and 15 mg and IM haloperidol 7.5 mg demonstrated significantly greater reduction in the primary efficacy measure versus placebo . These changes were statistically significant as early as 45 minutes for the IM aripiprazole 9.75-mg group , with a trend toward significance ( p = .051 ) at 30 minutes . Intramuscular haloperidol 7.5 mg first showed a significant reduction in PEC score versus placebo at 105 minutes . At 30 minutes , significantly more patients responded ( defined as a greater than or equal to 40 % reduction in PEC score ) to IM aripiprazole 9.75 mg versus placebo ( 27 % vs. 13 % , p = .05 ) . Intramuscular aripiprazole 9.75 mg significantly improved agitation , without oversedation , as measured by change in ACES score from baseline to 2 hours versus placebo ( p = .003 ) . No patient discontinued the study because of treatment-emergent adverse events . Extrapyramidal symptoms occurred most frequently in the IM haloperidol group . The most common adverse event in IM aripiprazole recipients was headache . CONCLUSION Intramuscular aripiprazole 9.75 mg is a rapidly effective and well-tolerated alternative to IM haloperidol for the control of agitation , without oversedation , in patients with schizophrenia , schizo-affective disorder , or schizophreniform disorder . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00036127", "This double-blind , multicenter study aim ed to investigate the efficacy and safety of aripiprazole 10 , 15 or 20 mg/day versus placebo . Patients requiring inpatient hospitalization for acute exacerbation of schizophrenia were r and omized to once-daily aripiprazole 10 , 15 or 20 mg/day or placebo for 6 weeks . The primary efficacy outcome was the mean change from baseline to Week 6 in the Positive and Negative Syndrome Scale ( PANSS ) Total score ( last observation carried forward ) . Patients with no improvement by Week 3 ( Clinical Global Impression-Global Improvement score > or = 4 ) could transfer to open-label aripiprazole 20mg/day . In total , 420 patients were r and omized to placebo ( n = 108 ) ; aripiprazole 10 mg/day ( n = 106 ) ; 15 mg/day ( n = 106 ) ; or 20 mg/day ( n = 100 ) . Of these , 142 patients ( 34 % ) completed 6 weeks of treatment , 131 ( 31 % ) discontinued to receive open-label aripiprazole , and 147 ( 35 % ) for other reasons . Aripiprazole 10 , 15 and 20 mg/day each showed significantly greater improvements from baseline than placebo for all efficacy measures , including PANSS Total , Positive and Negative scores , and the CGI-Severity of Illness score . Significantly greater improvements in PANSS Total score versus placebo were achieved by Week 1 with 10 or 20 mg/day and Week 3 with 15 mg/day . All three doses were well tolerated . Overall , aripiprazole was not associated with clinical ly meaningful differences in extrapyramidal symptoms , prolactin or weight changes versus placebo . Aripiprazole 10 mg/day is effective and well tolerated for patients experiencing an acute exacerbation of schizophrenia", "BACKGROUND An intramuscular ( IM ) formulation of olanzapine has been developed because there are no rapid-acting IM atypical antipsychotic drugs currently available in the United States for treating acute agitation in patients with schizophrenia . METHODS Recently hospitalized acutely agitated patients with schizophrenia ( N = 270 ) were r and omized to receive 1 to 3 IM injections of olanzapine ( 2.5 , 5.0 , 7.5 , or 10.0 mg ) , haloperidol ( 7.5 mg ) , or placebo within 24 hours . A dose-response relationship for IM olanzapine in the reduction of agitation was assessed by measuring the reduction in Positive and Negative Syndrome Scale Excited Component ( PANSS-EC ) scores 2 hours after the first injection . Safety was assessed by recording adverse events and with extrapyramidal symptom scales and electrocardiograms at 24 hours after the first injection . RESULTS Olanzapine exhibited a dose-response relationship for reduction in agitation ( F(1,179)= 14.4 ; P Mean PANSS-EC reductions 2 hours after the first injection of olanzapine ( 2.5 mg = -5.5 ; 5.0 mg = -8.1 ; 7.5 mg = -8.7 ; 10.0 mg = -9.4 ) were superior to those with placebo ( -2.9 ; P = .01 vs olanzapine at 2.5 mg ; P haloperidol ( -7.5 ) . A dose of 5.0 , 7.5 , or 10.0 mg of olanzapine caused a greater reduction in agitation than placebo 30 minutes after the first injection . There were no differences between treatment groups for hypotension , the most frequently reported adverse event , or for clinical ly relevant changes in the QTc interval . There was a greater incidence of treatment-emergent parkinsonism during treatment with IM haloperidol ( 16.7 % ) than with 2.5 ( P = .03 ) , 5.0 ( P = .03 ) , or 7.5 mg ( P = .01 ) of IM olanzapine ( 0 % ) or with placebo ( 0 % ) ( P = .01 ) . CONCLUSIONS Intramuscular olanzapine at a dose of 2.5 to 10.0 mg per injection exhibits a dose-response relationship in the rapid treatment of acute agitation in patients with schizophrenia and demonstrates a favorable safety profile", "OBJECTIVES To study the effectiveness , frequency of administration and side effects of zuclopenthixol acetate ( ZPTA ) and haloperidol ( HAL ) in the treatment of acute psychotic disturbance with aggression . METHOD Purposive sampling method was employed in a group of psychotic patients with aggression admitted to Songkla Neuropsychiatric Hospital , they were r and omly divided into 2 groups : ZPTA group and HAL group . All of the patients were evaluated daily for 7 consecutive days using the Brief Psychiatric Rating Scale ( BPRS ) and the Clinical Global Impression Scale ( CGI ) . Statistical analysis was performed by using the Student t-test and Linear regression . RESULTS There were 70 patients with diagnosis of schizophrenia , mania and acute psychosis . Thirty-eight patients were r and omly assigned to the ZPTA group and were given 50 - 100 mg of the drug , while 32 patients received HAL 5 - 10 mg . The result showed a significant reduction in BPRS or CGI scores in both groups . Patients treated with ZPTA required less frequent administration than did those on HAL ( p in scores between the two groups . Nor was there a statistical difference in reduction of aggression based on BPRS rating . Each group of patients showed a few side effects of mild degree . CONCLUSION Both ZPTA and HAL were effective in the treatment of acute psychosis with aggression , but frequency of administration was lower in the ZPTA ", "Behavior and symptoms seen in 48 24‐h periods preceding violent episodes and 93 control observations were studied . Six behaviors were more common before violence : confusion , irritability , boisterousness , physical threats , verbal threats and attacks on objects . A logistic regression equation based on these behaviors in a r and omized half of the observations predicted the occurrence of subsequent violence in 92.1 % of the other half of the sample without any false positives , giving a sensitivity of 81.3 % and a specificity of 100 % . It is concluded that mentally ill people display the same behaviour before violent acts as we would expect in people without such disorder . The potential for short‐term prediction of violence seems good", "Abstract Rationale : Intramuscular ( IM ) conventional antipsychotics and /or benzodiazepines are effective in the short-term treatment of acutely agitated psychotic patients but may be associated with adverse effects . A short-acting IM formulation of the novel antipsychotic , ziprasidone , which may offer advantages over conventional agents , has been developed . Objective : To compare ziprasidone IM 2 mg ( n=38 ) and 20 mg ( n=41 ) in the acute control and short-term management of agitated psychotic patients . Methods : A prospect i ve , r and omized , double-blind , 24-h study assessed efficacy using the Behavioral Activity Rating Scale ( BARS ) and the PANSS . The BARS is a vali date d rating scale for the assessment of treatment response in acute agitation associated with psychosis . Following the initial dose , three more doses could be given 4 h apart if needed during the 24-h period . Results : The mean BARS score had decreased 15 min after the first 20 mg IM dose and was statistically significantly lower than the 2 mg group at 30 min post-dose . The improvement with the 20 mg dose increased until 2 h , and was maintained until at least 4 h post-dose ( P ziprasidone 20 mg were BARS responders compared with just one-third of those receiving 2 mg ziprasidone ( P PANSS agitation items ( P CGI-severity at 4 h ( P=0.008 ) . Both ziprasidone doses were very well tolerated . Ziprasidone IM 20 mg was not associated with EPS , dystonia , akathisia , respiratory depression or with excessive sedation . Conclusions : Ziprasidone IM 20 mg substantially and significantly reduced the symptoms of acute agitation in patients with psychotic disorders . Ziprasidone 20 mg IM was very well tolerated and produced no dystonia or akathisia", "INTRODUCTION Although the use of atypical antipsychotics is the st and ard of care in the maintenance treatment of psychosis , most clinicians still rely on conventional neuroleptics to treat acutely agitated psychotic patients . The objective of this study was to evaluate the effectiveness and safety of a fast orally disintegrating tablet formulation of risperidone in the initial treatment of a large sample of very acutely ill psychotic patients . METHODS In this multi-center , prospect i ve , open-label observational trial , 191 schizophrenic patients were treated upon admission to hospital with fast orally disintegrating risperidone tablets for up to seven days . Co-medication was per usual clinical practice and at physician 's discretion . Psychopathology was rated at baseline , 2 , 24 and 48 hours and 4 and 7 days after initiation of therapy . RESULTS A mean PANSS total score of 114.3+/-23.4 at baseline reflected a severely exacerbated patient population . The PANSS total score was significantly reduced to 83.6+/-26.8 ( p median time to calmness was 70 min and the associated PANSS item 4 ( excitation ) dropped two hours after the first intake of the study medication from 4.3+/-1.5 to 3.1+/-1.5 ( p A total of 172 patients ( 90.1 % ) out of 191 completed the study . The median risperidone dose was 2 mg/d at the initiation of therapy and 4 mg/d after one week . CONCLUSION Oral treatment of acutely exacerbated schizophrenic patients with fast orally disintegrating risperidone tablets , alone or in combination with benzodiazepines , was associated with a rapid onset of action and a significant and clinical ly relevant improvement of acute symptoms", "Objective To compare the effect of intramuscular olanzapine with intramuscular haloperidol plus promethazine on rapid tranquillisation of agitated or violent people with mental illness . Design Pragmatic , allocation concealed , r and omised controlled trial . Setting Emergency services of a general hospital psychiatry department in Vellore , south India . Participants 300 adults with agitated or violent behaviour as a result of mental illness ; 150 r and omised to intramuscular olanzapine and 150 r and omised to intramuscular haloperidol plus promethazine . Interventions Open treatment with intramuscular olanzapine or intramuscular haloperidol plus promethazine . Main outcome measures Primary outcome was proportion of patients who were tranquil or asleep at 15 minutes and 240 minutes . Secondary outcomes were proportion of patients who were tranquil , asleep , restrained , absconding , or clinical ly improved at 15 , 30 , 60 , 120 , and 240 minutes ; additional medical interventions and adverse effects over four hours ; and compliance with oral drugs and adverse effects over two weeks . Results Of 300 people r and omised to receive either intramuscular olanzapine or intramuscular haloperidol plus promethazine , follow-up data were available for primary outcomes for 298 ( 99 % ) . Both treatments result ed in similar proportions of people being tranquil or asleep at 15 minutes ( olanzapine 131/150 ( 87 % ) , haloperidol plus promethazine 136/150 ( 91 % ) ; relative risk 0.96 , 95 % confidence interval 0.34 to 1.47 ) and 240 minutes ( olanzapine 144/150 ( 96 % ) , haloperidol plus promethazine 145/150 ( 97 % ) ; relative risk 0.99 , 0.95 to 1.03 ) . However , more people given olanzapine than those given haloperidol plus promethazine required additional drugs over four hours ( 65/150 ( 43 % ) v 31/150 ( 21 % ) ; relative risk 2.07 , 1.43 to 2.97 ) . Adverse effects were uncommon with both treatments . Conclusions Intramuscular olanzapine and intramuscular haloperidol plus promethazine were effective at rapidly tranquillising or sedating agitated or violent patients with mental illness but the combination result ed in fewer additional medical interventions within four hours of intervention . Trial registration Clinical trials NCT00455234", "Two studies tested the reliability and validity of the Overt Agitation Severity Scale ( OASS ) , a new instrument developed to define and objective ly rate the severity of agitated behavior . The authors postulate that agitation should be conceptualized as vocal and motor behaviors on a continuum of expressions that extends from anxiety to aggression . Content validity through expert agreement was achieved in the development of test construction over a 2-year period . Results of two pilot studies ( n = 25 and n = 14 subjects ) established the reliability and validity of the OASS to measure agitation severity . The OASS differs from other agitation scales in that it confines its rating exclusively to observable behavioral manifestations of agitation ", "This double-blind clinical trial studied 16 acutely agitated psychotic patients with manic or manic-like symptoms who needed rapid tranquilization and were therefore on maintenance treatment . They were r and omized to receive intramuscular preparations of clonazepam ( 1 to 2 mg ) or haloperidol ( 5 to 10 mg ) at 0 , 0.5 , and 1.0 hours . Both medications produced significant reduction of manic symptoms within two hours of initial treatment ; however , haloperidol produced beneficial results more rapidly than clonazepam . All patients completed the study , with the exception of one haloperidol-treated patient who developed severe parkinsonism . It was concluded that I.M. clonazepam is an effective , safe , but slower-acting alternative to I.M. haloperidol in the treatment of agitated psychiatric patients in need of rapid tranquilization", "OBJECTIVE The authors evaluated the comparative efficacy and safety of intramuscular olanzapine , intramuscular haloperidol , and intramuscular placebo for the treatment of acute agitation in schizophrenia . METHOD Hospitalized patients with schizophrenia received one to three injections of intramuscular olanzapine , 10 mg , intramuscular haloperidol , 7.5 mg , or intramuscular placebo over a 24-hour period . Agitation was measured with the excited component of the Positive and Negative Syndrome Scale and two additional scales . RESULTS According to scores on the excited component of the Positive and Negative Syndrome Scale , both intramuscular olanzapine and intramuscular haloperidol reduced agitation significantly more than intramuscular placebo 2 and 24 hours following the first injection . Intramuscular olanzapine reduced agitation significantly more than intramuscular haloperidol 15 , 30 , and 45 minutes following the first injection . No patients treated with intramuscular olanzapine experienced acute dystonia , compared with 7 % of those who were treated with intramuscular haloperidol . No significant QT(c ) interval changes were observed in any patients . CONCLUSIONS Intramuscular olanzapine represents a rapid , effective , and safe treatment for acute agitation in schizophrenia", "We conducted a prospect i ve double-blind study of accelerated dose titration of olanzapine in the treatment of newly admitted acutely agitated patients with schizophrenia . Patients were r and omized to either oral olanzapine ( 10 mg per day ) or oral haloperidol ( 10 mg per day ) , plus lorazepam as needed ( up to 12 mg per day ) . Antipsychotic dosage was increased to 20 mg per day as early as day 3 . Patients were evaluated with the Positive and Negative Syndrome Scale ( PANSS ) Agitation subscale during the first 24 hours of treatment , daily for the first week , then weekly until study completion . Significant within-group improvement was demonstrated in PANSS Agitation scores for both groups as early as 1 hour after initiating therapy ( -5.79 + /- 6.30 for olanzapine and -4.89 + /- 6.05 for haloperidol , P olanzapine is as efficacious as oral haloperidol in reducing acute agitation in patients with schizophrenia", "OBJECTIVE The objective of this study was to assess the efficacy and safety of inhaled loxapine in the treatment of agitation in patients with psychotic disorders . METHOD In this r and omized , double-blind , placebo-controlled study , 129 agitated patients with schizophrenia or schizoaffective disorder ( DSM-IV criteria ) were r and omized to receive in a clinical or hospital setting a single inhalation of 5 or 10 mg of loxapine or placebo administered using the Staccato loxapine for inhalation device . The inhalation device delivered thermally generated drug aerosol to the deep lung for rapid absorption . The primary efficacy measure was change on the Positive and Negative Syndrome Scale-excited component ( PANSS-EC ) 2 hours following treatment . Secondary outcomes included the Clinical Global Impressions-Improvement scale ( CGI-I ) , Behavioral Activity Rating Scale ( BARS ) , and time to first rescue medication . The study was conducted between September 2006 and January 2007 . RESULTS Differences were statistically significant ( P placebo and both 5-mg and 10-mg doses on the CGI-I and the CGI-I responder analyses at 2 hours and in time to first rescue medication , and they were statistically significant ( P placebo and 10-mg loxapine on the PANSS-EC 20 minutes after administration continuing through 2 hours and in change from baseline BARS . Three serious adverse events occurred at least 6 days after treatment , but none were judged related to study treatment . The most common adverse events were sedation and dysgeusia ( 22 % and 17 % , respectively , in the 10-mg group , and 14 % and 9 % , respectively , in the placebo group ) . CONCLUSIONS Inhaled loxapine was generally safe and well tolerated and produced rapid improvement in agitated patients with psychotic disorders . Statistically significant differences in efficacy were found for the 10-mg dose compared with placebo , with results suggesting 5 mg may be effective . The delivery of loxapine by inhalation may provide a rapid , well-tolerated option for treating acute psychotic agitation that allows patients to avoid the aversive effects and loss of autonomy often associated with use of intramuscular medications . Further investigation of this new loxapine formulation is warranted . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00369577", "Background Patients experiencing an acute decompensation of schizophrenia or bipolar disorder often present in an agitated state . Agitation presents a barrier to therapy , interrupting the typical physician-patient alliance and creating a disruptive , even hazardous , environment . Rapid assessment and effective treatment are necessary to manage agitation and , potentially , to shorten the time to recovery . Methods One hundred forty-eight acutely agitated patients received either : rapid initial dose escalation ( RIDE ) in which up to 40 mg of oral olanzapine was allowed on days 1 and 2 , up to 30 mg on days 3 and 4 , and 5 to 20 mg thereafter ; or usual clinical practice ( UCP ) in which patients received 10 mg/d olanzapine plus up to 4 mg lorazepam on days 1 and 2 , up to 2 mg on days 3 and 4 , and olanzapine 5 to 20 mg/d thereafter . The Positive and Negative Syndrome Scale-Excited Component ( PANSS-EC : poor impulse control , tension , hostility , uncooperativeness , and excitement ) measured at 24 hours was the primary measure . Secondary assessment s of agitation and safety were also performed . Results Agitation improved significantly from baseline for both treatment groups ; however , improvement with the RIDE strategy was superior to UCP . The RIDE group improvement was superior on the primary efficacy measure ( PANSS-Excited ) at 24 hours ; it was superior on all agitation measures at the end of double-blind treatment . Both treatments were well tolerated , with no clinical ly significant differences in safety measures . Treatment was not limited by oversedation and attention improved from baseline in both groups . Conclusions This study demonstrates the value of olanzapine in the treatment of acutely agitated patients . A new approach to olanzapine dosing that exp and s the initial dose range up to 40 mg/d may offer superior efficacy in rapidly and effectively controlling the symptoms of agitation", "BACKGROUND There is a clear need for effective , well-tolerated intramuscular ( i.m . ) agents for the acute control of agitated psychotic patients . Currently used agents , including conventional antipsychotics and /or benzodiazepines , may be associated with distressing side effects such as extrapyramidal side effects and excessive sedation . OBJECTIVE The objective of this study was to evaluate the efficacy and tolerability of the rapid-acting i.m . formulation of the novel antipsychotic ziprasidone in the treatment of in patients with psychosis and acute agitation ( DSM-IV diagnoses ) . METHOD In a 24-hour , double-blind , fixed-dose clinical trial , patients were r and omly assigned to receive up to 4 injections ( every 2 hours p.r.n . ) of 2 mg ( N = 54 ) or 10 mg ( N = 63 ) of ziprasidone i.m . The Behavioral Activity Rating Scale measured behavioral symptoms at baseline and the response to treatment up to 4 hours after the first i.m . injection . RESULTS Ziprasidone i.m . , 10 mg , rapidly reduced symptoms of acute agitation and was significantly more effective ( p acute dystonia or behavioral disinhibition was reported . One patient who received the 10-mg dose experienced the extrapyramidal side effect akathisia . CONCLUSION Ziprasidone i.m . , 10 mg , is rapidly effective and well tolerated in the short-term management of the agitated psychotic patient . Comparison with a study of identical design comparing 2-mg with 20-mg doses in patients with similar levels of psychopathology suggests that efficacy with 10 mg or 20 mg of ziprasidone i.m . is significant and dose related", "ABSTRACT Objective : A sub- population analysis of 325 patients with agitation ( Positive and Negative Syndrome Scale Excited Component [ PEC ] score ≥ 15 and ≤ 32 ; score of ≥ 4 on ≥ 2 items ) associated with schizophrenia in a r and omized , double-blind study investigating the efficacy and tolerability of intramuscular ( IM ) aripiprazole 9.75 mg , IM haloperidol 6.5 mg , or IM placebo and the transition to oral therapy . Research design and methods : Over 24 h , patients could receive up to three IM injections ; the second and third administered ≥ 2 and ≥ 4 h , respectively , after the first , if deemed clinical ly necessary . Following IM treatment , oral aripiprazole or haloperidol was administered for 4 days . The primary efficacy measure was the mean change in PEC score from baseline at 2 h. Results : At 2 h , mean improvements in PEC scores with IM aripiprazole ( –8.0 ) were significantly greater versus IM placebo ( –5.7 ; p ≤ 0.01 ) , and similar versus IM haloperidol ( –8.3 ) . Secondary efficacy measures also significantly improved with active IM treatment versus IM placebo . Continuation with oral treatment provided continued efficacy with both active treatments . The safety profiles of IM and oral aripiprazole were similar . The incidence of extrapyramidal symptom-related adverse events was 0 % with IM aripiprazole , 1.6 % with IM placebo and 16.5 % with IM haloperidol . Conclusion : Intramuscular aripiprazole is effective in patients with acute agitation associated with schizophrenia , comparable to IM haloperidol , and enables convenient transfer to oral aripiprazole therapy", "STUDY OBJECTIVE To compare the utility of intramuscular lorazepam ( LZ ) with the combination of intramuscular haloperidol ( HDL ) and LZ to control acutely agitated behavior . DESIGN R and omized double-blind comparison . SETTING Psychiatric emergency service of a large , university-affiliated , municipal hospital . PATIENTS Twenty subjects treated on the psychiatric emergency service . INTERVENTIONS Patients received an injection of either LZ 2 mg ( 11 patients ) or HDL 5 mg plus LZ 2 mg ( 9 patients ) . The Overt Aggression Scale ( OAS ) , visual analog scales reflecting agitation and hostility , and the Clinical Global Impressions ( CGI ) severity scale were administered at baseline and 30 , 60 , 120 , and 180 minutes after the injection . MEASUREMENTS AND MAIN RESULTS Planned data comparisons included categoric assignment of patients as improved , as defined by decreases in outcome measures 60 minutes after the injection , as well as continuous variables up to 180 minutes after the injection . A significantly greater percentage of subjects receiving combined treatment improved on the specific measures 60 minutes after dosing ( p survival analyses showed significant between-group differences in survival curves plotted for the entire study period ( p serious adverse effects occurred in either treatment group . CONCLUSION Our results suggest superior efficacy for HDL-LZ over LZ alone . Categoric tests of improvement at 60 minutes provided the strongest evidence of group differences", "Agitation is a vexing problem frequently observed in emergency department acute psychiatric patients , yet no instruments to measure agitation in this setting and population were found upon review of the literature . Previously developed agitation rating scales are limited by the length of observation they require , their need for participation by the patient , complexity in scoring , and a lack of validity in this setting and population . The purpose of this study was to psychometrically evaluate and refine an observation-based agitation scale for use with emergency department acute psychiatric patients . Using a method ological design , the 21-item Agitation Severity Scale was utilized to assess 270 adult psychiatric patients in the emergency setting in a prospect i ve , observational fashion . Reliability analysis , item analysis , exploratory factor analysis , and validity assessment s were completed . The relationship between Agitation Severity Scale scores and scores on the previously established Overt Agitation Severity Scale was evaluated . The instrument was reduced to 17 items representing four factors ( Aggressive Behaviors , Interpersonal Behaviors , Involuntary Motor Behaviors , and Physical Stance ) that accounted for nearly 70 % of observed variance , Cronbach 's & agr ; = 0.91 . Evidence of internal consistency reliability , equivalence reliability , construct validity , and convergent validity was established . Through this study , the 17-item Agitation Severity Scale demonstrated acceptable levels of reliability and validity when used with acute psychiatric patients in the emergency setting . This instrument holds promise as a method of enhancing clinical communication about agitation , evaluating the efficacy of interventions aim ed at decreasing agitation , and as a research tool", "STUDY OBJECTIVE Parenteral benzodiazepines or antipsychotics are often used to manage acute agitation in emergency department ( ED ) setting s in which alternative strategies have failed or are not feasible . There are scant data comparing parenteral medication regimens . We aim to determine the efficacy and safety of intravenous droperidol or olanzapine as an adjunct to intravenous midazolam for rapid patient sedation . METHODS We undertook a r and omized , double-blind , placebo-controlled , double-dummy , clinical trial in 3 EDs ( August 2009 to March 2011 ) . Adult patients ( n=336 ) requiring intravenous drug sedation for acute agitation were r and omized to receive a saline solution ( control ) , droperidol ( 5 mg ) , or olanzapine ( 5 mg ) bolus . This was immediately followed by incremental intravenous midazolam boluses ( 2.5 to 5 mg ) until sedation was achieved . The primary outcome was time to sedation . Secondary outcomes were need for \" rescue \" drugs and adverse events . RESULTS Three hundred thirty-six patients were r and omized to the 3 groups . Baseline characteristics were similar across groups . The differences in medians for times to sedation between the control and droperidol and control and olanzapine groups were 4 minutes ( 95 % confidence interval [ CI ] 1 to 6 minutes ) and 5 minutes ( 95 % CI 1 to 6 minutes ) , respectively . At any point , patients in the droperidol and olanzapine groups were approximately 1.6 times more likely to be se date d compared with controls : droperidol and olanzapine group hazard ratios were 1.61 ( 95 % CI 1.23 to 2.11 ) and 1.66 ( 95 % CI 1.27 to 2.17 ) , respectively . Patients in the droperidol and olanzapine groups required less rescue or alternative drug use after initial sedation . The 3 groups ' adverse event profiles and lengths of stay did not differ . CONCLUSION Intravenous droperidol or olanzapine as an adjunct to midazolam is effective and decreases the time to adequate sedation compared with midazolam alone", "Objective To determine whether haloperidol alone results in swifter and safer tranquillisation and sedation than haloperidol plus promethazine . Design Pragmatic r and omised open trial ( January-July 2004 ) . Setting Psychiatric emergency room , Rio de Janeiro , Brazil . Participants 316 patients who needed urgent intramuscular sedation because of agitation , dangerous behaviour , or both . Interventions Open treatment with intramuscular haloperidol 5 - 10 mg or intramuscular haloperidol 5 - 10 mg plus intramuscular promethazine up to 50 mg ; doses were at the discretion of the prescribing clinician . Main outcome measures The primary outcome was proportion tranquil or asleep by 20 minutes . Secondary outcomes were asleep by 20 minutes ; tranquil or asleep by 40 , 60 , and 120 minutes ; physically restrained or given additional drugs within 2 hours ; severe adverse events ; another episode of agitation or aggression ; additional visit from the doctor during the subsequent 24 hours ; overall antipsychotic load in the first 24 hours ; and still in hospital after 2 weeks . Results Primary outcome data were available for 311 ( 98.4 % ) people , 77 % of whom were thought to have a psychotic illness . Patients allocated haloperidol plus promethazine were more likely to be tranquil or asleep by 20 minutes than those who received intramuscular haloperidol alone ( relative risk 1.30 , 95 % confidence interval 1.10 to 1.55 ; number needed to treat 6 , 95 % confidence interval 4 to 16 ; P=0.002 ) . No differences were found after 20 minutes . However , 10 cases of acute dystonia occurred , all in the haloperidol alone group . Conclusions Haloperidol plus promethazine is a better option than haloperidol alone in terms of speed of onset of action and safety . Enough data are now available to change guidelines that continue to recommend treatments that leave people exposed to longer periods of aggression than necessary and patients vulnerable to distressing and unsafe adverse effects . Trial registration Current Controlled Trials IS RCT N83261243", "There are no rapid-acting intramuscular formulations of atypical antipsychotics available for quickly calming an agitated patient with bipolar disorder . In this study , 201 agitated patients with bipolar mania were r and omly assigned to receive one to three injections of the atypical antipsychotic olanzapine ( 10 mg , first two injections ; 5 mg , third injection ) , the benzodiazepine lorazepam ( 2 mg , first two injections ; 1 mg , third injection ) , or placebo ( placebo , first two injections ; olanzapine , 10 mg , third injection ) within a 24-hour period . Agitation was measured at baseline , every 30 minutes for the first 2 hours , and at 24 hours after the first injection using the Positive and Negative Syndrome Scale – Excited Component subscale and two additional agitation scales . At 2 hours after the first injection , patients treated with olanzapine showed a significantly greater reduction in scores on all agitation scales compared with patients treated with either placebo or lorazepam . At 24 hours after the first injection , olanzapine remained statistically superior to placebo in reducing agitation in patients with acute mania , whereas patients treated with lorazepam were not significantly different from those treated with placebo or olanzapine . Furthermore , no significant differences among the three treatment groups were observed in safety measures , including treatment-emergent extrapyramidal symptoms , the incidence of acute dystonia , or QTc interval changes . These findings suggest that intramuscular olanzapine is a safe and effective treatment for reducing acute agitation in patients with bipolar mania", "A comparison of loxapine and haloperidol parenterally in acute psychotic , agitated patients was carried out as a r and omized double‐blind trial . The trial covered 15 patients in each group , and the diagnoses were psychogenic psychosis ( 18 cases ) and acute schizophrenia ( 12 cases ) . The patients received 25–50 mg loxapine or 2.5–5 mg haloperidol combined with biperiden 2.5–5 mg every 6–12 hours over a 72‐hour period . The average daily dose was 130 mg loxapine or 12 mg haloperidol", "BACKGROUND Aripiprazole is an investigational agent for treating schizophrenia that has a novel pharmacologic profile . The present study investigated the efficacy , safety , and tolerability of aripiprazole and haloperidol compared with placebo . METHOD A 4-week , double-blind , r and omized study , conducted at 36 U.S. centers between July 1997 and June 1998 , compared aripiprazole ( 15 mg/day , 30 mg/day ) to placebo , with haloperidol ( 10 mg/day ) as an active control . Fixed doses of each agent were administered from day 1 throughout the study . A total of 414 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were r and omized . Efficacy measures included the Positive and Negative Syndrome Scale ( PANSS ) total , PANSS positive , PANSS negative , PANSS-derived Brief Psychiatric Rating Scale ( BPRS ) core , Clinical Global Impressions (CGI)-Severity of Illness , and mean CGI-Improvement scores . Safety and tolerability evaluations included extrapyramidal symptoms ( EPS ) , weight gain , serum prolactin level , and QTc interval . RESULTS Both doses of aripiprazole and haloperidol , 10 mg , produced statistically significant ( p PANSS total , PANSS positive , PANSS-derived BPRS core , and CGI-Severity scores and significantly lower CGI-Improvement scores at endpoint , compared with placebo . Aripiprazole , 15 mg , and haloperidol , 10 mg , significantly improved PANSS negative score compared with placebo . Both aripiprazole doses and haloperidol separated from placebo for PANSS total scores at week 2 . Unlike haloperidol , aripiprazole was not associated with significant EPS or prolactin elevation at endpoint compared with placebo . There were no statistically significant differences in mean changes in body weight across the treatment groups versus placebo , and no patients receiving aripiprazole experienced clinical ly significant increases in QTc interval . CONCLUSION Aripiprazole , effective against positive and negative symptoms , is a safe and well-tolerated potential treatment for schizophrenia and schizoaffective disorder", "Abstract Objective To compare two widely used drug treatments for people with aggression or agitation due to mental illness . Design Pragmatic , r and omised clinical trial . Setting Three psychiatric emergency rooms in Rio de Janeiro , Brazil . Subjects 301 aggressive or agitated people . Interventions Open treatment with intramuscular midazolam or intramuscular haloperidol plus promethazine . Main outcome measures Patients tranquil or se date d at 20 minutes . Secondary outcomes : patients tranquil or asleep by 40 , 60 , and 120 minutes ; restrained or given extra drugs within 2 hours ; severe adverse events ; another episode of agitation or aggression ; needing extra visits from doctor during first 24 hours ; overall antipsychotic load in first 24 hours ; and not discharged by two weeks . Results 151 patients were r and omised to midazolam , and 150 to haloperidol-promethazine mix . Follow up for the primary outcome was available for 298 ( 99 % ) : 134/151 ( 89 % ) of patients given midazolam were tranquil or asleep after 20 minutes compared with 101/150 ( 67 % ) of those given haloperidol plus promethazine ( relative risk 1.32 ( 95 % confidence interval 1.16 to 1.49 ) ) . By 40 minutes , midazolam still had a statistically and clinical ly significant 13 % relative advantage ( 1.13 ( 1.01 to 1.26 ) ) . After 1 hour , about 90 % of both groups were tranquil or asleep . One important adverse event occurred in each group : a patient given midazolam had transient respiratory depression , and one given haloperidol-promethazine had a gr and e mal seizure . Conclusions Both treatments were effective . Midazolam was more rapidly sedating than haloperidol-promethazine , reducing the time people are exposed to aggression . Adverse effects and re sources to deal with them should be considered in the choice of the treatment", "BACKGROUND The pharmacological management of violence in people with psychiatric disorders is under- research ed . AIMS To compare interventions commonly used for controlling agitation or violence in people with serious psychiatric disorders . METHOD We r and omised 200 people to receive intramuscular lorazepam ( 4 mg ) or intramuscular haloperidol ( 10 mg ) plus promethazine ( 25 - 50 mg mix ) . RESULTS At blinded assessment s 4 h later ( 99.5 % follow-up ) , equal numbers in both groups ( 96 % ) were tranquil or asleep . However , 76 % given the haloperidol-promethazine mix were asleep compared with 45 % of those allocated lorazepam ( RR=2.29,95 % CI 1.59 - 3.39 ; NNT=3.2,95 % CI 2.3 - 5.4 ) . The haloperidol-promethazine mix produced a faster onset of tranquillisation/sedation and more clinical improvement over the first 2 h. Neither intervention differed significantly in the need for additional intervention or physical restraints , numbers absconding , or adverse effects . CONCLUSIONS Both interventions are effective for controlling violent/agitated behaviour . If speed of sedation is required , the haloperidol-promethazine combination has advantages over lorazepam", "OBJECTIVE The treatment of agitation in drug- and alcohol-using emergency patients is understudied . METHOD We performed a retrospective chart review of 105 agitated emergency department patients who received either intramuscular ( IM ) haloperidol or IM olanzapine , comparing prescribing patterns , level of agitation , response to treatment and side effects in patients positive for drugs or alcohol [ D/A(+ ) ] and patients negative for drugs or alcohol [ ( D/A(- ) ] . RESULTS The haloperidol-benzodiazepine combination was the most frequently prescribed treatment in both groups , although alcohol(+ ) status biased clinicians toward using haloperidol alone . Overall , D/A(+ ) and D/A(- ) patients responded to the initial intervention at similar rates , although D/A(+ ) patients were rated as more agitated and had more posttreatment sedation than D/A(- ) patients . In D/A(+ ) patients , haloperidol+benzodiazepine and IM olanzapine performed better than haloperidol alone . There were no serious adverse events with any treatment . CONCLUSION Findings support the generalization of efficacy data from more rarified agitated sample s to population s with high rates of substance use and highlight the need for prospect i ve , inclusive , r and omized trials comparing the commonly used haloperidol-benzodiazepine combination with newer injectable antipsychotics", "Objective . To compare oral risperidone and intramuscular ( IM ) haloperidol , both in combination with IM lorazepam , in the management of acute agitation and psychosis in the medical emergency department . Methods . In this prospect i ve , r and omized , placebo-controlled , double-blind study of 30 patients presenting to the emergency department with acute agitation and /or psychosis , three groups of 10 patients received oral and IM medications : 1 ) 2 mg oral risperidone and 2 mg IM lorazepam ; 2 ) 5 mg oral haloperidol and 2 mg IM lorazepam ; 3 ) oral placebo and 2 mg IM lorazepam . Each treatment group received both an injection and a tablet to reduce treatment group variability . Patients were evaluated using the Brief Psychiatric Rating Scale ( BPRS ) and the Positive and Negative Syndrome Scale ( PANSS ) before receiving medication and at 30 and 90 minutes after medication was administered . The intergroup mean percent reductions in rating scale scores were compared using ANOVA , chi-square , and Kruskal-Wallis tests . Results . There were no statistically significant differences among the groups at any point . The two groups receiving an antipsychotic plus lorazepam showed a trend towards increased symptom reduction compared with the group receiving lorazepam alone , although this trend was not statistically significant . Conclusions . Lorazepam alone was as effective as lorazepam plus haloperidol or lorazepam plus risperidone in this small trial . While not statistically significant , a trend toward better outcomes with combined treatment warrants further study", "STUDY OBJECTIVE We compare intravenous midazolam and droperidol for the onset of sedation of acutely agitated patients in the emergency department ( ED ) . METHODS This was a double-blind , r and omized , clinical trial set in the ED of a university teaching hospital . Subjects were adults , acutely agitated because of mental illness , intoxication , or both , who received midazolam or droperidol , 5 mg intravenously , every 5 minutes until se date d. We analyzed time to sedation using survival analysis , median times to sedation , and proportions se date d at 5 and 10 minutes . RESULTS Seventy-four patients received midazolam ; 79 patients , droperidol . Survival analysis showed no difference in time to sedation ( hazard ratio 0.86 ; 95 % confidence interval [ CI ] 0.61 to 1.23 ) , P=.42 . Median time to sedation was 6.5 minutes for midazolam ( median dose 5 mg ) and 8 minutes for droperidol ( median dose 10 mg ) , P=.075 ( effect size 1.5 minutes ; 95 % CI 0 to 4 minutes ) . At 5 minutes , 33 of 74 ( 44.6 % ) patients from the midazolam group were adequately se date d compared with 13 of 79 ( 16.5 % ) patients from the droperidol group , a difference of 28.1 % ( 95 % CI 12.9 % to 43.4 % ; P adverse events occurred in the midazolam group and 10 in the droperidol group . Three patients required active airway management ( 3 patients with assisted ventilation and 1 patient intubated ) ; all received midazolam . CONCLUSION There is no difference in onset of adequate sedation of agitated patients using midazolam or droperidol . Patients se date d with midazolam may have an increased need for active airway management", "OBJECTIVE Patients with acute schizophrenia who are agitated typically manifest worse overall symptomatology and are generally more challenging to treat than nonagitated patients . In order to determine whether baseline agitation level influences treatment response , the effects of oral aripiprazole in acute patients with schizophrenia experiencing either higher or lower levels of agitation were examined . METHOD A post hoc analysis of pooled data from the first 4 or 6 weeks of 4 r and omized , double-blind , placebo-controlled aripiprazole trials was conducted . Patients with a DSM-IV diagnosis of acute schizophrenia r and omly assigned to treatment with either aripiprazole 10 , 15 , 20 , or 30 mg/day ( N = 790 ) or placebo ( N = 397 ) were divided into groups experiencing higher or lower agitation at baseline . Higher agitation was defined as a baseline Positive and Negative Syndrome Scale (PANSS)-Excited Component ( PEC ) score of > or = 14 and a score of > or = 4 on at least 1 PEC item ( excitement , hostility , tension , uncooperativeness , or poor impulse control ) . Analysis of covariance was used to evaluate PANSS total , Clinical Global Impressions-Improvement scale ( CGI-I ) , and PEC scores between aripiprazole and placebo within the higher and lower agitation groups . RESULTS In both the higher and lower agitation groups , aripiprazole treatment produced significantly lower PANSS total , CGI-I , and PEC scores at weeks 2 to 6 , compared with placebo ( p placebo , and adverse events were generally mild across groups . CONCLUSIONS Aripiprazole significantly improved the core symptoms of acute schizophrenia regardless of baseline agitation level . In particular , agitation symptoms were significantly decreased in patients with higher baseline agitation . Improvements appeared to be independent of benzodiazepine use or excessive sedation effects . These results suggest that oral aripiprazole is an effective and safe treatment option for patients with acute schizophrenia who manifest agitation symptoms", "OBJECTIVE To examine the antimanic efficacy of the relatively nonsedating antipsychotic aripiprazole in patients with bipolar I disorder and high or low baseline levels of agitation . METHOD Data were pooled for this post hoc analysis from two 3-week , placebo-controlled trials of aripiprazole in acute mania ( DSM-IV ) . Patients r and omly assigned to aripiprazole 30 mg/day ( N = 259 ) or placebo ( N = 254 ) were classified as having either high ( Positive and Negative Syndrome Scale [ PANSS ] Excited Component [ PEC ] score of > or=14 and a score of > or= 4 on at least one PEC item ) or low ( PEC Efficacy measures were changes in Young Mania Rating Scale ( YMRS ) scores , Clinical Global Impressions-Bipolar ( CGI-BP ) scores , and PEC scores . Efficacy and agitation measurements were assessed by analysis of covariance . RESULTS From the first week of therapy onward , aripiprazole-treated subjects had significantly greater reduction from baseline in YMRS total scores than placebo-treated subjects in both the high- and low-agitation groups ( p CGI-BP scores vs. placebo at end point ( p highly agitated patients receiving aripiprazole , PEC scores were significantly decreased versus placebo at end point ( p patients with low agitation receiving aripiprazole , no increases in PEC scores were seen , and a significant reduction in agitation symptoms was apparent after adjustment for baseline PEC scores . CONCLUSIONS Aripiprazole was superior to placebo in reducing the severity of both mania and agitation in highly agitated patients with bipolar I disorder and showed significant antimanic activity in patients with low levels of agitation without increasing agitation . These findings suggest that aripiprazole 's antimanic effect is specific and not limited to control of agitation through sedation", "Objectives . Behavioral emergencies are a common and serious problem for consumers , their communities , and the healthcare setting s on which they rely , but there is little research to guide provider responses to this challenge . Key constructs such as agitation have not been adequately operationalized so that the criteria defining a behavioral emergency are vague . A significant number of deaths of patients in restraint has focused government and regulators on these issues , but a consensus about key elements in the management of behavioral emergencies has not yet been articulated by the provider community . The authors assembled a panel of 50 experts to define the following elements : the threshold for emergency interventions , the scope of assessment for varying levels of urgency and cooperation , guiding principles in selecting interventions , and appropriate physical and medication strategies at different levels of diagnostic confidence and for a variety of etiologies and complicating conditions . Method . A written survey with 808 decision points was completed by 50 experts . A modified version of the R AND Corporation 9-point scale for rating appropriateness of medical decisions was used to score options . Consensus on each option was defined as a non-r and om distribution of scores by chi-square “ goodness-of-fit ” test . We assigned a categorical rank ( first line/preferred choice , second line/ alternate choice , third line/usually inappropriate ) to each option based on the 95 % confidence interval around the mean rating . Guideline tables were constructed describing the preferred strategies in key clinical situations . Results . The expert panel reached consensus on 83 % of the options . The relative appropriateness of emergency interventions was ascertained for a continuum of behaviors . When asked about the frequency with which emergency interventions ( parenteral medication , restraint , seclusion ) were required in their services , 47 % of the experts reported that such interventions were necessary for 1%–5 % of patients seen in their services and 32 % for 6%–20 % . In general , the consensus of this panel lends support to many elements of recent regulations from the Health Care Financing Administration ( now the Centers for Medicare and Medicaid Services ) , including the timing of clinician assessment and re assessment and the intensity of nursing care . However , the panel did not endorse the concept of “ chemical restraint , ” instead favoring the idea that medications are treatments for target behaviors in behavioral emergencies even when the causes of these behaviors are not well understood . Control of aggressive behavior emerged as the highest priority during the emergency ; however , preserving the physician-patient relationship was rated a close second and became the top priority in the long term . Oral medications , particularly concentrates , were clearly preferred if it is possible to use them . Benzodiazepines alone were top rated in 6 of 12 situations . High-potency conventional antipsychotics used alone never received higher ratings than benzodiazepines used alone . A combination of a benzodiazepine and an antipsychotic was preferred for patients with suspected schizophrenia , mania , or psychotic depression . There was equal support for high-potency conventional or atypical antipsychotics ( particularly liquids ) in oral combinations with benzodiazepines . Droperidol emerged in fourth place in some situations requiring an injection . Conclusions . To evaluate many of the treatment options in this survey , the experts had to extrapolate beyond controlled data . Within the limits of expert opinion and with the expectation that future research data will take precedence , these guidelines provide some direction for addressing common clinical dilemmas in the management of psychiatric emergencies and can be used to inform clinicians in acute care setting s regarding the relative merits of various strategies", "Patients with methamphetamine toxicity often present to the emergency department ( ED ) agitated , violent and psychotic . To determine the efficacy of a benzodiazepine versus a butyrophenone for chemical restraint we conducted a prospect i ve , r and omized study at a large urban university ED between January 1995 and January 1997 . Patients were r and omized to receive either lorazepam or droperidol intravenously . A 6-point sedation scale was devised , with 6 representing extreme agitation and 1 deep sleep . Sedation scores were recorded at time 0 , 5 , 10 , 15 , 30 and 60 min . Vital signs were recorded at time 0 and at 60 min . If sedation was inadequate , repeat dosages of each drug could be repeated at 30 min . Toxicology screen , ethanol and creatinine phosphokinase levels were obtained . A total of 146 patients were evaluated . Seventy-four patients received lorazepam and 72 received droperidol . Both drugs had similar sedation profiles at 5 min . Patients receiving droperidol had significantly improved sedation scores at times 10 , 15 , 30 and 60 min than lorazepam ( p lorazepam were given ( 26 ) than droperidol ( 6 ) at 30 min . Both drugs produced significant reduction in pulse , systolic blood pressure , respiratory rate , and temperature over 60 min . We conclude droperidol produces a more rapid and profound sedation than lorazepam for methamphetamine toxicity . Lorazepam is more likely to require repeat dosing than droperidol", "Abstract Studies of intramuscular ( IM ) olanzapine in Asian and Taiwanese population s are limited . This study examined the efficacy and safety of IM olanzapine in Taiwanese patients with schizophrenia and acute agitated behavior . This was a multicenter , double-blind , r and omized , parallel study comparing the efficacy and safety of 10 mg/d IM olanzapine ( n = 25 ) against 7.5 mg/d haloperidol ( n = 24 ) . The primary objective was to assess the change of agitation from baseline to 2 hours after the first IM injection on the Positive and Negative Symptom Scale – Excited Component Scale . The changes of Positive and Negative Symptom Scale – Excited Component Scale score from baseline to 2 hours after the first IM injection did not show statistically significant difference between study groups ( olanzapine −9.0 ± 5.7 , haloperidol −7.9 ± 4.0 , P = 0.254 ) . Both groups reported insomnia as the most common treatment-emergent adverse event , and no serious adverse event was reported . Intramuscular olanzapine and IM haloperidol are similarly effective antipsychotic agents in treating agitated symptoms in Taiwanese patients with schizophrenia . Both IM olanzapine and IM haloperidol were proven to be safe and well tolerated , which also provided alternative options in the treatment of patients with schizophrenia with agitation", "Behavioral agitation and prominent positive psychotic symptoms often characterize the acute presentation of schizophrenia . The clinical treatment goal is a rapid control of these symptoms . The relative efficacy of olanzapine , a novel antipsychotic drug , was compared with that of the conventional antipsychotic drug haloperidol . A post hoc analysis conducted on a large multicenter , double-blind , 6-week study of acute-phase patients with DSM-III-R schizophrenia or schizophreniform or schizoaffective disorders treated with olanzapine ( 5 - 20 mg/day ) or haloperidol ( 5 - 20 mg/day ) assessed the treatment effects on agitation ( Brief Psychiatric Rating Scale [ BPRS ] agitation score ) and positive symptoms ( BPRS positive symptom score ) . Overall , olanzapine-treated patients experienced significantly greater improvement in behavioral agitation than did haloperidol-treated patients ( last observation carried forward [ LOCF ] ; p reductions in agitation scores during the first 3 weeks of therapy ; olanzapine was associated with significantly greater improvements at weeks 4 , 5 , and 6 ( observed cases [ OC ] ) . Similarly , patients with predominantly positive psychotic symptoms experienced significantly greater improvement in BPRS positive symptom scores with olanzapine compared with haloperidol ( LOCF ; p = .013 ) . In olanzapine-treated patients , improvement in BPRS agitation and positive symptom scores was significantly greater at weeks 4 , 5 , and 6 ( agitation scores , p olanzapine may be considered a first-line treatment for the patient in an acute episode of schizophrenia", "BACKGROUND Aripiprazole is a dopamine D2 receptor partial agonist with partial agonist activity at serotonin 5HT1A receptors and antagonist activity at 5HT2A receptors . This multicenter trial examined the efficacy , safety , and tolerability of aripiprazole in patients with acute exacerbation of schizophrenia or schizoaffective disorder . METHODS In this 4-week double-blind study , 404 patients were r and omized to 20 mg/d ( n = 101 ) or 30 mg/d ( n = 101 ) of aripiprazole , placebo ( n = 103 ) , or 6 mg/d of risperidone ( n = 99 ) . Efficacy assessment s included Positive and Negative Syndrome Scale ( PANSS ) scores and Clinical Global Impression scores . Safety and tolerability evaluations included extrapyramidal symptoms and effects on weight , prolactin , and corrected QT ( QTc ) interval . RESULTS Aripiprazole ( 20 and 30 mg/d ) and risperidone ( 6 mg/d ) were significantly better than placebo on all efficacy measures . Separation from placebo occurred at week 1 for PANSS total and positive scores with aripiprazole and risperidone and for PANSS negative scores with aripiprazole . There were no significant differences between aripiprazole and placebo in mean change from baseline in the extrapyramidal symptom rating scales . Mean prolactin levels decreased with aripiprazole but significantly increased 5-fold with risperidone . Mean change in QTc interval did not differ significantly from placebo with any active treatment group . Aripiprazole and risperidone groups showed a similar low incidence of clinical ly significant weight gain . CONCLUSIONS Aripiprazole is effective , safe , and well tolerated for the positive and negative symptoms in schizophrenia and schizoaffective disorder . It is the first non-D2 receptor antagonist with clear antipsychotic effects and represents a novel treatment development for psychotic disorders", "INTRODUCTION Patterns of use of antipsychotics are not well described in emergency units . The objective of this study was to describe the effectiveness and safety of use of olanzapine in patients with acute psychosis and agitation in the emergency rooms . METHODS In this prospect i ve observational study 278 patients with acute psychosis and agitation were consecutively admitted in 16 psychiatric emergency wards and treated with any oral psychopharmacology treatment , including olanzapine , according to investigators clinical criteria . Data were collected prospect ively including demographics , diagnosis , concomitant medications , utilization of mechanical restraints , and severity of agitation . Clinical evolution during emergency room stay was assessed with PANSS-Excitement Component , CGI-S and Agitation and Calmness Evaluation Scale ( ACES ) at baseline , before any re-intervention ( if needed ) and at discharge from the emergency room . Safety was also evaluated . RESULTS Olanzapine alone was used in 148 ( 53.2 % ) patients . Most of them ( 77.7 % ) were diagnosed of Schizophrenia and related psychoses . Up to 38 patients ( 25.7 % ) required mechanical restraints . Mean change ( confidence interval [ CI ] 95 % ) from baseline to discharge was significant in all rating scales ; PANSS-EC : -7.46 ( -8.2 , -6.7 ) ; CGI-S : -1.82 ( -2 , -1.6 ) ACES : 1.28 ( 1.1 , 1.5 ) . At discharge 70.3 % of patients went to inpatient units . Five patients ( 3.4 % ) reported adverse events including : bradycardia , dry mouth , sedation , hypertension , hypotension , and orthostatic hypotension . None of them was serious . CONCLUSIONS The utilization of olanzapine alone decreased agitation in psychotic patients in emergency room setting s. Incidence of adverse events was low and it was well tolerated", "BACKGROUND This study compared the safety , tolerability and switch to oral medication in patients with bipolar disorder or schizophrenia who received intramuscular ( IM ) olanzapine or other IM antipsychotics for the treatment of acute agitation . METHODS Patients ( N = 2011 ) from 15 countries participated in this prospect i ve , observational , non-interventional study . In patients requiring treatment with at least one IM injection of a short-acting antipsychotic were assessed at baseline and within 7 days after the first IM injection . Treatment groups comprised : ( i ) patients prescribed IM olanzapine at baseline ; and ( ii ) patients prescribed any other IM antipsychotic medication at baseline . Outcome measures included : treatment-emergent adverse events , concomitant psychotropic medication and the time taken to switch to oral medication . RESULTS Fewer patients in the IM olanzapine group experienced an adverse event than patients in the other IM antipsychotic group ( 34.4 % vs. 46.2 % , p adverse events in both groups were : sedation , Parkinsonism , disturbance in attention , akathisia , dystonia and orthostatic hypotension . Fewer patients in the IM olanzapine group used anticholinergics ( 13.9 % vs. 42.5 % , p anxiolytics/hypnotics ( 47.6 % vs. 51.6 % , p = 0.023 ) . Patients in the IM olanzapine group switched to oral medication earlier than patients in the other IM antipsychotic group ( median time = 46.5 vs. 48.0 h , p = 0.009 ) . CONCLUSIONS These findings suggest that IM olanzapine may have a favourable impact on individual patients . However , the high rate of oral concomitant medication used throughout the study limits these findings from being associated with IM olanzapine alone", "STUDY OBJECTIVE To assess acute efficacy and safety of 9.75 mg of intramuscular ( IM ) injections of the atypical antipsychiatric aripiprazole in patients with schizophrenia or bipolar disorder and acute agitation . DESIGN Open-label trial of IM injections of aripiprazole and 24-hour monitoring of clinical response in patients with major psychoses and acute agitation . Partial analysis of blood levels of the administered drug to correlate with clinical response . SETTING Acute psychiatric care wards in a single university hospital . PATIENTS A total of 201 acutely agitated patients ( 79 with schizophrenia and 122 with bipolar disorder I ) . INTERVENTION Aripiprazole 9.75 mg IM injection . MEASUREMENTS AND MAIN RESULTS We evaluated clinical response using the Excitatory Component of the Positive and Negative Syndrome Scale ( PANSS-EC ) , the Agitation/Calmness Evaluation Scale ( ACES ) , and the Clinical Global Impressions scale ( CGI ) . Assessment s were conducted 30 , 60 , 90 , and 120 minutes and 24 hours after the first injection for PANSS-EC and ACES , and 2 , 4 , 6 , and 24 hours for CGI . Response was at least a 40 % decrease in PANSS-EC scores . We measured serum aripiprazole and dehydroaripiprazole levels in a sub sample . IM aripiprazole significantly improved clinical measures . PANSS-EC improved progressively , starting after 30 minutes . ACES improved after 90 minutes and continued thereafter . Effects were sustained , with steadily decreasing CGI scores , until the 24th hour . Response rate was 83.6 % after 2 hours , but with repeat injections , it rose to over 90 % with no differences among diagnostic groups . Although there were gender differences in the response to individual PANSS-EC items , the responses were similar overall . Neither clinical monitoring nor patient reporting revealed any side effects . No therapeutic window was identified , and levels did not correlate with any clinical measure . CONCLUSION Aripiprazole was effective and safe in reducing acute agitation in patients with bipolar disorder or schizophrenia . Our results compare favorably to double-blind trials , probably due to higher expectations in trials involving no placebo arm . Absence of side effects could be related to the short observation time", "Five fixed doses of the atypical antipsychotic \" Seroquel \" ( quetiapine ) were evaluated to delineate a dose-response relationship , as measured by changes from baseline in Brief Psychiatric Rating Scale ( BPRS ) , Clinical Global Impression ( CGI ) , and Modified Scale for the Assessment of Negative Symptoms ( SANS ) summary scores , and to compare efficacy and tolerability opposite placebo and haloperidol . Three hundred sixty-one patients from 26 North American centers entered this double-blind , placebo-controlled trial with acute exacerbation of chronic schizophrenia ( DSM-III-R ) . Patients who completed a single-blind , placebo washout phase were r and omized to double-blind treatment with quetiapine ( 75 , 150 , 300 , 600 , or 750 mg daily ) , haloperidol ( 12 mg daily ) , or placebo and evaluated weekly for 6 weeks . At end point , significant differences ( p mean changes from baseline were identified between the four highest doses of quetiapine and placebo for BPRS total , BPRS positive-symptom cluster , and CGI Severity of Illness item scores and between quetiapine 300 mg and placebo for SANS summary score . Differences between quetiapine and haloperidol were not significant . Dose-response modeling showed significant linear and quadratic functions of quetiapine dose for all primary efficacy variables . Notably , no significant safety concerns were identified as dose increased . Quetiapine was no different from placebo across the dose range studied regarding incidence of extrapyramidal symptoms or change in prolactin concentrations . Quetiapine is well tolerated and clinical ly effective in the treatment of schizophrenia . It is both superior to placebo and comparable to haloperidol in reducing positive symptoms at doses ranging from 150 to 750 mg/day and in reducing negative symptoms at a dose of 300 mg/day", "Rationale Conventional intramuscular ( IM ) antipsychotics used in managing acute exacerbation of schizophrenia are associated with side effects such as acute dystonia . Objectives To compare the efficacy and tolerability of sequential IM/oral ziprasidone with haloperidol in acute exacerbation of schizophrenia or schizoaffective disorder . Methods In a 6-week , multicenter , parallel-group , flexibly dosed study , patients were r and omized to ziprasidone ( IM up to 3 days , then oral 40–80 mg , b.i.d . ) or haloperidol ( IM up to 3 days , then oral 5–20 mg/day ) . Assessment s were rater-blinded . Results At the end of IM treatment , patients receiving ziprasidone ( n=427 ) showed significantly improved Brief Psychiatric Rating Scale Total ( BPRS total ) scores compared with those receiving haloperidol ( n=138 ) [ least-squares ( LS ) mean change −6.14 for ziprasidone versus −4.13 for haloperidol , P in BPRS total scores . There was a significantly greater improvement in BPRS negative subscale scores in ziprasidone-treated patients , both at the end of IM treatment ( LS mean change −1.15 for ziprasidone and −0.28 for haloperidol , P haloperidol , P Haloperidol-treated patients exhibited significantly greater increases in Extrapyramidal Symptom Rating Scale at end of IM treatment and at endpoint ( P the Barnes Akathisia Scale ( P the Movement Disorder Burden Score ( P incidences of movement disorder-related adverse events . Conclusions Sequential IM and oral ziprasidone offers important efficacy and tolerability advantages over haloperidol in acute schizophrenia", "BACKGROUND This 7-day , r and omized , open-label , multicenter , international study compared the efficacy and tolerability of intramuscular ( i.m . ) ziprasidone with haloperidol i.m . and the transition from i.m . to oral treatment in hospitalized patients with acute psychotic agitation ( related to DSM-III-R diagnoses ) . METHOD Patients received up to 3 days of flexible-dose ziprasidone i.m . ( N = 90 ) or haloperidol i.m . ( N = 42 ) followed by oral treatment to day 7 . After an initial ziprasidone i.m . dose of 10 mg , subsequent i.m . doses of 5 to 20 mg could be given every 4 to 6 hours ( maximum daily dose = 80 mg ) if needed , followed by oral ziprasidone , 80 - 200 mg/day . Haloperidol i.m . doses of 2.5 to 10 mg were given on entry , followed by 2.5 to 10 mg i.m . every 4 to 6 hours ( maximum daily dose = 40 mg ) if needed , then by oral haloperidol , 10 - 80 mg/day . RESULTS The mean reductions in Brief Psychiatric Rating Scale ( BPRS ) total , BPRS agitation items , and Clinical Global Impressions-Severity scale scores were statistically significantly greater ( p ziprasidone i.m . treatment compared with haloperidol i.m . treatment . Further reductions in these scores also occurred in both groups following transition to oral treatment . Ziprasidone was associated with a lower incidence of movement disorders and a reduced requirement for anticholinergic medication during both i.m . and oral treatment compared with haloperidol . Movement disorder scale scores improved with ziprasidone i.m . and oral treatment , but deteriorated with haloperidol . Other adverse events were rare with both treatments . CONCLUSION Ziprasidone i.m . was significantly more effective in reducing the symptoms of acute psychosis and was better tolerated than haloperidol i.m . , particularly in movement disorders . The transition from ziprasidone i.m . to oral ziprasidone was effective and well tolerated ", "Kwentus J , Riesenberg RA , Mar and i M , Manning RA , Allen MH , Fishman RS , Spyker DA , Kehne JH , Cassella JV . Rapid acute treatment of agitation in patients with bipolar I disorder : a multicenter , r and omized , placebo‐controlled clinical trial with inhaled loxapine . Bipolar Disord 2012 : 14 : 31–40 . © 2012 The Authors . Journal compilation © 2012 John Wiley & Sons", "BACKGROUND While lithium is effective in treating the majority of bipolar patients during a manic episode , the addition of neuroleptic during the early phase of treatment has been common clinical practice in inpatient setting s. In an earlier open study , we demonstrated the utility of the short-acting benzodiazepine lorazepam as an adjunct to lithium for the clinical management of manic agitation . METHOD We now present data from a r and omized , double-blind clinical study of lorazepam versus haloperidol in 20 hospitalized patients with a DSM-III-R diagnosis of bipolar disorder who were being treated concomitantly with lithium . Patients were rated using the Mania Rating Scale , Brief Psychiatric Rating Scale , Physician Global Impression Scale , and side effects scales . Data were analyzed using st and ard group comparisons and survival analysis . RESULTS There was no evidence for a significant difference between the two treatment groups in the magnitude of or time to response ( 5.0 + /- .82 days for haloperidol ; 6.5 + /- .93 days for lorazepam ) . Of the patients who were terminated from the protocol early , nonresponse was the primary reason in the lorazepam group while side effects were the reason in the haloperidol group . CONCLUSION Lorazepam may offer an efficacious and safe alternative to haloperidol as an adjunctive treatment to lithium in the clinical management of the early phase of manic agitation in a subgroup of bipolar patients", "Objective . To report efficacy and safety of transitioning patients receiving intramuscular ( IM ) formulations of aripiprazole or haloperidol to their respective oral formulations . Methods . 448 agitated patients with schizophrenia ( 73 % ) or schizoaffective disorder ( 27 % ) were r and omized to receive aripiprazole IM 9.75 mg , haloperidol IM 6.5 mg , or placebo IM within 24 hours . Patients treated with aripiprazole IM or haloperidol IM who completed this 24-hour IM phase were transitioned to the respective blinded oral formulations for 4 days ( aripiprazole 10 - 15 mg/day , n = 153 ; haloperidol 7.5 - 10 mg/day , n = 151 ) . Patients treated with placebo IM were transitioned to oral aripiprazole ( analysis not included ) . The primary efficacy measure was mean change in Positive and Negative Syndrome Scale-Excited Component ( PEC ) score from baseline of oral phase ( last value from 24-hour IM phase ) to endpoint ( study day 5 , last observation carried forward ) . Results . During the oral phase , aripiprazole 15 mg and haloperidol 10 mg were both effective in maintaining responses achieved on all efficacy measures during the 24-hour IM phase . Mean improvements in PEC scores from study day 1 to 5 were −1.37 for aripiprazole and −1.40 for haloperidol ( p = NS for aripiprazole versus haloperidol ) . Oral aripiprazole was well tolerated . Extrapyramidal symptom-related adverse events were lower for aripiprazole ( 1.3 % ) than haloperidol ( 8.0 % ) . Nausea and vomiting occurred more frequently in patients receiving aripiprazole ( 3.9 % and 2.6 % , respectively ) than in those receiving haloperidol ( 0.7 % and 1.3 % , respectively ) . Conclusions . Acutely agitated patients with schizophrenia or schizoaffective disorder treated with aripiprazole IM or haloperidol IM demonstrated similar effective and safe transition to their respective oral formulations . Initial benefits of reduced agitation and improved clinical status during the IM phase of the study were maintained throughout the oral phase of the study with good tolerability", "To investigate the efficacy and safety of intramuscular ( IM ) aripiprazole for the treatment of agitation in patients with bipolar I disorder , manic or mixed episodes . In total , 301 patients experiencing acute agitation were r and omized to IM aripiprazole 9.75 mg per injection ( n = 78 ) , IM aripiprazole 15 mg per injection ( n = 78 ) , IM lorazepam 2 mg per injection ( n = 70 ) , or IM placebo ( n = 75 ) in this double-blind multicenter study . Patients could receive up to 3 injections over 24 hours . Primary efficacy measure was mean change in Positive and Negative Syndrome Scale Excited Component score from baseline at 2 hours after first injection . Mean improvements in Positive and Negative Syndrome Scale Excited Component score at 2 hours were significantly greater with IM aripiprazole ( 9.75 mg , −8.7 ; 15 mg , −8.7 ) and IM lorazepam ( −9.6 ) versus IM placebo ( −5.8 ; P ≤ 0.001 ) . For all other efficacy measures , all 3 active treatments showed significantly greater improvements over IM placebo at 2 hours ( P several efficacy parameters . Both IM aripiprazole doses were well tolerated ; the safety profile was similar to oral aripiprazole . Oversedation ( Agitation-Calmness Evaluation Scale score of 8 or 9 ) during 2 hours after first injection was less frequent with IM aripiprazole 9.75 mg ( 6.7 % ) and IM placebo ( 6.8 % ) versus IM aripiprazole 15 mg ( 17.3 % ) and IM lorazepam ( 19.1 % ) . IM aripiprazole 9.75 and 15 mg are effective and well tolerated for acute agitation in bipolar disorder , although the low incidence of oversedation suggests a risk-benefit profile for IM aripiprazole 9.75 mg", "In a parallel groups , double-blind study , 54 acutely psychotic schizophrenics were given loxapine or haloperidol parenterally for 24 to 72 hours , then orally for a total study period of up to 10 days . Dosage ratios of loxapine to haloperidol ranged from a minimum of 2.7:1 to a maximum of 4.4:1 . Both groups showed significant and rapid improvement from baseline . Forty-eight percent of the loxapine patients and 33 % of the haloperidol patients achieved and maintained a global severity of illness rating of mild or better . By the end of the study , 84 % of the loxapine patients and 63 % of the haloperidol patients had achieved an improvement rating of moderate or marked . This difference approached significance ( p less than .10 ) . The most frequently reported adverse experiences were dystonic reactions and akathisia . The number and severity of adverse experiences did not differ significantly between drug groups . Intramuscular loxapine was at least as effective as haloperidol in the initial management of hostile and aggressive schizophrenic patients . The maintenance of therapeutic response after conversion to oral concentrate was comparable with the two drugs", "ABSTRACT Objective : To evaluate the efficacy and safety of quetiapine monotherapy for mania in bipolar disorder by an a priori defined combined analysis of data from two placebo-controlled studies . Method : The intent-to-treat ( ITT ) population s from two studies of patients with DSM-IV bipolar I disorder , manic episode , r and omised to 12 weeks of double-blind treatment with quetiapine ( up to 800 mg/day ) or placebo were combined . The primary efficacy endpoint was change in Young Mania Rating Scale ( YMRS ) score from baseline to Day 21 . Secondary endpoints included change from baseline in YMRS to Day 84 , YMRS response and remission rates and change from baseline to Days 21 and 84 in the Montgomery – Asberg Depression Rating Scale ( MADRS ) , Clinical Global Impressions ( CGI ) , Clinical Global Impressions – Bipolar ( CGI-BP ) and the Positive and Negative Syndrome Scale ( PANSS ) . These endpoints were analysed as continuous variables , using an analysis of covariance ( ANCOVA ) , with the baseline as covariate . In order to account for any difference in response between studies , the analyses were stratified by study as a fixed effect , and centre as a r and om effect . The Cochran – Mantel – Haenszel test was used to analyse binary variables . A chi square test was used to compare the frequency of adverse events between the treatment groups . Results : The combined analysis included a total of 403 patients from two quetiapine monotherapy studies in patients with bipolar I disorder . A significant improvement in YMRS score was observed from Day 4 ( p = 0.021 ) onward in the quetiapine group compared with placebo . The treatment advantage of quetiapine over placebo continued to increase to Day 21 ( p more quetiapine-treated than placebo-treated patients achieved a response ( p average quetiapine dose in responders was approximately 600 mg daily . Of adverse events occurring in ≥ 5 % of patients , quetiapine-treated patients had a significantly greater incidence versus placebo of somnolence ( 16.3 % vs. 4.0 % ) , dry mouth ( 15.8 % vs. 3 % ) , weight gain ( 9.1 % vs. 1.5 % ) and dizziness ( 6.7 % vs. 2.5 % ) . Conclusions : The data from this combined analysis support the results from the individual studies and indicate that quetiapine monotherapy is effective across a broad range of mood symptoms , fast-acting and well tolerated in the treatment of mania", "We report psychometric results of the Behavioural Activity Rating Scale ( BARS ) using data from three Phase III clinical trials of intramuscular ziprasidone in acutely agitated patients with psychosis ( Studies 1 and 2 ) or in stable psychotic patients ( Study 3 ) . Convergent validity and divergent validity were assessed with baseline data from Studies 1 and 2 in subjects with acute agitation . To investigate convergent validity , we sought Pearson and Spearman correlation of BARS scores with scores on the Clinical Global Impression of Severity ( CGI-S ) Scale and a predefined cluster of agitation-related items from the Positive and Negative Syndrome Scale ( PANSS ) . For divergent validity , we sought Pearson and Spearman correlation between BARS scores and a predefined cluster of PANSS items measuring negative symptoms . Discriminant validity was investigated with the help of subjects with moderate psychopathology ( Study 3 ) . Wilcoxon rank-sum and two- sample t tests determined whether mean ( or median ) BARS scores differed between subjects with acute agitation ( Studies 1 and 2 ) and moderate psychopathology ( Study 3 ) . Responsiveness to treatment effect and rater reliability were also evaluated . In Study 2 , Pearson correlation coefficients of BARS scores with PANSS agitation items and CGI-S were moderate ( convergent validity ) and statistically significant ( P correlation between BARS scores and PANSS negative component scores was low ( divergent validity ) . Treatment effect size was larger for BARS than for PANSS agitation items and CGI-S ( responsive to treatment differences ) . Virtually perfect inter- and intra-rater reliability was achieved . Study 1 produced similar results . BARS showed psychometrically valid properties for measurement of behavioral activity in acutely agitated patients with psychosis", "Introduction Agitation is a major problem in acute schizophrenia . Only a few studies have tested antipsychotic agents in severely agitated patients , mainly because of legal issues . Furthermore , most studies were limited to the first 24 hours . We aim ed to investigate the efficacy of oral haloperidol , risperidone , and olanzapine in reducing psychotic agitation in severely agitated patients with schizophrenia or schizophreniform or schizoaffective disorder over 96 hours using a prospect i ve , r and omized , rater-blinded , controlled design within a naturalistic treatment regimen . Methods In total , 43 severely agitated patients at acute care psychiatric units were enrolled . Participants were r and omly assigned to receive either daily haloperidol 15 mg , olanzapine 20 mg , or risperidone 2 to 6 mg over 5 days . Positive and Negative Syndrome Scale psychotic agitation subscale score was the primary outcome variable . A mixed-model analysis was applied . Results All drugs were effective for rapid tranquilization within 2 hours . Over 5 days , the course differed between agents ( P Dropouts occurred only in the risperidone and olanzapine groups . Men responded better to treatment than did women during the initial 2 hours ( P = 0.046 ) as well as over the 5-day course ( P diazepam or biperiden use . Conclusions Oral haloperidol , risperidone , and olanzapine seem to be suitable for treating acute severe psychotic agitation in schizophrenia spectrum disorders . Response to oral antipsychotics demonstrated a gender effect with poorer outcome in women throughout the study", "In this double-blind study , haloperidol ( n = 15 ) and thiothixene ( n = 15 ) , administered parenterally in emergency rooms and outpatient facilities to 30 acutely excited , agitated psychotic patients in hourly doses of 4 mg . or 8 mg . , as needed over a four-hour period ( total dosage ranging from 4 to 32 mg . ) , achieved rapid tranquilization in 30 patients . Significant improvement was shown over a six-hour period on BPRS Total Score , the four factors -- Thinking Disorder , Anergic state , Excitement and Disorientation , and Depression and also on hourly ratings of 17 symptoms of a Psychiatric Target Symptom Profile . No significant differences were found between the haloperidol-treated and thiothixene-treated groups . Few adverse reactions were noted , all of them mild , the most frequent being drowsiness in six patients", "METHODS Patients ( n=302 ) with bipolar I disorder ( manic episode ) were r and omised to 12 weeks ' double-blind treatment with quetiapine ( flexibly dosed up to 800 mg/day ) , placebo , or haloperidol ( up to 8 mg/day ) . The primary efficacy outcome variable was change from baseline to Day 21 in Young Mania Rating Scale ( YMRS ) score . RESULTS YMRS score improved with quetiapine at Day 21 ( -12.29 versus -8.32 for placebo ; P Haloperidol also showed an advantage over placebo at Days 21 and 84 ( P significant difference in efficacy measures between quetiapine and haloperidol groups at any assessment except Day 21 . The only common adverse event with quetiapine was somnolence ( 12.7 % ) . Extrapyramidal symptoms ( EPS ) , including akathisia , occurred at 59.6 % with haloperidol , 12.7 % with quetiapine , 15.8 % with placebo . Most quetiapine responders ( 84 % ) received a dose of 400 - 800 mg/day . CONCLUSIONS Quetiapine was effective and well tolerated . The efficacy and tolerability profile of haloperidol ( including its propensity for EPS ) supported study validity", "OBJECTIVES Due to inherent dangers and barriers to research in emergency setting s , few data are available to guide clinicians about how best to manage behavioral emergencies . Key constructs such as agitation are poorly defined . This lack of empirical data led us to undertake a survey of expert opinion , results of which were published in the 2001 Expert Consensus Guidelines on the Treatment of Behavioral Emergencies . Several second-generation ( atypical ) antipsychotics ( SGAs ) are now available in new formulations for treating behavioral emergencies ( e.g. , intramuscular [ i.m . ] olanzapine and ziprasidone ; rapidly dissolving tablets of olanzapine and risperidone ) . Critical questions face the field . The SGAs are significantly different from the FGAs and from each other and have not been studied in unselected patients as were the FGAs . Can the SGAs can be thought of as a class , do all antipsychotics have similar anti-agitation effects in different conditions , and , if equally effective , what limits might their safety profiles impose ? Should antipsychotics be used more specifically to treat psychotic conditions , while benzodiazepines ( BNZs ) alone are used nonspecifically ? Few data are available concerning combinations of SGAs and BNZs , and findings concerning the traditional combination of haloperidol plus a BNZ may not be relevant to combinations with SGAs . The culture is also evolving with more emphasis on patient involvement in treatment decisions . An international consensus has been developing that calming rather than sedation is the appropriate endpoint of behavioral emergency interventions . We undertook a new survey of expert opinion to up date recommendations from the earlier survey . METHOD A written survey of 61 questions ( 1,020 options ) was mailed to 50 experts in the field , 48 ( 96 % ) of whom completed it . The survey sought to define level of agitation at which emergency interventions are appropriate , scope of assessment depending on urgency and patients ' ability to cooperate , guiding principles for selecting interventions , and appropriate physical and medication strategies at different levels of diagnostic confidence for a variety of provisional diagnoses and complicating conditions . A modified version of the R AND Corporation 's 9-point scale for rating appropriateness of medical decisions was used to score most options . Consensus was defined as a non-r and om distribution of scores by chi-square \" goodness-of-fit \" test . We assigned a categorical rank ( first line/preferred , second line/alternate , third line/usually inappropriate ) to each option based on the 95 % confidence interval around the mean . Ratings were used to develop guidelines for preferred strategies in key clinical situations . This study received financial support from multiple sponsors , with the panel kept blind to sponsorship to reduce possible bias . Medication ratings were based on responses of only those respondents with direct experience with each drug . In reporting practice patterns , the panel was asked to respond based on actual data rather than estimates . RESULTS The expert panel reached consensus on 78 % of the options rated on the 9-point scale . The responses suggest that physicians can make provisional diagnoses with some confidence and that pharmacological and nonpharmacological interventions are selected differentially based on diagnosis and other salient demographic and medical features . BNZs are recommended when no data are available , when there is no specific treatment ( e.g. , personality disorder ) , or when they may have specific benefits ( e.g. , intoxication ) . No single SGA emerges as a nonspecific replacement for haloperidol ; instead , different SGAs are preferred in various circumstances consistent with current evidence . To the degree that haloperidol is recommended , it is almost always in combination with a BNZ ; haloperidol alone is preferred only in the medically compromised . In contrast , the SGAs are more often recommended for use alone , and the panel would avoid combining BNZs with some SGAs . Oral risperidone alone or combined with a BNZ receives strong support in a variety of situations . Oral olanzapine was rated very similarly to risperidone , with slightly higher ratings than risperidone in situations where it has been studied ( e.g. , schizophrenia , mania ) and slightly lower ratings where it has not been studied or safety may be a concern ; there was less support for combining oral olanzapine with a BNZ . For oral treatment of agitation related to schizophrenia or mania , olanzapine alone , risperidone alone or combined with a BNZ , and haloperidol plus a BNZ are first line , with strong support also for combining divalproex with the antipsychotic for presumed mania . Oral ziprasidone and quetiapine generally received similar second-line ratings in most situations . If a parenteral agent is needed , i.m . olanzapine alone received somewhat more support than i.m . ziprasidone alone ; however , there was more support for i.m . ziprasidone alone or combined with a BNZ than for i.m . olanzapine plus a BNZ , probably reflecting safety concerns . For example , for a provisional diagnosis of schizophrenia , first-line parenteral options are i.m . olanzapine or ziprasidone alone or i.m . haloperidol or ziprasidone combined with a BNZ . Neither of the new parenteral formulations received as much support as traditional agents ( i.m . BNZs , i.m . haloperidol ) when no data are available or the diagnosis involves medical comorbidity or intoxication . When initial intervention with risperidone , ziprasidone , or haloperidol is unsuccessful , the panel recommended adding a BZD to the antipsychotic . However , when initial treatment with olanzapine or quetiapine is unsuccessful , increasing the dosage is recommended . Perphenazine was consistently rated second line and droperidol and chlorpromazine received third-line ratings throughout . CONCLUSIONS Within the limits of expert opinion and with the expectation that future research data will take precedence , these guidelines suggest that the SGAs are now preferred for agitation in the setting of primary psychiatric illnesses but that BNZs are preferred in other situations", "INTRODUCTION A transition from IM to oral formulation of an antipsychotic agent is often required during the long-term management of schizophrenia . This multicenter trial evaluates the IM/oral sequential administration of ziprasidone in agitated subjects with an exacerbation of schizophrenia . METHODS Adult patients requiring IM therapy for schizophrenic symptoms were assigned to IM ziprasidone 10 mg for 3 days , followed by oral ziprasidone ( initial dose : 80 mg/day ) for 8 weeks . The primary efficacy outcomes were the change in the total PANSS and in the CGI-S scores vs. baseline values . RESULTS In total , 150 patients were included in the study . A decline in the PANSS and CGI-S scores was observed throughout the study ( p ziprasidone is an effective and well tolerated therapeutic option in the management of acute exacerbations of schizophrenia in agitated patients", "In a double-blind clinical study , 27 acutely agitated patients were treated with an intramuscular injection of 5 mg of droperidol or 5 mg of haloperidol from identical appearing vials . At 30 minutes following treatment , 81 % of the patients treated with haloperidol but only 36 % treated with droperidol required a second injection ( p less than .05 ) . Thus , droperidol , a safe butyrophenone neuroleptic , appears to be a drug of choice for rapid and reliable control of acute agitation", "OBJECTIVE This study was a comparative investigation of the clinical efficacy and safety of intramuscular ( IM ) olanzapine , IM haloperidol , and IM levomepromazine in acute agitated patients with schizophrenia . METHODS The subjects were 122 in patients . Their clinical symptoms were assessed using Positive and Negative Syndrome Scale Excited Component ( PANSS-EC ) , PANSS , and Agitation-Calmness Evaluation Scale , and their safety were assessed using the Abnormal Involuntary Movement Scale , Barnes Akathisia Rating Scale ( BARS ) , and Drug-induced Extrapyramidal Symptoms Scale ( DIEPSS ) . RESULTS The mean changes from baseline on the PANSS-EC , Agitation-Calmness Evaluation Scale , Abnormal Involuntary Movement Scale , BARS , and DIEPSS scores were significantly better in both IM olanzapine and IM levomepromazine than in IM haloperidol . Of these , the mean changes from baseline on the BARS and DIEPSS scores were significantly better in IM olanzapine than in IM levomepromazine . The mean change from baseline on the PANSS positive score was significantly better in both IM olanzapine and IM haloperidol than in IM levomepromazine . CONCLUSIONS The results of this study suggest the possibility that the anti-agitation effects of IM olanzapine and IM levomepromazine are more rapid than those of IM haloperidol . No worsening of EPS was observed . Our results also suggest that compared with IM levomepromazine , IM olanzapine is safer and affords greater improvement in symptoms", "OBJECTIVE The authors conducted a r and omized , placebo-controlled study of nicotine replacement therapy for the reduction of agitation and aggression in smokers with schizophrenia . METHOD Participants were 40 smokers 18 - 65 years of age admitted to a psychiatric emergency service with a diagnosis of schizophrenia confirmed by the Mini International Neuropsychiatric Interview . Patients were screened for agitation with the excited component subscale of the Positive and Negative Syndrome Scale ( PANSS ) and for nicotine dependence with the Fagerström Test for Nicotine Dependence . A score of at least 14 on the PANSS excited component subscale and at least 6 on the Fagerström test were required for study eligibility . Participants in the nicotine replacement group received a 21-mg nicotine transdermal patch , and those in the placebo group were treated with a placebo patch . Participants received usual care with antipsychotics . The Agitated Behavior Scale and other agitation measures were administered at baseline and again at 4 and 24 hours . RESULTS At baseline , participants were at least moderately agitated , and 28 % reported aggressive behavior in the previous week . The mean Agitated Behavior Scale score for the nicotine replacement group was 33 % lower at 4 hours and 23 % lower at 24 hours than for the placebo group . Participants with lower levels of nicotine dependence responded better than those with higher levels of dependence . CONCLUSIONS The drug-placebo difference in this study was similar to that obtained in trials of parenteral antipsychotics in similar population s. This finding suggests that in patients with schizophrenia , smoking status should be included in the assessment of agitation and nicotine replacement included in the treatment of those who are smokers" ]

[ "Study Design From a r and om population sample , those experiencing frequent headaches were identified . They were examined to determine how many fulfilled the 1990 international Headache Society classification criteria for cervicogenic headache . Objective To estimate the prevalence of cervicogenic headache in the general population and in the group experiencing frequent headaches . Summary of Background Data Only with the publication of the 1990 headache classification criteria did a generally accepted clinical definition of cervicogenic headache emerge . The prevaience of this form of headache has been estimated only in two highly selected in-clinic patient population s. No data exist regading the prevalence in representative unselected population s. Methods . A short question naire on headaches was mailed to 826 r and omly selected residents of a midsized Danish town . A group of 57 individuale in the age range 20–59 years who reported having headache episodes on 5 or more days in the previous month were identified . Forty-five of the 57 were eventually interviewed and examined with respect to the IHS criteria for cervicogenic headache ( the radiological criteria were omitted on ethical grounds ) . Results Of the 45 persons examined , eight fulfilled the diagnostic criteria for cervicogenic headache , equivalent to a prevalence in the headache group of 17.8 % ( 95 % confidence interval = 8%-32 % ) . Conclusions Cervicogenic headache appears to be a relatively common form of headache , similar to migraine in prevaience", "OBJECTIVE This article evaluates reliability and diagnostic validity of the cervical flexion-rotation test ( FRT ) to discriminate subjects with headache because of C1/2 dysfunction . In addition , this study evaluates agreement between experienced and inexperienced examiners . METHODS These were 2 single blind comparative measurement study design s. In study 1 , 2 experienced blinded examiners evaluated the FRT in 10 asymptomatic controls , 20 subjects with cervicogenic headache ( CeH ) where C1/2 was the primary dysfunctional level , and 10 subjects with CeH but without C1/2 as the primary dysfunctional level . In study 2 , 2 inexperienced and 1 experienced blinded examiners evaluated the FRT in 12 subjects with CeH and 12 asymptomatic controls . Examiners were required to state whether the FRT was positive and also to determine range of rotation using a goniometer . An analysis of variance with planned orthogonal comparison , single measure intraclass correlation coefficient ( 2,1 ) , and Bl and -Altman plot were used to analyze FRT range of rotation between the examiners . Sensitivity , specificity , and examiner agreement for test interpretation were analyzed using cross tabulation and kappa . RESULTS In study 1 , sensitivity and specificity of the FRT was 90 % and 88 % with 92 % agreement for experienced examiners ( P Overall diagnostic accuracy was 89 % ( P FRT mobility was significantly greater than for experienced examiners , but sensitivity , specificity , agreement , and kappa values were all within clinical ly acceptable levels . CONCLUSIONS The FRT can be used accurately and reliably by inexperienced examiners and may be a useful aid in CeH evaluation", "A single blind , age and gender matched , comparative measurement study was design ed to assess active range of cervical motion and passive range of rotation in cervical flexion in asymptomatic and cervicogenic headache subjects . Both procedures are commonly used in clinical practice to evaluate patients with cervicogenic headache . We studied 20 women and eight men with side dominant cervicogenic headache ( mean age 43.3 years ) matched with 28 asymptomatic subjects . Two experienced manipulative therapists , who were blind to each other 's measurement , noted active ranges of cervical motion and passive cervical rotation performed in the flexion-rotation test using the Cervical Range of Motion Device . Headache severity was assessed by a question naire . Additionally , one therapist prior to neck motion assessment determined the dominant symptomatic cervical motion segment . Active cervical motion in each direction was identical between the cervicogenic and control groups . In contrast , average rotation in flexion was 44 degrees to each side in the asymptomatic group and 28 degrees towards the headache side in the symptomatic group . C1 - 2 was deemed to be the dominant segmental level of headache origin in 24 of 28 subjects . In those 24 subjects range of rotation during the flexion-rotation test was inversely correlated to headache severity", "Persistent intermittent headache is a common disorder and is often accompanied by neck aching or stiffness , which could infer a cervical contribution to headache . However , the incidence of cervicogenic headache is estimated to be 14 - 18 % of all chronic headaches , highlighting the need for clear criterion of cervical musculoskeletal impairment to identify cervicogenic headache sufferers who may benefit from treatments such as manual therapy . This study examined the presence of cervical musculoskeletal impairment in 77 subjects , 27 with cervicogenic headache , 25 with migraine with aura and 25 control subjects . Assessment s included a photographic measure of posture , range of movement , cervical manual examination , pressure pain thresholds , muscle length , performance in the cranio-cervical flexion test and cervical kinaesthetic sense . The results indicated that when compared to the migraine with aura and control groups who scored similarly in the tests , the cervicogenic headache group had less range of cervical flexion/extension ( P=0.048 ) and significantly higher incidences of painful upper cervical joint dysfunction assessed by manual examination ( all P muscle tightness ( P Sternocleidomastoid normalized EMG values were higher in the latter three stages of the cranio-cervical flexion test although they failed to reach significance . There were no between group differences for other measures . A discriminant analysis revealed that manual examination could discriminate the cervicogenic headache group from the other subjects ( migraine with aura and control subjects combined ) with an 80 % sensitivity", "Purpose : Dysfunction of cervical and shoulder girdle muscles as reason of cervicogenic headache ( CEH ) was reinvestigated with clinical and neurophysiological studies . Methods : Forty office workers were r and omized into two groups to verify efficiency of supervised kinesiotherapy ( N = 20 ) aim ed with improvement of muscle ’s activity and headache symptoms releasing . Headache intensity was evaluated with visual analog scale ( VAS ) , range of cervical movement ( ROM ) with goniometer , trigger points ( TrPs ) incidence with palpation and muscle ’s strength with Lovett ’s scale . Reaction of patients for muscle ’s elongation was also evaluated . Surface electromyographical recordings were bilaterally analyzed at rest ( rEMG ) and during maximal contraction ( mcEMG ) . Results : Deficits of cervical flexion and muscles strength were found in all patients . TrPs occurred predominantly in painful trapezius muscle . Incidence of trigger points coexisted with intensity of CEH . Results indicated on muscles dysfunction which improved only after supervised therapy . Positive correlations between increase in rEMG amplitudes and high VAS scores , high-amplitude rEMG recordings incidence and increased number of TrPs were found . Negative correlation was detected between amplitude in mcEMG and amplitude of rEMG recordings . Conclusions : Dysfunction of trapezius muscle was most responsible for CEH etiology . Proposed algorithm of kinesiotherapy was effective as complementary method of the CEH patients treatment" ]

[ "INTRODUCTION Erectile dysfunction ( ED ) and lower urinary tract symptoms suggestive of benign prostatic hyperplasia ( LUTS/BPH ) are common in aging males and frequently occur together . Tadalafil has demonstrated efficacy in treating both conditions . AIM The study aims to evaluate the efficacy and safety of tadalafil 5 mg once daily vs. placebo over 12 weeks in treating both LUTS/BPH and ED in sexually active men . We also assessed relationships of baseline disease severity and prostate specific antigen ( PSA ) to outcomes . METHODS Data were pooled from four multinational , r and omized studies of men ≥45 years with LUTS/BPH , with analyses restricted to sexually active men with ED . R and omization ( baseline ) followed a 4-week placebo run-in ; changes from baseline were assessed vs. placebo using analysis of covariance . MAIN OUTCOME MEASURES International Prostate Symptom Score ( IPSS ) , IPSS subscores , Quality -of-Life Index ( IPSS-QoL ) , BPH Impact Index ( BII ) , and International Index of Erectile Function-Erectile Function ( IIEF-EF ) Domain score were used in this study . RESULTS Tadalafil ( N = 505 ) significantly improved total IPSS vs. placebo ( N = 521 ) ; mean changes from baseline were -6.0 and -3.6 , respectively ( P Improvements in IIEF-EF Domain score ( tadalafil , 6.4 ; placebo , 1.4 ) were also significant vs. placebo , as were the IPSS storage and voiding subscores , IPSS-QoL , and BII ( all P of baseline ED severity or PSA category on IPSS response was observed ( interaction P values , 0.463 and 0.149 , respectively ) . Similarly , improvement in IIEF-EF Domain score was not significantly impacted by baseline LUTS/BPH severity or PSA category ( interaction P values , 0.926 and 0.230 , respectively ) . Improvements in IPSS and IIEF-EF Domain score during treatment were weakly correlated ( r = -0.229 ) . Treatment-emergent adverse events were consistent with previous reports . CONCLUSIONS Tadalafil was efficacious and well tolerated in treating ED and LUTS/BPH in sexually active men with both conditions . Improvements in both conditions were significant regardless of baseline severity . Improvements in the total IPSS and the IIEF-EF Domain score were weakly correlated", "PURPOSE We assessed urodynamic changes after vardenafil administration in spinal cord injured male patients on oxybutynin treatment . MATERIAL S AND METHODS We performed a single center , r and omized , double-blind , placebo controlled trial in 25 patients with spinal cord injury who had erectile dysfunction and micturition disorders . A baseline urodynamic test was performed as well as a second urodynamic test 1 to 3 hours after the administration of 20 mg vardenafil and placebo in 15 and 10 cases , respectively . In all patients st and ard oral oxybutynin administration was not discontinued . Statistical assessment included the 3 urodynamic parameters maximum detrusor pressure during voiding , maximum cystometric capacity and detrusor overactivity volume . RESULTS Placebo administration did not affect urodynamic parameters . After vardenafil administration maximum detrusor pressure was significantly decreased ( 59.3 vs 52.1 cm H(2)O , p maximum cystometric capacity considerably improved ( 233.5 vs 272 ml , p detrusor overactivity volume ( 174 vs 218 ml , p 7 patients with American Spinal Injury Association classification A and spinal cord injury above T6 we observed the most significant improvement in the evaluated urodynamic items , including maximum detrusor pressure 57 vs 52 cm H(2)O ( p = 0.039 ) , maximum cystometric capacity 253 vs 296 ml ( p = 0.004 ) and detrusor overactivity volume 177 vs 229 ml ( p = 0.003 ) . CONCLUSIONS This trial demonstrates that in spinal cord injured patients a single 20 mg vardenafil administration achieved a significant decrease in maximum detrusor pressure , an improvement in maximum cystometric capacity and a remarkable increase in detrusor overactivity volume value", "INTRODUCTION Lower urinary tract symptoms ( LUTS ) associated with benign prostatic hyperplasia ( BPH ) and erectile dysfunction are common disorders of advancing age . AIM To evaluate the efficacy and safety of tamsulosin and tadalafil in patients with LUTS due to BPH . METHODS In this prospect i ve r and omized study , 133 men complaining of LUTS due to BPH were included . Forty-five patients received tamsulosin 0.4 mg/day alone ( Group A ) , 44 patients received tadalafil 10 mg/day ( Group B ) , and combination therapy ( tamsulosin and tadalafil both ) was instituted in 44 patients ( Group C ) . After a 2-week medication free run-in period , they were evaluated for International Prostatic Symptom Score ( IPSS ) , International Index of Erectile Function score ( IIEF5 ) , quality of life ( IPSS QoL ) , maximum urinary flow rate ( Qmax ) , post-void residual urine ( PVR ) volume , and safety parameters before and at 3 months of treatment . MAIN OUTCOME MEASURES There were primary ( IPSS , IPSS QoL index , Qmax , and PVR ) and secondary ( erectile function [ EF ] domain scores from IIEF5 ) efficacy end points . Safety assessment included laboratory tests and patient 's reporting of adverse event . RESULTS A significant improvement in IPSS score was observed in all the 3 groups A , B , and C ( -50.90 % , P IIEF5 score increased significantly in these three groups ( + 39.28 % , P increase in Qmax and decrease in PVR were also observed ( 33.99 % , P QoL scores improved significantly ( -73.35 % , P P , respectively ) . Side effects were dyspepsia , heartburn , headache , flushing , myalgia , and backache . Adverse effect dropout was 3.7 % . No participant experienced any severe or serious adverse events . CONCLUSIONS In patients with LUTS due to BPH , tamsulosin and tadalafil alone or in combination cause a significant improvement in patients with LUTS . Their EF also improves with these medications . The improvement is better with combination therapy compared with single agent alone", "PURPOSE Tadalafil significantly improves lower urinary tract symptoms suggestive of benign prostatic hyperplasia . We post hoc characterized changes in the maximum urinary flow rate using integrated data from 4 international , placebo controlled studies of tadalafil once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia . MATERIAL S AND METHODS After a 4-week placebo lead-in period 1,500 men were r and omized to tadalafil 5 mg or placebo for 12 weeks . Data were analyzed using ANCOVA . Maximum urinary flow rate values were rank transformed for analysis . RESULTS Baseline maximum urinary flow rate data were available on 1,371 men with a mean age of 63.1 years and end point data were available on 1,197 . Tadalafil 5 mg significantly increased maximum urinary flow vs placebo ( median 1.1 vs 0.4 ml per second , p = 0.003 ) . At a baseline voided volume of 125 to less than 250 ml the median change in the maximum urinary flow rate was 0.9 and 1.2 ml per second ( p = 0.142 ) in 731 patients , at a baseline of 250 to 450 ml the change was -0.3 and 0.7 ml per second ( p = 0.011 ) in 428 , and at a baseline of greater than 450 ml the change was -0.2 and 2.0 ml per second ( p = 0.186 ) in 38 for placebo and tadalafil , respectively . The difference was 0.3 , 1.0 and 2.2 ml per second , respectively . At a baseline maximum urinary flow rate of greater than 15 ml per second in 128 patients the median flow rate change was -2.1 and -0.8 ml per second ( p = 0.246 ) , at a maximum of 10 to 15 ml per second in 522 the change was 0.2 and 0.8 ml per second ( p = 0.044 ) , and at a maximum of less than 10 ml per second in 547 the change was 1.2 and 1.8 ml per second ( p = 0.189 ) for placebo and tadalafil , respectively . Tadalafil improved I-PSS ( International Prostate Symptom Score ) voiding subscores significantly vs placebo across all baseline maximum urinary flow subgroups ( each p median maximum urinary flow rate improvement for tadalafil vs placebo . The numerical difference in the maximum urinary flow change from baseline between tadalafil and placebo increased with increased voided volume ", "PURPOSE Tadalafil has regulatory approval for the treatment of men with signs/symptoms of benign prostatic hyperplasia with and without erectile dysfunction . We assessed whether the effects of treatment with tadalafil for lower urinary tract symptoms/benign prostatic hyperplasia are independent of improvements in erectile dysfunction . MATERIAL S AND METHODS Four separate analyses used integrated data from 4 r and omized , double-blind , placebo controlled studies in men with lower urinary tract symptoms/benign prostatic hyperplasia with and without erectile dysfunction to test whether total I-PSS ( International Prostate Symptom Score ) improvement was due to improvement in IIEF-EF ( International Index of Erectile Function-Erectile Function domain score ) . Unidirectional and bidirectional path analysis models determined direct and indirect treatment effects mediated by improvements in lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction symptoms . RESULTS A total of 1,496 men , of whom 77 % had erectile dysfunction , received at least 1 dose of tadalafil 5 mg once daily or placebo . The placebo adjusted treatment effect for men with erectile dysfunction was represented by a mean decrease of -2.3 ( p total I-PSS vs -2.2 ( p = 0.0007 ) for men without erectile dysfunction . The correlation between change from baseline in total I-PSS and IIEF-EF was weak ( r(2 ) = 0.08 , p total I-PSS score improvement ( 2.25 ) was derived from a direct treatment effect of 1.57 ( 70 % , p total I-PSS improvement was largely attributed to direct ( 92.5 % , p IIEF-EF improvement . CONCLUSIONS Regardless of the analytical approach , self-reported erectile dysfunction status did not appreciably influence tadalafil treatment response in men with lower urinary tract symptoms/benign prostatic hyperplasia , supporting the dual action of tadalafil on lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction", "BACKGROUND Metabolic syndrome ( MetS ) and benign prostate hyperplasia (BPH)/low urinary tract symptoms ( LUTS ) are often comorbid . Chronic inflammation is one of the putative links between these diseases . Phosphodiesterase type 5 inhibitors ( PDE5i ) are recognized as an effective treatment of BPH-related LUTS . One proposed mechanism of action of PDE5 is the inhibition of intraprostatic inflammation . In this study we investigate whether PDE5i could blunt inflammation in the human prostate . METHODS Evaluation of the effect of tadalafil and vardenafil on secretion of interleukin 8 ( IL-8 , a surrogate marker of prostate inflammation ) by human myofibroblast prostatic cells ( hBPH ) exposed to different inflammatory stimuli . We preliminary evaluate histological features of prostatic inflammatory infiltrates in BPH patients enrolled in a r and omized , double bind , placebo controlled study aim ed at investigating the efficacy of vardenafil ( 10 mg/day , for 12 weeks ) on BPH/LUTS . RESULTS In vitro treatment with tadalafil or vardenafil on hBPH reduced IL-8 secretion induced by either TNFα or metabolic factors , including oxidized low-density lipoprotein , oxLDL , to the same extent as a PDE5-insensitive PKG agonist Sp-8-Br-PET-cGMP . These effects were reverted by the PKG inhibitor KT5823 , suggesting a cGMP/PKG-dependency . Treatment with tadalafil or vardenafil significantly suppressed oxLDL receptor ( LOX-1 ) expression . Histological evaluation of anti-CD45 staining ( CD45 score ) in prostatectomy specimens of BPH patients showed a positive association with MetS severity . Reduced HDL-cholesterol and elevated triglycerides were the only MetS factors significantly associated with CD45 score . In the MetS cohort there was a significant lower CD45 score in the vardenafil-arm versus the placebo-one", "Purpose The phosphodiesterase type 5 inhibitor tadalafil is approved for the treatment of signs and symptoms of benign prostatic hyperplasia ( BPH ) . While tadalafil significantly improves overall lower urinary tract symptoms suggestive of BPH ( LUTS/BPH ) , improvements in nocturia were not significant in individual studies . We therefore sought to further assess nocturia based on data integrated from four tadalafil registration al studies . Methods Data were integrated from four r and omized , placebo-controlled , double-blind , 12-week registration al studies of tadalafil for LUTS/BPH . Nocturia was assessed as nighttime voiding frequency using the International Prostate Symptom Score question 7 ( IPSS Q7 ) . Efficacy results were analyzed using analysis of covariance . Results For the tadalafil 5 mg once daily ( N = 752 ) and placebo ( N = 748 ) groups , baseline characteristics were well balanced , and the overall severity of nocturia per mean IPSS Q7 was 2.3 ± 1.2 . The mean treatment change was −0.4 with placebo and −0.5 with tadalafil ; the least-squares mean ( st and ard error ) treatment difference was −0.2 ( 0.05 ) , p = 0.002 . For patients receiving placebo and tadalafil , respectively , the proportion with improved nocturnal frequency was 41.3 and 47.5 % , with no change was 44.8 and 41.0 % , and with worsening was 13.9 and 11.5 % . Conclusions A statistically significant improvement in nocturnal frequency was seen with tadalafil over placebo ; however , the treatment difference was small and not considered clinical ly meaningful . Further studies using voiding diaries and excluding patients with nocturnal polyuria would be needed to more precisely estimate the impact of tadalafil on nocturia associated with LUTS/BPH", "OBJECTIVE To assess the efficacy and safety of tadalafil , a phosphodiesterase 5 ( PDE5 ) inhibitor efficacious for erectile dysfunction and lower urinary tract symptoms suggestive of benign prostatic hyperplasia ( LUTS/BPH ) , in population subgroups , using pooled data from 4 international , r and omized , placebo-controlled studies in men with LUTS/BPH . METHODS The safety data base included 1500 men r and omized to tadalafil 5 mg once daily or placebo for 12 weeks . Changes in total International Prostate Symptom Score ( IPSS ) , IPSS- quality of life index , and BPH impact index were examined overall , and changes in IPSS or adverse events ( AEs ) were examined across subgroups of interest . Treatment-group differences were assessed using analysis of covariance . RESULTS Results of pooled data confirmed that tadalafil ( N = 752 ) result ed in significant improvements from baseline vs placebo ( N = 746 ) in IPSS ( mean difference -2.3 ; P in BPH impact index and IPSS- quality of life index ( both P IPSS improvements were significant regardless of baseline LUTS severity ( IPSS 65 years ) , recent previous use of α-blockers or PDE5 inhibitors , total testosterone level ( prostate-specific antigen predicted prostate volume ( 65 years ) , previous PDE5 inhibitor use , and the presence or absence of pre-existing diabetes , hypertension , or cardiovascular disease ( including hypertension ) , but somewhat higher for recent previous α-blocker use . CONCLUSION In these pooled data analyses , tadalafil 5 mg improved LUTS/BPH across subgroups of age , LUTS severity , testosterone levels , and prostate volume . Rates of AEs were similar across the subgroups assessed", "INTRODUCTION Tadalafil , a long-acting phosphodiesterase type 5 inhibitor , is approved for treating signs and symptoms of benign prostatic hyperplasia ( BPH ) and erectile dysfunction ( ED ) ; tamsulosin , an alpha-blocker , is approved for treating signs and symptoms of BPH . AIM To determine the effects of tadalafil or tamsulosin on sexual function , including ejaculation and orgasm , satisfaction , and erectile function , in sexually active men with ED and lower urinary tract symptoms suggestive of BPH ( LUTS/BPH ) . METHODS A r and omized , double-blind , placebo-controlled study of tadalafil 5 mg once daily for 12 weeks in men with LUTS/BPH ; tamsulosin 0.4 mg once daily was an active control . MAIN OUTCOME MEASURES The International Index of Erectile Function ( IIEF ) question naire was administered at baseline and 4 , 8 , and 12 weeks . Analysis of orgasm and ejaculation was post hoc based on the IIEF-Orgasmic Function ( OF ) domain ( IIEF-Q9 [ ejaculatory frequency ] and Q10 [ orgasmic frequency ] ) . Other measures included IIEF-Intercourse Satisfaction ( IS ) , Overall Satisfaction ( OS ) , and Erectile Function ( EF ) domains . Changes from baseline to 12 weeks ( or last observation ) vs. placebo were analyzed using analysis of covariance . Higher IIEF scores indicate better functioning . RESULTS Of 511 study participants , 310 ( 60.7 % ) had ED and were sexually active . The IIEF-OF increased significantly through 12 weeks with tadalafil vs. placebo ( P = 0.048 ) , as did IIEF-Q9 ( P = 0.045 ) but not IIEF-Q10 ( P = 0.100 ) . Compared with placebo , IIEF-OF , Q9 , and Q10 decreased significantly with tamsulosin ( all P IIEF-IS and OS increased significantly at end point with tadalafil ( both P OS decreased significantly ( P = 0.009 ) . The IIEF-EF domain increased significantly vs. placebo with tadalafil ( P Tadalafil 5 mg once daily significantly improved ejaculation and orgasm , intercourse and overall satisfaction , and erectile function . Men receiving tamsulosin 0.4 mg once daily experienced a decrease in both ejaculatory/orgasmic frequency and overall satisfaction vs. placebo , with no significant effect on erectile function", "INTRODUCTION Tadalafil ( TAD ) 5 mg coadministered with finasteride ( FIN ) 5 mg significantly improves lower urinary tract symptoms ( LUTS ) in men with benign prostatic hyperplasia ( BPH ) and prostatic enlargement . However , its effects on erectile/sexual function have yet to be fully described . AIM Assess the effects of TAD/FIN coadministration ( compared with placebo [PBO]/FIN ) on erectile and sexual function in sexually active men with LUTS and prostatic enlargement secondary to BPH with or without baseline comorbid erectile dysfunction ( ED ) . METHODS A r and omized , double-blind , PBO-controlled study of 695 men ( 610 sexually active ; 450 with baseline ED ; 404 sexually active with baseline ED ) conducted at 70 sites in 13 countries . TAD 5 mg or PBO once daily coadministered with FIN 5 mg once daily for 26 weeks . MAIN OUTCOME MEASURES International Index of Erectile Function ( IIEF ) domain and single-item scores ; proportions of patients who demonstrated minimal clinical ly important differences ( MCIDs ) in IIEF-Erectile Function domain scores ( IIEF-EF ; MCID defined as ≥4-point improvement ) ; and sexual dysfunction adverse events ( AEs ) . RESULTS Compared with PBO/FIN , TAD/FIN result ed in improvements for all IIEF domain and single-item scores assessed among patients with baseline ED ( P ≤ 0.002 for all measures ) and among patients without baseline ED ( P ≤ 0.041 for all measures ) . Compared with PBO/FIN , significantly larger percentages of sexually active men with baseline ED treated with TAD/FIN achieved an IIEF-EF MCID after 4 , 12 , and 26 weeks of therapy ( P TAD/FIN and PBO/FIN at all 3 three postbaseline timepoints ) . The incidence of sexual AEs was low : five TAD/FIN patients and seven PBO/FIN patients reported sexual AEs , including ED , decreased/lost libido , and ejaculation disorders . CONCLUSIONS TAD/FIN coadministration for the treatment of men with LUTS and prostatic enlargement secondary to BPH concurrently leads to statistically significant improvements in erectile/sexual function and is well-tolerated , regardless of the presence/absence of ED at treatment initiation", "OBJECTIVE To assess effects of tadalafil vs placebo on prostatic blood flow measured by transrectal ultrasonography in men aged ≥45 years with moderate-to-severe benign prostatic hyperplasia-lower urinary tract symptoms . METHODS After screening and washout , patients were r and omized to placebo ( n = 50 ) or tadalafil 5 mg ( n = 47 ) once daily for 8 weeks . Transrectal ultrasonography was performed at baseline , 4 , and 8 weeks . The primary efficacy measure was the prostate transition zone ( TZ ) resistive index ( RI ) . Secondary efficacy measures were RI in the peripheral zone and bladder neck , color pixel intensity ( CPI ) , and color pixel density ( CPD ) in all 3 regions . Outcomes were assessed using mixed-model repeated- measures analyses . RESULTS The overall treatment effect ( tadalafil vs placebo ) for the change from baseline through week 8 in prostate TZ RI was not statistically significant ( least squares mean change : placebo , -0.01 ; tadalafil , 0.00 ; P = .118 ) , nor was the change from baseline in prostate TZ CPI ( P = .564 ) or CPD ( P = .592 ) . Results were similar for all flow measures in prostate peripheral zone and bladder neck . The adverse event profile was consistent with previous studies with no new safety findings . CONCLUSION Tadalafil for 8 weeks in men with BPH-LUTS did not result in detectable decreases in arterial RI or increases in CPI or CPD in the prostate or bladder neck . Detection of changes may not be possible because of already low baseline RI , insufficient sensitivity of techniques used , or may have been confounded by method ologic variability across sites . Alternatively , other possible mechanisms not assessed in this study may be more prominently involved" ]

[ "CONTEXT Despite evidence of efficacy of antihypertensive agents in treating hypertensive patients , safety and efficacy of antihypertensive agents for coronary artery disease ( CAD ) have been discerned only from subgroup analyses in large trials . OBJECTIVE To compare mortality and morbidity outcomes in patients with hypertension and CAD treated with a calcium antagonist strategy ( CAS ) or a non-calcium antagonist strategy ( NCAS ) . DESIGN , SETTING , AND PARTICIPANTS R and omized , open label , blinded end point study of 22 576 hypertensive CAD patients aged 50 years or older , which was conducted September 1997 to February 2003 at 862 sites in 14 countries . INTERVENTIONS Patients were r and omly assigned to either CAS ( verapamil sustained release ) or NCAS ( atenolol ) . Strategies specified dose and additional drug regimens . Tr and olapril and /or hydrochlorothiazide was administered to achieve blood pressure goals according to guidelines from the sixth report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) of less than 140 mm Hg ( systolic ) and less than 90 mm Hg ( diastolic ) ; and less than 130 mm Hg ( systolic ) and less than 85 mm Hg ( diastolic ) if diabetes or renal impairment was present . Tr and olapril was also recommended for patients with heart failure , diabetes , or renal impairment . MAIN OUTCOME MEASURES Primary : first occurrence of death ( all cause ) , nonfatal myocardial infa rct ion , or nonfatal stroke ; other : cardiovascular death , angina , adverse experiences , hospitalizations , and blood pressure control at 24 months . RESULTS At 24 months , in the CAS group , 6391 patients ( 81.5 % ) were taking verapamil sustained release ; 4934 ( 62.9 % ) were taking tr and olapril ; and 3430 ( 43.7 % ) were taking hydrochlorothiazide . In the NCAS group , 6083 patients ( 77.5 % ) were taking atenolol ; 4733 ( 60.3 % ) were taking hydrochlorothiazide ; and 4113 ( 52.4 % ) were taking tr and olapril . After a follow-up of 61 835 patient-years ( mean , 2.7 years per patient ) , 2269 patients had a primary outcome event with no statistically significant difference between treatment strategies ( 9.93 % in CAS and 10.17 % in NCAS ; relative risk [ RR ] , 0.98 ; 95 % confidence interval [ CI ] , 0.90 - 1.06 ) . Two-year blood pressure control was similar between groups . The JNC VI blood pressure goals were achieved by 65.0 % ( systolic ) and 88.5 % ( diastolic ) of CAS and 64.0 % ( systolic ) and 88.1 % ( diastolic ) of NCAS patients . A total of 71.7 % of CAS and 70.7 % of NCAS patients achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg . CONCLUSION The verapamil-tr and olapril-based strategy was as clinical ly effective as the atenolol-hydrochlorothiazide-based strategy in hypertensive CAD patients", "Aims Whereas product labels of beta blockers list peripheral arterial disease ( PAD ) as a contraindication , current PAD guidelines state otherwise . We aim ed to evaluate the clinical efficacy and safety of the ß1 selective blocker nebivolol in hypertensive patients with PAD . Methods and results This multicentre , prospect i ve , double-blind , active controlled , parallel-group study compared once-daily treatment with nebivolol ( Neb ) 5 mg vs. hydrochlorothiazide ( HCTZ ) 25 mg , in hypertensive patients with Fontaine stage II ( intermittent claudication ) . The primary endpoint was the initial claudication distance ( ICD ) during treadmill exercise after 24-week treatment in the per protocol population , using a noninferiority statistical approach . A total of 177 patients ( mean age was 66.3 ± 9.2 years , 76.7 % men ) were r and omized to study treatment and 127 completed the study ; the intent-to-treat ( ITT ) analysis was performed on 163 patients , the per protocol analysis on 127 patients . Both drugs lowered blood pressure significantly . After 24-week treatment , ICD increased in the Neb group in the ITT population by 28.3 % ( 95 % CI 15.6–41.0 ) vs. in the HCTZ group by 26.5 % ( 14.4–38.5 ) , and in the per protocol population in the Neb group by 26.4 % ( 13.4–39.4 ) vs. in the HCTZ group by 32.1 % ( 18.4–45.7 ) . Thus , noninferiority of Neb could neither be confirmed nor rejected . An increase of absolute claudication distance ( ACD , mean percentage increase after 24 weeks on Neb 15.8 ± 33.2 vs. on HCTZ 20.2 ± 46.6 ) was observed without statistical differences between groups . Ankle-brachial index ( ABI ) increased slightly in both groups . Generally , both treatments were well tolerated . Conclusion The increases in ICD , ACD and ABI with nebivolol suggest that this medication does not have negative effects on hypertensive patients with symptomatic PAD , and can be used for treatment of hypertension in these patients at high cardiovascular risk without reducing the walking ability", "In a six month placebo-controlled cross-over trial twenty patients with hypertension and peripheral arterial disease were r and omised to captopril 25 mg twice daily , atenolol 100 mg once daily , labetalol 200 mg twice daily , or pindolol 10 mg twice daily for one month . Although all treatments were equally effective at lowering blood pressure , pain-free and maximum walking distances on a treadmill were decreased by atenolol , labetalol , and pindolol , but not by captopril . Post-exercise calf blood flow availability was impaired by atenolol , labetalol , and pindolol , but not by captopril . Despite ancillary characteristics of cardioselectivity , intrinsic sympathomimetic activity , or combination with alpha-blockade , beta-blockers seem to impair the lower limb circulation in such patients , whereas captopril seems to preserve it , possibly by maintaining the collateral blood supply", "BACKGROUND Trials of beta blockers in patients undergoing non-cardiac surgery have reported conflicting results . This r and omised controlled trial , done in 190 hospitals in 23 countries , was design ed to investigate the effects of perioperative beta blockers . METHODS We r and omly assigned 8351 patients with , or at risk of , atherosclerotic disease who were undergoing non-cardiac surgery to receive extended-release metoprolol succinate ( n=4174 ) or placebo ( n=4177 ) , by a computerised r and omisation phone service . Study treatment was started 2 - 4 h before surgery and continued for 30 days . Patients , health-care providers , data collectors , and outcome adjudicators were masked to treatment allocation . The primary endpoint was a composite of cardiovascular death , non-fatal myocardial infa rct ion , and non-fatal cardiac arrest . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00182039 . FINDINGS All 8351 patients were included in analyses ; 8331 ( 99.8 % ) patients completed the 30-day follow-up . Fewer patients in the metoprolol group than in the placebo group reached the primary endpoint ( 244 [ 5.8 % ] patients in the metoprolol group vs 290 [ 6.9 % ] in the placebo group ; hazard ratio 0.84 , 95 % CI 0.70 - 0.99 ; p=0.0399 ) . Fewer patients in the metoprolol group than in the placebo group had a myocardial infa rct ion ( 176 [ 4.2 % ] vs 239 [ 5.7 % ] patients ; 0.73 , 0.60 - 0.89 ; p=0.0017 ) . However , there were more deaths in the metoprolol group than in the placebo group ( 129 [ 3.1 % ] vs 97 [ 2.3 % ] patients ; 1.33 , 1.03 - 1.74 ; p=0.0317 ) . More patients in the metoprolol group than in the placebo group had a stroke ( 41 [ 1.0 % ] vs 19 [ 0.5 % ] patients ; 2.17 , 1.26 - 3.74 ; p=0.0053 ) . INTERPRETATION Our results highlight the risk in assuming a perioperative beta-blocker regimen has benefit without substantial harm , and the importance and need for large r and omised trials in the perioperative setting . Patients are unlikely to accept the risks associated with perioperative extended-release metoprolol ", "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", "Context Few therapies substantially reduce symptoms and improve exercise performance in patients with peripheral arterial disease ( PAD ) . Contribution In this double-blind trial , investigators r and omly assigned 40 older adults without diabetes and with symptomatic PAD to receive either ramipril or placebo , 10 mg once daily for 24 weeks . Compared with placebo , ramipril increased maximum and pain-free walking time and walking speed and distance . Caution s The trial was small and involved selected patients with limited mobility and exercise tolerance . Implication s Ramipril may improve symptoms in some patients with PAD . The Editors This article has been retracted . See Notice of Retraction . Peripheral arterial disease ( PAD ) is a common disorder , with 12 % of adults older than 50 years of age having an anklebrachial index ( ABI ) that is diagnostic of PAD ( ) ( 1 ) . Approximately one third of these patients experience intermittent claudication during walking , limiting normal activities . Medical treatments to improve walking distance are limited . The angiotensin-converting enzyme ( ACE ) inhibitor ramipril reduced cardiovascular morbidity and mortality compared with placebo in patients with established atherosclerotic disease , including PAD , in the Heart Outcomes Prevention Evaluation ( HOPE ) study ( 2 ) . This effect seemed to be independent of blood pressure reduction ( 3 ) and may relate to the known benefits of ACE inhibitors on both coronary and brachial endothelial function ( 4 ) . No previous controlled studies have investigated the effect of ACE inhibitors on symptoms of intermittent claudication . Given the positive effects of ramipril in the HOPE trial and its convenient once-daily dosing formulation , we hypothesized that therapy with ramipril would improve intermittent claudication symptoms . We aim ed to examine the effect of 6-month ramipril therapy on walking distance and claudication pain in a defined group of patients with claudication due to infrainguinal PAD by using a double-blind , r and omized , placebo-controlled design . Methods This article has been retracted . See Notice of Retraction . We screened 152 patients with PAD from general practice clinics in the Melbourne , Australia , metropolitan area ( Figure 1 ) . Of them , 40 patients ( mean age , 66 years [ SD , 4 ] ) were recruited and completed the trial . All patients gave written informed consent to participate in the study . The Ethics Committee of the Alfred Hospital , Melbourne , Australia , approved the study , and we performed the study in accordance with the Declaration of Helsinki 2000 . All participants had an ABI less than 0.9 at rest in at least 1 leg ; had a history of intermittent claudication ( unilateral or bilateral ) , which was stable for 6 months ; had evidence of superficial femoral artery stenosis or occlusion on duplex ultrasonography ; had blood pressure of 160/90 mm Hg or less ; had a stable medication regimen for at least 6 months ; and had not previously been treated with ACE inhibitors . We excluded patients with limiting coronary artery disease , renal failure , history of hypertension , or type 2 diabetes mellitus . Figure 1 . Flow of patients through the study . Computer-generated numbers specified the allocation sequence . A tamper-proof r and omization process generated by the hospital research center r and omly assigned participants into blocks of 10 to receive either ramipril ( Tritace , Aventis Pharma Pty . Ltd. , Macquarie Park , Australia , 10 mg once daily for 24 weeks ) or placebo ( 10 mg once daily for 24 weeks ) in a parallel-group , double-blind design . Both investigators and patients were blinded to drug assignment . Furthermore , investigators did not have access to baseline data when they performed follow-up measurements and patients were not asked which treatment they thought they were receiving . No patient assigned to placebo crossed over to ramipril during the trial or vice versa . We advised participants to maintain all aspects of their lifestyle throughout the trial and requested them to refrain from exercise , smoking , and caffeine for 24 hours before all testing . On the morning of testing , patients rested in a supine position for 15 minutes in a quiet room before the measurements . We assessed blood pressure , ABI , walking distance , duplex ultrasounds of leg arteries , and the Walking Impairment Question naire ( WIQ ) scores before and after both interventions . We advised patients about potential side effects and requested that they report any adverse event to the study coordinator . All patients performed a treadmill exercise test at a speed of 3.2 km/h and a grade of 12 % ( 5 ) , and we recorded pain-free walking time ( time to onset of claudication pain ) and maximum walking time . In our study , all patients reached a maximal level of claudication pain that limited exercise during the grade d treadmill test . The WIQ was developed and vali date d against treadmill walking and is used to evaluate limitations in community-based walking ability ( 6 ) . The WIQ assessed walking distance , speed , and stair-climbing ability , using a weighted st and ardized formula and returning a summary score between 0 % and 100 % ( 6 , 7 ) . Statistical Analyses All analysts were blinded to treatment assignment , and an independent investigator double-checked all measurement calculations and data base entries . The study was powered to detect a 180-second change in maximum walking time with ramipril , assuming a st and ard deviation of 250 seconds ( = 0.05 [ 2-sided ] ; power , 86 % ) . We compared 24-week changes from baseline in pain-free walking time , maximum walking time , and WIQ scores between treatments by using an analysis of covariance model with terms for treatment and baseline value as the analysis end points . We log-transformed the WIQ data to achieve a normal distribution before analysis . We conducted all statistical analyses by using Stata software , version 8.2 ( Stata Corp. , College Station , Texas ) . We expressed normally distributed data as means ( SDs ) or 95 % CIs and non-normally distributed data as medians ( ranges ) . A P value less 0.05 was deemed to be significant . No data were missing for any clinical variable measured in our study . Role of the Funding Sources This work was funded by the National Health and Medical Research Council of Australia . Aventis Pharma Pty . Ltd. provided ramipril ( Tritace ) and matching placebo capsules but provided no other funding for the study or to the investigators . The funding sources had no role in the design , conduct , or reporting of the study or in the decision to su bmi t the manuscript for publication . Results This article has been retracted . See Notice of Retraction . The ramipril and placebo groups were similar in age , other cardiovascular risk factors , medication use , and PAD severity , as evidence d by clinical symptoms ( walking times ) , WIQ scores , and resting ABI ( Table ) . No patient was taking cilostazol or pentoxifylline . On duplex ultrasonography , 6 of 40 patients had a superficial femoral artery occlusion ( 2 placebo patients and 4 ramipril patients ) , and the remaining patients had stenotic disease in the superficial femoral artery . Only 25 % of patients were taking antiplatelet or lipid-lowering therapy . No adverse events were reported . Table . Baseline Characteristics AnkleBrachial Index Ramipril significantly increased ABI both at rest ( change with placebo , 0.05 mm Hg [ SD , 0.04 ] ; change with ramipril , 0.07 mm Hg [ SD , 0.08 ] ; P brachial systolic blood pressure with ramipril treatment ( 0.85 mm Hg [ SD , 1.57 ] vs. 5.05 mm Hg [ SD , 2.33 ] ; P limiting leg pressure ( 0.75 mm Hg [ SD , 1.71 ] vs. 0.15 mm Hg [ SD , 1.27 ] ; P= 0.26 ) . After exercise , both a reduction in brachial pressure ( change with placebo , 0.30 mm Hg [ SD , 2.45 ] ; change with ramipril , 6.80 mm Hg [ SD , 6.07 ] ; P limiting leg pressure ( change with placebo , 5.40 mm Hg [ SD , 7.56 ] ; change with ramipril , 7.10 mm Hg [ SD , 4.59 ] ; P increase in ABI . Treadmill Test After adjustment for the baseline pain-free walking time , mean pain-free walking time after ramipril treatment was 227 seconds ( 95 % CI , 175 seconds to 278 seconds ; P maximum walking time significantly improved over the 24-week treatment period by 451 seconds ( CI , 367 seconds to 536 seconds ; P placebo group ( change in mean walking time , 10 seconds [ SD , 9 ] [ CI , 14 seconds to 6 seconds ] ; P advanced age of participants and the fact that they all had limiting infrainguinal disease , which would probably give more reproducible treadmill data than aortoiliac disease . In addition , we asked patients to maintain all aspects of their lifestyle throughout the trial . Figure 2 . Effect of ramipril on maximum treadmill walking times . Walking Impairment Question naire Ramipril improved WIQ median distance score from 5 % ( range , 1 % to 39 % ) to 21 % ( range , 12 % to 58 % ) ( P 0.001 ) , speed score from 3 % ( range , 3 % to 39 % ) to 18 % ( range , 8 % to 50 % ) ( P stair-climbing score from 17 % ( range , 4 % to 80 % ) to 67 % ( range , 38 % to 88 % ) ( P Duplex Ultrasonography Volume flow was unaltered in the limiting leg at the stenotic site . However , ramipril significantly increased volume flow in the common femoral artery proximal to the site of stenosis in both the limiting leg ( change with placebo , 0.014 L/min [ SD , 0.022 ] ; change with ramipril , 0.017 L/min [ SD , 0.034 ] ; P= 0.008 ) and the nonlimiting leg ( change with placebo , 0.006 L/min [ SD , 0.041 ] ; change with ramipril , 0.019 L/min [ SD , 0.019 ] ; P= 0.035 ) . Discussion This article has been retracted . See Notice of Retraction . Our study shows that", "Tertatolol is a noncardioselective beta-blocker without intrinsic sympathomimetic activity . In a preliminary 3-month open study , it was shown that T was devoid of any atherogenic effect since HDL-cholesterol ( HDL-C ) and apoprotein levels did not change for 3 months of therapy . To investigate the long-term effects of tertatolol on the lipid profile and its safety in hypertensive patients with peripheral arterial disease ( PAD ) , a 9-month , r and omized , double-blind , parallel group study was carried out in 40 patients . Tertatolol 5 mg once daily was compared with metoprolol 200 mg once daily . If BP was not controlled after 2 months , a vasodilatator agent , dihydralazine , was added at the lowest dose required to control BP ( diastolic BP Lipoprotein fractions and apoproteins were assayed before ( M0 ) and after 2 , 6 and 9 months of therapy . At the same occasions , peripheral arterial disease ( PAD ) was evaluated on exercise tests carried out on a treadmill and on the regional blood flow measured in the ankle arteries by the Doppler technique . Four patients were not eligible for analysis . In the tertatolol group , 1 patient with a normal BP , and 2 patients who dropped out , 1 because of persistent nausea and 1 because of personal reasons . In the metoprolol group , 1 patient refused to take dihydralazine . In the 35 fully documented patients , BP control was achieved in both groups . The mean reductions in supine systolic/diastolic BP were 31.4/14.6 and 34.7/17.1 mm Hg in the tertatolol and metoprolol groups , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS", "The use of & bgr;-receptor blockers in peripheral arterial disease is controversial for their impact on vasomotor tone . The & bgr;-blocker nebivolol possesses vasodilating , endothelium-dependent , NO-releasing properties that might be beneficial in peripheral arterial disease . The aim of the study was to evaluate the effects and tolerability of nebivolol in comparison with metoprolol in these patients . A total of 128 patients with intermittent claudication and essential hypertension were included and double-blind r and omized to receive 5 mg of nebivolol ( N=65 ) or 95 mg of metoprolol ( N=63 ) once daily . End points were changes in ankle-brachial index , initial and absolute claudication distance , endothelial function assessed by flow-mediated dilatation of the brachial artery , blood pressure , and quality of life using the claudication scale question naire . End point analysis was possible in 109 patients ( 85.2 % ) . After the 48-week treatment period , ankle-brachial index and absolute claudication distance improved significantly in both patient groups ( P of initial claudication distance was found in the nebivolol group . Adjusted mean change of initial claudication distance was 33.9 % after nebivolol ( P=0.003 ) and 16.6 % after metoprolol ( P=0.12 ) treatment . Quality of life was not influenced by either treatment , and there was no relevant change in flow-mediated dilatation in patients treated with nebivolol or metoprolol ( P=0.16 ) . Both drugs were equally effective in lowering blood pressure . In conclusion , & bgr;-blocker therapy was well tolerated in patients with intermittent claudication and arterial hypertension during a treatment period of ≈1 year . In the direct comparison , there was no significant difference between nebivolol and metoprolol", "OBJECTIVES The primary objective of the International Verapamil SR/Tr and olapril Study ( INVEST ) is to compare the risk for adverse outcomes ( all-cause mortality , nonfatal myocardial infa rct ion [ MI ] or nonfatal stroke ) in hypertensive patients with coronary artery disease ( CAD ) treated with either a calcium antagonist-based or a noncalcium antagonist-based strategy . BACKGROUND Treatment recommendations for hypertension include initial therapy with a diuretic or beta-adrenergic blocking agent , for which reductions in morbidity and mortality are documented from r and omized trials but are less than expected from epidemiologic data . For this reason , recent attention has focused on calcium antagonists or angiotensin-converting enzyme inhibitors . While these agents reduce blood pressure , outcome data from large r and omized trials are lacking , but some case-control data , dominated by short-acting dihydropyridines , suggest an increased risk of cardiovascular events . These studies had method ologic limitations and did not differentiate among calcium antagonist types and formulations . Several studies differentiating among calcium antagonist types and an overview of published r and omized trials show no increased risk with verapamil and suggestion for benefit in CAD patients . METHODS A total of 27,000 CAD patients with hypertension will be r and omized at 1,500 primary care sites to receive either a calcium antagonist-based ( verapamil ) or beta-blocker/diuretic-based ( atenolol/hydrochlorothiazide ) antihypertensive care strategy . The study uses a novel , electronic \" paper-less \" system for direct on-screen data entry , r and omization and drug distribution from a mail pharmacy linked to the coordination center via the Internet . RESULTS Contract negotiations with the United States and international sites are ongoing . Patients being enrolled are predominantly elderly ( 72 % aged 60 years or older ) men ( 54 % ) , with either an abnormal coronary angiogram or prior MI ( 71 % ) . In addition to hypertension , CAD and elderly age , most patients ( 89 % ) have one or more associated conditions ( diabetes , dyslipidemia , smoking , cerebral or peripheral vascular disease , etc . ) contributing to increased risk for adverse outcome . While 26 % have diabetes , most of these are noninsulin dependent . Using the protocol strategies , target blood pressures ( according to JNC VI ) have been reached in 58 % at the fourth visit , and as expected most ( 89 % ) are requiring multiple antihypertensive drugs . CONCLUSION The design and baseline characteristics of the initial patients recruited for a prospect i ve , r and omized , international , multicenter study comparing two therapeutic strategies to control hypertension in CAD patients are described", "Ten patients with chronic intermittent claudication were included in a double-blind , r and omized cross-over study of placebo , propranolol 80 mg b.i.d . and metoprolol 100 mg b.i.d . , each given for two months . At the end of each treatment period , the patients were tested on a treadmill and the time to first claudication pain and to intolerable claudication pain was noted . There was no decrease in time to first claudication pain or to intolerable pain with either propranolol or metoprolol as compared to placebo", "Ninety patients with chronic ischemic heart disease and stage IIb peripheral arterial occlusive disease were investigated to determine the effect of celiprolol , atenolol and isosorbide dinitrate on peripheral arterial blood flow . Walking distance and the resistance index in the femoral artery were measured before and after 3 months medication and compared with the findings in controls ( 30 patients with chronic ischemic heart disease and stage IIb peripheral arterial occlusive disease ) who received placebo . Patients with peripheral arterial occlusive disease who were treated with atenolol 50 mg/day demonstrated significant decreases in both pain-free and maximal walking distance . In contrast , the walking distances in those given celiprolol 200 mg/day and those who received isosorbide dinitrate 80 mg/day did not differ from the distances in control subjects . The Doppler flow through the femoral artery , as measured by color duplex sonography , showed a significant decrease in resistance index , both in patients given celiprolol and in those given isosorbide dinitrate . In patients treated with atenolol the resistance index rose significantly . The results of this study confirm that the beta-adrenoceptor blocker celiprolol exerts a supplementary vasodilatory action resembling that of nitrates and hence can be used in patients with chronic ischemic heart disease and impaired peripheral arterial perfusion", "Background —Peripheral arterial disease ( PAD ) and diabetes are both associated with a high risk of ischemic events , but the role of intensive blood pressure control in PAD has not been established . Methods and Results —The Appropriate Blood Pressure Control in Diabetes study followed 950 subjects with type 2 diabetes for 5 years ; 480 of the subjects were normotensive ( baseline diastolic blood pressure of 80 to 89 mm Hg ) . Patients r and omized to placebo ( moderate blood pressure control ) had a mean blood pressure of 137±0.7/81±0.3 mm Hg over the last 4 years of treatment . In contrast , patients r and omized to intensive treatment with enalapril or nisoldipine had a mean 4-year blood pressure of 128±0.8/75±0.3 mm Hg ( P cardiovascular events ( 13.6 % ) on intensive treatment compared with 12 events ( 38.7 % ) on moderate treatment ( P = 0.046 ) . After adjustment for multiple cardiovascular risk factors , an inverse relationship between ankle-brachial index and cardiovascular events was observed with moderate treatment ( P = 0.009 ) , but not with intensive treatment ( P = 0.91 ) . Thus , with intensive blood pressure control , the risk of an event was not increased , even at the lowest ankle-brachial index values , and was the same as in a patient without PAD . Conclusions —In PAD patients with diabetes , intensive blood pressure lowering to a mean of 128/75 mm Hg result ed in a marked reduction in cardiovascular events ", "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 ] . )", "Hypertension is a common risk factor for peripheral arterial disease ( PAD ) . Guidelines suggest treating PAD patients to a blood pressure hypertensive patients with concomitant PAD and coronary artery disease . There were 2699 PAD patients followed for a mean of 2.7 years ( 60 970 patient-years ) . The primary outcome , all-cause death , nonfatal myocardial infa rct ion , or nonfatal stroke , occurred in 16.3 % of PAD patients versus 9.2 % without PAD ( adjusted hazard ratio : 1.26 [ 95 % CI : 1.13 to 1.40 ] ; P PAD patients treated to an average systolic blood pressure of 135 to 145 mm Hg and an average diastolic blood pressure of 60 to 90 mm Hg . PAD patients displayed a J-shape relationship with systolic blood pressure and the primary outcome , although individuals without PAD did not . PAD patients may require a different target blood pressure than those without PAD ", "In a placebo-controlled double-blind crossover trial , the effect of a 3-week course of treatment with metoprolol ( 100 - 200 mg daily ) and methyldopa ( 500 - 1000 mg daily ) on walking capacity on a treadmill with increasing work load was studied in 14 hypertensive patients with intermittent claudication . The walking capacity was not affected by the antihypertensive treatment", "Objective Claudication is a debilitating consequence of peripheral arterial disease . Evidence is accumulating to suggest that large artery stiffness may influence peripheral perfusion and walking time through effects on peripheral hemodynamics as well as microvascular structure and function . We have previously shown that the angiotensin-converting enzyme inhibitor ramipril increased systemic arterial compliance by 64 % , and increased maximum walking time by over 200 % in patients with peripheral arterial disease . In the current analysis in the same patient cohort , we hypothesized that this relationship may , in part , be causal . Methods Forty patients with peripheral arterial disease [ 66 ± 4 years ( mean ± SD ) ; n = 20 per group ] were r and omized to ramipril , 10 mg once daily , or placebo for 24 weeks in a double-blind study . Maximum walking time was recorded during a st and ard treadmill test . Indices of arterial stiffness were assessed globally by systemic arterial compliance and augmentation index and regionally via central pulse wave velocity . Results Ramipril increased maximum walking time by 243 % and improved arterial stiffness parameters by between 17 and 64 % ( all P compared with placebo ) . There were moderately strong correlations between the pre/post intervention change in maximum walking time and the change in indices of arterial stiffness ( systemic arterial compliance , r = 0.65 , P maximum walking time observed in our peripheral arterial disease population are , at least partly , a consequence of reduced arterial stiffness", "OBJECTIVES We sought to investigate the effect of cardiac medication on long-term mortality in patients with peripheral arterial disease ( PAD ) . BACKGROUND Peripheral arterial disease is associated with increased cardiovascular morbidity and mortality . Treatment guidelines recommend aggressive management of risk factors and lifestyle modifications . However , the potential benefit of cardiac medication in patients with PAD remains ill defined . METHODS In this prospect i ve observational cohort study , 2,420 consecutive patients ( age , 64 + /- 11 years , 72 % men ) with PAD ( ankle-brachial index were screened for clinical risk factors and cardiac medication . Follow-up end point was death from any cause . Propensity scores for statins , beta-blockers , aspirin , angiotensin-converting enzyme ( ACE ) inhibitors , calcium channel blockers , diuretics , nitrates , coumarins , and digoxin were calculated . Cox regression models were used to analyze the relation between cardiac medication and long-term mortality . RESULTS Medical history included diabetes mellitus in 436 patients ( 18 % ) , hypercholesterolemia in 581 ( 24 % ) , smoking in 837 ( 35 % ) , hypertension in 1,162 ( 48 % ) , coronary artery disease in 1,065 ( 44 % ) , and a history of heart failure in 214 ( 9 % ) . Mean ankle-brachial index was 0.58 ( + /-0.18 ) . During a median follow-up of eight years , 1,067 patients ( 44 % ) died . After adjustment for risk factors and propensity scores , statins ( hazard ratio [ HR ] 0.46 , 95 % confidence interval [ CI ] 0.36 to 0.58 ) , beta-blockers ( HR 0.68 , 95 % CI 0.58 to 0.80 ) , aspirins ( HR 0.72 , 95 % CI 0.61 to 0.84 ) , and ACE inhibitors ( HR 0.80 , 95 % CI 0.69 to 0.94 ) were significantly associated with a reduced risk of long-term mortality . CONCLUSIONS On the basis of this observational longitudinal study , statins , beta-blockers , aspirins , and ACE inhibitors are associated with a reduction in long-term mortality in patients with PAD", "Background Peripheral artery disease ( PAD ) is associated with high cardiovascular mortality and a poor quality of life . The AT1-receptor blocker telmisartan has been shown to have pleiotropic effects and it may also improve endothelial function . The aim of this study was to analyze the effects of telmisartan on absolute walking distance ( WD ) and endothelial function in patients with PAD . Methods In a single centre , single-blinded , prospect i ve study , 36 patients with PAD at stage Fontaine II or higher and mild to moderate arterial hypertension were treated with telmisartan 40/80 mg once daily or placebo for 12 months . Primary endpoint was the improvement of the absolute treadmill WD . Flow-mediated vasodilation ( FMD ) , carotid intima-media thickness ( IMT ) , ankle-brachial index ( ABI ) and disease-related quality of life ( DRQL ) were examined as well . Results After 12 months , maximum WD increased by 26 % in the telmisartan group ( P FMD rose by 40 % in the telmisartan group while it deteriorated in the placebo group ( P IMT and ABI were comparable in both groups at baseline and did not change considerably after 12 months . In non-diabetic patients ( 72.2 % ) , the ABI did not change in the placebo group , whereas it increased by 11 % in the telmisartan group ( P DRQL remained stable in the telmisartan group , placebo treatment was associated with a marked deterioration ( P Telmisartan improves WD and endothelial function , the ABI in non-diabetic patients and it may prevent further loss of quality of life in patients with advanced PAD", "Ramipril improves cardiovascular outcome in patients with peripheral arterial disease ; however , the precise mechanisms of benefit remain to be eluci date d. The effect of ramipril on large-artery stiffness in patients with peripheral arterial disease was examined . In addition , we determined the effect of ramiprilat on extracellular matrix from human aortic smooth muscle cell culture . Forty patients with peripheral arterial disease were r and omized to receive ramipril , 10 mg once daily or placebo for 24 weeks . Arterial stiffness was assessed globally via systemic arterial compliance and augmentation index ( carotid tonometry and Doppler velocimetry ) , and regionally via carotid – femoral pulse wave velocity . Angiotensin-converting enzyme inhibition increased arterial compliance by 0.10±0.02 mL/mm Hg , ( P reduced pulse wave velocity by 1.7±0.2 m/s ( P augmentation index by 4.1±0.3 % ( P , and systolic blood pressure by 5±1 mm Hg ( P ) . Ramipril did not reduce mean arterial pressure significantly compared with placebo ( P=0.59 ) . In cell culture , ramiprilat decreased collagen deposition by > 50 % and increased elastin and fibrillin-1 deposition by > 3- and 4-fold respectively ( histochemistry and immunohistochemistry ) . Fibrillin-1 gene expression was increased 5-fold ( real-time reverse-transcriptase polymerase chain reaction ) . Ramiprilat also reduced gene and protein ( Western ) expression of both matrix metalloproteinase (MMP)-2 and MMP-3 . In conclusion , ramipril promoted an elastogenic matrix profile that may contribute to the observed clinical reduction in large-artery stiffness and carotid pressure augmentation , which occurred independently of mean arterial blood pressure reduction in patients with peripheral arterial disease", "Beta-Adrenergic blockers have not been widely used in patients with peripheral vascular disease because these drugs have been reported to worsen the symptoms of intermittent claudication . To test this assumption we studied the effects of a beta 1-selective and a nonselective beta-adrenergic blocker on postexercise calf blood flow and symptoms of claudication in 19 patients with mild-to-moderate peripheral vascular disease . Subjects received placebo for 3 weeks , and then were r and omized to 120 mg/day propranolol or 150 mg/day metoprolol with the use of a crossover design . Blood flow in the calf was measured by strain-gauge plethysmography at rest and immediately after exercise on a bicycle ergometer at a low and a high workload . The symptoms of claudication were monitored during bicycle exercise and by patient diaries maintained between visits . Maximal exercise heart rate was reduced an equivalent amount by metoprolol ( 19 beats/min ) and propranolol ( 16 beats/min ) . Mean arterial pressure was reduced by propranolol at rest and by both drugs with exercise . Calf blood flow was not affected by either drug compared with placebo at rest or at either workload . In addition , the symptoms of claudication were not worsened by either drug . We conclude that despite evidence of beta 1-adrenergic blockade and a lowering of arterial pressure , neither beta-adrenergic blocker adversely affected the peripheral circulation", "The effect of celiprolol at a daily dosage of 300 mg ( 19 patients ) was compared with that of propranolol at a daily dosage of 120 mg ( 14 patients ) on peripheral blood flow of the calf and foot in a r and omized double-blind trial . Altogether 33 patients ( 47 extremities ) suffering from arterial occlusive disease ( stage II according to Fontaine ) and hypertension , were treated for 25 days . Blood flow was measured by strain-gauge plethysmography . Celiprolol led to a small , insignificant increase in resting blood flow of the muscle . Propranolol produced a small decrease in resting blood flow of the muscle , and a significant fall in resting blood flow of the skin of the foot . At the completion of treatment with celiprolol there was a small increase in the initial value of reactive hyperaemia of the calf . Propranolol led to a decrease in the initial , and in the maximum values of reactive hyperaemia of the calf and foot . Celiprolol and propranolol led to a comparable decrease in resting blood pressure", "METHODS The effect of 6 months ' administration of celiprolol , atenolol and isosorbide dinitrate on peripheral arterial occlusive disease ( PAOD ) , double-blind and placebo-controlled , was investigated in 56 patients with chronic ischaemic heart disease and stage IIb PAOD , using as criteria the walking distance and the change in resistance index in the femoral artery . The placebo group consisted of 14 patients with chronic ischaemic heart disease and the same stage of PAOD . RESULTS Patients on 50 mg/day atenolol showed a significant reduction in both pain-free and maximal walking range compared with the controls . In contrast , those taking 200 mg/day celiprolol and those on 80 mg/day isosorbide dinitrate demonstrated significant increases in pain-free and maximal , walking distance compared with the control group . The colour duplex sonographically measured Doppler flow through the femoral artery showed a significant decrease both in the patients taking celiprolol and in those on isosorbide dinitrate , while in those receiving atenolol the resistance index increased significantly . CONCLUSIONS The study shows that the beta-adrenoceptor blocker celiprolol also possesses a nitrate-like vasodilatory property and can be used in patients with chronic ischaemic heart disease and impaired peripheral arterial blood flow", "BACKGROUND AND PURPOSE The Systolic Hypertension in the Elderly Program ( SHEP ) demonstrated a significant reduction in stroke and coronary event rates among participants r and omly assigned to active blood pressure treatment . Selected participants were evaluated for peripheral atherosclerosis and followed up for cardiovascular events beyond the end of the SHEP trial . Antihypertensive treatment effects were evaluated based on the presence or absence of clinical or sub clinical atherosclerosis . METHODS As an ancillary study to SHEP , 190 participants at the Pittsburgh center were evaluated for peripheral atherosclerosis , defined as either an internal carotid stenosis ( by duplex scan ) or lower extremity arterial disease ( identified by ankle blood pressure ) . Participants were subsequently followed up for cardiovascular events . RESULTS Estimates of 4-year mortality rates were 4.8 % for participants with no atherosclerosis , 16.7 % for those with sub clinical atherosclerosis , and 23 % among those with clinical evidence of atherosclerosis ( P Fatal plus nonfatal cardiovascular event rates were 10.9 % , 29.8 % , and 58.3 % for the three groups , respectively ( P placebo at the beginning of SHEP had higher cardiovascular event rates than individuals assigned to active treatment ( P = .011 ) , with the most striking difference 3 or more years after the end of the SHEP trial . When this analysis was stratified by the presence or absence of detectable atherosclerosis , the absolute treatment effect was largest among those with evidence of disease . CONCLUSIONS Individuals with systolic hypertension and evidence of peripheral atherosclerosis are at high risk for cardiovascular events . Targeting this group for antihypertensive therapy would result in the prevention of a large number of cardiovascular events", "BACKGROUND Angiotensin-converting enzyme ( ACE ) inhibitors reduce mortality , myocardial infa rct ion , stroke , heart failure , need for revascularization , nephropathy , and diabetes and its complications . Although angiotensin-II receptor blockers ( ARBs ) have been less extensively evaluated , theoretically they may have \" protective \" effects similar to those of ACE inhibitors , but with better tolerability . Currently , there is uncertainty about the role of ARBs when used alone or in combination with an ACE inhibitor in high-risk population s with controlled hypertension . OBJECTIVES Primary objectives of the ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial ( ONTARGET ) are to determine if the combination of the ARB telmisartan and the ACE inhibitor ramipril is more effective than ramipril alone , and if telmisartan is at least as effective as ramipril . The Telmisartan R and omized AssessmeNt Study in aCE iNtolerant subjects with cardiovascular Disease ( TRANSCEND ) will determine if telmisartan is superior to placebo in patients who are intolerant of ACE inhibitors . The primary outcome for both trials is the composite of cardiovascular death , myocardial infa rct ion , stroke , or hospitalization for heart failure . METHOD High-risk patients with coronary , peripheral , or cerebrovascular disease or diabetes with end-organ damage are being recruited and followed for 3.5 to 5.5 years in 2 parallel , r and omized , double-blind clinical trials . PROGRESS Recruitment from 730 centers in 40 countries for ONTARGET ( n = 25,620 ) was completed in July 2003 . For TRANSCEND , 5776 patients ( out of a projected total of 6000 ) have been recruited ( by May 10 , 2004 ) . Baseline patient characteristics are comparable to the Heart Outcomes Prevention Evaluation ( HOPE ) trial , the basis of the design of the current study , confirming that patients are at high-risk", "BACKGROUND Observational studies suggest a synergistic effect of hypertension and hyperlipidaemia on the progression of atherosclerosis . The alpha-blocker doxazosin has favourable effects on plasma lipids , insulin resistance and blood pressure , while the diuretic hydrochlorothiazide ( HCTZ ) principally affects blood pressure and increases insulin resistance . METHODS A r and omised double-blind study over 36 months was performed to compare the effects of doxazosin and HCTZ on fasting lipids and on progression of peripheral atherosclerosis . Eighty males ( 45 to 70 years ) with peripheral atherosclerotic disease and increased cholesterol levels ( 5.2 - 8.0 mmol/l ) were treated for essential hypertension with either doxazosin ( n = 41 ) or HCTZ ( n = 39 ) . Main outcome measures were arterial intima-media thickness ( IMT ) of the carotid and femoral arteries and fasting lipid parameters . RESULTS In the doxazosin-treated group , significant changes were observed in the concentration of triglycerides ( -13.7 % , p HDLc ( + 25.7 % , p IDLc ( -30.1 % , P HCTZ-treated group no significant changes in plasma lipid levels were observed . On follow-up visits systolic blood pressure in the doxazosin-treated group was 6 mm higher than in the HCTZ group . Nevertheless , the groups treated with doxazosin or HCTZ showed no differential effect on IMT after three years of treatment ( p = 0.8 ) . A significant reduction of the IMT of combined carotid and femoral arterial walls was shown in both treatment groups ( p doxazosin or HCTZ result ed in a comparable change in arterial IMT after three years , in spite of differences in effect on plasma lipids . The study emphasises the importance of blood pressure control in patients with peripheral vascular disease and hypercholesterolaemia", "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 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 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", "OBJECTIVE To describe the design of the HOPE ( Heart Outcomes Prevention Evaluation ) study . DESIGN Description of the key design features of HOPE , a large , simple r and omized trial of two widely applicable treatments -- ramipril , an angiotensin-converting enzyme inhibitor ; and vitamin E , a naturally occurring antioxidant vitamin -- in the prevention of myocardial infa rct ion , stroke or cardiovascular death . SETTING Two-hundred and sixty-seven hospitals , physician offices and clinics in Canada , the United States , Mexico , Europe and South America . PATIENTS Over 9000 women and men aged 55 years and above at high risk for cardiovascular events such as myocardial infa rct ion and stroke were recruited over 18 months . INTERVENTIONS A 2X2 factorial design with ramipril and vitamin E with follow-up for up to four years . CONCLUSIONS HOPE will be one of the largest trials of two new interventions to prevent myocardial infa rct ion , stroke or cardiovascular death in high risk patients . The results of HOPE will have direct public health impact and are likely to be readily incorporated into clinical practice . Key design features of HOPE are inclusion of individuals at high risk of cardiovascular disease , inclusion of a substantial proportion of patients with diabetes ( 36 % ) and women ( 27 % ) , and detailed sub studies to provide data on mechanisms of benefit", "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", "OBJECTIVES We sought to determine predictors for adverse outcomes in hypertensive patients with coronary artery disease ( CAD ) . BACKGROUND Factors leading to adverse outcomes in hypertensive patients with CAD are poorly understood . The INternational VErapamil-tr and olapril STudy ( INVEST ) compared outcomes in hypertensive patients with CAD that were assigned r and omly to either a verapamil sustained-release (SR)- or an atenolol-based strategy for blood pressure ( BP ) control . Tr and olapril and hydrochlorothiazide were used as added agents . During follow-up ( 61,835 patient-years ) , BP control and the primary outcome ( death , nonfatal myocardial infa rct ion , and nonfatal stroke ) were not different between strategies . METHODS We investigated risk for adverse outcome associated with baseline factors , follow-up BP , and drug treatments using Cox modeling . RESULTS Previous heart failure ( adjusted hazard ratio [ HR ] 1.96 ) , as well as diabetes ( HR 1.77 ) , increased age ( HR 1.63 ) , U.S. residency ( HR 1.61 ) , renal impairment ( HR 1.50 ) , stroke/transient ischemic attack ( HR 1.43 ) , smoking ( HR 1.41 ) , myocardial infa rct ion ( HR 1.34 ) , peripheral vascular disease ( HR 1.27 ) , and revascularization ( HR 1.15 ) predicted increased risk . Follow-up systolic BP and olapril with verapamil SR ( HRs 0.78 and 0.79 ) were associated with reduced risk . CONCLUSIONS In hypertensive patients with CAD , increased risk for adverse outcomes was associated with conditions related to the severity of CAD and diminished left ventricular function . Lower follow-up BP and addition of tr and olapril to verapamil SR each were associated with reduced risk", "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", "The treatment of hypertension mainly with diuretics and beta blockers reduces cardiovascular mortality and morbidity , largely due to a decreased incidence of stroke , whereas the beneficial effects of antihypertensive therapy on the occurrence of coronary events have been less than expected from epidemiological studies . Furthermore , treated hypertensive patients still have a higher cardiovascular complication rate , compared with matched normotensives . This is particularly evident in patients with left ventricular hypertrophy ( LVH ) , a major independent risk indicator for cardiovascular disease . In addition to elevating blood pressure , angiotensin II ( A-II ) exerts an important influence on cardiac structure and function , stimulating cell proliferation and growth . Thus , to further reduce morbidity and mortality when treating hypertensive patients , it may be important to effectively block the effects of A-II . This can be achieved directly at the A-II receptor level by losartan , the first of a new class of antihypertensive agents . It therefore seems pertinent to investigate whether selective A-II receptor blockade with losartan not only lowers blood pressure but also reduces LVH more effectively than current therapy , and thus improves prognosis . The Losartan Intervention For Endpoint reduction ( LIFE ) in Hypertension study is a double-blind , prospect i ve , parallel group study design ed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality in approximately 8,300 hypertensive patients ( initial sitting diastolic blood pressure 95 to 115 mm Hg or systolic blood pressure 160 to 200 mm Hg ) with electrocardiographically documented LVH . The study , which will continue for at least 4 years and until 1,040 patients experience one primary endpoint , has been design ed with a statistical power that will detect a difference of at least 15 % between groups in the incidence of combined cardiovascular morbidity and mortality . It is also the first prospect i ve study with adequate power to link reversal of LVH to reduction in major cardiovascular events . The rationale of the study , which will involve more than 800 clinical centers in Sc and inavia , the United Kingdom , and the United States , is discussed , and the major features of its design and general organization are described . On April 30 , 1997 , when inclusion was stopped , 9,218 patients had been r and omized", "Essential hypertension is a major Public Health issue . Although the number of treated hypertensive patients has increased , only 25 % of treated patients have their blood pressure levels under control . The benefit of treating hypertension has been proven , but cardiovascular morbidity and mortality rates remain high . The ideal antihypertensive drug should not only normalize blood pressure levels , but also reduce the associated cardiovascular morbidity and mortality rates . The role of angiotensin II in systemic hypertension and its complications has been recently redefined . The potent trophic effects of angiotensin II on blood vessels and on cardiac cells have been well demonstrated , especially the role of angiotensin II in left ventricular hypertrophy , vascular hypertrophy , endothelial dysfunction , and congestive heart failure . Of all ongoing mortality and morbidity trials in systemic hypertension , VALUE ( Valsartan Antihypertensive Long-term Use Evaluation ) is the only one comparing an angiotensin II antagonist ( valsartan ) with a third-generation calcium channel blocker ( amlodipine ) . The main hypothesis of the VALUE trial is that , for an equivalent decrease in blood pressure , valsartan will be more effective than amlodipine in decreasing cardiac mortality and morbidity . VALUE is a prospect i ve , multinational , multicentre , double-blind , r and omized , active-controlled , 2-arm parallel group comparison with a response-dependent dose titration scheme . VALUE involves 14,400 patients in over 30 countries , who will be followed for 4 years or until 1450 patients experience a primary endpoint . The population to be included in VALUE consists of hypertensive men and women , aged 50 years or older , and at a relatively high risk of sustaining a cardiovascular event . The high risk profile is defined taking into account age , gender , and a list of cardiovascular risk factors and disease factors . Risk factors are cigarette smoking , hypercholesterolaemia , diabetes mellitus , uncomplicated left ventricular hypertrophy , proteinuria , and high serum creatinine . Disease factors include documented history of myocardial infa rct ion , peripheral vascular disease , stroke or transient ischaemic attack , or the presence of left ventricular hypertrophy with strain on the ECG . A unique feature of VALUE is the assessment of the predictive power of this cardiovascular risk factor scale in a large population of treated hypertensive patients . The trial started on 10 September 1997", "The Omapatrilat in Persons with Enhanced Risk of Atherosclerotic events ( OPERA ) trial is a large clinical trial of omapatrilat , a vasopeptidase inhibitor , in patients with stage 1 isolated systolic hypertension ( ISH ) . OPERA is the first study to examine whether effective antihypertensive treatment can provide survival and clinical end point benefits in older persons with this common condition . This 5-year multinational , r and omized , double-blind , parallel-group , placebo-controlled , forced-titration study will be conducted in approximately 12,600 subjects r and omized by approximately 1100 study centers worldwide over a recruitment period of approximately 2 years . The primary objective of OPERA is to determine whether treatment with once-daily omapatrilat ( target dose 40 mg ) will reduce cardiovascular ( CV ) morbidity and mortality in older ( > or = 65 years ) men and women with enhanced risk for atherosclerotic events due to stage 1 ISH plus other risk factors for which currently there is no evidence -based requirement for treatment . Blood pressure inclusion criteria are systolic blood pressure ( SBP ) 140 to 159 mm Hg ( SBP 125 to 139 mm Hg in diabetic individuals ) and diastolic blood pressure ( DBP ) The primary end point is defined as the composite of fatal/nonfatal stroke , fatal/nonfatal myocardial infa rct ion , fatal/nonfatal heart failure , and other CV mortality . Secondary end points include the individual components of the primary end point , CV mortality , and major cardiovascular end points , as well as effects on cognitive function and initiation of treatment for diabetes . Additional analyses will be conducted in men and women , in diabetic patients , in different risk classes and according to prior evidence of vascular disease", "BACKGROUND In patients with prior myocardial infa rct ion ( MI ) , beta-blockers reduce mortality by 23 % to 40 % . However , despite this favorable effect , adverse effects limit compliance to this medication . The purpose of the study was to compare a beta-blocker-based strategy with a heart rate-lowering calcium antagonists-based strategy in patients with prior MI . METHODS We evaluated 7,218 patients with prior MI enrolled in the INternational VErapamil SR-Tr and olapril ( INVEST ) sub study r and omized to verapamil-sustained release (SR)- or atenolol-based strategies . Primary outcome was time to first occurrence of death ( all-cause ) , nonfatal MI , or nonfatal stroke . Secondary outcomes included death , total MI ( fatal and nonfatal ) , and total stroke ( fatal and nonfatal ) considered separately . RESULTS During the 2.8 + /- 1.0 years of follow-up , patients assigned to the verapamil-SR-based and atenolol-based strategies had comparable blood pressure control , and the incidence of the primary outcome was equivalent . There was no difference between the 2 strategies for the outcomes of either death or total MI . However , more patients reported excellent/good well-being ( 82.3 % vs 78.0 % , P = .02 ) at 24 months with a trend toward less incidence of angina pectoris ( 12.0 % vs 14.3 % , adjusted P = .07 ) , nonfatal stroke ( 1.4 % vs 2.0 % ; P = .06 ) , and total stroke ( 2.0 % vs 2.5 % , P = .18 ) in the verapamil-SR-based strategy group . CONCLUSIONS In hypertensive patients with prior MI , a verapamil-SR-based strategy was equivalent to a beta-blocker-based strategy for blood pressure control and prevention of cardiovascular events , with greater subjective feeling of well-being and a trend toward lower incidence of angina pectoris and stroke in the verapamil-SR-based group", "The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial ( ONTARGET ) showed that the angiotensin receptor blocker telmisartan 80 mg was not inferior to the angiotensin-converting enzyme inhibitor ramipril 10 mg , and the combination no more effective than ramipril alone , in decreasing morbidity and mortality in patients with cardiovascular disease or high-risk diabetes . Although therapy targeting angiotensin II is known to decrease left ventricular ( LV ) mass and volume , the relative influence of angiotensin-converting enzyme inhibitor inhibitors and angiotensin receptor blocker , and their combination , on the heart remains unclear in this population . Magnetic resonance imaging was performed in 287 patients enrolled in ONTARGET , across 8 centers in 6 countries , at r and omization and after 2-year treatment ( 90 , 100 , and 97 patients in the ramipril , telmisartan , and combination therapy groups , respectively ) . Baseline patient characteristics showed higher frequencies of coronary artery disease , Asian ethnicity , and use of statins and beta blockers than the main ONTARGET trial . LV mass decreased in all groups ( p LV mass or volume among groups , except that LV mass index decreased more on combination versus telmisartan ( p = 0.04 ) . Key determinants of LV mass decrease were a history of hypertension ( p = 0.03 ) , baseline mass ( p in systolic blood pressure ( p end-systolic volume ( p telmisartan and ramipril had similar effects on LV mass and volume , and combination therapy was not more effective , in high-risk patients with cardiovascular disease . These results are consistent with the major outcome findings of the main ONTARGET study", "BACKGROUND It has recently been reported that the use of calcium-channel blockers for hypertension may be associated with an increased risk of cardiovascular complications . Because this issue remains controversial , we studied the incidence of such complications in patients with non-insulin-dependent diabetes mellitus and hypertension who were r and omly assigned to treatment with either the calcium-channel blocker nisoldipine or the angiotensin-converting-enzyme inhibitor enalapril as part of a larger study . METHODS The Appropriate Blood Pressure Control in Diabetes ( ABCD ) Trial is a prospect i ve , r and omized , blinded trial comparing the effects of moderate control of blood pressure ( target diastolic pressure , 80 to 89 mm Hg ) with those of intensive control of blood pressure ( diastolic pressure , 75 mm Hg ) on the incidence and progression of complications of diabetes . The study also compared nisoldipine with enalapril as a first-line antihypertensive agent in terms of the prevention and progression of complications of diabetes . In the current study , we analyzed data on a secondary end point ( the incidence of myocardial infa rct ion ) in the subgroup of patients in the ABCD Trial who had hypertension . RESULTS Analysis of the 470 patients in the trial who had hypertension ( base-line diastolic blood pressure , > or = 90 mm Hg ) showed similar control of blood pressure , blood glucose and lipid concentrations , and smoking behavior in the nisoldipine group ( 237 patients ) and the enalapril group ( 233 patients ) throughout five years of follow-up . Using a multiple logistic-regression model with adjustment for cardiac risk factors , we found that nisoldipine was associated with a higher incidence of fatal and nonfatal myocardial infa rct ions ( a total of 24 ) than enalapril ( total , 4 ) ( risk ratio , 9.5 ; 95 percent confidence interval , 2.7 to 33.8 ) . CONCLUSIONS In this population of patients with diabetes and hypertension , we found a significantly higher incidence of fatal and nonfatal myocardial infa rct ion among those assigned to therapy with the calcium-channel blocker nisoldipine than among those assigned to receive enalapril . Since our findings are based on a secondary end point , they will require confirmation", "OBJECTIVES We sought to determine whether treatment with high dose verapamil prevents restenosis in patients at high risk for reoccurrence after successful percutaneous transluminal coronary angioplasty ( PTCA ) . BACKGROUND Restenosis is the major limitation of PTCA . Calcium antagonists have demonstrated some potential as inhibitors of this process . METHODS A total of 98 patients with peripheral occlusive arterial disease ( POAD ) , stable angina pectoris , mild hypertension and at least one additional risk factor increasing the likelihood of restenosis after angioplasty were selected for this placebo-controlled , double-blind , r and omized trial . Verapamil ( 240 mg twice daily ) or placebo was taken for 6 months . Efficacy variables assessed before and after angioplasty and at 6 weeks and 6 months after PTCA included thickness of the intima/media complex degree of stenosis , interventricular septal thickness , crurobrachial pressure ratios of dorsalis pedis and posterior tibial arteries , distance to claudication and total vessel diameter . RESULTS No significant intergroup differences emerged before or immediately after PTCA . Six weeks after angioplasty , a significant thickening of the intima/media complex in the treated vascular segment of 14.3 % occurred in the placebo group versus 0 % among verapamil patients ( p intima/media thickness was 35.7 % greater in the placebo group but had decreased by 14.3 % in the verapamil group ( p reduction in septal thickness was observed in the verapamil group versus that in the placebo group ( p rate of restenosis was also significantly lower in the verapamil group ( p minor side effects were reported . CONCLUSIONS In patients with POAD at increased risk for restenosis , the administration of high dose verapamil prevented recurrent stenosis for 6 months after successful peripheral angioplasty and was well tolerated", "BACKGROUND Observational and experimental studies suggest that the amount of vitamin E ingested in food and in supplements is associated with a lower risk of coronary heart disease and atherosclerosis . METHODS We enrolled a total of 2545 women and 6996 men 55 years of age or older who were at high risk for cardiovascular events because they had cardiovascular disease or diabetes in addition to one other risk factor . These patients were r and omly assigned according to a two-by-two factorial design to receive either 400 IU of vitamin E daily from natural sources or matching placebo and either an angiotensin-converting-enzyme inhibitor ( ramipril ) or matching placebo for a mean of 4.5 years ( the results of the comparison of ramipril and placebo are reported in a companion article ) . The primary outcome was a composite of myocardial infa rct ion , stroke , and death from cardiovascular causes . The secondary outcomes included unstable angina , congestive heart failure , revascularization or amputation , death from any cause , complications of diabetes , and cancer . RESULTS A total of 772 of the 4761 patients assigned to vitamin E ( 16.2 percent ) and 739 of the 4780 assigned to placebo ( 15.5 percent ) had a primary outcome event ( relative risk , 1.05 ; 95 percent confidence interval , 0.95 to 1.16 ; P=0.33 ) . There were no significant differences in the numbers of deaths from cardiovascular causes ( 342 of those assigned to vitamin E vs. 328 of those assigned to placebo ; relative risk , 1.05 ; 95 percent confidence interval , 0.90 to 1.22 ) , myocardial infa rct ion ( 532 vs. 524 ; relative risk , 1.02 ; 95 percent confidence interval , 0.90 to 1.15 ) , or stroke ( 209 vs. 180 ; relative risk , 1.17 ; 95 percent confidence interval , 0.95 to 1.42 ) . There were also no significant differences in the incidence of secondary cardiovascular outcomes or in death from any cause . There were no significant adverse effects of vitamin E. CONCLUSIONS In patients at high risk for cardiovascular events , treatment with vitamin E for a mean of 4.5 years had no apparent effect on cardiovascular outcomes", "Ketanserin is a new strong antiserotoninergic drug that , unlike the previous ones , is selective for 5-hydroxytryptamine receptors . This drug has been employed successfully in the treatment of arterial hypertension and of some peripheral vascular diseases . The authors are carrying out a trial on medium term treatment with ketanserin ( K ) or propranolol ( P ) in comparison with placebo , to evaluate their effects on blood pressure , haemocoagulative parameters and peripheral circulation . The trial is a double-blind cross-over r and om trial on subjects with mild or moderate hypertension . Until now 13 patients have ended the study ; six of them are suffering from arteriosclerosis obliterans of the lower limbs at 1st or 2nd stage according to Fontaine . Both propranolol and ketanserin significantly reduced the blood pressure , although the decrease in systolic blood pressure was more evident after propranolol . Heart rate diminished significantly only after propranolol administration . The noninvasive , intermittent ( every 30 min ) monitoring of blood pressure showed a significant 24-hour reduction of blood pressure after administration of propranolol or ketanserin without significant changes of circadian behaviour of the blood pressure . After administration of ketanserin a slight improvement in peripheral circulation was demonstrated , evaluated by using strain-gauge plethysmography . As regards the results obtained for platelet function and other haemocoagulative parameters examined , adenosine diphosphate-induced platelet aggregation , adenosine diphosphate slope , collagen lag period , antithrombin III biological activity , and serum fibrinogen did not show noticeable modifications after treatment , while beta-thromboglobulin levels decreased slightly after ketanserin administration", "Search ing for a possibility of an effective therapy of disturbances of peripheral arterial blood supply ( stage I and II ) , the authors examined a medicamentously untreated group of patients as well as a comparable group of patients which was pretreated with propranolol . The two groups of patients performed twice a week an interval run exercise . Under the three-month training therapy in the two groups significant systolic and diastolic blood pressure reductions as well as statistically ascertained shortenings of the xenon-133-half-value time under working conditions and enlargements of the average functional vascular cross section A appeared . The distance of the intermittent claudication and the st and ardized moving up and down test prolonged . An influence on the microcirculation caused by propranolol could not be proved . The results are discussed on the basis of literature", "This paper summarizes the results of two studies carried out to evaluate the effects of the cardioselective betablockers atenolol , acebutolol and metoprolol on peripheral circulation of the lower limbs . The 1st study was a double dummy double blind cross over placebo controlled trial carried out for 13 weeks to evaluate the effects of acebutolol ( 600 mg/die ) and metoprolol ( 300 mg/die ) , two cardioselective betablockers , on peripheral haemodynamics in patients suffering from mild to moderate hypertension . The 2nd study was a placebo controlled trial on the effects of atenolol ( 100 mg/day ) on haemodynamics at the calf carried out for 8 weeks in patients suffering from essential to severe moderate hypertension , part of which aged over 65 years and affected by arteriosclerosis obliterans of the lower limbs , stage I and II according to Fontaine 's classification . Calf blood flow in basal condition ( R.F. ) and after ischemic stimulus ( P.F. ) was evaluated by strain gauge plethysmography ; basal ( B.V.R. ) and minimal ( M.V.R. ) vascular resistances at the calf by the ratio between M.B.P./R.F. and M.B.P./P.F. respectively , Windsor 's index ( W.I. ) by ultrasound . Neither the patients with hypertension only nor the elderly hypertensive suffering from arteriosclerosis obliterans of the lower limbs showed changes in R.F. and P.F. , in B.V.R. and M.V.R. and in W.I. after chronic treatment with cardioselective beta-blockers . Many patients --about 17 % of all patients , and 40 % of arteriopathics -- in the two trials had cold h and s and feet . These studies suggest that chronic administration of selective beta-blockers does not exert unfavourable effects on muscular blood flow at the calf in patients with hypertension with or without arteriosclerosis obliterans of the lower limbs at I and II stage . ( ABSTRACT TRUNCATED AT 250 WORDS", " Background : The INternational VErapamil SR‐Tr and olapril Study ( INVEST ) , a prospect i ve , r and omized , antihypertensive trial , found that two different medication regimens produced similar blood pressure ( BP ) control with equivalent cardiovascular ( CV ) outcomes ( death from any cause , nonfatal myocardial infa rct ion [ MI ] , or nonfatal stroke ) ", "OBJECTIVE --To determine the effects of the beta 1 selective adrenoceptor blocker atenolol , the dihydropyridine calcium antagonist nifedipine , and the combination of atenolol plus nifedipine on objective and subjective measures of walking performance and foot temperature in patients with intermittent claudication . DESIGN --R and omised controlled double blind four way crossover trial . SETTING --Royal Hallamshire Hospital , Sheffield . SUBJECTS--49 patients ( 40 men ) aged 39 - 70 with chronic stable intermittent claudication . INTERVENTIONS --Atenolol 50 mg twice daily ; slow release nifedipine 20 mg twice daily ; atenolol 50 mg plus slow release nifedipine 20 mg twice daily ; placebo . Each treatment was given for four weeks with no washout interval between treatments . MAIN OUTCOME MEASURES --Claudication and walking distances on treadmill ; skin temperature of feet as measured by thermistor and probe ; blood pressure before and after exercise ; subjective assessment s of walking difficulty and foot coldness with visual analogue scales . RESULTS --Atenolol did not significantly alter claudication distance ( mean change -6 % ; 95 % confidence interval 1 % to -13 % ) , walking distance ( -2 % ; 4 % to -8 % ) , or foot temperature . Nifedipine did not alter claudication distance ( -4 % ; 3 % to -11 % ) , walking distance ( -4 % ; 3 % to -10 % ) , or foot temperature . Atenolol plus nifedipine did not alter claudication distance but significantly reduced walking distance ( -9 % ; -3 % to -15 % ( p less than 0.003 ) ) and skin temperature of the more affected foot ( -1.1 degrees C ; 0 to -2.2 degrees C ( p = 0.05 ) ) . These effects on walking distance and foot temperature seemed unrelated to blood pressure changes . CONCLUSIONS --There was no evidence of adverse or beneficial effects of atenolol or nifedipine , when given singly , on peripheral vascular disease . The combined treatment , however , affected walking ability and foot temperature adversely . This may have been due to beta blockade plus reduced vascular resistance , which might also explain the reported adverse effects of pindolol and labetalol on claudication", "The aim was to determine if certain risk factors in the general population are more strongly related to peripheral arterial disease than to ischemic heart disease . Arterial disease in the lower limbs was measured by means of the World Health Organization question naire on intermittent claudication , the ankle brachial pressure index , and a reactive hyperemia test in 1,592 men and women aged 55 - 74 years selected r and omly in 1988 from the age-sex registers of 10 general practice s in Edinburgh , Scotl and . Peripheral arterial disease was strongly related to lifetime cigarette smoking , with additional risks in current and exsmokers of less than 5 years . Multiple regression of risk factors on measures of peripheral arterial disease showed associations with diabetes mellitus ( but not impaired glucose tolerance ) , systolic blood pressure , and serum cholesterol ; inverse association with high-density lipoprotein cholesterol ; and only univariate association with triglycerides . In multiple logistic regressions of risk factors on six separate indicators of cardiovascular disease , the only consistent difference was that smoking increased the risk of peripheral arterial disease ( range of odds ratios , 1.8 - 5.6 ) more than heart disease ( range of odds ratios , 1.1 - 1.6 ) . Diabetes mellitus was not a stronger risk factor for peripheral arterial disease", "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", "To evaluate the role of β‐adrenoceptor blockade on lower limb circulation in patients with peripheral arterial disease , heart rate , blood pressure , calf blood flow and vascular resistance were measured at rest and during reactive hyperemia in seven patients with hypertension and intermittent claudication . The study was performed as a placebo‐controlled , double‐blind , crossover trial of 10 days with doses of propranolol , 80 mg twice a day , pindolol , 5 mg twice a day , labetalol , 200 mg twice a day , and labetalol , 400 mg twice a day as active drug . Heart rate was lowest during propranolol dosing and blood pressure was lowest during labetalol dosing irrespective of the labetalol dose used . The degree of peripheral arterial disease modulated the effect of β‐blockade on limb circulation . In the less symptomatic limbs , reactive hyperemic flow was greater after pindolol than after the other drugs and did not differ from the level recorded after placebo . These differences were inconsistent and small in the more symptomatic limbs . Thus as the peripheral arterial disease became more severe and extensive , β‐blockade , irrespective of its type , lost its hemodynamic effect on lower limb circulation", "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", "The effects of acebutolol ( with intrinsic sympathomimetic activity ( ISA ] and metoprolol ( without ISA ) on arm blood pressure , ankle systolic blood pressure , claudication distances ( CD ) and maximal walking distances ( MWD ) were compared in patients with essential hypertension and intermittent claudication . Fourteen patients participated in a long-term , open , r and omized cross-over study . After r and omization the patients received either acebutolol , 200 mg b.i.d . , or metoprolol , 100 mg b.i.d . After eight weeks the drugs were shifted and after another eight weeks they were withdrawn . Arm and ankle blood pressure , CD and MWD were determined before r and omization and after 4 , 8 , 12 and 16 weeks , and again 4 - 6 weeks after withdrawal of the drugs . The arm blood pressure was reduced by 20/13 mmHg after acebutolol and by 22/21 mmHg after metoprolol . In spite of a significant decrease in arm blood pressure there were no significant changes in ankle blood pressure , CD or MWD after the two drugs . After withdrawal of the drugs and after the arm blood pressure had returned to the control value no significant changes were seen in CD , MWD or ankle blood pressure . It is concluded that beta-blockers have no deleterious effect on CD , MWD or ankle blood pressure in patients with hypertension and intermittent claudication . No effect of ISA was demonstrated", "OBJECTIVE To determine whether long-term treatment with cilazapril ( CIL ) may improve pulse pressure ( PP ) , arterial compliance and ankle-arm systolic index ( AAI ) in patients with lower-extremity arterial disease ( LEAD ) . Indeed , in both systolic hypertension and LEAD , the increase in pulse pressure has been attributed to a reduced compliance . DESIGN AND METHODS Thirteen patients ( age : 65 + /- 5 yrs ; AAI : 0.78 + /- 0.15 ; m + /- SD ) were included in a double-blind r and omized parallel study to compare the effects of a 6 month treatment with CIL ( 10 mg per day ; n = 6 ) to those of placebo ( PL ; n = 7 ) Blood pressure , AAI and arterial compliance were determined at baseline ( MO ) and after 3 ( M3 ) and 6 months ( M6 ) . Common carotid ( CC ) and common femoral ( CF ) artery compliances were noninvasively determined from pulsatile changes in arterial diameter ( Wall Track System , Hoeks et al. , 1990 ) and pressure ( PP ) . RESULTS Both groups were comparable at MO . Compared to PL , CIL significantly reduced PP ( -22 + /- 4 vs -2 + /- 9 mmHg ) and MAP ( -16 + /- 11 vs -4 + /- 7 mmHg ) and improved CC ( + 54 + /- 34 vs + 5 + /- 21 mm2.mmHg-1.10(-3 ) ) at M6 . Weaker effects were observed at M3 . No significant changes in AAI and CF compliance were observed . CONCLUSIONS A direct effect of CIL on the large artery wall was suggested by 1 ) a greater reduction in PP than in MAP and 2 ) a disproportionately greater improvement in CC compliance compared with the reduction in distending pressure ( MAP ) . These results indicate that long-term treatment with CIL may improve large artery function in patients with LEAD", "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 ", "OBJECTIVES To examine the central hemodynamic and blood gas responses to sublingual captopril and nifedipine administration in patients with arterial hypertension after abdominal aortic surgery . DESIGN Prospect i ve , r and omized , parallel-group clinical study . SETTING Twenty-nine-bed medical-surgical intensive care unit in a university hospital . PATIENTS Twenty patients with arterial hypertension ( mean arterial pressure of > or = 115 mm Hg ) the day after abdominal aortic surgery . Patients with bilateral renal artery stenoses , identified with the preoperative angiogram , were excluded . INTERVENTIONS Pressures were measured using intravascular catheters and cardiac output was determined by thermodilution for 2 hrs after captopril 25 mg ( n = 10 ) or nifedipine 10 mg ( n = 10 ) was administered by the sublingual route . MEASUREMENTS AND MAIN RESULTS Captopril administration and nifedipine administration decreased mean arterial pressure ( from 121 + /- 1 to 94 + /- 4 mm Hg and from 121 + /- 2 to 94 + /- 2 [ sem ] mm Hg , respectively ) , pulmonary arterial pressure , pulmonary artery occlusion pressure , and right atrial pressure ( p heart rate and in cardiac output were not significant . PaO2 decreased after nifedipine , from 101 + /- 8 to 81 + /- 3 torr [ 13.5 + /- 1.1 to 10.8 + /- 0.4 kPa ] ( p captopril ( 104 + /- 9 to 100 + /- 7 torr [ 13.9 + /- 1.2 to 13.3 + /- 0.9 kPa ] ) . Excessive or symptomatic decreases in blood pressure were not observed , nor was deterioration in renal function observed . CONCLUSIONS Sublingual captopril and nifedipine were equally effective for the treatment of arterial hypertension after abdominal aortic surgery . Nifedipine , but not captopril , caused a deterioration in pulmonary gas exchange", "IMPORTANCE Approximately one-third of patients with peripheral artery disease experience intermittent claudication , with consequent loss of quality of life . OBJECTIVE To determine the efficacy of ramipril for improving walking ability , patient-perceived walking performance , and quality of life in patients with claudication . DESIGN , SETTING , AND PATIENTS R and omized , double-blind , placebo-controlled trial conducted among 212 patients with peripheral artery disease ( mean age , 65.5 [ SD , 6.2 ] years ) , initiated in May 2008 and completed in August 2011 and conducted at 3 hospitals in Australia . INTERVENTION Patients were r and omized to receive 10 mg/d of ramipril ( n = 106 ) or matching placebo ( n = 106 ) for 24 weeks . MAIN OUTCOME MEASURES Maximum and pain-free walking times were recorded during a st and ard treadmill test . The Walking Impairment Question naire ( WIQ ) and Short-Form 36 Health Survey ( SF-36 ) were used to assess walking ability and quality of life , respectively . RESULTS At 6 months , relative to placebo , ramipril was associated with a 75-second ( 95 % CI , 60 - 89 seconds ) increase in mean pain-free walking time ( P maximum walking time ( P placebo , ramipril improved the WIQ median distance score by 13.8 ( Hodges-Lehmann 95 % CI , 12.2 - 15.5 ) , speed score by 13.3 ( 95 % CI , 11.9 - 15.2 ) , and stair climbing score by 25.2 ( 95 % CI , 25.1 - 29.4 ) ( P overall SF-36 median Physical Component Summary score improved by 8.2 ( Hodges-Lehmann 95 % CI , 3.6 - 11.4 ; P = .02 ) in the ramipril group relative to placebo . Ramipril did not affect the overall SF-36 median Mental Component Summary score . CONCLUSIONS AND RELEVANCE Among patients with intermittent claudication , 24-week treatment with ramipril result ed in significant increases in pain-free and maximum treadmill walking times compared with placebo . This was associated with a significant increase in the physical functioning component of the SF-36 score . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00681226", "The aim of the present study was to evaluate whether beta blockade presents a risk of intermittent claudication and how it affects the walking capacity and lower limb haemodynamics in patients with intermittent claudication . The study was divided into six parts : A case-control study with 55 pairs , cases with hypertension and intermittent claudication and controls with hypertension only , matched for age , sex , place of residence , and time of examination , all without coronary heart disease , which is a known confounding factor . An open controlled study on the effect of withdrawal of beta blockade on walking capacity of 28 patients with intermittent claudication . A placebo-controlled double-blind crossover study on the effect of antihypertensive treatment on the walking capacity of 14 patients with intermittent claudication . Three placebo-controlled double-blind crossover studies on the effect of propranolol , metoprolol , pindolol , labetalol , and /or methyldopa on calf blood flow in 34 hypertensive subjects without peripheral arterial disease and in altogether 21 patients with intermittent claudication . Walking capacity was measured on a treadmill . Calf blood flow was measured with strain gauge plethysmography by the venous occlusion technique . The case-control comparison showed that beta blockers were used as often by patients with intermittent claudication as by controls . Walking capacity increased during the first month of the open controlled study irrespective of whether the beta blockade was withdrawn or continued . There was no difference in this respect between the various types of beta blockers . Antihypertensive treatment with metoprolol or methyldopa did not affect walking capacity . Resting calf blood flow was unaffected by propranolol or metoprolol , regardless of the presence or absence of peripheral arterial disease , as well as by pindolol , labetalol , or methyldopa in patients with intermittent claudication . During reactive hyperaemia , propranolol and metoprolol reduced flow in patients without peripheral arterial disease . Propranolol also reduced hyperaemic blood flow in the limb with less or no symptoms in patients with intermittent claudication . None of the active drugs decreased the hyperaemic flow consistently in the limb with the stronger symptoms . In a comparison of haemodynamic effects between the drugs , calf blood flow at rest was higher after pindolol than after propranolol and hyperaemic flow of the better limb was higher after pindolol than after propranolol and labetalol . ( ABSTRACT TRUNCATED AT 400 WORDS", "BACKGROUND The results from the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial ( ONTARGET ) indicated that the angiotensin-receptor blocker telmisartan was not inferior to the angiotensin-converting-enzyme inhibitor ramipril in reducing the composite endpoint of cardiovascular death , myocardial infa rct ion , stroke or hospitalization for congestive heart failure in high-risk patients , and telmisartan was associated with slightly superior tolerability . The combination of the two drugs was associated with more adverse events without an increase in benefit . This study aim ed to analyze the data from ONTARGET obtained from a subgroup of patients enrolled in China and to evaluate the demographic and baseline characteristics , the compliance , efficacy , and safety of the different treatment strategies in r and omized patients in China . METHODS A total of 1159 high-risk patients were r and omized into three treatment groups : with 390 assigned to receive 80 mg of telmisartan , 385 assigned to receive 10 mg of ramipril and 384 assigned to receive both study medications . The median follow-up period was 4.3 years . RESULTS The mean age of Chinese patients was 65.6 years , 73.6 % of patients were male . The proportion of patients with stroke/transient ischemic attacks at baseline in China was two times more than the entire study population ( 47.7 % vs. 20.9 % ) . In Chinese patients the proportion of permanent discontinuation of study medication due to cough was 0.5 % in the telmisartan group , which was much less than that in the combination or the ramipril group . There were no significant differences in the incidence of primary outcome among three treatment groups of Chinese patients . More strokes occurred in Chinese patients than in the entire study population ( 8.5 % vs. 4.5 % ) . Greater systolic blood pressure reduction ( -9.8 mmHg ) , and more renal function failure were noted in the combination treatment group than in the ramipril or telmisartan group ( 2.6 % vs. 1.6 % and 1.0 % ) . CONCLUSIONS There was no evidence that the results of ONTARGET differed between Chinese patients and the entire study population with respect to the incidence of primary outcome , particularly safety . Compliance with study medications was good . The evidence from ONTARGET indicated that the treatment strategies in ONTARGET were applicable to patients in China", "A multicenter , double-blind , r and omized , and placebo-controlled trial , the Perindopril Therapeutic Safety Study ( PUTS ) , was design ed to assess the interaction between angiotensin-converting enzyme ( ACE ) inhibition and the diseases and therapies commonly found associated with mild hypertension . A total of 480 male and female patients aged 30 - 70 years with a diastolic pressure of 90 - 104 mm Hg were included after a 3-week placebo run-in if they satisfied st and ard criteria for any of the following : hyperlipidemia , type II diabetes , ischemic heart disease , cardiac arrhythmia , peripheral arterial occlusive disease , nephropathy with proteinuria , chronic obstructive lung disease or treatment with nonsteroidal anti-inflammatory drugs ( NSAIDs ) . At the end of the placebo run-in period , patients were r and omly assigned to either placebo or perindopril 4 mg once daily . A total of 460 patients completed the 6-week double-blind phase , comprising 3 assessment s at 1 , 3 , and 6 weeks . In this report , the principal results obtained in 5 disease groups ( hyperlipidemia , type II diabetes , ischemic heart disease , nephropathy with proteinuria , and NSAID treatment ) will be reported . A total of 269 patients belonging to one of the aforementioned 5 disease groups completed the double-blind phase of the study and were included for statistical evaluation . In the perindopril group , systolic and diastolic blood pressures decreased significantly more than in the placebo group , and a sitting diastolic blood pressure of 90 mm Hg was achieved in 65 % of patients in the perindopril group and 30 % of patients in the placebo group . The incidence of symptoms spontaneously reported by the patients was low : 2 patients of the perindopril group complained of cough . ( ABSTRACT TRUNCATED AT 250 WORDS", "Objective To test the primary hypothesis that a newer antihypertensive treatment regimen ( calcium channel blocker ± an angiotensin converting enzyme inhibitor ) is more effective than an older regimen ( β-blocker ± a diuretic ) in the primary prevention of coronary heart disease ( CHD ) . To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol ⩽ 6.5 mmol/l . Design Prospect i ve , r and omized , open , blinded endpoint trial with a double-blinded 2 × 2 factorial component . Setting Patients were recruited mainly from general practice s. Patients Men and women aged 40–79 were eligible if their blood pressure was ⩾160 mmHg systolic or ⩾ 100 mmHg diastolic ( untreated ) or ⩾140 mmHg systolic or ⩾ 90 mmHg diastolic ( treated ) at r and omization . Interventions Patients received either amlodipine ( 5/10 mg ) ± perindopril ( 4/8 mg ) or atenolol ( 50/100 mg ) ± bendroflumethiazide ( 1.25/2.5 mg ) + K+ with further therapy as required to reach a blood pressure of ⩽140 mmHg systolic and 90 mmHg diastolic . Patients with a total cholesterol of ⩽ 6.5 mmol/l were further r and omized to receive either atorvastatin 10 mg or placebo daily . Main outcome measure Non-fatal myocardial infa rct ion ( MI ) and fatal coronary heart disease ( CHD ) . Results 19 342 men and women were initially r and omized , of these 10 297 were also r and omized into the lipid-lowering limb . All patients had three or more additional cardiovascular risk factors . Conclusions The study has 80 % power ( at the 5 % level ) to detect a relative difference of 20 % in CHD endpoints between the calcium channel blocker-based regimen and the β-blocker-based regimen . The lipid-lowering limb of the study has 90 % power at the 1 % level to detect a relative difference of 30 % in CHD endpoints between groups", "In a comparative cross-over trial we examined the influence of the betablocker bisoprolol and the ACE-inhibitor lisinopril on the peripheral blood flow of 2 groups of hypertensive patients with and without concomitant intermittent claudication . In 11 patients with hypertension without peripheral arterial obstructive disease and 11 patients with hypertension and claudication we assessed the blood pressure , leg blood flow , vascular resistance , walking distance , transcutaneous oxygen consumption and Laser-Doppler flow after treatment of one month with 10 mg bisoprolol once daily or 20 mg lisinopril once daily . The walking distance of patients with claudication improved in all patients while participating in an exercise program . For both treatment groups this improvement was significant ( p bisoprolol and to 400 m with lisinopril . The difference was not significant between the both drugs . In patients without peripheral vascular obstructive disease we found a significant ( p in blood flow for both drugs . The peripheral blood flow parameters of 38 legs showed no statistical significant effect of bisoprolol nor lisinopril on the local vascular resistance at rest , after occlusion or after exercise", "The ABCD ( Appropriate Blood Pressure Control in Diabetes ) trial is a large , prospect i ve , r and omized clinical trial design ed to compare the effects of intensive with moderate blood pressure control on the prevention and progression of diabetic nephropathy , retinopathy , cardiovascular disease , and neuropathy in non-insulin-dependent diabetes ( NIDDM ) . The secondary objective is to determine equivalency of the effects of a calcium channel blocker ( nisoldipine ) and of an angiotensin-converting enzyme inhibitor ( enalapril ) as a first-line antihypertensive agent in the prevention and /or progression of these diabetic vascular complications . The study consists of two study population s : a hypertensive one ( diastolic blood pressure of > or = 90.0 mm Hg at the time of r and omization ) and a normotensive one ( diastolic blood pressure of 80.0 - 89.0 mm Hg at the time of r and omization ) . A total of 950 men and women aged 40 - 74 years were r and omized and are being followed for 5 years at a single center . There were 470 r and omized participants in the hypertensive population and 480 r and omized participants in the normotensive population . This report summarizes the demographic , biochemical , and clinical characteristics of the r and omized patients at the time of entry into the trial and evaluates the balance between the treatment groups within each population", "The effect of a four-week treatment with propranolol and metoprolol on blood pressure and regional haemodynamics of the lower extremity at rest , after exercise and during reactive hyperaemia was studied in 34 patients with essential hypertension , but without peripheral arterial disease , in a r and omized placebo-controlled trial . No significant difference in side-effects recorded during the trial was observed between these two drugs . Treatment with beta-adrenergic blocking drugs reduced systemic blood pressure . Calf blood flow during vasodilatation was also decreased . The most marked changes were observed during reactive hyperaemia ; mean calf blood flow was reduced from about 250 ml/min/litre of tissue to 200 ml/min/litre of tissue ( P less than 0.01 ) by propranolol and to 214 ml/min/litre of tissue ( P less than 0.01 ) by metoprolol . Both drugs caused a significant increase in peripheral resistance above the initial level during reactive hyperaemia ( P less than 0.05 ) . No significant difference in peripheral resistance was observed , however , when the active drugs were compared with the placebo . There was no difference between propranolol and metoprolol in any of the parameters . Thus , the flow reduction can mainly be attributed to the diminished perfusion pressure due to the decreased cardiac output caused by beta-blockade of the heart", "The effects of two potent vasodilating drugs , captopril ( C ) ( 25 mg tid ) , nicar dipine ( N ) ( 20 mg tid ) , and placebo ( P ) were evaluated and compared , in 10 men ( mean age of sixty-five years ) with intermittent claudication from moderate to severe multilevel chronic occlusive arterial disease ( COAD ) of the lower extrem ity , by use of the Doppler ultrasonic method , at rest and after Carter 's exercise test . All the examined subjects were normotensive , without diabetes or cardio pathy ; all have been smokers . The eight-week total protocol consisted of an initial two-week placebo run-in period followed by two active drug phases and a two-week placebo phase , ac cording to a double-blind , r and omized , crossover design . At the end of each two-week period , ankle-arm index ( AAI ) and , following exercise , onset of lower extremity discomfort time ( ODT ) , duration of exercise ( ET ) , decrease of ankle systolic pressure after test ( APD ) , and recovery time ( RT ) were determined . Moreover , at rest , just after exercise , and after recovery , simultaneous common femoral artery velocity waves were recorded and analyzed by a quantitative approach to detect the peripheral vasomotor adjustments . None of the patients required the withdrawal of the active treatments . Com pared with P , C significantly reduced APD and RT , and N reduced RT and AAI ; furthermore N caused a significant decrease in ODT , whereas C showed a trend , although not statistically significant , to increase ODT . Neither active therapy modified ET . These results suggest that C and N have different short-term effects on pe ripheral circulation in COAD . During exercise , C induces hemodynamic i m provement in the ischemic lower extremity probably by inhibition of the sympathetic system and consequent reduction in collateral vessel vasoconstric tion", "Many factors , both local and systemic , are known to influence the caliber of peripheral vessels and regional blood flow . Methods of study ing limb blood flow and its alteration by disease and drugs present considerable problems . We compared the effects of a series of antihypertensive drugs on limb blood flow and their functional effects in patients with hypertension and peripheral vascular disease . Results from studies with new antihypertensive drugs such as carvedilol are awaited", "PURPOSE Many hypertensive patients have other , usually long-term diseases . Antihypertensive therapy may interfere with these diseases and their therapies . In the present study , the possible interactions of the ACE-inhibitor perindopril with several of the most common long-term diseases was evaluated . PATIENTS AND METHODS In a multicenter , double-blind , r and omized , placebo-controlled trial , the effect of perindopril was evaluated in 490 patients with mild essential hypertension and any one of the following concomitant diseases : hyperlipidemia , type II diabetes mellitus , ischemic heart disease , cardiac arrhythmia , peripheral arterial occlusive disease , nephropathy with proteinuria , chronic obstructive pulmonary disease , or degenerative joint disease treated with nonsteroidal anti-inflammatory drugs ( NSAIDs ) . After a 3-week single-blind placebo run-in , the patients received either perindopril ( 4 mg/d ) or matching placebo for 6 weeks . RESULTS Blood pressure was effectively reduced by perindopril irrespective of the associated disease . The rate of spontaneously reported side effects was low . Treatment with perindopril was free from adverse interactions with the concomitant diseases and therapies . Moreover , favorable actions could be observed in patients with ischemic heart disease ( reduction of maximal ST-segment depression during peak exercise and decrease in the number of angina attacks ) , in patients with proteinuria ( decrease in albuminuria in patients with normal serum creatinine levels ) , and in patients with NSAID-treatment ( increase in prostagl and in E2 concentration in gastric mucosa suggesting gastric cytoprotection ) . CONCLUSION This trial shows that ACE-inhibition with perindopril represents a simple , safe , and effective short-term therapeutic option for the large proportion of patients with mild essential hypertension and concomitant diseases and therapies", "In a double-blind , crossover trial 12 patients with hypertension and peripheral arterial disease were r and omized to three months ' treatment with captopril 25 - 50 mg twice daily or nifedipine SR 20 - 40 mg twice daily . While both treatments were equally effective at lowering blood pressure , postexercise calf blood flow availability was greater during treatment with captopril ( P walking capacity assessed by treadmill exercise . The results sug gest that both captopril and nifedipine are appropriate antihypertensive agents in patients with peripheral arterial disease", "A high prevalence of increased intima/media thickness of the arterial wall has been documented in hypertension . These alterations in vascular wall structure may be potent determinants for the promotion of the development of atherosclerosis . Direct histologic data from animal models of hypertension , and indirect data from hypertensive patients , have demonstrated a marked regression of increased intima/media thickness by angiotensinconverting enzyme ( ACE ) inhibition . Long-term effects of ACE inhibition on structural wall changes in humans have not been examined . Therefore , a multicenter , r and omized , double-blind European trial was design ed to compare the effects of the ACE inhibitor perindopril and the diuretic hydrochlorothiazide in slowing or reversing progression of increased intima/media thickness of carotid and femoral arteries in hypertensive patients . A total of 800 patients at 17 clinical centers in 7 European countries , aged 35–65 years , with hypertension and ultrasonographically proven intima/media thickness ≥0.8 mm of the common carotid artery will be r and omly assigned to receive in a doubleblind fashion either perindopril or hydrochlorothiazide and will be followed for 24 months . High resolution duplex sonography will be used to quantify intima/media thickness at baseline and twice a year during follow-up . A change of 0.1 mm of intima/media thickness from baseline is considered to be detectable , and the st and ard deviations of the changes from baseline are expected not to be higher than 0.2 mm . The primary endpoint of the study is the comparison of changes in intima/media thickness of the common carotid artery . Secondary endpoints include comparison of the effectiveness of the two treatments on left ventricular mass , posterior wall thickness , intraventricular septal thickness , left ventricular end-diastolic diameter , and comparison of the 2 treatments on ultrasonographically determined thickness of the intima/media complex of the common femoral artery . Further analyses will assess the relation between intima/ media thickness changes and the changes of blood pressure , heart rate , low and high density lipoprotein cholesterol , triglycerides , and glucose . The study is design ed to assess the impact of antihypertensive therapy on early pathological vascular wall changes and to clarify whether this is due to a drug-specific action or only dependent on the blood pressure lowering effect ", "Authors report results on a comparative multicenter double blind trial carried out to assess the efficacy of Ifenprodil tartrate ( * ) ( 60 mg a.d . ) versus placebo in symptomatic treatment of stable peripheral arterial occlusive disease ( Fontaine stage II ) . Ninety four patients were included in this six months , two parallel group study ( 2 homogeneous groups ) which shows a statistically significant functional improvement in the treatment group versus the placebo group . After six months of treatment , the maximum walking distance (MWD)--main assessment criteria --was 126.0 + /- 18.5 meters in the Ifenprodil group versus 46.4 + /- 20.2 meters in the placebo group ( p = 0.005 ) . This represents an improvement of 62.1 % in the Ifenprodil group versus 21.0 % in the placebo group . An improvement of at least 50 % in MWD was observed in 41.3 % of patients treated by Ifenprodil and in only 12.5 % of patients receiving placebo ( p = 0.002 ) . The evolution of ankle/brachial systolic post exercise index from JO to J180 was not significantly different in the two groups . Clinical and biological tolerance of Ifenprodil tartrate was excellent", "This double-blinded , r and omized , placebo-controlled study was design ed to investigate the acute effect of felodipine on regional blood supply and collateral vascular resistance in patients with peripheral arterial occlusive disease ( PAOD ) . Thirty men with PAOD were treated with a single dose of 5 mg felodipine or placebo . Systolic blood pressure ( SBP ) , Doppler ankle pressure ( DAP ) , calf blood flow ( CBF ) by venous occlusion plethysmography and calf transcutaneous oxygen tension ( tcpO2 ) were measured during a cycle ergometry . Felodipine reduced SBP significantly ( from 149 to 136 mmHg , p placebo did not . DAP increased slightly but not significantly in both groups . The pressure gradient between SBP and DAP fell significantly in the felodipine group ( 60 vs 39 mmHg , p placebo group ( 59 vs 56 mmHg ) . There was a trend for lower velocity in tcpO2 decrease during the stress test and higher velocity of tcpO2 increase during recovery from exercise in the felodipine group although the differences between both groups were not significant . In the felodipine group , CBF increased by 35.6 % ( p SBP , felodipine increased slightly , or at least maintained , the blood supply to the calves in PAOD patients , which probably results from reducing collateral vascular resistance", "OBJECTIVES To ascertain the baseline characteristics of the high-risk hypertensive patients entering the International Nifedipine GITS Study : Intervention as a Goal in Hypertension Treatment ( INSIGHT ) . To determine the success of single and combination therapy in achieving target blood pressures in such a population . DESIGN INSIGHT is a double-blind , prospect i ve outcome trial comparing the efficacy of the calcium channel blocker , nifedipine GITS , and the thiazide , co-amilozide , in preventing myocardial infa rct ion and stroke . We recruited 2996 men and 3454 women , aged 55 - 80 years , with blood pressure during placebo run-in > 150/95 mmHg or isolated systolic blood pressure > 160 mmHg from nine countries . Treatment allocation to nifedipine GITS 30 mg daily or co-amilozide ( hydrochlorothiazide 25 mg/amiloride 5 mg ) once daily was performed by minimization rather than r and omization to balance additional risk factors . This was followed by four optional increases in treatment : dose-doubling of the primary drug , addition of atenolol 25/50 mg or enalapril 5/10 mg , and then any other hypotensive drug excluding calcium blockers or diuretics . Target blood pressure was 140/90 mmHg or a fall > or = 20/10 mmHg . RESULTS Blood pressure at r and omization was 172+/-15 / 99+/-9 mmHg . Thirteen per cent of the patients were previously untreated . The proportions of each additional risk factors were : smoking > 10/day , 29 % ; cholesterol > 6.43 mmol/l , 52 % ; family history of premature myocardial infa rct ion or stroke , 21 % ; diabetes mellitus 20 % ; left ventricular hypertrophy , 10 % ; previous myocardial infa rct ion , other presentations of coronary heart disease , and peripheral vascular disease , each 6 % ; proteinuria , 3 % . Fifty-five per cent of patients had one additional risk factor , whereas 33 % , 9 % and 3 % had two , three or more additional risk factors , respectively . The blood pressure ( and falls in blood pressure ) at the end of titration and at 1 year after minimization was 139+/-12 / 82+/-7 mmHg ( 33+/-15 / 17+/-9 ) in the 5226 patients still on r and omized treatment The numbers requiring the four treatment increments were , respectively , 1591 , 780 , 597 and 294 , meaning that almost 70 % of patients on r and omized treatment in INSIGHT are receiving only the primary drug . At one year , 69 % of patients had a blood pressure blood pressure control in most patients without the addition of multiple additional treatments that may dilute any differences between the primary agents", "BACKGROUND Erectile dysfunction ( ED ) is a common disorder in middle-aged men and is significantly influenced by cardiovascular risk factors ( CVRFs ) and cardiovascular disease . The sub study of the ONTARGET/TRANSCEND trials evaluates the relationship of erectile function to baseline characteristics and current treatment in cardiovascular high-risk patients who have been enrolled in these trials . The effects of treatment with telmisartan and ramipril , alone or in combination , including a telmisartan versus placebo arm will be determined prospect ively during a follow-up of 4 years . METHODS One thous and three hundred fifty-seven patients were evaluated in 13 countries at baseline , 2 years , and 4 years , with ED determined using the ED score of the Cologne Male Survey ( Kölner [ Cologne ] Evaluation of Erectile Dysfunction ) and the 5-item International Index of Erectile Function . Erectile dysfunction scores were related to CVRF and the use of cardiovascular drugs . RESULTS Prevalence of ED was 50.7 % ( Kölner [ Cologne ] Evaluation of Erectile Dysfunction ) and 54.3 % ( 5-item International Index of Erectile Function ) , respectively , with a decline of sexual activity after the diagnosis of cardiovascular disease . In multivariate analysis , diabetes mellitus ( P 65 years ( P cholesterol levels , hypertension , and smoking status as well as current treatment with angiotensin-converting enzyme inhibitors , angiotensin I antagonists , diuretics , beta-blockers , or calcium-channel blockers . CONCLUSIONS The ONTARGET/TRANSCEND-ED sub study shows a significant influence of cardiovascular disease on erectile function . In contrast to prior smaller studies , drug therapy and CVRF seem to play a minor role in cardiovascular high-risk patients . Follow-up data will provide information whether angiotensin-converting enzyme inhibitors , angiotensin I antagonists , or a combination thereof are able to improve erectile function", "Seven patients ( 5 with arteriosclerosis obliterans and 2 with Buerger 's disease ) completed a two‐phase double‐blind crossover trial of propranolol in intermittent claudication . Performance was measured on a moving treadmill . In the initial phase , the patients were hospitalized in order to determine an “ effective ” dose of propranolol . Improvement was noted in all : after 1,600 mg in 5 and after 240 mg and 600 mg in the others . The controlled phase was carried out on an outpatient basis over 8 weeks , the patients receiving propranolol and placebo in a r and om manner , each for two 2‐week periods . Comparison of matched periods of drug and placebo revealed no advantage for propranolol . Patients ’ performances deteriorated with time . None of the patients evidence d deterioration of occlusive peripheral arterial disease that could be attributed to propranolol , in spite of the high doses used", "Background — Although erectile dysfunction ( ED ) is associated with cardiovascular risk factors and atherosclerosis , it is not known whether the presence of ED is predictive of future events in individuals with cardiovascular disease . We evaluated whether ED is predictive of mortality and cardiovascular outcomes , and because inhibition of the renin-angiotensin system in high-risk patients reduces cardiovascular events , we also tested the effects on ED of r and omized treatments with telmisartan , ramipril , and the combination of the 2 drugs ( ONTARGET ) , as well as with telmisartan or placebo in patients who were intolerant of angiotensin-converting enzyme inhibitors ( TRANSCEND ) . Methods and Results — In a prespecified sub study , 1549 patients underwent double-blind r and omization , with 400 participants assigned to receive ramipril , 395 telmisartan , and 381 the combination thereof ( ONTARGET ) , as well as 171 participants assigned to receive telmisartan and 202 placebo ( TRANSCEND ) . ED was evaluated at baseline , at 2-year follow-up , and at the penultimate visit before closeout . ED was predictive of all-cause death ( hazard ratio [ HR ] 1.84 , 95 % confidence interval [ CI ] 1.21 to 2.81 , P=0.005 ) and the composite primary outcome ( HR 1.42 , 95 % CI 1.04 to 1.94 , P=0.029 ) , which consisted of cardiovascular death ( HR 1.93 , 95 % CI 1.13 to 3.29 , P=0.016 ) , myocardial infa rct ion ( HR 2.02 , 95 % CI 1.13 to 3.58 , P=0.017 ) , hospitalization for heart failure ( HR 1.2 , 95 % CI 0.64 to 2.26 , P=0.563 ) , and stroke ( HR 1.1 , 95 % CI 0.64 to 1.9 , P=0.742 ) . The study medications did not influence the course or development of ED . Conclusions — ED is a potent predictor of all-cause death and the composite of cardiovascular death , myocardial infa rct ion , stroke , and heart failure in men with cardiovascular disease . Trial treatment did not significantly improve or worsen ED . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT 00153101" ]

[ "AIMS AND OBJECTIVES To compare drug adherence to lipid-lowering therapy among out patients with coronary artery disease who received information via short message service , via short message service and Micro Letter , or via phone only . BACKGROUND Messaging applications and short message service are commonly used internationally . However , little is known about how coronary artery disease out patients in China may benefit from receiving health education through these technologies . DESIGN R and om sampling method . METHODS Data were collected from March-December 2013 . Subjects from Chengdu City , China , were r and omised to three groups : short message service , short message service + Micro Letter , and phone ( control ) . Appointment reminders and health information were delivered to patients in accordance with design ations . After six months , adherence to statin prescriptions was compared among the groups by using the Morisky Medication Adherence Scale . Logistic regression analysis was applied to determine those independent variables that were related to adherence . RESULTS The short message service and short message service + Micro Letter groups had better cumulative adherence ( lower Morisky Medication Adherence Scale scores ) after six months than phone group , and the short message service + Micro Letter group had better cumulative adherence ( lower Morisky Medication Adherence Scale scores ) than the short message service group . Female sex , older age and marriage show positive associations with adherence . CONCLUSIONS Short message service and messaging applications , such as Micro Letter , are effective means of providing discharged patients with reminders and coronary artery disease-related health information . Implementation of a short message service + Micro Letter program can improve outpatient adherence to medication . RELEVANCE TO CLINICAL PRACTICE This research offers useful information to help medical staff design effective interventions to improve medication compliance among coronary artery disease patients", "Background Effective use of proven treatments for high blood pressure , a preventable health risk , is challenging for many patients . Prompts via mobile phone SMS-text messaging may improve adherence to clinic visits and treatment , though more research is needed on impact and patient perceptions of such support interventions , especially in low-re source setting s. Method An individually-r and omised controlled trial in a primary care clinic in Cape Town ( 2012–14 ) , tested the effect of an adherence support intervention delivered via SMS-texts , on blood pressure control and adherence to medication , for hypertensive patients . ( Trial registration : Clinical Trials.gov NCT02019823 ) . We report on a qualitative evaluation that explored the trial participants ’ experiences and responses to the SMS-text messages , and identified barriers and facilitators to delivering adherence support via patients ’ own mobile phones . Two focus groups and fifteen individual interviews were conducted . We used comparative and thematic analysis approaches to identify themes and triangulated our analysis amongst three research ers . Results Most participants were comfortable with the technology of using SMS-text messages . Messages were experienced as acceptable , relevant and useful to a broad range of participants . The SMS-content , the respectful tone and the delivery ( timing of reminders and frequency ) and the relational aspect of trial participation ( feeling cared for ) were all highly valued . A subgroup who benefitted the most , were those who had been struggling with adherence due to high levels of personal stress . The intervention appeared to coincide with their readiness for change , and provided practical and emotional support for improving adherence behaviour . Change may have been facilitated through increased acknowledgement of their health status and attitudinal change towards greater self-responsibility . Complex interaction of psycho-social stressors and health service problems were reported as broader challenges to adherence behaviours . Conclusion Adherence support for treatment of raised blood pressure , delivered via SMS-text message on the patient ’s own phone , was found to be acceptable , relevant and helpful , even for those who already had their own reminder systems in place . Our findings begin to identify for whom and what core elements of the SMS-text message intervention appear to work best in a low-re source operational setting , issues that future research should explore in greater depth", "Background Mobile phone based programs for kidney transplant recipients are promising tools for improving long-term graft outcomes and better managing comorbidities ( eg , hypertension , diabetes ) . These tools provide an easy to use self-management framework allowing optimal medication adherence that is guided by the patients ’ physiological data . This technology is also relatively inexpensive , has an intuitive interface , and provides the capability for real-time personalized feedback to help motivate patient self-efficacy . Automated summary reports of patients ’ adherence and blood pressure can easily be uploaded to providers ’ networks helping reduce clinical inertia by reducing regimen alteration time . Objective The aim of this study was to assess the feasibility , acceptability , and preliminary outcomes of a prototype mobile health ( mHealth ) medication and blood pressure ( BP ) self-management system for kidney transplant patients with uncontrolled hypertension . Methods A smartphone enabled medication adherence and BP self-management system was developed using a patient and provider centered design . The development framework utilized self-determination theory with iterative stages that were guided and refined based on patient/provider feedback . A 3-month proof-of-concept r and omized controlled trial was conducted in 20 hypertensive kidney transplant patients identified as non-adherent to their current medication regimen based on a month long screening using an electronic medication tray . Participants r and omized to the mHealth intervention had the reminder functions of their electronic medication tray enabled and received a bluetooth capable BP monitor and a smartphone that received and transmitted encrypted physiological data and delivered reminders to measure BP using text messaging . Controls received st and ard of care and their adherence continued to be monitored with the medication tray reminders turned off . Providers received weekly summary reports of patient medication adherence and BP readings . Results Participation and retention rates were 41/55 ( 75 % ) and 31/34 ( 91 % ) , respectively . The prototype system appears to be safe , highly acceptable , and useful to patients and providers . Compared to the st and ard care control group ( SC ) , the mHealth intervention group exhibited significant improvements in medication adherence and significant reductions in clinic-measured systolic blood pressures across the monthly evaluations . Physicians made more anti-hypertensive medication adjustments in the mHealth group versus the st and ard care group ( 7 adjustments in 5 patients versus 3 adjustments in 3 patients ) during the 3-month trial based on the information provided in the weekly reports . Conclusions These data support the acceptability and feasibility of the prototype mHealth system . Further trials with larger sample sizes and additional biomarkers ( eg , whole blood medication levels ) are needed to examine efficacy and effectiveness of the system for improving medication adherence and blood pressure control after kidney transplantation over longer time periods . Trial Registration Clinical trials.gov NCT01859273 ; http:// clinical trials.gov/ct2/show/NCT01859273 ( Archived by WebCite at http://www.webcitation.org/6IqfCa3A3 )", "Background The effectiveness of mobile technology to improve medication adherence via customized Short Messaging Service ( SMS ) reminders for stroke has not been tested in re source poor areas . We design ed a r and omized controlled trial to test the effectiveness of SMS on improving medication adherence in stroke survivors in Pakistan . Methods This was a parallel group , assessor-blinded , r and omized , controlled , superiority trial . Participants were central ly r and omized in fixed block sizes . Adult participants on multiple medications with access to a cell phone and stroke at least 4 weeks from onset ( Onset as defined by last seen normal ) were eligible . The intervention group , in addition to usual care , received reminder SMS for 2 months that contained a ) Personalized , prescription tailored daily medication reminder(s ) b ) Twice weekly health information SMS . The Health Belief Model and Social Cognitive theory were used to design the language and content of messages . Frontline SMS software was used for SMS delivery . Medication adherence was self-reported and measured on the vali date d Urdu version of Morisky Medication Adherence Question naire . Multiple linear regression was used to model the outcome against intervention and other covariates . Analysis was conducted by intention-to-treat principle . Results Two hundred participants were enrolled . 38 participants were lost to follow-up . After 2 months , the mean medication score was 7.4 ( 95 % CI : 7.2–7.6 ) in the intervention group while 6.7 ( 95 % CI : 6.4–7.02 ) in the control group . The adjusted mean difference ( Δ ) was 0.54 ( 95 % CI : 0.22–0.85 ) . The mean diastolic blood pressure in the intervention group was 2.6 mmHg ( 95 % CI ; −5.5 to 0.15 ) lower compared to the usual care group . Conclusion A short intervention of customized SMS can improve medication adherence and effect stroke risk factors like diastolic blood pressure in stroke survivors with complex medication regimens living in re source poor areas .Trial registration Clinical trials.gov NCT01986023 last accessed at https:// clinical", "Background : Medication non-adherence leads to a vast range of negative outcomes in patients with coronary artery disease . An automated web-based system managing short message service ( SMS ) reminders is a telemedicine approach to optimise adherence among patients who frequently forget to take their medications or miss the timing . Aim : This paper sought to investigate the effect of automated SMS-based reminders on medication adherence in patients after hospital discharge following acute coronary syndrome ( ACS ) . Methods : An interventional study was conducted at a tertiary teaching hospital in Malaysia . A total of 62 patients with ACS were equally r and omised to receive either automated SMS reminders before every intake of cardiac medications or only usual care within eight weeks after discharge . The primary outcome was adherence to cardiac medications . Secondary outcomes were the heart functional status , and ACS-related hospital readmission and death rates . Results : There was a higher medication adherence level in the intervention group rather than the usual care group , ( χ2 (2)=18.614 , p of being low adherent among the control group was 4.09 times greater than the intervention group ( relative risk = 4.09 , 95 % confidence interval ( CI ) 1.82–9.18 ) . A meaningful difference was found in heart functional status between the two study groups with better results among patients who received SMS reminders , ( χ2 ( 1 ) = 16.957 , p automated SMS-based reminder system can potentially enhance medication adherence in ACS patients during the early post-discharge period", "Patient adherence to immunosuppressive medications adherence is crucial to survival of the patient and a transplanted kidney , yet adherence is variable . Using a prospect i ve , descriptive design , immunosuppressive medication adherence of 44 renal transplant recipients was followed for 6 months at a Midwestern transplant center using electronic monitoring . Four medication adherence patterns emerged from a hierarchical cluster analysis : those who took medications on time , those who took medications on time with late/missed doses , those who rarely took medications on time and who were late with morning and /or evening doses , and those who missed doses . This study is a step toward developing and implementing interventions targeted to specific patterns of poor adherence", "OBJECTIVES Evaluate the utility of 2 electronic medical record (EMR)-linked , automated phone reminder interventions for improving adherence to cardiovascular disease medications . STUDY DESIGN A 1-year , parallel arm , pragmatic clinical trial in which 21,752 adults were r and omized to receive either usual care ( UC ) or 1 of 2 interventions in the form of interactive voice recognition calls-regular ( IVR ) or enhanced ( IVR+ ) . The interventions used automated phone reminders to increase adherence to cardiovascular disease medications . The primary outcome was medication adherence ; blood pressure and lipid levels were secondary outcomes . METHODS The study took place in 3 large health maintenance organizations . We enrolled participants who were 40 years or older , had diabetes mellitus or atherosclerotic cardiovascular disease , and were suboptimally adherent . IVR participants received automated phone calls when they were due or overdue for a refill . IVR+ participants received these phone calls , plus personalized reminder letters , live outreach calls , EMR-based feedback to their primary care providers , and additional mailed material s. RESULTS Both interventions significantly increased adherence to statins and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers ( ACEIs/ARBs ) compared with UC ( 1.6 to 3.7 percentage points ) . Adherence to ACEIs/ARBs was also significantly higher for IVR+ relative to IVR participants . These differences persisted across subgroups . Among statin users , IVR+ participants had significantly lower low-density lipoprotein ( LDL ) levels at follow-up compared with UC ( Δ = -1.5 ; 95 % CI , -2.7 to -0.2 mg/dL ) ; this effect was seen mainly in those with baseline LDL levels ≥ 100 mg/dL ( Δ = -3.6 ; 95 % CI , -5.9 to -1.3 mg/dL ) . CONCLUSIONS Technology-based tools , in conjunction with an EMR , can improve adherence to chronic disease medications and measured cardiovascular disease risk factors", "OBJECTIVE To evaluate medication adherence and treatment outcomes in elderly out patients using daily-dose blister packaging ( Pill Calendar ) compared with medications packaged in bottles of loose tablets . DESIGN R and omized controlled trial . SETTING Ambulatory care clinics at Ohio State University Medical Center , Columbus ; University of Arizona Health Science Center , Tucson ; and Riverside Method ist Hospital Family Medicine Clinic , Columbus , Ohio , from July 1 , 2002 , to December 31 , 2004 . PATIENTS 85 individuals 65 years of age or older being treated with lisinopril for hypertension . INTERVENTION Patients were r and omly assigned to receive lisinopril in either daily-dose blister packaging ( Pill Calendar ) or traditional bottles of loose tablets . MAIN OUTCOME MEASURES Adherence was assessed by prescription refill regularity and medication possession ratio ( MPR ) . Treatment outcome and use of medical services were assessed by medical record review of blood pressure and morbidity associated with poorly controlled hypertension . RESULTS Patients receiving lisinopril in the daily-dose blister packaging ( Pill Calendar ) refilled their prescriptions on time more often ( P = 0.01 ) , had higher MPRs ( P = 0.04 ) , and had lower diastolic blood pressure ( P = 0.01 ) than patients who had their medications packaged in traditional bottles of loose tablets . CONCLUSION Providing medications in a package that identifies the day each dose is intended to be taken and provides information on proper self-administration can improve treatment regimen adherence and treatment outcomes in elderly patients", "OBJECTIVE Pharmacologic treatment for secondary prevention of coronary heart disease ( CHD ) is critical to prevent adverse clinical outcomes . In a r and omized controlled trial , we compared antiplatelet and statin adherence among patients with CHD who received : ( 1 ) text messages ( TM ) for medication reminders and education , ( 2 ) educational TM only , or ( 3 ) No TM . METHODS A mobile health intervention delivered customized TM for 30 days . We assessed and analyzed medication adherence with electronic monitoring devices [ Medication Event Monitoring System ( MEMS ) ] by one-way ANOVA and Welch tests , two-way TM response rates by t-tests , and self-reported adherence ( Morisky Medication Adherence Scale ) by Repeated Measures ANOVA . RESULTS Among 90 patients ( 76 % male , mean age 59.2 years ) , MEMS revealed patients who received TM for antiplatelets had a higher percentage of correct doses taken ( p=0.02 ) , percentage number of doses taken ( p=0.01 ) , and percentage of prescribed doses taken on schedule ( p=0.01 ) . TM response rates were higher for antiplatelets than statins ( p=0.005 ) . Self-reported adherence revealed no significant differences among groups . CONCLUSION TM increased adherence to antiplatelet therapy demonstrated by MEMS and TM responses . PRACTICE IMPLICATION S Feasibility and high satisfaction were established . Mobile health interventions show promise in promoting medication adherence", "Background About one third of patients prescribed blood pressure or lipid-lowering drugs for the prevention of coronary heart disease and stroke do not take their medication as prescribed . We conducted a r and omized trial to evaluate text messaging as a means of improving adherence to cardiovascular disease preventive treatment . Methods 303 patients taking blood pressure and /or lipid-lowering medications were r and omly assigned to being sent text messages ( Text group , 151 ) or not being sent them ( No text group , 152 ) . Texts were sent daily for 2 weeks , alternate days for 2 weeks and weekly thereafter for 22 weeks ( 6 months overall ) , using an automated computer programme . Patients were asked to respond on whether they had taken their medication , whether the text reminded them to do so if they had forgotten , and if they had not taken their medication to determine if there was a reason for not doing so . At 6 months , use of medication was assessed . Results Two patients were lost to follow-up , providing data on 301 for analysis . In the No text group 38/151 ( 25 % ) took less than 80 % of the prescribed regimen ( ie . stopped medication completely or took it on fewer than 22 of the last 28 days of follow-up ) compared to 14/150 patients ( 9 % ) in the Text group – an improvement in adherence affecting 16 per 100 patients ( 95 % CI 7 to 24 ) , p take medication on at least one occasion and lead to 20/151 ( 13 % ) who stopped taking medication because of concern over efficacy or side-effects , resuming treatment . Conclusions In patients taking blood pressure or lipid-lowering treatment for the prevention of cardiovascular disease , text messaging improved medication adherence compared with no text messaging . Trial Registration Controlled-Trials.com IS RCT", "We conducted a feasibility study of a telehealth intervention ( an electronic pill box ) and an m-health intervention ( an app on a smartphone ) for improving medication adherence in older adults with heart failure . A secondary aim was to compare patient acceptance of the devices . The participants were 60 adults with HF ( 65 % male ) . Their average age was 69 years and 83 % were Caucasian . Patients were r and omized using a 2 × 2 design to one of four groups : pillbox silent , pillbox reminding , smartphone silent , smartphone reminding . We examined adherence to 4 medications over 28 days . The overall adherence rate was 78 % ( SD 35 ) . People with the telehealth device adhered 80 % of the time and people with the smartphone adhered 76 % of the time . Those who received reminders adhered 79 % of the time , and those with passive medication reminder devices adhered 78 % of the time , i.e. reminding did not improve adherence . Patients preferred the m-health approach . Future interventions may need to address other contributors to poor adherence such as motivation", "Background — In rural areas in China and India , the cardiovascular disease burden is high but economic and healthcare re sources are limited . This study ( the Simplified Cardiovascular Management Study [ SimCard ] ) aims to develop and evaluate a simplified cardiovascular management program delivered by community health workers with the aid of a smartphone-based electronic decision support system . Methods and Results — The SimCard study was a yearlong cluster-r and omized , controlled trial conducted in 47 villages ( 27 in China and 20 in India ) . Recruited for the study were 2086 individuals with high cardiovascular risk ( aged ≥40 years with self-reported history of coronary heart disease , stroke , diabetes mellitus , and /or measured systolic blood pressure ≥160 mm Hg ) . Participants in the intervention villages were managed by community health workers through an And roid-powered app on a monthly basis focusing on 2 medication use and 2 lifestyle modifications . In comparison with the control group , the intervention group had a 25.5 % ( P primary outcome of the proportion of patient-reported antihypertensive medication use pre- and post-intervention . There were also significant differences in certain secondary outcomes : aspirin use ( net difference : 17.1 % ; P ) and systolic blood pressure ( –2.7 mm Hg ; P=0.04 ) . However , no significant changes were observed in the lifestyle factors . The intervention was culturally tailored , and country-specific results revealed important differences between the regions . Conclusions — The results indicate that the simplified cardiovascular management program improved quality of primary care and clinical outcomes in re source -poor setting s in China and India . Larger trials in more places are needed to ascertain the potential impacts on mortality and morbidity outcomes . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01503814" ]

[ "Major Depression with Psychotic Features ( psychotic depression ) is a common , debilitating psychiatric disease . We hypothesized that mifepristone , a cortisol receptor ( GRII ) antagonist , would significantly reduce psychotic symptoms in psychotic depression . Two hundred fifty-eight patients with psychotic depression enrolled at 29 sites were r and omized to mifepristone or placebo for 7 days . The primary outcome was rapid and sustained response , defined as a 50 % or greater decrease in Brief Psychiatric Rating Scale - Positive Symptom Subscale scores at the end of treatment ( day7 ) and 49 days later ( day 56 ) . Cochran-Mantel-Haenszel compared proportions of responders to mifepristone versus placebo adjusting for site . Exploratory analyses compared response of patients with mifepristone plasma concentrations of > or = 1800 ng/ml to placebo . The primary endpoint was not statistically significant . However , the Breslow-Day test indicated a statistically significant site-by-treatment interaction . Mifepristone produced significantly higher response among the twenty sites who participated from the trial onset ( p mifepristone plasma levels > or = 1800 ng/ml were significantly more likely to respond than placebo patients ( Intent-to-Treat : OR=2.4 , p=.03 ; Initial 20 sites : OR=4.1 , p=.002 ) . The results of this trial are instructive in two respects . First , while statistical adjustments for [ corrected ] site are common in multisite clinical trials , this study reminds trialists to formally evaluate the interaction of site by treatment . Second , the association between increased mifepristone plasma concentration levels and greater clinical response , detected despite the site-by-treatment interaction , suggests that higher plasma levels may be needed for maximizing the probability of a positive response", "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", "This article reports on the evidence for the validity of psychotic major depression as a distinct subtype based on cross-sectional and 1-year prospect i ve data from the Epidemiologic Catchment Area study . Consistent with findings from previous clinical studies , only about 14 % of major depressions were accompanied by psychotic features . Psychotic as compared with nonpsychotic depression had a more severe course , as reflected in increased risk of relapse , persistence over 1 year , suicide attempts , hospitalization , comorbidity , and financial dependency . These differences could not be explained by differences in demographic characteristics or by symptom severity , as assessed by symptom profile or number of symptoms . The boundary problem with schizophrenia and bipolar affective disorder that is seen in clinical studies was also found in this sample . To our knowledge , this is the first study to examine the validity of psychotic depression in a community sample ; the findings are consistent with those from clinical sample s. They support the clinical significance of psychotic depression and the continuation of its inclusion as a distinct subtype in DSM-IV", "The rationale for treating psychotic major depression with glucocorticoid receptor ( GR ) antagonists is review ed . Five patients with psychotic major depression were given 600 mg of mifepristone in a 4-day , double-blind , placebo-controlled crossover study . All the patients completed the protocol and adverse effects were not observed or reported . All of the five patients showed substantial improvements in their Hamilton Rating Scale for Depression scores while they were receiving mifepristone , and four of the five patients showed substantial improvement in their Brief Psychiatric Rating Scale scores . Little , if any , improvement was seen with placebo . These preliminary results suggest that short-term use of GR antagonists may be effective in the treatment of psychotic major depression and that additional study , perhaps using higher doses or more treatment days , seems warranted", "Patients with psychotic depression respond well when treated with a combination of an antidepressant and antipsychotic medication . We previously reported that they will respond in a similar fashion when treated with amoxapine monotherapy . There are few prospect i ve studies on the pharmacologic treatment response of psychotic depression subtypes . We treated 37 in patients , 21 with mood congruent ( MC ) psychotic depression and 16 with mood incongruent ( MI ) psychotic depression , in a r and omized double-blind fashion with either the combination of amitriptyline and perphenazine or with amoxapine for 4 weeks . Depression and psychosis ratings improved in a similar manner in both the MC or MI patients irrespective of medication treatment group . Global response rates were similar in the MI patients and MC patients . The data suggest that classifying psychotic depression into MC versus MI subtypes may have limited acute prognostic value in pharmacotherapy response rates", "High rates of attrition have been reported in r and omized controlled trials of patients with severe psychiatric illness , including psychotic depression ( MDpsy ) . The purpose of this study is to examine factors associated with overall attrition and with subtypes of attrition in the Study of the Pharmacotherapy of Psychotic Depression ( STOP-PD ) . Secondary analysis of data collected in a multi-site , r and omized , placebo-controlled trial . Clinical services of academic hospitals . Participants comprised 259 persons with MDpsy , aged 18 - 93 years . The intervention consisted of the r and om allocation to 12 weeks of treatment of either olanzapine plus sertraline or olanzapine plus placebo . Demographic and clinical variables associated with overall non-completion and sub-types of non-completion of r and omized treatment . One hundred and seventeen ( 45.2 % ) subjects did not complete 12 weeks of r and omized treatment . In a logistic regression analysis , inpatient entry status , olanzapine monotherapy , and higher cumulative medical burden were statistically significant independent predictors of overall non-completion . In a multinomial logistic regression model that examined predictors of subtypes of non-completion , subjects who entered the study as an inpatient were less likely to complete because of inadequate efficacy as determined by the investigator , and older subjects were less likely to complete because of poorer tolerability . Subjects who were assigned to olanzapine monotherapy , younger subjects , and subjects who entered the study as in patients were less likely to complete because of reasons other than efficacy or tolerability . Underst and ing factors that contribute to premature discontinuation in studies of MDpsy , and to the specific reasons for attrition , has the potential to improve the management of this disorder , as well as improve the design of future clinical trials of MDpsy", "Abstract : This prospect i ve study assessed the influence of resistance to antidepressant pharmacotherapy on the short-term response to subsequent electroconvulsive therapy ( ECT ) . Previous research has shown that patients with medication resistance were less likely to respond to ECT . This finding may be applicable to the population of depressed in patients in The Netherl and s , where ECT is often preceded by several medication trials . Eighty-five patients ( 61 female and 24 male patients ) with DSM-IV criteria for depressive disorder , both with and without mood congruent psychotic features , were included for analysis . Medication resistance was rated with the Antidepressant Treatment History Form . Medication resistance was predefined in accordance with the previous research in this field . When a reduction of at least 50 % on the 17-item version of the Hamilton Rating Scale for Depression ( HRSD ) between pre- and post-ECT is used as response criterion , medication-resistant patients were equally likely to respond to subsequent ECT ( 30/48 = 82.5 % ) than patients without medication resistance ( 30/37 = 81.1 % ) . Even when post-ECT HRSD score ≤7 was used ( full remission ) , there was no significant difference between medication-resistant patients ( 21/48 = 43.8 % ) and patients without medication resistance ( 15/37 = 40.5 % ) . When potential confounding variables were taken into account , these differences remain nonsignificant . In contrast to earlier research , medication resistance does not influence short-term response to subsequent ECT and it can still be of considerable efficacy", "Psychotic major depression ( PMD ) is found to be a relatively common psychiatric condition that affects up to nearly 20 % of patients with major depression . Previous studies by our group have shown rapid reversal of psychotic symptoms in some PMD patients treated with mifepristone , in addition to restoring a more normal afternoon cortisol release . The rationale for treating patients with PMD with a glucocorticosteroid receptor antagonist is further discussed . In total , 30 patients with PMD were treated with either 600 mg/day mifepristone or placebo for 8 days in a r and omized double-blind manner . The Hamilton Depression Rating Scale ( HDRS ) and the Brief Psychiatric Rating Scale ( BPRS ) were administered at baseline and again after 8 days of treatment . Cortisol and ACTH were measured hourly from 1800 to 0900 at baseline and after 8 days of treatment . Significantly , more patients in the mifepristone group ( seven of 15 ) showed a 50 % or greater decline on the BPRS positive symptom subscale , an index of psychotic symptoms , as compared to the placebo group ( two of 15 ) . Patients who received mifepristone had lower HDRS and BPRS scores at study completion compared to those who received placebo , but these differences were not statistically significant . In addition , mifepristone significantly elevated cortisol and ACTH levels and steepened ascending slopes from 1800 to 0100 and from 0100 to 0900 as compared to placebo . Clinical and biological effects of mifepristone were comparable among males and females . Age was found to significantly and positively correlate with changes in cortisol and ACTH . These results suggest that short-term use of mifepristone may be effective in the treatment of PMD and may re-regulate the HPA axis . Additional blinded studies are warranted", "The authors investigated the pharmacological treatment of delusional depression by assigning patients on a r and om double-blind basis to amitriptyline alone , perphenazine alone , or a combination of the two . Fourteen ( 78 % ) of the 18 patients assigned to amitriptyline plus perphenazine were responders , compared with seven ( 41 % ) of 17 patients treated with amitriptyline alone and three ( 19 % ) of the 16 patients treated with perphenazine alone . The combination of amitriptyline and perphenazine was clearly superior ( p less than .01 )", "Preliminary open trials performed by the authors and others with Moclobemide , a new MAO-A inhibitor , indicated that the drug has a satisfactory antidepressant activity . In the present double-blind study Moclobemide has been compared to placebo in a group of 34 unipolar psychotic or neurotic depressed patients . The mean daily dose of Moclobemide was 297 mg and treatment lasted from two to four weeks . Drug effectiveness was measured by improvements in the Hamilton Rating Scale for Depression ( HRSD ) , Clinical Global Impression ( CGI ) and 100 mm Visual Analogue Scale ( VAS ) . The results have shown that the active drug was markedly superior to placebo . The mean total score of HRSD was reduced from 41.7 to 16.5 in 18 pts . treated with Moclobemide and from 36.3 to 29.1 in 16 pts . who received placebo . Self- assessment with VAS showed a mean reduction from 82.7 mm to 42.2 mm and from 84.3 to 70.6 mm respectively . Moderate to marked improvement was observed by the CGI in 15 cases treated with Moclobemide and mild to moderate in 5 cases who received placebo . The treatment was well tolerated", "Open-label studies and r and omized clinical trials have suggested that mifepristone may be effective for the treatment of major depression with psychotic features ( psychotic depression ) . A recent study reported a correlation between mifepristone plasma concentration and clinical response . The current study aim ed to evaluate the safety and efficacy of mifepristone and , secondarily , to test whether response was significantly greater among patients with mifepristone plasma concentrations above an a priori hypothesized threshold . A total of 433 patients who met criteria for psychotic depression were r and omly assigned to receive 7 days of either mifepristone ( 300 , 600 , or 1200 mg ) or placebo . Response was defined as a 50 % reduction in psychotic symptoms on both days 7 and 56 . Cochran-Mantel-Haenszel tests compared ( 1 ) the proportion of responders among patients assigned mifepristone versus placebo and ( 2 ) the proportion of responders among the subset of patients with plasma concentrations greater than 1660 ng/mL versus placebo . Mifepristone was well tolerated at all 3 doses . The proportion of responders r and omized to mifepristone did not statistically differ from placebo . Patients with trough mifepristone plasma concentrations greater than 1660 ng/mL were significantly more likely to have a rapid and sustained reduction in psychotic symptoms than those who received placebo . The study failed to demonstrate efficacy on its primary end point . However , the replication of a statistically significant linear association between mifepristone plasma concentration and clinical response indicates that mifepristone at sufficient plasma levels may potentially be effective in rapidly and durably reducing the psychotic symptoms of patients with psychotic depression", "BACKGROUND Patients with delusional depression are difficult to treat . The atypical antidepressant trimipramine was effective in a previous 4-week open label pilot study in patients with this disorder . The major neurobiological effect of trimipramine is the inhibition of the hypothalamic-pituitary-adrenocortical ( HPA ) system . In delusional depression HPA overactivity is more distinct than in other subtypes of depression . HPA suppression is thought to contribute to the action of trimipramine . METHODS In a double-blind , r and omized , placebo controlled multicenter trial we compared the effects of trimipramine monotherapy versus a combination of amitriptyline and haloperidol . Dosage was increased stepwise from 100 mg up to 400 mg trimipramine and from 100 mg up to 200 mg amitriptyline combined with 2 mg up to 7.5 mg haloperidol . The average dose of trimipramine was higher than that of amitriptyline throughout the trial . During sixth week mean dosage ( + /-st and ard deviation ) were 356.1+/-61.2 mg trimipramine , 184.0+/-23.6 mg amitriptyline and 6.3+/-1.8 mg haloperidol . During six weeks psychometric assessment s were performed weekly . For HPA monitoring a dexamethasone/corticotropin-releasing hormone ( Dex/CRH ) test was performed before active medication and at the end of treatment . Additionally tolerability was monitored by ECG , EEG assessment of extrapyramidal symptoms and akathisia , clinical laboratory routine and recording of blood pressure and heart rate . Adverse events were documented . RESULTS 94 patients were enclosed into the study . The per protocol sample consisted of 33 patients of the trimipramine group and of 24 patients of the amitriptyline/haloperidol group . The decrease of the Hamilton depression ( HAMD ) score ( 24 items ) showed non-inferiority of trimipramine compared to amitriptyline/haloperidol . Twenty-eight patients ( 84.84 % ) in the trimipramine arm and 17 patients ( 70.83 % ) in the amitriptyline/haloperidol arm were responders ( HAMD Remission ( HAMD trimipramine and in 11 ( 45.83 % ) patients after amitriptyline/haloperidol . No significant differences were found concerning response and remission . The cortisol and ACTH response in the Dex/CRH test decreased between days 1 and 42 in both groups . Serious side effects were not reported . CONCLUSION In all , trimipramine monotherapy appears to be an effective treatment in delusional depression", "BACKGROUND Most studies report a poor response of psychotic depressed patients to treatment with a tricyclic antidepressant alone compared to combined treatment with an antipsychotic preparation and compared to non-psychotic depressed patients . However , the issue of optimal treatment of psychotic depressed patients has not been resolved as yet . Previously , we reported a significant difference in response to mirtazapine compared to imipramine in a r and omised , double-blind , fixed-blood-level study with in- patients with major depression . In the current study we focus on the treatment response to imipramine in a group of patients with psychotic depression and compare this to patients who manifest no psychotic features . Our aim in presenting these findings was to contribute to the discussion on the optimal treatment of psychotic depressed patients . METHODS Fifty-two patients with a unipolar major depression ( DSM-IIIR ) , comprising 15 patients with mood-congruent psychotic features and 37 patients with no psychotic features , were commenced on treatment with imipramine after a drug-free and placebo-washout period of 7 days . The dose of imipramine was adjusted for all patients to a predetermined blood level . The Hamilton ( HRSD ) and Montgomery-Asberg ( MADRS ) Depression Rating Scales were used to evaluate treatment response . RESULTS Of the 45 patients who completed the study , nine of the 13 psychotic patients ( 69.2 % ) and 14 of the 32 non-psychotic patients ( 43.8 % ) responded to treatment . The patients with psychotic features demonstrated a lower mean final HRSD score , together with a greater fall in MADRS score over time , compared to the non-psychotic group . Both these findings remained statistically significant after controlling for a number of possible confounding factors . CONCLUSIONS These results demonstrate that , in this group of patients with mood-congruent psychotic depression , imipramine used on its own together with strict control of serum drug levels produced a high treatment response rate of 70 % . CLINICAL IMPLICATION S If replicated , these findings suggest that imipramine with control of blood levels of medication may be a useful first-line treatment for depressed patients with mood-congruent psychotic features . LIMITATIONS Our sample size was modest . This fact may caution against generalisation of the results", "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 Traditionally , it has been widely assumed that the likelihood of response to ECT is independent of the adequacy of previous treatment with antidepressant medications . However , recent research has raised the possibility that medication-resistant patients with depression have a poorer clinical ECT outcome than patients who have not failed previous adequate medication trials . METHOD Medication resistance of 100 patients with primary , unipolar , nonpsychotic major depression was evaluated during the index episode with the Antidepressant Treatment History Form . Patients were recruited and treated with ECT at three sites ; st and ardized ECT and clinical assessment procedures were used . Clinical outcome was assessed immediately and 1 week after completion of the ECT course . RESULTS Patients who previously had failed one or more adequate antidepressant medication trials were less likely to respond to subsequent ECT than patients not known to be medication resistant . This finding held within each study site , whether clinical response was assessed categorically or in terms of the magnitude of symptomatic improvement and after the authors accounted for other potential predictors of clinical outcome . Resistance to heterocyclic antidepressants predicted poorer outcome after ECT , while resistance to selective serotonin reuptake inhibitors and monoamine oxidase inhibitors did not show significant predictive relations . CONCLUSIONS While a substantial percentage of medication-resistant patients respond to ECT , clinical outcome in this group is inferior to that of patients without established medication resistance . The predictive power of medication resistance is generalizable across diverse clinical setting s , particularly for heterocyclic antidepressants , which perhaps suggests an overlap in the mechanisms of actions of ECT and this medication class", "This paper describes the results obtained by combining data from the Northwick Park and Leicester r and omised controlled trials of ECT . Patients who suffered from depression in which retardation and delusions were features and who received real ECT had a significantly improved outcome at the end of four weeks of treatment ( as measured by improvement in the HRSD ) in comparison with those who received simulated ECT . However , this treatment effect was not detectable at six-month follow-up . Patients who were neither retarded nor deluded did not benefit significantly from real as opposed to simulated ECT", "In a multicenter , double-blind , parallel group trial , the efficacy of risperidone ( RIS ) was compared with a combination of haloperidol and amitriptyline ( HAL/AMI ) over 6 weeks in patients with coexisting psychotic and depressive symptoms with either a schizoaffective disorder , depressive type , a major depression with psychotic features , or a nonresidual schizophrenia with major depressive symptoms according to DSM-III-R criteria . A total of 123 patients ( 62 RIS ; 61 HAL/AMI ) were included ; the mean daily dosage at endpoint was 6.9 mg RIS versus 9 mg HAL combined with 180 mg AMI . Efficacy results for those 98 patients ( 47 RIS ; 51 HAL/AMI ) who completed at least 3 weeks of double-blind treatment revealed in both treatment groups large reductions in the Positive and Negative Syndrome Scale-derived Brief Psychiatric Rating Scale ( RIS 37 % ; HAL/AMI 51 % ) and the Bech-Rafaelsen Melancholia Scale total scores ( RIS 51 % ; HAL/AMI 70 % ) . The reductions in the Brief Psychiatric Rating Scale and the Bech-Rafaelsen Melancholia Scale scores in the total group were significantly larger in the HAL/AMI group than in the RIS group ( p incidence of extrapyramidal side effects as assessed by the Extrapyramidal Symptom Rating Scale was slightly higher under RIS ( 37 % ) than under HAL/AMI ( 31 % ) . Adverse events were reported by 66 % of RIS and 75 % of HAL/AMI patients . The results of this trial suggest that the therapeutic effect of HAL/AMI is superior to RIS in the total group of patients with combined psychotic and depressive symptoms . However , subgroup differences have to be considered", "OBJECTIVE To conduct the first r and omized study comparing the efficacy of an antidepressant alone versus an antidepressant plus a neuroleptic in the treatment of late-life psychotic depression . METHOD The efficacy of nortriptyline plus placebo versus nortriptyline plus perphenazine was compared in 36 patients aged 50 years or older presenting with a major depressive episode with psychotic features ( DSM-III-R criteria ) . Patients were started openly on nortriptyline treatment titrated to therapeutic levels . They were then r and omly assigned under double-blind conditions to addition of perphenazine or placebo . Outcomes were compared in the 2 treatment groups using measures including the Hamilton Rating Scale for Depression ( HAM-D ) and the Brief Psychiatric Rating Scale ( BPRS ) ; side effects were assessed with the Geriatric Movement Disorder Assessment . RESULTS Both treatments were well tolerated . Of the 36 r and omly assigned patients , 2 ( 1 in each group ) dropped out due to treatment-related adverse effects . Four additional patients dropped out for administrative reasons . Thirty patients received nortriptyline for at least 4 weeks combined with either perphenazine ( N = 14 ) or placebo ( N = 16 ) for at least 2 weeks ( median = 9 weeks ) . There was no significant difference between the completers in the 2 treatment groups when comparing their scores on the HAM-D , the BPRS , its psychoticism subscale , or any side effects measure . Rates of response ( defined as resolution of both depression and psychosis ) did not differ significantly in the 2 groups ( nortriptyline-plus-perphenazine group , 50 % vs. nortriptyline-plus-placebo group , 44 % ) . CONCLUSION When treating older patients with psychotic depression , the addition of a moderate dose of a traditional neuroleptic to a tricyclic antidepressant was well tolerated but did not improve efficacy . This finding supports existing data suggesting that the pathophysiology ( and thus the required treatment ) of psychotic depression may be different early and late in life", " Wijkstra J , Burger H , van den Broek WW , Birkenhäger TK , Janzing JGE , Boks MPM , Bruijn JA , van der Loos MLM , Breteler LMT , Ramaekers GMGI , Verkes RJ , Nolen WA . Treatment of unipolar psychotic depression : a r and omized , double‐blind study comparing imipramine , venlafaxine , and venlafaxine plus quetiapine", "BACKGROUND Abnormalities in the hypothalamic pituitary adrenal axis have been implicated in the pathophysiology of psychotic major depression ( PMD ) . Recent studies have suggested that the antiglucocorticoid , mifepristone might have a role in the treatment of PMD . The current study tested the efficacy of mifepristone treatment of the psychotic symptoms of PMD . METHODS 221 patients , aged 19 to 75 years , who met DSM-IV and SCID criteria for PMD and were not receiving antidepressants or antipsychotics , participated in a double blind , r and omized , placebo controlled study . Patients were r and omly assigned to either 7 days of mifepristone ( n = 105 ) or placebo ( n = 116 ) followed by 21 days of usual treatment . RESULTS Patients treated with mifepristone were significantly more likely to achieve response , defined as a 30 % reduction in the Brief Psychiatric Rating Scale ( BPRS ) . In addition , mifepristone treated patients were significantly more likely to achieve a 50 % reduction in the BPRS Positive Symptom Scale ( PSS ) . No significant differences were observed on measures of depression . CONCLUSION A seven day course of mifepristone followed by usual treatment appears to be effective and well tolerated in the treatment of psychosis in PMD . This study suggests that the antiglucocorticoid , mifepristone , might represent an alternative to traditional treatments of psychosis in psychotic depression", "BACKGROUND Previous studies have reported the efficacy of selective serotonin reuptake inhibitors as monotherapy in the treatment of delusional depression . The clinical efficacy of venlafaxine , a serotonin-norepinephrine reuptake blocker , has been demonstrated in the treatment of patients with moderate-to-severe depression , but , to date , no evidence is available about its use in depressed patients with psychotic features . METHOD Under double-blind conditions , 28 hospitalized patients who met DSM-IV criteria for major depression , severe with psychotic features , were r and omly assigned to receive fluvoxamine or venlafaxine , 300 mg/day , for 6 weeks . Severity was evaluated using the Hamilton Rating Scale for Depression ( HAM-D ) and the Dimensions of Delusional Experience Rating Scale ( DDERS ) administered at baseline and every week thereafter . Side effects were also recorded . Clinical response was defined as a reduction of the scores in the 21-item HAM-D to 8 or below and in the DDERS to 0 . RESULTS At study completion , the response rates were 78.6 % ( N = 11 ) and 58.3 % ( N = 7 ) for fluvoxamine and venlafaxine , respectively . No significant difference was found between drugs ( Fisher exact test , p = .40 ) . Analysis of covariance on HAM-D scores did not reveal a significantly different decrease of depressive symptomatology between the 2 treatment groups ( p = .14 ) . Treatment response appeared to be unrelated to the demographic and clinical characteristics recorded . The overall safety profile of both fluvoxamine and venlafaxine was favorable . CONCLUSION The results of this pilot double-blind trial show that fluvoxamine is useful in the treatment of delusional depression and suggest that venlafaxine may also be an effective compound in the treatment of this disorder . The latter finding , although promising , warrants further replication in a larger sample of patients", "OBJECTIVE In this study the authors evaluated the efficacy and the tolerability of sertraline and paroxetine in the treatment of delusional depression . METHOD Under double-blind conditions , 46 hospitalized patients who met the DSM-III-R criteria for major depression with psychotic features were treated with sertraline or paroxetine for 6 weeks . RESULTS The response rates were 75 % and 46 % for sertraline and paroxetine , respectively . The dropout rate was substantial ( 41 % ) in the paroxetine group and was attributable to side effects . CONCLUSIONS Selective serotonin reuptake inhibitors administered alone are useful in the treatment of delusional depression", "Abstract : The purpose of this study was to compare the efficacy and safety of olanzapine ( OLZ ) monotherapy and an olanzapine/fluoxetine combination ( OFC ) with placebo ( PLA ) for unipolar major depression with psychotic features . Under a single protocol , two 8-week , double-blind trials were conducted at 27 sites . Patients ( n = 124 trial 1 , n = 125 trial 2 ) were r and omized to 1 of 3 treatment groups : OLZ ( 5 to 20 mg/d ) , PLA , or OFC ( olanzapine 5 to 20 mg/d + fluoxetine 20 to 80 mg/d ) . The primary outcome measure was the 24-item Hamilton Depression Rating Scale total score . For trial 1 , endpoint improvement for the OLZ group ( −14.9 ) was not significantly different from the PLA or OFC groups . The OFC group had significantly greater endpoint improvement ( −20.9 ) than the PLA group ( −10.4 , P = 0.001 ) ; this significant difference was present within 7 days of therapy and maintained at every subsequent visit . The OFC group also had significantly higher response rate ( 63.6 % ) than the PLA ( 28.0 % , P = 0.004 ) or OLZ ( 34.9 % , P = 0.027 ) groups . For trial 2 , there were no significant differences among treatment groups on the 24-item Hamilton Depression Rating Scale total scores or response rates . The combination exhibited a comparable safety profile with OLZ monotherapy and no significant increases in extrapyramidal symptoms compared with placebo . Patients with major depression with psychotic features treated with OLZ monotherapy did not demonstrate significant depressive symptom improvement compared with placebo in either trial ; however , an olanzapine/fluoxetine combination was associated with significant improvement compared with placebo in one trial and was well tolerated", "The authors examined the efficacy of ketoconazole in 16 adults with treatment-refractory major depressive disorder . Subjects participated in a 6-week , double-blind , placebo-controlled trial . Assessment s of mood were made using the Hamilton Rating Scale for Depression ( HAM-D ) , the Beck Depression Inventory ( BDI ) , and the Clinical Global Impression Scale ( CGI ) . Results showed that none of eight patients r and omly assigned to receive placebo and two of eight patients r and omly assigned to receive ketoconazole met criteria for response . As a group , patients assigned to receive ketoconazole showed no significant reductions in HAM-D , BDI , or CGI scores during the 6-week trial compared with those receiving placebo . These findings suggest a limited efficacy for ketoconazole in patients with treatment-refractory major depression", "This study investigated the pharmacological treatment of delusional depressives by assigning patients on a r and om double-blind basis to amitriptyline ( AT ) alone , perphenazine ( PER ) alone , or AT + PER . As reported in an earlier paper , the combination of AT + PER was the superior treatment with a response rate of 78 % compared with 41 % for AT alone and 19 % for PER alone . This difference is both clinical ly and statistically significant ( p the patients on AT + PER had higher plasma levels of AT and its pharmacologically active metabolite nortriptyline ( NT ) than the patients on AT alone . Although the response rate had a direct relationship to AT + NT plasma levels , an analysis of variance showed that the group of patients treated with AT + PER still had a significantly higher response rate , even after controlling for the plasma levels of AT + NT ( p PER plasma levels and clinical response", "Having failed to respond to an adequate antidepressant treatment course predicts poorer treatment outcomes in patients with major depression . However , little is known about the impact of prior treatment on the outcome of major depression with psychotic features ( MDpsy ) . We examined the effect of prior treatment history on the outcome of pharmacotherapy of MDpsy in patients who participated in the STOPD-PD study , a r and omized , double-blind , clinical trial comparing a combination of olanzapine plus sertraline vs. olanzapine plus placebo . The strength of treatment courses received prior to r and omization was classified using a vali date d method . A hierarchy of outcomes was hypothesized based on treatments received prior to r and omization and r and omized treatment . A high remission rate was observed in subjects with a history of no prior treatment or inadequate treatment who were treated with a combination of olanzapine and sertraline . A low remission rate was observed in subjects who had previously failed to respond to an antidepressant alone and who were treated with olanzapine monotherapy . A low remission rate was also observed in subjects who had previously failed to respond to a combination of an antipsychotic and an antidepressant . Similar to patients with major depression , these results emphasize the impact of prior pharmacotherapy on treatment outcomes in patients with MDpsy", "OBJECTIVE Practice guidelines recommend the use of a combination of an antidepressant and an antipsychotic for the pharmacologic treatment of major depressive disorder with psychotic features ( MD-Psy ) . We assessed the extent to which the pharmacotherapy received by patients with MD-Psy under usual care conforms to these recommendations . METHOD We assessed the pharmacotherapy received under usual care conditions by 100 patients with MD-Psy prior to enrollment in STOP-PD ( Study of the Pharmacotherapy of Psychotic Depression ) , a 12-week r and omized , controlled trial comparing olanzapine plus sertraline to olanzapine plus placebo . Our assessment took place from January 2003 to May 2004 . The strength of antidepressant trials was rated using the Antidepressant Treatment History Form ( ATHF ) . The strength of antipsychotic trials or combinations of antidepressants and antipsychotics was rated using a modified version of the ATHF . We also determined whether the strength of antipsychotic or combination trials was associated with age , the duration of the current depressive episode , medical burden , cognitive status , or the severity of depressive or psychotic symptoms . RESULTS Most patients with MD-Psy were treated with antidepressants ( N = 82 , 82 % ) or antipsychotics ( N = 65 , 65 % ) . About half of the patients ( N = 48 , 48 % ) received therapeutic doses of an antidepressant ; 10 % ( N = 10 ) received an intermediate dose of an antipsychotic , and 6 % ( N = 6 ) received a high dose . Overall , only 5 % ( N = 5 ) received a combination of an adequate dose of an antidepressant and a high dose of an antipsychotic . The strength of both antipsychotic trials ( p = .021 ) and combination trials ( p = .039 ) was significantly associated only with a longer duration of the current depressive episode . CONCLUSIONS These findings show a persisting low use of antipsychotics in the treatment of MD-Psy . Given the high morbidity rates associated with MD-Psy , it is important to continue to educate clinicians regarding its identification and treatment . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00056472", "Phenelzine and imipramine were compared double-blind , in 43 depressed in patients . A placebo week preceded drug treatment ; this allowed early identification of placebo responders who did not therefore enter the study . After three weeks treatment , the two drugs were equally effective on Hamilton , Beck and SCL-90 measures of depression and anxiety . On the the SCL-90 scales of hostility and paranoia imipramine was more effective ; in some patients phenelzine was associated with increased hostility . Measurement of MAO inhibition and plasma tricyclic levels indicated that adequate doses were generally used - ( mean 81 mg/day phenelzine and 144 mg/day imipramine ) ", "Tricyclic antidepressants and more recent antidepressants are generally considered to have equivalent efficacy in the treatment of depression . After a previous report of a marked difference in the response to mirtazapine compared to imipramine , we report here an analysis of different symptom clusters . One hundred seven consecutive in- patients with major depression ( Diagnostic and Statistical Manual III-R , DSM-III-R ) and a Hamilton Rating Scale for Depression ( HRS-D ) score of 18 points or more were r and omly assigned to double-blind treatment . Two and four weeks after predefined blood levels had been obtained , the severity of depression was assessed using the HRS-D. The mean dosages used were 235 mg/day of imipramine and 77 mg/day of mirtazapine , the latter being in excess of the 15 - 45 mg/day range currently advised . Total HRS-D scores and seven symptom clusters were analyzed in the 85 patients ( 79 % ) who were not receiving any co-medication . Imipramine was more effective against the clusters related to core symptoms of depression : \" depression and guilt \" , \" retardation \" , and \" melancholia \" , respectively . Mirtazapine showed a biphasic response with regard to the clusters \" sleep \" and \" anxiety/agitation \" , respectively , which consisted of a marked response after two weeks of predefined blood level , but with a waning of this effect at four weeks . Imipramine produced a more gradual response on these clusters , which was more pronounced at four weeks than with mirtazapine . Two aspects of the present study could be related to this finding : blood level control result ed in optimal treatment with imipramine but not mirtazapine , and - most importantly - the patients were not receiving any anxiolytic or hypnotic co-medication . These findings suggest that mirtazapine may have anxiolytic and sedative properties and fewer antidepressant properties than imipramine in severely depressed in- patients", "This double-blind , controlled study was undertaken to investigate whether the addition of pindolol could improve the therapeutic response to fluvoxamine of depressed patients with psychotic features . After a 1-week placebo run-in period , 72 patients received fluvoxamine 300 mg/day in combination with placebo or pindolol 7.5 mg/day . At study completion , 28 ( 80 % ) of 35 patients treated with fluvoxamine plus placebo and 29 ( 80.5 % ) of 36 patients treated with fluvoxamine plus pindolol were categorized as responders ( reduction of their score on the 21-item Hamilton Rating Scale for Depression to 8 or less and on the Dimension for the Delusional Experience Rating Scale to 0 ) . In the third and fourth weeks , the response rates were significantly superior in the fluvoxamine plus pindolol group ( p = 0.0001 , p = 0.023 , respectively ) . Treatment response seemed to be unrelated to the demographic and the clinical characteristics recorded . No significant difference was found comparing plasma levels of fluvoxamine between groups , thus excluding a pharmacokinetic interaction . Other than mild nausea and sedation in a few patients , treatments were well tolerated . No medically significant adverse events occurred . Depressed patients with psychotic features who were administered pindolol experienced a more rapid improvement during fluvoxamine treatment . Thus , the combination of fluvoxamine with pindolol may be a useful pharmacologic strategy in the treatment of this disorder . A rapid clinical response in such patients is of relevance in clinical practice as well as in economic fields , given the direct and indirect costs of depression", "The authors reanalyzed data from two earlier studies that used double-blind placebo-controlled formats to study the efficacy of amitriptyline . Using a 14-day drug-free ' wash-out ' period , they found that the placebo response rates were 0 % for psychotic depressives and 13.3 % for nonpsychotic depressives . Amitriptyline was significantly superior to placebo for both psychotic ( P less than or equal to 0.05 ) and nonpsychotic ( P less than or equal to 0.05 ) depressed patients", "CONTEXT Evidence for the efficacy of combination pharmacotherapy has been limited and without positive trials in geriatric patients with major depression ( MD ) with psychotic features . OBJECTIVES To compare remission rates of MD with psychotic features in those treated with a combination of atypical antipsychotic medication plus a serotonin reuptake inhibitor with those treated with antipsychotic monotherapy ; and to compare response by age . DESIGN Twelve-week , double-blind , r and omized , controlled trial . SETTING Clinical services of 4 academic sites . Patients Two hundred fifty-nine subjects with MD with psychotic features r and omized by age ( or = 60 years ) ( mean [ st and ard deviation ( SD ) ] , 41.3 [ 10.8 ] years in 117 younger adults vs 71.7 [ 7.8 ] years in 142 geriatric participants ) . Intervention Target doses of 15 to 20 mg of olanzapine per day plus masked sertraline or placebo at 150 to 200 mg per day . Main Outcome Measure Remission rates of MD with psychotic features . RESULTS Treatment with olanzapine/sertraline was associated with higher remission rates during the trial than olanzapine/placebo ( odds ratio [ OR ] , 1.28 ; 95 % confidence interval [ CI ] , 1.12 - 1.47 ; P in remission at their last assessment compared with 23.9 % of subjects treated with monotherapy ( chi(2)(1 ) = 9.53 , P = .002 ) . Combination therapy was comparably superior in both younger ( OR , 1.25 ; 95 % CI , 1.05 - 1.50 ; P = .02 ) and older ( OR , 1.34 ; 95 % CI , 1.09 - 1.66 ; P = .01 ) adults . Overall , tolerability was comparable across age groups . Both age groups had significant increases in cholesterol and triglyceride concentrations , but statistically significant increases in glucose occurred only in younger adults . Younger adults gained significantly more weight than older subjects ( mean [ SD ] , 6.5 [ 6.6 ] kg vs 3.3 [ 4.9 ] kg , P = .001 ) . CONCLUSIONS Combination pharmacotherapy is efficacious for the treatment of MD with psychotic features . Future research must determine the benefits vs risks of continuing atypical antipsychotic medications beyond 12 weeks . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00056472" ]

[ "BACKGROUND Depression is common and the efficacy of antidepressants is suboptimal . High plasma homocysteine has been consistently associated with depression , and treatment with certain B vitamins demonstrably reduces its concentration . AIMS To determine whether vitamins B6 , B12 and folic acid enhance response to antidepressant treatment over 52 weeks . METHOD R and omised , double-blind , placebo-controlled trial of citalopram ( 20 - 40 g ) together with 0.5 mg of vitamin B12 , 2 mg of folic acid and 25 mg of vitamin B6 for 52 weeks ( Australian and New Zeal and Clinical Trials Registry : 12609000256279 ) . Participants were community-dwelling adults aged 50 years or over with DSM-IV-TR major depression . We measured severity of symptoms with the Montgomery-Åsberg Depression Rating Scale ( MADRS ) . The primary outcome was remission of the depressive episode after 12 , 26 and 52 weeks . Secondary outcomes included reduction of MADRS scores over time and relapse of major depression after recovery by week 12 . Results In total , 153 people were r and omised ( 76 placebo , 77 vitamins ) . Remission of symptoms was achieved by 78.1 and 79.4 % of participants treated with placebo and vitamins by week 12 ( P = 0.840 ) , by 76.5 and 85.3 % at week 26 and 75.8 and 85.5 % at week 52 ( effect of intervention over 52 weeks : odds ratio ( OR ) = 2.49 , 95 % CI 1.12 - 5.51 ) . Group differences in MADRS scores over time were not significant ( P = 0.739 ) . The risk of subsequent relapse among those who had achieved remission of symptoms at week 12 was lower in the vitamins than placebo group ( OR = 0.33 , 95 % CI 0.12 - 0.94 ) . CONCLUSIONS B vitamins did not increase the 12-week efficacy of antidepressant treatment , but enhanced and sustained antidepressant response over 1 year . Replication of these findings would m and ate that treatment guidelines adopt the adjunctive use of B vitamins as a safe and inexpensive strategy to manage major depression in middle-aged and older adults ", "Objective Major depression is a mood disorder that causes changes in physical activity , appetite , sleep and weight . Regarding the role of zinc in the pathology of depression , the present study was aim ed to investigate the effects of zinc supplementation in the treatment of this disease . Methods This study was a double-blind r and omized clinical trial . Forty four patients with major depression were r and omly assigned to groups receiving zinc supplementation and placebo . Patients in Zinc group received daily supplementation with 25 mg zinc adjunct to antidepressant ; Selective Serotonin Reuptake Inhibitors ( SSRIs ) , while the patients in placebo group received placebo with antidepressants ( SSRIs ) for twelve weeks . Severity of depression was measured using the Beck Depression Inventory at baseline and was repeated at the sixth and twelfth weeks . ANOVA with repeated measure was used to compare and track the changes during the study . Results The mean score of Beck test decreased significantly in the zinc supplement group at the end of week 6 ( P mean score of Beck Depression Inventory reduced significantly compared to the placebo group at the end of 12th week ( P that zinc supplementation together with SSRIs antidepressant drug improves major depressive disorders more effectively in patients with placebo plus antidepressants ( SSRIs )", "BACKGROUND Epidemiological evidence supports a relationship between vitamin D and mental well-being , although evidence from large-scale placebo-controlled intervention trials is lacking . AIMS To examine if vitamin D supplementation has a beneficial effect on mood in community-dwelling older women ; if a single annual large dose of vitamin D has a role in the prevention of depressive symptoms ; and if there is an association between serum 25-hydroxyvitamin D levels and mental health . METHOD A double-blind , r and omised , placebo-controlled trial of women aged 70 or older ( the Vital D Study : IS RCT N83409867 and ACTR12605000658617 ) . Participants were r and omly assigned to receive 500 000 IU vitamin D(3 ) ( cholecalciferol ) orally or placebo every autumn/winter for 3 - 5 consecutive years . The tools utilised at various time points were the General Health Question naire , the 12-item Short Form Health Survey , the Patient Global Impression-Improvement scale and the WHO Well-Being Index . Serum 25-hydroxyvitamin D levels were measured in a subset of 102 participants . RESULTS In this non- clinical population , no significant differences between the vitamin D and placebo groups were detected in any of the measured outcomes of mental health . Serum 25-hydroxyvitamin D levels in the vitamin D group were 41 % higher than the placebo group 12 months following their annual dose . Despite this difference , scores from the question naires did not differ . Furthermore , there was no interaction between those on antidepressant/anxiety medication at baseline and the treatment groups . CONCLUSIONS The lack of improvement in indices of mental well-being in the vitamin D group does not support the hypothesis that an annual high dose of vitamin D(3 ) is a practical intervention to prevent depressive symptoms in older community-dwelling women", "Patients with depression have been extensively reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids ( PUFAs ) , including significantly low eicosapentaenoic acid and docosahexaenoic acid in cell tissue contents ( red blood cell membrane , plasma , etc . ) and dietary intake . However , more evidence is needed to support its relation . In this study , we conducted an 8-week , double-blind , placebo-controlled trial , comparing omega-3 PUFAs ( 6.6 g/day ) [ corrected ] with placebo , on the top of the usual treatment , in 28 patients with major depressive disorder . Patients in the omega-3 PUFA group had a significantly decreased score on the 21-item Hamilton Rating Scale for Depression than those in the placebo group ( P omega-3 PUFAs could improve the short-term course of illness and were well tolerated in patients with major depressive disorder", "The efficacy of a deficit oriented add-on therapy with free amino acids in depressive patients treated with the antidepressant Remeron ® was evaluated . About 40 in- patients were investigated by a r and omised double-blind placebo-controlled study during 4 weeks . Plasma levels of 20 amino acids and measures of depression , suicidal behaviour and aggression were surveyed on admission and after a 4 weeks ’ therapy with Remeron ® plus an individualized amino acid mixture or placebo . The preparation of the amino acid mixture was based on an aminogram and consisted of essential amino acids plus vitamins and trace elements as co-factors for the amino acid metabolism . Patients of the experimental group showed a significantly better improvement of depression and a higher responder rate than those of the placebo group . The results suggest that oral application of a deficit oriented amino acid mixture can improve the therapeutic outcome of an antidepressant . Furthermore , lacking side effects of the amino acids result ing also in a better patient compliance may improve the benefit/risk ratio ", "Controversy exists as to whether eicosapentaenoic acid ( EPA ) or docosahexaenoic acid ( DHA ) or both are responsible for the efficacy of n-3 polyunsaturated fatty acids in depression . We conducted a single-center , r and omized , double-blind , placebo-controlled , multi-arm , parallel-group trial , comparing the efficacy of EPA versus DHA as adjuvants to maintenance medication treatments for mild-to-moderate depression . Eighty-one mild-to-moderately depressed out patients were r and omly assigned to receive either 1g/d of EPA or DHA or placebo ( coconut oil ) for 12 weeks . The primary outcome measure was the 17-item Hamilton Depression Rating Scale ( HDRS ) final score in the modified intention-to-treat population , which comprised of all r and omized patients with at least 1 post-r and omization observation ( n=62 ; 61.3 % female ; mean age 35.1 ± 1.2 years ) . Allocated treatments were well tolerated . Although there was no significant difference between groups at baseline , patients in the EPA group showed a significantly lower mean HDRS score at study endpoint compared with those in the DHA ( p the baseline HDRS score ) was only observed in 6 patients receiving EPA , while no one in any of DHA or placebo groups responded to treatment . Overall , these data suggest greater efficacy of EPA compared to DHA or placebo as an adjunctive treatment in mild-to-moderate depression . However , further , r and omized controlled trials are needed to support these findings", " One hundred and fifteen patients from 5 general practice s participated in a 12-week , double-blind study comparing L-tryptophan , amitriptyline , L-tryptophan-amitriptyline combination and placebo in the treatment of depression . Analysis of total score on the Hamilton Depression Scale and a global rating of depression showed that all 3 active treatments were more effective than placebo . Significantly more patients were withdrawn as treatment failures in the placebo group compared with the active treatment groups . Side-effects necessitated withdrawal of more patients from the amitriptyline group than from the other active treatment groups , but this difference was not significant . Plasma amitriptyline and nortriptyline levels were similar in the amitriptyline and combined treatment groups . St and ard haematological and biochemical profiles did not alter significantly in any group , but mean heart rate was significantly increased in patients receiving amitriptyline . There was no change in free or total plasma tryptophan concentration with treatment or on remission of symptoms", "CONTEXT Studies of depressed psychiatric patients have shown that antidepressant efficacy can be increased by augmentation with omega-3 fatty acids . OBJECTIVE To determine whether omega-3 improves the response to sertraline in patients with major depression and coronary heart disease ( CHD ) . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial . Between May 2005 and December 2008 , 122 patients in St Louis , Missouri , with major depression and CHD were r and omized . INTERVENTIONS After a 2-week run-in period , all patients were given 50 mg/d of sertraline and r and omized in double-blind fashion to receive 2 g/d of omega-3 acid ethyl esters ( 930 mg of eicosapentaenoic acid [ EPA ] and 750 mg of docosahexaenoic acid [ DHA ] ) ( n=62 ) or to corn oil placebo capsules ( n=60 ) for 10 weeks . MAIN OUTCOME MEASURES Scores on the Beck Depression Inventory ( BDI-II ) and the Hamilton Rating Scale for Depression ( HAM-D ) . RESULTS Adherence to the medication regimen was 97 % or more in both groups for both medications . There were no differences in weekly BDI-II scores ( treatment x time interaction = 0.02 ; 95 % confidence interval [ CI ] , -0.33 to 0.36 ; t(112 ) = 0.11 ; P = .91 ) , pre-post BDI-II scores ( placebo , 14.8 vs omega-3 , 16.1 ; 95 % difference-in-means CI , -4.5 to 2.0 ; t(116 ) = -0.77 ; P = .44 ) , or HAM-D scores ( placebo , 9.4 vs omega-3 , 9.3 ; 95 % difference-in-means CI , -2.2 to 2.4 ; t(115 ) = 0.12 ; P = .90 ) . The groups did not differ on predefined indicators of depression remission ( BDI-II response ( > 50 % reduction in BDI-II from baseline : placebo , 49.0 % vs omega-3 , 47.7 % ; OR , 1.06 ; 95 % CI , 0.51 - 2.19 ; t(112 ) = 0.15 ; P = .88 ) . CONCLUSIONS Treatment of patients with CHD and major depression with sertraline and omega-3 fatty acids did not result in superior depression outcomes at 10 weeks , compared with sertraline and placebo . Whether higher doses of omega-3 or sertraline , a different ratio of EPA to DHA , longer treatment , or omega-3 monotherapy can improve depression in patients with CHD remains to be determined . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00116857", "OBJECTIVE Because the initial phase of treatment of depression with a selective serotonin reuptake inhibitor is often complicated by a delayed onset of action of the antidepressant or severe insomnia or both , we investigated whether tryptophan , an amino acid with both antidepressant-augmenting and hypnotic effects , would benefit patients with depression at the beginning of treatment with fluoxetine . DESIGN R and omized , double-blind , placebo-controlled trial . PATIENTS Thirty individuals with major depressive disorder . INTERVENTIONS Treatment over 8 weeks with 20 mg of fluoxetine per day and either tryptophan ( 2 to 4 g per day ) or placebo . OUTCOME MEASURES Mood was assessed using the 29-item Hamilton Depression Rating Scale ( HDRS-29 ) and the Beck Depression Inventory ( BDI ) . Laboratory sleep studies were done at baseline and after 4 and 8 weeks of treatment using st and ard procedures . RESULTS During the first week of treatment , there was a significantly greater decrease in HDRS-29 depression scores , and a similar trend in BDI scores , in the tryptophan/fluoxetine group than in the placebo/fluoxetine group . No significant differences were noted at later time points . With respect to sleep measures , there was a significant group-by-time interaction for slow-wave sleep at week 4 . Further analysis revealed a significant decrease in slow-wave sleep after 4 weeks of treatment in the placebo/fluoxetine group , but not in the tryptophan/fluoxetine group . No cases of serotonin syndrome occurred , and the combination was well tolerated , although the 4 g per day dosage of tryptophan produced daytime drowsiness . CONCLUSIONS Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep . Further large-scale studies are needed to confirm these initial findings", "We investigated the efficacy of S-Adenosyl-L-Methionine ( SAMe ) augmentation in patients with treatment-resistant depressive disorder ( TRD ) . Thirty-three out patients with major depressive episode who failed to respond to at least 8 weeks of treatment with two adequate and stable doses of antidepressants were treated openly with fixed dose of SAMe ( 800 mg ) for 8 weeks , added to existing medication . The primary outcome measure was the change from baseline in total score on Hamilton Rating Scale for Depression ( HAM-D ) . The Clinical Global Impression of Improvement ( CGI-I ) was rated at the endpoint . Patients with a reduction of 50 % or more on HAM-D total score and a CGI-I score of 1 or 2 at endpoint were considered responders ; remission was defined as a HAM-D score ≤7 . Secondary outcome measures included the Snaith-Hamilton Pleasure Scale ( SHAPS ) and the Sheehan Disability Scale ( SDS ) . At 8 weeks , a significant decrease in HAM-D score was observed with response achieved by 60 % of the patients and remission by 36 % . Also a statistically significant reduction in SHAPS and SDS was observed . Our findings indicate that SAMe augmentation may be effective and well tolerated in stage II TRD . However , limitations of the present study must be considered and further placebo-controlled trials are needed", "Objective The objective of this study was to explore the efficacy of combination therapy with citalopram plus omega-3 fatty acids versus citalopram plus placebo ( olive oil ) in the initial treatment of individuals with major depressive disorder ( MDD ) . We hypothesized that combination therapy would lead not only to greater efficacy but also to a more rapid onset of therapeutic response . Methods Forty-two subjects participated in this 9-week r and omized , masked , placebo-controlled study of combination therapy ( two 1 g capsules containing a blend of 900 mg of eicosapentaenoic acid , 200 mg of and docosahexaenoic acid , and 100 mg of other omega-3 fatty acids twice daily plus citalopram ) versus monotherapy ( two 1 g capsules of olive oil per day plus citalopram ) treatment of MDD . Results The combination therapy demonstrated significantly greater improvement in Hamilton Depression Rating scale scores over time ( F = 7.32 ; df 1,177 ; P = 0.008 ) beginning at week 4 ( t = −2.48 ; df 177 ; P = 0.014 ) . Conclusions Combination therapy was more effective than monotherapy in decreasing signs and symptoms of MDD during the 8 weeks of active treatment ; however , combination therapy did not seem to enhance the speed of the initial antidepressant response . These findings suggest that there may be an advantage to combining omega-3 fatty acids with a selective serotonin uptake inhibitor in the initial treatment of individuals with MDD . A larger definitive study is warranted", "This study explores whether inflammatory biomarkers act as moderators of clinical response to omega-3 ( n-3 ) fatty acids in subjects with major depressive disorder ( MDD ) . One hundred fifty-five subjects with Diagnostic and Statistical Manual of Mental Disorders , 4th Edition ( DSM-IV ) MDD , a baseline 17-item Hamilton Depression Rating Scale ( HAM-D-17 ) score ⩾15 and baseline biomarker data ( interleukin (IL)-1ra , IL-6 , high-sensitivity C-reactive protein ( hs-CRP ) , leptin and adiponectin ) were r and omized between 18 May 2006 and 30 June 2011 to 8 weeks of double-blind treatment with eicosapentaenoic acid (EPA)-enriched n-3 1060 mg day−1 , docosahexaenoic acid (DHA)-enriched n-3 900 mg day−1 or placebo . Outcomes were determined using mixed model repeated measures analysis for ‘ high ’ and ‘ low ’ inflammation groups based on individual and combined biomarkers . Results are presented in terms of st and ardized treatment effect size ( ES ) for change in HAM-D-17 from baseline to treatment week 8 . Although overall treatment group differences were negligible ( ES=−0.13 to + 0.04 ) , subjects with any ‘ high ’ inflammation improved more on EPA than placebo ( ES=−0.39 ) or DHA ( ES=−0.60 ) and less on DHA than placebo ( ES=+0.21 ) ; furthermore , EPA-placebo separation increased with increasing numbers of markers of high inflammation . Subjects r and omized to EPA with ‘ high ’ IL-1ra or hs-CRP or low adiponectin ( ‘ high ’ inflammation ) had medium ES decreases in HAM-D-17 scores vs subjects ‘ low ’ on these biomarkers . Subjects with ‘ high ’ hs-CRP , IL-6 or leptin were less placebo-responsive than subjects with low levels of these biomarkers ( medium to large ES differences ) . Employing multiple markers of inflammation facilitated identification of a more homogeneous cohort of subjects with MDD responding to EPA vs placebo in our cohort . Studies are needed to replicate and extend this proof-of-concept work", "BACKGROUND A consistent finding in major depression has been a low plasma and red cell folate which has also been linked to poor response to antidepressants . The present investigation was design ed to investigate whether the co-administration of folic acid would enhance the antidepressant action of fluoxetine . METHODS 127 patients were r and omly assigned to receive either 500 microg folic acid or an identical looking placebo in addition to 20 mg fluoxetine daily . All patients met the DSM-III-R criteria for major depression and had a baseline Hamilton Rating Scale ( 17 item version ) score for depression of 20 or more . Baseline and 10-week estimations of plasma folate and homocysteine were carried out . RESULTS Patients receiving folate showed a significant increase in plasma folate . This was less in men than in women . Plasma homocysteine was significantly decreased in women by 20.6 % , but there was no significant change in men . Overall there was a significantly greater improvement in the fluoxetine plus folic acid group . This was confined to women where the mean Hamilton Rating Scale score on completion was 6.8 ( S.D. 4 . 1 ) in the fluoxetine plus folate group , as compared to 11.7 ( S.D. 6 . 7 ) in the fluoxetine plus placebo group (P folic acid supplement , showed a good response ( > 50 % reduction in score ) as compared to 61.1 % of women who received placebo supplement ( P fluoxetine plus folic acid group reported symptoms possibly or probably related to medication , whereas in the fluoxetine plus placebo group 19 ( 29.7 % ) patients reported such symptoms ( P Folic acid is a simple method of greatly improving the antidepressant action of fluoxetine and probably other antidepressants . Folic acid should be given in doses sufficient to decrease plasma homocysteine . Men require a higher dose of folic acid to achieve this than women , but more work is required to ascertain the optimum dose of folic acid ", "Depressed patients ( unipolar ) were given one of the following combinations in an attempt to test aspects of the ' amine hypothesis ' and to find a preferential therapy : ( 1 ) clomipramine ; ( 2 ) clomipramine and tryptophan ; ( 3 ) desipramine and clomipramine , and ( 4 ) desipramine and tryptophan . Treatment ( 2 ) should have given optimal potentiation of 5-HT neurones and ( 3 ) and ( 4 ) should have acted similarly on both serotoninergic and adrenergic pathways . In no group was there any evidence of accelerated recovery , indicating that the process of conversion to normal mood may be more complex than suggested by most versions of the amine hypothesis", "OBJECTIVE The authors conducted two multicenter sequential parallel comparison design trials to investigate the effect of L-methylfolate augmentation in the treatment of major depressive disorder in patients who had a partial response or no response to selective serotonin reuptake inhibitors ( SSRIs ) . METHOD In the first trial , 148 out patients with SSRI-resistant major depressive disorder were enrolled in a 60-day study divided into two 30-day periods . Patients were r and omly assigned , in a 2:3:3 ratio , to receive L-methylfolate for 60 days ( 7.5 mg/day for 30 days followed by 15 mg/day for 30 days ) , placebo for 30 days followed by L-methylfolate ( 7.5 mg/day ) for 30 days , or placebo for 60 days . SSRI dosages were kept constant throughout the study . In the second trial , with 75 patients , the design was identical to the first , except that the l-methylfolate dosage was 15 mg/day during both 30-day periods . RESULTS In the first trial , no significant difference was observed in outcomes between the treatment groups . In the second trial , adjunctive L-methylfolate at 15 mg/day showed significantly greater efficacy compared with continued SSRI therapy plus placebo on both primary outcome measures ( response rate and degree of change in depression symptom score ) and two secondary outcome measures of symptom severity . The number needed to treat for response was approximately six in favor of adjunctive L-methylfolate at 15 mg/day . L-Methylfolate was well tolerated , with rates of adverse events no different from those reported with placebo . CONCLUSIONS Adjunctive L-methylfolate at 15 mg/day may constitute an effective , safe , and relatively well tolerated treatment strategy for patients with major depressive disorder who have a partial response or no response to SSRIs", "BACKGROUND Though encouraging evidence exists for the use of folic acid as an augmenting agent to antidepressants , evidence regarding its optimal dosage is lacking . METHODS Forty-two female out- patients with moderate ( with or without somatic syndrome ) or severe depressive episodes ( without psychotic symptoms ) diagnosed as per ICD-10 criteria , were r and omized in a double-blind fashion to receive either 20 mg fluoxetine and a relatively low dose folic acid ( 1.5 mg/day ; n=23 ; Group I ) or 20 mg fluoxetine and high dose folic acid ( 5 mg/day ; n=19 ; Group II ) . Primary outcome measures were weekly changes of scores on Hamilton Depression Rating Scale ( HDRS ) and Beck Depression Inventory ( BDI ) for 6 weeks . RESULTS Group II patients showed greater improvement in both HDRS [ Mean ( SD ) baseline HDRS score=21 ( 2.3 ) for group I and 20.0 ( 1.4 ) for group-II ; time X group interaction effect : p=0.01 ] and BDI [ Mean ( SD ) baseline BDI score=25.1 ( 5.2 ) for group-1 and 23.1 ( 2.7 ) for group-II ; time X group interaction effect : p=0.01 ] . With regard to HDRS , 7 ( 36.8 % ) group II patients remitted compared to 2 ( 8.7 % ) group I patients ( p=0.03 ) ; 9 ( 47.4 % ) patients of group II responded when compared to 6 ( 26.1 % ) from group I ( p=0.15 ) . When BDI was considered , 5 ( 26.3 % ) group II patients remitted when compared to 2 ( 8.7 % ) from group I ( p=0.13 ) ; 10 patients ( 52.6 % ) from group II responded when compared to 5 ( 21.7 % ) from group I ( p=0.04 ) . No adverse effects were noted in either group . LIMITATIONS Lack of a placebo arm and small sample size . CONCLUSION Compared to folic acid 1.5 mg/day , augmentation with 5 mg/day may be more beneficial in female patients with depressive episodes taking fluoxetine 20 mg/day", "BACKGROUND Depression is common in individuals with diabetes . The present study is the first r and omized controlled trial to test the efficacy of omega-3 ethyl-eicosapentaenoic acid ( E-EPA ) as adjuvant to antidepressant medication in the treatment of depression in adults with diabetes mellitus . METHODS In the VU University Medical Center , we conducted a 12-week , placebo-controlled , double-blind , parallel-group intervention study of E-EPA ( 1g/day ) versus placebo in 25 diabetes patients meeting DSM-IV criteria for major depressive disorder , who were already using antidepressant medication . The primary outcome was severity of depressive symptoms , assessed by the Montgomery Asberg Depression Rating Scale ( MADRS ) at baseline and 12-week follow-up at two-weekly intervals . Blood sample s were collected at baseline and at 12-week follow-up to determine EPA levels in erythrocyte membranes . Data were analyzed with ANOVA for repeated measures . RESULTS Thirteen participants were r and omly assigned to E-EPA ; 12 participants were given placebo . At 12-week follow-up , erythrocyte membranes from patients receiving E-EPA contained tripled levels of EPA , while no changes were noted in participants receiving placebo . In both groups , depressive symptoms significantly decreased over time ( F=21.14 , p E-EPA versus placebo ( F=1.63 , p=0.17 ) . LIMITATIONS Although having sufficient study power , this study had a relatively small sample size . Small effects could not be detected , and dose-dependent effects could not be studied . CONCLUSIONS No evidence was found for the efficacy of adding E-EPA to antidepressants in reducing depressive symptoms in diabetic patients with co-morbid depression", "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", "Only 70 % of patients respond to current treatments for panic disorder , and many discontinue drugs because of side effects . myo-Inositol , a natural isomer of glucose and a precursor for the second-messenger phosphatidyl-inositol system , has previously been found superior to placebo in the treatment of depression , panic disorder , and obsessive-compulsive disorder ( OCD ) , but a direct comparison with an established drug has never been performed . A double-blind , controlled , r and om-order crossover study was undertaken to compare the effect of inositol with that of fluvoxamine in panic disorder . Twenty patients completed 1 month of inositol up to 18 g/day and 1 month of fluvoxamine up to 150 mg/day . Improvements on Hamilton Rating Scale for Anxiety scores , agoraphobia scores , and Clinical Global Impressions Scale scores were similar for both treatments . In the first month , inositol reduced the number of panic attacks per week ( mean and SD ) by 4.0 ( 2 ) compared with a reduction of 2.4 ( 2 ) with fluvoxamine ( p = 0.049 ) . Nausea and tiredness were more common with fluvoxamine ( p = 0.02 and p = 0.01 , respectively ) . Because inositol is a natural compound with few known side effects , it is attractive to patients who are ambivalent about taking psychiatric medication . Continuing reports of inositol ’s efficacy in the treatment of depression , panic disorder , and OCD should stimulate replication studies", "Summary . Some antidepressants , such as Lithium , can augment the antidepressant effect of serotonin selective uptake inhibitors ( SSRI ) in patients who have failed to respond to SSRI . Inositol has demonstrated antidepressant effects but in a controlled double blind augmentation trial did not improve depression in SSRI treatment failures", "Objective : To compare the therapeutic effects of vitamin D3 plus fluoxetine and fluoxetine alone in patients with major depressive disorder . Methods : In the present double-blind , r and omized , placebo-controlled trial , 42 patients with a diagnosis of major depressive disorder based on DSM-IV criteria were r and omly assigned into two groups to receive daily either 1500 IU vitamin D3 plus 20 mg fluoxetine or fluoxetine alone for 8 weeks . Depression severity was assessed at 2-week intervals using the 24-item Hamilton Depression Rating Scale ( HDRS ) as a primary outcome measure and the 21-item Beck Depression Inventory ( BDI ) as a secondary outcome measure . Serum 25(OH ) vitamin D was measured at baseline and after intervention . Results : Forty patients completed the trial . A two-way repeated- measures analysis of variance showed that depression severity based on HDRS and BDI decreased significantly after intervention , with a significant difference between the two groups . The vitamin D + fluoxetine combination was significantly better than fluoxetine alone from the fourth week of treatment . Conclusions : In the present 8-week trial , the vitamin D + fluoxetine combination was superior to fluoxetine alone in controlling depressive symptoms", "Objective ( s ) : Folic acid , a micronutrient supporting the natural defense system , may elevate antidepressant responses , although the lymphocyte serotonergic system has not been explored in folate-supplemented depressed patients . Methods : Twenty-seven patients were r and omly assigned to groups receiving fluoxetine ( 20 mg ) and folic acid ( 10 mg/day ) or fluoxetine and placebo for 6 weeks . Clinical outcome was assessed according to the Hamilton Depression Rating Scale ( HDRS ) at the beginning , during and at the end of treatment . Blood sample s were taken , plasma was separated , and lymphocytes were obtained by density gradient centrifugation with Ficoll/Hypaque and differential adhesion to plastic dishes . Fifteen healthy subjects served as controls . Plasma folate , homocysteine and vitamin B12 , and serotonin concentration in lymphocytes were determined by HPLC . The HDRS score was significantly lower in patients receiving fluoxetine and folic acid compared with those receiving fluoxetine and placebo after 6 weeks of treatment ( 7.43 ± 1.65 vs. 11.43 ± 1.31 , respectively ; p = 0.04 ) . Plasma homocysteine statistically significant decreased after folic acid ( p = 0.02 ) , but no significant changes were observed in vitamin B12 . Results : Serotonin was significantly reduced after fluoxetine either with folate ( p = 0.03 ) or placebo ( p = 0.01 ) probably by the effect of transporter blockade . 5-Hydroxyindoleacetic acid was lower in lymphocytes of patients receiving folate ( p = 0.04 ) , indicating a reduced turnover rate , thus accumulating serotonin in the cells . A significant negative correlation was noted between homocysteine and folate . No significant correlations were present among biochemical parameters and depression severity . Conclusion : Modifications due to treatment with fluoxetine and folic acid may alter lymphocyte function in depression probably indirectly by reducing homocysteine levels and directly on lymphocytes by modifying the serotonergic system", "OBJECTIVE Despite the progressive increase in the number of antidepressants , many patients with major depressive disorder continue to be symptomatic . Clearly , there is an urgent need to develop better tolerated and more effective treatments for this disorder . The use of S-adenosyl methionine ( SAMe ) , a naturally occurring molecule that serves as a methyl donor in human cellular metabolism , as adjunctive treatment for antidepressant nonresponders with major depressive disorder represents one such effort toward novel pharmacotherapy development . METHOD Participants were 73 serotonin reuptake inhibitor ( SRI ) nonresponders with major depressive disorder enrolled in a 6-week , double-blind , r and omized trial of adjunctive oral SAMe ( target dose : 800 mg/twice daily ) . Patients continued to receive their SRI treatment at a stable dose throughout the 6-week trial . The primary outcome measure for the study was the response rates according to the 17-item Hamilton Depression Rating Scale ( HAM-D ) . RESULTS The HAM-D response and remission rates were higher for patients treated with adjunctive SAMe ( 36.1 % and 25.8 % , respectively ) than adjunctive placebo ( 17.6 % versus 11.7 % , respectively ) . The number needed to treat for response and remission was approximately one in six and one in seven , respectively . There was no statistically significant difference in the proportion of SAMe- versus placebo-treated patients who discontinued the trial for any reason ( 20.6 % versus 29.5 % , respectively ) , due to adverse events ( 5.1 % versus 8.8 % , respectively ) , or due to inefficacy ( 5.1 % versus 11.7 % , respectively ) . CONCLUSIONS These preliminary results suggest that SAMe can be an effective , well-tolerated , and safe adjunctive treatment strategy for SRI nonresponders with major depressive disorder and warrant replication", "Low folate is associated with poorer response to selective serotonin reuptake inhibitors ( SSRIs ) in major depressive disorder ( MDD ) . Folate supplementation in MDD has been studied in other setting s with promising results . The objective of this study was to assess the efficacy of methylfolate as an adjunctive treatment among adults with MDD and inadequate response to an SSRI . Twenty-two adults ( 59 % female ; mean age 45.2 + /- 11.0 years ) with DSM-IV MDD , partial or nonresponse to an SSRI after at least 4 weeks of treatment , and a 17-item Hamilton Depression Rating Scale ( HAM-D-17 ) score > or = 12 were enrolled in this 8-week prospect i ve open trial . Exclusion criteria included current use of anticonvulsants or psychotropics other than an SSRI , or B12 deficiency . Leucovorin ( folinic acid ) , which is metabolized to methylfolate , was added to SSRIs at 15 - 30 mg/day . Folate levels rose from 28 + /- 19 ng/mL to 301 + /- 203 ng/mL ( p HAM-D-17 scores among the 16 completers decreased from 19.1 + /- 3.9 to 12.8 + /- 7.0 ( p response ( > or = 50 % reduction in HAM-D-17 scores ) , and only 19 % of completers and 18 % of the ITT sample achieved remission ( HAM-D-17 Leucovorin appears to be modestly effective as an adjunct among SSRI-refractory depressed individuals with normal folate levels . The application of leucovorin as an adjunct in the setting of refractory depression deserves further study", "OBJECTIVE Studies have reported that countries with high rates of fish oil consumption have low rates of depressive disorder . The authors studied a specific omega-3 fatty acid , the ethyl ester of eicosapentaenoic acid ( E-EPA ) , as an adjunct to treatment for depressive episodes occurring in patients with recurrent unipolar depressive disorder who were receiving maintenance antidepressant therapy . METHOD Twenty patients with a current diagnosis of major depressive disorder participated in a 4-week , parallel-group , double-blind addition of either placebo or E-EPA to ongoing antidepressant therapy . Seventeen of the patients were women , and three were men . RESULTS Highly significant benefits of the addition of the omega-3 fatty acid compared with placebo were found by week 3 of treatment . CONCLUSIONS It is not possible to distinguish whether E-EPA augments antidepressant action in the manner of lithium or has independent antidepressant properties of its own", "BACKGROUND One of the main problems in the therapy of depression is the limited efficacy of antidepressants and the limited utility of augmentation strategies . Zinc , a non competitive NMDA receptor antagonist exhibits pre clinical antidepressant efficacy . Moreover , a preliminary clinical report suggests augmentation of antidepressant therapy by zinc in depression . METHODS A placebo-controlled , double blind study of zinc supplementation in imipramine therapy was conducted in sixty , 18 - 55-year old , unipolar depressed patients fulfilling the DSM-IV criteria for major depression without psychotic symptoms . After a one week washout period , patients were r and omized into two groups treated with imipramine ( approximately 140 mg/day ) and receiving once daily either placebo ( n=30 ) or zinc supplementation ( n=30 , 25 mgZn/day ) for 12 weeks . RESULTS No significant differences in CGI , BDI , HADRS and MADRS scores were demonstrated between zinc-supplemented and placebo-supplemented antidepressant treatment non-resistant patients . However , zinc supplementation significantly reduced depression scores and facilitated the treatment outcome in antidepressant treatment resistant patients . CONCLUSION Zinc supplementation augments the efficacy and speed of onset of therapeutic response to imipramine treatment , particularly in patients previously nonresponsive to antidepressant pharmacotherapies . These data suggest the participation of disturbed zinc/glutamatergic transmission in the pathophysiology of drug resistance", "BACKGROUND Previous studies of vitamin C and kidney stones were conducted mostly in men and either reported disparate results for supplemental and dietary vitamin C or did not examine dietary vitamin C. STUDY DESIGN Prospect i ve cohort analysis . SETTING & PARTICIPANTS 156,735 women in the Nurses ' Health Study ( NHS ) I and II and 40,536 men in the Health Professionals Follow-up Study ( HPFS ) . PREDICTOR Total , dietary , and supplemental vitamin C intake , adjusted for age , body mass index , thiazide use , and dietary factors . OUTCOMES Incident kidney stones . RESULTS During a median follow-up of 11.3 to 11.7 years , 6,245 incident kidney stones were identified . After multivariable adjustment , total vitamin C intake ( stones among women , but was among men ( HRs of 1.00 [ reference ] , 1.19 [ 95 % CI , 0.99 - 1.46 ] , 1.15 [ 95 % CI , 0.93 - 1.42 ] , 1.29 [ 95 % CI , 1.04 - 1.60 ] , and 1.43 [ 95 % CI , 1.15 - 1.79 ] , respectively ; P for trend = 0.005 ) . Median total vitamin C intake for the 500- to 999-mg/d category was ∼700mg/d . Supplemental vitamin C intake ( no use [ reference ] , 0.001 ) . Dietary vitamin C intake was not associated with stones among men or women , although few participants had dietary intakes > 700mg/d . LIMITATIONS Nutrient intakes derived from food-frequency question naires , lack of data on stone composition for all cases . CONCLUSIONS Total and supplemental vitamin C intake was significantly associated with higher risk for incident kidney stones in men , but not in women", "Background : The purpose of this open trial was to evaluate the safety , tolerability , and efficacy of oral S-adenosyl-l-methionine as an antidepressant adjunct among partial and nonresponders to serotonin reuptake inhibitors or venlafaxine . Method : Thirty antidepressant-treated adult out patients with persisting major depressive disorder received 800 to 1600 mg of S-adenosyl-l-methionine tosylate over a 6-week trial . Results : Intent-to-treat analyses based on the Hamilton Depression Rating Scale revealed a response rate of 50 % and a remission rate of 43 % following augmentation with S-adenosyl-l-methionine . Gastrointestinal symptoms and headaches were the most common side effects . Conclusion : Augmentation of selective serotonin reuptake inhibitors or venlafaxine with S-adenosyl-l-methionine warrants a placebo-controlled trial in resistant depression ", "OBJECTIVE CSF levels of inositol have been reported to be lower than normal in depressed subjects . The authors administered inositol to depressed patients in a double-blind , controlled trial . METHOD Under double-blind conditions , 12 g/day of inositol ( N = 13 ) or placebo ( N = 15 ) was administered to depressed patients for 4 weeks . RESULTS The overall improvement in scores on the Hamilton Depression Rating Scale was significantly greater for inositol than for placebo at week 4 . No changes were noted in hematology or in kidney or liver function . CONCLUSIONS This may be the first use of the precursor strategy for a second messenger rather than a neurotransmitter in treating depression . Although inositol had a significant antidepressant effect in this study , replication is crucial", "A double-blind clinical trial was carried out involving 26 hospitalized , depressed patients who were r and omized into two groups . Patients in each group received chlorimipramine ( 50 mg/day ) , combined with L-5-HTP ( 300 mg/day ) in Group A , and with placebo in Group B. The trial lasted 28 days . Two Group B patients dropped out . All the patients were evaluated by HRSD each week , and by ZDSI and CGI at the beginning and end of treatment . Several statistical analyses of the mean HRSD scores of each item presenting initial positive response and of ZDSI scores for both reactive and endogenous depression were performed , using Student 's t-test . To evaluate the efficacy of the chlorimipramine + L-5-HTP combination versus control therapy the Mann-Whitney test was applied to the reduction in HRSD scores , showing 0.05 significance . The results for both types of pathology were quantitatively and qualitatively more positive for Group A than for Group B. Cluster analysis of HRSD item scores alone and between this scale and ZDSI , according to Carrol 's correlation method for the symptoms of the cluster ( mood , anxiety and somatic symptoms ) , was carried out to confirm the above results", "BACKGROUND In depressed patients , low blood levels of eicosapentaenoic acid are seen . We tested the antidepressive effect of ethyl-eicosapentaenoate in these patients . METHODS We included 70 patients with persistant depression despite ongoing treatment with an adequate dose of a st and ard antidepressant . Patients were r and omized on a double-blind basis to placebo or ethyl-eicosapentaenoate at dosages of 1 , 2 , or 4 g/d for 12 weeks in addition to unchanged background medication . Patients underwent assessment using the 17-item Hamilton Depression Rating Scale , the Montgomery-Asberg Depression Rating Scale , and the Beck Depression Inventory . RESULTS Forty-six ( 88 % ) of 52 patients receiving ethyl-eicosapentaenoate and 14 ( 78 % ) of 18 patients receiving placebo completed the 12-week study with no serious adverse events . The 1-g/d group showed a significantly better outcome than the placebo group on all 3 rating scales . In the intention-to-treat group , 5 ( 29 % ) of 17 patients receiving placebo and 9 ( 53 % ) of 17 patients receiving 1 g/d of ethyl-eicosapentaenoate achieved a 50 % reduction on the Hamilton Depression Rating Scale score . In the per- protocol group , the corresponding figures were 3 ( 25 % ) of 12 patients for placebo and 9 ( 69 % ) of 13 patients for the 1-g/d group . The 2-g/d group showed little evidence of efficacy , whereas the 4-g/d group showed nonsignificant trends toward improvement . All of the individual items on all 3 rating scales improved with the 1-g/d dosage of ethyl-eicosapentaenoate vs placebo , with strong beneficial effects on items rating depression , anxiety , sleep , lassitude , libido , and suicidality . CONCLUSION Treatment with ethyl-eicosapentaenoate at a dosage of 1 g/d was effective in treating depression in patients who remained depressed despite adequate st and ard therapy", "BACKGROUND Folate deficiency is associated with depression . Despite the biological plausibility of a causal link , the evidence that adding folate enhances antidepressant treatment is weak . OBJECTIVES ( 1 ) Estimate the clinical effectiveness and cost-effectiveness of folic acid as adjunct to antidepressant medication ( ADM ) . ( 2 ) Explore whether baseline folate and homocysteine predict response to treatment . ( 3 ) Investigate whether response to treatment depends on genetic polymorphisms related to folate metabolism . DESIGN FolATED ( Folate Augmentation of Treatment - Evaluation for Depression ) was a double-blind and placebo-controlled , but otherwise pragmatic , r and omised trial including cost-utility analysis . To yield 80 % power of detecting st and ardised difference on the Beck Depression Inventory version 2 ( BDI-II ) of 0.3 between groups ( a ' small ' effect ) , FolATED trialists sought to analyse 358 participants . To allow for an estimated loss of 21 % of participants over three time points , we planned to r and omise 453 . SETTING S Clinical - Three centres in Wales - North East Wales , North West Wales and Swansea . Trial management - North Wales Organisation for R and omised Trials in Health in Bangor University . Biochemical analysis - University Hospital of Wales , Cardiff . Genetic analysis - University of Liverpool . PARTICIPANTS Four hundred and seventy-five adult patients presenting to primary or secondary care with confirmed moderate to severe depression for which they were taking or about to start ADM , and able to consent and complete assessment s , but not ( 1 ) folate deficient , vitamin B12 deficient , or taking folic acid or anticonvulsants ; ( 2 ) misusing drugs or alcohol , or suffering from psychosis , bipolar disorder , malignancy or other unstable or terminal illness ; ( 3 ) ( planning to become ) pregnant ; or ( 4 ) participating in other clinical research . INTERVENTIONS Once a day for 12 weeks experimental participants added 5 mg of folic acid to their ADM , and control participants added an indistinguishable placebo . All participants followed pragmatic management plans initiated by a trial psychiatrist and maintained by their general medical practitioners . MAIN OUTCOME MEASURES Assessed at baseline , and 4 , 12 and 25 weeks thereafter , and analysed by ' area under curve ' ( main ) ; by analysis of covariance at each time point ( secondary ) ; and by multi-level repeated measures ( sensitivity analysis ): Mental health - BDI-II ( primary ) , Clinical Global Impression ( CGI ) , Montgomery-Åsberg Depression Rating Scale ( MADRS ) , UKU side effects scale , and Mini International Neuropsychiatric Interview ( MINI ) suicidality subscale ; General health - UK 12-item Short Form Health Survey ( SF-12 ) , European Quality of Life scale - 5 Dimensions ( EQ-5D ) ; Biochemistry - serum folate , B12 , homocysteine ; Adherence - Morisky Question naire ; Economics - re source use . RESULTS Folic acid did not significantly improve any of these measures . For example it gained a mean of just 2.9 quality -adjusted life-days [ 95 % confidence interval ( CI ) from -12.7 to 7.0 days ] and saved a mean of just £ 48 ( 95 % CI from -£292 to £ 389 ) . In contrast it significantly reduced mental health scores on the SF-12 by 3.0 % ( 95 % CI from -5.2 % to -0.8 % ) . CONCLUSIONS The FolATED trial generated no evidence that folic acid was clinical ly effective or cost-effective in augmenting ADM . This negative finding is consistent with improving underst and ing of the one-carbon folate pathway suggesting that methylfolate is a better c and i date for augmenting ADM . Hence the findings of FolATED undermine treatment guidelines that advocate folic acid for treating depression , and suggest future trials of methylfolate to augment ADM . TRIAL REGISTRATION Current Controlled Trials IS RCT N37558856 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 18 , No. 48 . See the HTA programme website for further project information", "Abstract This double blind study investigated the reported potentiation of an MAO inhibitor by tryptophan . Twenty seriously depressed patients were placed on phenelzine sulfate . Half of these patients received supplements of tryptophan while the remainder received a placebo . Those receiving the tryptophan supplements showed significantly more improvement as measured by a modified version of the Hamilton scale . The possible pathways for the mediation of this tryptophan effect are discussed", "BACKGROUND Inositol has been reported to be an effective treatment in depression , and we hypothesized that inositol addition might enhance or speed up response to serotonin selective reuptake inhibitors ( SSRI ) . METHODS Twenty-seven depressed patients completed a double-blind controlled 4-week trial of SSRI plus placebo or SSRI plus inositol . Hamilton Depression Rating Scale was used as an assessment tool at baseline , and 1 , 2 , 3 , and 4 weeks . RESULTS No significant difference was found between the two treatment groups . CONCLUSIONS Previous studies combining different effective antidepressant therapies similarly found no evidence for additive effects [ e.g. , monoamine oxidase inhibitors ( MAOI ) plus tricyclic antidepressants ( TCA ) , TCA plus lithium ] . By contrast , augmentation by lithium or MAOI after a failed course of antidepressant treatment is effective and should be studied with inositol", "Objective : To compare therapeutic effects of eicosapentaenoic acid ( EPA ) , fluoxetine and a combination of them in major depression . Method : Sixty out patients with a diagnosis of major depressive disorder based on DSM-IV criteria and a score ≥15 in the 17-item Hamilton Depression Rating Scale ( HDRS ) were r and omly allocated to receive daily either 1000 mg EPA or 20 mg fluoxetine , or their combination for 8 weeks . Double dummy technique was used to double blind the study . Patients were assessed at 2 week intervals . Change in HDRS was the primary outcome measure . Results : Analysis of covariance for HDRS at week 8 across treatment groups was performed in 48 patients who completed at least 4 weeks of the study , with the last observation carried forward . Treatment , age of onset and baseline HDRS had a significant effect on HDRS at week 8 . EPA + fluoxetine combination was significantly better than fluoxetine or EPA alone from the fourth week of treatment . Fluoxetine and EPA appear to be equally effective in controlling depressive symptoms . Response rates ( ≥50 % decrease in baseline HDRS ) were 50 % , 56 % and 81 % in the fluoxetine , EPA and combination groups , respectively . Conclusions : In the present 8 week trial EPA and fluoxetine had equal therapeutic effects in major depressive disorder . EPA + fluoxetine combination was superior to either of them alone" ]

[ "OBJECTIVE To evaluate the effectiveness of a program to increase walking to and from school . DESIGN A cluster r and omised controlled trial . SETTING 24 primary public schools in inner west Sydney , Australia . PARTICIPANTS 1996 students aged 10 - 12 years and their parents . INTERVENTION A two-year multi-component program included classroom activities , development of school Travel Access Guides , parent newsletters and improving environments with local councils . MEASURES Two measures were used : a survey completed by students on how they travelled to and from school over five days , and a survey completed by their parents on how their child travelled to and from school in a usual week . RESULTS The percentage of students who walked to and from school increased in both the intervention and control schools . Data from parent surveys found that 28.8 % of students in the intervention group increased their walking , compared with 19 % in the control group ( a net increase of 9.8 % , p=0.05 ) . However this effect was not evident in the student data . CONCLUSION The study produced a mixed result , with a high variation in travel patterns from school to school . Intervention research should address the complexity of multiple factors influencing student travel to school with a focus on changing local environments and parents ' travel to work", "BACKGROUND The aim of this study was to determine the impact of pedometer use and self-regulation strategies on adolescents ' daily physical activity . METHODS Junior high school students ( n=113 ) enrolled in seventh- and eighth- grade physical education classes ( 52 girls , 61 boys ) volunteered to participate in a 5-week study to assess daily step counts . Ten physical education classes were r and omly assigned to 1 of 3 groups : ( a ) self-regulation , ( b ) open , and ( c ) control . RESULTS A repeated- measures , mixed-model analysis of variance revealed a significant 3x4 ( Group by Time ) interaction effect , F6,290=2.64 , P self-regulation group took 2071 to 4141 more steps/d than the control . No other significant differences emerged among groups on step counts . CONCLUSIONS It appears that having access to and charting daily step counts ( ie , self-regulatory strategies ) positively influenced young adolescents to attain a higher number of steps/d", "Background Levels of physical activity ( PA ) in UK children are much lower than recommended and novel approaches to its promotion are needed . The Children , Parents and Pets Exercising Together ( CPET ) study is the first exploratory r and omised controlled trial ( RCT ) to develop and evaluate an intervention aim ed at dog-based PA promotion in families . CPET aim ed to assess the feasibility , acceptability and potential efficacy of a theory-driven , family-based , dog walking intervention for 9–11 year olds . Methods Twenty-eight families were allocated r and omly to either receive a 10-week dog based PA intervention or to a control group . Families in the intervention group were motivated and supported to increase the frequency , intensity and duration of dog walking using a number of behaviour change techniques . Parents in the intervention group were asked to complete a short study exit question naire . In addition , focus groups with parents and children in the intervention group , and with key stakeholders were undertaken . The primary outcome measure was 10 week change in total volume of PA using the mean accelerometer count per minute ( cpm ) . Intervention and control groups were compared using analysis of covariance . Analysis was performed on an intention to treat basis . Results Twenty five families were retained at follow up ( 89 % ) and 97 % of all outcome data were collected at baseline and follow up . Thirteen of 14 ( 93 % ) intervention group parents available at follow up completed the study exit question naire and noted that study outcome measures were acceptable . There was a mean difference in child total volume of PA of 27 cpm ( 95 % CI -70 , 123 ) and -3 cpm ( 95 % CI -60 , 54 ) for intervention and control group children , respectively . This was not statistically significant . Approximately 21 % of dog walking time for parents and 39 % of dog walking time for children was moderate-vigorous PA . Conclusions The acceptability of the CPET intervention and outcome measures was high . Using pet dogs as the agent of lifestyle change in PA interventions in children and their parents is both feasible and acceptable , but did not result in a significant increase in child PA in this exploratory trial . Trial registration IS RCT", "Objective To describe levels of physical activity , sedentary time and adherence to Chief Medical Officers ( CMO ) physical activity guidelines among primary school-aged children across the UK using objective accelerometer-based measurements . Design Nationally representative prospect i ve cohort study . Setting Children born across the UK , between 2000 and 2002 . Participants 6497 7-year-old to 8-year-old singleton children for whom reliable accelerometer data were available for at least 10 h a day for at least 2 days . Main outcome measures Physical activity in counts per minute ( cpm ) ; time spent in sedentary and moderate-to-vigorous intensity physical activity ( MVPA ) ; proportion of children meeting CMO guidelines ( ≥60 min/day MVPA ) ; average daily steps . Explanatory measures Gender , ethnicity , maternal current/most recent occupation , lone parenthood status , number of children in the household and country/region of residence . Results The median daily physical activity level was 595 cpm ( IQR 507 , 697 ) . Children spent a median of 60 min ( IQR 47–76 ) in MVPA/day and were sedentary for a median of 6.4 h/day ( IQR 6–7 ) . Only 51 % met CMO guidelines , with girls ( 38 % ) less active than boys ( 63 % ) . Children took an average of 10 229 ( 95 % CI ( 8777 to 11 775 ) ) steps each day . Children of Indian ethnicity were significantly less active overall than all other ethnic groups . Children of Bangladeshi origin and those living in Northern Irel and were least likely to meet CMO guidelines . Conclusions Only half of 7-year-old children in the UK achieve recommended levels of physical activity , with significant gender , ethnic and geographic variations . Longitudinal studies are needed to better underst and the relevance of these (in)activity patterns for long-term health and well-being . In the meantime population -wide efforts to boost physical activity among young people are needed which are likely to require a broad range of policy interventions", "Background To evaluate the impact of a walking school bus ( WSB ) program on student transport in a low-income , urban neighborhood . Methods The design was a controlled , quasi-experimental trial with consecutive cross-sectional assessment s. The setting was three urban , socioeconomically disadvantaged , public elementary schools ( 1 intervention vs. 2 controls ) in Seattle , Washington , USA . Participants were ethnically diverse students in kindergarten-5th grade ( aged 5–11 years ) . The intervention was a WSB program consisting of a part-time WSB coordinator and parent volunteers . Students ' method of transportation to school was assessed by a classroom survey at baseline and one-year follow-up . The Pearson Chi-squared test compared students transported to school at the intervention versus control schools at each time point . Due to multiple testing , we calculated adjusted p-values using the Ryan-Holm stepdown Bonferroni procedure . McNemar 's test was used to examine the change from baseline to 12-month follow-up for walking versus all other forms of school transport at the intervention or control schools . Results At baseline , the proportions of students ( n = 653 ) walking to the intervention ( 20 % + /- 2 % ) or control schools ( 15 % + /- 2 % ) did not differ ( p = 0.39 ) . At 12-month follow up , higher proportions of students ( n = 643 , p = 0.001 ) ) walked to the intervention ( 25 % + /- 2 % ) versus the control schools ( 7 % + /- 1 % ) . No significant changes were noted in the proportion of students riding in a car or taking the school bus at baseline or 12-month follow up ( all p > 0.05 ) . Comparing baseline to 12-month follow up , the numbers of students who walked to the intervention school increased while the numbers of students who used the other forms of transport did not change ( p numbers of students who walked to the control schools decreased while the numbers of students who used the other forms of transport did not change ( p WSB program is a promising intervention among urban , low-income elementary school students that may promote favorable changes toward active transport to school . Trial Registration Clinical Trials.gov", "PURPOSE This intervention compares the effectiveness of daily step count targets with time-based prescription for increasing the health-related physical activity of low-active adolescent girls . METHODS We assigned participants ( N = 85 , mean age 15.8 + /- 0.8 yr ) depending on school attended to a control ( CON ) , pedometer ( PED ) , or minutes ( MIN ) group . The intervention groups were involved in a 12-wk physical activity self-monitoring and educative program . The only difference between the intervention groups was that the PED group set daily step count targets whereas the MIN group set daily time-based goals for physical activity involvement . Pre- , mid- , and postintervention changes in physical activity ( 4-d blinded step count and 3-d physical activity recall ) and body mass index ( BMI ) were assessed using a series of 3 ( group assignment ) x 3 ( time ) ANOVA . Where significant interactions were found , separate follow-up simple main effects tests were used . RESULTS At postintervention , only the PED group had significantly increased their total activity as measured by a 4-d step count , when compared with the control ( P = 0.03 , ES = 0.13 ) . The group , time , and interaction effects for 4-d step count were significant , indicating that although both the participants in the PED and the MIN groups significantly increased their step count across the 12-wk intervention ( P = 0.00 - 0.01 ) , the participants in the PED group had a greater increase at the midintervention time point ( P = 0.04 , ES = 0.10 ) . No pre- , mid- , or postintervention changes were reported in any group for BMI ( F = 1.18 , P = 0.32 ) . CONCLUSION The use of pedometers and daily step count targets with low-active adolescent girls may result in short-term ( 6 wk ) enhanced physical activity related outcomes when compared with traditional time-based physical activity prescriptions . However , both interventions appear to result in similar improvements in physical activity when duration of the observation is extended to 12 wk", "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", "PURPOSE To derive a regression equation that estimates metabolic equivalent ( MET ) from accelerometer counts , and to define thresholds of accelerometer counts that can be used to delineate sedentary , light , moderate , and vigorous activity in adolescent girls . METHODS Seventy-four healthy 8th grade girls , age 13 - 14 yr , were recruited from urban areas of Baltimore , MD , Minneapolis/St . Paul , MN , and Columbia , SC , to participate in the study . Accelerometer and oxygen consumption (.-)VO(2 ) ) data for 10 activities that varied in intensity from sedentary ( e.g. , TV watching ) to vigorous ( e.g. , running ) were collected . While performing these activities , the girls wore two accelerometers , a heart rate monitor and a Cosmed K4b2 portable metabolic unit for measurement of (.-)VO(2 ) . A r and om-coefficients model was used to estimate the relationship between accelerometer counts and (.-)VO(2 ) . Activity thresholds were defined by minimizing the false positive and false negative classifications . RESULTS The activities provided a wide range in (.-)VO(2 ) ( 3 - 36 mL x kg x min ) with a correspondingly wide range in accelerometer counts ( 1- 3928 counts x 30 s ) . The regression line for MET score versus counts was MET = 2.01 + /- 0.00171 ( counts x 30 s ) ( mixed model R = 0.84 , SEE = 1.36 ) . A threshold of 1500 counts x 30 s defined the lower end of the moderate intensity ( approximately 4.6 METs ) range of physical activity . That cutpoint distinguished between slow and brisk walking , and gave the lowest number of false positive and false negative classifications . The threshold ranges for sedentary , light , moderate , and vigorous physical activity were found to be 0 - 50 , 51- 1499 , 1500 - 2600 , and > 2600 counts x 30 s , respectively . CONCLUSION The developed equation and these activity thresholds can be used for prediction of MET score from accelerometer counts and participation in various intensities of physical activity in adolescent girls", "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", "AIM To study the effect of an intervention combining self-efficacy theory and pedometers on promoting physical activity among adolescents . BACKGROUND The beneficial effects of regular physical activity on health in youths are well-documented . However , adolescence is found to be the age of greatest decline in physical activity participation . Physical activity participation among girls was generally less frequent and less intense than boys . Therefore , there is a strong need for effective interventions that can help promote physical activity in this population . DESIGN An experimental design . METHODS Two classes of female junior college students ( mean age = 16 ) were r and omly sample d from a total of four classes and , of those , one each was r and omly assigned to either the intervention ( n = 46 ) or the control group ( n = 48 ) . Self-efficacy was used as a core theoretical foundation of the intervention design , and pedometers were provided to the students in the intervention group . Distances between each domestic scenic spot were illustrated graphically in a walking log for students to mark the extent of their walking or running . Students in the control group participated in a usual physical education programme . The primary outcome was a change in the number of aerobic steps . The secondary outcomes were changes in cardiopulmonary endurance and exercise self-efficacy . RESULTS At 12-week follow-up , the mean change in aerobic steps was 371 steps and 108 steps in the intervention and control group , respectively . The difference in mean change between the two groups was 467 steps . Effects of the intervention on changes of cardiopulmonary endurance and perceived exercise self-efficacy scores were not found . CONCLUSIONS Among adolescent girls , a 12-week intervention design ed on the theoretical foundation of self-efficacy theory and provision of pedometers was found to have an effect on increasing their physical activity . The intervention , using graphs of domestic scenic spots to represent the distance of walking or running as monitored by pedometers , might enhance motivation regarding physical activity . RELEVANCE TO CLINICAL PRACTICE It is important for health professionals , including school health nurses , involved in the care of adolescent health , to design and provide a physical activity intervention combining self-efficacy theory and provision of pedometer to promote physical activity ", "BACKGROUND : Concern has been raised regarding the increased prevalence of physical inactivity among children . Active transportation , such as walking and cycling to school , is an opportunity for children to be physically active . OBJECTIVE : To identify the sociodemographic predictors of active transportation to schools across time among school-aged children participating in the Canadian National Longitudinal Survey of Children and Youth ( NLSCY ) . METHODS : The sample included 7690 school-aged children attending public schools who were drawn from cycle 2 ( 1996 and 1997 ) of the Canadian NLSCY . Data were collected through interviews with the person most knowledgeable about the child . Parents were asked how their child usually gets to school . Responses were dichotomized into active ( walking or bicycling ) or inactive ( school bus , public transit , is driven , or multiple ) modes . Using 3 waves of data from the Canadian NLSCY ( 1996–2001 ) , we estimated the effect of sociodemographic factors on the likelihood of active transportation to school across time using r and om-effects models . RESULTS : Longitudinal analyses indicated that as children aged , the likelihood of using active transportation to school increased , peaked at the age of 10 years , and then decreased . Urban setting s ( odds ratio [ OR ] : 3.66 [ 95 % confidence interval ( CI ) : 3.23–4.15 ] ) , households with inadequate income ( OR : 1.21 [ 95 % CI : 1.06–1.38 ] ) , living with 1 parent ( OR : 1.46 [ 95 % CI : 1.29–1.65 ] ) , and having an older sibling living at home ( OR : 1.14 [ 95 % CI : 1.04–1.25 ] ) were significant predictors of active transportation to school at baseline and carried through across time . CONCLUSIONS : Underst and ing the factors that influence active transportation may support its adoption by children , which in turn may contribute to meeting physical activity guidelines", " OBJECTIVE : To evaluate the impact of a “ walking school bus ” program on children 's rates of active commuting to school and physical activity . METHODS : We conducted a pilot cluster r and omized controlled trial among 4th- grade rs from 8 schools in Houston , Texas ( N = 149 ) . R and om allocation to treatment or control conditions was at the school level . Study staff walked with children to and from school up to 5 days/week . Outcomes were measured the week before ( time 1 ) and during weeks 4 and 5 of the intervention ( time 2 ) . The main outcome was the weekly rate of active commuting , and a secondary outcome was moderate-to-vigorous physical activity . Covariates included sociodemographics , distance from home to school , neighborhood safety , child BMI z score , parent self-efficacy/ outcome expectations , and child self-efficacy for active commuting . A mixed-model repeated measures regression accounted for clustering by school , and stepwise procedures with backward elimination of nonsignificant covariates were used to identify significant predictors . RESULTS : Intervention children increased active commuting ( mean ± SD ) from 23.8 % ± 9.2 % ( time 1 ) to 54 % ± 9.2 % ( time 2 ) , whereas control subjects decreased from 40.2 % ± 8.9 % ( time 1 ) to 32.6 % ± 8.9 % ( time 2 ) ( P increased their minutes of daily moderate-to-vigorous physical activity from 46.6 ± 4.5 ( time 1 ) to 48.8 ± 4.5 ( time 2 ) , whereas control children decreased from 46.1 ± 4.3 ( time 1 ) to 41.3 ± 4.3 ( time 2 ) ( P = .029 ) . CONCLUSIONS : The program improved children 's active commuting to school and daily moderate-to-vigorous physical activity", "Active commuting to school ( e.g. walking or bicycling ) has been suggested as a strategy to increase children ’s physical activity 1 , 2 and a number of walk-to-school websites now exist . 3–5 Several observational studies have found positive associations between walking to school and physical activity 6–9 but they are unable to determine the causal direction . Adult-chaperoned walks to school ( i.e. , walking school bus1 , 5 ) have been evaluated 10–12 but no research was found that assessed objective ly measured changes in physical activity from walking to school . Walk-to-school programs can be a component of comprehensive school health plans , have particular relevance for school nurse/health staff and physical education faculty and can be adapted to suit the schools ’ physical and social environment . Therefore , we completed a small , short-term pilot and feasibility r and omized control trial to 1 ) test the feasibility of the walking school bus as an intervention strategy and 2 ) to identify any changes in physical activity from walking to school . A r and omized controlled trial design was used with all participants completing one week of baseline automobile commuting . Students were then r and omized , for the second week , to either a control group that continued to be driven to school or an intervention group that participated in the walking school bus . Families were recruited from one elementary school ( Menlo Park , CA ) . Eighteen families responded and met the inclusion criteria : 1 ) student in 3rd–5th grade and 2 ) currently being driven to school at least four days/week . Six families declined to participate , due to time constraints ( n=4 ) , shared custody ( n=1 ) , and general concern ( n=1 ) . Therefore , 12 students were r and omized to a control ( CON , n=6 ) or intervention ( WALK , n=6 ) group . All students completed the study protocol as design ed . One student in the WALK group was excluded from analysis due to activity monitor malfunction , leaving five WALK and six CON students in the analysis sample . This study was approved by the Stanford University Administrative Panel on Human Subjects in Medical Research . This study was conducted during March and April of 2005 . The ActiGraph physical activity monitor was used to measure physical activity . 13–15 One-minute data collection time intervals ( epochs ) were used for this study . An elastic belt with an attached monitor was fit to each student on the first day of the study ( always a weekend ) . Students were instructed to wear the monitor at all times for 14 consecutive days except when swimming , bathing , or sleeping . All students were instructed to maintain their normal activities during the baseline week . On the fifth day , families were notified of their group r and omization and , for the WALK group , the planned route and schedule . The morning commute for the CON group was not altered . A walking school bus , led by one study personnel , followed the safest route to school based on the location of the students ’ homes relative to each other and the school . Students walked at their normal pace but were encouraged to stay together as a group . A wagon , pulled by the study personnel , was used to transport backpacks and instruments . If a student lived more than 1.6 Km from the school , the parent/guardian dropped the student off at one of the other student ’s homes ( 1.1 Km from school ) and he/she walked the remainder of the trip . Raw accelerometer data were reduced to summary variables using a custom software program . 9 For analysis , accelerometer data were summarized for the total week and weekdays . Each weekday was also divided into four time blocks ; before- , during- , and after-school and evening . Average monitor counts·min−1 and the average percent of time spent in moderate-tovigorous physical activity ( % MVPA ) were calculated for each student using age-specific count cutoffs 16 and change scores ( intervention – baseline ) calculated . Between group comparisons used non-parametric Wilcoxon Rank Sum tests with a two-tailed alpha=0.05 . CON ( n=6 ) and WALK ( n=5 ) students were ( mean±SD ) 9.5±1.02 and 9.7±0.90 years old . The CON group had four boys ( all Caucasian ) and two girls ( 1 Caucasian , 1 Chinese ) . The WALK group had two boys and three girls ( all Caucasian ) . On average , CON and WALK students lived 1.3±0.68 and 0.9±0.46 Km from school . The time required to walk to school for the WALK students ranged from 10–36 minutes and was proportional to the distance traveled 0.4–1.1 Km ( mean , 0.8 Km ) ( Spearman r=0.95 ) . Compared to students in the CON group , WALK students significantly increased their counts·min-1 and % MVPA ( p≤0.02 ) before school ( Table 1 ) . This difference was even more pronounced when only looking at the General Commute Time ( GCT ) , defined as the 45 minutes before school ( p Average counts·min-1 and percent of time spent in MVPA by group by weekday time blocks , all days , and weekdays To our knowledge , this is the first experimental study to investigate the effect of walking to school on physical activity . The walking school bus did prove feasible in this small sample . Compared to students that were driven to school , those that walked to school increased their MVPA during the GCT by 14 minutes per day . Qualitative data collected at the end of the intervention indicated that the walking school bus was well liked . Parents noted that it was a , “ less stressful start to the day ” and another mentioned , “ She can do it ! And she enjoys walking . She even wanted to walk home ” . Students indicated that they enjoyed walking with others and one student noted that he , “ Did n't feel as tired in the morning compared to when I am driven to school ” . Two students indicated they did not like getting up earlier and none of the students liked the “ loud , embarrassing wagon ” . Five of the six students in the WALK group said they would continue to walk to school . In this experimental study we found no significant group differences for total daily or weekday physical activity or percent of time spent in MVPA . This was likely due to insufficient power to detect such differences , given the high variability of physical activity behavior and measurement error . The 14 minute increase in MVPA during the general commute time for the WALK students represents approximately 25 % of the recommended 60-minutes of MVPA per day . The promising results of this small experimental study justify larger walk to school experiments to examine whether walk to school interventions can impact total daily physical activity and MVPA , as well as other health and behavior outcomes . Additional community level benefits include less car congestion and emissions and improved neighborhood safety via more frequent social interactions with neighbors and greater community cohesion . Since walking to school will likely take longer than being driven , the morning routine may change to accommo date this . The child may need to get up earlier , potentially reducing the amount of time for sleeping and eating breakfast . Therefore , quality and quantity of sleep , consumption of breakfast and overall dietary behavior of students that walk to school should be considered . Lastly , such school- and community-based efforts should seek to engage school personnel and parent and community volunteers as walking school bus chaperones.17 The experiences from such programs can be incorporated into physical education and science curriculums as experiential learning opportunities ( e.g. , walkability audits ; car , bike , and pedestrian counts ; step or distance goals for active commuting , etc … ) ", "Background Recess provides a daily opportunity for children to engage in moderate-to-vigorous ( MVPA ) and vigorous physical activity ( VPA ) . Limited research has investigated the effects of recess-based interventions on physical activity using large sample sizes whilst investigating variables that may influence the intervention effect . The aim of the study was to investigate the short-term effects of a playground markings and physical structures intervention on recess physical activity . A secondary aim was to investigate the effects of covariates on the intervention . Methods 150 boys and 147 girls were r and omly selected from 26 elementary schools to wear uni-axial accelerometers that quantified physical activity every 5 seconds during recess . Fifteen schools located in deprived areas in one large urban city in Engl and received funding through a national initiative to re design the playground environment . Eleven schools served as matched socioeconomic controls . Data were collected at baseline and 6-weeks following playground intervention . Recess MVPA and VPA levels adjusted for pupil- and school-level covariates ( baseline physical activity , age , gender , recess length , body mass index ) were analysed using multilevel analyses . Results Positive but non-significant intervention effects were found for MVPA and VPA when confounding variables were added to the model . Gender was a significant predictor of recess physical activity , with boys engaging in more MVPA and VPA than girls . Significant interactions for MVPA revealed that the intervention effect was stronger for younger elementary aged school children compared to older children , and the intervention effect increased as daily recess duration increased . Conclusion The playground re design intervention result ed in small but non-significant increases in children 's recess physical activity when school and pupil level variables were added to the analyses . Changing the playground environment produced a stronger intervention effect for younger children , and longer daily recess duration enabled children to engage in more MVPA following the intervention . This study concludes that the process of increasing recess physical activity is complex when school and pupil-level covariates are considered , though they should be taken into account when investigating the effects of playground intervention studies on children 's physical activity during recess" ]

[ "BACKGROUND Implantable cardioverter defibrillator ( ICD ) implantation is a common approach in patients at high risk of sudden cardiac death . To check for normal function , it is necessary to test the ICD . For this purpose , repetitive induction and termination of ventricular fibrillation by direct current shocks is required . This may lead to minor myocardial damage . Cardiac troponin T ( cTnT ) and I ( cTnI ) are specific markers for the detection of myocardial injury . Because these proteins usually are undetectable in healthy individuals , they are excellent markers for detecting minimal myocardial damage . The objective of this study was to evaluate the effect of defibrillation of induced ventricular fibrillation on markers of myocardial damage . METHODS This study included 14 patients who underwent ICD implantation and intraoperative testing . We measured cTnT , cTnI , creatine kinase MB ( CK-MB ) mass , CK activity , and myoglobin before and at definite times after intraoperative shock application . RESULTS Depending on the effectiveness of shocks and the energy applied , the cardiac-specific markers cTnT and cTnI , as well as CK-MB mass , showed a significant increase compared with the baseline value before testing and peaked for the most part 4 h after shock application . In contrast , the increases in CK activity and myoglobin were predominantly detectable in patients who received additional external shocks . CONCLUSIONS ICD implantation and testing leads to a short release of cardiac markers into the circulation . This release seems to be of cytoplasmic origin and depends on the number and effectiveness of the shocks applied", "BACKGROUND The implantable cardioverter-defibrillator ( ICD ) is highly effective in reducing mortality among patients at risk for fatal arrhythmias , but inappropriate ICD activations are frequent , with potential adverse effects . METHODS We r and omly assigned 1500 patients with a primary -prevention indication to receive an ICD with one of three programming configurations . The primary objective was to determine whether programmed high-rate therapy ( with a 2.5-second delay before the initiation of therapy at a heart rate of ≥200 beats per minute ) or delayed therapy ( with a 60-second delay at 170 to 199 beats per minute , a 12-second delay at 200 to 249 beats per minute , and a 2.5-second delay at ≥250 beats per minute ) was associated with a decrease in the number of patients with a first occurrence of inappropriate antitachycardia pacing or shocks , as compared with conventional programming ( with a 2.5-second delay at 170 to 199 beats per minute and a 1.0-second delay at ≥200 beats per minute ) . RESULTS During an average follow-up of 1.4 years , high-rate therapy and delayed ICD therapy , as compared with conventional device programming , were associated with reductions in a first occurrence of inappropriate therapy ( hazard ratio with high-rate therapy vs. conventional therapy , 0.21 ; 95 % confidence interval [ CI ] , 0.13 to 0.34 ; P vs. conventional therapy , 0.24 ; 95 % CI , 0.15 to 0.40 ; P ) and reductions in all-cause mortality ( hazard ratio with high-rate therapy vs. conventional therapy , 0.45 ; 95 % CI , 0.24 to 0.85 ; P=0.01 ; hazard ratio with delayed therapy vs. conventional therapy , 0.56 ; 95 % CI , 0.30 to 1.02 ; P=0.06 ) . There were no significant differences in procedure-related adverse events among the three treatment groups . CONCLUSIONS Programming of ICD therapies for tachyarrhythmias of 200 beats per minute or higher or with a prolonged delay in therapy at 170 beats per minute or higher , as compared with conventional programming , was associated with reductions in inappropriate therapy and all-cause mortality during long-term follow-up . ( Funded by Boston Scientific ; MADIT-RIT Clinical Trials.gov number , NCT00947310 . )", "OBJECTIVES The purpose of this study was to prospect ively examine the role of clinical , laboratory , echocardiographic , and electrophysiological variables as predictors of appropriate initial implantable cardioverter-defibrillator ( ICD ) therapy for ventricular tachycardia ( VT ) or ventricular fibrillation ( VF ) or death in the Multicenter Automatic Defibrillator Implantation Trial II ( MADIT-II ) population . BACKGROUND There is limited information regarding the determinants of appropriate ICD therapy in patients with reduced ventricular function after a myocardial infa rct ion . METHODS We used secondary analysis in one arm of a multicenter r and omized clinical trial in patients with a previous myocardial infa rct ion and reduced left ventricular function . RESULTS We analyzed baseline and follow-up data on 719 patients enrolled in the ICD arm of the MADIT-II study . Appropriate ICD therapy was observed in 169 subjects . Clinical , laboratory , echocardiographic , and electrophysiological variables , along with measures of clinical instability such as interim hospitalization for congestive heart failure ( IH-CHF ) and interim hospitalization for coronary events ( IH-CE ) , were examined with proportional hazards models and Kaplan-Meier time-to-event curves before and after first interim hospitalization . Interim hospitalization-CHF , IH-CE , no beta-blockers , digitalis use , blood urea nitrogen ( BUN ) > 25 , body mass index ( BMI ) > or = 30 kg/m2 , and New York Heart Association functional class > II were associated with increased risk for appropriate ICD therapy for VT , VF , or death . In a multivariate ( stepwise selection ) analysis , IH-CHF was associated with an increased risk for the end point of either VT or VF ( hazard ratio [ HR ] 2.52 , 95 % confidence interval [ CI ] 1.69 to 3.74 , p point of VT , VF , or death ( HR 2.97 , 95 % CI 2.15 to 4.09 , p risk for VT , VF , or death ( HR 1.66 , 95 % CI 1.09 to 2.52 , p = 0.02 ) . CONCLUSIONS These results provide important mechanistic information , suggesting that worsening clinical condition and cardiac instability , as reflected by an IH-CHF or IH-CE , are subsequently associated with a significant increase in the risk for appropriate ICD therapy ( for VT/VF ) and death", "AIMS AND OBJECTIVE Outcome data of patients with implantable cardioverter defibrillators ( ICD ) and atrial fibrillation ( AF ) are conflicting . The German DEVICE registry aims to add further information on this particular cohort . METHODS AND RESULTS The German DEVICE registry is a nationwide prospect i ve multicenter data base of ICD implantations . 3261 patients are included ( 81 % males , 2701 ( 82.8 % ) first ICD implantations , 560 ( 17.2 % ) ICD replacements ) . Cardiac resynchronization therapy ( CRT-D ) was performed in 882 patients ( 27.0 % ) . Sinus rhythm ( SR ) was present in 2654 ( 81.4 % ) and atrial fibrillation ( AF ) in 607 ( 18.6 % ) . Left ventricular ejection fraction ( LVEF ) did not differ between groups ( SR 32.3 % , AF 30.4 % ; p = 0.09 ) . AF patients were older ( AF 70.9 versus SR 63.9 years ; p co-morbidities ( diabetes , hypertension , chronic kidney disease ; all p In-hospital complications were not significantly different between groups ( p = 0.58 ) . Follow-up information after one year was available in 2967 patients ( 91 % ) . One-year overall mortality after first ICD implantation was 4.9 % for SR and 11.2 % for AF patients ( p mortality one year after ICD replacement was 8.4 % for SR and 12.0 % for AF ( p = 0.34 ) . No statistically significant difference between SR and AF patients receiving a CRT device was observed ( SR 6.9 % , AF 10.7 % , p = 0.16 ) in terms of one-year mortality . CONCLUSION The German DEVICE registry demonstrates that patients with AF who receive ICD devices are older , have more co-morbidity and more severe heart failure . AF carries an independent 1.39 fold risk ( 95 % CI 1.02 - 1.89 ) of death after one year in patients only with first ICD implantation", "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", "BACKGROUND Patients with heart failure who receive an implantable cardioverter-defibrillator ( ICD ) for primary prevention ( i.e. , prevention of a first life-threatening arrhythmic event ) may later receive therapeutic shocks from the ICD . Information about long-term prognosis after ICD therapy in such patients is limited . METHODS Of 829 patients with heart failure who were r and omly assigned to ICD therapy , we implanted the ICD in 811 . ICD shocks that followed the onset of ventricular tachycardia or ventricular fibrillation were considered to be appropriate . All other ICD shocks were considered to be inappropriate . RESULTS Over a median follow-up period of 45.5 months , 269 patients ( 33.2 % ) received at least one ICD shock , with 128 patients receiving only appropriate shocks , 87 receiving only inappropriate shocks , and 54 receiving both types of shock . In a Cox proportional-hazards model adjusted for baseline prognostic factors , an appropriate ICD shock , as compared with no appropriate shock , was associated with a significant increase in the subsequent risk of death from all causes ( hazard ratio , 5.68 ; 95 % confidence interval [ CI ] , 3.97 to 8.12 ; P the risk of death ( hazard ratio , 1.98 ; 95 % CI , 1.29 to 3.05 ; P=0.002 ) . For patients who survived longer than 24 hours after an appropriate ICD shock , the risk of death remained elevated ( hazard ratio , 2.99 ; 95 % CI , 2.04 to 4.37 ; P death among patients who received any ICD shock was progressive heart failure . CONCLUSIONS Among patients with heart failure in whom an ICD is implanted for primary prevention , those who receive shocks for any arrhythmia have a substantially higher risk of death than similar patients who do not receive such shocks", "INTRODUCTION Atrial fibrillation ( AF ) is associated with significant morbidity and mortality that may be related to hemodynamic impairment , thromboembolic events , or enhanced electrical instability of the ventricular myocardium . There is , however , a lack of data concerning the association of AF and ventricular tachyarrhythmias . METHODS AND RESULTS Consecutive patients with indication for an implantable cardioverter defibrillator ( ICD ) were classified for the presence or absence of persistent AF at the time of device implantation . Incidence of device therapy , stored electrograms , and clinical events during follow-up were evaluated prospect ively . Two hundred fifty patients were included . During follow-up ( 20+/-14 months ) , patients in AF experienced appropriate device therapy for recurrent ventricular arrhythmias more frequently compared with patients in sinus rhythm ( SR ) ( 63 % vs 38 % , P = 0.01 ) . On multivariate analysis , AF was an independent predictor of appropriate ICD therapy ( relative risk 1.8 ; 95 % confidence interval [ CI ] 1.2 to 2.9 ) and inappropriate device therapy ( relative risk 2.3 ; 95 % CI 1.2 to 4.5 ) . Predefined clinical events ( cluster endpoint : death , syncope , and hospitalizations ) were observed more frequently in AF than in SR patients ( 55 % vs 31 % , P = 0.01 ) . Analysis of device-stored electrograms revealed a higher incidence of short-long-short cycles preceding ventricular arrhythmias in AF compared with SR patients ( 50 % vs 16 % , P = 0.002 ) . Baseline heart rate preceding ventricular arrhythmias did not differ between the two groups . CONCLUSION AF is an independent predictor of recurrent ventricular arrhythmias in ICD recipients . The underlying electrophysiologic mechanism seems to be irregular rather than rapid ventricular activation , with a high incidence of short-long-short sequences preceding ventricular tachyarrhythmias in AF patients", "IMPORTANCE Using more intervals to detect ventricular tachyarrhythmias has been associated with reducing unnecessary implantable cardioverter-defibrillator ( ICD ) therapies . OBJECTIVE To determine whether using 30 of 40 intervals to detect ventricular arrhythmias ( VT ) ( long detection ) during spontaneous fast VT episodes reduces antitachycardia pacing ( ATP ) and shock delivery more than 18 of 24 intervals ( st and ard detection ) . DESIGN , SETTING , AND PARTICIPANTS R and omized , single-blind , parallel-group trial that enrolled 1902 primary and secondary prevention patients ( mean [ SD ] age , 65 [ 11 ] years ; 84 % men ; 75 % primary prevention ICD ) with ischemic and nonischemic etiology undergoing first ICD implant at 1 of 94 international centers ( March 2008-December 2010 ) . INTERVENTIONS Patients were r and omized 1:1 to programming with long- ( n = 948 ) or st and ard-detection ( n = 954 ) intervals . MAIN OUTCOMES AND MEASURES Total number of ATPs and shocks delivered for all episodes ( primary outcomes ) and inappropriate shocks , mortality , and syncopal rate ( secondary outcomes ) . RESULTS During a median follow-up of 12 months ( interquartile range , 11 - 13 ) , long-detection group had 346 delivered therapies ( 42 therapies per 100 person-years , 95 % CI , 38 - 47 ) vs 557 in the st and ard-detection group ( 67 therapies per 100 person-years [ 95 % CI , 62 - 73 ] ; incident rate ratio [ IRR ] , 0.63 [ 95 % CI , 0.51 - 0.78 ] ; P probability of therapy occurrence ( P first occurrence of inappropriate shock ( 5.1 per 100 patient-years [ 95 % CI , 3.7 - 6.9 ] vs 11.6 [ 95 % CI , 9.4 - 14.1 ] ; IRR , 0.55 [ 95 % CI , 0.36 - 0.85 ] ; P = .008 ) . Mortality ( 5.5 [ 95 % CI , 4.0 - 7.2 ] vs 6.3 [ 95 % CI , 4.8 - 8.2 ] per 100 patient-years ; HR , 0.87 ; P = .50 ) and arrhythmic syncope rates ( 3.1 [ 95 % CI , 2.6 - 4.6 ] vs 1.9 [ 95 % CI , 1.1 - 3.1 ] per 100 patient-years ; IRR , 1.60 [ 95 % CI , 0.76 - 3.41 ] ; P = .22 ) did not differ significantly between groups . CONCLUSIONS AND RELEVANCE Among patients receiving an ICD , the use of a long- vs st and ard-detection interval result ed in a lower rate of ATP and shocks , and inappropriate shocks . This programming strategy may be an appropriate alternative . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00617175", "AIMS Strategically chosen ventricular tachycardia (VT)/ventricular fibrillation ( VF ) detection and therapy parameters aim ed at reducing shock deliveries were proven effective in studies that utilized single manufacturer devices with a follow-up of up to 1 year . Whether these beneficiary effects can be generalized to additional manufacturers and be maintained for longer periods is to be determined . Our aim was to evaluate the durability and applicability of the programming of strategic implantable cardioverter-defibrillators ( ICDs ) of various manufacturers , which is aim ed at reducing the shock delivery burden in primary prevention ICD recipients . METHODS AND RESULTS A retrospective analysis of prospect ively collected data of 300 ICD recipients of various manufacturers was conducted ; 160 devices were strategically programmed to reduce shocks and 140 were not . The primary endpoint was the composite of death and appropriate shocks . Additional outcomes were inappropriate shocks , syncope events , and non-sustained VTs . At a median follow-up of 24 months , 19 patients died , 31 received appropriate shocks , and 41 received inappropriate shocks . Multivariate analysis showed that strategic programming dedicated to shock reduction was associated with a 64 % risk reduction in the primary endpoint [ hazard ratio ( HR ) : 0.13 - 0.93 ; P = 0.03 ] and a 70 % reduction in inappropriate shock deliveries ( HR : 0.16 - 0.72 ; P = 0.01 ) . Very few syncope events occurred ( five patients , 1.6 % ) , and there was no between-group difference in this outcome . CONCLUSION Utilization of strategically chosen VT/VF detection and therapy parameters was found to be effective and safe in ICDs of various manufacturers at a median follow-up period of 2 years among primary prevention patients", "OBJECTIVE This study undertook to determine if the presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular dysfunction was associated with increased mortality and , if so , whether the increase could be attributed to progressive heart failure or arrhythmic death . BACKGROUND Atrial fibrillation is a common condition in heart failure with the potential to impact hemodynamics and progression of left ventricular systolic dysfunction as well as the electrophysiologic substrate for arrhythmias . The available data do not conclusively define the effect of atrial fibrillation on prognosis in heart failure . METHODS A retrospective analysis of the Studies of Left Ventricular Dysfunction Prevention and Treatment Trials was conducted that compared patients with atrial fibrillation to those in sinus rhythm at baseline for the risk of all-cause mortality , progressive pump-failure death and arrhythmic death . RESULTS The patients with atrial fibrillation at baseline , compared to those in sinus rhythm , had greater all-cause mortality ( 34 % vs. 23 % , p death attributed to pump-failure ( 16.7 % vs. 9.4 % , p end point of death or hospitalization for heart failure ( 45 % vs. 33 % , p arrhythmic deaths . After multivariate analysis , atrial fibrillation remained significantly associated with all-cause mortality ( relative risk [ RR ] 1.34 , 95 % confidence interval [ CI ] 1.12 to 1.62 , p=0.002 ) , progressive pump-failure death ( RR 1.42 , 95 % CI 1.09 to 1.85 , p=0.01 ) , the composite end point of death or hospitalization for heart failure ( RR 1.26 , 95 % CI 1.03 to 1.42 , p=0.02 ) , but not arrhythmic death ( RR 1.13 ; 95 % CI 0.75 to 1.71 ; p=0.55 ) . CONCLUSIONS The presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular systolic dysfunction is associated with an increased risk for all-cause mortality , largely explained by an increased risk for pump-failure death . These data suggest that atrial fibrillation is associated with progression of left ventricular systolic dysfunction", "Implantable cardioverter-defibrillator ( ICD ) therapy decreases arrhythmic and all-cause mortality in patients at high risk of sudden death . However , its clinical benefit in elderly patients is uncertain . The aim of this study was to assess the long-term efficacy of ICD treatment in elderly patients and to identify markers of successful ICD therapy and risk factors of mortality . We performed multivariate analysis of a prospect i ve long-term data base from 2 tertiary care centers including 936 consecutive patients with an ICD . Predictors of ICD therapy and risk factors for mortality were assessed in patients ≥75 years old at ICD implantation compared to younger patients . Mean follow-up time was 43 ± 40 months . Rates of ICD therapy were similar in the 2 age groups . No significant predictors of ICD therapy could be identified in older patients . Median estimated survival was 132 months in patients . Decreased ejection fraction ( hazard ratio 1.62 per 10 % decrease , p = 0.03 ) and impaired renal function ( hazard ratio 1.57 per 10 ml/kg/m(2 ) decrease in estimated glomerular filtration rate , p = 0.02 ) were independent risk factors of mortality in patients ≥75 years old . However , mortality of older patients was similar to that of the age-matched general population irrespective of delivery of ICD therapy . In conclusion , ICD therapy is effective for treatment of life-threatening arrhythmias in all age groups . However , prevention of sudden cardiac death may have limited impact on overall mortality in older patients . Despite a similar rate of appropriate ICD therapies , risk of death is increased 1.6-fold in ICD recipients ≥75 years old compared to younger patients . Patients with decreased ejection fraction and impaired renal function are at highest risk", "OBJECTIVES This study aim ed to assess the prevalence of different types of atrial fibrillation ( AF ) and their prognostic importance in implantable cardioverter-defibrillator ( ICD ) patients . BACKGROUND The prevalence of AF has taken epidemic proportions in the population with cardiovascular disease . The prognostic importance of different types of AF in ICD patients remains unclear . METHODS Data on 913 consecutive patients ( 79 % men , mean age 62 + or - 13 years ) receiving an ICD at the Leiden University Medical Center were prospect ively collected . Among other characteristics , the existence and type of AF ( paroxysmal , persistent , or permanent ) were assessed at implantation . During follow-up , the occurrence of appropriate or inappropriate device therapy as well as mortality was noted . RESULTS At implantation , 73 % of patients had no history of AF , 9 % had a history of paroxysmal AF , 7 % had a history of persistent AF , and 11 % had permanent AF . During 833 + or - 394 days of follow-up , 117 ( 13 % ) patients died , 228 ( 25 % ) patients experienced appropriate device discharge , and 139 ( 15 % ) patients received inappropriate shocks . Patients with permanent AF exhibited more than double the risk of mortality , ventricular arrhythmias triggering device discharge , and inappropriate device therapy . Patients with paroxysmal or persistent AF did not show a significant increased risk of mortality or appropriate device therapy but demonstrated almost 3 times the risk of inappropriate device therapy . CONCLUSIONS In the population currently receiving ICD treatment outside the setting of clinical trials , a large portion has either a history of AF or permanent AF . Both types of AF have prognostic implication s for mortality and appropriate as well as inappropriate device discharge", "AIMS The benefit of implantable cardioverter-defibrillators ( ICDs ) in patients at risk of sudden death has been established in r and omized clinical trials ( RCTs ) using the ICD models available at the time . However , observational large-scale data on the incidence of arrhythmias in up-to- date ICDs implanted according to the current guidelines are scarce . The aim was to assess the incidence of arrhythmias in a large , current ICD population based on a blinded peer review of the detected episodes . METHODS AND RESULTS UMBRELLA is a multicentre , observational registry of ICD patients followed by remote monitoring . Stored episodes were classified by a blinded committee of experts . Subgroup analyses were based on clinical profiles established by previous pivotal RCTs of ICDs . Of 1514 enrolled patients , 605 ( 39.9 % ) patients had 5951 episodes after 26 ± 17 months follow-up , being 3353 of them ( 56.3 % ) sustained ventricular arrhythmias ( SVA ) , and 13.2 % of SVA were self-terminated . Appropriate and inappropriate shocks occurred in 11.6 and 5 % of patients , respectively . The 3 years cumulative incidence of SVA was 25 % ( 95 % CI : 21 - 28 % ) in primary prevention patients and 41 % ( 95 % CI : 36 - 47 % ) in secondary prevention patients ( P higher incidence of SVA . CONCLUSION This real-world analysis suggests that modern ICD patients have a low rate of appropriate and inappropriate shocks . The risk of SVA in secondary prevention patients is less than what has been reported in RCTs", "AIMS To evaluate the incidences of and risk factors predisposing to appropriate and inappropriate shocks and mortality in a ' real-world ' population of patients with ischaemic heart disease ( IHD ) and implantable cardioverter defibrillators ( ICD ) for primary prevention of sudden cardiac death ( SCD ) . METHODS AND RESULTS In this nationwide cohort , we prospect ively followed 1609 patients with IHD and left ventricular dysfunction from the Danish ICD Register who received an ICD for primary prevention of SCD ( 1 January 2007 to 30 November 2011 ) . Primary study outcomes were appropriate shocks , inappropriate shocks , and all-cause mortality . Secondary study outcomes included the composite endpoints : appropriate therapy and inappropriate therapy ( defined as shock or anti-tachycardia pacing ) . All-cause mortality was 12.1 % during a mean follow-up time of 1.9 ± 1.3 years . Inappropriate shocks and therapy occurred in 2.6 % and 3.7 % during follow-up , respectively . Appropriate shocks and therapy was identified in 7.8 % and 13.4 % , respectively . Time-dependent multivariable Cox regression analyses were used to identify risk factors of inappropriate/appropriate shock , therapy and mortality . Implantation of a dual-chamber ICD was associated with increased risk of both inappropriate shocks and any inappropriate therapy compared to single-chamber ICD [ hazard ratios ( HR ) = 2.45 ; confidence intervals (CI):1.16 - 5.14 and HR = 2.38 ; CI:1.28 - 4.42 , respectively ] . No excess risk of mortality was associated with any device type . CONCLUSION In this nationwide study of IHD patients with an ICD for primary prevention of SCD , the incidence of appropriate shocks as well as inappropriate shocks were significantly lower than reported in r and omized trials . Implantation of a dual-chamber ICD was associated with more inappropriate shocks compared with single chamber devices ", "INTRODUCTION Recent studies suggest a worse impact of inappropriate shock therapies on the outcome of patients with an implantable cardioverter-defibrillator ( ICD ) . However , it is not known whether the worse impact is attributed to the ICD shock itself or due to the underlying heart disease . The aim of the study was to evaluate the impact of inappropriate ICD shocks on clinical outcome by comparing ICD shocks triggered by atrial fibrillation ( AF ) with shocks caused by lead failure . METHODS AND RESULTS A total of 1,411 consecutive patients of the prospect i ve single-center ICD-registry Ludwigshafen who underwent an ICD implantation between 1992 and 2008 for primary or secondary prevention of sudden cardiac death were analyzed . During the median follow-up of 3 years , 297 ( 21 % ) patients experienced inappropriate ICD shocks . Sixty percent of patients had inappropriate shocks due to AF and 24 % due to lead defect or T-wave oversensing . Multiple ICD shocks ( ≥2 ) triggered by AF were associated with a worse prognosis , whereas a single shock due to AF or 1 or multiple shocks result ing from lead failure were not . ICD shocks caused by AF occurred more often in t and em with a serious adverse event than in patients with a lead failure ( 15 % vs 6 % , P Multiple ICD shocks triggered by AF are associated with a worse prognosis in ICD patients , whereas a single shock due to AF or shocks result ing from lead failure are not . These data support that the ICD shock itself has no worse impact on the outcome of ICD patients" ]

[ "PURPOSE Major primary care reforms have been introduced in recent years in the United Kingdom , including financial incentives to improve clinical quality and provide more rapid access to care . Little is known about the impact of these changes on patient experience . We examine patient reports of quality of care between 2003 and 2007 , including r and om sample s of patients on practice lists and patients with long-term conditions . METHODS We conducted a cross-sectional design study of family practice s in which question naires were sent to serial sample s of patients in 42 representative general practice s in Engl and . Question naires sent to sample s of patients with chronic disease ( asthma , angina , and diabetes ) and r and om sample s of adult patients ( excluding patients who reported any long-term condition ) in 2003 , 2005 , and 2007 addressed issues of access , communication , continuity of care , coordination , nursing care , and overall satisfaction . RESULTS There were no significant changes in quality of care reported by either group of patients between 2003 and 2007 for communication , nursing care , coordination , and overall satisfaction . Some aspects of access improved significantly for patients with chronic disease , but not for the r and om sample s of patients . Patients in both sample s reported seeing their usual physician less often and gave lower satisfaction ratings for continuity of care . Most scores were significantly higher for the chronic illness sample s than for the r and om sample s of patients in 2003 , even after adjusting for age . CONCLUSIONS There was a modest improvement in access to care for patients with chronic illness , but all patients now find it somewhat harder to obtain continuity of care . This outcome may be related to the incentives to provide rapid appointments or to the increased number of specialized clinics in primary care . The possibility of unintended effects needs to be considered when introducing pay for performance schemes", "Abstract Objectives : To assess variation in the quality of care in general practice and identify factors associated with high quality care . Design : Observational study . Setting : Stratified r and om sample of 60 general practice s in six areas of Engl and . Outcome measures : Quality of management of chronic disease ( angina , asthma in adults , and type 2 diabetes ) and preventive care ( rates of uptake for immunisation and cervical smear ) , access to care , continuity of care , and interpersonal care ( general practice assessment survey ) . Multiple logistic regression with multilevel modelling was used to relate each of the outcome variables to practice size , routine booking interval for consultations , socioeconomic deprivation , and team climate . Results : Quality of clinical care varied substantially , and access to care , continuity of care , and interpersonal care varied moderately . Scores for asthma , diabetes , and angina were 67 % , 21 % , and 17 % higher in practice s with 10 minute booking intervals for consultations compared with practice s with five minute booking intervals . Diabetes care was better in larger practice s and in practice s where staff reported better team climate . Access to care was better in small practice s. Preventive care was worse in practice s located in socioeconomically deprived areas . Scores for satisfaction , continuity of care , and access to care were higher in practice s where staff reported better team climate . Conclusions : Longer consultation times are essential for providing high quality clinical care . Good teamworking is a key part of providing high quality care across a range of areas and may need specific support if quality of care is to be improved . Additional support is needed to provide preventive care to deprived population s. No single type of practice has a monopoly on high quality care : different types of practice may have different strengths . What is already known on this topic Quality of care varies in virtually all aspects of medicine that have been studied Most studies look at quality of care from a single perspective or for a single condition What this study adds Quality of care varies for both clinical care and assessment s by patients of access and interpersonal care Practice s with longer booking intervals provide better management of chronic disease ; preventive care is less good in practice s in deprived areas No single type of practice has a monopoly on high quality care — small practice s provide better access but poorer diabetes care Good team climate reported by staff is associated with a range of aspects of high quality", "BACKGROUND Evidence from cost-effective smoking cessation programs is scarce . This study determined the cost-effectiveness of 3 smoking cessation strategies as provided by general practitioners ( GPs ) in Germany . METHODS In a cluster-r and omized smoking cessation trial , rates and intervention costs for 577 smoking patients of 82 GPs were followed up for 12 months . Three smoking cessation treatments were tested : ( 1 ) GP training plus GP remuneration for each abstinent patient , ( 2 ) GP training plus cost-free nicotine replacement medication and /or bupropion hydrochloride for the patient , and ( 3 ) a combination of both strategies . Smoking abstinence at 12 months was the primary outcome used to calculate incremental cost-effectiveness ratios and net monetary benefits . RESULTS Intervention 1 was not effective compared with treatment as usual ( TAU ) . Interventions 2 and 3 each proved to be cost-effective compared separately with TAU . When applying a 95 % level of certainty of cost-effectiveness against TAU , euro 9.80 or euro 6.96 , respectively , had to be paid for each additional 1 % of patients abstinent at 12 months ( maximum willingness to pay ) . That means that in intervention 2 , euro 92.12 per patient in the program must be invested to gain 1 additional quitter ( as opposed to euro 39.10 paid per patient during the trial ) . In intervention 2 , the cost was euro 82.82 , as opposed to euro 50.04 . Neither of these 2 cost-effective treatments proved to be superior to the other . The cost-effectiveness of both treatments was stable against TAU in sensitivity analyses . ( The exchange rate from October 1 , 2003 , was used ; euro1 = $ 1.17 . ) CONCLUSIONS Both treatments have a high potential to reduce smoking-related morbidity at a low cost . It is highly recommended that they be implemented as a routine service offered by GPs because in many countries , health insurance plans currently do not fund nicotine replacement therapy", "BACKGROUND Tobacco quitlines offer clinicians a means to connect their patients with evidence -based treatments . Innovative methods are needed to increase clinician referral . METHODS This is a clinic r and omized trial that compared usual care ( n = 25 clinics ) vs a pay-for-performance program ( intervention ) offering $ 5000 for 50 quitline referrals ( n = 24 clinics ) . Pay-for-performance clinics also received monthly up date s on their referral numbers . Patients were eligible for referral if they visited a participating clinic , were 18 years or older , currently smoked cigarettes , and intended to quit within the next 30 days . The primary outcome was the clinic 's rate of quitline referral ( ie , number of referrals vs number of smokers seen in clinic ) . RESULTS Pay-for-performance clinics referred 11.4 % of smokers ( 95 % confidence interval [ CI ] , 8.0%-14.9 % ; total referrals , 1483 ) compared with 4.2 % ( 95 % CI , 1.5%-6.9 % ; total referrals , 441 ) for usual care clinics ( P = .001 ) . Rates of referral were similar in intervention vs usual care clinics ( n = 9 ) with a history of being very engaged with quality improvement activities ( 14.1 % vs 15.1 % , respectively ; P = .85 ) . Rates were substantially higher in intervention vs usual care clinics with a history of being engaged ( n = 22 clinics ; 10.1 % vs 3.0 % ; P = .001 ) or less engaged ( n = 18 clinics ; 10.1 % vs 1.1 % ; P = .02 ) with quality improvement . The rate of patient contact after referral was 60.2 % ( 95 % CI , 49.7%-70.7 % ) . Among those contacted , 49.4 % ( 95 % CI , 42.8%-55.9 % ) enrolled , representing 27.0 % ( 95 % CI , 21.3%-32.8 % ) of all referrals . The marginal cost per additional quitline enrollee was $ 300 . CONCLUSION A pay-for-performance program increases referral to tobacco quitline services , particularly among clinics with a history of less engagement in quality improvement activities", "OBJECTIVE This study determined the effect of 2 financial incentives --- bonus and enhanced fee-for-service --- on documented immunization rates during a second period of observation . METHODS Incentives were given to 57 r and omly selected inner-city physicians 4 times at 4-month intervals based on the performance of 50 r and omly selected children . Coverage from linked records from all sources was determined for a sub sample of children within physician offices . RESULTS Up-to- date coverage rates documented in the charts increased significantly for children in the bonus group ( 49.7 % to 55.6 % ; P enhanced fee-for-service group ( 50.8 % to 58.2 % ; P control group . The number of immunizations given by these physicians did not change significantly , although the number of immunizations given by others and documented by physicians in the bonus group did increase ( P Up-to- date coverage for all groups increased from 20 to 40 percentage points when immunizations from physician charts were combined with other sources . CONCLUSIONS Both financial incentives produced a significant increase in coverage levels . Increases were primarily due to better documentation not to better immunizing practice s. The financial incentives appeared to provide motivation to physicians but were not sufficient to overcome entrenched behavior patterns . However , true immunization coverage was substantially higher than that documented in the charts", "BACKGROUND This study tested the effects of two organizational support processes , the provision of financial incentives for superior clinical performance and the availability of a patient ( smoker ) registry and proactive telephone support system for smoking cessation , on provider adherence to accepted practice guidelines and associated patient outcomes . METHODS Forty clinics of a large multispecialty medical group practice providing primary care services were r and omly allocated to study conditions . Fifteen clinics each were assigned to the experimental conditions \" control \" ( distribution of printed versions of smoking cessation guidelines ) and \" incentive \" ( financial incentive pay-out for reaching preset clinical performance targets ) . Ten clinics were r and omized to receive financial incentives combined with access to a central ized patient registry and intervention system ( \" registry \" ) . Main outcome measures were adherence to smoking cessation clinical practice guidelines and patients ' smoking cessation behaviors . RESULTS Patients ' tobacco use status was statistically significant ( P accessed counseling programs statistically significantly more often ( P financial incentives and a patient registry/intervention system in improving smoking cessation clinical practice s and patient behaviors was mixed . Additional research is needed to identify conditions under which such organizational support processes result in significant health care quality improvement and warrant the investment", "The study aim was to evaluate the impact of the experimental introduction of salaried contracts in Engl and on general practitioner ( GP ) behaviour and the quality of care . A controlled before- and -after design was implemented involving ten practice s of st and ard contract GPs , paid largely by capitation and fee-for-service , and ten salaried GP practice s. Diaries and routinely available data were used to assess GP workload , and patient assessment s of the quality of care were obtained by postal question naire . GPs in salaried practice s spent less time on practice administration but more working out-of-hours and in direct patient care , allowing more patients to be seen . Total list sizes were smaller in salaried compared with st and ard contract practice s , but lists per GP were higher because of staffing policies . Salaried GPs tended to provide shorter consultations compared with st and ard contract GPs , prescribe in fewer consultations , but referral rates were similar . Quality was rated as higher for seven out of thirteen aspects of care examined in salaried practice s and two in st and ard contract practice s. However , none of these differences were statistically significant . To conclude , salaried contracts did not adversely affect GP productivity and had little impact on other aspects of GP behaviour or the quality of care provided", "Objective : To evaluate new strategies to enhance the promotion of smoking cessation in general practice . Design : Cluster r and omised trial , 2 × 2 factorial design . Setting : 82 medical practice s in Germany , including 94 general practitioners . Participants : 577 patients who smoked at least 10 cigarettes per day ( irrespective of their intention to stop smoking ) and were aged 36–75 years . Interventions : Provision of a 2-h physician group training in smoking cessation methods and direct physician payments for every participant not smoking 12 months after recruitment ( TI , training+incentive ) ; provision of the same training and direct participant reimbursements for pharmacy costs associated with nicotine replacement therapy or bupropion treatment ( TM , training+medication ) . Main outcome measure : Self-reported smoking abstinence obtained at 12 months follow-up and vali date d by serum cotinine . Results : In intention-to-treat analysis , smoking abstinence at 12 months follow-up was 3 % ( 2/74 ) , 3 % ( 5/144 ) , 12 % ( 17/140 ) and 15 % ( 32/219 ) in the usual care , and interventions TI , TM and TI+TM , respectively . Applying a mixed logistic regression model , no effect was identified for intervention TI ( odds ratio ( OR ) 1.26 , 95 % confidence interval ( CI ) 0.65 to 2.43 ) , but intervention TM strongly increased the odds of cessation ( OR 4.77 , 95 % CI 2.03 to 11.22 ) . Conclusion : Providing cost-free effective drugs to patients along with improved training opportunities for general practitioners could be an effective measure to achieve successful promotion of smoking cessation in general practice" ]

[ "OBJECTIVE To assess the serum level of 25 hydroxyvitamin D 25OHD among healthy Saudi Arabian women living in the eastern province . METHODS A cross-sectional r and omized study was conducted between February 1st 2008 and May 31st 2008 at the King Fahd University Hospital , Al-Khobar , Kingdom of Saudi Arabia in 200 Saudi women between 25 - 35 years group 1 and women of > or = 50 years group 2 . Clinical examination , laboratory tests , a complete blood picture , serum calcium , phosphorous , alkaline phosphatase , parathormone , and the serum levels of 25OHD levels were carried out . Data on lifestyle , dietary , and demographic question naires were collected . Vitamin D was defined as deficient with serum level normal 25OHD , and in women of group 2 , 45 % had normal levels of 25OHD . Alkaline phosphatase and parathormone levels were significantly higher in women with low vitamin D levels . Sun exposure and consumption of dairy products were minimal . CONCLUSION Vitamin D deficiency among healthy young Saudi women of 25 - 35 years was 30 % and 55 % in women of > or = 50 years . This study indicates that hypovitaminosis D is common in young and postmenopausal women . Efforts are require to augment and encouraged women for adequate exposure to sunlight and increased intake of fortified vitamin D products to maintain skeletal health", "Background : Calcium absorption is generally considered to be impaired under conditions of vitamin D deficiency , but the vitamin D status that fully normalizes absorption is not known for humans . Objective : To quantify calcium absorption at two levels of vitamin D repletion , using pharmacokinetic methods and commercially marketed calcium supplements . Design : Two experiments performed in the spring of the year , one year apart . In the first , in which participants were pretreated with 25-hydroxyvitamin D ( 25OHD ) , mean serum 25OHD concentration was 86.5 nmol/L ; and in the other , with no pretreatment , mean serum concentration was 50.2 nmol/L. Participants received 500 mg oral calcium loads as a part of a st and ard low calcium breakfast . A low calcium lunch was provided at mid-day . Blood was obtained fasting and at frequent intervals for 10 to 12 hours thereafter . Methods : Relative calcium absorption at the two 25OHD concentrations was estimated from the area under the curve ( AUC ) for the load-induced increment in serum total calcium . Results : AUC9 ( ± SEM ) , was 3.63 mg hr/dL ± 0.234 in participants pretreated with 25OHD and 2.20 ± 0.240 in those not pretreated ( P brief , absorption was 65 % higher at serum 25OHD levels averaging 86.5 nmol/L than at levels averaging 50 nmol/L ( both values within the nominal reference range for this analyte ) . Conclusions : Despite the fact that the mean serum 25OHD level in the experiment without supplementation was within the current reference ranges , calcium absorptive performance at 50 nmol/L was significantly reduced relative to that at a mean 25OHD level of 86 nmol/L. Thus , individuals with serum 25-hydroxyvitamin D levels at the low end of the current reference ranges may not be getting the full benefit from their calcium intake . We conclude that the lower end of the current reference range is set too low", "Summary This study aim ed to compare the vitamin D status in healthy Moroccan men and women aged 50 years and older . A total of 186 Moroccan women and 68 men , who had no previous diagnosis of osteoporosis , were recruited prospect ively . We found in this study a high prevalence of hypovitaminosis D with no difference between men and women . Purpose The main purpose of this study was to describe and compare the vitamin D status , parathormone , calcium , and phosphate of healthy Moroccan men and women aged 50 years and older . Methods We conducted two cross-sectional studies , in postmenopausal women from October 2008 to November 2009 and in men over 50 years old , from December 2009 to August 2010 . A total of 186 Moroccan women and 68 men , who had no previous diagnosis of osteoporosis , were recruited prospect ively . For the definition of hypovitaminosis D , the preferred level for 25-hydroxyvitamin D ( 25(OH)D ) insufficiency , which is now recommended by many experts , is 30 ng/mL ( 75 nmol/L ) , and the levels below 10 ng/ml ( 25 nmol/L ) indicate deficiency . Results The prevalence of vitamin D deficiency in men and women was 4.4 and 8.6 % , respectively , and the prevalence of vitamin D(25(OH ) D ) insufficiency in men and women were 85.2 and 77.4 % , respectively . In men and women , no correlations were found between intact parathormone ( PTHi ) and 25(OH ) D ( r = 0.056 ) . Conclusions Despite a sunny environment , we found in this study a high prevalence of hypovitaminosis D ( insufficiency + deficiency ) in Moroccan men over 50 years old and postmenopausal women", "INTRODUCTION Vitamin D status is considered as an important determinant of bone health but supplementation trials with vitamin D(3 ) have yielded conflicting results . The aim of this study was to investigate the associations between serum 25-hydroxyvitamin D ( 25-OH D ) , bone turnover markers , bone mineral density ( BMD ) , radius bone loss and incidence of fracture in postmenopausal women . METHODS 669 postmenopausal women ( mean age : 62.2 years ) belonging to a population -based cohort were followed prospect ively for a median of 11.2 years . At baseline , 25-OH D levels , BMD , bone turnover markers and clinical risk factors of osteoporosis were assessed . BMD loss at the radius was estimated by annual measurements of BMD and all incident fractures which occurred in 134 women were confirmed by radiographs . RESULTS 73 % and 35 % of women had serum 25-OH D levels below 75 and 50 nmol/l which correspond respectively to the median and lowest optimal values recently proposed for fracture prevention . 11 % of women had levels below 30 nmol/l . Serum 25-OH D correlated modestly with intact PTH ( r(2)=0.023 , p bone turnover markers or BMD at the hip and radius after adjustment for age . When levels of 25-OH D were considered as a continuous variable , there was no significant association between 25-OH D levels and radius BMD loss or fracture risk . After adjustment for age , there was no significant difference in incidence of fracture , BMD , radius BMD loss , bone turnover markers , grip strength and the percentage of fallers in the previous year between women with 25-OH D levels below or above 75 , 50 or 30 nmol/l . CONCLUSIONS In a population of home-dwelling healthy postmenopausal women with few of them with severe vitamin D deficiency , vitamin D status may not be an important determinant of bone health", "Objective : The aim of this study was to evaluate serum N-aminoterminal propeptide of type I collagen ( P1NP ) , C-terminal telopeptide of type I collagen ( & bgr;-CTX ) , and vitamin D status in healthy Chinese postmenopausal women . The study was also design ed to investigate their possible relationships with osteoporosis phenotypes . Methods : A community-based population of 1,724 postmenopausal women in Beijing was r and omly selected . Serum bone turnover markers and 25-hydroxyvitamin D [ 25(OH)D ] were tested by an automated Roche electrochemiluminescence system . Dual-energy x-ray absorptiometry was used to measure bone mineral density ( BMD ) . Results : The mean ( SD ) values of serum & bgr;-CTX and P1NP were 0.439 ( 0.210 ) and 56.7 ( 27.9 ) ng/mL , respectively . The 25(OH)D level of postmenopausal women in Beijing was remarkably low ( 13.2 ± 5.4 ng/mL ) . Serum & bgr;-CTX and P1NP levels were negatively correlated with BMDs of lumbar spine , femoral neck , and total hip ( all P relationships of BMD and bone turnover markers . Serum & bgr;-CTX levels were significantly higher in women with sustained osteoporotic fracture or vertebral fracture ( P = 0.006 and 0.012 , respectively ) . No association between P1NP and fracture or vertebral fracture was detected . The same situation applied to 25(OH)D. 25(OH)D was negatively correlated with & bgr;-CTX and P1NP ( r = −0.073 and −0.088 , P = 0.002 and Conclusions : Serum & bgr;-CTX and P1NP levels were negatively correlated with BMD . & bgr;-CTX was significantly higher in postmenopausal women with sustained fracture or vertebral fracture . Vitamin D deficiency was highly prevalent in postmenopausal women in Beijing", "There is an increase in the incidence of falls with aging and about 10 % of falls lead to fractures . Nearly all hip fractures are due to falls and hip fractures are the most severe of the osteoporotic fractures because they lead to a 20 % mortality rate and a loss of independent living in 50 % of cases . Although there are multiple factors associated with falls , our interest is the role that vitamin D metabolism plays in the pathogenesis of falls . Recent clinical trials show that both vitamin D and the metabolite calcitriol reduce the number of falls by 30 - 40 % in elderly subjects . This should also reduce the number of fractures . In European studies , the decrease in falls could be attributed to an improvement in the muscle weakness that often accompanies vitamin D deficiency . However , in the studies using calcitriol there was no vitamin D deficiency , so the mechanism of its efficacy is less clear . It could be due to increased muscle strength , an improvement in the neurological control of balance or both . Underst and ing these mechanisms would allow us to search for analogs of vitamin D that act more selectively on muscle and on the central nervous system", "Throughout evolution , exposure to sunlight and the photo synthesis of vitamin D(3 ) in the skin has been critically important for the evolution of l and vertebrates . During exposure to sunlight , the solar UVB photons with energies 290 - 315 nm are absorbed by 7-dehydrocholesterol in the skin and converted to previtamin D(3 ) . Previtamin D(3 ) undergoes a rapid transformation within the plasma membrane to vitamin D(3 ) . Excessive exposure to sunlight will not result in vitamin D intoxication because both previtamin D(3 ) and vitamin D(3 ) are photolyzed to several noncalcemic photoproducts . During the winter at latitudes above approximately 35 degrees , there is minimal , if any , previtamin D(3 ) production in the skin . Altitude also has a significant effect on vitamin D(3 ) production . At 27 degrees N in November , very little ( approximately 0.5 % ) previtamin D(3 ) synthesis was detected in Agra ( 169 m ) and Katm and u ( 1400 m ) . There was an approximately 2- and 4-fold increase in previtamin D(3 ) production at approximately 3400 m and at Everest base camp ( 5300 m ) , respectively . Increased skin pigmentation , application of a sunscreen , aging , and clothing have a dramatic effect on previtamin D(3 ) production in the skin . It is estimated that exposure in a bathing suit to 1 minimal erythemal dose ( MED ) is equivalent to ingesting between 10,000 and 25,000 IU of vitamin D(2 ) . The importance of sunlight for providing most humans with their vitamin D requirement is well documented by the seasonal variation in circulating levels of 25-hydroxyvitamin D [ 25(OH)D ] . Vitamin D deficiency [ i.e. , 25(OH)D children and adults worldwide . Exposure to lamps that produce UVB radiation is an excellent source for producing vitamin D(3 ) in the skin and is especially efficacious in patients with fat malabsorption syndromes . The major cause of vitamin D deficiency globally is an underappreciation of sunlight 's role in providing humans with their vitamin D(3 ) requirement . Very few foods naturally contain vitamin D , and those that do have a very variable vitamin D content . Recently it was observed that wild caught salmon had between 75 % and 90 % more vitamin D(3 ) compared with farmed salmon . The associations regarding increased risk of common deadly cancers , autoimmune diseases , infectious diseases , and cardiovascular disease with living at higher latitudes and being prone to vitamin D deficiency should alert all health care professionals about the importance of vitamin D for overall health and well being", "INTRODUCTION There is emerging evidence on the widespread tissue effects of vitamin D. AIMS To formulate a position statement on the role of vitamin D in postmenopausal women . MATERIAL S AND METHODS Literature review and consensus of expert opinion . RESULTS AND CONCLUSIONS Epidemiological and prospect i ve studies have related vitamin D deficiency with not only osteoporosis but also cardiovascular disease , diabetes , cancer , infections and neurodegenerative disease . However the evidence is robust for skeletal but not nonskeletal outcomes where data from large prospect i ve studies are lacking . The major natural source of vitamin D is cutaneous synthesis through exposure to sunlight with a small amount from the diet in animal-based foods such as fatty fish , eggs and milk . Vitamin D status is determined by measuring serum 25-hydroxyvitamin D [ 25(OH)D ] levels . Optimal serum 25(OH)D levels are in the region of 30 - 90 ng/mL ( 75 - 225 nmol/L ) though there is no international consensus . Levels vary according to time of the year ( lower in the winter ) , latitude , altitude , air pollution , skin pigmentation , use of sunscreens and clothing coverage . Risk factors for low serum 25(OH)D levels include : obesity , malabsorption syndromes , medication use ( e.g. anticonvulsants , antiretrovirals ) , skin aging , low sun exposure and those in residential care . Fortified foods do not necessarily provide sufficient amounts of vitamin D. Regular sunlight exposure ( without sunscreens ) for 15 min , 3 - 4 times a week , in the middle of the day in summer generate healthy levels . The recommended daily allowance is 600 IU/day increasing to 800 IU/day in those aged 71 years and older . Supplementation can be undertaken with either vitamin D2 ( ergocalciferol ) or vitamin D3 ( cholecalciferol ) with monitoring depending on the dose used and the presence of concomitant medical conditions such as renal disease", "This study aim ed to describe vitamin D status in postmenopausal women in urban and rural areas in Guilan , northern Iran . Between October 2004 and February 2005 a group of 750 women older than 50 years was r and omly selected from urban and rural areas in Guilan . The participants were interviewed to collect data on age , educational level , body weight , height , employment status , reproductive history , medications , history of illness , and supplement use . Serum 25(OH ) D was measured in 646 women ( 427 in urban areas and 219 women in rural areas ) . Serum 25(OH ) D levels in urban and rural postmenopausal women were 18.5 ± 13.5 ng/ml and 22.9 ± 13.8 ng/ml ( P had serum 25(OH ) D levels less than 30 ng/ml , respectively . In this study , serum vitamin D levels and prevalence of vitamin D insufficiency was related to educational level in urban women . The urban women in the lowest educational level ( postmenopausal women living in Guilan province had vitamin D insufficiency . Vitamin D inadequacy was more common in urban areas and especially in the upper social class . Supplement use and national strategies to prevent vitamin D insufficiency are strongly needed in this community", "BACKGROUND The maximal calcium absorption in response to vitamin D has been proposed as a biomarker for vitamin D sufficiency . OBJECTIVE The objective was to determine whether there is a threshold beyond which increasing doses of vitamin D , or concentrations of serum 25-hydroxyvitamin D [ 25(OH)D ] , no longer increase calcium absorption . DESIGN This was a placebo-controlled , dose-response , r and omized , double-blind study of the effect of vitamin D on calcium absorption in healthy postmenopausal women . Seventy-six healthy postmenopausal women were r and omly assigned to placebo or 800 IU ( 20 μg ) , 2000 IU ( 50 μg ) , or 4000 IU ( 100 μg ) vitamin D₃ for 8 wk . The technique of dual isotopes of stable calcium was used with a calcium carrier to measure calcium absorption at baseline and after 8 wk . RESULTS Seventy-one women with a mean ± SD age of 58.8 ± 4.9 y completed the study . The mean calcium intake was 1142 ± 509 mg/d and serum 25(OH)D was 63 ± 14 nmol/L at baseline . A statistically significant linear trend of an increase in calcium absorption adjusted for age and body mass index with increasing vitamin D₃ dose or serum 25(OH)D concentration was observed . A 6.7 % absolute increase in calcium absorption was found in the highest vitamin D₃ group ( 100 μg ) . No evidence of nonlinearity was observed in the dose-response curve . CONCLUSIONS No evidence of a threshold of calcium absorption was found with a serum 25(OH)D range from 40 to 130 nmol/L. Calcium absorption in this range is not a useful biomarker to determine nutritional recommendations for vitamin " ]

[ "The effect of bone cement viscosity and cement mantle thickness on the migration of the Exeter total hip prosthesis was studied in a prospect i ve , r and omized , double-blind clinical Roentgen Stereophotogrammetric Analysis study . Forty-one cemented total hip arthroplasty in 39 patients were included and r and omized into a low/medium Simplex P cement group and a high-viscosity Simplex AF cement group . At time of stem introduction , 5 minutes after mixing , the Simplex AF was more viscous than Simplex P. No statistical difference existed between the 2 cement groups , for neither translation nor rotation migration data . Subsidence of the stem at 2-year follow-up was 1.1 + /- 0.56 mm for Simplex AF cement and 1.5 + /- 1.00 mm for Simplex P cement . The mean rotation of the acetabular components about the sagittal axis was 1.7 degrees + /- 3.8 degrees in the Simplex AF group and 0.7 degrees + /- 2.1 degrees for the Simplex P group . No effect of cement mantle thickness on migration of neither the acetabular cups nor the femoral stems was found . Although there were no differences in migration data for the cups and the stems , 2 acetabular cups in the Simplex AF group ( almost 10 % ) were revised because of mechanical loosening . Because of these findings , we suggest caution before using this new high-viscosity bone cement for fixation of acetabular components", "Background In uncemented total hip arthroplasty with hydroxyapatite coating , early weight bearing is frequently practice d but there is still not much evidence to support this recommendation . Method In a prospect i ve r and omized study we evaluated the effect of partial and full weight bearing after cementless total hip arthroplasty ( ABG ; Stryker-Howmedica ) using radiostereometric analysis ( RSA ) . Between February 1996 and February 2000 , 43 consecutive patients ( mean age 53 ( 41–63 ) years , 23 women ) with hip osteoarthrosis received an uncemented and hydroxyapatite-coated prosthesis with an anteverted stem . All patients were operated in a st and ardized way by three experienced surgeons and they were r and omized to partial ( P ) or full ( F ) weight bearing during the first 6 weeks after surgery . The patients in the partial weight bearing group were equipped with a pressuresensitive insole signaling when their load exceeded the prescribed weight limit . Results At 3-month follow-up , the mean proximal (+)/ distal ( - ) migration of the stem was -0.14 mm ( -1.93– 0.11 ) in group P and -0.31 mm ( -4.30–0.16 ) in group F ( p = 0.6 ) . At 1-year follow-up , the mean migration was –0.17 mm ( -2.18–0.21 ) and -0.28 mm ( -4.31–0.11 ) , respectively ( p = 0.9 ) . There was no significant difference in stem rotations either ( p ) . The cup translations , rotations , and femoral head penetration were similar in the two groups ( p adverse effect of full weight bearing immediately after operation , which justifies use of this regimen after uncemented total hip arthroplasty of the ABG type", " One hundred consecutive ABG ( Anatomique Benoist Giraud , Howmedica ) hydroxyapatite-coated hip arthroplasties in 97 patients were evaluated prospect ively with a follow-up time of 4 to 10 years ( mean , 6 years ) . Clinical results were excellent with an improvement in the Merle d'Aubigne score from 9 preoperatively to 17.4 at 5 years . Thigh pain was persistent in only 3 % ; it was mild in nature and controlled with simple analgesics . Kaplan-Meyer survivorship analysis was 100 % for the femoral stem and 95 % for the acetabular cup at 6 years . Of concern was the high polyethylene wear measured with an average of 0.24 mm/y ( range , 0.05 - 0.76 mm/y )", " 155 patients ( 171 hips ) with a mean age of 50 years ( 24 - 64 ) were r and omized to uncemented PCA ( 84 hips ) or Harris-Galante type I ( 87 hips ) total hip arthroplasty . Clinical and radiographic evaluations were done regularly . The improvements in the Harris hip and pain scores did not differ . Osteolysis developed in 5 PCA and 17 Harris-Galante hips . 13 hips in the PCA and 16 in the Harris-Galante ( HG ) group were revised because of mechanical failures and 1 hip ( HG ) because of infection after a mean follow-up of 9 years . Decreased 10-year survival rate , based on revision as end-point , was noted for the PCA ( 85 % ) , compared with the Harris-Galante cup ( 99 % ) . The corresponding survival rate of the PCA stem ( 96 % ) was higher than that observed for the Harris-Galante design ( 86 % ) . When radiographic failures were included , the survival rates of the 4 different components dropped to between 73 % and 94 % . These findings indicate that further revisions will be necessary and continuous radiographic follow-up is indicated to enable revision before severe bone destruction has occurred . Although the PCA and the Harris-Galante design s differed as regards the survival of the individual components , the overall clinical and radiographic survival rates of these cementless total hip arthroplasties were poor", "Surgery and other invasive therapies are complex interventions , the assessment of which is challenged by factors that depend on operator , team , and setting , such as learning curves , quality variations , and perception of equipoise . We propose recommendations for the assessment of surgery based on a five-stage description of the surgical development process . We also encourage the widespread use of prospect i ve data bases and registries . Reports of new techniques should be registered as a professional duty , anonymously if necessary when outcomes are adverse . Case series studies should be replaced by prospect i ve development studies for early technical modifications and by prospect i ve research data bases for later pre-trial evaluation . Protocol s for these studies should be registered publicly . Statistical process control techniques can be useful in both early and late assessment . R and omised trials should be used whenever possible to investigate efficacy , but adequate pre-trial data are essential to allow power calculations , clarify the definition and indications of the intervention , and develop quality measures . Difficulties in doing r and omised clinical trials should be addressed by measures to evaluate learning curves and alleviate equipoise problems . Alternative prospect i ve design s , such as interrupted time series studies , should be used when r and omised trials are not feasible . Established procedures should be monitored with prospect i ve data bases to analyse outcome variations and to identify late and rare events . Achievement of improved design , conduct , and reporting of surgical research will need concerted action by editors , funders of health care and research , regulatory bodies , and professional societies", "In a prospect i ve study of 100 consecutive Wagner resurfacing hip arthroplasties in ninety-three patients , the outcomes for all hips were determined for an eight to ten-year follow-up period . By survivorship analysis , the rate of survival of the arthroplasty was calculated to be 70 per cent at five years , but only 40 per cent at eight years . The major cause of failure was aseptic loosening of the acetabular or femoral component , or both . Fracture of the neck of the femur occurred in three hips . Although the medium-term results ( at fifty-six to eighty-three months ) were better than those in most comparable studies of resurfacing arthroplasty , the poor long-term results ( at ninety-one to 118 months ) show that meaningful studies of new prosthetic design s must continue for at least eight years , and , if at all possible , must include 100 per cent follow-up . The survival curve for the resurfacing arthroplasties in this study can serve as the basis for comparison of the early , medium , and long-term results of future design s of resurfacing hip prostheses", "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", "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", " 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", "AIM The present work aims at evaluating the clinical and radiological long-term results of the Harris-Galante press-fit cup . METHOD At an average follow-up time of 9.5 years ( min . 9 , max . 10.3 ) 123 patients with 138 Harris-Galante press-fit cups ( HGP ) were examined clinical ly and radiology . The clinical evaluation was done with the Harris hip score . Together with the HGP , which was inserted in all cases , five different femoral stems were implanted . A lateral approach , according to the technique of Watson-Jones , was used in all cases . RESULTS The mean follow-up Harris hip score was 89 of 100 points and is assessed as a good result . 7 cups ( 5 % ) were classed as being radiological loose , but only one case had also clinical symptoms . A total of 10 cups ( 6.8 % ) had to be revised . 3 cups ( 2 % ) had to be revised because of aseptic loosening . This result represents a survival rate of 93.2 % according to Kaplan-Meier . CONCLUSION The long-term clinical and radiological results of the Harris-Galante press-fit cup and there fixation method can assessed as good", "Ninety patients ( 96 hips ) scheduled for THA were stratified to fixation of the acetabular component in three main groups of about equal size . Fluoride cement , porous coated press-fit cup with ceramic coating or Palacos cum Gentamicin cement were used . All patients received Spectron EF stem . The migration of the cups and the femoral head penetration into the socket were measured with radiostereometric analysis . At 2 years the choice of fixation did not influence the migration or rotation of the cup . Patients with compromised bone quality showed increased three-dimensional ( 3D or total ) migration . Proximal and 3D penetration rates were increased in cemented compared with the uncemented cups ( p Appearance of radiolucent lines was almost equal in the two cemented groups . Uncemented cups had less radiolucent lines at 2 years . Fluoride containing cement or uncemented fixation did not improve the early postoperative stability of the socket", "Abstract . We prospect ively studied 250 patients with a proximal hydroxyapatite coated hip prosthesis . The follow-up period was 5 years . All components showed osseointegration except for one deep infection . The morphology of bone remodeling with either endosteal bone formation or periosteal bone formation was dependent on the way the stem filled the medullary canal . No linear or distal osteolysis around the stems was observed . Résumé . 250 patients avec une prothèse de la hanche revêtue d ' hydroxyapatite ont été étudiés avec un suivi de 5 années . Tous les composants ont montré une ostéointégration à l'exception d'un cas avec une infection profonde . La formation osseuse endostée ou periostée était dépendante du remplissage du canal médullaire par la tige . Aucune ostéolyse autour des tiges n'a été observée", "The early migration of porous acetabular cups was studied in 43 patients with osteoarthrosis . The patients were r and omly allocated to additional fixation of the cup with either biodegradable poly-L-lactic acid screws or titanium screws . Radiostereometric evaluation was done during the first 2 years after the procedure in 43 hips ( 23 with poly-L-lactic acid screws and 20 with titanium screws ) . At the 2-year follow-up , cups fixed with poly-L-lactic acid screws had migrated significantly more in the proximal-distal ( p titanium screws displayed more pronounced rotations around the longitudinal axis ( p occurrence of radiolucencies at the dome of the cups fixed with poly-L-lactic acid screws ( p result did not differ between the two groups . Inferior implant-bone contact in the poly-L-lactic acid group , local changes of the bone quality , and diminishing support of the poly-L-lactic acid screws caused by their degradation with time could be reasons for the different pattern of migration observed", "At the authors ' hospital , 410 primary total hip replacements were performed on 372 patients between September 1 , 1985 , and May 31 , 1989 . All hips were assigned r and omly to receive a Charnley prosthesis with an ogee flanged cup or a Spectron prosthesis with a metal backed cup . Eleven-year survivor analysis , using revision as the end point definition of failure , revealed a survival rate of 93.2 % ± 5.8 % for the Charnley replacement and 95.9 % ± 3.0 % for the Spectron . If each component of the systems was analyzed ( concerning aseptic loosening ) , the ogee cup and the Spectron stem had 100 % survival . The survivorship for all 410 hips was 94.5 % ± 3.4 % . If the end point definition of failure was exp and ed to include patient dissatisfaction , the survival rate decreased to 86.3 % ± 4.9 % . These survival rates were compared with the rates obtained by the Swedish National Hip Registry . The national cohort included all patients in Sweden who were treated surgically with a Charnley ( 14,053 patients ) or Spectron ( metal backed cup ) prosthesis ( 726 patients ) between September 1 , 1985 , and May 31 , 1989 . Eleven-year survivor analysis revealed a national survival rate of 92.1 % ± 0.7 % for the Charnley replacement and 88.6 % ± 6.1 % for the Spectron . The analyses from the Swedish Registry are based on more than 160,000 primary operations and 11,500 revisions . Despite the enormous amount of data , there are drawbacks , and registries never can replace the prospect i ve , r and omized trial . One reason is the Swedish National Registry is unable to discriminate between the individual cup and stem components when analyzing the cause of revision , and no clinical or radiographic information is collected . A potential drawback for the r and omized trial is performance bias because surgeons from specialized centers might perform better than the general orthopaedic surgeon", "The senior author systematic ally began collecting preoperative and postoperative data on all the total hip arthroplasties he performed starting in July 1970 . The data collected represent a 26-year experience using practice surveillance ( preoperative and regular interval postoperative collection and analysis of outcomes ) as a method to document the outcome of the total hip arthroplasty procedure and as a method to evaluate the need for changes in the procedure . As the senior author made few selected changes in the operative procedure during the followup period , the primary author has been able to evaluate the change in outcome based on these changes . The six studies reported in the current study show the durability of the long-term results of cemented total hip arthroplasty , the improvement in radiographic reproducibility obtained on the femoral side of the construct with improved cementing techniques , the deleterious effects of using cable to reattach the greater trochanter , the deleterious effects of changing femoral component design that included a change in surface finish , the improvement in acetabular fixation using cementless fixation , and the optimization of bearing surface wear using smaller diameter femoral heads . All of these findings have been incorporated into the primary surgeon 's practice based on this practice surveillance . As shown , practice surveillance also has provided a tool for performing clinical research . Although practice surveillance of controlled cohorts never will supplant prospect i ve r and omized clinical trials in evidence based medicine , it should help each surgeon with his or her own practice and can be used as an important research tool to study the optimization of outcomes of a surgical procedure", "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", "60 patients with arthrosis who received a Charnley total hip replacement were r and omly assigned to either an uncemented porous Harris-Galante type I socket or a cemented all-polyethylene Charnley socket . Socket migration and rotation were studied by radiostereometry ( RSA ) for 2 years . After 2 years , all sockets were still in situ . There was no difference in migration or rotation between the 2 socket design s , nor was there any difference in pain or function . We conclude that the initial fixation of the Harris-Galante socket resembles that of the Charnley socket", "Background Minor design changes may cause major changes in implant performance . Thus , as part of a stepwise introduction of a new low-profile cup , we performed a r and omized trial comparing it to a well-docu-mented st and ard cup . Patients and methods 60 patients , stratified according to sex , weight , and age , underwent cemented total hip arthroplasty using a Lubinus SP2 stem with ceramic head and were r and omized to either the new low-profile Lubinus Flanged Anti-Luxation cup ( FAL ) or the Lubinus St and ard Eccentric cup ( St and ard ) . 7 patients were excluded and 53 ( 28 FAL ) were evaluated at 3 , 6 , 12 , and 36 months postoperatively . Primary outcome variables , cup migration ( MTPM ) , and wear ( total 3-dimensional femoral head penetration ) were measured with radiostereometry ( RSA ) . Clinical outcome was evaluated with the western Ontario and McMaster osteoarthritis index ( Womac ) and the visual analog pain score ( VAS ) . Results We found no difference in migration between the FAL and St and ard cups . There was no difference in wear between the two cups and there was no correlation between wear and migration . 3 cups ( 2 FAL and 1 St and ard ) showed continuous migration of a magnitude that indicated an increased risk of early loosening . Clinical outcome was excellent , without any difference between the 2 groups", "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", "In this issue of Spine , a novel method for managing chronic discogenic low back pain with a thermal intradiscal catheter is reported . This study raises some general questions regarding the introduction of new treatment techniques and devices . Decisions about medical treatment should be based on a careful appraisal of the best evidence available . A step-wise introduction is necessary to increase the use of evidence -based decision making in the implementation of new surgical techniques and implants while exposing as few patients as possible to the potential risk of failure . The development of the total hip arthroplasty procedure , for example , could have been different if the introduction of new devices and techniques had been done more carefully and performed in a step-wise manner . Inferior properties could have been revealed earlier , thus reducing the number of failures and allowing for necessary improvements . It is also desirable , therefore , that members of this profession agree on a st and ardized way to introduce new surgical techniques and implants in the field of spinal disorders . Based on the results of Swedish reports and practice , the following schedule for step-wise clinical introduction of new implants is suggested ( Figure 1 ) : The initial step is a pre clinical testing and is beyond the scope of this discussion . The first clinical step is the open prospect i ve and preferably r and omized trial that includes a minimum of patients but yields a relevant evaluation . The strict rules of prospect i ve , r and omized trials should be adhered to . In this first clinical phase , methods associated with high accuracy , such as radiostereometric analysis ( RSA ) , are required . Within 6 to 24 months , this method has the potential to identify implants/ methods that provide inferior fixation and increased polyethylene wear . Results from this first step determine whether further clinical evaluation is worthwhile . It should be noted and stressed that all types of complications can not be predicted and that further follow-up study is necessary . If favorable results are obtained in the first step , the second step , a multicenter trial exposing the new procedure to a broader aspect in the orthopedic community , can be initiated . In the first step , there is a risk for susceptibility and performance bias because the inventors themselves often perform this introductory investigation . The protocol in the multicenter trial must be prepared carefully and agreed on by all participating inventors . A sufficient number of patients should be included to allow adequate statistical analysis . The ultimate goal for step two is to make even the multicenter trial r and omized by using well-documented methods /implants as the gold st and ard . The final step in the evaluation , step three , is to include a continuous control group by using register studies based on large cohorts to reveal early or unusual and potential clinical catastrophic complications . In a rather small and closed community such as Sweden , the register should be nationwide and include all units in a specific field . When applying the principles for step-wise introduction to the investigation of chronic discogenic low back pain with a thermal intradiscalcatheterbySaal and Saal , oneobserves that the current study falls between the pre clinical step and step one . The lack of r and omization toward either conservative or surgical intervention is a definite limitation of the study , and before this method is introduced to a larger study group , a r and omized trial must be considered . A multicenter trial exposing the new procedure to a broader aspect of the orthopedic community is recommended before using it in general orthopedic practice . The length of the follow-up period was very short in this study , and no long-term clinical conclusions can be drawn based on the results", "Roentgen stereophotogrammetry was used to measure the migration of the centre of the femoral head in 84 cemented Lubinus SP I hip arthroplasties ( 58 primary operations , 26 revisions ) . Four to seven years later , seven femoral components had been revised because of painful loosening . These implants showed greater subsidence , medial migration and posterior migration during the first two postoperative years than did the hips which had not been revised . Six months after operation , subsidence of more than 0.33 mm combined with a total migration of more than 0.85 mm predicted an increased risk of subsequent revision ; the amount of subsidence at two years was an even better predictor . The probability of revision was greater than 50 % if the subsidence at two years was 1.2 mm or more", "We evaluated the mechanical , chemical and clinical properties of Boneloc cement using radiostereometry and a series of laboratory tests . Compared to a st and ard cement ( Palacos ) the new cement displayed reduced tensile strength , elastic modulus , curing and glass transition temperatures . The amount of MMA extracted during 3 weeks in methanol was smaller for the Boneloc , but the total amount of released monomers was larger . The adhesion to stainless steel and bone did not differ . Radiostereometric analysis during the first postoperative year in 30 patients r and omized to fixation of hip prostheses using either of the 2 cements displayed increased proximal migration of the cup and increased stem subsidence when Boneloc had been used . Part of the stem subsidence occurred inside the cement mantle . On the basis of these findings , we conclude that the inferior fixation in the Boneloc group is mainly caused by its mechanical properties . Other mechanisms , such as increased release of monomers , may also be important", "Twenty-one patients who had primary osteoarthrosis were managed with a bilateral total hip arthroplasty with insertion of a Charnley femoral component . In each patient , one hip was r and omly allocated to have a Harris-Galante acetabular component inserted without cement , and the contralateral hip was treated with an all-polyethylene Charnley acetabular component fixed with cement . The clinical result was satisfactory in all patients . All forty-two hips were followed , with respect to migration of the acetabular component , with use of roentgenstereophotogrammetric analysis for a median of twenty-seven months ( range , twenty-three to forty-nine months ) . Each patient served as his or her own control . Maximum migration in any direction was 1.7 and 2.1 millimeters , and maximum rotation was 2.2 and 2.0 degrees for the Harris-Galante and Charnley acetabular components , respectively . There was no significant difference in migration between the two design s of acetabular components ( p = 0.98 , p = 0.75 , and p = 0.06 for the transverse , longitudinal , and sagittal axes , respectively ) . However , the Harris-Galante acetabular components rotated significantly more than the Charnley acetabular components around two of the three axes ( p = 0.008 , p = 0.08 , and p = 0.03 for the transverse , longitudinal , and sagittal axes , respectively ) . The Charnley hip implant has been used clinical ly for a long time , with successful results . Comparison of new design s of implants with the Charnley prosthesis is therefore important . Roentgenstereophotogrammetric analysis provides a potential for detection of problems with fixation at an early stage rather than after long-term follow-up . No major difference in terms of skeletal fixation was found between the two design s of components after short to medium-term follow-up", "The possibility of migration of cementless cups in total joints after prophylaxis of heterotopic ossification with irradiation or nonsteroidal antiinflammatory drugs is a concern . Data investigating component stability with digital methods are lacking . This prospect i ve study analyzed the migration of cementless cups after indomethacin and irradiation prophylaxis with the digital Einzel-Bild-Röntgen-Analyse tool . The irradiation group ( 106 hips ) and the indomethacin group ( 98 hips ) were compared with 82 hips that did not receive any prophylaxis . The same cementless acetabular implants were used in all cases , and patients were observed clinical ly and radiographically at 2 and 5 years . At the 5-year followup , the number of cups that showed migration greater than 1 mm in the irradiation group ( five ) , the indomethacin group ( three ) , and the control group ( four ) were not different . No cup was considered loose on the radiographs and no patient underwent revision surgery . The results of our study indicate irradiation or short-course use of indomethacin for prophylaxis of heterotopic ossification did not negatively affect the stability of cementless cups in primary total hip arthroplasties . Level of Evidence : Level II , prognostic study . See the Guidelines for Authors for a complete description of levels of evidence" ]

[ "Background The prevalent raise of type 2 diabetes ( T2D ) around the globe , are creating higher risk for cardiovascular diseases ( CVDs ) and increasing strain on each country ’s health care budget in the world . Microalbuminuria has appeared as a key parameter in diabetic patients . Microalbuminuria is also related to increased cardiovascular morbidity in people who are non-obese diabetic . Some studies have suggested that consumption of symbiotic foods might help improve the metabolic profile , inflammatory factors and biomarkers of oxidative stress . The aim of trial was to determine the effect of symbiotic supplementation on glycemic control , lipid profiles and microalbuminuria in non-obese T2D . Methods In this r and omized , double-blind , clinical ly controlled trial , 70 patients with T2D ( 28 females , 42 males ) were r and omly divided into two groups ( n = 35 for each group ) . The symbiotic group ( SG ) consumed 500 mg/d of symbiotic supplementations containing probiotics ( Lactobacillus family , Bifidobacterium family , Streptococus thermophilus ) , Prebiotics ( Fructo oligosaccharide ) and B group vitamins ( 1 mg ) , lactose ( 0.5 mg ) , malt-dextrin , magnesium saturate and the placebo group ( PG ) consumed capsules filled with row starch and also B group vitamins ( 1 mg ) , lactose ( 0.5 mg ) , malt-dextrin , magnesium saturate for 9 weeks . Fasting blood glucose ( FBG ) , hemoglobin A1c ( HbA1c ) , blood lipid profiles , 24-h dietary recalls , and anthropometric measurements were measured at the baseline and at the end of trial . SPSS software , version 16 was used to test the data and the results were expressed as mean ± st and ard deviation . Paired sample s T-Test were used to compare continuous variables within groups . Comparison between different groups was performed through two independent sample s T-Test . In the absence of normal distribution , the comparison between the groups was made using non-parametric Wilcoxon on signed ranks and Mann – Whitney tests . P values Results Symbiotic supplementation decreased significantly , FBG ( P = 0.05 ) and HbA1c ( P no significant differences in lipid profiles within and between the groups at the end of study ( P > 0.05 ) . Microalbuminuria ( P are increased significantly in PG at the end of the study . Furthermore , the mean changes of microalbuminuria and HbA1c experienced significant between the two groups . There was significant reduction in urea between two groups from baseline ( P = 0.051 ) . No significant changes in baseline were shown in creatinine among the two groups or within either groups ( P > 0.05 ) . Conclusion The consumption of 500 mg/d symbiotic supplementation for 9 weeks could improve the HbA1c , BMI and Microalbuminuria in T2D . Although , No effect has been indicated on FBS , lipid profiles , urea and creatinine . Trial Registration The trial has been registered in the Iranian Registry of Clinical Trials I RCT 2015072223284N1 , identifier . Registered 21 May 2016 “ retrospectively registered ”", "Background Increased exposure to intestinal bacterial products may contribute to the pathogenesis of non alcoholic steatohepatitis ( NASH ) . Bifidobacteria are predominant bacterial species in the human gut microbiota and have been considered to exert a beneficial effect on human health by maintaining the equilibrium of the resident microbiota . Aims To evaluate the effects of Bifidobacterium longum with fructo-oligosaccharides ( Fos ) in the treatment of NASH . Methods A total of 66 patients were r and omly and equally divided into two groups receiving Bifidobacterium longum with Fos and lifestyle modification ( i.e. , diet and exercise ) versus lifestyle modification alone . The following variables were assessed at −4 ( beginning of the dietary lead-in period ) , 0 ( r and omization ) , 6 , 12 , 18 , and 24 weeks : aspartate transaminase ( AST ) , alanine transaminase ( ALT ) , bilirubin , albumin , total cholesterol , high-density lipoprotein ( HDL ) cholesterol , low-density lipoprotein ( LDL ) cholesterol , triglycerides , fasting plasma glucose , insulin , C-peptide , C-reactive protein ( CRP ) , tumor necrosis factor (TNF)-α , homeostasis model assessment of insulin resistance ( HOMA-IR ) , and serum endotoxins . Liver biopsies were performed at entry and repeated after 24 weeks of treatment . Results At the end of study period , we observed that the Bifidobacterium longum with Fos and lifestyle modification group versus the lifestyle modification alone group showed significant differences in the AST −69.6 versus −45.9 IU/mL ( P LDL cholesterol −0.84 versus −0.18 mmol/L ( P ) , HOMA-IR −1.1 versus −0.6 ( P serum endotoxin −45.2 versus −30.6 pg/mL ( P steatosis ( P , and the NASH activity index ( P 0.05 ) . Conclusions Bifidobacterium longum with Fos and lifestyle modification , when compared to lifestyle modification alone , significantly reduces TNF-α , CRP , serum AST levels , HOMA-IR , serum endotoxin , steatosis , and the NASH activity index ", "To our knowledge , no reports are available indicating the favorable effects of synbiotic bread consumption on blood lipid profiles among patients with type 2 diabetes mellitus ( T2DM ) . This study was conducted to evaluate the effects of the daily consumption of synbiotic bread on blood lipid profiles of patients with T2DM . This r and omized double-blinded controlled clinical trial was performed with 78 diabetic patients , aged 35–70 years . After a 2-week run-in period , subjects were r and omly assigned to consume either synbiotic ( n = 26 ) , probiotic ( n = 26 ) or control bread ( n = 26 ) for 8 weeks . The synbiotic bread contained viable and heat-resistant probiotic Lactobacillus sporogenes ( 1 × 108 CFU ) and 0.07 g inulin ( HPX ) as prebiotic per 1 g. The probiotic bread contained L. sporogenes ( 1 × 108 CFU ) per 1 g. Patients were asked to consume the synbiotic , probiotic and control breads three times a day in a 40 g package for a total of 120 g/day . Biochemical measurements including blood lipid profiles were conducted before and after 8 weeks of intervention . Consumption of the synbiotic bread , compared to the probiotic and control breads , led to a significant decrease in serum TAG ( P = 0.005 ) , VLDL-C ( P = 0.005 ) , TC/HDL-C ( P = 0.002 ) and a significant increase in serum HDL-C levels ( P = 0.01 ) . No significant effect of synbiotic bread consumption on FPG , TC , LDL-C and non-HDL-C levels was seen compared to the probiotic and control breads ( P > 0.05 ) . Trial registry code : http://www.i rct .ir I RCT 201311215623N13", "Background The consumption of foods containing probiotic and prebiotic ingredients is growing consistently every year , and in view of the limited number of studies investigating their effect in the elderly . Objective The objective of this study was to evaluate the effect of the consumption of a symbiotic shake containing Lactobacillus acidophilus , Bifidobacterium bifidum and fructooligosaccharides on glycemia and cholesterol levels in elderly people . Methods A r and omized , double-blind , placebo-controlled study was conducted on twenty volunteers ( ten for placebo group and ten for symbiotic group ) , aged 50 to 60 years . The criteria for inclusion in the study were : total cholesterol > 200 mg/dL ; triglycerides > 200 mg/dL and glycemia > 110 mg/dL. Over a total test period of 30 days , 10 individuals ( the symbiotic group ) consumed a daily dose of 200 mL of a symbiotic shake containing 108 UFC/mL Lactobacillus acidophilus , 108 UFC/mL Bifidobacterium bifidum and 2 g oligofructose , while 10 other volunteers ( the placebo group ) drank daily the same amount of a shake that did not contain any symbiotic bacteria . Blood sample s were collected 15 days prior to the start of the experiment and at 10-day intervals after the beginning of the shake intake . The st and ard lipid profile ( total cholesterol , triglycerides and HDL cholesterol ) and glycemia , or blood sugar levels , were evaluated by an enzyme colorimetric assay . Results The results of the symbiotic group showed a non-significant reduction ( P > 0.05 ) in total cholesterol and triglycerides , a significant increase ( P HDL cholesterol and a significant reduction ( P fasting glycemia . No significant changes were observed in the placebo group . Conclusion The consumption of symbiotic shake result ed in a significant increase in HDL and a significant decrease of glycemia . Trial Registration Clinical Trials.gov :", "Nonalcoholic fatty liver disease is the most prevalent chronic liver disease in Western countries ; it can progress to nonalcoholic steatohepatitis ( NASH ) , cirrhosis and hepatocarcinoma . The importance of gut-liver-adipose tissue axis has become evident and treatments targeting gut microbiota may improve inflammatory and metabolic parameters in NASH patients . In a r and omized , controlled clinical trial , involving 50 biopsy-proven NASH patients , we investigated the effects of synbiotic supplementation on metabolic parameters , hepatic steatosis , intestinal permeability , small intestinal bacterial overgrowth ( SIBO ) and lipopolysaccharide ( LPS ) serum levels . Patients were separated into two groups receiving Lactobacillus reuteri with guar gum and inulin for three months and healthy balanced nutritional counseling versus nutritional counseling alone . Before and after the intervention we assessed steatosis by magnetic resonance imaging , intestinal permeability by lactulose/mannitol urinary excretion and SIBO by glucose breath testing . NASH patients presented high gut permeability , but low prevalence of SIBO . After the intervention , only the synbiotic group presented a reduction in steatosis , lost weight , diminished BMI and waist circumference measurement . Synbiotic did not improve intestinal permeability or LPS levels . We concluded that synbiotic supplementation associated with nutritional counseling seems superior to nutritional counseling alone for NASH treatment as it attenuates steatosis and may help to achieve weight loss", "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 : Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in the world . Oral administration of symbiotic and Vitamin E has been proposed as an effective treatment in NAFLD patients . This study was carried out to assess the effects of symbiotic and /or Vitamin E supplementation on liver enzymes , leptin , lipid profile , and some parameters of insulin resistance ( IR ) in NAFLD patients . Material s and Methods : We r and omly assigned sixty NAFLD adult patients to receive ( 1 ) symbiotic twice daily + Vitamin E-like placebo capsule ; ( 2 ) 400 IU/d Vitamin E + symbiotic-like placebo ; ( 3 ) symbiotic twice daily + 400 IU/d Vitamin E ; and ( 4 ) symbiotic-like placebo + Vitamin E-like placebo for 8 weeks . Results : Symbiotic plus Vitamin E supplementation led to a significant decrease in concentrations of liver transaminase ( P ≤ 0.05 ) . Mean difference of apolipoprotein A-1 was more significant in symbiotic group compared to control . However , mean difference of apolipoprotein B100/A-1 was only significant in symbiotic group compared to control . At the end of the study , significant differences in total cholesterol ( TC ) and low-density lipoprotein cholesterol ( LDL-C ) were seen between the symbiotic plus Vitamin E and control groups ( P of symbiotic plus Vitamin E supplements led to a significant decrease in concentrations of triglycerides ( TG ) after the intervention . Significant differences in leptin , fasting blood sugar ( FBS ) , and insulin levels were seen between the symbiotic plus Vitamin E and control groups at the end of the study ( P contrast , symbiotic and /or Vitamin E supplementation did not affect high-density lipoprotein cholesterol and homeostasis model assessment for IR levels . Conclusion : In our study , symbiotic plus Vitamin E supplementation was the most effective treatment in lowering liver enzymes , leptin , FBS , insulin , TG , TC , and LDL-C among NAFLD patients", "The present study investigated the impact of a Lactobacillus rhamnosus CGMCC1.3724 ( LPR ) supplementation on weight loss and maintenance in obese men and women over 24 weeks . In a double-blind , placebo-controlled , r and omised trial , each subject consumed two capsules per d of either a placebo or a LPR formulation ( 1.6 × 10(8 ) colony-forming units of LPR/capsule with oligofructose and inulin ) . Each group was su bmi tted to moderate energy restriction for the first 12 weeks followed by 12 weeks of weight maintenance . Body weight and composition were measured at baseline , at week 12 and at week 24 . The intention-to-treat analysis showed that after the first 12 weeks and after 24 weeks , mean weight loss was not significantly different between the LPR and placebo groups when all the subjects were considered . However , a significant treatment × sex interaction was observed . The mean weight loss in women in the LPR group was significantly higher than that in women in the placebo group ( P = 0.02 ) after the first 12 weeks , whereas it was similar in men in the two groups ( P= 0.53 ) . Women in the LPR group continued to lose body weight and fat mass during the weight-maintenance period , whereas opposite changes were observed in the placebo group . Changes in body weight and fat mass during the weight-maintenance period were similar in men in both the groups . LPR-induced weight loss in women was associated not only with significant reductions in fat mass and circulating leptin concentrations but also with the relative abundance of bacteria of the Lachnospiraceae family in faeces . The present study shows that the Lactobacillus rhamnosus CGMCC1.3724 formulation helps obese women to achieve sustainable weight loss", "With increasing age , a number of physiological changes take place which are reflected in immune and bowel function . These changes may relate to the commonly assumed age-related changes in intestinal microbiota ; most noticeably a reduction in bifidobacteria . The current study aim ed at modifying the intestinal microbiota with a potential synbiotic on selected immune and microbiota markers . Healthy elderly subjects were r and omised to consume during 2 weeks either a placebo ( sucrose ) or a combination of lactitol and Lactobacillus acidophilus NCFM twice daily in a double-blind parallel trial . After the intervention , stool frequency was higher in the synbiotic group than in the placebo group and a significant increase in faecal L. acidophilus NCFM levels was observed in the synbiotic group , after baseline correction . In contrast to the generally held opinion , the study subjects had faecal Bifidobacterium levels that were similar to those reported in healthy young adults . These levels were , nevertheless , significantly increased by the intervention . Levels of SCFA were not changed significantly . Of the measured immune markers , PGE2 levels were different between treatments and IgA levels changed over time . These changes were modest which may relate to the fact that the volunteers were healthy . Spermidine levels changed over time which may suggest an improved mucosal integrity and intestinal motility . The results suggest that consumption of lactitol combined with L. acidophilus NCFM twice daily may improve some markers of the intestinal microbiota composition and mucosal functions", "Although non-alcoholic fatty liver disease ( NAFLD ) is the leading aetiology of liver disorders in the world , there is no proven treatment for NAFLD patients with normal or low BMI . The aim of this study was to evaluate the efficacy of synbiotics supplementation in NAFLD patients with normal or low BMI . In this r and omised , double-blind , placebo-controlled , clinical trial , fifty patients with NAFLD were assigned to take either a synbiotic supplement or a placebo capsule for 28 weeks . Both groups were advised to follow a healthy lifestyle . At the end of the study , hepatic steatosis and fibrosis reduced in both groups ; however , the mean reduction was significantly greater in the synbiotic group rather than in the placebo group ( P Furthermore , serum levels of fasting blood sugar , TAG and most of the inflammatory mediators reduced in the synbiotic group significantly compared with the placebo group ( P that synbiotic supplementation improves the main features of NAFLD in patients with normal and low BMI , at least partially through reduction in inflammatory indices . Further studies are needed to address the exact mechanism of action of these effects", "Background / Aims Non-alcoholic fatty liver disease ( NAFLD ) is one of the most prevalent chronic liver diseases in recent years . The aim of this study was to evaluate the effects of sitagliptin with and without a synbiotic supplement in the treatment of patients with NAFLD . Methods In total , 138 NAFLD patients aged 18 - 60 years were enrolled in the study . Patients were r and omized to one of the following treatments for 16 weeks : Group I ( n=68 ) , sitagliptin 50 mg daily plus placebo ( one capsule per day ) or group II ( n=70 ) sitagliptin 50 mg daily plus synbiotic ( one capsule per day ) . Changes in fasting blood glucose ( FBS ) , liver enzymes , lipid profile , and body mass index were compared between the groups . Results The mean change in FBS with sitagliptin-placebo from baseline was -10.47±5.77 mg/dL , and that with sitagliptin-synbiotic was -13.52±4.16 mg/dL. There was a significant difference between the groups ( P The mean change in cholesterol ( Chol ) was -8.34±28.83 mg/dL with sitagliptin-placebo and -21.25±15.50 mg/dL with sitagliptinsynbiotic . There was a significant difference between the two groups ( P=0.029 ) . The administration of sitagliptin-placebo induced an increase of 6.13±27.04 mg/dL in low density lipoprotein ( LDL ) , whereas sitagliptin-synbiotic induced a decrease of 14.92±15.85 mg/dL in LDL . A significant difference was observed between the two groups ( P in the sitagliptin-synbiotic group , there was significant improvement in aspartate aminotransferase ( AST ) level compared to the sitagliptin-placebo group ( P=0.018 ) . Conclusions Sitagliptin-synbiotic produced greater improvement in FBS , AST , Chol , and LDL compared to sitagliptin alone in patients with NAFLD", "Background Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in developed and developing countries . The use of synbiotics has been proposed as a probable management strategy for patients with NAFLD . Objective We investigated the effects of synbiotic yogurt on hepatic steatosis and liver enzymes as primary outcomes and on oxidative stress markers , adipokine concentration , and gut peptide concentration as secondary outcomes in patients with NAFLD . Methods In this 24-wk , open-label , r and omized controlled clinical trial , 102 patients [ 50 men and 52 women ; mean age : 40 y ; body mass index ( in kg/m2 ) ( mean ± SD ) : 31.2 ± 4.9 ] were r and omly assigned to 3 groups , including 2 intervention groups and 1 control group . The intervention groups consumed 300 g synbiotic yogurt containing 108 colony-forming units Bifidobacterium animalis/mL and 1.5 g inulin or conventional yogurt daily and were advised to follow a healthy lifestyle ( i.e. , diet and exercise ) . The control group was advised to follow a healthy lifestyle alone . We evaluated differences between groups in liver function measures by using repeated- measures ANOVA , ANCOVA , and logistic regression . Results At the end of the study , the grade s of NAFLD , as determined by ultrasonography , showed a significant decrease in the synbiotic group compared with the conventional and control groups ( P respectively : serum concentration of alanine aminotransferase ( -14.5 ± 15.6 compared with 4.6 ± 15.4 and 3.1 ± 14.4 IU/L ; P = 0.008 ) , aspartate aminotransferase ( -7.5 ± 6.1 compared with 3.0 ± 8.2 and 3.1 ± 5.7 IU/L ; P ) , alkaline phosphatase ( -26.2 ± 16.8 compared with 3.4 ± 30.1 and 1.5 ± 31.9 IU/L ; P = 0.024 ) , and γ-glutamyltransferase ( -6.0 ± 6.0 compared with 1.0 ± 6.4 and 7.6 ± 11.4 IU/L ; P ) . Conclusion Synbiotic yogurt consumption improved hepatic steatosis and liver enzyme concentrations in patients with NAFLD . This trial was registered at the Iranian Registry of Clinical Trials website ( www.i rct .ir ) as I RCT 2017020932417N2" ]

[ "Objective : The first goal of phase I drug development is the determination of maximal tolerated dose , which must be established by case-by-case analysis , sometimes using a laboratory adverse event . Since no accurate rule defining lab adverse events , has been vali date d yet , we propose a new “ combined method ” based on combination of two thresholds : inclusion values and magnitude of variation . Using this combined method , the label “ lab adverse event ” is applied if any lab value exceeds the inclusion threshold and is associated with a variation from baseline exceeding the variation threshold defined from reference change limit . Thus , this study aim ed to test this combined method on a large healthy volunteer population , studied in 19 phase I centres worldwide , and on five lab parameters : alanine amino transferase , aspartate amino transferase , alkaline phosphatases , creatinine and polymorphonuclear leukocytes . Methods : The inclusion threshold from each center was used . Reference change limits were defined from volunteers previously included in comparable studies and were expressed as absolute values : increases of 10 IU · l−1 for alanine amino transferase or aspartate amino transferase , 15 IU · l−1 for alkaline phosphatases , 15 μmol · l−1 for creatinine and a 0.34 109 · l−1 decrease for polymorphonuclear leukocytes . Comparison between the “ combined method ” and a normal range method was made using positive predictive value and a ratio between relevant and irrelevant results . This application was implemented in all young healthy volunteers ( 1134 ) included in 38 phase I studies sponsored by Rhône Poulenc Rorer from 1991 to 1993 . Results : Seventy seven subjects ( 6.7 % ) were indicated in final study reports as having a lab adverse event ( reference group ) . Of 179 subjects with lab abnormalities defined by the normal range method , 77 belonged to the reference group , inducing a poor 0.43 positive predictive value . Of ninety subjects with lab adverse events defined by the “ combined method ” , seventy-five belonged to the reference group , inducing a two-fold higher 0.83 positive predictive value . The combined method produced a high ratio of relevant/irrelevant results ( ) compared with the low ratio ( ) achieved using the normal range method . Conclusion : This new “ combined method ” , leading to a better definition of lab adverse event , seems an accurate and useful tool for routine case-by-case analysis within phase I drug development studies", "BACKGROUND While the promotion of health-related fitness is thereby widespread , less focus is currently being given on the biological influence that physical activity might exert on results of laboratory testing . As such , this study was undertaken to assess the kinetics of liver injury markers following physical exercise . DESIGN AND METHODS Total and direct bilirubin as well as the activity of biochemical markers of liver injury including aspartate aminotransferase ( AST ) , alanine aminotransferase ( ALT ) , alkaline phosphatase ( ALP ) , lactate dehydrogenase ( LDH ) , gamma-glutamyl transpeptidase ( GGT ) and creatine kinase ( CK ) , were measured before and after a half-marathon . RESULTS Significant increases occurred for GGT , AST , LDH , CK , total and direct bilirubin immediately after the run . AST , LDH , CK , total and direct bilirubin were still increased 24h thereafter , whereas GGT decreased after 6h . None of the athletes exceed the upper reference limit for ALT , ALP and GGT , whereas significant variations were instead observed for LDH , AST , CK , total and direct bilirubin . CONCLUSIONS Taken together , the results of our prospect i ve investigation clearly attest that an acute bulk of aerobic physical exercise , such as a half-marathon , might produce significant changes in the activity of traditional biomarkers of liver injury , which should be carefully considered when investigating physically active individuals undergoing laboratory testing", "Context Current upper limits ( 500 nkat/L [ 30 U/L ] for women , 667 nkat/L [ 40 U/L ] for men ) for serum alanine aminotransferase ( ALT ) level were defined in population s that included persons with nonalcoholic fatty liver disease ( NAFLD ) and persons with hepatitis C virus ( HCV ) infection . Contribution This study redefined ALT limits in blood donors at low risk for NAFLD and without hepatitis B or C ( 317 nkat/L [ 19 U/L ] in women , 500 nkat/L [ 30 U/L ] in men ) . When applied to 209 anti-HCV-positive donors , the new thresholds had 76.3 % sensitivity and 88.5 % specificity in identifying patients with hepatitis C viremia compared with 55 % and 97.4 % for old thresholds . Implication s Laboratories should consider revising the upper limits of normal for ALT to improve the sensitivity of this test in identifying sub clinical liver disease . The Editors Serum alanine aminotransferase ( ALT ) concentration is the most commonly used variable for assessment of liver disease ( 1 , 2 ) . However , particularly in the case of chronic hepatitis C virus ( HCV ) infection , ALT measurement often fails to identify patients with minimal to mild necroinflammatory activity ( 3 - 7 ) . Current upper limits of normal for ALT level were set , on average , at 667 nkat/L ( 40 U/L ) ( range , 500 to 833 nkat/L [ 30 to 50 U/L ] ) in studies conducted over the past 10 years ( 1 , 3 - 5 , 7 , 8) . Such thresholds , however , were mostly computed in the 1980s , when ALT testing was introduced as a surrogate marker for the screening of non-A , non-B hepatitis among blood donors and before anti-HCV testing and restrictive behavioral criteria for donor selection were implemented . Furthermore , so-called reference population s were likely to include many persons with nonalcoholic fatty liver disease , now recognized as the most prevalent cause of chronic liver disease in developed countries ( 8 - 10 ) . Current reference ranges for ALT level probably underestimate the frequency of chronic liver disease . Because dietary and behavioral risks for liver disease are widespread in many countries , a critical revision of ALT limits would require the definition of healthy ranges rather than a generic up date of normal ranges . Thus far , several factors have hampered this task . For example , to obtain solid data , many clinical , biochemical , and behavioral variables potentially related to liver disease must be investigated , requiring screening of large numbers of persons . Furthermore , repeated blood donors , who currently represent the vast majority of blood-donation c and i date s , can not be included in the sampling frame , because they have been selected on the basis of ALT activity during the past two decades . We report the results of a 4-year study of first-time blood-donation c and i date s. To up date the definitions of healthy ranges for serum ALT level , we identified a population at low risk for sub clinical liver disease by exploring factors related to enzyme activity in both healthy persons and those with mild abnormalities on liver tests . Next , we tested the sensitivity and specificity of the ranges obtained from these participants in the clinical evaluation of anti-HCVpositive persons with and without chronic liver damage . Methods Participants Figure 1 summarizes the selection of the study participants . Figure 1 . Procedures for selection of the study participants . * Donor c and i date s were not suitable for the following reasons : previous blood transfusion ( 2 % ) ; use of major illicit drugs ( 1.5 % ) ; at-risk sexual exposures ( 9 % ) ; history of hepatitis or other blood borne infections ( 4 % ) ; recent exposure in a malaria-endemic area ( 5 % ) ; low hemoglobin level ( 15 % ) ; use of medication not compatible with blood donation ( 4 % ) ; seizure or central nervous system disorders ( 12 % ) ; hypertension , arrhythmias , or cardiac disease ( 8 % ) ; hypotension ( 9 % ) ; recent surgery ( 2 % ) or other medical or behavioral risks ( 26 % ) ; serologic reactivity on screening assays ( antiHIV 1 , antiHIV 2 , hepatitis B surface antigen , antihepatitis C virus [ HCV ] , or syphilis ) on the sample collected at blood donation ( 2.5 % ) . St and ard upper limits were 667 nkat/L ( 40 U/L ) in men , and 500 nkat/L ( 30 U/L ) in women . Two trained hepatologists used a recently proposed algorithm ( 2 ) to re-evaluate medical history and physical examination . Participants also underwent additional blood testing , including measurement of the following values : aspartate aminotransferase , alanine aminotransferase ( ALT ) , alkaline phosphatase , -glutamyl transpeptidase , total proteins , bilirubin , iron , total iron-binding capacity , serum ferritin , serum protein electrophoresis , creatine kinase , ceruloplasmin , 1-antitrypsin , antibodies to cytomegalovirus and EpsteinBarr virus , and autoantibodies . Participants also underwent ultrasonography of the liver . Anti-HCVNegative First-Time Blood Donors From 1 September 1995 through 26 October 1999 , 9221 blood-donor c and i date s presenting for first-time donation underwent clinical and laboratory examinations as part of procedures for donor selection at Centro Transfusionale e di Immunologia dei Trapianti in Milan , Italy . A blood-bank physician 1 ) administered a psychosocial question naire [ 11 , 12 ] , which was aim ed at identifying and excluding from donation persons at high risk for blood-borne infections ; 2 ) took a medical history ; and 3 ) examined all potential participants and measured body weight and height . Donors c and i date s had blood drawn for laboratory testing . Clinical data and laboratory-test results were recorded in a relational data base management system , as described previously ( 11 ) . We included in the study donor c and i date s who had no medical or behavioral contraindication to blood donation ( 12 ) and who had negative results on tests for hepatitis B surface antigen ( HBsAg ) , anti-HCV , antiHIV 1 , antiHIV 2 , and hemagglutination ( to assess for presence of syphilis ) . In addition , we used a recently recommended diagnostic algorithm ( 2 ) to conduct a diagnostic work-up in donors who repeatedly had abnormal ALT measurements ( that is , they had increased values , according to current ALT ranges , in three subsequent measurements taken at 1-month intervals in the absence of HBsAg and anti-HCV reactivity ) ( 2 ) . Anti-HCVPositive Blood Donors We also studied 209 blood-donor c and i date s with confirmed anti-HCV reactivity between 1990 and 1999 who presented to our outpatient liver disease clinic for regular follow-up . Of these patients , 78 were HCV RNA negative at initial screening ( 59 patients ) or after antiviral treatment ( 19 patients ) , and 131 were HCV RNA positive . Serum ALT activity was determined at presentation and in at least two other serial serum sample s collected at 1- to 3-month intervals over at least 6 months . In patients with viremia who underwent treatment , the pattern of serum ALT levels was defined during the period of presumed viremia ( that is , not during or after therapy ) . Liver biopsy was performed in 133 anti-HCVpositive blood donors ( 103 of whom were HCV RNA positive and 30 of whom were HCV RNA negative ) for diagnostic reasons ( 32 patients ) or within clinical trials . These clinical trials were conducted between 1993 and 1998 to define the optimal management of anti-HCVpositive patients with normal or slightly altered ALT levels ( 101 patients ) ( 3 , 4 , 11 , 13 , 14 ) . Laboratory Methods A fasting blood sample was collected in the morning and was centrifuged within 30 minutes of collection . The Laboratory of Biochemistry and the Laboratory of Virology of the Centro Trasfusionale e di Immunologia dei Trapianti at IRCCS Ospedale MaggioreMilan , Italy , performed all analyses by using consistent methods throughout the study period . Complete blood counts were performed by using an NE 8000 automatic cell counter ( Sysmex , Kobe , Japan ) . Analyses of serum biochemistry were performed by using an Olympus AU510 analyzer ( EppendorfNetheler , Hamburg , Germany ) . Upper reference limits for serum biochemistry analyses were computed in 1983 on the basis of findings from 5093 women and 9849 men who were apparently healthy donors with negative results on hepatitis B surface antigen and syphilis tests ( 4 , 15 ) . These limits were as follows : for total cholesterol level , 5.70 mmol/L ( 220 mg/dL ) ; for triglyceride level , 2.26 mmol/L ( 200 mg/dL ) ; for blood glucose level , 5.83 mmol/L ( 105 mg/dL ) in men and 5.44 mmol/L ( 98 mg/dL ) in women ; for ALT level , 667 mmol/L ( 40 U/L ) in men and 500 nkat/L ( 30 U/L ) in women . Virologic tests included an hepatitis B surface antigen test ( Wellcozyme HBsAg , Abbott Laboratories , Chicago , Illinois ) , an anti-HIV test ( Ortho HIV1/HIV2 , Ortho Diagnostic Systems , Raritan , New Jersey ) , and an anti-HCV test ( Ortho HCV 3.0 , Ortho Diagnostic Systems ) . Anti-HCV reactivity was confirmed by third-generation recombinant immunoblot assay ( RIBA-3 , Ortho Diagnostic Systems ) . Qualitative analysis of serum HCV RNA was performed by using the Amplicor HCV kit ( Roche Molecular Systems , Basel , Switzerl and ) . Body mass index ( BMI ) was calculated by dividing the weight ( in kg ) by the squared height ( in m ) . On the basis of a recent recommendation ( 16 ) , we considered a BMI of 24.9 kg/m2 the upper limit for healthy weight . The laboratory and the blood donor center were certified according to International Organization for St and ardization 9002 st and ards . The laboratory intra-assay coefficient of variation ( CV ) for ALT was 1.1 % , and the interassay CV over a 2-week period was 2.4 % . Within-individual and between-individual variability were estimated on the basis of 20 donors who were r and omly chosen among those with two measurements taken at 3-month intervals . Within-individual variability , expressed as CV , was 21.4 % ( CI , 16.4 % to 31.0 % ) ; between-individual variability was 49.8 % ( CI , 37.9%- to 72.8 % ) . Statistical Analysis Statistical analyses were performed by using the SAS package version 6.12 ( SAS Institute , Inc. , Cary , North Carolina ) . The 5th , 25th , 50th ( median ) , 75th , and 95th percentiles for ALT level were calculated on the basis of the empirical distribution of the data .", "BACKGROUND Eligible subjects with mildly elevated serum creatine kinase ( CK ) activity are often excluded before r and omization in statin trials , but patients may potentially be misclassified as having hyperCKemia when inappropriate reference limits are used . Little information is usually given regarding how reference limit data were established , although evidence suggests that the variation of CK activity in the general population is wider than reflected in reference intervals in current use . METHODS We determined reference intervals for serum CK according to National Committee on Clinical Laboratory St and ards/Nordic Reference Interval Project guidelines , in a stratified r and om sample of the population , including 1444 individuals , aged 34 to 60 years , after 3 days of rest . Participants were mainly of white European ( n = 503 ) , South Asian ( n = 292 ) , or African descent ( n = 580 ) . RESULTS The calculated upper reference limits ( 97.5th percentile ) for nonblack and black women and men were 2 to 5 times higher than recommended by the assay manufacturer . Respectively 13 % of the white Europeans , 23 % of South Asians , and 49 % of the black people had serum CK activities above the manufacturer-provided limits . CONCLUSION The variation in CK activity within the population is wider than previously suggested in smaller , nonr and om sample s , and relatively high values occur frequently in all subgroups studied after rest . Therefore , we infer that upward adjustment of the upper reference limit is necessary for all population subgroups studied . The use of appropriately established reference intervals may improve the use of statins and particularly benefit the control of dyslipidemia in those with relatively high baseline CK activity", "In Phase I clinical studies , the maximum tolerated dose has to be determined by a case by case analysis sometimes using a laboratory adverse effect , e.g. an increase in alanine amino transferase ( ALT ) . For this reason a threshold to discriminate between significant or non significant adverse changes in ALT is required particularly in Phase I studies , in order to deal with the very common “ close to the limit values ” . Previous methods ( limit of normal range or normal range plus an arbitrary margin ) do not solve this problem . The authors propose a new method taking into account the threshold used as inclusion criteria for ALT ( R ) and the range of spontaneous variations measured under identical Phase I study conditions ( V ) . The ( R ) and ( V ) thresholds , respectively , are defined as 50 IU·1−1 and a 50 % increase , from baseline . Thus an ALT value is recognized as a “ significant adverse experience ” if it exceeds 50 IU·1−1 above an increase from baseline exceeding 50 % of the baseline value . To highlight the value of the method , it was implemented in a one year period including 8 studies and 134 subjects . The sensitivity , specificity and positive predictive value of various methods were compared . The results showed the following : Six out of 134 subjects had significant adverse changes in ALT ( 4 % ) ; and all these 6 subjects were detected by the proposed new method without error . Eight subjects including two false positives , were detected by an use of the normal range limit , and only 4 were detected using , the 10 % margin . Thus , use of the new method showed 1 . keeping the normal range limit as the detection threshold led to preserved sensitivity ; 2 . it reduced the background noise of false positive results related to chance variation around the upper limit , mainly in subjects with a baseline value close to the limit ; 3 . it allowed better judgment of the significance of a value which lay just beyond the limit when variation from the baseline exceeding the normal range . The new method produced the best combination of sensitivity , specificity and positive predictive value . Given the small number of subjects in the study , further evaluation with a larger population is required . Finally , the proposed new method seems to be a tool easy to use determining the significance of adverse changes in ALT when the values are close to the limit that is common in Phase I studies", "OBJECTIVE This report analyzes all adverse events ( AEs ) which occurred in healthy volunteers in a phase I center over a five-year period . It included 142 phase I studies with a total of 1,559 participants receiving 2,955 treatments with 32 different active drugs and placebo ( ratio 6.5 : 1 in terms of follow-up days ) . The observation period covered a total of 29,664 follow-up days . METHODS All adverse events ( AEs ) as well as clinical ly relevant laboratory findings were counted . The incidence of AEs was defined as the ratio between the number of AEs and the number of follow-up days . Severity of AEs was classified as mild , moderate and severe ; serious AEs were analyzed separately . A chi2-test was used to compare incidence rates of the AEs . Statistical tests based on the normal distribution were used for comparison of demographic data and relative frequencies ; p headache ( 2.23 % ) , diarrhea ( 1.37 % ) and common cold ( 0.72 % ) being the most frequent . The overall incidence of AEs was 8.8 % with no significant difference between those occurring with active drug and those on placebo when the studies were taken as a whole ( 8.5 % vs. 9.1 % ) , but the incidence of AEs in the active treatment groups was higher than under placebo ( 14.1 % vs. 9.1 % ; p overall rate of AEs was 1.7 per subject and 0.9 per treatment . The vast majority of AEs were of mild or moderate intensity ( 99.2 % ) . Only six AEs were serious as defined by GCP but two , a pseudoallergic reaction and a prolonged orthostatic dysregulation were rated as possibly or probably drug-related and these resolved completely . The incidence of AEs was three-fold ( all AEs ) and six-fold ( AEs with probable relationship to study medication ) higher ( p AEs occurred with a significantly higher incidence on the first day of the study drug administration , in the first study period , with respect to the overall population in elderly subjects and in volunteers with a high body weight . CONCLUSION AEs in phase I studies are common , but usually of mild or moderate intensity . Placebo effects and study conditions contribute significantly to the rate of their occurrence . Multiple-dose placebo-controlled studies are of particular importance in determining the substance-specific AE profile" ]

[ "BACKGROUND Extraction socket remodeling and ridge preservation strategies have been extensively explored . PURPOSE To evaluate the efficacy of applying a micro-titanium stent as a pressure bearing device on extraction socket remodeling of maxillary anterior tooth . MATERIAL S AND METHODS Twenty-four patients with a extraction socket of maxillary incisor were treated with spontaneous healing ( control group ) or by applying a micro-titanium stent as a facial pressure bearing device over the facial bone wall ( test group ) . Two virtual models obtained from cone beam computed tomography data before extraction and 4 months after healing were 3-dimenionally superimposed . Facial bone wall resorption , extraction socket remodeling features and ridge width preservation rate were determined and compared between the groups . RESULTS Thin facial bone wall result ed in marked resorption in both groups . The greatest palatal shifting distance of facial bone located at the coronal level in the control group , but middle level in the test group . Compared with the original extraction socket , 87.61 ± 5.88 % ridge width was preserved in the test group and 55.09 ± 14.46 % in the control group . CONCLUSIONS Due to the facial pressure bearing property , the rigid micro-titanium stent might preserve the ridge width and alter the resorption features of extraction socket", "BACKGROUND Tooth extraction typically leads to loss of ridge width and height . The primary aim of this 6-month r and omized , controlled , blinded , clinical study was to determine whether ridge preservation would prevent post- extraction resorptive changes as assessed by clinical and histologic parameters . METHODS Twenty-four patients , 10 males and 14 females , aged 28 to 76 ( mean 51.5 + /- 13.6 ) , requiring a non-molar extraction and delayed implant placement were r and omly selected to receive either extraction alone ( EXT ) or ridge preservation ( RP ) using tetracycline hydrated freeze-dried bone allograft ( FDBA ) and a collagen membrane . A replaced flap , which did not completely cover the sockets , was used . Following extraction , horizontal and vertical ridge dimensions were determined using a modified digital caliper and an acrylic stent , respectively . Prior to implant placement , a 2.7 x 6.0 mm trephine core was obtained and preserved in formalin for histologic analysis . RESULTS The width of the RP group decreased from 9.2 + /- 1.2 mm to 8.0 + /- 1.4 mm ( P ridge width , although an improved result was obtained in the RP group . Most of the resorption occurred from the buccal ; maxillary sites lost more width than m and ibular sites . The vertical change for the RP group was a gain of 1.3 + /- 2.0 mm versus a loss of 0.9 + /- 1.6 mm for the EXT group ( P bone in the RP group : about 65 + /- 10 % versus 54 + /- 12 % in the EXT group . The RP group included both vital bone ( 28 % ) and non-vital ( 37 % ) FDBA fragments . CONCLUSIONS Ridge preservation using FDBA and a collagen membrane improved ridge height and width dimensions when compared to extraction alone . These dimensions may be more suitable for implant placement , especially in areas where loss of ridge height would compromise the esthetic result . The quantity of bone observed on histologic analysis was slightly greater in preservation sites , although these sites included both vital and non-vital bone . The most predictable maintenance of ridge width , height , and position was achieved when a ridge preservation procedure was employed", "OBJECTIVE This systematic review aims to evaluate the scientific evidence on the efficacy in the surgical protocol s design ed for preserving the alveolar ridge after tooth extraction and to evaluate how these techniques affect the placement of dental implants and the final implant supported restoration . MATERIAL AND METHODS A thorough search in MEDLINE - PubMed , Embase and the Cochrane Central Register of controlled trials ( CENTRAL ) was conducted up to February 2011 . R and omized clinical trials and prospect i ve cohort studies with a follow-up of at least 3 months reporting changes on both the hard and soft tissues ( height and /or width ) of the alveolar process ( mm or % ) after tooth extraction were considered for inclusion . RESULTS The screening of titles and abstract s result ed in 14 publications meeting the eligibility criteria . Data from nine of these 14 studies could be grouped in the meta-analyses . Results from the meta-analyses showed a statistically significant greater ridge reduction in bone height for control groups as compared to test groups ( weighted mean differences , WMD = -1.47 mm ; 95 % CI [ -1.982 , -0.953 ] ; P greater reduction in bone width for control groups compared to the test groups ( WMD = -1.830 mm ; 95 % CI [ -2.947 , -0.732 ] ; P = 0.001 ; heterogeneity : I(2 ) = 0 % ; χ(2 ) P-value = 0.837 ) . Subgroup analysis was based on the surgical protocol used for the socket preservation ( flapless/flapped , barrier membrane/no membrane , primary intention healing/no primary healing ) and on the measurement method utilized to evaluate morphological changes . Meta-regression analyses demonstrated a statistically significant difference favoring the flapped subgroup in terms of bone width ( meta-regression ; slope = 2.26 ; 95 % IC [ 1.01 ; 3.51 ] ; P = 0.003 ) . CONCLUSIONS The potential benefit of socket preservation therapies was demonstrated result ing in significantly less vertical and horizontal contraction of the alveolar bone crest . The scientific evidence does not provide clear guidelines in regards to the type of bio material , or surgical procedure , although a significant positive effect of the flapped surgery was observed . There are no data available to draw conclusions on the consequences of such benefits on the long-term outcomes of implant therapy ", "OBJECTIVE To evaluate dimensional alterations of the alveolar ridge that occurred following tooth extraction at sites grafted with Bio-Oss ( ® ) Collagen . MATERIAL AND METHODS Twenty-eight subjects with maxillary incisors , canines , and premolars scheduled for extraction were included . The tooth was carefully removed . The patients were r and omly assigned to a test or a control group . In the test group patients , Bio-Oss ( ® ) Collagen was placed in the fresh extraction socket while in the controls no grafting was performed . Radiographic examination ( cone beam computed tomograms , CBCT ) was performed immediately after tooth extraction and socket treatment . Four months later , a new CBCT was obtained . In the radiographs , ( i ) the distance ( mm ) between base of the alveolar process ( apex ) and the buccal and palatal crests was determined , ( ii ) the outer profile of alveolar process of the experimental sites was outlined , and the cross section of the area ( mm(2 ) ) determined . RESULTS After 4 months of healing , the buccal and to a less extent also the palatal bone plate had become markedly reduced in height . The placement of a bio material in the socket failed to prevent resorption of the buccal and palatal bone walls . The cross-sectional area of the control ridge was reduced about 25 % and of the test ridge with 3 % . CONCLUSION The placement of a xenograft in fresh extraction sockets markedly counteracted the reduction in the hard tissue component of the edentulous sites" ]

[ "The two senior authors ( PMP , RP ) independently began using an identical enhanced posterior soft tissue repair after total hip replacement through a posterior approach . In the first author 's experience , a dislocation rate of 4 % in 395 patients before using the enhanced closure was reduced to 0 % in 395 patients in whom the enhanced closure was performed . In the second author 's experience , 160 total hip replacements had a dislocation rate of 6.2 % before the enhanced closure whereas 124 total hip replacements had a dislocation rate of 0.8 % after the enhanced closure . These results are highly statistically significant", "Benefits of a direct anterior approach ( DAA ) versus a posterior-lateral ( PA ) approach to THA were assessed in a single-surgeon , IRB-approved , prospect i ve , r and omized clinical study . Subjects ( 43 DAA and 44 PA ) were evaluated at 6 weeks , and 3 , 6 and 12 months . The primary end point was ability to climb stairs normally and walk unlimited at each time point . Secondary end points included assessment by several outcome instruments . DAA subjects performed better during the immediate post-operative period ; they had lower VAS pain scores on the first post-operative day , more subjects climbing stairs normally and walking unlimited at 6 weeks , and higher HOOS Symptoms scores at 3 months . There were no significant differences between groups at later time points . Findings confirm previous reports of benefits of DAA versus PA in early post-operative phases", "Minimally invasive total hip arthroplasty ( MIS THA ) aims at minimizing damage to muscles and tendons to accelerate postoperative recovery . Computer navigation allows a precise prosthesis alignment without complete visualization of the bony l and marks during MIS THA . A r and omized controlled trial ( RCT ) was conducted to determine the effectiveness of a computer-navigated MIS anterior approach for THA compared to a conventional posterolateral THA technique on the restoration of physical functioning during recovery following surgery . Thirty-five patients underwent computer-navigated MIS THA via the anterior approach , and 40 patients underwent conventional THA using the conventional posterolateral approach . Gait analysis was performed preoperatively , 6 weeks , and 3 and 6 months postoperatively using a body-fixed-sensor based gait analysis system . Walking speed , step length , cadence , and frontal plane angular movements of the pelvis and thorax were assessed . The same data were obtained from 30 healthy subjects . No differences were found in the recovery of spatiotemporal parameters or in angular movements of the pelvis and thorax following the computer-navigated MIS anterior approach or the conventional posterolateral approach . Although gait improved after surgery , small differences in several spatiotemporal parameters and angular movements of the trunk remained at 6 months postoperatively between both patient groups and healthy subjects", "The goal of the current study was to investigate whether preoperative rehabilitation advice reinforced by a patient information booklet can aid recovery after total hip arthroplasty in terms of pain , function , satisfaction , and quality of life . Thirty-five patients awaiting primary total hip arthroplasty were recruited into this study and r and omly allocated before admission to receive either the st and ard pathway of care or the rehabilitation program and booklet . All patients showed increases in function and psychological variables with time . The preoperative class and booklet , however , seemed to have the greatest impact on length of hospital stay , reducing the hospital stay by 3 days , and therapy input required , significantly influencing the cost of the procedure ( the rehabilitation class led to a cost saving of 587 British pounds ; approximately 810 dollars , per patient ) . In addition , patients attending the class reported higher levels of satisfaction ( 99 % satisfied in the preoperative rehabilitation class compared with 80 % in the control group 3 months postoperatively ) and had more realistic expectations of surgery", "Objective : To evaluate the outcome after spinal surgery when adding prehabilitation to the early rehabilitation . Design : A r and omized clinical study . Setting : Orthopaedic surgery department . Subject : Sixty patients scheduled for surgery followed by inpatient rehabilitation for degenerative lumbar disease . Interventions : The patients were computer r and omized to prehabilitation and early rehabilitation ( 28 patients ) or to st and ard care exclusively ( 32 patients ) . The intervention began two months prior to the operation . The prehabilitation included an intensive exercise programme and optimization of the analgesic treatment . Protein drinks were given the day before surgery . The early postoperative rehabilitation included balanced pain therapy with self-administered epidural analgesia , doubled intensified mobilization and protein supplements . Main measures : The outcome measurements were postoperative stay , complications , functionality , pain and satisfaction . Results : At operation the intervention group had improved function , assessed by Rol and Morris Question naire ( P = 0.001 ) . After surgery the intervention group reached the recovery milestones faster than the control group ( 1—6 days versus 3—13 , P = 0.001 ) , and left hospital earlier ( 5 ( 3—9 ) versus 7 ( 5—15 ) days , P = 0.007 ) . There was no difference in postoperative complications , adverse events , low back pain and radiating pain , timed up and go , sit-to-st and or in life quality . Patient satisfaction was significantly higher in the intervention group compared with the control group . Conclusion : The integrated programme of prehabilitation and early rehabilitation improved the outcome and shortened the hospital stay — without more complications , pain or dissatisfaction", "BACKGROUND It is currently unknown whether functional restrictions following total hip arthroplasty can reduce the prevalence of early postoperative dislocation . Our hypothesis was that dislocation was more likely to occur in patients who were not placed on these restrictions . METHODS We performed a prospect i ve , r and omized study to evaluate the role of postoperative functional restrictions on the prevalence of dislocation following uncemented total hip arthroplasty through an anterolateral approach . Of the 630 eligible consecutive patients , 265 patients ( 303 hips ) consented to be r and omized into one of two groups ( the \" restricted \" group or the \" unrestricted \" group ) . The patients in both groups were asked to limit the range of motion of the hip to for the first six weeks after the procedure . The patients in the restricted group were instructed to comply with additional hip pre caution s during the first six weeks postoperatively . Specifically , these patients were managed with the placement of an abduction pillow in the operating room before bed transfer and used pillows to maintain abduction while in bed ; used elevated toilet seats and elevated chairs in the hospital , in the rehabilitation facility , and at home ; and were prevented from sleeping on the side , from driving , and from being a passenger in an automobile . All patients were followed for a minimum of six months postoperatively . RESULTS There was one dislocation in the entire cohort ( prevalence , 0.33 % ) . This dislocation occurred in a patient in the restricted group during transfer from the operating table to a bed with an abduction pillow in place . Patients in the unrestricted group were found to return to side-sleeping sooner ( p ride in automobiles more often ( p drive automobiles more often ( p return to work sooner ( p higher level of satisfaction with the pace of their recovery ( p additional expenditure of approximately $ 655 per patient in the restricted group . CONCLUSIONS Total hip arthroplasty through an anterolateral approach is likely to be associated with a low dislocation rate . Removal of several restrictions did not increase the prevalence of dislocation following primary hip arthroplasty at our institution . However , it did promote substantially lower costs and was associated with a higher level of patient satisfaction as patients achieved a faster return to daily functions in the early postoperative period", "BACKGROUND Improvements in surgical techniques and increase of femoral head size might have changed the rationale for movement restrictions after total hip replacement ( THR ) . AIM To evaluate the influence of movement restrictions and assistive devices on rehabilitation after fast track THR . DESIGN Non-r and omized , controlled study . SETTING Inpatient . POPULATION 365 consecutively included THR patients . METHODS Patients included the 3 initial month of the study underwent rehabilitation with restrictions in hip movement and a st and ard package of assistive devices ( restricted group ) . This group was compared to patients included the following 3 months with less restricted hip movement and use of assistive devices according to individual needs ( unrestricted group ) . Question naires on function , pain , quality of life ( HOOS ) , anxiety ( HADS ) , working status and patient satisfaction were completed before THR , 3 and 6 weeks after . RESULTS The HOOS function score at the 3 measurement times was ( mean ± SD ) ; unrestricted group : 46 ± 17 - 76 ± 9 - 83 ± 14 compared to restricted group : 43 ± 16 - 81 ± 14 - 83 ± 13 . Changes over time was significantly higher in the restricted group ( P=0.004 ) . Return to work 6 weeks after THR for the unrestricted group compared to restricted group was : 53 % versus 32 % ( P=0.045 ) . No significant differences between groups in pain , symptoms , quality of life , anxiety/depression , hip dislocations and patient satisfaction . CONCLUSION This study showed slightly slower recovery in patient-reported function after reduction in movement restrictions and use of assistive devices , but the difference was eliminated after 6 weeks . Reduced movement restrictions did not affect the other patient-reported outcomes and led to earlier return to work . CLINICAL REHABILITATION IMPACT It is possible to reduce movement restrictions and use of assistive devices considerably . More research on safety issues is needed to eluci date the effect of unrestricted rehabilitation on hip dislocation", "Currently , many rehabilitation protocol s for total hip replacements ( THRs ) include activity restrictions to prevent postoperative dislocation . There is increasing dem and for more efficient and safe rehabilitation protocol s. This r and omized prospect i ve study evaluates the need for hip restrictions following a modified anterolateral procedure . From 2004 to 2008 , 81 patients seeking elective THRs were r and omly assigned into a st and ard rehabilitation group or an early rehabilitation group . The st and ard group included restrictions to avoid hip flexion > 90 degrees and avoidance of riding in a car for the first postoperative month . The early group had no flexion or car riding restrictions . Forty-three patients were in the st and ard group and 38 patients were in the early group . There were no significant demographic differences between the 2 groups . All patients completed the Short Form 12- question Health Survey and Harris Hip Score preoperatively and at 4 weeks , 1 month , 3 months , and 1 year postoperatively . The time-points at which the patient first drove and ambulated with a cane , without a cane , and without a limp were also collected . No incidents of dislocation occurred . Patients in the early group were faster to ambulate with only a cane ( P=.03 ) , without a cane ( P without a limp ( P=.003 ) . They also drove earlier ( P=.02 ) . Pace of recovery was the only significant difference between the 2 groups . The early rehabilitation protocol increases the pace of recovery compared to a pathway with hip pre caution s without increasing complications", "OBJECTIVE Dislocation is a well-known complication after total hip arthroplasty ( THA ) , and is the second-highest cause of revision surgery . Our objective was to assess the effect of preoperative patient education on the occurrence of hip dislocation within 6 months after primary THA . METHODS Between 1998 and 2007 , we conducted a prospect i ve cohort study at the Geneva University Hospital Department of Orthopaedic Surgery , including all primary THAs performed via an anterolateral transgluteal approach with the use of a 28-mm diameter head . The preoperative education session was introduced in June 2002 and included advice on muscle strengthening exercises and postoperative restrictions of range of motion as a means of preventing dislocation . The main outcome was the incidence of dislocation within 6 months of surgery . RESULTS A total of 597 patients who underwent 656 THAs between June 2002 and June 2007 participated in the education session , whereas 1,641 patients who underwent 1,945 procedures did not . Forty-six dislocations occurred over the study period , 5 ( 0.8 % ) in participants and 41 ( 2.1 % ) in non participants ( absolute risk reduction 1.3 % ; 95 % confidence interval [ 95 % CI ] 0.4 , 2.3 ) , with the time interval between surgery and dislocation being significantly shorter among participants ( 0.2 versus 1.2 months ) . Non participants had a 2.8 times higher risk of dislocation than participants ( unadjusted odds ratio [ OR ] 2.80 ; 95 % CI 1.10 , 7.13 ) . Adjustment for age , sex , comorbidities , and prior surgery did not change the results ( adjusted OR 2.79 ; 95 % CI 1.09 , 7.15 ) . CONCLUSION Our findings suggest that participation in a preoperative patient education session may reduce the risk of dislocation within 6 months after THA" ]

[ "Calcium and vitamin D are essential nutrients for bone health . Periods of activity with repetitive mechanical loading , such as military training , may result in increases in parathyroid hormone ( PTH ) , a key regulator of Ca metabolism , and may be linked to the development of stress fractures . Previous studies indicate that consumption of a Ca and vitamin D supplement may reduce stress fracture risk in female military personnel during initial military training , but circulating markers of Ca and bone metabolism and measures of bone density and strength have not been determined . This r and omized , double-blind , placebo-controlled trial sought to determine the effects of providing supplemental Ca and vitamin D ( Ca+Vit D , 2000 mg and 1000IU/d , respectively ) , delivered as 2 snack bars per day throughout 9weeks of Army initial military training ( or basic combat training , BCT ) on PTH , vitamin D status , and measures of bone density and strength in personnel undergoing BCT , as well as independent effects of BCT on bone parameters . A total of 156 men and 87 women enrolled in Army BCT ( Fort Sill , OK ; 34.7 ° N latitude ) volunteered for this study . Anthropometric , biochemical , and dietary intake data were collected pre- and post-BCT . In addition , peripheral quantitative computed tomography was utilized to assess tibia bone density and strength in a subset of volunteers ( n=46 ) . Consumption of supplemental Ca+Vit D increased circulating ionized Ca ( group-by-time , P=0.022 ) , maintained PTH ( group-by-time , P=0.032 ) , and increased the osteoprotegerin : RANKL ratio ( group-by-time , P=0.006 ) . Consistent with the biochemical markers , Ca+Vit D improved vBMD ( group-by-time , P=0.024 ) at the 4 % site and cortical BMC ( group-by-time , P=0.028 ) and thickness ( group-by-time , P=0.013 ) at the 14 % site compared to placebo . These data demonstrate the benefit of supplemental Ca and vitamin D for maintaining bone health during periods of elevated bone turnover , such as initial military training . This trial was registered with ClincialTrials.gov , NCT01617109", "It is hypothesized that vitamin D insufficiency in athletes might negatively affect sport performance . The objective of this study was to examine the effect of vitamin D3 supplementation on physical performance of adolescent swimmers with vitamin D insufficiency . Fifty-three adolescent competitive swimmers with vitamin D insufficiency ( serum 25-hydroxyvitamin-D concentrations ( 25(OH)D ) were r and omized to receive 2,000 IU/day of vitamin D3 or placebo for 12 weeks . Swimming performance at several speeds , arm-grip strength , and one-legged balance , were measured before and after supplementation . The age-adjusted changes in performance variables during the study were compared between groups . 25(OH ) D concentrations at study end were significantly higher in the vitamin group compared with the placebo group ( 29.6 ± 6.5 ng/ml vs. 20.3 ± 4.2 ng/ml , p the performance variables tested . No significant differences in performance were found between participants that became vitamin D sufficient , and those who did not . No significant correlation was found between the change in serum 25(OH)D and age-adjusted balance , strength or swimming performance at study end . Vitamin D3 supplementation that raised serum 25(OH)D concentrations by a mean of 9.3 ng/ml above placebo in adolescent swimmers with vitamin D insufficiency , did not improve physical performance more than placebo", "Young male jockeys compromise bone health by engaging in caloric restriction and high volumes of physical activity during periods of musculoskeletal growth and development . The aim of this r and omised , double-blinded , placebo-controlled trial was to establish whether calcium and vitamin D supplementation would improve bone properties of young male jockeys . We conducted a 6-month trial with two groups of weight- , height- and age-matched apprentice male jockeys ( age=20.2 ± 3.2 yrs ) . Participants were supplemented with 800 mg of calcium and 400 IU of vitamin D ( S , n=8 ) or a placebo ( cellulose ) ( P , n=9 ) daily for 6-months . Baseline calcium intake was ( 669.7 ± 274.3 ( S ) vs 790.4 ± 423.9 ( P ) and vitamin D 64.6 ± 19.5 ( S ) vs 81.2 ± 24.4 ( P ) with no statistical differences . Peripheral quantitative computed tomography ( pQCT ) measured ultra-distal ( 4 % ) and proximal ( 66 % ) tibial bone properties at baseline and 6 months . Blood-borne markers of bone turnover , P1NP and CTX and vitamin D concentration were assessed . After co-varying for height , weight and baseline bone measurements , the supplemented group displayed greater post-intervention bone properties at the 66 % proximal site with cortical content ( mgmm ) 6.6 % greater ( p cortical density ( mgcm(2 ) ) 1.3 % greater ( p=0.001 ) , and total area ( mm(2 ) ) 4 % larger ( p=0.003 ) . No other between group differences in bone variables were observed . Blood analysis indicated higher vitamin D levels ( 18.1 % , p=0.014 ) and lower CTx ( ng/L ) ( -24.8 % , p=0.011 ) in the supplemented group with no differences observed in P1NP . This is the first r and omised controlled trial to examine the efficacy of calcium and vitamin D supplementation in improving bone properties in a highly vulnerable , young athletic , weight-restricted population . Results using pQCT indicate beneficial effects of supplementation on bone properties in as little as six months . Although the study size is small , this intervention appears promising as a strategy for improving bone health in young athletes in weight-restricted sports", "Purpose Vitamin D inadequacy is a global health concern in athletes as well as the general population . Whilst the role of vitamin D in skeletal health is well defined , there remains uncertainty over whether vitamin D supplementation has an added benefit beyond bone health . Methods This r and omised placebo-controlled trial in healthy male and female Gaelic footballers ( n = 42 ) investigated the effect of vitamin D3 supplementation [ 3000 IU ( 75 µg ) daily for 12 weeks , via an oral spray solution ] on VO2 max which was the primary outcome measure . Secondary outcomes included skeletal muscle and lung function . Results Supplementation significantly increased total 25-hydroxyvitamin D concentrations compared to the placebo group ( mean ± SD change from baseline , 36.31 ± 32.34 vs. 6.11 ± 23.93 nmol/L , respectively ; P = 0.006 ) . At baseline , 50 and 22 % of footballers presented with vitamin D insufficiency ( 31–49 nmol/L ) and deficiency ( respectively . Total 25-hydroxyvitamin D concentration did not significantly correlate with any measure of physical performance . Analysis of covariance ( ANCOVA ) models demonstrated that vitamin D supplementation over 12 weeks had no significant effect on VO2 max ( P = 0.375 ) , vertical jump height ( P = 0.797 ) , left and right h and grip strength ( P = 0.146 and P = 0.266 , respectively ) , forced vital capacity ( P = 0.573 ) or forced expiratory volume at 1 s ( P = 0.665 ) , after adjusting for confounders . The high prevalence of vitamin D inadequacy observed in this cohort of collegiate Gaelic footballers supports the need for vitamin D supplementation during wintertime to avoid being at risk of poor bone health . Conclusions Twelve-week daily supplementation with 3000 IU ( 75 µg ) vitamin D3 successfully resolved deficiency but did not have any significant effect on VO2 max , skeletal muscle or lung function ", "This study determined if 6-weeks vitamin D2 supplementation ( vitD2 , 3800 IU/day ) had an influence on muscle function , eccentric exercise-induced muscle damage ( EIMD ) , and delayed onset of muscle soreness ( DOMS ) in National Association for Stock Car Auto Racing ( NASCAR ) NASCAR pit crew athletes . Subjects were r and omized to vitD2 ( n = 13 ) and placebo ( n = 15 ) , and ingested supplements ( double-blind ) for six weeks . Blood sample s were collected and muscle function tests conducted pre- and post- study ( leg-back and h and grip dynamometer strength tests , body weight bench press to exhaustion , vertical jump , 30-s Wingate test ) . Post- study , subjects engaged in 90 min eccentric-based exercise , with blood sample s and DOMS ratings obtained immediately after and 1- and 2-days post-exercise . Six weeks vitD2 increased serum 25(OH)D2 456 % and decreased 25(OH)D3 21 % versus placebo ( p function test scores . The post- study eccentric exercise bout induced EIMD and DOMS , with higher muscle damage biomarkers measured in vitD2 compared to placebo ( myoglobin 252 % , 122 % increase , respectively , p = 0.001 ; creatine phosphokinase 24 h post-exercise , 169 % , 32 % , p 25(OH)D2 and decreased 25(OH)D3 , had no effect on muscle function tests , and amplified muscle damage markers in NASCAR pit crew athletes following eccentric exercise", "Summary The aim of this study was to investigate vitamin D status and stress fracture risk during Royal Marine military training . Poor vitamin D status was associated with an increased risk of stress fracture . Vitamin D supplementation may help to reduce stress fracture risk in male military recruits with low vitamin D status . Introduction Stress fracture is a common overuse injury in military recruits , including Royal Marine ( RM ) training in the UK . RM training is recognised as one of the most arduous basic training programmes in the world . Associations have been reported between serum 25-hydroxyvitamin D ( 25(OH)D ) and risk of stress fracture , but the threshold of 25(OH)D for this effect remains unclear . We aim ed to determine if serum 25(OH)D concentrations were associated with stress fracture risk during RM training . Methods We prospect ively followed 1082 RM recruits ( males aged 16–32 years ) through the 32-week RM training programme . Troops started training between September and July . Height , body weight and aerobic fitness were assessed at week 1 . Venous blood sample s were drawn at weeks 1 , 15 and 32 . Serum sample s were analysed for 25(OH)D and parathyroid hormone ( PTH ) . Results Seventy-eight recruits ( 7.2 % ) suffered a total of 92 stress fractures . Recruits with a baseline serum 25(OH)D concentration below 50 nmol L−1 had a higher incidence of stress fracture than recruits with 25(OH)D concentration above this threshold ( χ2(1 ) = 3.564 , p = 0.042 ; odds ratio 1.6 ( 95 % confidence interval ( CI ) 1.0–2.6 ) ) . Baseline serum 25(OH)D varied from 47.0 ± 23.7 nmol L−1 in February , to 97.3 ± 24.6 nmol L−1 in July ( overall mean 69.2 ± 29.2 nmol L−1 , n = 1016 ) . There were weak inverse correlations between serum 25(OH)D and PTH concentrations at week 15 ( r = −0.209 , p Conclusion Baseline serum 25(OH)D concentration below 50 nmol L−1 was associated with an increased risk of stress fracture . Further studies into the effects of vitamin D supplementation on stress fracture risk are certainly warranted", "Abstract : The first part of this study consisted of an 18 month follow-up of the vitamin D status and parathyroid function in a group of 54 French male adolescents , aged from 13 to 16 years old and all pupils of a jockey training school . During the 18 month period four samplings were made , one every 6 months . The first was during September of the first year , the second and third during March and October of the second year , and the last in March of the third year . Therefore we had two main periods : summer and winter . The summer 25-hydroxyvitamin D ( 25(OH)D ) concentrations were higher ( 71.6 ± 19.9 and 52.4 ± 16.5 nmol/l ) than the winter ones ( 20.4 ± 6.9 and 21.4 ± 6.1 nmol/l ) . Conversely , the winter intact parathyroid hormone ( iPTH ) serum levels ( 4.18 ± 1.18 and 4.11 ± 1.35 pmol/l ) were higher than the summer ones ( 2.44 ± 0.82 and 2.71 ± 0.71 pmol/l ) . At the two winter time points the 25(OH)D concentrations were lower than 25 nmol/l ( 10 ng/ml ) in 72 % ( 2nd year ) and 68 % ( 3rd year ) of the adolescents . In the second part of the study we tried a vitamin D3 supplementation procedure design ed to maintain the 25(OH)D and iPTH postsummer serum levels throughout the winter . Pairs of male adolescents matched for height , weight and Tanner pubertal stage were r and omly assigned to either vitamin D3 supplementation ( 2.5 mg , i.e. , 100 000 IU ) administered orally at three specific periods ( end of September , November and January ) or no vitamin D3 treatment ( control subjects ) . Blood was collected just before the first intake of vitamin D3 and 2 months after the last intake ( March ) . The control subjects had blood drawn at the same time points . In the vitamin D3-treated subjects , the concentrations of 25 (OH)D ( 55.3 ± 11.5 nmol/l ) and of iPTH ( 3.09 ± 1.16 pmol/l ) in March and September ( 53.8 ± 12.3 nmol/l and 2.75 ± 1.26 pmol/l ) were not significantly different . In the control subjects , March 25(OH)D levels ( 21.0 ± nmol/l were low , with values below 25 nmol/l in 78 % of subjects , and iPTH concentrations ( 3.97 ± 1.08 pmol/l ) were significantly ( p vitamin D wintertime deficiency and wintertime rise in iPTH in adolescent French males throughout puberty has been demonstrated . In adolescents with low dairy calcium intakes , the vitamin D3 treatment was sufficient to maintain 25(OH)D concentrations at their summer levels throughout winter and to prevent an excessive wintertime rise in iPTH levels ", "Submariners spend prolonged periods submerged without sunlight exposure and may benefit from vitamin D supplementation to maintain vitamin D status . The primary objective of this study was to determine the efficacy of daily vitamin D supplementation on maintenance of 25-hydroxyvitamin D ( 25(OH)D ) during a 3-month submarine patrol . Submariners were r and omly divided into three groups : placebo ( n = 16 ) , 1,000 IU/day ( n = 20 ) , or 2,000 IU/day ( n = 17 ) . Anthropometrics , self-reported dietary calcium and vitamin D intake , serum markers of vitamin D and bone metabolism , and peripheral quantitative computed tomography ( pQCT ) parameters of the tibia were determined before and after the patrol . Prior to departure , 49 % of the subjects were vitamin D insufficient ( . Following the patrol , 25(OH)D increased in all groups ( p ( placebo ) , 4.6 ± 11.3 ( 1,000 IU/day ) , and 13 ± 14 nmol/L ( 2,000 IU/day ) . The changes in 25(OH)D levels were dependent upon the baseline concentration of 25(OH)D and body mass ( p increased by 38 % ( p increases in indices of tibial structure and strength ( p that vitamin D status was low prior to the patrol , and the subsequent changes in vitamin D status were dependent on the baseline 25(OH)D levels and body mass . Furthermore , short-term skeletal health does not appear to be negatively affected by 3 months of submergence in spite of a suboptimal response to vitamin D supplementation", "The purpose of this 6-month r and omized , placebo-controlled trial was to determine the effect of season-long ( September-March ) vitamin D supplementation on changes in vitamin D status , which is measured as 25(OH ) D , body composition , inflammation , and frequency of illness and injury . Forty-five male and female athletes were r and omized to 4,000 IU vitamin D ( n = 23 ) or placebo ( n = 22 ) . Bone turnover markers ( NTx and BSAP ) , 25(OH)D , and inflammatory cytokines ( TNF-alpha , IL-6 , and IL1-β ) were measured at baseline , midpoint , and endpoint . Body composition was assessed by DXA and injury and illness data were collected . All athletes had sufficient 25(OH)D ( > 32 ng/ml ) at baseline ( mean : 57 ng/ml ) . At midpoint and endpoint , 13 % and 16 % of the total sample had 25(OH)D respectively . 25(OH)D was not positively correlated with bone mineral density ( BMD ) in the total body , proximal dual femur , or lumbar spine . In men , total body ( p = .04 ) and trunk ( p = .04 ) mineral-free lean mass ( MFL ) were positively correlated with 25(OH)D. In women , right femoral neck BMD ( p = .02 ) was positively correlated with 25(OH)D. 25(OH)D did not correlate with changes in bone turnover markers or inflammatory cytokines . Illness ( n = 1 ) and injury ( n = 13 ) were not related to 25(OH)D ; however , 77 % of injuries coincided with decreases in 25(OH)D. Our data suggests that 4,000 IU vitamin D supplementation is an inexpensive intervention that effectively increased 25(OH)D , which was positively correlated to bone measures in the proximal dual femur and MFL . Future studies with larger sample sizes and improved supplement compliance are needed to exp and our underst and ing of the effects of vitamin D supplementation in athletes", "UNLABELLED The effect of vitamin D supplementation on bone mineral augmentation in 212 adolescent girls with adequate calcium intake was studied in a r and omized placebo-controlled setting . Bone mineral augmentation determined by DXA increased with supplementation both in the femur and the lumbar vertebrae in a dose-responsive manner . Supplementation decreased the urinary excretion of resorption markers , but had no impact on formation markers . INTRODUCTION Adequate vitamin D intake protects the elderly against osteoporosis , but there exists no indisputable evidence that vitamin D supplementation would benefit bone mineral augmentation . The aim of this 1-year study was to determine in a r and omized double-blinded trial the effect of 5 and 10 microg vitamin D3 supplementation on bone mineral augmentation in adolescent girls with adequate dietary calcium intake . MATERIAL S AND METHODS Altogether , 228 girls ( mean age , 11.4 + /- 0.4 years ) participated . Their BMC was measured by DXA from the femur and lumbar spine . Serum 25-hydroxyvitamin D [ S-25(OH)D ] , intact PTH ( S-iPTH ) , osteocalcin ( S-OC ) , and urinary pyridinoline ( U-Pyr ) and deoxypyridinoline ( U-Dpyr ) were measured . Statistical analysis was performed both with the intention-to-treat ( IT ) and compliance-based ( CB ) method . RESULTS In the CB analysis , vitamin D supplementation increased femoral BMC augmentation by 14.3 % with 5 microg and by 17.2 % with 10 microg compared with the placebo group ( ANCOVA , p = 0.012 ) . A dose-response effect was observed in the vertebrae ( ANCOVA , p = 0.039 ) , although only with the highest dose . The mean concentration of S-25(OH)D increased ( p S-iPTH or S-OC , but it decreased U-DPyr ( p = 0.042 ) . CONCLUSIONS Bone mineral augmentation in the femur was 14.3 % and 17.2 % higher in the groups receiving 5 and 10 microg of vitamin D , respectively , compared with the placebo group , but only 10 mug increased lumbar spine BMC augmentation significantly . Vitamin D supplementation decreased the concentration of bone resorption markers , but had no impact on bone formation markers , thus explaining increased bone mineral augmentation . However , the positive effects were noted with the CB method but not with IT", "Background Vitamin D deficiency is common in the general public and athletic population s and may impair skeletal muscle function . We therefore assessed the effects of vitamin D3 supplementation on serum 25[OH]D concentrations and physical performance . Methods 30 club-level athletes were block r and omised ( using baseline 25[OH]D concentrations ) into one of three groups receiving either a placebo ( PLB ) , 20 000 or 40 000 IU/week oral vitamin D3 for 12 weeks . Serum 25[OH]D and muscle function ( 1-RM bench press and leg press and vertical jump height ) were measured presupplementation , 6 and 12 weeks postsupplementation . Vitamin D deficiency was defined in accordance with the US Institute of Medicine guideline ( 57 % of the subject population were vitamin D deficient at baseline ( mean±SD value 51±24 nmol/l ) . Following 6 and 12 weeks supplementation with 20 000 IU ( 79±14 and 85±10 nmol/l , respectively ) or 40 000 IU vitamin D3 ( 98±14 and 91±24 nmol/l , respectively ) , serum vitamin D concentrations increased in all participants , with every individual achieving concentrations greater than 50 nmol/l . In contrast , vitamin D concentration in the PLB group decreased at 6 and 12 weeks ( 37±18 and 41±22 nmol/l , respectively ) . Increasing serum 25[OH]D had no significant effect on any physical performance parameter ( p>0.05 ) . Conclusions Both 20 000 and 40 000 IU vitamin D3 supplementation over a 6-week period elevates serum 25[OH]D concentrations above 50 nmol/l , but neither dose given for 12 weeks improved our chosen measures of physical performance ", "Objective : Indoor athletes have been shown to be prone to vitamin D3 deficiency . The aim of the study was to examine the acute effects of vitamin D supplementation on muscle function using isokinetic dynamometry . Design : R and omized placebo-controlled , double-blind study . Setting : Institutional . Participants : Adult male white national level judoka athletes ( n = 22 ) who were involved in full-time training . Exclusion criteria were vitamin supplementation , overseas travel to sunny climes , and /or an injury incurred during the last 3 months before testing . Interventions : Subjects were r and omly allocated to the treatment ( 150 000IU vitamin D3 ) or placebo and given blinded supplements by an independent research er . Participants were tested twice , 8 days apart , on a Monday morning before the start of judo training and after 2 days of rest . A 5 to 7 mL of blood sample was collected followed by isokinetic concentric quadriceps and hamstring muscle function assessment s on the right leg at 30 and 200 ° ·s−1 . Main Outcome Measures : Repeated- measures analysis of variance was used to analyze isokinetic muscle force and serum 25(OH)D3 . Regression to the mean was used to examine changes in 25(OH)D3 levels over the study period . Results : The treatment group demonstrated a significant increase in serum 25(OH)D levels ( 34 % , P ⩽ 0.001 ) and muscle strength ( 13 % , P = 0.01 ) between days 1 and 8 . No significant differences were found for the placebo group for the same period . Conclusions : A single bolus of 150 000IU vitamin D3 had a significant positive effect on serum 25(OH)D levels and muscle function in vitamin D insufficient elite indoor athletes . Clinical Relevance : Serum 25(OH)D3 levels of indoor athletes should be monitored throughout the year and especially during winter months . Beneficial responses , in muscle strength and serum 25(OH)D3 , to 1 dose of vitamin D3 supplementation can be observed within 1 week of ingestion . Muscle strength is linked to serum 25(OH)D levels", "Observational studies identified associations between vitamin D insufficiency ( serum 25(OH)D risk of upper respiratory infection ( URI ) . Swimmers are highly prone to URIs , which might hinder their performance . The aim of this study was to examine if vitamin D3 supplementation reduces URI burden in vitamin D-insufficient swimmers . Fifty-five competitive adolescent swimmers with vitamin D insufficiency were r and omized to receive vitamin D3 ( 2,000IU·d-1 ) or placebo for 12 winter weeks . A URI symptom question naire was completed weekly . Serum 25(OH)D concentrations were measured by radio-immunoassay before and after supplementation . We used linear regression to examine the relation between the change in 25(OH)D concentrations during the trial , and the duration and severity of URIs . There were no between-group differences in the frequency , severity , or duration of URIs . Exploratory analyses revealed that in the placebo group only , the change in 25(OH)D concentrations during the trial was highly associated with the duration of URIs ( r = -0.90,p the severity of URIs ( r = -0.65,p = .043 ) . The between-group differences for duration were highly significant . Vitamin D3 supplementation in adolescent swimmers with vitamin D insufficiency did not reduce URI burden . However , larger decreases in serum 25(OH)D concentrations were associated with significantly longer and more severe URI episodes", "OBJECTIVES Athletes who train indoors during the winter months exhibit low serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations due to a lack of sunlight exposure . This has been linked to impaired exercise performance . The purpose of this study was to assess the effects of oral vitamin D₃ supplementation on selected physical fitness and injury parameters in elite ballet dancers . DESIGN Controlled prospect i ve study . METHODS 24 elite classical ballet dancers ( intervention n=17 ; control n=7 ) participated in a controlled 4-month oral supplementation of vitamin D₃ ( 2000 IU per day ) . Isometric muscular strength and vertical jump height were measured pre and post intervention . Injury occurrence during the intervention period was also recorded by the in-house medical team . Repeated measures ANOVA and Mann-Whitney-U statistical tests were used and significance was set at p ≤ 0.05 . RESULTS Significant increases were noted for the intervention group for isometric strength ( 18.7 % , p ) and vertical jump ( 7.1 % , p significantly less injuries than the controls during the study period ( p Oral supplementation of vitamin D₃ during the winter months has beneficial effects on muscular performance and injury occurrence in elite ballet dancers", "Abstract Incidence of vitamin D deficiency is increasing worldwide . The purpose of this study was to determine if supplementation with vitamin D2 from Portobello mushroom powder would enhance skeletal muscle function and attenuate exercise-induced muscle damage in low vitamin D status high school athletes . Participants were r and omised to Portobello mushroom powder ( 600 IU/d vitamin D2 ) or placebo for 6 weeks . Participants then completed a 1.5-h exercise session design ed to induce skeletal muscle damage . Blood sample s and measures of skeletal muscle function were taken pre-supplementation , post-supplementation/pre-exercise and post-exercise . Six weeks supplementation with vitamin D2 increased serum 25(OH)D2 by 9.9-fold and decreased serum 25(OH)D3 by 28 % . Changes in skeletal muscle function and circulating markers of skeletal muscle damage did not differ between groups . In conclusion , 600 IU/d vitamin D2 increased 25(OH)D2 with a concomitant decrease in 25(OD)D3 , with no effect on muscular function or exercise-induced muscle damage in high school athletes", "Background / Objectives : To assess the prevalence of vitamin D deficiency in Dutch athletes and to define the required dosage of vitamin D3 supplementation to prevent vitamin D deficiency over the course of a year . Subjects/ Methods : Blood sample s were collected from 128 highly trained athletes to assess total 25(OH)D concentration . Of these 128 athletes , 54 male and 48 female athletes ( 18–32 years ) were included in a r and omized , double blind , dose – response study . Athletes with either a deficient ( were r and omly assigned to take 400 , 1100 or 2200 IU vitamin D3 per day orally for 1 year . Athletes who had a total 25(OH)D concentration above 75 nmol/l at baseline continued with the study protocol without receiving vitamin D supplements . Serum total 25(OH)D concentration was assessed every 3 months , as well as dietary vitamin D intake and sunlight exposure . Results : Nearly 70 % of all athletes showed an insufficient ( 50–75 nmol/l ) or a deficient ( months , serum 25(OH)D concentration had increased more in the 2200 IU/day group ( + 50±27 nmol/l ) than the sufficient group receiving no supplements ( + 4±17 nmol/l ; P vitamin D result ed in a sufficient 25(OH)D concentration in 80 % of the athletes after 12 months . Conclusions : Vitamin D deficiency is highly prevalent in athletes . Athletes with a deficient or an insufficient 25(OH)D concentration can achieve a sufficient 25(OH)D concentration within 3 months by taking 2200 IU/day", "Abstract Heavy training is associated with increased respiratory infection risk and antimicrobial proteins are important in defence against oral and respiratory tract infections . We examined the effect of 14 weeks of vitamin D3 supplementation ( 5000 IU/day ) on the resting plasma cathelicidin concentration and the salivary secretion rates of secretory immunoglobulin A ( SIgA ) , cathelicidin , lactoferrin and lysozyme in athletes during a winter training period . Blood and saliva were obtained at the start of the study from 39 healthy men who were r and omly allocated to vitamin D3 supplement or placebo . Blood sample s were also collected at the end of the study ; saliva sample s were collected after 7 and 14 weeks . Plasma total 25(OH)D concentration increased by 130 % in the vitamin D3 group and decreased by 43 % in the placebo group ( both P = 0.001 ) . The percentage change of plasma cathelicidin concentration in the vitamin D3 group was higher than in the placebo group ( P = 0.025 ) . Only in the vitamin D3 group , the saliva SIgA and cathelicidin secretion rates increased over time ( both P = 0.03 ) . A daily 5000 IU vitamin D3 supplement has a beneficial effect in up-regulating the expression of SIgA and cathelicidin in athletes during a winter training period , which could improve resistance to respiratory infections", "INTRODUCTION Stress fractures ( SFx ) are one of the most common and debilitating overuse injuries seen in military recruits , and they are also problematic for nonmilitary athletic population s. The goal of this r and omized double-blind , placebo-controlled study was to determine whether a calcium and vitamin D intervention could reduce the incidence of SFx in female recruits during basic training . MATERIAL S AND METHODS We recruited 5201 female Navy recruit volunteers and r and omized them to 2000 mg calcium and 800 IU vitamin D/d or placebo . SFx were ascertained when recruits reported to the Great Lakes clinic with symptoms . All SFx were confirmed with radiography or technetium scan according to the usual Navy protocol . RESULTS A total of 309 subjects were diagnosed with a SFx result ing in an incidence of 5.9 % per 8 wk . Using intention-to-treat analysis by including all enrolled subjects , we found that the calcium and vitamin D group had a 20 % lower incidence of SFx than the control group ( 5.3 % versus 6.6 % , respectively , p = 0.0026 for Fisher 's exact test ) . The per protocol analysis , including only the 3700 recruits who completed the study , found a 21 % lower incidence of fractures in the supplemented versus the control group ( 6.8 % versus 8.6 % , respectively , p = 0.02 for Fisher 's exact test ) . CONCLUSIONS Generalizing the findings to the population of 14,416 women who entered basic training at the Great Lakes during the 24 mo of recruitment , calcium and vitamin D supplementation for the entire cohort would have prevented approximately 187 persons from fracturing . Such a decrease in SFx would be associated with a significant decrease in morbidity and financial costs" ]

[ "BACKGROUND AND AIMS Cardiovascular diseases are the major cause of mortality among diabetic patients . The concentration of malondialdehyde ( MDA ) and homocysteine is believed to play a role in cardiovascular diseases . Omega-3 fatty acid supplementation could be effective in some diabetes complications and in the control of the glycemic index . However , it may increase lipid peroxidation . The objective of this study was to determine the effect of omega-3 fatty acids on the concentration of homocysteine and MDA in diabetic patients . METHODS AND RESULTS A r and omized double-blind , placebo-controlled clinical trial was conducted on 81 patients with type 2 diabetes . The patients were r and omly assigned to either the treatment or control groups . Each subject received three capsules of omega-3 fatty acids or a placebo every day for a period of 2months . The two groups were similar in terms of body mass index and food intake . At the beginning of the study and after 2months of supplementation their levels of HbA(1)c , homocysteine , MDA , C-reactive protein ( CRP ) , total cholesterol , LDL-cholesterol and fasting blood sugar ( FBS ) were determined . Due to omega-3 fatty acid supplementation , homocysteine was changed significantly in both treatment and control groups up to -3.10mumol/L and 0.10mumol/L respectively , and HbA(1)c decreased by 0.75 % in the treatment group and increased by 0.26 % in the control group . However , the changes in fasting blood sugar ( FBS ) , malondialdehyde ( MDA ) , C-reactive protein ( CRP ) , total cholesterol and LDL-cholesterol levels were not significant . CONCLUSION The consumption of omega-3 fatty acid supplements ( 3g/day ) for 2months decreases the levels of homocysteine in diabetic patients with no change in FBS , MDA and CRP levels", "The aim of this study was to examine the effect of Max EPA ( a commercially available fish oil preparation ) on serum cholesterol lipoproteins and apolipoproteins in insulin-dependent diabetic ( IDDM ) men with dosages that were likely to be acceptable to patients . Twenty-two male IDDM patients aged 20–41 yr , 6 of whom had retinopathy , were recruited from the Royal Perth Hospital diabetic clinic . After screening , subjects were divided into three groups . Six of the subjects without retinopathy were r and omly selected and allocated to a control group . The remaining 16 patients ( 10 without and 6 with retinopathy ) received a fish oil supplement . All subjects were advised to maintain their usual dietary patterns . Sixteen patients , including the 6 with retinopathy , were instructed to take 15 Max EPA fish oil capsules/day with meals . Patients in the control group did not take Max EPA . Three weeks of Max EPA supplementation without other dietary modification led to a significant rise in total cholesterol ( P increases in low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) cholesterol . The increase in HDL cholesterol was explained by a 33 % rise ( P Changes in apolipoproteins were examined and showed that the level of apolipoprotein A-l increased after ingestion of fish oil and correlated significantly ( P rise in HDL cholesterol . Apolipoprotein A-ll showed a significant fall at the end of Max EPA intake in a subgroup of patients with retinopathy , and this correlated significantly ( P fall in HDL3 cholesterol observed at this time . A significant rise in apolipoprotein B ( P rise in LDL cholesterol . Possible adverse effects of the increase in both total and LDL cholesterol after 15 g/day Max EPA may be compensated for by a rise in the protective HDL2 subclass . However , in view of this hypercholesterolemic effect and evidence that suggests that LDL apolipoprotein B may be a risk factor for coronary heart disease , these findings raise questions regarding the safety of fish oils in patients with IDDM", "BACKGROUND Information is lacking on the potential effect of n-3 polyunsaturated fatty acids ( PUFAs ) on the adipose tissue of patients with type 2 diabetes . OBJECTIVE We evaluated whether n-3 PUFAs have additional effects on adiposity , insulin sensitivity , adipose tissue function ( production of adipokines and inflammatory and atherogenic factors ) , and gene expression in type 2 diabetes . DESIGN Twenty-seven women with type 2 diabetes without hypertriglyceridemia were r and omly allocated in a double-blind parallel design to 2 mo of 3 g/d of either fish oil ( 1.8 g n-3 PUFAs ) or placebo ( paraffin oil ) . RESULTS Although body weight and energy intake measured by use of a food diary were unchanged , total fat mass ( P subcutaneous adipocyte diameter ( P Insulin sensitivity was not significantly different between the 2 groups ( measured by homeostasis model assessment in all patients and by euglycemic-hyperinsulinemic clamp in a subgroup of 5 patients per group ) . By contrast , atherogenic risk factors , including plasma triacylglycerol ( P ratio of triacylglycerol to HDL cholesterol ( atherogenic index , P plasma plasminogen activator inhibitor-1 ( P inflammation-related genes was reduced in subcutaneous adipose tissue after the fish oil , but not the placebo , treatment . CONCLUSIONS A moderate dose of n-3 PUFAs for 2 mo reduced adiposity and atherogenic markers without deterioration of insulin sensitivity in subjects with type 2 diabetes . Some adipose tissue inflammation-related genes were also reduced . These beneficial effects could be linked to morphologic and inflammatory changes in adipose tissue . This trial was registered at clinical trials.gov as NCT0037", "The effects of ( n-3 ) fatty acids on the postpr and ial state were investigated by monitoring the alimentary responses to identical test meals fed to adults [ n = 11 ; fasting triacylglycerol ( TG ) 2.55 + /- 0.24 mmol/L ; mean + /- SEM ] after a self-selected diet baseline period ( BLP ) and then after a 6-wk ( n-3 ) fatty acid period ( FOP ) [ approximately 5.2 g ( n-3 ) fatty acids ] and a 6-wk control oil period ( COP ) administered in r and om order . Sample s were drawn immediately prior to the test meal ( time 0 ) and then hourly from 2 to 6 h postmeal . Postpr and ial plasma triacylglycerol ( TG ) and TG-rich lipoprotein ( TRL ) TG apo B48 , and B100 absolute concentrations were significantly lower after FOP than after COP or BLP , while plasma cholesterol was unchanged . Normalizing the results as increments over time 0 eliminated the diet effect on all but plasma TG . Time remained a significant effect for plasma TG , TRL TG , and TRL TC . Finally , only absolute TRL B48 and absolute and incremental plasma TG concentrations displayed significant time-diet interactions . These results suggest that postpr and ial TRL apo B reductions are likely caused by ( n-3 ) fatty acid suppression of both hepatic and intestinal apoB secretion/ synthesis . Altered TRL metabolism , i.e. changes in postpr and ial TG , cholesterol , apo B48 , and increase in LDL particle size , may represent an additional mechanism for the reduced heart disease risk associated with fish [ ( n-3 ) fatty acid ] consumption", "BACKGROUND Plasma lipoproteins may be classified by their apolipoprotein composition . The lipoprotein subclass containing apolipoproteins B and C ( LpB : C ) is considered the most atherogenic . OBJECTIVE We evaluated the acute effects of individual fatty acids on apolipoprotein B ( apo B)-containing lipoproteins in adults with type 2 diabetes ( n = 15 ) . DESIGN We administered 3 meals in a r and omized , double-blind , crossover design . Treatments contained skim milk and 50 g fat from high-oleic acid safflower and canola oils ( monounsaturated fatty acid ; MUFA ) , MUFA + 3.5 g alpha-linolenic acid ( ALA ; MUFA + ALA ) from high-ALA canola oil , or MUFA + 4.0 g both eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ; MUFA + EPA/DHA ) from sardine oil . Apo B , LpB , LpB : C , LpB : E + LpB : C : E , and LpA-II : B : C : D : E were measured at baseline and 2 and 4 h after the meal . Flow-mediated dilation was measured at baseline and 4 h after the meal . RESULTS The treatments significantly increased apo B and LpB postpr and ially ( P postpr and ial change in LpB : C was 23 % lower after MUFA + EPA/DHA than after MUFA ( treatment x time interaction , P + ALA attenuated the increase in LpA-II : B : C : D : E in those with high triacylglycerols ( > /=1.69 mmol/L ) but was the only treatment to significantly increase this particle in those with low triacylglycerols ( treatment x group interaction , P change scores did not reveal the source of the interaction of treatment and time ( P LpB : E + LpB : C : E. Furthermore , the subjects with the largest increases in LpB : C exhibited the largest impairment in endothelial function . CONCLUSIONS The results suggest that unsaturated fatty acids differentially affect concentrations of apo B-containing lipoprotein subclasses . A rise in LpB : C adversely affects endothelial function . Meals containing MUFA + EPA/DHA attenuated the postpr and ial rise in LpB : C and the impairment of endothelial function", "OBJECTIVE Dietary interventions can improve pregnancy outcomes in women with gestational diabetes mellitus ( GDM ) . We compared the effect of a low – glycemic index ( GI ) versus a conventional high-fiber ( HF ) diet on pregnancy outcomes , birth weight z score , and maternal metabolic profile in women at high risk of GDM . RESEARCH DESIGN AND METHODS One hundred thirty-nine women [ mean ( SD ) age 34.7 ( 0.4 ) years and prepregnancy BMI 25.2 ( 0.5 ) kg/m2 ] were r and omly assigned to a low-GI ( LGI ) diet ( n = 72 ; target GI ∼50 ) or a high-fiber , moderate-GI ( HF ) diet ( n = 67 ; target GI ∼60 ) at 14–20 weeks ’ gestation . Diet was assessed by 3-day food records and infant body composition by air-displacement plethysmography , and pregnancy outcomes were assessed from medical records . RESULTS The LGI group achieved a lower GI than the HF group [ mean ( SD ) 50 ( 5 ) vs. 58 ( 5 ) ; P in glycosylated hemoglobin , fructosamine , or lipids at 36 weeks or differences in birth weight [ LGI 3.4 ( 0.4 ) kg vs. HF 3.4 ( 0.5 ) kg ; P = 0.514 ] , birth weight z score [ LGI 0.31 ( 0.90 ) vs. HF 0.24 ( 1.07 ) ; P = 0.697 ] , ponderal index [ LGI 2.71 ( 0.22 ) vs. HF 2.69 ( 0.23 ) kg/m3 ; P = 0.672 ] , birth weight centile [ LGI 46.2 ( 25.4 ) vs. HF 41.8 ( 25.6 ) ; P = 0.330 ] , % fat mass [ LGI 10 ( 4 ) vs. HF 10 ( 4 ) ; P = 0.789 ] , or incidence of GDM . CONCLUSIONS In intensively monitored women at risk for GDM , a low-GI diet and a healthy diet produce similar pregnancy outcomes", "Background Omega–3 fatty acids prevent cardiovascular disease ( CVD ) events in patients with myocardial infa rct ion or heart failure . Benefits in patients without overt CVD have not been demonstrated , though most studies did not use treatment doses ( 3.36 g ) of omega-3 fatty acids . Arterial stiffness measured by pulse wave velocity ( PWV ) predicts CVD events independent of st and ard risk factors . However , no therapy has been shown to reduce PWV in a blood pressure-independent manner . We assessed the effects of esterified omega–3 fatty acids on PWV and serum markers of inflammation among patients with hypertension . Design and methods We performed a prospect i ve , r and omized ; double-blinded pilot study of omega-3 fatty acids among 62 patients in an urban , safety net hospital . Patients received 3.36 g of omega–3 fatty acids vs. matched placebo daily for 3-months . The principal outcome measure was change in brachial-ankle PWV . Serum inflammatory markers associated with CVD risk were also assessed . Results The majority ( 71 % ) were of Latino ethnicity . After 3-months , mean change in arterial PWV among omega-3 and placebo groups was −97 cm/s vs. −33 cm/s respectively ( p = 0.36 for difference , after multivariate adjustment for baseline age , systolic blood pressure , and serum adiponectin ) . Non-significant reductions in lipoprotein-associated phospholipase A2 ( LpPLA2 ) mass and high sensitivity C-reactive protein ( hsCRP ) relative to placebo were also observed ( p = 0.08 , and 0.21 , respectively ) . Conclusion High-dose omega-3 fatty acids did not reduce arterial PWV or markers of inflammation among patients within a Latino-predominant population with hypertension . Clinical trial registration NCT00935766 , registered July 8 2009", "OBJECTIVE To our knowledge , no reports are available indicating the effects of the dietary approaches to stop hypertension ( DASH ) eating plan on insulin resistance , inflammation , and oxidative stress among pregnant women with gestational diabetes mellitus ( GDM ) . This study was design ed to investigate the effects of the DASH diet on insulin resistance , serum high-sensitivity C-reactive protein ( hs-CRP ) and biomarkers of oxidative stress among pregnant women with GDM . METHODS This r and omized controlled clinical trial was performed with 32 pregnant women diagnosed with GDM at 24 to 28 wk gestation . Participants were r and omly assigned to consume either the control ( n = 16 ) or DASH diet ( n = 16 ) for 4 wk . The DASH diet was rich in fruits , vegetables , whole grains , and low-fat dairy products and was low in saturated fats , total fats , cholesterol , refined grains , and sweets , with a total of 2400 mg/d of sodium . The control diet contained 40 % to 55 % of its energy as carbohydrates , 10 % to 20 % as proteins , and 25 % to 30 % as total fats . Fasting blood sample s were taken at baseline and after 4 wk of intervention to measure fasting plasma glucose ( FPG ) , serum insulin , and hs-CRP , homeostasis model of assessment -insulin resistance ( HOMA-IR ) , plasma total antioxidant capacity ( TAC ) , and total glutathione levels ( GSH ) . RESULTS Consumption of the DASH diet compared with the control diet result ed in decreased FPG ( -7.62 versus 3.68 mg/dL ; P = 0.02 ) , serum insulin levels ( -2.62 versus 4.32 μIU/mL , P = 0.03 ) , and HOMA-IR score ( -0.8 versus 1.1 ; P = 0.03 ) . Increased concentrations of plasma TAC ( 45.2 versus -159.2 mmol/L ; P of serum hs-CRP levels between the two diets . Within-group comparisons revealed significant reductions in plasma TAC and GSH levels in the control diet , while a significant increase in these biomarkers in the DASH diet . CONCLUSION Consumption of the DASH diet in pregnant women with GDM had beneficial effects on FPG , serum insulin levels , HOMA-IR score , plasma TAC , and total GSH levels . The effects of this dietary pattern on pregnancy outcomes need to be investigated in future studies", "BackgorundMixed hyperlipidemia is common in patients with diabetes . Statins , the choice drugs , are effective at reducing lipoproteins that contain apolipoprotein B100 , but they fail to exert good control over intestinal lipoproteins , which have an atherogenic potential . We describe the effect of prescription omega 3 fatty acids on the intestinal lipoproteins in patients with type 2 diabetes who were already receiving fluvastatin 80 mg per day . Methods Patients with type 2 diabetes and mixed hyperlipidemia were recruited . Fasting lipid profile was taken when patients were treated with diet , diet plus 80 mg of fluvastatin and diet plus fluvastatin 80 mg and 4 g of prescription omega 3 fatty acids . The intestinal lipoproteins were quantified by the fasting concentration of apolipoprotein B48 using a commercial ELISA . Results The addition of 4 g of prescription omega 3 was followed by significant reductions in the levels of triglycerides , VLDL triglycerides and the triglyceride/HDL cholesterol ratio , and an increase in HDL cholesterol ( P Fluvastatin induced a reduction of 26 % in B100 ( P omega 3 fatty acids enhanced this reduction to 32 % in B100 ( NS ) and up to 36 % in B48 ( P < 0.05 ) . Conclusion Our preliminary findings therefore suggest an additional benefit on postpr and ial atherogenic particles when omega 3 fatty acids are added to st and ard treatment with fluvastatin", "INTRODUCTION Consumption of omega-3 fatty acids can alter the inflammatory response in diabetic patients . This study aim ed to determine the effects of omega-3 fatty acid supplementation on the serum levels of C-reactive protein ( CRP ) , interleukin (IL)-2 and tumour necrosis factor-alpha ( TNF-α ) in type 2 diabetes mellitus patients . METHODS A r and omised , double-blind , placebo-controlled clinical trial was conducted on 84 subjects aged 45 - 85 years with at least a two-year history of type 2 diabetes mellitus . Participants were r and omly assigned to the treatment or control group . Each subject in the treatment group received three omega-3 capsules per day ( eicosapentaenoic acid 1,548 mg ; docosahexaenoic acid 828 mg ; other omega-3 fatty acids 338 mg ) , while each subject in the control group received three placebo capsules ( sunflower oil 2,100 mg ) for a period of eight weeks . At the beginning of the study and post intervention , fasting blood sample s were taken and serum concentrations of IL-2 , TNF-α and CRP were assessed and compared . RESULTS Serum IL-2 and TNF-α levels were significantly reduced in the treatment group compared to the controls ( p in serum CRP levels . CONCLUSION Short-term omega-3 fatty acid supplementation ( 3 g/day for eight weeks ) can decrease the serum levels of TNF-α and IL-2 in diabetic patients , with no change in CRP levels . Consumption of omega-3 fatty acid supplements is highly recommended to alleviate inflammation caused by type 2 diabetes mellitus", "Dietary n-3 fatty acids ( FAs ) found in fish oils markedly lower plasma triglyceride ( TG ) and very low density lipoprotein ( VLDL ) levels in both normal and hypertriglyceridemic subjects . The present study examined the mechanism of this effect . Ten subjects with widely different plasma triglyceride levels ( 82 to 1002 mg/dl ) were fed metabolically controlled diets containing 20 % fat . The control diet contained a blend of cocoa butter and peanut oil ( P/S = 0.8 ) . The test diet contained fish oil ( P/S = 1.1 ) and provided 10 - 17 g of n-3 FAs per day ( depending on calorie intake ) . After 3 to 5 weeks of each diet , the kinetics of VLDL-TG were determined over a 48-h period after the injection of [3H]glycerol . The fish oil diet reduced the VLDL-TG synthetic rate from 23 + /- 14.3 ( mean + /- SD ) to 12.6 + /- 7.5 mg/h per kg ideal weight ( P less than 0.005 ) and increased the fractional catabolic rate ( FCR ) for VLDL-TG from 0.23 + /- 0.12 to 0.38 + /- 0.16 h -1 ( P less than 0.005 ) . At the same time , there was a 66 % reduction of plasma triglyceride levels , result ing largely from a 78 % decrease in VLDL-TG levels ( 398 + /- 317 to 87 + /- 77 mg/dl ; P less than 0.005 ) . There was a strong correlation ( r = 0.83 ; P less than 0.01 ) between the change in synthetic rates and pool sizes , but there was no correlation ( r = 0.24 ; NS ) between changes in FCRs and pool sizes . The VLDL cholesterol : triglyceride ratio increased during the n-3 diet suggesting that smaller VLDL particles were present . These particles would be expected to leave the VLDL fraction more rapidly than larger particles producing a higher FCR . We conclude that the hypotriglyceridemic effect of fish oil appears to be caused primarily by an inhibition of very low density lipoprotein-triglyceride synthesis , but an additional , independent effect upon VLDL catabolism can not be ruled out", "Objectives N-3 fatty acids reduce the risks of cardiovascular morbidity and mortality . Administration of N-3 fatty acids to patients treated with statins may potentiate the treatment effects . We examined the operating mechanisms underlying such a combination . Methods Thirty-two hypercholesterolemic patients aged 30–70 years with hypercholesterolemia controlled by statins , received sequential treatments with placebo followed by 1.9 g/day of N-3 fatty acids for 23 weeks . Scheduled clinical visits included physical examination , 24-h blood pressure measurement , endothelial function evaluated by pulse wave analysis , analyses for platelet function , inflammation markers [ interleukin (IL)-6 , plasminogen activator inhibitor-1 ( PAI-1 ) ] and oxidative stress parameters ( STAT-8-Isoprostane ) were undertaken at baseline , after placebo treatment , and after 6 and 20 weeks of N-3 fatty acid intake . Results Platelets functions were significantly inhibited , whereas endothelial function parameters were unaltered . IL-6 significantly decreased whereas PAI-1 and STAT-8-Isoprostane levels remained unaffected . Daytime blood pressure significantly decreased ; however , nighttime pressure and heart rate remained unchanged . No evidence of lipid-profile improvement was observed following combined treatment with statins and N-3 fatty acids . Conclusions In hypercholesterolemic patients , combination of statins and N-3 fatty acid inhibits platelet aggregation , alters inflammatory status , and positively affects daytime blood pressure . Close long-term follow-up might reveal additional beneficial effects of N-3 fatty acids in this patient population", "BACKGROUND Patients with elevated serum triglyceride ( TG ) levels often have elevations in non-high-density lipoprotein cholesterol ( non-HDL-C ) levels as well . The National Cholesterol Education Program Adult Treatment Panel III ( NCEP ATP III ) has identified non-HDL-C as a secondary therapeutic target in these patients , but treatment goals may not be reached with statin monotherapy alone . OBJECTIVE This study evaluated the effects on non-HDL-C and other variables of adding prescription omega-3-acid ethyl esters ( P-OM3 ; Lovaza , formerly Omacor [ Reliant Pharmaceuticals , Inc. , Liberty Corner , New Jersey ] ) to stable statin therapy in patients with persistent hypertriglyceridemia . METHODS This was a multicenter , r and omized , double-blind , placebo-controlled , parallel-group study in adults who had received > or = 8 weeks of stable statin therapy and had mean fasting TG levels > or = 200 and low-density lipoprotein cholesterol levels The study regimen consisted of an initial 8 weeks of open-label simvastatin 40 mg/d and dietary counseling , followed by 8 weeks of r and omized treatment with double-blind P-OM3 4 g/d plus simvastatin 40 mg/d or placebo plus simvastatin 40 mg/d . The main outcome measure was the percent change in non-HDL-C from baseline to the end of treatment . RESULTS The evaluable population included 254 patients , of whom 57.5 % ( 146 ) were male and 95.7 % ( 243 ) were white . The mean ( SD ) age of the population was 59.8 ( 10.4 ) years , and the mean weight was 92.0 ( 19.6 ) kg . At the end of treatment , the median percent change in non-HDL-C was significantly greater with P-OM3 plus simvastatin compared with placebo plus simvastatin ( -9.0 % vs -2.2 % , respectively ; P P-OM3 plus simvastatin was associated with significant reductions in TG ( 29.5 % vs 6.3 % ) and very-low-density lipoprotein cholesterol ( 27.5 % vs 7.2 % ) , a significant increase in high-density lipoprotein cholesterol ( HDL-C ) ( 3.4 % vs -1.2 % ) , and a significant reduction in the total cholesterol : HDL-C ratio ( 9.6 % vs 0.7 % ) ( all , P Adverse events ( AEs ) reported by > or= 1 % of patients in the P-OM3 group that occurred with a higher frequency than in the group that received simvastatin alone were nasopharyngitis ( 4 [ 3.3 % ] ) , upper respiratory tract infection ( 4 [ 3.3 % ] ) , diarrhea ( 3 [ 2.5 % ] ) , and dyspepsia ( 3 [ 2.5 % ] ) . There was no significant difference in the frequency of AEs between groups . No serious AEs were considered treatment related . CONCLUSION In these adult , mainly white patients with persistent hypertriglyceridemia , P-OM3 plus simvastatin and dietary counseling improved non-HDL-C and other lipid and lipoprotein parameters to a greater extent than simvastatin alone", "Background . Women with polycystic ovary syndrome ( PCOS ) are at a high risk to develop Gestational Diabetes mellitus ( GDM ) . We hypothesized that metformin due to its metabolic , endocrine , vascular , and anti-inflammatory effects may reduce the incidence of GDM in PCOS women . Patient and method . We carried out a prospect i ve cohort study to determine the beneficial effects of metformin on PCOS patients during pregnancy . Three-hundred and sixty non-diabetic PCOS patients were included who were conceived on metformin by different treatment modalities . Two-hundred pregnant women continued on metformin at a dose of 1000–2000 mg daily throughout pregnancy ( study group ) and 160 women discontinued metformin use at the time of conception ( control group ) . Results . There is a statistically significant reduction in the incidence of GDM in favor of metformin group ( OR : 0.17 , 95 % CI : 0.07–0.37 ) . There is a statistically significant reduction in the incidence of pre-eclampsia in favor of metformin group ( OR : 0.35 , 95 % CI : 0.13–0.94 ) . Conclusion . Metformin is a promising medication for the prevention or reduction of the incidence of GDM and pre-eclampsia in PCOS women", "BACKGROUND Marine fish oils improve vascular function , but the mechanism of benefit is unclear . We conducted a study to examine the effects of fish oils given to hypercholesterolemic patients on small artery function in vitro . METHODS AND RESULTS In a r and omized , double-blind , placebo-controlled trial , subcutaneous gluteal fat biopsies were taken from 16 hypercholesterolemic patients ( serum total cholesterol , 7.97+/-0.16 mmol/L [ mean+/-SEM ] ) and 12 age- and sex-matched control subjects ( mean cholesterol , 5.11+/-0.34 mmol/L ) . Small arteries were mounted on a wire myograph for isometric tension experiments . Patients and control subjects were r and omized to receive fish oil ( Maxepa 5 capsules BID ) or placebo for 3 months . A second biopsy was taken and the studies were repeated . Relaxation to acetylcholine was significantly improved in the hypercholesterolemic group given Maxepa but not in the placebo group ( mean maximum relaxation before and after , 48+/-6.2 % and 68.83+/-2.19 % , P=.0054 ) . The dysfunction was not restored to control values ( 84.3+/-5.2 % , P=.0002 ) . There was also a smaller but significant impairment in endothelium-independent relaxation provoked by sodium nitroprusside ( P eicosapentanoic acid ( n=3 ) in red cell membrane and improvement in relaxation in the hypercholesterolemic group given fish oils was seen ( r=.781 , P fish oil significantly improved endothelial function in peripheral small arteries in hypercholesterolemia patients . This may provide a mechanism for the beneficial effects of these fatty acids in coronary heart disease", "Background Little is known about the effect of fish consumption on gene expression of inflammation-related genes in immune cells in coronary heart disease ( CHD ) . Aim of the study We sought to evaluate the effect of a fatty fish ( FF ) or a lean fish ( LF ) diet on the modulation of inflammatory and endothelial function-related genes in peripheral blood mononuclear cells ( P BMC s ) of subjects with CHD , and its association with serum fatty acid ( FA ) profile and lipid metabolic compounds . Methods Data from 27 patients r and omized into an 8-week FF ( n = 10 ; mean ± SD : 4.3 ± 0.4 portions of fish per week ) , LF ( n = 11 ; 4.7 ± 1.1 portions of fish per week ) , or control diet ( n = 6 ; 0.6 ± 0.4 portions of fish per week ) were analyzed . The mRNA expression was measured using real-time PCR . Results The effect of the intervention on the mRNA expression of the genes studied did not differ among groups . In the FF group , however , the decrease in arachidonic acid to eicosapentaenoic acid ( AA : EPA ) ratio in cholesterol ester and phospholipid fractions strongly correlated with the change in IL1B mRNA levels ( rs = 0.60 , P = 0.06 and rs = 0.86 , P = 0.002 , respectively ) . In the LF group , the decrease in palmitic acid and total saturated FAs in cholesterol esters correlated with the change in intercellular cell adhesion molecule-1 ( ICAM1 ) expression ( rs = 0.64 , P = 0.04 for both ) . Circulating levels of soluble ICAM-1 decreased only in the LF group ( P the expression of inflammatory and endothelial function-related genes in P BMC s of patients with CHD . However , the decrease in AA : EPA ratio in serum lipids in the FF group may induce an anti-inflammatory response at mRNA levels in P BMC s. A LF diet might benefit endothelial function , possibly mediated by the changes in serum FA composition", "Objective —The association between serum antibody levels to major periodontal pathogens and coronary heart disease ( CHD ) was analyzed in a prospect i ve population -based study . Methods and Results —The population comprised 1023 men ( aged 46 to 64 years ) in the Kuopio Ischemic Heart Disease Study . The subjects with CHD at baseline ( n=113 ) were more often seropositive for Porphyromonas gingivalis IgA ( 38.9 % versus 28.5 % , P=0.021 ) and IgG ( 60.2 % versus 46.7 % , P=0.007 ) than those without CHD . During the 10-year follow-up , 109 men free from CHD at baseline experienced an acute myocardial infa rct ion or CHD death . The men with an end point were more often seropositive for Actinobacillus actinomycetemcomitans IgA ( 15.5 % versus 10.2 % , P=0.019 ) than those who remained healthy . In the highest tertile of A. actinomycetemcomitans IgA-antibodies compared with the lowest one , the relative risk ( RR ) for an end point adjusted for CHD risk factors was 2.0 ( 95 % confidence interval [ CI ] , 1.2 to 3.3 ) . In the Porphyromonas gingivalis IgA-antibody tertiles , the highest RR of 2.1 ( 1.3 to 3.4 ) was observed in the second tertile . All antibody levels correlated positively with the carotid artery intima-media thickness . Conclusions —High-serum antibody levels to major periodontal pathogens are associated with sub clinical , prevalent , and future incidence of CHD . Periodontal pathogens or host response against them may contribute to the pathogenesis of CHD", "BACKGROUND AND OBJECTIVES Epidemiological and interventional studies suggest that a high dietary intake of n-3 polyunsaturated fatty acids may confer a protective effect against atherosclerotic disease and reduce serum triglycerides levels . The aim of our study was to investigate the effectivity on triglyceride levels and inflammatory markers of a concentrated of n-3 fatty acids in patients with type 2 diabetes mellitus and hypertriglyceridaemia . SUBJECTS A total of 30 patients ( 16 males and 14 females ) with diabetes mellitus type 2 and hypertriglyceridemia ( > 200 mg/dl ) were included in the study . Patients received two capsules of eicosapentaenoic 465 mg and docosahexanoic 375 mg daily for 12 weeks . RESULTS Triglycerides levels and non HDL-cholesterol decreased ( 326 + /- 113.5 vs. 216.4 + /- 57 mg/dl ; p HDL-cholesterol levels increased ( 39.6 + /- 10.7 vs. 46.4 + /- 8.7 mg/dl ; p C reactive protein decreased ( 5.98 + /- 3.9 vs. 3.9 + /- 1.6 mg/dl ; p TNF-alpha levels decreased ( 16.24 + /- 5.5 vs. 13.3 + /- 5.8 pg/dl ; p IL-6 levels . In conclusion , an n-3 polyunsaturated intervention improved lipid profile and inflammatory markers in patients with diabetes mellitus type 2 and hypertriglyceridaemia", "Accelerated coronary artery disease is the most serious obstacle to long-term survival in cardiac transplant recipients . Lipid abnormalities are found frequently in these patients , and there is growing evidence that even minimally increased levels of cholesterol and triglycerides contribute to the development of accelerated coronary artery disease . However , the optimal lipid-lowering therapy after cardiac transplantation has not been defined . In an open , r and omized study , the efficacy and safety of bezafibrate ( 400 mg/day ) and fish oil ( Maxepa ) ( 10 g/day ) for 3 months were compared in 87 cardiac transplant recipients with serum total cholesterol > 6.5 or triglycerides > 2.8 mmol/liter , or both . After 1 month , bezafibrate reduced total cholesterol by 13 % , low-density lipoprotein cholesterol by 20 % and apolipoprotein B by 13 % . It also increased apolipoprotein A1 and high-density lipoprotein cholesterol by 12 and 20 % , respectively , and significantly reduced fibrinogen at 3 months . Maxepa had no significant effect on these variables , but was as effective as bezafibrate in reducing triglycerides ( 36 and 31 % , respectively ) . Both drugs increased lipoprotein ( a ) to a similar extent , and bezafibrate significantly increased serum creatinine . These results suggest that bezafibrate has better lipid- , apolipoprotein- and hemostatic modifying properties than does Maxepa , but its potentially adverse effect on renal function needs further investigation", "BACKGROUND N-3 polyunsaturated fatty acids ( PUFAs ) from oily fish protect against death from cardiovascular disease . We aim ed to assess the hypothesis that incorporation of n-3 and n-6 PUFAs into advanced atherosclerotic plaques increases and decreases plaque stability , respectively . METHODS We did a r and omised controlled trial of patients awaiting carotid endarterectomy . We r and omly allocated patients control , sunflower oil ( n-6 ) , or fish-oil ( n-3 ) capsules until surgery . Primary outcome was plaque morphology indicative of stability or instability , and outcome measures were concentrations of EPA , DHA , and linoleic acid in carotid plaques ; plaque morphology ; and presence of macrophages in plaques . Analysis was per protocol . FINDINGS 188 patients were enrolled and r and omised ; 18 withdrew and eight were excluded . Duration of oil treatment was 7 - 189 days ( median 42 ) and did not differ between groups . The proportions of EPA and DHA were higher in carotid plaque fractions in patients receiving fish oil compared with those receiving control ( absolute difference 0.5 [ 95 % CI 0.3 - 0.7 ] , 0.4 [ 0.1 - 0.6 ] , and 0.2 [ 0.1 - 0.4 ] g/100 g total fatty acids for EPA ; and 0.3 [ 0.0 - 0.8 ] , 0.4 [ 0.1 - 0.7 ] , and 0.3 [ 0.1 - 0.6 ] g/100 g total fatty acids for DHA ; in plaque phospholipids , cholesteryl esters , and triacylglycerols , respectively ) . Sunflower oil had little effect on the fatty acid composition of lipid fractions . Fewer plaques from patients being treated with fish oil had thin fibrous caps and signs of inflammation and more plaques had thick fibrous caps and no signs of inflammation , compared with plaques in patients in the control and sunflower oil groups ( odds ratio 0.52 [ 95 % CI 0.24 - 0.89 ] and 1.19 [ 1.02 - 1.57 ] vs control ; 0.49 [ 0.23 - 0.90 ] and 1.16 [ 1.01 - 1.53 ] vs sunflower oil ) . The number of macrophages in plaques from patients receiving fish oil was lower than in the other two groups . Carotid plaque morphology and infiltration by macrophages did not differ between control and sunflower oil groups . INTERPRETATION Atherosclerotic plaques readily incorporate n-3 PUFAs from fish-oil supplementation , inducing changes that can enhance stability of atherosclerotic plaques . By contrast , increased consumption of n-6 PUFAs does not affect carotid plaque fatty-acid composition or stability over the time course studied here . Stability of plaques could explain reductions in non-fatal and fatal cardiovascular events associated with increased n-3 PUFA intake", "BACKGROUND Fish oils have been shown to reduce production of tumor necrosis factor-alpha ( TNF-alpha ) in healthy subjects . We sought to evaluate the effects of fish oils on pro-inflammatory cytokines and body weight in patients with advanced heart failure . METHODS Fourteen patients ( New York Heart Association [ NYHA ] Class III to IV heart failure ) were r and omized in a double-blinded trial to active therapy with 8 g of n-3 fatty acids ( Group A , n = 7 ) or placebo ( Group B , n = 7 ) for 18 weeks . TNF-alpha and interleukin-1 ( IL-1 ) production were measured by radioimmunoassay after endotoxin stimulation of peripheral blood mononuclear cells . RESULTS Placebo-treated patients had a 44 % increase in TNF-alpha ( from 1.28 to 1.84 pg/ml ; p = 0.07 ) but no significant change in IL-1 ( from 0.68 to 0.78 pg/ml ) production . n-3 fatty acids result ed in a 59 % reduction in TNF-alpha ( from 1.64 to 0.68 pg/ml ; p = 0.02 ) and 39 % decrease in IL-1 ( from 1.98 to 1.21 pg/ml ; p = 0.09 ) production . There was an inverse correlation between change in TNF-alpha production and change in percent body fat ( r = -0.6 ; p = 0.02 ) . CONCLUSIONS Fish oils decrease TNF-alpha production in heart failure and improve body weight . Fish oil therapy may represent a novel therapeutic approach in late-stage heart failure characterized by cardiac cachexia", "OBJECTIVE To determine the effects of n-3 PUFAs supplementation on plasma indices of coagulation ( fibrinogen ) , fibrin D-Dimer ( an index of thrombogenesis and fibrin turnover ) , endothelial damage/dysfunction ( von Willebr and factor ( vWf ) ) , platelet activation ( soluble P-selectin ( sP-sel ) ) and inflammation ( interleukin-6 , IL-6 ) in patients following acute myocardial infa rct ion . METHODS Open-labelled r and omised controlled trial . Seventy-seven post-myocardial infa rct ion ( MI ) patients stabilized on st and ard secondary prevention therapy were r and omised either to 3 months ' treatment with Omacor 1 g/day ( n=37 ) or ' usual care ' control ( n=40 ) . Plasma levels of fibrinogen , D-Dimer , vWf , sP-sel , IL-6 and plasma viscosity at baseline and after 3 months were determined . RESULTS At baseline , there were no significant differences between the groups in all research indices , except vWf levels were higher in patients allocated to Omacor supplementation . After 3 months , there were no significant changes in the levels of any research indices in either the Omacor supplemented or the ' usual care ' control patients when compared to baseline . Patients who received Omacor experienced a fall in total cholesterol ( p=0.019 ) , total/HDL-cholesterol ratio ( p=0.009 ) and LDL-cholesterol ( p=0.023 ) . However , the relative changes in plasma lipids and lipoproteins did not differ between the two groups . CONCLUSIONS Three-month supplementation of Omacor at 1 g per day in post-MI patients is not associated with an improvement in the levels of peripheral indices of coagulation potential , endothelial function , platelet reactivity and inflammation", "AIM To test whether the use of collagen matrix seal ( CMS ) results in similar hard and soft tissue remodelling to that with collagen sponge ( CS ) used as barriers 4 months following alveolar ridge preservation ( ARP ) , in combination with freeze-dried bone allograft ( FDBA ) . MATERIAL S AND METHODS Twenty-eight patients were r and omly assigned to the two groups . Clinical and radiographic measurements were recorded with the same stent at baseline and 4 months for st and ardization . The flapless technique following a traumatic extraction was used for the two types of barriers . RESULTS All patients completed the study , 14 in the CMS group and 14 in the CS group . Reduction in coronal ridge width ( 1.21 mm-14.91 % CMS and 1.47 mm-20.40 % CS ) and vertical buccal bone resorption ( 0.30 mm CMS and 0.79 mm CS ) were not significantly different . A slight increase in buccal gingival thickness at the coronal part was observed in both groups ( 0.9 mm CMS and 0.5 mm CS ) . CONCLUSIONS Collagen matrix seal and CS , when combined with FDBA , significantly minimized ridge resorption in all dimensions and maintained buccal soft tissue thickness in sockets with a buccal plate loss of < 2 mm in comparison to previously reported findings recorded after tooth extraction without ARP", "n-3 fatty acids reduce the risk of cardiovascular disease via a number of possible mechanisms . Despite this , there has been concern that these fatty acids may increase lipid peroxidation . The data in vivo are inconclusive , due in part to limitations in the method ologies . In this regard , the measurement of F2-isoprostanes provides a reliable assessment of in vivo lipid peroxidation and oxidant stress . This study aim ed to assess the effects of supplementation with purified eicosapentaenoic acid ( EPA ) or docosahexaenoic acid ( DHA ) , the two major n-3 fatty acids , on urinary F2-isoprostanes and markers of inflammation , in type 2 diabetic patients . In a double-blind , placebo controlled trial of parallel design , 59 nonsmoking , treated-hypertensive , type 2 diabetic subjects , were r and omized to 4 g daily of purified EPA , DHA , or olive oil for 6 weeks , while maintaining their usual diet . F2-isoprostanes , measured using gas chromatography-mass spectrometry in 24 h urines and C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) and tumor necrosis factor-alpha ( TNF-alpha ) , were measured before and after intervention . Thirty-nine men and 12 women aged 61.2 + /- 1.2 years , with body mass index ( BMI ) , 29.5 + /- 0.5 kg/m2 ; 24 h blood pressure , 138/73 mmHg ; HbA1c , 7.3 + /- 0.1 % and fasting glucose , 7.9 + /- 0.2 mmol/l completed the intervention . Baseline urinary F2-isoprostanes were positively associated with HbA1c ( p=.011 ) and fasting glucose ( p=.032 ) . Relative to the olive oil group , postintervention urinary F2-isoprostanes were decreased 19 % by EPA ( p=.017 ) and 20 % by DHA ( p=.014 ) . There were no significant changes in CRP , IL-6 , and TNF-alpha following EPA or DHA supplementation . In regression analysis , Delta F2-isoprostanes were positively associated with Delta HbA1c ( p=.007 ) independent of treatment group ; and with Delta TNF-alpha ( p=.034 ) independent of age , gender , BMI , and treatment group . There were no associations with Delta CRP or Delta IL-6 . This study is the first report demonstrating that either EPA or DHA reduce in vivo oxidant stress without changing markers of inflammation , in treated hypertensive , type 2 diabetic subjects", "The aim of this study was to evaluate the effects of a fish oil preparation ( MaxEPA ) on hemostatic function and fasting lipid and glucose levels in non-insulin-dependent diabetic ( NIDDM ) subjects . Eighty NIDDM out patients aged 55.9 yr ( mean SD 11.5 yr ) participated in a prospect i ve double-blind placebo-controlled study of MaxEPA capsules ( 10 g/day ) or olive oil ( control ) treatment over 6 wk . Patients received either MaxEPA or olive oil in addition to preexisting therapy . Metabolic and hemostatic variables were measured before treatment and after 3 and 6 wk . Platelet membrane eicosapentaenoic acid ( EPA ) content increased in the treatment group ( P total triglycerides ( P total cholesterol ( P = 0.7 ) compared with control treatment . Fasting plasma glucose increased after 3 wk ( P = 0.01 ) but not after 6 wk ( P = 0.17 ) treatment with MaxEPA . Spontaneous platelet aggregation in whole blood fell in the MaxEPA group ( P agonist-induced platelet aggregation , thromboxane generation in platelet-rich plasma , or plasma P-thromboglobulin and platelet factor IV levels . An increase in clotting factor VII ( P = 0.02 ) , without changes in fibrinogen or factor X levels , occurred in the MaxEPA group . Similar reductions in blood pressure were observed in both groups . Dietary supplementation with MaxEPA capsules ( 10 g/day ) in NIDDM subjects is associated with improvement in hypertriglyceridemia but with deleterious effects in factor VII and blood glucose levels . Most indices of platelet function are unaffected by this therapy", "Aims To assess the bone dimensional changes after extraction and alveolar ridge preservation ( ARP ) using primary coverage ( closed flap technique , CFT ) or healing by secondary intention ( open flap technique , OFT ) . Material s and Methods Ten patients ( split mouth design ) were planned for extraction and ARP . All sites received ARP with freeze-dried bone allograft ( FDBA ) and nonresorbable membrane after extraction . Clinical st and ardized measurements were used to assess the dimensional alterations of the alveolar ridge . Results All patients completed the study , and a total of 20 sites were r and omized to CFT or OFT group . Center height ( mean difference of 8.1 mm , SD = 1.9 CFT , and 7.5 mm , SD= 1.8 OFT ) and buccal height ( mean difference of 0.8 mm , SD = 1.0 CFT , and 0.3 mm , SD= 1.1 OFT ) were significantly different within the same group . However , there was no statistically significant difference between groups . In the OFT group , the keratinized tissue width was higher and the pain VAS scores at 24 hours were lower compared with the CFT ( p = 0.004 and p = 0.006 , respectively ) . Conclusions Leaving the flap open did not have any effects on the dimensional changes of bone height or width . However , there was a wider b and of keratinized tissue and less pain with the CFT compared with the OFT . The study protocol was registered at Clinical Trials.gov , Identifier NCT03136913" ]

[ "Purpose . To compare erectile function ( EF ) recovery of patients treated by early penile rehabilitation therapy ( PRT ) with sildenafil and with control group . Method . Forty men treated by bilateral nerve sparing radical prostatectomy ( NSRP ) and with a normal pre-operative EF were enrolled . Fourteen days after surgery , they were r and omised to a flexible-dose sildenafil group and to a control group . The International Index of Erectile Function ( IIEF ) question naire was completed before surgery and at 3 , 6 , 12 and 24 weeks after NSRP . Results . In the group treated , the mean IIEF score before surgery was 26.2 and 14.1 , 16.2 , 22.5 and 25.2 at 3 , 6 , 12 and 24 weeks after NSRP , respectively . In the control group , the respective scores were 26.5 and 12.4 , 15.8 , 15.3 and 17.4 . There was a significant difference in IIEF mean score ( 25 ± 6 vs. 17 ± 9 , p the potency rate ( 87 % vs. 56 % ) between the groups at 24 weeks after NSRP . The percentage of patients who were capable of having medication-unassisted intercourse was 54 % vs. 21 % ; 34 % vs. 18 % of patients had a normal EF with 72 % vs. 32 % of responders to sildenafil . Conclusions . PRT with PDE-5 inhibitors should be offered early after RP to allow the recovery of EF ", "Four weeks after bilateral nerve-sparing radical retropubic prostatectomy , men with normal erectile function before surgery were r and omized to double-blind sildenafil ( 50 or 100 mg ) or placebo nightly for 36 weeks , followed by an 8-week drug-free period before assessment of erectile function . Enrollment was prematurely ceased and only 76 men completed because , assuming a placebo response rate similar to the published literature ( for example , 34 % in meta- analysis ) , the 25 % response at blinded interim review suggested a lack of treatment effect . On the contrary , spontaneous erectile function ( a combined score of ⩾8 for questions 3 and 4 of the International Index of Erectile Function and a positive response to ‘ Were erections good enough for satisfactory sexual activity ? ’ ) occurred in only 4 % of the placebo group ( n=1 of 25 ) versus 27 % ( n=14 of 51 , P=0.0156 , Fisher 's exact test ) of the sildenafil group . Nightly sildenafil administration for 36 weeks after surgery markedly increased the return of normal spontaneous erections", "BACKGROUND The potential rehabilitative and protective effect of phosphodiesterase type 5 inhibitors ( PDE5-Is ) on penile function after nerve-sparing radical prostatectomy ( NSRP ) remains unclear . OBJECTIVE The primary objective was to compare the efficacy of tadalafil 5 mg once daily and tadalafil 20 mg on dem and versus placebo taken over 9 mo in improving unassisted erectile function ( EF ) following NSRP , as measured by the proportion of patients achieving an International Index of Erectile Function-Erectile Function domain ( IIEF-EF ) score ≥ 22 after 6-wk drug-free washout ( DFW ) . Secondary measures included IIEF-EF , Sexual Encounter Profile question 3 ( SEP-3 ) , and penile length . DESIGN , SETTING , AND PARTICIPANTS R and omised , double-blind , double-dummy , placebo-controlled trial in men ≤ 68 yr of age with adenocarcinoma of the prostate ( Gleason ≤ 7 ) and normal preoperative EF who underwent NSRP at 50 centres from nine European countries and Canada . INTERVENTIONS 1:1:1 r and omisation to 9 mo of treatment with tadalafil 5 mg once daily , tadalafil 20 mg on dem and , or placebo followed by a 6-wk DFW and 3-mo open-label tadalafil once daily ( all patients ) . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Logistic regression , mixed-effects model for repeated measures , and analysis of covariance , adjusting for treatment , age , and country , were applied to IIEF-EF scores ≥ 22 , SEP-3 , and penile length . RESULTS AND LIMITATIONS Four hundred twenty-three patients were r and omised to tadalafil once daily ( n=139 ) , on dem and ( n=143 ) , and placebo ( n=141 ) . The mean age was 57.9 yr of age ( st and ard deviation : 5.58 yr ) ; 20.9 % , 16.9 % , and 19.1 % of patients in the tadalafil once daily , on dem and , and placebo groups , respectively , achieved IIEF EF scores ≥ 22 after DFW ; odds ratios for tadalafil once daily and on dem and versus placebo were 1.1 ( 95 % confidence interval [ CI ] , 0.6 - 2.1 ; p=0.675 ) and 0.9 ( 95 % CI , 0.5 - 1.7 ; p=0.704 ) . At the end of double-blind treatment ( EDT ) , least squares ( LS ) mean IIEF-EF score improvement significantly exceeded the minimally clinical ly important difference ( MCID : ΔIIEF-EF ≥ 4 ) in both tadalafil groups ; for SEP-3 ( MCID ≥ 23 % ) , this was the case for tadalafil once daily only . Treatment effects versus placebo were significant for tadalafil once daily only ( IIEF-EF : p=0.016 ; SEP-3 : p=0.019 ) . In all groups , IIEF-EF and SEP-3 decreased during DFW but continued to improve during open-label treatment . At month 9 ( EDT ) , penile length loss was significantly reduced versus placebo in the tadalafil once daily group only ( LS mean difference 4.1 mm ; 95 % CI , 0.4 - 7.8 ; p=0.032 ) . CONCLUSIONS Tadalafil once daily was most effective on drug-assisted EF in men with erectile dysfunction following NSRP , and data suggest a potential role for tadalafil once daily provided early after surgery in contributing to the recovery of EF after prostatectomy and possibly protecting from penile structural changes . Unassisted EF was not improved after cessation of active therapy for 9 mo . TRIAL REGISTRATION Clinical Trials.gov identifier NCT01026818", "PURPOSE We evaluated the safety and efficacy of 100 and 200 mg avanafil for the treatment of adult males with erectile dysfunction after bilateral nerve sparing radical prostatectomy . MATERIAL S AND METHODS This was a double-blind , placebo controlled , parallel group , phase 3 study in males age 18 to 70 years with a history of erectile dysfunction of 6 months or more after bilateral nerve sparing radical prostatectomy . Patients were r and omized to 100 or 200 mg avanafil or placebo ( taken 30 minutes before sexual activity ) for 12 weeks . Primary end points included successful vaginal insertion ( Sexual Encounter Profile [ SEP ] question 2 ) , successful intercourse ( SEP3 ) and change in score on the erectile function domain of the International Index of Erectile Function ( IIEF-EF ) question naire . RESULTS A total of 298 patients were r and omized and 84.6 % completed the study . At baseline 16.1 % were age 65 years or older and 71.5 % had severe erectile dysfunction ( mean overall IIEF-EF domain score 9.2 ) . After 12 weeks there were significantly greater increases in SEP2 and SEP3 and change in mean IIEF-EF domain score with 100 and 200 mg avanafil vs placebo ( p avanafil 36.4 % ( 28 of 77 ) of sexual attempts ( SEP3 ) at 15 minutes or less were successful vs 4.5 % ( 2 of 44 ) for placebo ( p Avanafil was generally well tolerated . No serious adverse events were reported and fewer than 2 % of patients discontinued the study due to an adverse event . CONCLUSIONS Avanafil in 100 and 200 mg doses was effective and well tolerated in improving erectile function after prostatectomy . Results suggest a rapid onset of action and sustained duration of effect , with all 3 primary end points being achieved at both dose levels", "PURPOSE We evaluated the efficacy and safety of tadalafil 20 mg , taken on dem and , in men with erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy ( BNSRRP ) . MATERIAL S AND METHODS This r and omized , double-blind , placebo controlled multicenter study consisted of a 4-week treatment-free run-in period ( baseline ) followed by 12 weeks of treatment . A total of 303 men ( mean age 60 years ) with preoperative normal erectile function who had undergone a BNSRRP 12 to 48 months before study were r and omized ( 2:1 ) to tadalafil ( 201 ) or placebo ( 102 ) . The 3 co- primary end points were changes from baseline in the International Index of Erectile Function erectile function domain score , and the percentage of positive responses to Sexual Encounter Profile questions 2 ( successful penetration ) and 3 ( successful intercourse ) . The Global Assessment Question and the Erectile Dysfunction Inventory of Treatment Satisfaction question naire were secondary end points . We defined a priori a subgroup of 201 patients reporting evidence of postoperative tumescence , defined as 50 % or greater \" yes \" responses to Sexual Encounter Profile question 1 ( ability to achieve at least some erection ) during baseline intercourse attempts and stratified r and omization based on this criterion . RESULTS Patients receiving tadalafil reported greater improvement on all primary and secondary end points ( p placebo . For all r and omized patients and for the subgroup with evidence of postoperative tumescence , the mean International Index of Erectile Function erectile function domain score increased for patients receiving tadalafil ( mean + /- SEM 5.3 + /- 0.5 and 5.9 + /- 0.7 , respectively , p tadalafil , the mean percentage of successful penetration attempts was 54 % and the mean percentage of successful intercourse attempts was 41 % . For the subgroup with evidence of postoperative tumescence these values were 69 % and 52 % , respectively . Of all patients r and omized to tadalafil 62 % and of the subgroup patients r and omized to tadalafil 71 % reported improved erections . Patients receiving tadalafil reported greater treatment satisfaction on the Erectile Dysfunction Inventory of Treatment Satisfaction than those receiving placebo . Headache ( 21 % ) , dyspepsia ( 13 % ) and myalgia ( 7 % ) were the most commonly reported adverse events . CONCLUSIONS Tadalafil 20 mg , taken on-dem and , was an efficacious and well tolerated treatment for erectile dysfunction following BNSRRP", "OBJECTIVE To evaluate the change in penile size r bilateral nerve sparing retropubic radical prostatectomy ( BNSRRP ) and possible effect of Tadalafil . MATERIAL S AND METHODS A total of 65 patients underwent BNSRRP and they were evaluated prospect ively for a whole year of follow-up . The patients were r and omized to control without rehabilitation ( Group 1 ) or Tadalafil rehabilitation group ( Group 2 ) . The patients were evaluated at months 3 , 6 and 12 postoperatively for erectile function , penile measurements ( flaccid penile length , penile length at maximum erection , penile circumference at flaccid status , and penile circumference at maximum erection ) , penile abnormalities and general health status . Statistical analysis was performed by Chi-Square test and significance was defined as p value penile measurements at month 3 compared to preoperative measurements . There was decrease in all parameters at month 6 compared to month 3 but only the decrease in penile length at maximum erection was significant . There were no significant differences between postoperative months 6 and 12 for all measurements . In Group 2 there was a tendency to decrease in all measurements at month 3 compared to baseline . There was no significant difference for penile measurements between postoperative 3rd and 6th months and between 6th month and the first year . CONCLUSION Although further large sample d trials are needed to describe the possible positive effect of tadalafil or other PDE5-I 's on penile size after BNSRRP , tadalafil rehabilitation is effective in preserving penile size especially in the early postoperative period after BNSRRP", "OBJECTIVE To examine the preference for 2 dosing regimens ( on dem and or 3 times/week ) for tadalafil , a phosphodiesterase 5 inhibitor with a duration of effectiveness up to 36 hours in men with erectile dysfunction ( ED ) . DESIGN AND METHODS SURE is a 14 European country , multicenter , crossover , and open-label study . Men with ED ( N=4262 ) were r and omized to tadalafil 20 mg treatment on dem and ( maximum one dose per day and before sexual activity ) or 3 times/week for 5 - 6 weeks . After a 1-week washout period , patients were crossed over to the alternate regimen for 5 - 6 weeks . The patient 's response to a treatment preference question ( TPQ ) was used to determine the preferred treatment regimen . RESULTS The mean age of the r and omized patients was 55 years and 85.2 % reported a history of ED for one year or greater . Overall , the responses of 3861 men to the TPQ assessment showed that 57.8 % preferred the on-dem and regimen and 42.2 % preferred the 3 times/week dosing . Both regimens were efficacious and well tolerated . CONCLUSIONS In this study , while 57.8 % of men preferred the on-dem and regimen of tadalafil 20 mg , a substantial number ( 42.2 % ) preferred the 3 times/week treatment . The two regimens provide additional treatment options by giving men with erectile dysfunction unique flexibility in dosing with tadalafil ", "Abstract Background : Phosphodiesterase type 5 ( PDE5 ) inhibitors have discontinuation rates as high as 60 % in men with erectile dysfunction . Treatment satisfaction has been significantly associated with treatment continuation . Underst and ing key characteristics in terms of treatment preference , relationship , and lifestyle issues could provide direction on how to improve compliance with PDE5 inhibitor treatment globally . Objective : The objective was to identify subgroups of interest in the pooled data base of two observational studies conducted in Latin America ( LA ) and Middle East/North Africa ( MENA ) exploring patient characteristics and prescription of either a long- or short-acting PDE5 inhibitor at baseline . Methods : Two identical prospect i ve , non-interventional , observational , studies in MENA ( N = 493 ) and LA ( N = 511 ) treated men with an ‘ on dem and ’ ( pro re nata , PRN ) PDE5 inhibitor ( sildenafil , tadalafil , vardenafil , or lodenafil ) during 6 months . In this post-hoc meta- analysis of two observational studies with equal design , pooled data were analyzed to determine patient characteristics and PDE5 inhibitor prescribed/used most likely to be associated with patient expectations , satisfaction , self-esteem , and patient – partner relationships . Decision tree analyses , with and without weighting , were used to identify and describe key features . Results : In each analysis of patient expectations , patient – partner relationship , and self-esteem , we describe the two major subgroups at baseline for each decision tree . Analyses of patient expectations and sexual self-esteem revealed that patients prescribed long-acting PDE5 inhibitors ( 59 % ) highlighted the importance of treatment effect duration , second to partner satisfaction with treatment , while patients prescribed short-acting PDE5 inhibitors ( 32 % ) placed less importance on treatment effect duration but considerable importance on treatment effect lasting until intercourse completion . Further insights regarding patients , partner relationship characteristics , and treatment expectations were identified . Conclusion : Our analyses have described key characteristics , such as self- and partner perceptions , sexual attitudes , and treatment expectations in relation to the patients ’ country and prescribed treatment , which might guide treatment decisions in MENA and LA men with ED", "OBJECTIVES To examine the therapeutic effects of tadalafil on erectile dysfunction ( ED ) at 24 and 36 hours after dosing . METHODS A multicenter , r and omized , double-blind , placebo-controlled , parallel-group study of 348 men ( mean age 57 years ) with ED was conducted in Europe and the United States . Patients were stratified by baseline severity of ED using the Erectile Function domain score of the International Index of Erectile Function and then r and omly allocated within the severity group to receive tadalafil 20 mg ( n = 175 ) or placebo ( n = 173 ) . Subsequently , participants were r and omly assigned to two 4-week treatment intervals , during which they were requested to attempt sexual intercourse approximately 24 or 36 hours after tadalafil or placebo dosing . The primary outcome measure was the proportion of successful sexual intercourse attempts ( completed to ejaculation ) according to patient self-report using the Sexual Encounter Profile diary . RESULTS Of the 348 patients , 327 ( 94 % ) completed the trial ( 163 of 175 in the tadalafil group and 164 of 173 in the placebo group ) . Thirty-six hours after tadalafil dosing , 59.2 % of intercourse attempts were successful versus 28.3 % in the placebo group ( P proportion of successful intercourse attempts at approximately 24 hours after treatment was also significantly greater with tadalafil ( 52.9 % ) than with placebo ( 29.1 % ; P Tadalafil was well tolerated . The incidences of four treatment-emergent adverse events were significantly greater in the tadalafil group than in the placebo group ( all P headache , flushing , dyspepsia , and myalgia . CONCLUSIONS Tadalafil 20 mg is an effective and well-tolerated treatment for ED that has a period of responsiveness of up to 36 hours", "PURPOSE Nerve sparing radical retropubic prostatectomy ( NS-RRP ) results in erectile dysfunction in a significant number of patients . Vardenafil , a potent and selective phosphodiesterase type 5 inhibitor , is generally safe . It improves International Index of Erectile Function erectile function domain scores , and penetration and erection maintenance success rates in patients who have undergone NS-RRP . We report additional parameters important to patient perceptions regarding erection quality and satisfaction with sexual experience following NS-RRP . MATERIAL S AND METHODS A total of 440 men at 58 centers throughout the United States and Canada participated in this r and omized , placebo controlled , double-blind trial with 3 phases , namely baseline ( 4-week untreated period ) , treatment ( 12 weeks ) and followup ( 7 days ) . Participants received placebo ( 145 ) , 10 mg vardenafil ( 146 ) or 20 mg vardenafil ( 149 ) at home on dem and but no more than once per calendar day . Efficacy and satisfaction with erection quality and sexual experience were determined during the trial . RESULTS The 10 and 20 mg vardenafil doses were significantly superior to placebo for the International Index of Erectile Function domains for intercourse satisfaction , orgasmic function and overall satisfaction with sexual experience ( vs placebo p satisfaction rate with erection hardness were demonstrated for each vardenafil dose compared with placebo ( p well tolerated . Common adverse events were headache , vasodilatation and rhinitis . CONCLUSIONS In this difficult to treat population of men with erectile dysfunction subsequent to NS-RRP on dem and treatment with vardenafil during a 3-month period significantly improved key aspects of the sexual experience important to patient quality of life", "PURPOSE More than one-third of men may experience erectile dysfunction ( ED ) after nerve sparing radical retropubic prostatectomy . The efficacy and safety of vardenafil , a potent , selective , phosphodiesterase 5 inhibitor , was assessed for the treatment of ED after radical prostatectomy . MATERIAL S AND METHODS In this double-blind study 440 men with ED after nerve sparing radical prostatectomy were r and omized to take placebo , or 10 or 20 mg vardenafil . Efficacy was measured after 12 weeks using the erectile function domain of the International Index of Erectile Function , diary questions measuring vaginal penetration and intercourse success rates , and a global assessment question ( GAQ ) on erection . RESULTS Of the intent to treat population 70 % had severe ED ( erectile function less than 11 ) at baseline . After 12 weeks both vardenafil doses were significantly superior to placebo ( p Improved erections ( based on GAQ ) were reported by 65.2 % and 59.4 % of patients on 20 and 10 mg vardenafil , respectively , and by only 12.5 % of patients on placebo ( p positive GAQ responses were reported by 71.1 % and 59.7 % of patients on 20 and 10 mg vardenafil , respectively , versus 11.5 % of those on placebo ( p average intercourse success rate per patient receiving 20 mg vardenafil was 74 % in men with mild to moderate ED and 28 % in men with severe ED , compared to 49 % and 4 % for placebo , respectively . Few adverse events were observed . They were generally mild to moderate headache , flushing and rhinitis . CONCLUSIONS In men with severe ED after nerve sparing radical retropubic prostatectomy , vardenafil significantly improved key indices of erectile function", "Erectile dysfunction ( ED ) and urinary incontinence after bilateral nerve-sparing radical prostatectomy ( BNSRP ) still remain major causes of morbidity . Phosphodiesterase type 5 inhibitors ( PDE5-Is ) have a role in the treatment of ED after BNSRP . Several studies in patients with ED and lower urinary tract symptoms demonstrated that PDE5-Is could improve both erectile function and urinary symptoms . The aim of this study was to compare the efficacies of two dosing regimens of 20 mg tadalafil ( on-dem and and 3 times per week ) and to assess the role of tadalafil in recovery of erectile function and continence after BNSRP . We conducted a single-center , prospect i ve , r and omized controlled trial of three times per week versus on-dem and tadalafil 20 mg and a control group after BNSRP . A total of 129 preoperatively potent and continent patients were included in the study . The patients were evaluated at 6 weeks and 12 months postoperatively for erectile function and continence status . There was no significant difference between all three groups with respect to erectile function at 6 weeks after the surgery . Twelve months after the surgery , the International Index of Erectile Function score was significantly higher in the group using tadalafil 20 mg three times per week . However , there was no significant difference between the treated groups and the control group with respect to the continence status at 12 months after the surgery . There was no correlation between incontinence and ED after the surgery in all groups . Tadalafil 20 mg three times per week is an efficacious and well-tolerated treatment option for ED after BNSRP . Treatment with 20 mg tadalafil either three times per week or on dem and can not improve continence recovery after BNSRP compared with the control group" ]

[ "Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose", "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", "CONTEXT Observational studies suggest that surgically induced loss of weight may be effective therapy for type 2 diabetes . OBJECTIVE To determine if surgically induced weight loss results in better glycemic control and less need for diabetes medications than conventional approaches to weight loss and diabetes control . DESIGN , SETTING , AND PARTICIPANTS Unblinded r and omized controlled trial conducted from December 2002 through December 2006 at the University Obesity Research Center in Australia , with general community recruitment to established treatment programs . Participants were 60 obese patients ( BMI > 30 and INTERVENTIONS Conventional diabetes therapy with a focus on weight loss by lifestyle change vs laparoscopic adjustable gastric b and ing with conventional diabetes care . MAIN OUTCOME MEASURES Remission of type 2 diabetes ( fasting glucose level glycated hemoglobin [ HbA1c ] value weight and components of the metabolic syndrome . Analysis was by intention-to-treat . RESULTS Of the 60 patients enrolled , 55 ( 92 % ) completed the 2-year follow-up . Remission of type 2 diabetes was achieved by 22 ( 73 % ) in the surgical group and 4 ( 13 % ) in the conventional-therapy group . Relative risk of remission for the surgical group was 5.5 ( 95 % confidence interval , 2.2 - 14.0 ) . Surgical and conventional-therapy groups lost a mean ( SD ) of 20.7 % ( 8.6 % ) and 1.7 % ( 5.2 % ) of weight , respectively , at 2 years ( P Remission of type 2 diabetes was related to weight loss ( R2 = 0.46 , P lower baseline HbA1c levels ( combined R2 = 0.52 , P no serious complications in either group . CONCLUSIONS Participants r and omized to surgical therapy were more likely to achieve remission of type 2 diabetes through greater weight loss . These results need to be confirmed in a larger , more diverse population and have long-term efficacy assessed . TRIAL REGISTRATION actr.org Identifier : ACTRN012605000159651", "IMPORTANCE Controlling glycemia , blood pressure , and cholesterol is important for patients with diabetes . How best to achieve this goal is unknown . OBJECTIVE To compare Roux-en-Y gastric bypass with lifestyle and intensive medical management to achieve control of comorbid risk factors . DESIGN , SETTING , AND PARTICIPANTS A 12-month , 2-group unblinded r and omized trial at 4 teaching hospitals in the United States and Taiwan involving 120 participants who had a hemoglobin A1c ( HbA1c ) level of 8.0 % or higher , body mass index ( BMI ) between 30.0 and 39.9 , C peptide level of more than 1.0 ng/mL , and type 2 diabetes for at least 6 months . The study began in April 2008 . INTERVENTIONS Lifestyle-intensive medical management intervention and Roux-en-Y gastric bypass surgery . Medications for hyperglycemia , hypertension , and dyslipidemia were prescribed according to protocol and surgical techniques that were st and ardized . MAIN OUTCOMES AND MEASURES Composite goal of HbA1c less than 7.0 % , low-density lipoprotein cholesterol less than 100 mg/dL , and systolic blood pressure less than 130 mm Hg . RESULTS All 120 patients received the intensive lifestyle-medical management protocol and 60 were r and omly assigned to undergo Roux-en-Y gastric bypass . After 12-months , 28 participants ( 49 % ; 95 % CI , 36%-63 % ) in the gastric bypass group and 11 ( 19 % ; 95 % CI , 10%-32 % ) in the lifestyle-medical management group achieved the primary end points ( odds ratio [ OR ] , 4.8 ; 95 % CI , 1.9 - 11.7 ) . Participants in the gastric bypass group required 3.0 fewer medications ( mean , 1.7 vs 4.8 ; 95 % CI for the difference , 2.3 - 3.6 ) and lost 26.1 % vs 7.9 % of their initial body weigh compared with the lifestyle-medical management group ( difference , 17.5 % ; 95 % CI , 14.2%-20.7 % ) . Regression analyses indicated that achieving the composite end point was primarily attributable to weight loss . There were 22 serious adverse events in the gastric bypass group , including 1 cardiovascular event , and 15 in the lifestyle-medical management group . There were 4 perioperative complications and 6 late postoperative complications . The gastric bypass group experienced more nutritional deficiency than the lifestyle-medical management group . CONCLUSIONS AND RELEVANCE In mild to moderately obese patients with type 2 diabetes , adding gastric bypass surgery to lifestyle and medical management was associated with a greater likelihood of achieving the composite goal . Potential benefits of adding gastric bypass surgery to the best lifestyle and medical management strategies of diabetes must be weighed against the risk of serious adverse events . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00641251", "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 )", "Context Observational studies have shown sustained weight loss after surgery for extreme obesity . No r and omized trial of contemporary surgical methods has been performed . Contribution The authors r and omly assigned 80 mildly to moderately obese ( body mass index , 30 to 35 kg/m2 ) adults to laparoscopic placement of an adjustable gastric b and or to an intensive nonsurgical weight loss program . After 2 years , the surgical group had lost 21.6 % of initial weight , and the nonsurgical group had lost 5.5 % of initial weight . Four patients required laparoscopic revision of the gastric b and . Caution s The study was not design ed to detect uncommon adverse events . Implication s Laparoscopic gastric b and ing is effective treatment for mild to moderate obesity . The Editors The development of a safe and effective treatment for obesity is a leading challenge in health care today . Obesity is an increasing health problem across the world with a prevalence of more than 20 % among the adult population in Western countries and more than 30 % in the United States ( 1 , 2 ) . The increasing prevalence is associated with a parallel increase of several obesity-related diseases , in particular , the diseases of the metabolic syndrome ( 3 , 4 ) , which include type 2 diabetes , hypertension , and dyslipidemia , and are linked to nonalcoholic steatohepatitis , obstructive sleep apnea , and the polycystic ovary syndrome . For obese individuals , the options are limited . Behavioral therapies of reduced energy intake , improved eating practice s , and increased exercise and activity , supplemented by pharmacotherapy , generally achieve only modest and often transient effects ( 5 , 6 ) . Observational studies have shown that bariatric surgical therapies involving gastric restriction by various forms of stapling with or without diversion of the gut to generate malabsorption of food are effective in achieving major weight loss and clinical ly significant improvements in health and quality of life ( 7 - 11 ) . Strong direct evidence from r and omized , controlled trials of the relative benefits of nonsurgical and surgical therapies is lacking . We are aware of only a single study , performed in the 1980s , in which 60 morbidly obese patients were r and omly assigned , without informed consent , to diet plus an early form of gastric stapling or to diet alone ( 12 ) . The maximum weight losses did not differ between the groups . However , the weight regain was greater in the diet-only group . The advent of the laparoscopic adjustable gastric b and has provided a new bariatric surgical option , which has proved to be safe , minimally invasive in its application , gentle in its use through its adjustability and easy reversibility , and similarly effective to the other bariatric procedures ( 10 , 13 , 14 ) . Figure 1 shows the LAP-B AND System ( INAMED Health , Santa Barbara , California ) and demonstrates the key feature of adjustability of the area within the b and through which it induces satiety ( 15 ) . Patients require no more than an overnight hospital stay , and the procedure has been shown to be markedly safer than gastric bypass surgery ( 13 ) . Figure 1 . The laparoscopic adjustable gastric b and ( LAP-B AND System , INAMED Health , Santa Barbara , California ) with no added fluid ( top ) and with 2 mL of fluid added ( bottom ) . We hypothesized that surgical therapy would induce more weight loss , health benefit , and improvement in quality of life than nonsurgical therapy and have conducted a r and omized , controlled trial comparing the effectiveness of current nonsurgical therapy with laparoscopic adjustable gastric b and ing in a group of mildly to moderately obese adults ( body mass index , 30 kg/m2 to 35 kg/m2 ) . We did not study patients with a body mass index greater than 35 kg/m2 because current observational data suggest that outcomes after nonsurgical treatment were unlikely to be equal to those after surgical care for these patients . The principal outcome measures were weight change , health , quality of life , and complications of therapy . Methods Patient Recruitment We recruited patients for the study through a newspaper advertisement . All patient assessment s and outpatient treatments were conducted at a community clinic dedicated to obesity management or in the clinics of a university department of surgery . Surgical procedures were conducted at a private community hospital experienced in the care of bariatric surgical patients . Patients in both groups did not pay any medical costs generated by the study . The human ethics committees of The Alfred Hospital and The Avenue Hospital approved the study in accordance with the guidelines of the National Health and Medical Research Council ( www.nhmrc.gov.au/publications/synopses/e35syn.htm ) and with the Helsinki Declaration of 1975 , as revised in 2000 ( www.wma.net/e/ethicsunit/pdf/draft_historical_contemporary_perspectives.pdf ) . Inclusion Criteria We considered patients to be eligible if they were between 20 and 50 years of age ; had a body mass index of 30 kg/m2 to 35 kg/m2 ; had identifiable problems , including an obesity-related comorbid condition ( such as hypertension , dyslipidemia , diabetes , obstructive sleep apnea , or gastroesophageal reflux disease ) , severe physical limitations , or clinical ly significant psychosocial problems associated with their obesity ; had attempted to reduce weight over at least the previous 5 years ; could underst and the options offered and the r and omization process ; and were willing to comply with the requirements of each program . Exclusion Criteria We excluded c and i date s with a history of bariatric surgery or medical problems that contraindicated treatment in either study group , such as impaired mental status , drug or alcohol addiction , or portal hypertension . In addition , we excluded participants if they had undergone an intensive , physician-supervised program that used very-low-calorie diets or pharmacotherapy or if they did not attend the 2 initial patient information visits . Assessment We provided detailed information about the problems of obesity and about the 2 study groups through at least 2 discussion periods and a patient information booklet . Initial assessment included anthropometric measures ; identification of medical , physical , or psychosocial problems ( both weight-related and other ) ; and a discussion of previous weight loss efforts . The assessment included a detailed dietary history by the trial dietitian and a review by a specialist physician to determine the presence and severity of associated medical conditions . Initial investigations included measurements of fasting blood glucose level ; serum insulin level ; and a lipid profile , including HDL cholesterol and LDL cholesterol levels . After initial assessment , we instituted a program of advice on appropriate eating patterns and exercise and followed each patient on a monthly basis for 3 months . During this time , we assessed the patients ' fulfillment of tasks , such as completion of a food diary , and overall adherence to appointments . R and omization Process We r and omly allocated eligible patients to receive a conventional , intensive , nonsurgical program or laparoscopic adjustable gastric b and ing . A computer-derived r and om allocation sequence , without blocking or stratification , performed the r and omization . This was prepared at the trial office . The trial coordinator enrolled participants and informed them of the trial allocation . After assessment had confirmed a participant 's suitability for r and omization , the coordinator contacted the trial office by telephone for allocation . The study was not blinded . Description of Nonsurgical and Surgical Interventions Common Program We instructed and encouraged all patients to follow appropriate lifestyle behavior of good eating practice s and increased exercise and activity . We also encouraged them to exercise for at least 200 minutes per week . Nonsurgical Program This program centered on the use of behavioral modification , very-low-calorie diet , and pharmacotherapy with education and professional support on appropriate eating and exercise behavior . During the 2-year period , 3 trained physicians developed a program using all the available modalities for each individual on the basis of guidelines prepared and continually review ed by a panel of experienced bariatric physicians . The program began with an intensive 6-month period of very-low-calorie diet ( 500 to 550 kcal/d ) using 1 to 3 packets of Optifast ( Novartis , Fremont , Michigan ) daily for 12 weeks , followed by a transition phase over 4 weeks combining some very-low-calorie meals with 120 mg of orlistat before nonvery-low-calorie diet meals , and then 120 mg of orlistat before all meals until the completion of the intensive phase . This intensive 6-month program was followed by further courses of very-low-calorie diets or orlistat as tolerated , as well as continual behavioral , dietary , and exercise advice to assist the participant in maintaining weight loss over a prolonged period . Sibutramine was not approved for use in Australia during the first 12 months of the study and , therefore , was not incorporated into the medical program . The management program for each individual was design ed to reflect good clinical practice . A physician saw each patient every 2 weeks during the very-low-calorie diet program and every 4 to 6 weeks during the rest of the study . All patients were seen at least every 6 weeks . Surgical Program Two experienced surgeons performed the laparoscopic adjustable gastric b and ( LAP-B AND System ) procedure , by a st and ardized method ( 14 ) , within 1 month of r and omization . The b and was placed along the perigastric pathway in all cases ( 16 ) . The treating surgeon review ed patient progress every 4 to 6 weeks during the study period and made adjustments to the volume of saline within the b and in the office by using st and ard clinical criteria ( 17 ) . Adverse Events All patients in the study were question ed about the occurrence of adverse events at each consultation , and physicians recorded the", "Objective This report documents that the gastric bypass operation provides long-term control for obesity and diabetes . Summary Background Data Obesity and diabetes , both notoriously resistant to medical therapy , continue to be two of our most common and serious diseases . Methods Over the last 14 years , 608 morbidly obese patients underwent gastric bypass , an operation that restricts caloric intake by ( 1 ) reducing the functional stomach to approximately 30 mL , ( 2 ) delaying gastric emptying with a c. 0.8 to 1.0 cm gastric outlet , and ( 3 ) excluding foregut with a 40 to 60 cm Roux-en-Y gastrojejunostomy . Even though many of the patients were seriously ill , the operation was performed with a perioperative mortality and complication rate of 1.5 % and 8.5 % , respectively . Seventeen of the 608 patients ( Gastric bypass provides durable weight control . Weights fell from a preoperative mean of 304.4 lb ( range , 198 to 615 lb ) to 192.2 lb ( range , 104 to 466 ) by 1 year and were maintained at 205.4 lb ( range , 107 to 512 lb ) at 5 years , 206.5 lb ( 130 to 388 lb ) at 10 years , and 204.7 lb ( 158 to 270 lb ) at 14 years . The operation provides long-term control of non-insulin-dependent diabetes mellitus ( NIDDM ) . In those patients with adequate follow-up , 121 of 146 patients ( 82.9 % ) with NIDDM and 150 of 152 patients ( 98.7 % ) with glucose impairment maintained normal levels of plasma glucose , glycosylated hemoglobin , and insulin . These antidiabetic effects appear to be due primarily to a reduction in caloric intake , suggesting that insulin resistance is a secondary protective effect rather than the initial lesion . In addition to the control of weight and NIDDM , gastric bypass also corrected or alleviated a number of other comorbidities of obesity , including hypertension , sleep apnea , cardiopulmonary failure , arthritis , and infertility", "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", "AIMS The aim of this study was to evaluate the effect of laparoscopic Roux-en-Y gastric bypass ( RYGB ) surgery compared with usual care with and without Exenatide therapy in obese people with type 2 diabetes mellitus ( T2DM ) and hypertension . METHODS 108 obese T2DM with hypertension were enrolled and r and omly allocated to usual care ( group A ) , usual care plus Exenatide ( group B ) , and RYGB surgery ( group C ) . Demographic characteristics , metabolic parameters and cardiac structure/function along with inflammatory cytokines were measured and compared before and after 12 months . RESULTS At 12 months , diabetes remission had occurred in no patients in groups A and B versus 90 % in group C , and there was a significant decrease in requirement of antihypertensive drugs in group C compared with groups A and B ( P ( body mass index , hemoglobin A1c , homeostasis model assessment of insulin resistance , lipids ) , inflammation index ( high sensitivity C-reactive protein , tumor necrosis factor-α , high molecular weight adiponectin ) and cardiac structure ( left ventricular mass index ) were significantly improved in groups B and C , but patients in group C had the greatest degree of improvement ( P CONCLUSION RYGB surgery improves a number of parameters including cardiovascular function in obese hypertensive people with T2DM . This is likely to be due to , at least in part , an improvement in the abnormal metabolic panel and to reduced inflammation", "OBJECTIVE To assess changes in body composition with weight loss in obese subjects r and omized to a laparoscopic adjustable gastric b and surgical program or a medical program using a very-low-energy diet and orlistat . RESEARCH METHODS AND PROCEDURES Using body composition measurements by DXA , neutron activation for total body nitrogen , and whole body gamma counting for total body potassium , we studied changes in fat mass , fat distribution , fat-free mass , total bone mineral content , total body protein , and body cell mass at 6 ( n = 61 paired ) and 24 months ( n = 53 paired ) after r and omization . RESULTS At 24 months , the surgical group had lost significantly more weight ( surgical , 20.3 + /- 6.5 kg ; medical , 5.9 + /- 8.0 kg ) . There was favorable fat-free mass to fat mass loss ratios for both groups ( surgical , 1:5.5 ; medical , 1:5.9 ) . Changes in total body nitrogen or potassium were favorable in each group . A small reduction in mean bone mineral content occurred throughout the study but was not associated with extent of weight loss or treatment group . At 6 months , weight loss for both groups was similar ( surgical , 14.1 + /- 4.5 kg ; medical , 13.3 + /- 7.3 kg ) . The medical program subjects lost less fat-free mass and skeletal muscle and had increased total body protein . The proportion of body fat to limb fat remained remarkably constant throughout the study . DISCUSSION Weight loss programs used in this study induced fat loss without significant deleterious effects on the components of fat-free mass", "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", "CONTEXT Extreme obesity is associated with health and cardiovascular disease risks . Although gastric bypass surgery induces rapid weight loss and ameliorates many of these risks in the short term , long-term outcomes are uncertain . OBJECTIVE To examine the association of Roux-en-Y gastric bypass ( RYGB ) surgery with weight loss , diabetes mellitus , and other health risks 6 years after surgery . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve Utah-based study conducted between July 2000 and June 2011 of 1156 severely obese ( body mass index [ BMI ] ≥ 35 ) participants aged 18 to 72 years ( 82 % women ; mean BMI , 45.9 ; 95 % CI , 31.2 - 60.6 ) who sought and received RYGB surgery ( n = 418 ) , sought but did not have surgery ( n = 417 ; control group 1 ) , or who were r and omly selected from a population -based sample not seeking weight loss surgery ( n = 321 ; control group 2 ) . MAIN OUTCOME MEASURES Weight loss , diabetes , hypertension , dyslipidemia , and health-related quality of life were compared between participants having RYGB surgery and control participants using propensity score adjustment . RESULTS Six years after surgery , patients who received RYGB surgery ( with 92.6 % follow-up ) lost 27.7 % ( 95 % CI , 26.6%-28.9 % ) of their initial body weight compared with 0.2 % ( 95 % CI , -1.1 % to 1.4 % ) gain in control group 1 and 0 % ( 95 % CI , -1.2 % to 1.2 % ) in control group 2 . Weight loss maintenance was superior in patients who received RYGB surgery , with 94 % ( 95 % CI , 92%-96 % ) and 76 % ( 95 % CI , 72%-81 % ) of patients receiving RYGB surgery maintaining at least 20 % weight loss 2 and 6 years after surgery , respectively . Diabetes remission rates 6 years after surgery were 62 % ( 95 % CI , 49%-75 % ) in the RYGB surgery group , 8 % ( 95 % CI , 0%-16 % ) in control group 1 , and 6 % ( 95 % CI , 0%-13 % ) in control group 2 , with remission odds ratios ( ORs ) of 16.5 ( 95 % CI , 4.7 - 57.6 ; P incidence of diabetes throughout the course of the study was reduced after RYGB surgery ( 2 % ; 95 % CI , 0%-4 % ; vs 17 % ; 95 % CI , 10%-24 % ; OR , 0.11 ; 95 % CI , 0.04 - 0.34 compared with control group 1 and 15 % ; 95 % CI , 9%-21 % ; OR , 0.21 ; 95 % CI , 0.06 - 0.67 compared with control group 2 ; both P bariatric surgery-related hospitalizations were 33 ( 7.9 % ) , 13 ( 3.9 % ) , and 6 ( 2.0 % ) for the RYGB surgery group and 2 control groups , respectively . CONCLUSION Among severely obese patients , compared with nonsurgical control patients , the use of RYGB surgery was associated with higher rates of diabetes remission and lower risk of cardiovascular and other health outcomes over 6 years", "BACKGROUND R and omized controlled trials ( RCTs ) in surgery can provide valuable evidence of the efficacy of interventions if they are well- design ed , appropriately executed , and adequately reported . Adequate reporting of methodology in surgical RCTs is known to be poor , and adverse-event reporting in surgical research is inconsistent . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement is a framework to help authors report their findings in a transparent manner . Extensions to the CONSORT statement have been published recently to address deficiencies in adverse-event reporting and in reporting of specific criteria related to nonpharmacologic treatments . The aim of this study was to assess the quality of reporting of trial methodology and adverse events in a sample of general surgical RCTs published in high- quality surgical journals using the criteria specified in the CONSORT statements . STUDY DESIGN We used impact factor to identify the top three ranked surgical journals in 2004 . We then obtained information on all RCTs published in these journals in the 2005 calendar year . We assessed quality of reporting using Jadad score , compared the quality of RCTs from CONSORT-endorsing journals with nonendorsers , and assessed the number of RCTs adequately reporting key generic method ologic , adverse-event-related , and specific nonpharmacologic criteria . RESULTS Of 42 RCTs analyzed , only 40 % ( 17 of 42 ) had a Jadad score > or = 3 . There was no significant difference in the number of high- quality RCTs published in CONSORT-endorsing journals compared with nonendorsers ( p = 0.3 ) . The median percentage of RCTs adequately reporting generic method ologic , adverse-event-related , and specific nonpharmacologic criteria was 32.5 % , 17 % , and 36.5 % , respectively . CONCLUSIONS Quality of reporting of generic method ologic , adverse-event-related , and specific nonpharmacologic criteria in surgical RCTs is poor . Increased attention to quality of reporting of surgical RCTs is required if studies are to meet published criteria", "CONTEXT Adolescent obesity is a common and serious health problem affecting more than 5 million young people in the United States alone . Bariatric surgery is being evaluated as a possible treatment option . Laparoscopic adjustable gastric b and ing ( gastric b and ing ) has the potential to provide a safe and effective treatment . OBJECTIVE To compare the outcomes of gastric b and ing with an optimal lifestyle program on adolescent obesity . DESIGN , SETTING , AND PATIENTS A prospect i ve , r and omized controlled trial of 50 adolescents between 14 and 18 years with a body mass index ( BMI ) higher than 35 , recruited from the Melbourne , Australia , community , assigned either to a supervised lifestyle intervention or to undergo gastric b and ing , and followed up for 2 years . The study was performed between May 2005 and September 2008 . MAIN OUTCOME MEASURES Weight loss . Secondary outcomes included change in metabolic syndrome , insulin resistance , quality of life , and adverse outcomes . RESULTS Twenty-four of 25 patients in the gastric b and ing group and 18 of 25 in lifestyle group completed the study . Twenty-one ( 84 % ) in the gastric b and ing and 3 ( 12 % ) in the lifestyle groups lost more than 50 % of excess weight , corrected for age . Overall , the mean changes in the gastric b and ing group were a weight loss of 34.6 kg ( 95 % CI , 30.2 - 39.0 ) , representing an excess weight loss of 78.8 % ( 95 % CI , 66.6%-91.0 % ) , 12.7 BMI units ( 95 % CI , 11.3 - 14.2 ) , and a BMI z score change from 2.39 ( 95 % CI , 2.05 - 2.73 ) to 1.32 ( 95 % CI , 0.98 - 1.66 ) . The mean losses in the lifestyle group were 3.0 kg ( 95 % CI , 2.1 - 8.1 ) , representing excess weight loss of 13.2 % ( 95 % CI , 2.6%-21.0 % ) , 1.3 BMI units ( 95 % CI , 0.4 - 2.9 ) , and a BMI z score change from 2.41 ( 95 % CI , 2.21 - 2.66 ) to 2.26 ( 95 % CI , 1.91 - 2.43 ) . At entry , 9 participants ( 36 % ) in the gastric b and ing group and 10 ( 40 % ) in the lifestyle group had the metabolic syndrome . At 24 months , none of the gastric b and ing group had the metabolic syndrome ( P = .008 ; McNemar chi(2 ) ) compared with 4 of the 18 completers ( 22 % ) in the lifestyle group ( P = .13 ) . The gastric b and ing group experienced improved quality of life with no perioperative adverse events . However , 8 operations ( 33 % ) were required in 7 patients for revisional procedures either for proximal pouch dilatation or tubing injury during follow-up . CONCLUSIONS Among obese adolescent participants , use of gastric b and ing compared with lifestyle intervention result ed in a greater percentage achieving a loss of 50 % of excess weight , corrected for age . There were associated benefits to health and quality of life . TRIAL REGISTRATION ANZCTR Identifier : 12605000160639" ]

[ "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", "OBJECT The aim of this study was to develop a decision rule for physicians in developing countries to identify patients with minor head injury who will benefit from emergency brain CT scanning . METHODS Three hundred eighteen patients with a history of blunt head trauma and a Glasgow Coma Scale ( GCS ) score > or= 13 who had presented within 12 hours of trauma underwent nonenhanced brain CT and were included in this prospect i ve study . Computed tomography findings that necessitated neurosurgical care ( either observation or intervention ) were considered as positive findings . Logistic regression was used to develop the decision rule . RESULTS Computed tomography scans were always normal in patients obvious head wound , a raccoon sign , vomiting , memory deficit , or a decrease in their GCS score . Patients with 1 major criterion ( GCS score 65 years , or vomiting ) or 2 minor criteria ( wound at the scalp or GCS score abnormal CT scan in 13 % of the cases . CONCLUSIONS The decision rule developed by the authors appears to be 100 % sensitive and 46 % specific for positive findings on brain CT and will , in developing countries , help clarify the decision to obtain scans", "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", "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", "The purpose of the current study was to explore potential differences in pre- and post-concussion performance on a computerized neurocognitive concussion test between African American and White high-school and collegiate student-athletes . A prospect i ve case-control design was used to compare baseline and 2- and 7-day post-concussion computerized neurocognitive performance and symptoms between 48 White and 48 African American athletes matched for age , gender , and concussion history . The Immediate Post-Concussion Assessment Cognitive Test ( ImPACT ) version 2.0 ( NeuroHealth System , LLC , Pittsburgh , PA , USA ) computer software program was used to assess neurocognitive function ( i.e. , verbal and visual memory , motor processing speed , and reaction time ) and concussion symptoms . Regardless of race/ethnicity , there were significant decrements in computerized neurocognitive performance and increased symptoms following a concussion for the entire sample . African Americans and Whites did not differ significantly on baseline or post-concussion verbal memory , visual memory , reaction time , and total reported symptoms . However , African American participants were 2.4 × more likely to have at least one clinical ly significant cognitive decline on ImPACT at 7 days post-concussion and scored lower at 7 days post-concussion compared with baseline on processing speed than White participants . The authors concluded that the baseline ImPACT test was culturally equivalent and construct valid for use with these two racial/ethnic groups . However , in contrast , the findings support deleterious performance for the African American athletes compared with the White athletes on the ImPACT post-concussion evaluation that is of critical clinical relevance and warrants further research", "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", "BACKGROUND : This study compared early serum levels of ubiquitin C-terminal hydrolase ( UCH-L1 ) from patients with mild and moderate traumatic brain injury ( TBI ) with uninjured and injured controls and examined their association with traumatic intracranial lesions on computed tomography ( CT ) scan ( CT positive ) and the need for neurosurgical intervention ( NSI ) . METHODS : This prospect i ve cohort study enrolled adult patients presenting to three tertiary care Level I trauma centers after blunt head trauma with loss of consciousness , amnesia , or disorientation and a Glasgow Coma Scale ( GCS ) score 9 to 15 . Control groups included normal uninjured controls and nonhead injured trauma controls presenting to the emergency department with orthopedic injuries or motor vehicle crash without TBI . Blood sample s were obtained in all trauma patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for UCH-L1 ( ng/mL ± st and ard error of the mean ) . RESULTS : There were 295 patients enrolled , 96 TBI patients ( 86 with GCS score 13–15 and 10 with GCS score 9–12 ) , and 199 controls ( 176 uninjured , 16 motor vehicle crash controls , and 7 orthopedic controls ) . The AUC for distinguishing TBI from uninjured controls was 0.87 ( 95 % confidence interval [ CI ] , 0.82–0.92 ) and for distinguishing those TBIs with GCS score 15 from controls was AUC 0.87 ( 95 % CI , 0.81–0.93 ) . Mean UCH-L1 levels in patients with CT negative versus CT positive were 0.620 ( ±0.254 ) and 1.618 ( ±0.474 ) , respectively ( p the GCS score , CT lesions , and NSI . Further study is required to vali date these findings before clinical application . LEVEL OF EVIDENCE : II , prognostic study", "Previous studies have presented conflicting results regarding the predictive value of various clinical symptoms and signs for performing computed tomography ( CT ) scan in minor head injury . Moreover , despite the presence in the literature of several similar publications regarding whether or not CT should be employed at the time of presentation of minor head injured patients , data regarding delayed CT are limited . The objective of this study was to determine whether high-risk criteria represent a significant indication for initial CT scan in patients with minor head trauma , and whether or not analysis using delayed CT scan is necessary in patients with high-risk criteria before being discharged . Patients presenting to the Emergency Department with minor head trauma between September 1 , 2003 and September 1 , 2004 were evaluated prospect ively . After being divided into two main groups , low- and high-risk , four separate sub-groups based on age were established . Initial spiral CT examination was done within 3 h of trauma on all patients in addition to a delayed control CT scan in those with high-risk criteria between 16 and 24 h after trauma . The difference between the high- and low-risk groups in terms of abnormal CT findings was statistically significant ( p Glasgow Coma Scale ( GCS ) score of 13 or 14 and those with a GCS score of 15 ( p relationship between vomiting and abnormal CT scan was significant ( odds ratio 4.61 , 95 % confidence interval 2.20 - 9.64 , p = 0.0001 ) , and the relationship between abnormal CT scan and suspected skull fracture was also significant ( odds ratio 3.46 , 95 % confidence interval 1.52 - 7.91 , p = 0.0032 ) . No significant correlations between other high-risk criteria and abnormal CT scan were determined . The difference between initial and delayed CT scans in patients with high-risk criteria was not significant ( p = 0.161 ) . Low-risk patients with a GCS score of 15 may be discharged without initial CT scan being performed . Initial CT scan absolutely must be performed , however , on patients with GCS CT scans in patients with high-risk criteria is not significant , it is our opinion that it is still prudent for delayed CT scan to be performed , particularly on patients whose GCS score does not rise to 15 , or decreases", "Context Available prediction rules to guide selective use of computed tomography in patients with minor head injuries were developed for use in patients with a history of loss of consciousness . Contribution This prospect i ve study included 3181 adults with minor head injury with or without loss of consciousness . A prediction rule based on risk factors ( such as age ; Glasgow Coma Scale score ; skull fracture ; and posttraumatic vomiting , amnesia , or seizure ) successfully identified patients who had intracranial computed tomography findings ( sensitivity , approximately 95 % ) or neurosurgical intervention ( sensitivity , 100 % ) . Caution External validation in different population s is needed before widespread application of the rule . The Editors Minor head injury is one of the most common injuries seen in western emergency departments , with an estimated incidence of 100 to 300 per 100000 people ( 1 ) . Patients with minor head injury include those with blunt injury to the head who have a normal or minimally altered level of consciousness on presentation in the emergency department , that is , a Glasgow Coma Scale ( GCS ) score of 13 to 15 , and a maximum loss of consciousness of 15 minutes , posttraumatic amnesia for 60 minutes , or both ( 2 ) . Intracranial complications after minor head injury are infrequent but commonly require in-hospital observation and occasionally require neurosurgical intervention ( 3 , 4 ) . The imaging procedure of choice for reliable , rapid diagnosis of intracranial complications is computed tomography ( CT ) ( 5 , 6 ) . Because most patients with minor head injury do not show traumatic abnormalities on CT , it seems inefficient to scan all patients with minor head injury to exclude intracranial complications . Of the published prediction rules for the selective use of CT in patients with minor head injury , the New Orleans Criteria ( NOC ) and the Canadian CT Head Rule ( CCHR ) have been externally vali date d ( 79 ) . Research ers in internal and external validation studies have shown that both rules identify 100 % of patients requiring neurosurgical intervention and most patients with traumatic intracranial findings on CT ( 3 , 1012 ) . The external validation studies , however , yielded lower specificities than the development studies ( 10 , 12 ) . The originally reported specificities were probably too optimistic because of their partial derivation from data sets that were also used for the model development ( 13 ) . Also , in both studies research ers included only a subset of patients with minor head injury . Most notably , research ers developed the NOC and the CCHR for patients with minor head injury who have a history of loss of consciousness or amnesia , which many of these patients presenting to emergency departments do not have . Generalizability of the NOC and the CCHR is therefore limited . We aim ed to develop a widely applicable and easy-to-implement prediction rule for the selective use of CT in all patients with minor head injury with or without a history of loss of consciousness . To avoid optimism for the model 's performance , we used penalty factors and internal validation by using bootstrapping procedures to attain more realistic predictions of the model 's performance in an external patient population ( 13 ) . Methods Patients We prospect ively collected data on consecutive patients in 4 university hospitals in the Netherl and s that were participating in the CT in Head Injury Patients ( CHIP ) study ( Figure 1 ) ( 14 ) . Inclusion criteria included initial presentation within 24 hours of blunt injury to the head , a minimum age of 16 years , and a Glasgow Coma Scale ( GCS ) score of 13 to 14 or a GCS score of 15 , with at least 1 of the following risk factors : history of loss of consciousness , short-term memory deficit , amnesia for the traumatic event , posttraumatic seizure , vomiting , severe headache , clinical evidence of intoxication with alcohol or drugs , use of anticoagulants or history of coagulopathy , external evidence of injury above the clavicles , and neurologic deficit . Exclusion criteria were transfer from another hospital , contraindications for CT , or concurrent injuries precluding a head CT at presentation . Figure 1 . Study flow diagram . The number of patients presenting with head injury is an estimate based on the proportion of patients included out of the total number of trauma patients seen by a neurologist or neurologist-in-training in the emergency department of the participating center that included most patients . CT = computed tomography . A neurologist or a neurologist-in-training under telephone supervision of a neurologist examined patients , after which a head CT was performed as soon as possible , in accordance with the current Dutch guidelines ( 15 ) . We performed head CT according to a routine trauma protocol , with a maximum slice thickness of 5 mm infratentorially and 8 mm supratentorially , without intravenous contrast administration . A neuroradiologist or a trauma radiologist ( 9 in total , not blinded to the patients ' history and clinical findings ) interpreted scans in brain and bone window setting s. The institutional review board waived patient informed consent after review of our study protocol because current Dutch guidelines and European Federation of Neurological Societies ' guidelines recommend routine head CT for patients meeting our inclusion criteria ( 15 , 16 ) . Definitions We considered a patient to have a history of loss of consciousness when a witness or the patient reported it . We defined short-term memory deficit as persistent antero grade amnesia . We deemed amnesia present for the traumatic event if the patient could not recall the entire traumatic event . We defined posttraumatic seizure as a seizure witnessed or suspected after the injury and vomiting as an episode of emesis after the traumatic event . We classified headache as being either diffuse or localized . We evaluated the presence and severity of intoxication clinical ly by evidence of slurred speech , alcoholic fetor , or nystagmus ; we did not perform routine blood toxicology tests . Anticoagulant treatment included only coumarin derivatives . We scored the use of platelet aggregation inhibitors ( for example , aspirin and clopidrogel ) , but we did not consider it to be a risk factor . We assessed noniatrogenic coagulopathy , which we considered a risk factor , by patient history , but we did not perform routine blood coagulation tests . We defined external evidence of injury as clinical ly significant discontinuity of the skin or extensive bruising . We classified injury suspect of a fracture as clinical signs of fracture , whereas we classified other injuries , such as contusions , lacerations , or abrasions , as contusion . We defined focal neurologic deficit as any abnormality on routine clinical neurologic examination that indicated a focal cerebral lesion . Data Collection We collected data on patient and trauma characteristics , symptoms , and risk factors ; physical and neurologic examination ; CT findings ; and neurosurgical intervention . Examining physicians entered data on patient history and examination into a data base ( OpenSDE , Erasmus MCUniversity Medical Center Rotterdam , Rotterdam , the Netherl and s ) before the patient underwent CT . If this interfered with their clinical workflow , they entered the data after the CT ( 17 ) . The reading radiologist added the CT findings . We collected data on neurosurgical intervention , additional CT scans performed , and the clinical outcomes of patients by search ing the hospital 's patient information system . Outcome Measures Our primary outcome measure for this analysis was any intracranial traumatic finding on CT , which included all neurocranial traumatic findings except for isolated linear skull fractures . A secondary outcome measure was neurosurgical intervention contingent to initial CT . We defined neurosurgical intervention as any neurosurgical procedure ( craniotomy , intracranial pressure monitoring , elevation of skull fracture , or ventricular drainage ) within 30 days of the traumatic event . Risk Factors We selected all of the risk factors from the NOC and the CCHR ( 7 , 9 ) : age , headache , vomiting , intoxication , persistent antero grade amnesia , retro grade amnesia more than 30 minutes , injury above the clavicles ( including clinical signs of skull or basal skull fracture ) , GCS score less than 15 at 2 hours postinjury , and dangerous trauma mechanism ( pedestrian vs. vehicle , fall from height , and ejected from motor vehicle ) . We tested other risk factors from clinical guidelines for the use of CT in minor head injury ( 15 , 16 , 1821 ) for additional effects . We combined the variables cyclist versus vehicle and pedestrian versus vehicle into 1 variable ( pedestrian or cyclist vs. vehicle ) for statistical analysis because they are similar trauma mechanisms . Statistical Analysis We based sample size on an estimated 25 variables for multivariable logistic regression analysis . For reliable analysis , we required at least 10 events of the primary outcome measure per variable , that is , 250 events for 25 variables ( 22 ) . Given an incidence of traumatic findings on CT of 8 % to 10 % , we needed to include 3125 patients . We assumed that missing data were missing at r and om , and we imputed them on the basis of the available data means to avoid bias ( 2327 ) . The proportion of imputed data was 3.8 % , which included items documented as unknown and items that were not documented . Of all cases , 1956 ( 62 % ) were complete . Loss of consciousness and posttraumatic amnesia had the highest proportion of missing or unknown data ( 18 % and 10 % , respectively ) . We imputed both as present on the basis of the available variable means and as consistent with clinical practice . We used the entire data set , after missing value imputation , for all analyses . We evaluated the study sample for demographic characteristics , mechanism of injury , traumatic findings , neurosurgical intervention , GCS scores , and the presence of risk factors . We tested associations of each risk factor with the primary", "STUDY OBJECTIVE This study examines whether serum levels of glial fibrillary acidic protein breakdown products ( GFAP-BDP ) are elevated in patients with mild and moderate traumatic brain injury compared with controls and whether they are associated with traumatic intracranial lesions on computed tomography ( CT ) scan ( positive CT result ) and with having a neurosurgical intervention . METHODS This prospect i ve cohort study enrolled adult patients presenting to 3 Level I trauma centers after blunt head trauma with loss of consciousness , amnesia , or disorientation and a Glasgow Coma Scale ( GCS ) score of 9 to 15 . Control groups included normal uninjured controls and trauma controls presenting to the emergency department with orthopedic injuries or a motor vehicle crash without traumatic brain injury . Blood sample s were obtained in all patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for GFAP-BDP ( nanograms/milliliter ) . RESULTS Of the 307 patients enrolled , 108 were patients with traumatic brain injury ( 97 with GCS score 13 to 15 and 11 with GCS score 9 to 12 ) and 199 were controls ( 176 normal controls and 16 motor vehicle crash controls and 7 orthopedic controls ) . Receiver operating characteristic curves demonstrated that early GFAP-BDP levels were able to distinguish patients with traumatic brain injury from uninjured controls with an area under the curve of 0.90 ( 95 % confidence interval [ CI ] 0.86 to 0.94 ) and differentiated traumatic brain injury with a GCS score of 15 with an area under the curve of 0.88 ( 95 % CI 0.82 to 0.93 ) . Thirty-two patients with traumatic brain injury ( 30 % ) had lesions on CT . The area under these curves for discriminating patients with CT lesions versus those without CT lesions was 0.79 ( 95 % CI 0.69 to 0.89 ) . Moreover , the receiver operating characteristic curve for distinguishing neurosurgical intervention from no neurosurgical intervention yielded an area under the curve of 0.87 ( 95 % CI 0.77 to 0.96 ) . CONCLUSION GFAP-BDP is detectable in serum within an hour of injury and is associated with measures of injury severity , including the GCS score , CT lesions , and neurosurgical intervention . Further study is required to vali date these findings before clinical application", "OBJECTIVE To prospect ively measure the immediate neurocognitive effects and early course of recovery from concussion and to examine the effects of loss of consciousness ( LOC ) and posttraumatic amnesia ( PTA ) on the severity of neurocognitive impairment immediately after concussion . METHODS A sports-related concussion research model was used to allow prospect i ve immediate evaluation of concussion . A total of 2385 high school and college football players were studied . Ninety-one players ( 3.8 % ) sustained concussions during the study . A brief neurocognitive and neurological screening measure , the St and ardized Assessment of Concussion , was used to assess cognitive functioning before the football season , immediately after injury , and 15 minutes , 48 hours , and 90 days after injury . RESULTS St and ardized Assessment of Concussion scores immediately after concussion were significantly lower than the preseason baseline score and the noninjured population baseline mean , even for injured subjects without LOC or PTA . Subjects with LOC were most severely impaired immediately after injury , whereas those without LOC or PTA were least impaired . Significant impairment was also detected 15 minutes after injury , but all three groups returned to baseline levels of cognitive functioning within 48 hours . CONCLUSION These findings are the first to demonstrate not only that a gradient of increasing concussion severity is represented by PTA and LOC but also that measurable neurocognitive abnormalities are evident immediately after injury without PTA or LOC", "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", "OBJECT During recent years , several biomarkers have been introduced for use in the diagnosis of traumatic brain injury ( TBI ) . The primary objective of this investigation was to determine if S100B ( or S100 calcium-binding protein B ) and neuron-specific enolase ( NSE ) serum concentrations can effectively be used to discriminate between symptomatic and asymptomatic children with minor head trauma . METHODS The authors conducted a prospect i ve clinical study that involved patients age 6 months to 15 years who had sustained minor head trauma . Children with concomitant extracranial injuries were excluded . Blood sample s were obtained within 6 hours of injury to measure S100B and NSE levels in serum . The authors defined 2 diagnostic groups : a mild TBI group ( patients with Glasgow Coma Scale [ GCS ] scores of 13 - 15 ) in whom there were clinical signs of concussion ( short loss of consciousness , amnesia , nausea , vomiting , somnolence , headache , dizziness , or impaired vision ) and a head contusion group ( patients with a GCS score of 15 ) in whom symptoms were absent . Both S100B and NSE concentrations were compared between the 2 groups . Secondary end points were defined as follows : correlation of S100B/NSE and a ) the presence of scalp lacerations , b ) GCS score , c ) age , and d ) correlation between S100B and NSE . RESULTS One hundred forty-eight patients were enrolled ( 53 in the contusion group , 95 in the mild TBI group ) . After adjusting for differences in age and time of injury to blood sample withdrawal , there was no significant difference in S100B or NSE between patients in the 2 groups . Scalp lacerations and GCS score had no affect on posttraumatic S100B or NSE concentrations . The correlation between S100B and NSE was significant . Both markers showed a significant negative correlation with age . CONCLUSIONS The authors demonstrated that S100B and NSE do not discriminate between symptomatic and asymptomatic children with minor head injury . There seem to be limitations in marker sensitivity when investigating pediatric patients with mild TBI", "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 The authors examined the efficacy of intramuscular flunitrazepam compared with intramuscular haloperidol for the immediate control of agitated or aggressive behavior in acutely psychotic patients . METHOD Twenty-eight actively psychotic in patients , aged 20 - 60 years , who were under treatment with neuroleptic agents were selected for the study . Each was r and omly assigned on a double-blind basis to receive either 5 mg i.m . of haloperidol ( N=13 ) or 1 mg i.m . of flunitrazepam ( N=15 ) during an aggressive event . Verbal and physical aggression was measured over time with the Overt Aggression Scale . Patients were also rated with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale . RESULTS Both flunitrazepam and haloperidol exhibited acute antiaggressive activity . This beneficial effect , as assessed by the Overt Aggression Scale , was obtained within 30 minutes . CONCLUSIONS Intramuscular flunitrazepam may serve as a convenient , rapid , safe , and effective adjunct to neuroleptics in reducing aggressive behavior in emergency psychiatric setting", "BACKGROUND Acute psychotic illness , especially when associated with agitated or violent behaviour , can require urgent pharmacological tranquillisation or sedation . In several countries , clinicians often use benzodiazepines ( either alone or in combination with antipsychotics ) for this outcome . OBJECTIVES To estimate the effects of benzodiazepines , alone or in combination with antipsychotics , when compared with placebo or antipsychotics , alone or in combination with antihistamines , to control disturbed behaviour and reduce psychotic symptoms . SEARCH METHODS We search ed the Cochrane Schizophrenia Group 's register ( January 2012 ) , inspected reference lists of included and excluded studies and contacted authors of relevant studies . SELECTION CRITERIA We included all r and omised clinical trials ( RCTs ) comparing benzodiazepines alone or in combination with any antipsychotics , versus antipsychotics alone or in combination with any other antipsychotics , benzodiazepines or antihistamines , for people with acute psychotic illnesses . DATA COLLECTION AND ANALYSIS We reliably selected studies , quality assessed them and extracted data . For binary outcomes , we calculated st and ard estimates of relative risk ( RR ) and their 95 % confidence intervals ( CI ) using a fixed-effect model . For continuous outcomes , we calculated the mean difference ( MD ) between groups . If heterogeneity was identified , this was explored using a r and om-effects model . MAIN RESULTS We included 21 trials with a total of n = 1968 participants . There was no significant difference for most outcomes in the one trial that compared benzodiazepines with placebo , although there was a higher risk of no improvement in people receiving placebo in the medium term ( one to 48 hours ) ( n = 102 , 1 RCT , RR 0.62 , 95 % CI 0.40 to 0.97 , very low quality evidence ) . There was no difference in the number of participants who had not improved in the medium term when benzodiazepines were compared with antipsychotics ( n = 308 , 5 RCTs , RR 1.10 , 95 % CI 0.85 to 1.42 , low quality evidence ) ; however , people receiving benzodiazepines were less likely to experience extrapyramidal effects ( EPS ) in the medium term ( n = 536 , 8 RCTs , RR 0.15 , 95 % CI 0.06 to 0.39 , moderate quality of evidence ) . Data comparing combined benzodiazepines and antipsychotics versus benzodiazepines alone did not yield any significant results . When comparing combined benzodiazepines/antipsychotics ( all studies compared haloperidol ) with the same antipsychotics alone ( haloperidol ) , there was no difference between groups in improvement in the medium term ( n = 155 , 3 RCTs , RR 1.27 , 95 % CI 0.94 to 1.70 , very low quality evidence ) but sedation was more likely in people who received the combination therapy ( n = 172 , 3 RCTs , RR 1.75 , 95 % CI 1.14 to 2.67 , very low quality evidence ) . However , more participants receiving combined benzodiazepines and haloperidol had not improved by medium term when compared to participants receiving olanzapine ( n = 60,1 RCT , RR 25.00 , 95 % CI 1.55 to 403.99 , very low quality evidence ) or ziprasidone ( n = 60 , 1 RCT , RR 4.00 , 95 % CI 1.25 to 12.75very low quality evidence ) . When haloperidol and midazolam were compared with olanzapine , there was some evidence the combination was superior in terms of improvement , sedation and behaviour . AUTHORS ' CONCLUSIONS The evidence from trials for the use of benzodiazepines alone is not good . There were relatively little good data and most trials are too small to highlight differences in either positive or negative effects . Adding a benzodiazepine to other drugs does not seem to confer clear advantage and has potential for adding unnecessary adverse effects . Sole use of older antipsychotics unaccompanied by anticholinergic drugs seems difficult to justify . Much more high quality research is needed in this area", "Rapid tranquilization is a routinely practice d method of calming agitated psychotic patients by use of neuroleptics , benzodiazepines , or both in combination . Although several studies have examined the efficacy of the three approaches , none have compared these treatments in a prospect i ve , r and omized , double-blind , multicenter trial . Ninety-eight psychotic , agitated , and aggressive patients ( 73 men and 25 women ) were prospect ively enrolled during an 18-month period in emergency departments in five university or general hospitals . Patients were r and omly assigned to receive intramuscular injections of lorazepam ( 2 mg ) , haloperidol ( 5 mg ) , or both in combination . Patients in each treatment group received 1 to 6 injections of the same study drug within 12 hours , based on clinical need . They were evaluated hourly after the first injection until at least 12 hours after the last . Efficacy was assessed on the Agitated Behavior Scale ( ABS ) , a modified Brief Psychiatric Rating Scale ( MBPRS ) , Clinical Global impressions ( CGI ) scale , and an Alertness Scale . Effective symptom reduction was achieved in each treatment group with significant ( P ABS ( hour 1 ) and MBPRS ( hours 2 and 3 ) suggest that tranquilization was most rapid in patients receiving the combination treatment . Study event incidence ( side effects ) did not differ significantly between treatment groups , although patients receiving haloperidol alone tended to have more extrapyramidal system symptoms . The superior results produced by the combination treatment support the use of lorazepam plus haloperidol as the treatment of choice for acute psychotic agitation", "OBJECTIVE To compare the effectiveness of intramuscular olanzapine , ziprasidone , haloperidol plus promethazine , haloperidol plus midazolam and haloperidol alone as the first medication(s ) used to treat patients with agitation and aggressive behavior . METHOD One hundred fifty patients with agitation caused by psychotic or bipolar disorder were r and omly assigned under double-blind conditions to receive olanzapine , ziprasidone , haloperidol plus midazolam , haloperidol plus promethazine or haloperidol alone . The Overt Agitation Severity Scale , Overt Aggression Scale and Ramsay Sedation Scale were applied within 12 hours after the first dosage . RESULTS All medications produced a calming effect within one hour of administration , but only olanzapine and haloperidol reduced agitation by less than 10 points , and only olanzapine reduced aggression by less than four points in the first hour . After twelve hours , only patients treated with haloperidol plus midazolam had high levels of agitation and aggression and also more side effects . Ziprasidone , olanzapine and haloperidol alone had more stable results for agitation control , while ziprasidone , haloperidol plus promethazine and olanzapine had stable results for aggression control . CONCLUSION Olanzapine , ziprasidone , haloperidol plus promethazine , haloperidol plus midazolam and haloperidol were effective in controlling agitation and aggression caused by mental illness over 12 hours . Although all the drugs had advantages and disadvantages , haloperidol plus midazolam was associated with the worst results in all the observed parameters", "Sixteen healthy volunteers were administered midazolam followed by placebo or the benzodiazepine antagonist , flumazenil , in a double-blind , cross-over study . Flumazenil reversed midazolam-induced sedation on the subjective , psychophysiological and motor indices used . In contrast , there was little evidence of any reversal of amnesic effects , which were assessed using both direct ( explicit ) and indirect ( implicit ) measures of memory . Results are discussed in terms of dissociating the sedative and amnesic effects of benzodiazepines", "The combination of haloperidol , 5 mg , and lorazepam , 4 mg , was both effective and safe for managing agitated behavior in an open trial with acutely psychotic patients . The combination also appeared to be superior to its individual components when studied in a r and omized , nonblind trial . The principle of the combined use of antipsychotics and sedative-hypnotics was further tested by comparing two new combinations : thiothixene , 5 mg , and lorazepam , 4 mg , versus haloperidol , 5 mg , and phenobarbital sodium , 130 mg . These combinations had comparable efficacy and safety , and the level of transquilization approached that produced by the haloperidol-lorazepam combination in the preceding studies", "Objective To determine whether haloperidol alone results in swifter and safer tranquillisation and sedation than haloperidol plus promethazine . Design Pragmatic r and omised open trial ( January-July 2004 ) . Setting Psychiatric emergency room , Rio de Janeiro , Brazil . Participants 316 patients who needed urgent intramuscular sedation because of agitation , dangerous behaviour , or both . Interventions Open treatment with intramuscular haloperidol 5 - 10 mg or intramuscular haloperidol 5 - 10 mg plus intramuscular promethazine up to 50 mg ; doses were at the discretion of the prescribing clinician . Main outcome measures The primary outcome was proportion tranquil or asleep by 20 minutes . Secondary outcomes were asleep by 20 minutes ; tranquil or asleep by 40 , 60 , and 120 minutes ; physically restrained or given additional drugs within 2 hours ; severe adverse events ; another episode of agitation or aggression ; additional visit from the doctor during the subsequent 24 hours ; overall antipsychotic load in the first 24 hours ; and still in hospital after 2 weeks . Results Primary outcome data were available for 311 ( 98.4 % ) people , 77 % of whom were thought to have a psychotic illness . Patients allocated haloperidol plus promethazine were more likely to be tranquil or asleep by 20 minutes than those who received intramuscular haloperidol alone ( relative risk 1.30 , 95 % confidence interval 1.10 to 1.55 ; number needed to treat 6 , 95 % confidence interval 4 to 16 ; P=0.002 ) . No differences were found after 20 minutes . However , 10 cases of acute dystonia occurred , all in the haloperidol alone group . Conclusions Haloperidol plus promethazine is a better option than haloperidol alone in terms of speed of onset of action and safety . Enough data are now available to change guidelines that continue to recommend treatments that leave people exposed to longer periods of aggression than necessary and patients vulnerable to distressing and unsafe adverse effects . Trial registration Current Controlled Trials IS RCT N83261243", "A comparison of loxapine and haloperidol parenterally in acute psychotic , agitated patients was carried out as a r and omized double‐blind trial . The trial covered 15 patients in each group , and the diagnoses were psychogenic psychosis ( 18 cases ) and acute schizophrenia ( 12 cases ) . The patients received 25–50 mg loxapine or 2.5–5 mg haloperidol combined with biperiden 2.5–5 mg every 6–12 hours over a 72‐hour period . The average daily dose was 130 mg loxapine or 12 mg haloperidol", "In a double-blind , prospect i ve study , 2 mg of intramuscular lorazepam and 5 mg of intramuscular haloperidol were equally effective in controlling aggression , agitation , and assaultive behavior . Although lorazepam and haloperidol produced an equivalent mean decrease in aggression , significantly more subjects who received lorazepam had a greater decrease in aggression ratings than haloperidol recipients ; this effect was independent of sedation . Lorazepam produced significantly fewer extrapyramidal symptoms . These data support the current clinical practice of using lorazepam ( alone , or in combination with a neuroleptic ) for control of acute aggressive and assaultive behavior", "Abstract Objective To compare two widely used drug treatments for people with aggression or agitation due to mental illness . Design Pragmatic , r and omised clinical trial . Setting Three psychiatric emergency rooms in Rio de Janeiro , Brazil . Subjects 301 aggressive or agitated people . Interventions Open treatment with intramuscular midazolam or intramuscular haloperidol plus promethazine . Main outcome measures Patients tranquil or se date d at 20 minutes . Secondary outcomes : patients tranquil or asleep by 40 , 60 , and 120 minutes ; restrained or given extra drugs within 2 hours ; severe adverse events ; another episode of agitation or aggression ; needing extra visits from doctor during first 24 hours ; overall antipsychotic load in first 24 hours ; and not discharged by two weeks . Results 151 patients were r and omised to midazolam , and 150 to haloperidol-promethazine mix . Follow up for the primary outcome was available for 298 ( 99 % ) : 134/151 ( 89 % ) of patients given midazolam were tranquil or asleep after 20 minutes compared with 101/150 ( 67 % ) of those given haloperidol plus promethazine ( relative risk 1.32 ( 95 % confidence interval 1.16 to 1.49 ) ) . By 40 minutes , midazolam still had a statistically and clinical ly significant 13 % relative advantage ( 1.13 ( 1.01 to 1.26 ) ) . After 1 hour , about 90 % of both groups were tranquil or asleep . One important adverse event occurred in each group : a patient given midazolam had transient respiratory depression , and one given haloperidol-promethazine had a gr and e mal seizure . Conclusions Both treatments were effective . Midazolam was more rapidly sedating than haloperidol-promethazine , reducing the time people are exposed to aggression . Adverse effects and re sources to deal with them should be considered in the choice of the treatment", "The efficacy of a benzodiazepine was compared with that of a neuroleptic for the rapid tranquilization of patients presenting at a psychiatric emergency room service . Thirty-seven highly agitated patients exhibiting psychotic symptoms were r and omly assigned to receive either 2 mg lorazepam or 5 mg haloperidol as needed every 30 min for 4 h. Administration route was either intramuscular injection or oral concentrate . Symptom ratings were conducted each hour using double-blind procedures . Both medications reduced symptom ratings on the Brief Psychiatric Rating Scale and Global Clinical Impression of Overall Symptom Severity Scale . Global Clinical Impression scores for the two medication groups did not differ significantly either at baseline or at 4 h after entry into the study . However , Global Clinical Impression scores of patients in the lorazepam group were less severe at intermittent ratings . The groups did not differ on the Brief Psychiatric Rating Scale at any rating time . No differences were found either in the number of doses administered or in the administration route selected . Given the potential for severe extrapyramidal symptoms developing hours or days after a single dose of haloperidol , lorazepam may provide an excellent alternative for the rapid tranquilization of the acutely agitated psychotic patient in the emergency room setting", "In a double-blind comparative clinical study , both thiothixene and haloperidol were found to be effective agents for rapid tranquilization of manic and schizophrenic patients . While no statistically significant difference in any of the psychopathological areas which may create a psychiatric emergency was found , results of this study provide further substantiation of the notion that thiothixene has favorable effects on anergia" ]

[ "OBJECTIVE The purpose of this prospect i ve study was to determine whether the timing of prophylactic antibiotics at cesarean delivery influences maternal/neonatal infectious morbidity . STUDY DESIGN In this double-blind placebo-controlled trial , cefazolin was given at skin incision ( group A ) or at cord clamping ( group B ) . Patients were eligible for the trial if they had labored and required a cesarean delivery . RESULTS Over a 30-month period 303 patients with singleton pregnancies entered the trial ; 153-group A , 149-group B. Demographics , indication for cesarean delivery ( P = .54 ) , and operative time ( P = .999 ) , as well as rates of endometritis ( RR 0.67 , 95 % CI 0.42 - 1.07 ) , wound infection ( RR 0.84 , 95 % CI 0.45 - 1.55 ) , neonatal sepis ( RR 1.28 , 95 % CI 0.91 - 1.79 ) , and NICU admissions ( RR 1.28 , 95 % CI 0.91 - 1.79 ) were similar between the 2 groups . CONCLUSION There was no difference in maternal infectious morbidity whether antibiotics were given before skin incision or at cord clamping", "In an ongoing prospect i ve study at 2 hospitals , 114 cesarean section patients were studied to determine whether giving ampicillin after umbilical cord clamping is as effective as perioperative ampicillin in reducing maternal postoperative morbidity . The same patients have also been studied to determine the effect of prophylactic cesarean section ampicillin on the newborn . Results have shown that prophylactic ampicillin initiated after cord clamping is as effective in reducing maternal morbidity as ampicillin initiated prior to the surgery . There is also no evidence from our study that the transplacental passage of prophylactic ampicillin increases immediate or delayed neonatal infections", " Eighteen vaginally delivered women who developed late postpartum endometritis seven to 42 days after delivery were prospect ively studied . Multiple microorganisms were recovered from the endometrium , including Chl aim ydia trachomatis , genital mycoplasmas , and a wide variety of bacteria . Erythromycin therapy was successful in ten of the 13 women who were followed", "OBJECTIVES To assess prospect ively the efficiency and safety of two extended spectrum cephalosporins used as pre-operative prophylaxis in nonelective cesarean sections , and compare the results to those of a third group of patients that received cefamezine post cord clamping . METHODS Two hundred and forty one patients undergoing a nonscheduled cesarean section were assigned to receive either cefonicid or ceftriaxone prior to skin incision . These patients were followed prospect ively for infectious and fetal complications . The outcome of these patients was also compared with another group of 194 patients that received cefamezine prophylaxis post cord clamping , and whose data were collected retrospectively . Chi-square analysis of variance were performed with P febrile complications among the two groups of patients that received pre-operative prophylaxis . However , these patients had significantly less wound infections ( P = 0.008 ) and a significantly shorter hospital stay ( P antibiotics post cord clamping . CONCLUSIONS Extended-spectrum cephalosporins , when given pre-operatively , are both effective and safe , and may have an advantage over intra-operative first generation cephalosporins in the reduction of post cesarean section infectious morbidity", "OBJECTIVE : To describe the effect of an extended-spectrum prophylactic antibiotic regimen on postcesarean endometritis . METHODS : This is a cohort study of trends in postcesarean endometritis using data both from prospect i ve surveillance by the infection control unit and from query of our obstetric computerized data base to compare three periods of antibiotic prophylaxis : st and ard narrow-spectrum with intravenous first- or second-generation cephalosporin ( 1992–1996 ) , clinical trial of extended-spectrum with addition of intravenous doxycycline and oral azithromycin ( 1997–1999 ) , and routine use of extended-spectrum with addition of intravenous azithromycin ( 2001–2006 ) to st and ard cephalosporin prophylaxis . RESULTS : A total of 48,913 deliveries at 24 weeks or more of gestation occurred from 1992 to 2006 , of which 10,966 ( 22.4 % ) were cesarean deliveries . Annual cesarean rates increased from 16 % to 27.5 % . Trends in the incidence of postcesarean endometritis revealed a biphasic decrease consistent with the phased introduction of extended-spectrum prophylaxis . Incidence ( 95 % confidence interval [ CI ] ) of endometritis by prospect i ve surveillance dropped from 19.9 % ( 95 % CI 18.6–21.3 % ) to 15.4 % ( 95 % CI 13.2–17.9 % ) during the clinical trial period : relative risk ( RR ) 0.77 ( 95 % CI 0.66–0.91 ) , P=.002 ; and then to 6.3 % ( 95 % CI 5.0–7.9 % ) during routine use of extended-spectrum prophylaxis : RR 0.41 ( 95 % CI 0.31–0.54 ) , P Extended-spectrum antibiotic prophylaxis involving the addition of azithromycin to st and ard narrow-spectrum prophylaxis was associated with a significant reduction in postcesarean endometritis . LEVEL OF EVIDENCE :", "OBJECTIVE To determine if extended spectrum prophylactic antibiotic treatment ( with efficacy against Ureaplasma urealyticum ) reduces post – cesarean delivery clinical endometritis . METHODS After cord clamping at cesarean delivery , subjects received prophylaxis with cefotetan . Subjects were then simultaneously r and omized ( double blind ) to receive doxycyline plus azithromycin versus placebo . Post – cesarean delivery endometritis was defined clinical ly as fever of 100.4F or higher with one or more supporting clinical signs or a physician diagnosis of endometritis plus the absence of a nonpelvic source of fever . RESULTS A total of 597 women were enrolled , 301 in the doxycycline/azithromycin group and 296 in the placebo group . The study population was 56 % black , 25.5 ± 6.2 years of age , and 43 % Noneiparous . The groups were similar ( P > .05 ) for black race , parity , maternal age , and most risk factors for post – cesarean delivery endometritis . The frequency of post – cesarean delivery endometritis ( 16.9 % versus 24.7 % , P = .020 ) , wound infections ( 0.8 % versus 3.6 % , P = .030 ) , and a combination of these two outcomes ( 19.0 % versus 27.8 % , P = .019 ) were significantly lower in the doxycycline/azithromycin group compared with the placebo-treated group . The doxycycline/azithromycin versus placebo groups were dissimilar for maternal leukocytosis ( 24.9 % versus 12.5 % , P = .042 ) and frequency of classic uterine incision ( 7.6 % versus 12.5 % , P = .048 ) . Adjusting for these factors did not alter the risk ratio for post – cesarean delivery endometritis in the active versus placebo-treated group ( relative risk 0.65 , 95 % confidence interval 0.43 , 0.98 ) . Length of stay was longer in the placebo group overall ( 104 ± 56 versus 95 ± 32 hours , P = .016 ) and among women with endometritis ( 146 ± 52 versus 127 ± 46 hours , P = .047 ) . CONCLUSION Extended spectrum prophylactic antibiotic treatment ( with presumed efficacy against U urealyticum ) given to women undergoing cesarean delivery at term shortens hospital stay and reduces the frequency of post – cesarean delivery endometritis and wound infections ", "A protected , triple-lumen transcervical culture method was used to recover organisms from the endometrium . At least one facultative or one anaerobic species of bacteria was recovered from 82 % of the patients , and genital mycoplasmas were recovered from 76 % of the women with endometritis . Bacteria together with genital mycoplasmas were present in 61 % of the women , bacteria alone were present in 20 % , genital mycoplasmas alone were present in 16 % , and Chlamydia trachomatis was isolated from 2 % of the patients . The most common organisms included Gardnerella vaginalis , Peptococcus spp . , Bacteroides spp . , Staphylococcus epidermidis , group B Streptococcus , and Ureaplasma urealyticum . A r and omized , double-blind regimen of either piperacillin or cefoxitin was equally successful in treating the postpartum endometritis", "The objective of this study was to test the hypothesis that 1 g of cefazolin administered preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity . Ninety consecutive laboring subjects undergoing cesarean delivery at > or = 37 weeks gestation were r and omized by computer to receive 1 g of cefazolin intravenously preoperatively or after cord clamping in a double-blinded , placebo-controlled study . The 2 groups were compared for differences in maternal and neonatal demographics , and intrapartum and operative characteristics associated with postcesarean infection . Primary maternal outcome variables were endometritis or wound infection . Secondary outcomes included intra-abdominal abscess formation , septic pelvic thrombophlebitis , pneumonia , or urinary tract infection . Neonatal outcomes included sepsis screens , sepsis , pneumonia , and meningitis . Subjects were followed 6 weeks postoperatively for late complications . Subjects receiving cefazolin preoperatively or after cord clamping had similar maternal and neonatal demographics , and intrapartum and operative characteristics . One patient in the former group experienced both endometritis and wound infection . In the latter group , 2 wound infections and 1 case of endometritis occurred ( P = 0.35 ) . There were no secondary maternal infections . Two infants treated for pneumonia and 2 other infants readmitted with febrile illnesses were born to mothers receiving cefazolin preoperatively . Overall , 8 neonates were evaluated for suspected sepsis and all had negative studies . Six of these infants ' mothers received cefazolin preoperatively ( P = 0.28 ) . In conclusion , 1 gram of cefazolin preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity , but is associated with a trend toward increased suspected sepsis in the newborn . However , this trend may be related to differences between the study groups ' risk factors for infection", "OBJECTIVE The purpose of this study was to characterize the pharmacokinetics of orally administered azithromycin in the term gravid woman . STUDY DESIGN Twenty women who were scheduled for elective cesarean delivery were enrolled prospect ively and received 1 g of oral azithromycin at either 6 , 12 , 24 , 72 , or 168 hours before the operation . All women received spinal anesthesia , at which time a sample of cerebrospinal fluid was obtained for analysis . Maternal serum and urine were obtained immediately before the operation . Intraoperatively , sample s of myometrium , maternal adipose tissue , placenta , amniotic fluid , and umbilical arterial and venous cord blood were obtained . Azithromycin levels were determined quantitatively with high-pressure liquid chromatography with electrochemical detection . RESULTS All participants tolerated the preoperative azithromycin without significant adverse reactions . Peak maternal serum azithromycin levels occurred within 6 hours of drug administration . Although high serum levels of azithromycin were reached early , a rapid decline in drug concentration was noted over the initial 24 hours after the drug administration ( 6-hour : 311 ng/mL ; 24-hour : 63 ng/mL ) . In contrast , azithromycin levels in myometrial , adipose , and placental tissue were higher ( > 500 ng/mL ) and sustained for up to 72 hours after administration . High urine levels of azithromycin ( > 5000 ng/mL ) were noted similarly during the initial 72 hours after drug administration . Umbilical arterial and venous serum azithromycin levels were low ( 19 - 38 ng/mL ) during the first 72 hours . Amniotic fluid levels were highest at 6 hours ( 151 ng/mL ) and declined rapidly . Maternal cerebrospinal azithromycin concentrations were undetectable for all time points . CONCLUSION Azithromycin has a rapid serum half-life in the term gravid woman with a prolonged half-life and high-sustained antibiotic levels noted within myometrium , adipose , and placental tissue . Given the broad antimicrobial spectrum and placental penetration , azithromycin may have potential use for the treatment of perinatal infections", "OBJECTIVE To evaluate the relationship between the presence of microorganisms at the time of cesarean at different sites of the genital tract and the development of postpartum endometritus . METHODS One-hundred thirty-three healthy women who delivered by cesarean were enrolled in this prospect i ve study . Cultures were obtained during the surgery and on days 3 - 5 postoperatively . Gram staining of uterine cavity fluid was done on days 3 - 5 . Gram stains were examined under a high-power microscope for the presence of polymorphonuclear leukocytes . RESULTS Twenty patients ( 15.0 % ) met the criteria for postpartum endometritis . Forty-five patients ( 33.8 % ) had one or more positive cultures ( n = 133 ) at the time of surgery , result ing in 93 positive cultures and 123 bacterial isolates . Forty-four patients had positive postoperative uterine cavity cultures at days 3 - 5 postpartum , result ing in 65 isolates . Of 44 patients with a positive postoperative culture , 26 ( 59.1 % ) also had Gram stain positive for polymorphonuclear leukocytes in the uterine cavity fluid , whereas only six of 89 patients ( 6.7 % ) with negative postoperative culture had a positive Gram stain ( P relative risk of having a positive culture on postoperative day 3 - 5 if the culture at surgery was positive at any site was 15.6 ( 95 % confidence interval [ CI ] 5.9 , 42.2 ) , and it was 19.5 ( 95 % CI 6.8 , 57.8 ) if the culture was positive at the lower uterine segment . CONCLUSION The presence of bacteria in the lower uterine segment at the time of the surgery predicts their presence in the uterine cavity during puerperium . The Gram stain of uterine cavity fluid on postcesarean days 3 - 5 is another quick tool that can expedite the diagnosis of postpartum endometritis", "OBJECTIVE The objective of the study was to determine whether the administration of cefazolin prior to skin incision was superior to administration at the time of umbilical cord clamping for the prevention of postcesarean infectious morbidity . STUDY DESIGN This was a prospect i ve , r and omized , double-blind , placebo-controlled trial . Study subjects received cefazolin 15 - 60 minutes prior to incision and controls received cefazolin at the time of cord clamping . The occurrence of endomyometritis , wound infection , total infectious morbidity , and neonatal complications were compared . RESULTS There were 357 subjects enrolled . No demographic differences were observed between groups . There were decreased total infectious morbidity in the study group ( relative risk [ RR ] = 0.4 , 95 % confidence interval [ CI ] 0.18 to 0.87 ) , decreased endometritis ( RR = 0.2 , 95 % CI 0.15 to 0.94 ) . No increase in neonatal sepsis ( P = .99 ) , sepsis workups ( P = .96 ) , or length of stay ( P = .17 ) was observed . CONCLUSION Administration of prophylactic cefazolin prior to skin incision result ed in a decrease in both endomyometritis and total postcesarean infectious morbidity , compared with administration at the time of cord clamping . This dosing did not result in increased neonatal septic workups or complications", "Objective : To determine the microbiology of wound morbidity following cesarean deliveries . Methods : Nine hundred thirty‐nine wounds in post‐cesarean patients were followed prospect ively . Aspirates from the abdominal incision were collected if the wounds developed erythema , in duration , or pain and had demonstrable fluid collection noted on ultrasound . Cultures were also obtained of wound exu date s when there was spontaneous separation of the skin . Gram stains were performed concomitantly with culture . Results : The cumulative incidence of post‐cesarean wound morbidity between September 1990 and June 1991 was 6.9 % ( 65 of 939 ) , and the rate of culture‐positive wounds was 72 % ( 47 of 65 ) . Ureaplasma urealyticum was the most frequent isolate at a rate of 62 % ( 29 of 47 ) , followed by coagulase‐negative staphylococci at 32 % ( 15 of 47 ) and Enterococcus faecalis at 28 % ( 13 of 47 ) . Gram stains of the exu date s obtained were used to predict microbiologic results . Organisms present on Gram stain yielded a sensitivity of 0.55 , specificity of 1.0 , positive predictive value of 1.0 , and negative predictive value of 0.71 when used to predict positive culture results for bacterial wound infection other than with genital mycoplasmas . White blood cell counts greater than ten per 400 × high‐power fields yielded a sensitivity of 0.83 , specificity of 0.72 , positive predictive value of 0.89 , and negative predictive value of 0.62 when used to predict wound infection including genital mycoplasmas . Conclusions : Genital mycoplasmas are the most prevalent bacterium in post‐cesarean wound infections in this population . If genital mycoplasmas are pathogenic in this setting , then the Gram stain may be useful in predicting wound microbiology . More research is needed on the pathogenic role of genital mycoplasmas in wound infections", "Background Although prophylactic antibiotic medications have been shown to reduce the incidence of postoperative infectious morbidity after cesarean delivery , the most effective regimens have not been established . The purpose of this investigation was to compare the efficacy and costs of prophylaxis with cefazolin alone with cefazolin plus metronidazole . Methods Women undergoing cesarean delivery were r and omized to prophylaxis with 2 g cefazolin ( n = 81 ) or 1 g cefazolin plus 500 mg metronidazole ( n = 79 ) . Postoperative infectious morbidity and the duration of hospitalization in the two groups were compared . Results Thirty-seven ( 23 % ) of 160 patients developed endomyometritis . There was a significant reduction in the number of postoperative infections ( 14 versus 32 % ) and hospital days ( 3.12 versus 4.46 ) with cefazolin and metronidazole prophylaxis ( P = 0.0064 versus P = 0.014 ) compared with cefazolin alone . The estimated antibiotic prophylaxis cost per person was less with cefazolin and metronidazole than with cefazolin alone ( $ 9.12 versus $ 26.73 ) . Conclusion Antibiotic prophylaxis with metronidazole and cefazolin results in fewer postoperative infections , decreased duration of hospitalization , and lower medication cost than cefazolin alone", "OBJECTIVE To estimate the efficacy of preoperative administration of intravaginal metronidazole for the prevention of postcesarean endometritis . METHODS This double‐masked , placebo‐controlled r and omized trial included patients of at least 24 weeks ' gestation undergoing cesarean deliveries for various indications . Patients were r and omized to receive either 5 g of metronidazole gel intravaginally or matching placebo before the initiation of the cesarean . All patients underwent surgical cleansing of the abdomen , and most received prophylactic antibiotics after cord clamping . Patients with chorioamnionitis and /or suspected allergy to metronidazole were excluded . For a two‐sided α of 0.05 and β of 0.20 ( 80 % power ) , 120 subjects were required in each group . The main outcome variable was the incidence of postcesarean endometritis . Secondary outcome variables included presence of febrile morbidity , wound infection , days on antibiotics , and length of postpartum hospitalization . Neonatal outcomes included birth weight , Apgar scores less than 7 at 5 minutes , umbilical arterial pH less than 7.16 , admission and length of stay in the neonatal intensive care unit , and length of hospital stay . RESULTS Of 112 patients receiving metronidazole , eight ( 7 % ) developed postcesarean endometritis , compared with 19 of 112 ( 17 % ) of those receiving placebo gel ( relative risk 0.42 , 95 % confidence interval 0.19 , 0.92 ) . No significant differences were noted between treatment groups with respect to the other outcome variables . CONCLUSION The preoperative administration of 5 g of intravaginal metronidazole gel appears to reduce the incidence of postcesarean endometritis ", "BACKGROUND R and omized , controlled trials have shown that prophylactic antibiotics are effective in preventing surgical-wound infections . However , it is uncertain how the timing of antibiotic administration affects the risk of surgical-wound infection in actual clinical practice . METHODS We prospect ively monitored the timing of antibiotic prophylaxis and studied the occurrence of surgical-wound infections in 2847 patients undergoing elective clean or \" clean-contaminated \" surgical procedures at a large community hospital . The administration of antibiotics 2 to 24 hours before the surgical incision was defined as early ; that during the 2 hours before the incision , as preoperative ; that during the 3 hours after the incision , as perioperative ; and that more than 3 but less than 24 hours after the incision , as postoperative . RESULTS Of the 1708 patients who received the prophylactic antibiotics preoperatively , 10 ( 0.6 percent ) subsequently had surgical-wound infections . Of the 282 patients who received the antibiotics perioperatively , 4 ( 1.4 percent ) had such infections ( P = 0.12 ; relative risk as compared with the preoperatively treated group , 2.4 ; 95 percent confidence interval , 0.9 to 7.9 ) . Of 488 patients who received the antibiotics postoperatively , 16 ( 3.3 percent ) had wound infections ( P less than 0.0001 ; relative risk , 5.8 ; 95 percent confidence interval , 2.6 to 12.3 ) . Finally , of 369 patients who had antibiotics administered early , 14 ( 3.8 percent ) had wound infections ( P less than 0.0001 ; relative risk , 6.7 ; 95 percent confidence interval , 2.9 to 14.7 ) . Stepwise logistic-regression analysis confirmed that the administration of antibiotics in the preoperative period was associated with the lowest risk of surgical-wound infection . CONCLUSIONS We conclude that in surgical practice there is considerable variation in the timing of prophylactic administration of antibiotics and that administration in the two hours before surgery reduces the risk of wound infection", "Objectives . The aim of this study was to document the true incidence of post‐cesarean surgical site infections ( SSI ) , according to the definition of the US Centers for Disease Control and Prevention ( CDC ) , and to identify independent risk factors for infection . Design . Prospect i ve population ‐based cohort study in Norway . Setting . Sykehuset Asker og Bærum HF , a secondary community hospital , associated with the University of Oslo ( UiO ) , Norway , accounting for 2,000 deliveries per year . Participants . All cesarean deliveries during a 12‐month period from September 2003 . Main outcome measures . Rate and risk factors for SSI . Results . The total rate of SSI was 8.9 % , with an observation period of 30 days post‐operatively , compared to 1.8 % registered at hospital discharge . The total response rate was 100 % . There was no significant difference in SSI rate in elective or emergency cesarean section ( CS ) , respectively . All SSI were superficial . We found 2 significant independent risk factors : operating time ≥38 min and body mass index ( BMI ) > 30 . Conclusion . The rate of SSI is underestimated if the observation time is limited to the hospital stay . Operating time exceeding 38 min substantially increases the risk of SSI . The finding of no significant difference in SSI rate between elective and emergency CS should lead to a different approach concerning the use of antibiotics : subgroup at risk ( operating time ≥38 min and BMI > 30 ) may benefit from antibiotics in relation to the operation , whether the CS is an emergency or elective operation", " A r and omized , prospect i ve comparison of ampicillin and ampicillin-gentamicin therapy was conducted in a group of 123 women undergoing primary cesarean section after the onset of labor . All pretreatment patient profiles indicated similar high-risk factors for infection . Febrile morbidity , complication rate and hospital stay were all more favorable in women receiving ampicillin-gentamicin" ]

[ "Aim : To investigate the acceptability and feasibility of adapted group therapy for anxiety in children with autism spectrum disorder in a pilot r and omised controlled trial . Method : A total of 32 children aged 9–13 years were r and omised to immediate or delayed therapy using the ‘ Exploring Feelings ’ manual ( Attwood , 2004 ) . Child and parent groups were run in parallel , for seven weekly sessions , under the supervision of experienced psychologists . The primary blinded outcome measures addressed change in overall functioning and in severity of the primary anxiety diagnosis after 3 months . Results : Children met diagnostic criteria for 1–6 anxiety disorders ( median 3 ) . At end point , both parents and children in the immediate therapy group were more likely to report a reduction in anxiety symptoms . Fidelity of delivery of the group therapy was high , and attendance was 91 % . Conclusions : This pilot trial established that children and families were willing to be recruited and r and omised , the outcome measures were acceptable , the format and content of the groups were feasible within UK child and adolescent mental health services , the intervention was appreciated by families and attrition was very small", "BACKGROUND Children with high-functioning autism spectrum disorders ( ASD ) are at high risk for developing significant anxiety . Anxiety can adversely impact functioning across school , home and community environments . Cognitive behavioral therapies ( CBT ) are frequently used with success for children with anxiety symptoms . Modified CBT interventions for anxiety in children with ASD have also yielded promising results . METHODS Fifty children with high-functioning ASD and anxiety were r and omizedto group CBT or treatment-as-usual ( TAU ) for 12 weeks . Independent clinical evaluators , blind to condition , completed structured interviews ( Anxiety Disorders Interview Schedule – Parent Version;ADIS-P ) pre- and post-intervention condition . RESULTS Forty-seven children completed either the CBT or TAU condition . Results indicated markedly better outcomes for the CBT group . Significant differences by group were noted in Clinician Severity Ratings , diagnostic status , and clinician ratings of global improvement . In the intent-to-treat sample , 10 of 20 children ( 50 % ) in the CBT group had a clinical ly meaningful positive treatment response , compared to 2 of 23 children ( 8.7 % ) in the TAU group . CONCLUSIONS Initial results from this r and omized , design ed treatment study suggest that agroup CBT intervention specifically developed for children with ASD may be effective in decreasing anxiety . Limitations of this study include small sample size , lack of an attention control group , and use of outcome measures normed with typically developing", "Data from a r and omized clinical trial comparing the relative efficacy of individual cognitive-behavioral therapy ( ICBT ) , family CBT ( FCBT ) , and a family-based education/support/attention control ( FESA ) condition were used to examine associations between in-session therapeutic techniques related to parent training ( PT ) and treatment outcomes . This study explored the extent to which therapists ' use of PT techniques , specifically ( a ) parental anxiety management , ( b ) transfer of control from therapist to parent to child over child 's coping , ( c ) communication skills training , and ( d ) contingency management training , contributed to treatment outcome in family-based CBT . Children ( N = 53 ; 31 males ; 7.8 - 13.8 years of age ; M = 10.1 years , SD = 2.3 ; 85 % Caucasian , 9 % African American , 4 % Asian , 2 % \" other \" background ) with a principal anxiety disorder completed 16 sessions of CBT with their parents . The relative contributions of PT components on treatment outcome were evaluated . As hypothesized , both transfer-of-control and parental anxiety management techniques significantly contributed to improvement on clinician and parent ratings of child global functioning within FCBT . PT did not significantly contribute to improvement on measures of child anxiety . These preliminary findings suggest that when FCBT is conducted for child anxiety , PT ( i.e. , transfer-of-control and parental anxiety management techniques ) may contribute to improvements in the child 's global functioning", "Anxiety is common among adolescents with autism spectrum disorders ( ASD ) and may amplify the core social disability , thus necessitating combined treatment approaches . This pilot , r and omized controlled trial evaluated the feasibility and preliminary outcomes of the Multimodal Anxiety and Social Skills Intervention ( MASSI ) program in a sample of 30 adolescents with ASD and anxiety symptoms of moderate or greater severity . The treatment was acceptable to families , subject adherence was high , and therapist fidelity was high . A 16 % improvement in ASD social impairment ( within-group effect size = 1.18 ) was observed on a parent-reported scale . Although anxiety symptoms declined by 26 % , the change was not statistically significant . These findings suggest MASSI is a feasible treatment program and further evaluation is warranted", "OBJECTIVE To examine the efficacy of a modular cognitive-behavioral therapy ( CBT ) protocol relative to treatment as usual ( TAU ) among children with high-functioning autism spectrum disorders ( ASD ) and clinical ly significant anxiety . METHOD A total of 45 children ( 7 - 11 years of age ) with high-functioning ASD and clinical ly significant anxiety were r and omized to receive 16 sessions of weekly CBT or TAU for an equivalent duration . After screening , assessment s were conducted at baseline , post-treatment , and 3-month follow-up . Raters were blind to treatment condition . RESULTS Youth receiving CBT showed substantial improvement relative to TAU on primary anxiety outcomes . Of 24 children r and omized to the CBT arm , 18 ( 75 % ) were treatment responders , versus only 3 of 21 children ( 14 % ) in the TAU arm . Gains were generally maintained at 3-month follow-up for CBT responders . CONCLUSIONS Relative to usual care , CBT adapted for anxious youth with high-functioning ASD demonstrates large effects in reducing anxiety symptoms . This study contributes to the growing literature supporting adapted CBT approaches for treating anxiety in youth with ASD", "BACKGROUND High rates of anxiety disorders , particularly obsessive compulsive disorder ( OCD ) are reported in people with Autism spectrum disorders ( ASD ) . Group cognitive behavioral treatment ( CBT ) has been found effective for anxiety in young people with ASD but not been OCD specific . One uncontrolled pilot study of individual CBT for OCD for adults with ASD showed good treatment efficacy . METHODS Forty-six adolescents and adults ( mean age 26.9 years , 35 Males ) with ASD and comorbid OCD were r and omized to CBT for OCD or anxiety management ( AM ) , a plausible control treatment . Treatments were matched in duration ( mean of 17.4 sessions CBT ; 14.4 sessions AM ) , the Yale-Brown Obsessive Compulsive Severity Scale ( YBOCS ) as primary outcome measure and evaluations blind to treatment group . Treatment response was defined as > 25 % reduction in YBOCS total severity scores . RESULTS Both treatments produced a significant reduction in OCD symptoms , within-group effect sizes of 1.01 CBT group and 0.6 for the AM group . There were no statistically significant differences between the two groups at end of treatment , although more responders in the CBT group ( 45 versus 20 % ) . Effect sizes for self-rated improvement were small ( 0.33 CBT group ; -0.05 AM group ) . Mild symptom severity was associated with improvement in the AM but not the CBT group . Family/carer factors were important for both groups , in that increased family accommodation was associated with poorer outcome . CONCLUSIONS Evidence -based psychological interventions , both AM and CBT , were effective in treating comorbid OCD in young people and adults with ASD", "The purpose of this pilot study was to evaluate whether a modified version of the Coping Cat program could be effective in reducing anxiety in children with autism spectrum disorder ( ASD ) . Twenty-two children ( ages 8–14 ; IQ ≥ 70 ) with ASD and clinical ly significant anxiety were r and omly assigned to 16 sessions of the Coping Cat program ( cognitive-behavioral therapy ; CBT ) or a 16-week waitlist . Children in the CBT condition evidence d significantly larger reductions in anxiety than those in the waitlist . Treatment gains were largely maintained at two-month follow-up . Results provide preliminary evidence that a modified version of the Coping Cat program may be a feasible and effective program for reducing clinical ly significant levels of anxiety in children with high-functioning ASD", "This study aim ed to evaluate the Program for the Education and Enrichment of Relational Skills ( PEERS : Laugeson et al. in J Autism Dev Disord 39(4):596–606 , 2009 ) . PEERS focuses on improving friendship quality and social skills among adolescents with higher-functioning ASD . 58 participants aged 11–16 years-old were r and omly assigned to either an immediate treatment or waitlist comparison group . Results revealed , in comparison to the waitlist group , that the experimental treatment group significantly improved their knowledge of PEERS concepts and friendship skills , increased in their amount of get-togethers , and decreased in their levels of social anxiety , core autistic symptoms , and problem behaviors from pre-to post-PEERS . This study provides the first independent replication and extension of the empirically-supported PEERS social skills intervention for adolescents with ASD", "BACKGROUND Children with autism spectrum disorders often present with comorbid anxiety disorders that cause significant functional impairment . This study tested a modular cognitive behavioral therapy ( CBT ) program for children with this profile . A st and ard CBT program was augmented with multiple treatment components design ed to accommo date or remediate the social and adaptive skill deficits of children with ASD that could pose barriers to anxiety reduction . METHOD Forty children ( 7 - 11 years old ) were r and omly assigned to 16 sessions of CBT or a 3-month waitlist ( 36 completed treatment or waitlist ) . Therapists worked with individual families . The CBT model emphasized behavioral experimentation , parent-training , and school consultation . Independent evaluators blind to treatment condition conducted structured diagnostic interviews and parents and children completed anxiety symptom checklists at baseline and posttreatment/postwaitlist . RESULTS In intent-to-treat analyses , 78.5 % of the CBT group met Clinical Global Impressions-Improvement scale criteria for positive treatment response at posttreatment , as compared to only 8.7 % of the waitlist group . CBT also outperformed the waitlist on diagnostic outcomes and parent reports of child anxiety , but not children 's self-reports . Treatment gains were maintained at 3-month follow-up . CONCLUSIONS The CBT manual employed in this study is one of the first adaptations of an evidence -based treatment for children with autism spectrum disorders . Remission of anxiety disorders appears to be an achievable goal among high-functioning children with autism", "BACKGROUND The aim of the study was to evaluate the effectiveness of a brief CBT intervention for anxiety with children diagnosed with Asperger syndrome ( AS ) . A second interest was to evaluate whether more intensive parent involvement would increase the child 's ability to manage anxiety outside of the clinic setting . METHODS Seventy-one children aged ten to twelve years were recruited to participate in the anxiety programme . All children were diagnosed with AS and the presence of anxiety symptoms was accepted on parent report via brief interview . Children were r and omly assigned to one of three conditions : intervention for child only , intervention for child and parent , wait-list control . RESULTS The two intervention groups demonstrated significant decreases in parent-reported anxiety symptoms at follow-up and a significant increase in the child 's ability to generate positive strategies in an anxiety-provoking situation . There were a number of significant differences between the two interventions to suggest parent involvement as beneficial . CONCLUSIONS The sample of children with AS in this study presented with a profile of anxiety similar to a sample of clinical ly diagnosed anxious children . The intervention was endorsed by parents as a useful programme for children diagnosed with Asperger syndrome and exhibiting anxiety symptoms , and active parent involvement enhanced the usefulness of the programme . Limitations of the study and future research are discussed", "We compared the effects of a 16-week Cognitive-Behavioral Therapy ( CBT ) program and a Social Recreational ( SR ) program on anxiety in children with Autism Spectrum Disorders ( ASD ) . Seventy children ( 9–16 years old ) were r and omly assigned to either of the programs ( nCBT = 36 ; nSR = 34 ) . Measures on child ’s anxiety using the Spence Child Anxiety Scale — Child ( SCAS-C ) and the Clinical Global Impression — Severity scale ( CGI-S ) were administered at pre- , post-treatment , and follow-ups ( 3- and 6-month ) . Children in both programs showed significantly lower levels of generalized anxiety and total anxiety symptoms at 6-month follow-up on SCAS-C. Clinician ratings on the CGI-S demonstrated an increase in the percentage of participants rated as “ Normal ” and “ Borderline ” for both programs . Findings from the present study suggest factors such as regular sessions in a structured setting , consistent therapists , social exposure and the use of autism-friendly strategies are important components of an effective framework in the management of anxiety in children and adolescents with ASD" ]

[ "PURPOSE OF THE STUDY Older adults ' gait is disturbed when a dem and ing secondary cognitive task is added . Gait training has been shown to improve older adults ' walking performance , but it is not clear how training affects their cognitive performance . This study examined the impact on gait , in terms of cost or benefit to cognitive performance , of training healthy older adults to walk to a rhythmic musical beat . DESIGN AND METHODS In a mixed model design , 45 healthy older adults aged more than 65 years ( M = 71.7 years ) were r and omly assigned to 3 groups . One group received a rhythmic musical training and their dual-task ( DT ) walking and cognitive performances were compared with a group who had music playing in the background but no training , and a third group who heard no music and received no training . Outcomes in single-task ( ST ) and DT conditions were step-time variability and velocity for gait and correct cognitive responses for the cognitive task . RESULTS The Musical Training group 's step-time variability improved in both the ST ( p cognitive performance . No change was seen in the control groups . IMPLICATION S Rhythmic musical training can improve gait steadiness in healthy older adults with no negative impact on concurrent cognitive functioning . This could potentially enhance \" postural reserve \" and reduce fall risk", "Background Home-based exercise programs can improve physical functioning and health status of elderly people . Successful implementation of exercise interventions for older people presents major challenges and supporting elderly people properly while doing their home-based exercises is essential for training success . We developed a tablet-based system — ActiveLifestyle — that offers older adults a home-based strength-balance training program with incorporated motivation strategies and support features . Objective The goal was to compare 3 different home-based training programs with respect to their effect on measures of gait quality and physical performance through planned comparisons between ( 1 ) tablet-based and brochure-based interventions , ( 2 ) individual and social motivation strategies , and ( 3 ) active and inactive participants . Methods A total of 44 autonomous-living elderly people ( mean 75 , SD 6 years ) were assigned to 3 training groups : social ( tablet guided , n=14 ) , individual ( tablet guided , n=13 ) , and brochure ( brochure guided , n=17 ) . All groups joined a 12-week progressive home-based strength-balance training program . Outcome measures were gait performance under single and dual task conditions , dual task costs of walking , falls efficacy , and physical performance as measured by the Short Physical Performance Battery ( SPPB ) . Furthermore , active ( ≥75 % program compliance ) and inactive ( in single and dual task walking , whereas there were no significant changes observable in the brochure group . Between-groups comparisons revealed significant differences for gait velocity ( U=138.5 ; P=.03 , r=.33 ) and cadence ( U=138.5 , P=.03 r=.34 ) during dual task walking at preferred speed in favor of the tablet groups . The brochure group had more inactive participants , but this did not reach statistical significance ( U=167 , P=.06 , r=.29 ) . The active participants outperformed the inactive participants in single and dual task walking , dual task costs of walking , and SPPB scores . Significant between-groups differences were seen between the tablet groups and the brochure group , in favor of the tablet groups . Conclusions A tablet-based strength-balance training program that allows monitoring and assisting autonomous-living older adults while training at home was more effective in improving gait and physical performance when compared to a brochure-based program . Social or individual motivation strategies were equally effective . The most prominent differences were observed between active and inactive participants . These findings suggest that in older adults a tablet-based intervention enhances training compliance ; hence , it is an effective way to improve gait", "Background Community ambulation is a highly complex skill requiring the ability to adapt to increased environmental complexity and perform multiple tasks simultaneously . After stroke , individuals demonstrate a diminished ability to perform dual-tasks . Current evidence suggests that conventional rehabilitation does not adequately address gait-related dual-task impairments after stroke , which may be contributing to low levels of participation and physical inactivity in community-dwelling stroke survivors . The objective of this study is to investigate the efficacy of dual-task gait training in community-dwelling adults within 1 year of stroke . Specifically , we will compare the effects of dual-task gait training and single-task gait training on cognitive-motor interference during walking at preferred speed and at fastest comfortable speed ( Aim 1 ) , locomotor control during obstacle negotiation ( Aim 2 ) , and spontaneous physical activity ( Aim 3 ) . Methods / Design This single-blind r and omized controlled trial will involve 44 individuals within 12 months of stroke . Following baseline evaluation , participants will be r and omly allocated to single- or dual-task gait training . Both groups will receive 12 , 30-minute sessions provided one-on-one over 4–6 weeks in an outpatient therapy setting . Single-task gait training involves practice of gait activities incorporating motor relearning principles . Dual-task gait training involves an identical gait training protocol ; the critical difference being that the dual-task gait training group will practice the gait activities while simultaneously performing a cognitive task for 75 % of the repetitions . Blinded assessors will measure outcomes at baseline , post-intervention , and 6 months after completion of the intervention . The primary outcome measure will be dual-task effects on gait speed and cognition during unobstructed walking . Secondary outcomes include spatiotemporal and kinetic gait parameters during unobstructed single- and dual-task walking at preferred and fastest comfortable walking speeds , gait parameters during high and low obstacle crossing , spontaneous physical activity , executive function , lower extremity motor function , Timed Up and Go , balance self-efficacy , number of falls , and stroke-related disability . Hypotheses for each aim will be tested using an intention-to-treat analysis with repeated measures ANOVA design . Discussion This trial will provide evidence to help clinicians make decisions about the types of activities to include in rehabilitation to improve dual-task walking after stroke . Trial registration Clinical Trials.gov", "This study examined transfer effects of fall training on fear of falling ( Falls Efficacy Scale-International [ FES-I ] ) , balance performance , and spatiotemporal gait characteristics in older adults . Eighteen community-dwelling older adults ( ages 65 - 85 ) were r and omly assigned to an intervention or control group . The intervention group completed 12 training sessions ( 60 min , 6 weeks ) . During pre- and posttesting , we measured FES-I , balance performance ( double limb , closed eyes ; single limb , open eyes ; double limb , open eyes with motor-interfered task ) , and gait parameters ( e.g. , velocity ; cadence ; stride time , stride width , and stride length ; variability of stride time and stride length ) under single- and motor-interfered tasks . Dual tasks were applied to appraise improvements of cognitive processing during balance and gait . FES-I ( p = .33 ) and postural sway did not significantly change ( 0.36 for step width during normal walking and stride length variability during the motor dual task ( p = .05 , ηp 2 = .22 ) . Fall training did not sufficiently improve fear of falling , balance , or gait performance under single- or dual-task conditions in healthy older adults", "Objective : To evaluate the effects of a balance training program including dual- and multi-task exercises on fall-related self-efficacy , fear of falling , gait and balance performance , and physical function in older adults with osteoporosis with an increased risk of falling and to evaluate whether additional physical activity would further improve the effects . Design : R and omized controlled trial , including three groups : two intervention groups ( Training , or Training+Physical activity ) and one Control group , with a 12-week follow-up . Setting : Stockholm County , Sweden . Participants : Ninety-six older adults , aged 66 - 87 , with verified osteoporosis . Interventions : A specific and progressive balance training program including dual- and multi-task three times/week for 12 weeks , and physical activity for 30 minutes , three times/week . Main measures : Fall-related self-efficacy ( Falls Efficacy Scale-International ) , fear of falling ( single-item question – ‘ In general , are you afraid of falling ? ’ ) , gait speed with and without a cognitive dual-task at preferred pace and fast walking ( GAITRite ® ) , balance performance tests ( one-leg stance , and modified figure of eight ) , and physical function ( Late-Life Function and Disability Instrument ) . Results : Both intervention groups significantly improved their fall-related self-efficacy as compared to the controls ( p ≤ 0.034 , 4 points ) and improved their balance performance . Significant differences over time and between groups in favour of the intervention groups were found for walking speed with a dual-task ( p=0.003 ) , at fast walking speed ( p=0.008 ) , and for advanced lower extremity physical function ( p=0.034 ) . Conclusions : This balance training program , including dual- and multi-task , improves fall-related self-efficacy , gait speed , balance performance , and physical function in older adults with osteoporosis", "The purpose of this study was to compare the efficiency of three different balance training strategies in an effort to underst and the mechanisms underlying training-related changes in dual-task balance performance of older adults with balance impairment . Elderly individuals with balance impairment , age 65 and older , were r and omly assigned to one of three individualized training programs : single-task ( ST ) balance training ; dual-task training with fixed-priority ( FP ) instruction ; and dual-task training with variable-priority ( VP ) instruction . Balance control during gait , under practice d and novel conditions , was assessed by calculating the center of mass and ankle joint center inclination angles in the frontal plane . A smaller angle indicated better balance performance . Other outcomes included gait velocity , stride length , verbal reaction time , and rate of response . All measures were collected at baseline and the end of the 4-week training . Results indicated that all training strategies were equally effective ( P>.05 ) at improving balance performance ( smaller inclination angle ) under single-task context s. However , the VP training strategy was more effective ( P=.04 ) in improving both balance and cognitive performance under dual-task conditions than either the ST or the FP training strategies . Improved dual-task processing skills did not transfer to a novel dual-task condition . Results support Kramer et al. 's proposal that VP training improves both single-task automatization and the development of task-coordination skills", "Background Previous research has mainly targeted older people with high risk of falling . The effectiveness of exercise interventions in older people with mild levels of balance dysfunction remains unexplored . Objective This study evaluated the effectiveness of a home balance and strength exercise intervention in older people systematic ally screened as having mild balance dysfunction . Design This was a community-based , r and omized controlled trial with assessors blinded to group allocation . Participants Study participants were older people who reported concerns about their balance but remained community ambulant ( n=225 ) . After a comprehensive balance assessment , those classified as having mild balance dysfunction ( n=165 ) were r and omized into the trial . Intervention Participants in the intervention group ( n=83 ) received a 6-month physical therapist – prescribed balance and strength home exercise program , based on the Otago Exercise Program and the Visual Health Information Balance and Vestibular Exercise Kit . Participants in the control group ( n=82 ) continued with their usual activities . Outcome Measures Laboratory and clinical measures of balance , mobility , and strength were assessed at baseline and at a 6-month re assessment . Results After 6 months , the intervention group ( n=59 ) significantly improved relative to the control group ( n=62 ) for : the Functional Reach Test ( mean difference=2.95 cm , 95 % confidence interval [CI]=1.75 to 4.15 ) , the Step Test ( 2.10 steps/15 seconds , 95 % CI=1.17 to 3.02 ) , hip abductor strength ( 0.02 , 95 % CI=0.01 to 0.03 ) , and gait step width ( 2.17 cm , 95 % CI=1.23 to 3.11 ) . There were nonsignificant trends for improvement on most other measures . Fourteen participants in the intervention group ( 23.7 % ) achieved balance performance within the normative range following the exercise program , compared with 3 participants ( 4.8 % ) in the control group . Limitations Loss to follow-up ( 26.6 % ) was slightly higher than in some similar studies but was unlikely to have biased the results . Conclusions A physical therapist – prescribed home exercise program targeting balance and strength was effective in improving a number of balance and related outcomes in older people with mild balance impairment", "Background While many studies confirm the positive effect of cognitive and physical training on cognitive performance of older adults , only little is known about the effects of simultaneously performed cognitive and physical training . In the current study , older adults simultaneously performed a verbal working memory and a cardiovascular training to improve cognitive and motor-cognitive dual task performance . Twenty training sessions of 30 minutes each were conducted over a period of ten weeks , with a test session before , in the middle , and after the training . Training gains were tested in measures of selective attention , paired-associates learning , executive control , reasoning , memory span , information processing speed , and motor-cognitive dual task performance in the form of walking and simultaneously performing a working memory task . Results Sixty-three participants with a mean age of 71.8 ± 4.9 years ( range 65 to 84 ) either performed the simultaneous training ( N = 21 ) , performed a single working memory training ( N = 16 ) , or attended no training at all ( N = 26 ) . The results indicate similar training progress and larger improvements in the executive control task for both training groups when compared to the passive control group . In addition , the simultaneous training result ed in larger improvements compared to the single cognitive training in the paired-associates task and was able to reduce the step-to-step variability during the motor-cognitive dual task when compared to the single cognitive training and the passive control group . Conclusions The simultaneous training of cognitive and physical abilities presents a promising training concept to improve cognitive and motor-cognitive dual task performance , offering greater potential on daily life functioning , which usually involves the recruitment of multiple abilities and re sources rather than a single one", "Background Computer-based interventions have demonstrated consistent positive effects on various physical abilities in older adults . This study aims to compare two training groups that achieve similar amounts of strength and balance exercise where one group receives an intervention that includes additional dance video gaming . The aim is to investigate the different effects of the training programs on physical and psychological parameters in older adults . Methods Thirty-one participants ( mean age ± SD : 86.2 ± 4.6 years ) , residents of two Swiss hostels for the aged , were r and omly assigned to either the dance group ( n = 15 ) or the control group ( n = 16 ) . The dance group absolved a twelve-week cognitive-motor exercise program twice weekly that comprised progressive strength and balance training supplemented with additional dance video gaming . The control group performed only the strength and balance exercises during this period . Outcome measures were foot placement accuracy , gait performance under single and dual task conditions , and falls efficacy . Results After the intervention between-group comparison revealed significant differences for gait velocity ( U = 26 , P = .041 , r = .45 ) and for single support time ( U = 24 , P = .029 , r = .48 ) during the fast walking dual task condition in favor of the dance group . No significant between-group differences were observed either in the foot placement accuracy test or in falls efficacy . Conclusions There was a significant interaction in favor of the dance video game group for improvements in step time . Significant improved fast walking performance under dual task conditions ( velocity , double support time , step length ) was observed for the dance video game group only . These findings suggest that in older adults a cognitive-motor intervention may result in more improved gait under dual task conditions in comparison to a traditional strength and balance exercise program . Trial registration This trial has been registered under IS RCT N05350123 ( http://www.controlled-trials.com", "OBJECTIVES To estimate the magnitude of small meaningful and substantial individual change in physical performance measures and evaluate their responsiveness . DESIGN Secondary data analyses using distribution- and anchor-based methods to determine meaningful change . SETTING Secondary analysis of data from an observational study and clinical trials of community-dwelling older people and subacute stroke survivors . PARTICIPANTS Older adults with mobility disabilities in a strength training trial ( n=100 ) , subacute stroke survivors in an intervention trial ( n=100 ) , and a prospect i ve cohort of community-dwelling older people ( n=492 ) . MEASUREMENTS Gait speed , Short Physical Performance Battery ( SPPB ) , 6-minute-walk distance ( 6MWD ) , and self-reported mobility . RESULTS Most small meaningful change estimates ranged from 0.04 to 0.06 m/s for gait speed , 0.27 to 0.55 points for SPPB , and 19 to 22 m for 6MWD . Most substantial change estimates ranged from 0.08 to 0.14 m/s for gait speed , 0.99 to 1.34 points for SPPB , and 47 to 49 m for 6MWD . Based on responsiveness indices , per-group sample sizes for clinical trials ranged from 13 to 42 for substantial change and 71 to 161 for small meaningful change . CONCLUSION Best initial estimates of small meaningful change are near 0.05 m/s for gait speed , 0.5 points for SPPB , and 20 m for 6MWD and of substantial change are near 0.10 m/s for gait speed , 1.0 point for SPPB , and 50 m for 6MWD . For clinical use , substantial change in these measures and small change in gait speed and 6MWD , but not SPPB , are detectable . For research use , these measures yield feasible sample sizes for detecting meaningful change", "BACKGROUND Falls occur mainly while walking or performing concurrent tasks . We determined whether a music-based multitask exercise program improves gait and balance and reduces fall risk in elderly individuals . METHODS We conducted a 12-month r and omized controlled trial involving 134 community-dwelling individuals older than 65 years , who are at increased risk of falling . They were r and omly assigned to an intervention group ( n = 66 ) or a delayed intervention control group scheduled to start the program 6 months later ( n = 68 ) . The intervention was a 6-month multitask exercise program performed to the rhythm of piano music . Change in gait variability under dual-task condition from baseline to 6 months was the primary end point . Secondary outcomes included changes in balance , functional performances , and fall risk . RESULTS At 6 months , there was a reduction in stride length variability ( adjusted mean difference , -1.4 % ; P Balance and functional tests improved compared with the control group . There were fewer falls in the intervention group ( incidence rate ratio , 0.46 ; 95 % confidence interval , 0.27 - 0.79 ) and a lower risk of falling ( relative risk , 0.61 ; 95 % confidence interval , 0.39 - 0.96 ) . Similar changes occurred in the delayed intervention control group during the second 6-month period with intervention . The benefit of the intervention on gait variability persisted 6 months later . CONCLUSION In community-dwelling older people at increased risk of falling , a 6-month music-based multitask exercise program improved gait under dual-task condition , improved balance , and reduced both the rate of falls and the risk of falling . Trial Registration clinical trials.gov Identifier : NCT01107288", "Objective : The purpose of this pilot trial was to evaluate whether a 24-week program of rhythmic stepping exercise ( RSE ) would be effective in improving physical function and reducing fear of falling in older adults . Participants : Four units ( n = 52 ) r and omized into an RSE group ( two units , n = 25 ) and a non-rhythmic stepping exercise ( NRSE ) group ( two units , n = 27 ) participated in a pilot cluster r and omized controlled trial . Methods : Each exercise group received 60 min group training sessions once a week for 24 weeks . Measurement was based on the difference in physical functions between the RSE and NRSE groups . Results : Significant differences were observed between the two groups for locomotive function with significant group × time interaction . Relative risk was calculated as 2.778 ( 95 % CI : 1.030–7.492 ) for fear of falling for participants in the NRSE group compared with patients in the RSE group ( p = 0.037 ) . Conclusions : The results of this pilot trial suggest that the RSE program is more effective in improving locomotive function and fear of falling", "This r and omized controlled trial examined the effects of multicomponent training on muscle power output , muscle mass , and muscle tissue attenuation ; the risk of falls ; and functional outcomes in frail nonagenarians . Twenty-four elderly ( 91.9 ± 4.1 years old ) were r and omized into intervention or control group . The intervention group performed a twice-weekly , 12-week multicomponent exercise program composed of muscle power training ( 8–10 repetitions , 40–60 % of the one-repetition maximum ) combined with balance and gait retraining . Strength and power tests were performed on the upper and lower limbs . Gait velocity was assessed using the 5-m habitual gait and the time-up- and -go ( TUG ) tests with and without dual-task performance . Balance was assessed using the FICSIT-4 tests . The ability to rise from a chair test was assessed , and data on the incidence and risk of falls were assessed using question naires . Functional status was assessed before measurements with the Barthel Index . Midthigh lower extremity muscle mass and muscle fat infiltration were assessed using computed tomography . The intervention group showed significantly improved TUG with single and dual tasks , rise from a chair and balance performance ( P and a reduced incidence of falls . In addition , the intervention group showed enhanced muscle power and strength ( P the total and high-density muscle cross-sectional area in the intervention group . The control group significantly reduced strength and functional outcomes . Routine multicomponent exercise intervention should be prescribed to nonagenarians because overall physical outcomes are improved in this population", "Background This r and omized controlled pilot study aim ed to explore whether a cognitive-motor exercise program that combines traditional physical exercise with dance video gaming can improve the voluntary stepping responses of older adults under attention dem and ing dual task conditions . Methods Elderly subjects received twice weekly cognitive-motor exercise that included progressive strength and balance training supplemented by dance video gaming for 12 weeks ( intervention group ) . The control group received no specific intervention . Voluntary step execution under single and dual task conditions was recorded at baseline and post intervention ( Week 12 ) . Results After intervention between-group comparison revealed significant differences for initiation time of forward steps under dual task conditions ( U = 9 , P = 0.034 , r = 0.55 ) and backward steps under dual task conditions ( U = 10 , P = 0.045 , r = 0.52 ) in favor of the intervention group , showing altered stepping levels in the intervention group compared to the control group . Conclusion A cognitive-motor intervention based on strength and balance exercises with additional dance video gaming is able to improve voluntary step execution under both single and dual task conditions in older adults", "Objective : To investigate whether a four-week walking exercise programme in patients with knee osteoarthritis improves the ability of dual-task performance in older adults with knee osteoarthritis . Design : A r and omized controlled trial with two groups : a walking group and a control group . Subjects : Forty older adults with knee osteoarthritis , 20 participants in each group . Intervention : The walking intervention was design ed to increase the number of steps walked daily . The walking group was instructed to increase their number of steps to 3000 steps more than before the intervention . Main outcome measures : Dual-task performance was computed by an automaticity index : the walking velocity under single-task condition/under dual-task conditions × 100 ( % ) , defined as automaticity . The nearer to 100 % automaticity , the better the dual-task performance . Decrease of the Trail Making Test ( TMT ) performance was defined as ΔTMT . ΔTMT was calculated as the difference between times ( part B – part A ) as a measure of executive function . In addition , functional ability was measured by the Japanese Knee Osteoarthritis Measure . Results : The walking group improved significantly in automaticity ( P ( 10.4 ) , ΔTMT ( P ) and Japanese Knee Osteoarthritis Measure score ( P found that walking exercise improves executive function and dual-task performance ", "BACKGROUND Falls and fall-related injuries are a major public health concern , a financial challenge for health care providers , and critical issues for older adults . Poor balance and limited mobility are major risk factors for falls . OBJECTIVE The purpose of this study was to examine effects of Feldenkrais exercises in improving balance , mobility , and balance confidence in older adults . METHODS Participants ( N = 47 , mean age 75.6 ) were r and omly assigned to a Feldenkrais group ( FG , n = 25 ) or to a control group ( CG , n = 22 ) . The FG group attended a 5-week Feldenkrais program , 60 minutes three times per week , while the CG group was a waitlist control . The outcome measures were balance ( t and em stance ) , mobility ( Timed Up and Go ) , gait characteristics ( GAITRite Walkway System ) , balance confidence ( Balance Confidence Scale ; ABC ) , and fear of falling ( Falls Efficacy Scale ) . Pre- and post-tests were conducted . RESULTS After completion of the program , balance ( p = 0.030 ) and mobility ( p = 0.042 ) increased while fear of falling ( p = 0.042 ) decreased significantly for the FG group . No other significant changes were observed . However , participants of the FG group showed improvements in balance confidence ( p = 0.054 ) and mobility while performing concurrently a cognitive task ( p = 0.067 ) . CONCLUSIONS These results indicate that Feldenkrais exercises are an effective way to improve balance and mobility , and thus offer an alternative method to help offset age-related declines in mobility and reduce the risk of falling among community-dwelling older adults . A long-term follow-up study of balance and mobility is warranted . Further research is needed to identify whether Feldenkrais exercises may impact cognitive processes", "OBJECTIVE The purpose of this r and omized control trial study was to evaluate the effectiveness of a digital video disc (DVD)-based seated dual-task ( DT ) stepping exercise to improve the DT walking capability in elderly people . In the DT exercise , participants were asked to perform a verbal fluency task while stepping as quickly as possible . METHODS Eight clusters ( n=93 ) r and omized into a DVD group ( 4 clusters , n=48 ) and a nonexercise control group ( 4 clusters , n=45 ) participated in this trial . In the DVD group , participants received 20 min of group training twice a week for 24 weeks . The exercise class used an exercise DVD that included a 15-min basic exercise and a 5-min DT exercise . No exercise program was prescribed for the control group . The measurements were based on the difference in physical function , including DT walking , between the DVD and control groups . In the DT walking test , participants walked individually at a comfortable speed while carrying a ball on a tray . The relative DT lag was calculated by using simple walking as the comparison condition . The Timed Up and Go test and the 5-chair st and test were also performed . RESULTS The median relative adherence to the study was 87.5 % ( 25th-75th percentile , 83.3%-95.8 % ) in the DVD group . The outcome measurements , including the DT walking time and DT time lag ( p DVD group were significantly improved . However , other outcome measurements were not significantly different between the two groups ( p>0.05 ) . CONCLUSION The current study reports the effectiveness of a DVD-based exercise for the improvement of the DT walking capability . A larger study is needed to confirm the present results . Study of a Web-based exercise regime would be valuable to identify the most effective exercise for prevention of falls and fall-related fractures", "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 compare the effect of 3 different approaches to balance training on dual-task balance performance in older adults with balance impairment . DESIGN A double-blind , r and omized controlled trial . SETTING University research laboratory . PARTICIPANTS Older adults ( N=23 ) with balance impairment ( mean age , 74.8y ) . They scored 52 or less on the Berg Balance Scale ( BBS ) and /or walked with a self-selected gait speed of 1.1 m/s or less . INTERVENTIONS Participants were r and omly assigned to 1 of 3 interventions : single-task training , dual-task training with fixed-priority instructions , and dual-task training with variable-priority instructions . Participants received 45-minute individualized training sessions , 3 times a week for 4 weeks . MAIN OUTCOME MEASURES Gait speed under single-task and dual-task conditions was obtained at baseline , the second week , the end of training , and the twelfth week after the end of training . Other measures , including the BBS and the Activities-specific Balance Confidence ( ABC ) Scale , were collected at baseline and after training . RESULTS Participants in all groups improved on the BBS ( P walked significantly faster after training ( P=.02 ; ES=.27 ) . When a cognitive task was added , however , only participants who received dual-task training with fixed-priority instructions and dual-task training with variable-priority instructions exhibited significant improvements in gait speed ( P dual-task training with variable-priority instructions group demonstrated a dual-task training effect at the second week of training and maintained the training effect at the 12-week follow-up . Only the single-task training group showed a significant increase on the ABC after training ( P Dual-task training is effective in improving gait speed under dual-task conditions in elderly participants with balance impairment . Training balance under single-task conditions may not generalize to balance control during dual-task context s. Explicit instruction regarding attentional focus is an important factor contributing to the rate of learning and the retention of the dual-task training effect", "OBJECTIVES To evaluate the effects of a trail-walking exercise ( TWE ) program on the rate of falls in community-dwelling older adults . DESIGN Pilot r and omized controlled trial ( RCT ) . SETTING This trial was conducted in Japan and involved community-dwelling older adults as participants . PARTICIPANTS Sixty participants r and omized into a TWE group ( n=30 ) and a walking ( W ) group ( n=30 ) . INTERVENTION Exercise class combined with multicomponent trail walking program , versus exercise class combined with simple indoor walking program . MEASUREMENT Measurement was based on the difference in fall rates between the TWE and W groups . RESULTS Six months after the intervention , the incidence rate ratio ( IRR ) of falls for the TWE group compared with the W group was 0.20 ( 95 % confidence interval (CI)=0.04 - 0.91 ) ; 12 months after the intervention , the IRR of falls for the TWE group compared with the W group was 0.45 ( 95 % CI=0.16 - 1.77 ) . CONCLUSION The results of this pilot RCT suggest that the TWE program was more effective in improving locomotion and cognitive performance under trail-walking task conditions than walking . In addition , participants who took part in the TWE demonstrated a decrease in the incidence rate of falls 6 months after trial completion . Further confirmation is needed , but this preliminary result may promote a new underst and ing of accidental falls in older adults", "OBJECTIVES Few studies have examined the effects of physical training programs on gait variability while single and dual tasking , and they reported mixed results . The aim of this study was to compare the stride time variability while single and dual tasking before and after a physical training program developed to improve gait stability in French community-dwelling older adults . DESIGN A prospect i ve pre-post interventional cohort study . SETTING The community-dwelling area of \" Pays de la Loire \" , France . POPULATION Forty-eight older adults ( mean age ± st and ard deviation 72.2±8 years ; 75 % female ) . METHODS Physical training program consisted in 12 sessions scheduled to attend physical exercises 1 time a week with total time duration of 3 months . Coefficient of variation ( CoV ) of stride time under three walking conditions ( i.e. , walking alone , walking while backward counting , and while performing a verbal fluency task ) was determined while steady-state walking using the SMTEC ® footswitches system before and after the physical training program . Participants were separated into two groups based on being or not in the highest tertile ( i.e. , worst performance with cutpoint > 4.4 % ) of the CoV of stride time while walking alone . RESULTS After physical training compared to before period , a significant decrease in CoV of stride time ( i.e. , better gait performance ) while walking alone ( 2.8±2.8 % versus 7±7.1 % , P=0.001 ) but not while dual tasking ( P=0.600 for counting backward and P=0.105 for verbal fluency task ) was shown in participants who had highest ( i.e. , worst ) gait variability at baseline . In addition , physical training modified the strategy of dual tasking in participants with highest gait variability at baseline compared to the other participants . Before training , a significant decrease in CoV of stride time ( 7±7.1 % versus 4.9±4.6 % , P=0.017 ) while counting backward was shown , but there was a significant increase after training ( 2.8±2.8 % versus 5.4±5.8 % , P=0.007 ) . CONCLUSIONS Physical training reduced gait variability while walking alone in participants with gait instability , and influenced their strategy for dual tasking . CLINICAL REHABILITATION IMPACT Physical program training developed in the community to improve gait stability should included participants with high gait variability", "The present study highlights the effects of the dual-task cognitive-gait intervention ( CGI ) on working memory and gait functions in older adults with a history of falls . Thirteen older adults with a history of falls were recruited from local community centers and r and omly stratified into either the control ( n = 5 ) or experimental ( n = 8) group . The experimental group received the dual-task cognitive-motor intervention involving simultaneous motor ( walking ) and cognitive ( memory recall ) task whereas the control group received a placebo treatment ( walking with simple music ) . The intervention was provided 30 minutes per session , over a 6-week period . Memory measures included a combination of word recall and arithmetic task . Gait function measures included velocity and center of pressure ( COP ) stability . Non-parametric tests were used at p greater memory performance than the control ( p in gait velocity and stability were observed . Our findings provide the first evidence in literature to demonstrate that the long-term dual-task cognitive-motor intervention improved memory of older adults with a history of falls under the dual cognitive motor task condition ", "Objective : To evaluate the effects of a new , individually adjusted , progressive and specific balance group training programme on fear of falling , step execution , and gait in healthy elderly people with fear of falling and tend to fall . Design : R and omized controlled trial . Setting : The study was conducted in Stockholm County , Sweden . Subjects : Fifty-nine community dwelling elderly people were recruited by advertisement , and allocated at r and om to an intervention group ( n = 38 ) or a control group ( n = 21 ) . Intervention : Individually adjusted , progressive and specific balance group training was given three times a week for three months . The training incorporated elements included in , and required for , independent activities of daily living , and for reactions to loss of balance during dual or multiple tasks . Main measures : Fear of falling was assessed with Falls Efficacy Scale International ( FES-I ) . The reaction time of step execution was measured with the step-execution test , and gait was measured with GAITRite ® . Results : After three months the intervention group showed significant positive changes in the FES-I ( P = 0.008 ) , in the step-execution phase of dual-task performance ( P = 0.012 ) , and in gait at preferred speed during single-task performance ; in cadence ( P = 0.030 ) and , at fast speed , in velocity ( P = 0.004 ) and cadence ( P = 0.001 ) . Significant decreases were also found for the likelihood of depression after participating in the training programme . Conclusion : This new balance training programme is feasible and leads to decreased fear of falling , decreased time for step execution during dual-task performance and increased velocity during fast walking ", "Objective : ( 1 ) To develop a motor – cognition training programme ; ( 2 ) to evaluate the ability to recruit and retain elderly people ; ( 3 ) to assess the effects of the interventions . Design : Pilot r and omized controlled trial . Setting : Assisted living facility . Participants : Sixteen subjects ( 11 female ) living in an assisted living facility were r and omized to a motor or motor – cognition group . Interventions : Both groups received machine-driven strength training and balance exercises for 45 minutes , twice weekly , for 12 weeks . In addition , the motor – cognition group received computerized training for attention 3–5 times per week for 10 weeks . Main outcome measures : Baseline and post-intervention ( 12 weeks ) assessment s focused on recruitment , attrition and adherence . Secondary outcome measures assessed dual-task costs of gait ( velocity , cadence , step time , step length ) , exp and ed timed get-up- and -go , falls efficacy and reaction time . Results : Of 35 subjects initially approached , 16 started and 14 completed the study , result ing in 46 % recruitment , 19 % attrition and > 80 % adherence rates . There is more evidence of altered levels in the motor – cognitive treatment group with significant differences in average change for fear of falling ( P = 0.017 ) and foot reaction time ( P = 0.046 ) . No statistical significance was reached for gait parameters . Conclusions : Motor – cognition training is feasible and shows trends to stronger improvement in walking and reaction time . The application in a main study is deemed feasible . A minimum of ±55 subjects per group are required to achieve a power of 80 % at the 5 % level of significance based on step length and considering the expectable attrition rate in a required larger scale study", "Background Due to the many problems associated with reduced balance and mobility , providing an effective and engaging rehabilitation regimen is essential to progress recovery from impairments and to help prevent further degradation of motor skills . Objectives The purpose of this study was to examine the feasibility and benefits of physical therapy based on a task-oriented approach delivered via an engaging , interactive video game paradigm . The intervention focused on performing targeted dynamic tasks , which included reactive balance controls and environmental interaction . Design This study was a r and omized controlled trial . Setting The study was conducted in a geriatric day hospital . Participants Thirty community-dwelling and ambulatory older adults attending the day hospital for treatment of balance and mobility limitations participated in the study . Interventions Participants were r and omly assigned to either a control group or an experimental group . The control group received the typical rehabilitation program consisting of strengthening and balance exercises provided at the day hospital . The experimental group received a program of dynamic balance exercises coupled with video game play , using a center-of-pressure position signal as the computer mouse . The tasks were performed while st and ing on a fixed floor surface , with progression to a compliant sponge pad . Each group received 16 sessions , scheduled 2 per week , with each session lasting 45 minutes . Measurements Data for the following measures were obtained before and after treatment : Berg Balance Scale , Timed “ Up & Go ” Test , Activities-specific Balance Confidence Scale , modified Clinical Test of Sensory Interaction and Balance , and spatiotemporal gait variables assessed in an instrumented carpet system test . Results Findings demonstrated significant improvements in posttreatment balance performance scores for both groups , and change scores were significantly greater in the experimental group compared with the control group . No significant treatment effect was observed in either group for the Timed “ Up & Go ” Test or spatiotemporal gait variables . Limitations The sample size was small , and there were group differences at baseline in some performance measures . Conclusion Dynamic balance exercises on fixed and compliant sponge surfaces were feasibly coupled to interactive game-based exercise . This coupling , in turn , result ed in a greater improvement in dynamic st and ing balance control compared with the typical exercise program . However , there was no transfer of effect to gait function", "Few studies have reported the effect of exercise intervention for improving postural control deficit in older adults at high risk of falling . We have developed a \" Dual-task Switch Exercise ( DSE ) \" program that focuses on gait initiation performance under the dual-task condition . The purpose of this study was to evaluate whether gait initiation performance could be improved by a specific exercise intervention . Eighteen participants were r and omly assigned to either DSE or control groups . The DSE group received focused training to improve the ability to initiate movements quickly under the dual-task condition . The control group received steady-state walking training . After 30-min of seated training sessions , participants received 5-min individualized training sessions once a week for 24 weeks . In the pre- and post-training period , performance of the steady-state gait ( 10-m walking time ) and gait initiation ( reaction time , backward center of pressure ( COP ) displacement ) were measured under the single- and dual-task conditions . The results of a r and omized clinical trial showed that both groups showed improvement of steady-state walking time under the dual-task condition ( main effect of time ; p=0.018 ) . However , DSE was more effective in improving both the reaction time and backward COP displacement during gait initiation under the dual-task condition than control ( interaction effect of time × group ; reaction time , p=0.015 ; COP displacement , p=0.011 ) . There were no significant differences in steady-state gait and gait initiation performance under the single-task condition between pre- and post-training in both groups . Only the specific exercise intervention improved gait initiation performance under the dual-task condition", "OBJECTIVES To determine the effects of tai chi training on functional performance and walking with and without the addition of the performance of a cognitive task , in older adults living in supportive housing facilities . DESIGN Secondary data analysis comparing a single-blind , r and omized controlled trial of tai chi training with an attention-matched educational control intervention with crossover to tai chi . SETTING Two supportive housing facilities . PARTICIPANTS Sixty-six men and women living in supportive housing facilities entered the study , and 57 aged 87±7 completed all study procedures . INTERVENTION Interventions consisted of two 1-hour-long instructor-led group sessions per week for 12 weeks . Tai chi training consisted of movements based upon the Yang-style short form . Educational sessions consisted of lectures and discussion s of age-related health topics . MEASUREMENTS Subjects were tested for physical function ( Short Physical Performance Battery , SPPB ) , balance ( Berg Balance Scale , BBS ) , mobility ( timed up- and -go , TUG ) , and walking speed under normal and cognitive dual-task conditions . RESULTS The tai chi group exhibited greater improvement in SPPB scores ( baseline 8.1±2.9 , follow-up 9.0±2.6 ) than controls ( baseline 8.2±2.6 , follow-up 8.2±2.6 ) ( P=.005 ) . Tai chi also increased normal and dual-task walking speed ( P affect BBS ( P=.02 ) or TUG ( P=.02 ) after accounting for multiple comparisons . The dual-task cost ( percentage change ) to walking speed was unaffected . After the crossover tai chi intervention , the control group improved performance in the SPPB , BBS , and TUG , and increased walking speed under normal and dual-task conditions ( P=.008 ) . CONCLUSION Tai chi training may be a safe and effective therapy to help improve physical function and dual-task walking in very old adults living in supportive housing facilities", "Decline in dual-task walking performance is associated with increased risk of falls among older adults . The objective of this study is to determine whether 18 hr of participation in EnhanceFitness ( EF ) , an evidence -based group exercise program , improves dual-task walking performance among community-dwelling older adults . Twenty-eight healthy , community-dwelling older adults were evaluated before participating in EF and after 18 hr of participation . Gait speed was evaluated under single task and dual tasks using the TUG ( Timed Up and Go ) and 1-min walk tests . Dual-task costs ( DTC ) , the relative cost of dual-task performance compared to single-task performance , were calculated for both cognitive and motor tasks . Postural control and executive functions were evaluated as well . After 18 hr of EF , dual-task walking performance improved . Single-task performance improved as well as postural control and executive function . There was no significant change in DTC across all measurements , except for the cognitive task of the TUG" ]

[ "BACKGROUND The purpose of this study was to describe bone status in a large cohort of postmenopausal women with nonmetastatic breast cancer , at the initiation of aromatase inhibitor therapy . PATIENTS AND METHODS A prospect i ve , transversal and clinical study was conducted . Each woman had an extensive medical history , a biological evaluation , a bone mineral density ( BMD ) measurement and spinal X-rays . RESULTS Four hundred and ninety-seven women aged 63.8 ± 9.6 years were included in this study . Eighty-five percent of these women had a 25-OH vitamin D concentration T-score nonvertebral fracture with a total of 120 fractures . Spine X-rays evaluation revealed that 20 % of the women had at least one vertebral fracture . The presence of vertebral fracture was associated with nonvertebral fracture history [ odds ratio ( OR ) 1.6 , 95 % confidence interval ( CI ) 1.1 - 2.4 ] and with spine BMD ( OR 1.4 , 95 % CI 1.1 - 1.7 ) . The prevalence of vertebral fracture reached 62.9 % in women with age above 70 years and femoral T-score aromatase inhibitor therapy for breast cancer , a large proportion of women had a vitamin D insufficiency and vertebral fractures", "Objective To examine the association between pre-diagnostic circulating vitamin D concentration , dietary intake of vitamin D and calcium , and the risk of colorectal cancer in European population s. Design Nested case-control study . Setting The study was conducted within the EPIC study , a cohort of more than 520 000 participants from 10 western European countries . Participants 1248 cases of incident colorectal cancer , which developed after enrolment into the cohort , were matched to 1248 controls Main outcome measures Circulating vitamin D concentration ( 25-hydroxy-vitamin-D , 25-(OH)D ) was measured by enzyme immunoassay . Dietary and lifestyle data were obtained from question naires . Incidence rate ratios and 95 % confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models , with adjustment for potential dietary and other confounders . Results 25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer ( P for trend higher colorectal cancer risk ( of 25-(OH)D concentration , patients in the highest quintile had a 40 % lower risk of colorectal cancer than did those in the lowest quintile ( P colon but not rectal cancer ( P for heterogeneity=0.048 ) . Greater dietary intake of calcium was associated with a lower colorectal cancer risk . Dietary vitamin D was not associated with disease risk . Findings did not vary by sex and were not altered by corrections for season or month of blood donation . Conclusions The results of this large observational study indicate a strong inverse association between levels of pre-diagnostic 25-(OH)D concentration and risk of colorectal cancer in western European population s. Further r and omised trials are needed to assess whether increases in circulating 25-(OH)D concentration can effectively decrease the risk of colorectal cancer", "BACKGROUND Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers . However , interventional studies to test this effect are lacking . OBJECTIVE The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk of all types . DESIGN This was a 4-y , population -based , double-blind , r and omized placebo-controlled trial . The primary outcome was fracture incidence , and the principal secondary outcome was cancer incidence . The subjects were 1179 community-dwelling women r and omly selected from the population of healthy postmenopausal women aged > 55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were r and omly assigned to receive 1400 - 1500 mg supplemental calcium/d alone ( Ca-only ) , supplemental calcium plus 1100 IU vitamin D3/d ( Ca + D ) , or placebo . RESULTS When analyzed by intention to treat , cancer incidence was lower in the Ca + D women than in the placebo control subjects ( P unadjusted relative risks ( RR ) of incident cancer in the Ca + D and Ca-only groups were 0.402 ( P = 0.01 ) and 0.532 ( P = 0.06 ) , respectively . When analysis was confined to cancers diagnosed after the first 12 mo , RR for the Ca + D group fell to 0.232 ( CI : 0.09 , 0.60 ; P treatment and serum 25-hydroxyvitamin D concentrations were significant , independent predictors of cancer risk . CONCLUSIONS Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women . This trial was registered at clinical trials.gov as NCT00352170", "There is strong epidemiological and laboratory evidence that vitamin D may be protective against colorectal neoplasia . Therefore , we sought to assess the relationship between serum 25(OH)D levels , dietary intake of vitamin D , and colorectal adenoma recurrence in our ursodeoxycholic acid trial . A total of 568 participants were r and omly selected for analysis of serum 25(OH)D levels . The range of total 25(OH)D was 5.5 - 66.1 ng/ml , with a median of 25.6 ng/ml . After categorizing 25(OH)D levels into tertiles based on the population distribution , the adjusted odds ratios ( 95 % CI ) for adenoma recurrence in the second and third tertiles were 0.88 ( 0.56 - 1.39 ) and 0.78 ( 0.49 - 1.24 ) , respectively . The association between serum 25(OH)D and adenoma recurrence appeared to be stronger among women than men . As compared to those below the median value , women with serum 25(OH)D levels above the median had an OR ( 95 % CI ) of 0.59 ( 0.30 - 1.16 ) ; the corresponding OR ( 95 % CI ) for men was 0.95 ( 0.60 - 1.49 ) . Analyses by dietary vitamin D intake revealed no statistically significant associations . In summary , the results of this study show a moderate , nonsignificant inverse association between serum 25(OH)D levels and reduced risk for colorectal adenoma recurrence , particularly among women", "OBJECTIVE Aromatase inhibitors ( AI ) treatment leads to an increased risk of bone loss and fractures . In a group of women with early breast cancer ( EBC ) and baseline Vitamin D deficiency ( AI , we aim to describe : serum levels of Vitamin D , bone mineral density ( BMD ) , calcium intake , and the increase of serum 25(OH)D accomplished in 3 months of treatment with Vitamin D supplements . STUDY DESIGN Prospect i ve , non-r and omized clinical trial . METHODS In 232 consecutively included women with EBC in treatment with AI , we assessed baseline calcium intake , serum levels of 25(OH)D , BMD and , spine X-ray . All received Calcium and Vitamin D supplements , and those with vitamin deficiency received 16,000 IU Vitamin D every 2 weeks . Serum levels of 25(OH)D were newly assessed after treatment . All the baseline evaluation was performed before starting AI treatment . RESULTS Mean age at baseline ( + /-SD ) was 63.2+/-8.8 years . In 150 ( 64.9 % ) cases , the women had been treated previously with tamoxifen ; 101 ( 43.7 % ) started exemestane , 119 ( 51.5 % ) letrozole , and 11 ( 4.8 % ) anastrozole . The AI were initiated within 6 weeks after surgery or after the last cycle of chemotherapy . At baseline , 88.1 % had 25(OH)D levels severe deficiency ( osteoporosis . Mean daily calcium intake was low ( 841+/-338 ) . We found a significant association between 25(OH)D levels and BMD at baseline , which remained significant in femoral neck BMD after multivariate adjustment . Plasma 25(OH)D levels improved significantly at 3 months follow-up in those treated with high dose Vitamin D supplements : mean increase 32.55 ng/ml ( 95%CI 28.06 - 37.03 ) . CONCLUSIONS Our study suggests a high prevalence of commonly unrecognized Vitamin D deficiency in women with EBC treated with AI , a known osteopenic agent . Our results support the need for a routine assessment of 25(OH)D levels and , when necessary , supplementation in these patients", "Vitamin D deficiency in the patients treated for breast cancer is associated with numerous adverse effects ( bone loss , arthralgia , and falls ) . The first aim of this study was to assess vitamin D status , determined by 25-OH vitamin D levels , among women diagnosed with breast cancer according to demographic/ clinical variables and bone mineral density ( BMD ) . The second aim of this study was to evaluate the effect of daily low-dose and weekly high-dose vitamin D supplementation on 25-OH vitamin D levels . This retrospective study included 224 women diagnosed with stage 0–III breast cancer who received treatment at the James P. Wilmot Cancer Center at the University of Rochester Medical Center . Total 25-OH vitamin D levels ( D2 + D3 ) were determined at baseline for all participants . Vitamin D deficiency was defined as a 25-OH vitamin D level . BMD was assessed during the period between 3 months before and 6 months following the baseline vitamin D assessment . Based on the participants ’ baseline levels , they received either no supplementation , low-dose supplementation ( 1,000 IU/day ) , or high-dose supplementation ( ≥50,000 IU/week ) , and 25-OH vitamin D was reassessed in the following 8–16 weeks . Approximately 66.5 % had deficient/insufficient vitamin D levels at baseline . Deficiency/insufficiency was more common among non-Caucasians , women with later-stage disease , and those who had previously received radiation therapy ( P Breast cancer patients with deficient/insufficient 25-OH vitamin D levels had significantly lower lumbar BMD ( P = 0.03 ) . Compared to the no-supplementation group , weekly high-dose supplementation significantly increased 25-OH vitamin D levels , while daily low-dose supplementation did not significantly increase levels . Vitamin D deficiency and insufficiency were common among women with breast cancer and associated with reduced BMD in the spine . Clinicians should carefully consider vitamin D supplementation regimens when treating vitamin D deficiency/insufficiency in breast cancer patients", "Low pretreatment vitamin D status has been associated with worsened disease outcomes in patients with cancer at various sites . Its prognostic significance in head and neck cancer ( HNC ) patients has not been studied . Patients with HNC who participated in a r and omized trial were evaluated for : ( i ) total intake of vitamin D from diet and supplements using a vali date d food frequency question naire ( all trial participants , n = 540 ) and ( ii ) pretreatment serum 25‐hydroxyvitamin D through a radioimmunoassay ( n = 522 ) . The association of dietary/serum measures of vitamin D status with HNC recurrence , second primary cancer ( SPC ) incidence , and overall mortality was evaluated using multivariate Cox proportional hazard models . There was no significant association between dietary or serum vitamin D measures and the three HNC outcomes . The hazard ratios ( HRs ) comparing the highest with the lowest quartile of dietary/supplemental vitamin D intake were 1.10 ( 95 % confidence interval ( CI ) : 0.66–1.84 ) for recurrence , 1.05 ( 95 % CI : 0.63–1.74 ) for SPC , and 1.27 ( 95 % CI : 0.87–1.84 ) for overall mortality . HRs comparing the uppermost to the lowest quartile of serum 25‐hydroxyvitamin D levels were 1.12 ( 95 % CI : 0.65–1.93 ) for recurrence , 0.72 ( 95 % CI : 0.40–1.30 ) for SPC , and 0.85 ( 95 % CI : 0.57–1.28 ) for overall mortality . There was no effect modification by cancer stage , season of initial treatment , or trial arm . Among patients with HNC , vitamin D status before treatment does not influence disease outcomes . Our results contrast with those from most published studies , which suggest prognostic significance of vitamin D status in cancer patients at least in subgroups", "BACKGROUND Epidemiological studies have yielded inconsistent associations between vitamin D status and prostate cancer risk , and few studies have evaluated whether the associations vary by disease aggressiveness . We investigated the association between vitamin D status , as determined by serum 25-hydroxyvitamin D [ 25(OH)D ] level , and risk of prostate cancer in a case-control study nested within the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial . METHODS The study included 749 case patients with incident prostate cancer who were diagnosed 1 - 8 years after blood draw and 781 control subjects who were frequency matched by age at cohort entry , time since initial screening , and calendar year of cohort entry . All study participants were selected from the trial screening arm ( which includes annual st and ardized prostate cancer screening ) . Conditional logistic regression was used to estimate adjusted odds ratios ( ORs ) with 95 % confidence intervals ( CIs ) by quintile of season-st and ardized serum 25(OH)D concentration . Statistical tests were two-sided . RESULTS No statistically significant trend in overall prostate cancer risk was observed with increasing season-st and ardized serum 25(OH)D level . However , serum 25(OH)D concentrations greater than the lowest quintile ( Q1 ) were associated with increased risk of aggressive ( Gleason sum > or = 7 or clinical stage III or IV ) disease ( in a model adjusting for matching factors , study center , and history of diabetes , ORs for Q2 vs Q1 = 1.20 , 95 % CI = 0.80 to 1.81 , for Q3 vs Q1 = 1.96 , 95 % CI = 1.34 to 2.87 , for Q4 vs Q1 = 1.61 , 95 % CI = 1.09 to 2.38 , and for Q5 vs Q1 = 1.37 , 95 % CI = 0.92 to 2.05 ; P(trend ) = .05 ) . The rates of aggressive prostate cancer for increasing quintiles of serum 25(OH)D were 406 , 479 , 780 , 633 , and 544 per 100 000 person-years . In exploratory analyses , these associations with aggressive disease were consistent across subgroups defined by age , family history of prostate cancer , diabetes , body mass index , vigorous physical activity , calcium intake , study center , season of blood collection , and assay batch . CONCLUSION The findings of this large prospect i ve study do not support the hypothesis that vitamin D is associated with decreased risk of prostate cancer ; indeed , higher circulating 25(OH)D concentrations may be associated with increased risk of aggressive disease ", "Vitamin D insufficiency is common globally and low levels are linked to higher cancer incidence . Although vitamin D insufficiency is related to inferior prognosis in some cancers , no data exist for chronic lymphocytic leukemia/small lymphocytic lymphoma ( CLL/SLL ) . We evaluated the relationship of 25(OH)D serum levels with time-to-treatment ( TTT ) and overall survival ( OS ) in newly diagnosed CLL patients participating in a prospect i ve cohort study ( discovery cohort ) and a separate cohort of previously untreated patients participating in an observational study ( confirmation cohort ) . Of 390 CLL patients in the discovery cohort , 119 ( 30.5 % ) were 25(OH)D insufficient . After a median follow-up of 3 years , TTT ( hazard ratio[HR ] = 1.66 ; P = .005 ) and OS ( HR = 2.39 ; P = .01 ) were shorter for 25(OH)D-insufficient patients . In the validation cohort , 61 of 153 patients ( 39.9 % ) were 25(OH)D insufficient . After a median follow-up of 9.9 years , TTT ( HR = 1.59 ; P = .05 ) and OS ( HR 1.63 ; P = .06 ) were again shorter for 25(OH)D-insufficient patients . On pooled multivariable analysis of patients in both cohorts adjusting for age , sex , Rai stage , CD38 status , ZAP-70 status , immunoglobulin heavy chain variable ( IGHV ) gene mutation status , CD49d status , and cytogenetic abnormalities assessed by interphase fluorescent in situ hybridization testing , 25(OH)D insufficiency remained an independent predictor of TTT ( HR = 1.47 ; P = .008 ) , although the association with OS was not significant ( HR = 1.47 ; P = .07 ) . Vitamin D insufficiency is associated with inferior TTT and OS in CLL patients . Whether normalizing vitamin D levels in deficient CLL patients would improve outcome merits clinical testing", "PURPOSE Previous studies have suggested that higher plasma 25-hydroxyvitamin D(3 ) [ 25(OH)D ] levels are associated with decreased colorectal cancer risk and improved survival , but the prevalence of vitamin D deficiency in advanced colorectal cancer and its influence on outcomes are unknown . PATIENTS AND METHODS We prospect ively measured plasma 25(OH)D levels in 515 patients with stage IV colorectal cancer participating in a r and omized trial of chemotherapy . Vitamin D deficiency was defined as 25(OH)D lower than 20 ng/mL , insufficiency as 20 to 29 ng/mL , and sufficiency as ≥ 30 ng/mL. We examined the association between baseline 25(OH)D level and selected patient characteristics . Cox proportional hazards models were used to calculate hazard ratios ( HR ) for death , disease progression , and tumor response , adjusted for prognostic factors . RESULTS Among 515 eligible patients , 50 % of the study population was vitamin D deficient , and 82 % were vitamin D insufficient . Plasma 25(OH)D levels were lower in black patients compared to white patients and patients of other race ( median , 10.7 v 21.1 v 19.3 ng/mL , respectively ; P .001 ) , and females compared to males ( median , 18.3 v 21.7 ng/mL , respectively ; P = .0005 ) . Baseline plasma 25(OH)D levels were not associated with patient outcome , although given the distribution of plasma levels in this cohort , statistical power for survival analyses were limited . CONCLUSION Vitamin D deficiency is highly prevalent among patients with stage IV colorectal cancer receiving first-line chemotherapy , particularly in black and female patients", "PURPOSE Vitamin D insufficiency is common in the United States , with low levels linked in some studies to higher cancer incidence , including non-Hodgkin 's lymphoma ( NHL ) . Recent data also suggest that vitamin D insufficiency is related to inferior prognosis in some cancers , although there are no data for NHL . PATIENTS AND METHODS We tested the hypothesis that circulating 25-hydroxyvitamin D [ 25(OH)D ] levels are predictive of event-free survival ( EFS ) and overall survival ( OS ) in a prospect i ve cohort of 983 newly diagnosed patients with NHL . 25(OH)D and 1,25-dihydroxyvitamin D [ 1,25(OH)(2)D ] levels were measured by liquid chromatography-t and em mass spectrometry . RESULTS Mean age at diagnosis was 62 years ( range , 19 to 94 years ) ; 44 % of patients had insufficient 25(OH)D levels ( Median follow-up was 34.8 months ; 404 events and 193 deaths ( 168 from lymphoma ) occurred . After adjusting for known prognostic factors and treatment , 25(OH)D insufficient patients with diffuse large B-cell lymphoma ( DLBCL ) had inferior EFS ( hazard ratio [ HR ] , 1.41 ; 95 % CI , 0.98 to 2.04 ) and OS ( HR , 1.99 ; 95 % CI , 1.27 to 3.13 ) ; 25(OH)D insufficient patients with T-cell lymphoma also had inferior EFS ( HR , 1.94 ; 95 % CI , 1.04 to 3.61 ) and OS ( HR , 2.38 ; 95 % CI , 1.04 to 5.41 ) . There were no associations with EFS for the other NHL subtypes . Among patients with DLBCL and T-cell lymphoma , higher 1,25(OH)(2)D levels were associated with better EFS and OS , suggesting that any putative tumor 1-α-hydroxylase activity did not explain the 25(OH)D associations . CONCLUSION 25(OH)D insufficiency was associated with inferior EFS and OS in DLBCL and T-cell lymphoma . Whether normalizing vitamin D levels in these patients improves outcomes will require testing in future trials", "PURPOSE Vitamin D has been linked to breast cancer risk , but prognostic effects are unknown . Such effects are biologically plausible given the presence of vitamin D receptors in breast cancer cells , which act as nuclear transcription factors to regulate gene activity . PATIENTS AND METHODS The study was conducted in a prospect i ve inception cohort of 512 women with early breast cancer diagnosed 1989 to 1996 . Vitamin D levels were measured in stored blood . Clinical , pathologic , and dietary data were accessed to examine prognostic effects of vitamin D. RESULTS Mean age was 50.4 years , mean vitamin D was 58.1 + /- 23.4 nmol/L. Vitamin D levels were deficient ( 72 nmol/L ) in 24.0 % of patients . There was little variation in mean vitamin D levels between summer and winter months . Mean follow-up was 11.6 years ; 116 women had distant recurrences , and 106 women died . Women with deficient vitamin D levels had an increased risk of distant recurrence ( hazard ratio [ HR ] = 1.94 ; 95 % CI , 1.16 to 3.25 ) and death ( HR = 1.73 ; 95 % CI , 1.05 to 2.86 ) compared with those with sufficient levels . The association remained after individual adjustment for key tumor and treatment related factors but was attenuated in multivariate analyses ( HR = 1.71 ; 95 % CI , 1.02 to 2.86 for distant recurrence ; HR = 1.60 ; 95 % CI , 0.96 to 2.64 for death ) . CONCLUSION Vitamin D deficiency may be associated with poor outcomes in breast cancer", "Aromatase inhibitor (AI)-associated arthralgia limits adherence to therapy in breast cancer . The pathophysiology may involve vitamin D status . We wished to establish the optimal concentration of 25(OH)D that prevents or minimizes arthralgia . We used a prospect i ve cohort of 290 women starting AI in whom baseline vitamin D was measured . All received daily vitamin D3 ( 800 IU ) with calcium . Women with baseline 25(OH)D concentration IU of D3 orally every 2 weeks . The primary outcome was incident or worsening joint pain derived from baseline and 3-month visual analogic scale ( VAS ) for joint pain . Regression models were used to analyse the association between vitamin D concentrations at 3 months and pain adjusting for age , BMI , season when the sample was drawn , aromatase inhibitor ( exemestane vs. letrozole/anastrozole ) , prior tamoxifen therapy , baseline NTX , and previous fracture . 90 % of women had a 25(OH)D increase in joint pain ( mean 1.16 points SD 2.66 ; P of incident arthralgia ( OR 0.12 * * [ 0.03 to 0.40 ] ) . A target concentration of 40 ng/ml 25OHD may prevent development of AI arthralgia but higher loading doses are required to attain this level in women with deficiency at baseline ", "BACKGROUND Low serum levels of vitamin D , measured as serum 25-hydroxy-vitamin D ( S-25-OHD ) , have been observed in several cancers . METHODS Sixty-five adult patients with head and neck cancer , 50 men , median age 61 years ( range , 33 - 77 years ) , were enrolled in this prospect i ve cohort study . Concentrations of S-25-OHD and plasma calcium ( Ca ) and phosphate ( Pi ) were measured before cancer treatment . RESULTS The mean S-25-OHD was 42.0 ( SD 22 ) nmol/L. Hypovitaminosis D ( 37.5 - 50 nmol/L ) was found in 20 % of the patients and vitamin D deficiency ( Subnormal plasma Ca and Pi levels were found in 11 % and 9 % of the patients , respectively . CONCLUSION Subnormal vitamin D levels were found in a significant proportion of the patients . Because vitamin D deficiency may pose these patients to increased risk of therapy-related morbidity , special attention should be paid to correction of this nutritional deficiency" ]

[ "Abstract Background Diabetes prevalence is increasing . The Finnish Diabetes Prevention Study ( DPS ) showed a 58 % reduction in Type 2 Diabetes ( T2D ) incidence in adults with impaired glucose tolerance ( IGT ) . The European Diabetes Prevention Study ( EDIPS ) extends the DPS to different European population s , using the same study design . In the Newcastle arm of this study ( EDIPS-Newcastle ) , we tested the hypothesis that T2D can be prevented by lifestyle intervention and explored secondary outcomes in relation to diabetes incidence . Methods We recruited 102 participants ( 42 men and 60 women , mean age 57 years , mean BMI 34 kgm-2 ) with IGT to EDIPS-Newcastle and r and omised to Intervention and usual care Control groups . The intervention included individual motivational interviewing aim ed at : weight reduction , increase in physical activity , fibre and carbohydrate intake and reduction of fat intake ( secondary outcomes ) . The primary outcome was diagnosis of T2D . Results Mean duration of follow-up was 3.1 years . T2D was diagnosed in 16 participants ( I = 5 , C = 11 ) . Absolute incidence of T2D was 32.7 per 1000 person-years in the Intervention-group and 67.1 per 1000 person-years in the Control-group . The overall incidence of diabetes was reduced by 55 % in the Intervention-group , compared with the Control-group : RR 0.45 ( 95%CI 0.2 to 1.2).Explanatory survival analysis of secondary outcomes showed that those who sustained beneficial changes for two or more years reduced their risk of developing T2D . Conclusion Our results are consistent with other diabetes prevention trials . This study was design ed as part of a larger study and although the sample size limits statistical significance , the results contribute to the evidence that T2D can be prevented by lifestyle changes in adults with IGT . In explanatory analysis small sustained beneficial changes in weight , physical activity or dietary factors were associated with reduction in T2D incidence . Trial Registration International St and ard R and omised Controlled Trial Number registry ( IS RCT N)Registry number : IS RCT N 15670600 http://www.controlled-trials.com/is rct n/ search .html?srch=15670600%26sort=3%26dir =", "BACKGROUND Since the Diabetes Prevention Project ( DPP ) demonstrated that lifestyle weight-loss interventions can reduce the incidence of diabetes by 58 % , several studies have translated the DPP methods to public health-friendly context s. Although these studies have demonstrated short-term effects , no study to date has examined the impact of a translated DPP intervention on blood glucose and adiposity beyond 12 months of follow-up . PURPOSE To examine the impact of a 24-month , community-based diabetes prevention program on fasting blood glucose , insulin , insulin resistance as well as body weight , waist circumference , and BMI in the second year of follow-up . DESIGN An RCT comparing a 24-month lifestyle weight-loss program ( LWL ) to an enhanced usual care condition ( UCC ) in participants with prediabetes ( fasting blood glucose=95 - 125 mg/dL ) . Data were collected in 2007 - 2011 ; analyses were conducted in 2011 - 2012 . SETTING / PARTICIPANTS 301 participants with prediabetes were r and omized ; 261 completed the study . The intervention was held in community-based sites . INTERVENTION The LWL program was led by community health workers and sought to induce 7 % weight loss at 6 months that would be maintained over time through decreased caloric intake and increased physical activity . The UCC received two visits with a registered dietitian and a monthly newsletter . MAIN OUTCOME MEASURES The main measures were fasting blood glucose , insulin , insulin resistance , body weight , waist circumference , and BMI . RESULTS Intent-to-treat analyses of between-group differences in the average of 18- and 24-month measures of outcomes ( controlling for baseline values ) revealed that the LWL participants experienced greater decreases in fasting glucose ( -4.35 mg/dL ) ; insulin ( -3.01 μU/ml ) ; insulin resistance ( -0.97 ) ; body weight ( -4.19 kg ) ; waist circumference ( -3.23 cm ) ; and BMI ( -1.40 ) , all p-values reductions in metabolic indicators and adiposity ", "Background R and omised controlled trials demonstrate a 60 % reduction in type 2 diabetes incidence through lifestyle modification programmes . The aim of this study is to determine whether such programmes are feasible in primary health care . Methods An intervention study including 237 individuals 40–75 years of age with moderate or high risk of developing type 2 diabetes . A structured group programme with six 90 minute sessions delivered during an eight month period by trained nurses in Australian primary health care in 2004–2006 . Main outcome measures taken at baseline , three , and 12 months included weight , height , waist circumference , fasting plasma glucose and lipids , plasma glucose two hours after oral glucose challenge , blood pressure , measures of psychological distress and general health outcomes . To test differences between baseline and follow-up , paired t-tests and Wilcoxon rank sum tests were performed . Results At twelve months participants ' mean weight reduced by 2.52 kg ( 95 % confidence interval 1.85 to 3.19 ) and waist circumference by 4.17 cm ( 3.48 to 4.87 ) . Mean fasting glucose reduced by 0.14 mmol/l ( 0.07 to 0.20 ) , plasma glucose two hours after oral glucose challenge by 0.58 mmol/l ( 0.36 to 0.79 ) , total cholesterol by 0.29 mmol/l ( 0.18 to 0.40 ) , low density lipoprotein cholesterol by 0.25 mmol/l ( 0.16 to 0.34 ) , triglycerides by 0.15 mmol/l ( 0.05 to 0.24 ) and diastolic blood pressure by 2.14 mmHg ( 0.94 to 3.33 ) . Significant improvements were also found in most psychological measures . Conclusion This study provides evidence that a type 2 diabetes prevention programme using lifestyle intervention is feasible in primary health care setting s , with reductions in risk factors approaching those observed in clinical trials . Trial NumberCurrent Controlled Trials IS RCT", "The purpose of the present study was to evaluate the impact of a lifestyle intervention programme , combined with a daily low-glycaemic index meal replacement , on body-weight and glycaemic control in subjects with impaired glucose regulation ( IGR ) . Subjects with IGR were r and omly assigned to an intervention group ( n 46 ) and a control group ( n 42 ) . Both groups received health counselling at baseline . The intervention group also received a daily meal replacement and intensive lifestyle intervention to promote healthy eating habits during the first 3 months of the study , and follow-up visits performed monthly until the end of the 1-year study . Outcome measurements included changes in plasma glucose , glycated Hb ( HbA1c ) , plasma lipids , body weight , blood pressure and body composition ( such as body fat mass and visceral fat area ) . The results showed that body-weight loss after 1 year was significant in the intervention group compared with the control group ( -1·8 ( SEM 0·35 ) v. -0·6 ( SEM 0·40 ) 2·5 kg , P decreased 1·24 mmol/l in the intervention group and increased 0·85 mmol/l in the control group ( P 5 kg body-weight loss at 1 year was associated with a decrease of 1·49 mmol/l in 2 h plasma glucose ( P . The incidence of normal glucose regulation ( NGR ) in the two groups was significantly different ( P=0·001 ) . In conclusion , the combination of regular contact , lifestyle advice and meal replacement is beneficial in promoting IGR to NGR", "BACKGROUND The Diabetes Prevention Program ( DPP ) found that an intensive lifestyle intervention can reduce the development of diabetes by more than half in adults with prediabetes , but there is little information about the feasibility of offering such an intervention in community setting s. This study evaluated the delivery of a group-based DPP lifestyle intervention in partnership with the YMCA . METHODS This pilot cluster-r and omized trial was design ed to compare group-based DPP lifestyle intervention delivery by the YMCA to brief counseling alone ( control ) in adults who attended a diabetes risk-screening event at one of two semi-urban YMCA facilities and who had a BMI > or=24 kg/m2 , > or=2 diabetes risk factors , and a r and om capillary blood glucose of 110 - 199 mg/dL. Multivariate regression was used to compare between-group differences in changes in body weight , blood pressures , HbA1c , total cholesterol , and HDL-cholesterol after 6 and 12 months . RESULTS Among 92 participants , controls were more often women ( 61 % vs 50 % ) and of nonwhite race ( 29 % vs 7 % ) . After 6 months , body weight decreased by 6.0 % ( 95 % CI=4.7 , 7.3 ) in intervention participants and 2.0 % ( 95 % CI=0.6 , 3.3 ) in controls ( p total cholesterol ( -22 mg/dL vs + 6 mg/dL controls ; p YMCA sites , it was not possible to adjust for potential clustering by site . CONCLUSIONS The YMCA may be a promising channel for wide-scale dissemination of a low-cost approach to lifestyle diabetes prevention", "BACKGROUND Prior studies have provided evidence that lifestyle change prevents or delays the occurrence of type 2 diabetes mellitus . The challenge is to translate research evidence for type 2 diabetes mellitus prevention into health care setting s. OBJECTIVE We investigated the effect of medical nutrition therapy ( MNT ) compared with usual care on fasting plasma glucose values , glycated hemoglobin ( HbA1c ) , serum lipid levels , and Diabetes Risk Score , from baseline to the end of a 12-week intervention in overweight or obese adults with prediabetes . DESIGN Prospect i ve , r and omized , parallel group study of 76 adults with impaired fasting plasma glucose or an HbA1c of 5.7 % to 6.4 % , recruited between April 2010 and May 2011 who completed a 12-week intervention period . MAIN OUTCOME MEASURES The primary outcome measure was fasting plasma glucose . Secondary outcome measures were HbA1c , serum lipid levels , and Diabetes Risk Score . STATISTICAL ANALYSES A factorial repeated measures analysis of variance was used to make comparisons between the two groups ( the MNT and usual care groups ) and two measures of time ( baseline and 12 weeks postintervention ) . Data analysis was performed using the Statistical Package for the Social Sciences ( release 19.0 , 2010 , SPSS Inc ) . RESULTS There was a significant interaction for group assignment and HbA1c ( P=0.01 ) , with the MNT group experiencing significantly lower HbA1c levels than the usual care group ( 5.79 % vs 6.01 % ) after the 12-week intervention . There was a significant interaction for group assignment and Diabetes Risk Score ( P=0.001 ) . Diabetes Risk Score for the MNT group decreased from 17.54±3.69 to 15.31±3.79 compared with the usual care group score , which went from 17.23±4.69 to 16.83±4.73 . Regardless of group assignment , both groups experienced a reduction in total cholesterol ( P=0.01 ) and low-density lipoprotein cholesterol ( P=0.04 ) level . CONCLUSIONS The results demonstrate that individualized MNT is effective in decreasing HbA1c level in patients diagnosed with prediabetes", "Purpose The objective was to take prevention from the clinic to the community by including a high-risk group and working with the community to tailor , enhance , deliver , and evaluate a community-based version of the Diabetes Prevention Program ’s ( DPP ) clinic-based lifestyle intervention . Methods This was a nonr and omized prospect i ve study using a single-group design . Study eligibility included a screening glucose value in the normal to prediabetes range with no current diagnosis of diabetes , overweight , not pregnant nor planning to become pregnant during study period , aged 18 to 65 , Latino , living in the study target communities , and no reported medical restrictions related to the program goals . A total of 69 individuals participated . The Healthy Living Program ( HLP ) was based on the DPP ’s 1-year intensive lifestyle program , was tailored and enhanced for a Latino community , and was delivered by community health workers . Anthropometric and paper and pencil measures were administered to examine program outcome at 6 months and 12 months . Results In general , results indicate statistically significant improvements in anthropometrics and many behavioral outcomes , particularly at 6 months . Participants demonstrated forward movement through the stages of change during the program . Conclusions Results support the effectiveness of the intervention and show that delivery of the translated version of the DPP ’s lifestyle intervention in the community by community residents holds promise as one strategy to reach people at increased risk of developing diabetes . Use of this translation model , including collaboration with community health workers , offers diabetes educators an opportunity to extend their reach into underserved communities", "Asian Americans experience diabetes at a higher rate than non-Hispanic whites . Diabetes prevention programs using lifestyle interventions have been shown to produce beneficial results , yet there have been no culturally-tailored programs for diabetes prevention in the Korean community . We explore the impact and feasibility of a pilot Community Health Worker ( CHW ) intervention to improve health behaviors and promote diabetes prevention among Korean Americans using a r and omized controlled trial . Between 2011 and 2012 , a total of 48 Korean Americans at risk for diabetes living in New York City ( NYC ) participated in the intervention . Participants were allocated to treatment or control groups . A community-based participatory research approach guided development of the intervention , which consisted of 6 workshops held by CHWs on diabetes prevention , nutrition , physical activity , diabetes complications , stress and family support , and access to health care . Changes over 6 months were examined for clinical measurements ( weight , BMI , waist circumference , blood pressure , glucose , and cholesterol ) ; health behaviors ( physical activity , nutrition , food behaviors , diabetes knowledge , self-efficacy , and mental health ) ; and health access ( insurance and self-reported health ) . In this small pilot study , changes were seen in weight , waist circumference , diastolic blood pressure , physical activity nutrition , diabetes knowledge , and mental health . Qualitative findings provide additional context ual information that inform ways in which CHWs may influence health outcomes . These findings demonstrate that a diabetes prevention program can be successful among a Korean American population in NYC , and important insight is provided for ways that programs can be tailored to meet the needs of vulnerable population ", "Prevention of type 2 diabetes by intensive lifestyle intervention design ed to achieve and maintain ideal body weight was assessed in subjects with impaired glucose tolerance ( IGT ) . Male subjects with IGT recruited from health-screening examinees were r and omly assigned in a 4:1 ratio to a st and ard intervention group ( control group ) and intensive intervention group ( intervention group ) . The final numbers of subjects were 356 and 102 , respectively . The subjects in the control group and in the intervention group were advised to maintain body mass index ( BMI ) of 24.0 kg/m2 and of , respectively , by diet and exercise . In the intervention group , detailed instructions on lifestyle were repeated every 3 - 4 months during hospital visits . Diabetes was judged to have developed when two or more consecutive fasting plasma glucose ( FPG ) values exceeded 140 mg/dl . A 100 g oral glucose tolerance test was performed every 6 months to detect improvement of glucose tolerance . The subjects were seen in an ordinary outpatient clinic . The cumulative 4-year incidence of diabetes was 9.3 % in the control group , versus 3.0 % in the intervention group , and the reduction in risk of diabetes was 67.4 % ( P Body weight decreased by 0.39 kg in the control group and by 2.18 kg in the intervention group ( P decrease in body weight . The incidence of diabetes was positively correlated with the changes in body weight , and the improvement in glucose tolerance was negatively correlated . Subjects with higher FPG at baseline developed diabetes at a higher rate than those with lower FPG . Higher 2h plasma glucose values and higher BMI values at baseline were also associated with a higher incidence of diabetes , but the differences were not significant . Subjects with a low insulinogenic index ( DeltaIRI/DeltaPG 30 min after an oral glucose load ) developed diabetes at a significantly higher rate than those with a normal insulinogenic index . Comparison of the BMI data and incidence of diabetes in five diabetes prevention studies by lifestyle intervention revealed a linear correlation between the incidence of diabetes and the BMI values , with the exception of the DaQing Study . However , the slope of the reduction in incidence of diabetes in the intensive intervention groups was steeper than expected simply on the basis of the reduction of BMI , suggesting that the effect of lifestyle intervention can not be solely ascribed to the body weight reduction . We conclude that lifestyle intervention aim ed at achieving ideal body weight in men with IGT is effective and can be conducted in an outpatient clinic setting", "Aims /hypothesis . The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying Type II ( non-insulin-dependent ) diabetes mellitus in subjects with impaired glucose tolerance , to evaluate the effects of the intervention programme on cardiovascular risk factors and to assess the determinants for the progression to diabetes in persons with impaired glucose tolerance . Methods . A total of 523 overweight subjects with impaired glucose tolerance ascertained by two oral glucose tolerance tests were r and omised to either a control or intervention group . The control subjects received general information at the start of the trial about the lifestyle changes necessary to prevent diabetes and about annual follow-up visits . The intervention subjects had seven sessions with a nutritionist during the first year and a visit every 3 months thereafter aim ed at reducing weight , the intake of saturated fat and increasing the intake of dietary fibre . Intervention subjects were also guided individually to increase their physical activity . Results . During the first year , weight loss in the first 212 study subjects was 4.7 ± 5.5 vs 0.9 ± 4.1 kg in the intervention and control group , respectively ( p The plasma glucose concentrations ( fasting : 5.9 ± 0.7 vs 6.4 ± 0.8 mmol/l , p in blood pressure , serum lipids and anthropometric indices in the intervention group . Conclusion /interpretation . The interim results show the efficacy and feasibility of the lifestyle intervention programme . [ Diabetologia ( 1999 ) 42 : 793–801", "Background Lifestyle change is probably the most important single action to prevent type 2 diabetes mellitus . The purpose of this study was to assess the effects of a low-intensity individual lifestyle intervention by a physician and compare this to the same physician intervention combined with an interdisciplinary , group-based approach in a real-life setting . Methods The \" Finnish Diabetes Risk score \" ( FINDRISC ) was used by GPs to identify individuals at high risk . A r and omised , controlled design and an 18 month follow-up was used to assess the effect of individual lifestyle counselling by a physician ( individual physician group , ( IG ) ) every six months , with emphasis on diet and exercise , and compare this to the same individual lifestyle counselling combined with a group-based interdisciplinary program ( individual and interdisciplinary group , ( IIG ) ) provided over 16 weeks . Primary outcomes were changes in lifestyle indicated by weight reduction ≥ 5 % , improvement in exercise capacity as assessed by VO2 max and diet improvements according to the Smart Diet Score ( SDS ) . Results 213 participants ( 104 in the IG and 109 in the IIG group , 50 % women ) , with a mean age of 46 and mean body mass index 37 , were included ( inclusion rate > 91 % ) of whom 182 returned at follow-up ( drop-out rate 15 % ) . There were no significant differences in changes in lifestyle behaviours between the two groups . At baseline 57 % ( IG ) and 53 % ( IIG ) of participants had poor aerobic capacity and after intervention 35 % and 33 % , respectively , improved their aerobic capacity at least one metabolic equivalent . Unhealthy diets according to SDS were common in both groups at baseline , 61 % ( IG ) and 60 % ( IIG ) , but uncommon at follow-up , 17 % and 10 % , respectively . At least 5 % weight loss was achieved by 35 % ( IG ) and 28 % ( IIG ) . In the combined IG and IIG group , at least one primary outcome was achieved by 93 % while all primary outcomes were achieved by 6 % . Most successful was the 78 % reduction in the proportion of participants with unhealthy diet ( almost 50 % absolute reduction ) . Conclusion It is possible to achieve important lifestyle changes in persons at risk for type 2 diabetes with modest clinical efforts . Group intervention yields no additional effects . The design of the study , with high inclusion and low dropout rates , should make the results applicable to ordinary clinical setting s . Trial registration Clinical Trials.gov :", "OBJECTIVE Although the Diabetes Prevention Program ( DPP ) and the Finnish Diabetes Prevention Study ( FDPS ) demonstrated that weight loss from lifestyle change reduces type 2 diabetes incidence in patients with prediabetes , the translation into community setting s has been difficult . The objective of this study is to report the first-year results of a community-based translation of the DPP lifestyle weight loss ( LWL ) intervention on fasting glucose , insulin resistance , and adiposity . RESEARCH DESIGN AND METHODS We r and omly assigned 301 overweight and obese volunteers ( BMI 25–40 kg/m2 ) with fasting blood glucose values between 95 and 125 mg/dL to a group-based translation of the DPP LWL intervention administered through a diabetes education program ( DEP ) and delivered by community health workers ( CHWs ) or to an enhanced usual-care condition . CHWs were volunteers with well-controlled type 2 diabetes . A total of 42.5 % of participants were male , mean age was 57.9 years , 26 % were of a race/ethnicity other than white , and 80 % reported having an education beyond high school . The primary outcome is mean fasting glucose over 12 months of follow-up , adjusting for baseline glucose . RESULTS Compared with usual-care participants , LWL intervention participants experienced significantly greater decreases in blood glucose ( −4.3 vs. −0.4 mg/dL ; P 0.001 ) , insulin ( −6.5 vs. −2.7 μU/mL ; P ( −1.9 vs. −0.8 ; P ( −7.1 vs. −1.4 kg ; P ) , BMI ( −2.1 vs. −0.3 kg/m2 ; P ) , and waist circumference ( −5.9 vs. −0.8 cm ; P translation of the DPP intervention conducted in community setting s , administered through a DEP , and delivered by CHWs holds great promise for the prevention of diabetes by significantly decreasing glucose , insulin , and adiposity ", "OBJECTIVE The aim of this study was to assess the effectiveness of a new dietary education ( NDE ) program in reducing plasma glucose ( PG ) levels in Japanese male workers at high risk for type 2 diabetes through a r and omized controlled trial . RESEARCH DESIGN AND METHODS We r and omly assigned 173 high-risk men ( mean age , 55 years ) to either the NDE or the control ( conventional dietary education ) group . Each subject in the NDE group received two individualized interventions especially aim ed at reducing total energy intake at dinner by modifying dietary intake . The control group received conventional group counseling . An \" overintake/underintake fraction \" for total energy intake was used to measure the status of dietary intake . Our hypothesis was that the NDE group would have a 10 % decrease in 2-h PG 1 year after the start of the education . Outcome measures were compared with ANCOVA by adjusting for baseline values . RESULTS The NDE group had a significantly lower total energy intake at dinner and daily than the control group . The adjusted differences in changes from baseline in the absolute value of the ' overintake/underintake fraction ' were -15.3 % ( 95 % CI -24.6 to -6.0 % , P = 0.002 ) for dinner and -6.0 % ( -9.8 to -2.2 % , P = 0.002 ) for daily [ corrected ] . The NDE group had a decreased 2-h PG after 1 year , whereas that value was increased in the control group . The adjusted difference in the percent change of 2-h PG was significant ( -15.2 % , -22.0 to -8.4 % , P glucose levels in high-risk subjects for type 2 diabetes ", "BACKGROUND The Diabetes Prevention Program ( DPP ) lifestyle intervention reduced the incidence of type 2 diabetes mellitus ( DM ) among high-risk adults by 58 % , with weight loss as the dominant predictor . However , it has not been adequately translated into primary care . METHODS We evaluated 2 adapted DPP lifestyle interventions among overweight or obese adults who were recruited from 1 primary care clinic and had pre-DM and /or metabolic syndrome . Participants were r and omized to ( 1 ) a coach-led group intervention ( n = 79 ) , ( 2 ) a self-directed DVD intervention ( n = 81 ) , or ( 3 ) usual care ( n = 81 ) . During a 3-month intensive intervention phase , the DPP-based behavioral weight-loss curriculum was delivered by lifestyle coach-led small groups or home-based DVD . During the maintenance phase , participants in both interventions received lifestyle change coaching and support remotely-through secure email within an electronic health record system and the American Heart Association Heart360 website for weight and physical activity goal setting and self-monitoring . The primary outcome was change in body mass index ( BMI ) ( calculated as weight in kilograms divided by height in meters squared ) from baseline to 15 months . RESULTS At baseline , participants had a mean ( SD ) age of 52.9 ( 10.6 ) years and a mean BMI of 32.0 ( 5.4 ) ; 47 % were female ; 78 % , non-Hispanic white ; and 17 % , Asian/Pacific Isl and er . At month 15 , the mean ± SE change in BMI from baseline was -2.2 ± 0.3 in the coach-led group vs -0.9 ± 0.3 in the usual care group ( P self-directed group vs usual care ( P = .02 ) . The percentages of participants who achieved the 7 % DPP-based weight-loss goal were 37.0 % ( P = .003 ) and 35.9 % ( P = .004 ) in the coach-led and self-directed groups , respectively , vs 14.4 % in the usual care group . Both interventions also achieved greater net improvements in waist circumference and fasting plasma glucose level . CONCLUSION Proven effective in a primary care setting , the 2 DPP-based lifestyle interventions are readily scalable and exportable with potential for substantial clinical and public health impact . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00842426", "Introduction Although lifestyle interventions are effective in delaying the onset of diabetes , translating these lessons to routine health care setting s remains a challenge . We investigated the effectiveness of a theory-based , brief , small-group weight loss intervention for diabetes prevention . A secondary purpose was to determine the potential reach of the intervention . Methods A total of 14,379 members of an integrated health care organization newly diagnosed with prediabetes were potentially eligible to participate in this matched cohort longitudinal study . Of this group , 1,030 attended a 90-minute , small-group session that targeted personal action planning for healthful eating , physical activity , and weight management . We accessed electronic medical records to select 1 to 2 controls ( matched on impaired fasting glucose measurement , sex , age , and body mass index ) for each member who attended the small-group session ( n = 760 ) . Weight change , as recorded in the medical record , was the primary outcome . Mixed models analyses were used to adjust for matching variables and covariates and to account for individual r and om effects over time . Results Small-group participants lost significantly more weight than did their matched controls . A significantly higher proportion of small-group participants lost at least 5 % of their body weight compared with controls . Conclusion A brief , small-group weight loss intervention was effective . However , it did not reach broadly into the population that was at risk for diabetes", "OBJECTIVE To describe the 1 ) lifestyle intervention used in the Finnish Diabetes Prevention Study , 2 ) short- and long-term changes in diet and exercise behavior , and 3 ) effect of the intervention on glucose and lipid metabolism . RESEARCH DESIGN AND METHODS There were 522 middle-aged , overweight subjects with impaired glucose tolerance who were r and omized to either a usual care control group or an intensive lifestyle intervention group . The control group received general dietary and exercise advice at baseline and had an annual physician 's examination . The subjects in the intervention group received additional individualized dietary counseling from a nutritionist . They were also offered circuit-type resistance training sessions and advised to increase overall physical activity . The intervention was the most intensive during the first year , followed by a maintenance period . The intervention goals were to reduce body weight , reduce dietary and saturated fat , and increase physical activity and dietary fiber . RESULTS The intervention group showed significantly greater improvement in each intervention goal . After 1 and 3 years , weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control group , respectively . Measures of glycemia and lipemia improved more in the intervention group . CONCLUSIONS The intensive lifestyle intervention produced long-term beneficial changes in diet , physical activity , and clinical and biochemical parameters and reduced diabetes risk . This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system", "Objective To evaluate the use and effectiveness of two “ in-home ” strategies for delivering diabetes prevention programming using cable television . Methods An individually r and omized , two-arm intervention trial including adults with diabetes risk factors living in two US cities . Interventions involved a 16-session lifestyle intervention delivered via “ video-on-dem and ” cable television , offered alone versus in combination with web-based lifestyle support tools . Repeated measures longitudinal linear regression with imputation of missing observations was used to compare changes in body weight . Results A total of 306 individuals were r and omized and offered the interventions . After 5 months , 265 ( 87 % ) participants viewed at least 1 , and 110 ( 36 % ) viewed ≥9 of the video episodes . A total of 262 ( 86 % ) participants completed a 5-month weight measurement . In intention-to-treat analysis with imputation of missing observations , mean weight loss at 5 months for both treatment groups combined was 3.3 % ( 95 % CI 0.7 - 5.0 % ) , regardless of intervention participation ( with no differences between r and omized groups ( P = 0.19 ) ) , and was 4.9 % ( 95 % CI 2.1 - 6.5 % ) for participants who viewed ≥9 episodes . Conclusions In-home delivery of evidence -based diabetes prevention programming in a reality television format , offered with or without online behavioral support tools , can achieve modest weight losses consistent with past implementation studies of face-to-face programs using similar content", "Background A r and omized control trial was performed to test whether a lifestyle intervention program , carried out in a primary healthcare setting using existing re sources , can reduce the incidence of type 2 diabetes in Japanese with impaired glucose tolerance ( IGT ) . The results of 3 years ' intervention are summarized . Methods Through health checkups in communities and workplaces , 304 middle-aged IGT subjects with a mean body mass index ( BMI ) of 24.5 kg/m2 were recruited and r and omized to the intervention group or control group . The lifestyle intervention was carried out for 3 years by public health nurses using the curriculum and educational material s provided by the study group . Results After 1 year , the intervention had significantly improved body weight ( -1.5 ± 0.7 vs. -0.7 ± 2.5 kg in the control ; p = 0.023 ) and daily non-exercise leisure time energy expenditure ( 25 ± 113 vs. -3 ± 98 kcal ; p = 0.045 ) . Insulin sensitivity assessed by the Matsuda index was improved by the intervention during the 3 years . The 3-year cumulative incidence tended to be lower in the intervention group ( 14.8 % vs.8.2 % , log-rank test : p = 0.097 ) . In a sub- analysis for the subjects with a BMI > 22.5 kg/m2 , a significant reduction in the cumulative incidence was found ( p = 0.027 ) . Conclusions The present lifestyle intervention program using existing healthcare re sources is beneficial in preventing diabetes in Japanese with IGT . This has important implication s for primary healthcare-based diabetes prevention . Trial registration", "CONTEXT Weight loss programs on the Internet appear promising for short-term weight loss but have not been studied for weight loss in individuals at risk of type 2 diabetes ; thus , the longer-term efficacy is unknown . OBJECTIVE To compare the effects of an Internet weight loss program alone vs with the addition of behavioral counseling via e-mail provided for 1 year to individuals at risk of type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS A single-center r and omized controlled trial conducted from September 2001 to September 2002 in Providence , RI , of 92 overweight adults whose mean ( SD ) age was 48.5 ( 9.4 ) years and body mass index , 33.1 ( 3.8 ) . INTERVENTIONS Participants were r and omized to a basic Internet ( n = 46 ) or to an Internet plus behavioral e-counseling program ( n = 46 ) . Both groups received 1 face-to-face counseling session and the same core Internet programs and were instructed to su bmi t weekly weights . Participants in e-counseling su bmi tted calorie and exercise information and received weekly e-mail behavioral counseling and feedback from a counselor . MAIN OUTCOME MEASURES Measured weight and waist circumference at 0 and 12 months . RESULTS Intent-to-treat analyses showed the behavioral e-counseling group lost more mean ( SD ) weight at 12 months than the basic Internet group ( -4.4 [ 6.2 ] vs -2.0 [ 5.7 ] kg ; P = .04 ) , and had greater decreases in percentage of initial body weight ( 4.8 % vs 2.2 % ; P = .03 ) , body mass index ( -1.6 [ 2.2 ] vs -0.8 [ 2.1 ] ; P = .03 ) , and waist circumference ( -7.2 [ 7.5 ] vs -4.4 [ 5.7 ] cm ; P = .05 ) . CONCLUSION Adding e-mail counseling to a basic Internet weight loss intervention program significantly improved weight loss in adults at risk of diabetes", "OBJECTIVES Our community-academic partnership employed community-based participatory research to develop and pilot a simple , peer-led intervention to promote weight loss , which can prevent diabetes and eliminate racial/ethnic disparities in incident diabetes among overweight adults with prediabetes . METHODS We recruited overweight adults at community sites , performed oral glucose tolerance testing to identify persons with blood glucose levels in the prediabetes range , and r and omized eligible people to a peer-led lifestyle intervention group or delayed intervention in 1 year . Outcomes , including weight , blood pressure , and health behaviors , were measured at baseline and 3 , 6 , and 12 months . RESULTS More than half of those tested ( 56 % , or 99 of 178 ) had prediabetes and enrolled in the study . Participants were predominantly Spanish-speaking , low-income , undereducated women . The intervention group lost significantly more weight than the control group and maintained weight loss at 12 months ( 7.2 versus 2.4 pounds ; P to diabetes . CONCLUSIONS In underserved minority communities , prediabetes prevalence may be higher than previously reported . Low-cost , community-based interventions can succeed in encouraging weight loss to prevent diabetes", "BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects", "Purpose The purpose of this study was to evaluate the efficacy of Prevent , an online social network-based translation of the Diabetes Prevention Program ( DPP ) lifestyle intervention , against the Centers for Disease Control and Prevention ( CDC ) Diabetes Prevention and Recognition Program ( DPRP ) outcome st and ards and weight loss outcomes of other DPP translations . Methods Two hundred twenty participants previously diagnosed with prediabetes were recruited online and enrolled in Prevent , a DPP-based group lifestyle intervention that integrates a private online social network , weekly lessons , health coaching , and a wireless scale and pedometer . Participants underwent a core 16-week intensive lifestyle change intervention and were then offered to continue with a post-core lifestyle change maintenance intervention , with the entire intervention ( core plus post-core ) totaling 12 months . Results One hundred eighty-seven participants met inclusion criteria for the core program and achieved an average of 5.0 % and 4.8 % weight loss at 16 weeks and 12 months , respectively . They also had a 0.37 % reduction in their A1C level at final measurement . One hundred forty-four of these same participants also met inclusion criteria for the post-core program and achieved an average of 5.4 % and 5.2 % weight loss at 16 weeks and 12 months , respectively , and a 0.40 % reduction in A1C at final measurement . Conclusion Results indicate that Prevent meets CDC DPRP outcome st and ards for diabetes prevention programs and performs favorably to other DPP translations . Considering national initiatives to address the obesity and diabetes epidemics , online delivery platforms like Prevent offer an effective and scalable solution", "The objective of the present study was to explore whether a culturally adapted lifestyle education programme would improve the risk factor profile for type 2 diabetes ( T2D ) and the metabolic syndrome ( MetS ) among Pakistani immigrant women in Oslo , Norway . The r and omised controlled trial ( the InnvaDiab study ) , lasting 7 ± 1 months , comprised six educational sessions about blood glucose , physical activity and diet . Participants ( age 25 - 62 years ) were r and omised into either a control ( n 97 ) or an intervention ( n 101 ) group . Primary outcome variables were fasting and 2 h blood glucose , and secondary outcome variables were fasting levels of insulin , C-peptide , lipids , glycated Hb , BMI , waist circumference and blood pressure , measured 1 - 3 weeks before and after the intervention . During the intervention period , the mean fasting blood glucose decreased by 0·16 ( 95 % CI -0·27 , -0·05 ) mmol/l in the intervention group , and remained unchanged in the control group ( difference between the groups , P=0·022 ) . Glucose concentration 2 h after the oral glucose tolerance test decreased by 0·53 ( 95 % CI -0·84 , -0·21 ) mmol/l in the intervention group , but not significantly more than in the control group . A larger reduction in fasting insulin was observed in the intervention group than in the control group ( between-group difference , P= 0·036 ) . Among the individuals who attended four or more of the educational sessions ( n 59 ) , we found a more pronounced decrease in serum TAG ( -0·1 ( 95 % CI -0·24 , 0·07 ) mmol/l ) and BMI ( -0·48 ( 95 % CI -0·78 , -0·18 ) kg/m² ) compared with the control group . During the intervention period , there was a significant increase in participants having the MetS in the control group ( from 41 to 57 % ) , which was not seen in the intervention group ( from 44 to 42 % ) . Participation in a culturally adapted education programme may improve risk factors for T2D and prevent the development of the MetS in Pakistani immigrant women", "OBJECTIVE To determine the feasibility of implementing a large-scale primary care-based diabetes prevention trial . METHODS A feasibility cluster r and omized controlled trial was conducted in British Columbia , Canada , amongst adults with prediabetes using the Facilitated Lifestyle Intervention Prescription ( FLIP ) vs. usual care . FLIP included lifestyle advice , a pedometer , and telephone support from a lifestyle facilitator for 6 months . Indicators of feasibility included recruitment rates of family practice s , participants and facilitators , as well as feasibility and retention rates in the FLIP program and study protocol s. RESULTS Six family practice s participated ; 59 patients were enrolled between October 2012 and March 2013 . The trial protocol was acceptable to practice s and participants and had a 95 % participant retention rate over the 6 months ( 56/59 ) . Adherence to the intervention was high ( 97 % ) , with 34 of 35 patients continuing to receive telephone calls from the facilitator for 6 months . The mean cost of the intervention was C$ 144 per person . Compared with control , intervention participants significantly reduced weight by 3.2 kg ( 95 % CI , 1.7 to 4.6 ) ; body mass index by 1.2 ( 95 % CI , 0.7 to 1.7 ) and waist circumference by 3 cm ( 95 % CI , 0.3 to 5.7 ) . CONCLUSIONS It is feasible to implement FLIP and to conduct a trial to assess effectiveness . A larger trial with longer follow up to assess progression to diabetes is warranted", "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", "This study was a r and omised control trial with a waiting control group . It was design ed to evaluate the effectiveness of a 6-month , group-based diabetes prevention programme , The Healthy Living Course and assess whether participation in the programme led to changes in modifiable risk factors for type 2 diabetes among an already at-risk pre-diabetic population . Individuals design ated at risk for diabetes by their general practitioners ( GPs ) were screened using an Oral Glucose Tolerance Test . Volunteers ( N = 307 ) with pre-diabetes were assigned to an intervention or wait-control group in the ratio of approximately 2 : 1 . The sample was pre-tested on biochemical , anthropometric and self-report behavioural , cognitive and mood variables and post-tested either at the end of the educational/support-based lifestyle programme or the end of the wait period . The intervention group significantly improved their diabetes knowledge , motivation to change , positive affect , healthy eating and activity levels and showed significantly greater reductions in weight , body mass index , waist circumference , diastolic blood pressure and fasting plasma glucose in comparison with controls . The intervention group also changed their diagnostic status from pre-diabetes to non-diabetes at a greater rate than the wait group ( 43 % vs. 26 % ) who received st and ard care from their GPs", "The aim of this study was to evaluate the effects of a nutrition education program ( NEP ) on anthropometric , dietetic , and metabolic parameters in high-risk subjects for type 2 diabetes mellitus . Fifty-one participants , both sexes , were r and omly assigned to either the control ( 58.8 % ) or the intervention ( NEP ) group . The intervention group received frequent individual and group nutritional counseling from a team of nutritionists . Participants were assessed at baseline ( M0 ) and after 12 months ( M1 ) for anthropometric , dietetic , and metabolic parameters . The hypothesis was that high-risk subjects for type 2 diabetes mellitus participating in NEP would show an improvement in these parameters . At M1 , the intervention group showed a significant decline in body weight ( -3.4 % ) , body mass index ( -5.7 % ) , cholesterol intake ( -49.5 % ) , fasting glycemia ( -14.0 % ) , fasting insulin ( -9.0 % ) , postpr and ial glycemia ( -21.0 % ) , postpr and ial insulin ( -71.0 % ) , total serum cholesterol ( -23.0 % ) , and glycated hemoglobin ( -24.0 % ) . A decrease in energy intake ( 5 % , P = .06 ) and low-density lipoprotein cholesterol ( 25 % , P = .07 ) was observed in the interventional group , although it did not reach statistical significance . In contrast , the control group presented a significantly higher energy intake ( 19 % , P = .04 ) and a nonsignificant increase in consumption of all macronutrients . The long-term NEP was found to improve anthropometric , dietary , and metabolic parameters in high-risk subjects for type 2 diabetes mellitus ", "AIMS To determine the effectiveness of a 2.5-year lifestyle intervention for Type 2 diabetes prevention in Dutch general practice compared with usual care . METHODS A r and omized controlled trial of 925 individuals at high risk for Type 2 diabetes ( FINDRISC-score ≥ 13 ) in 14 general practice s in the Netherl and s. Intervention consisted of lifestyle counselling from the nurse practitioner and the general practitioner . Usual care consisted of oral and written information at the start of the study . Study groups were compared over 2.5 years regarding changes in clinical and lifestyle measures . RESULTS Both groups showed modest changes in body weight , glucose concentrations , physical activity and dietary intake [ weight : intervention group , -0.8 ( 5.1 ) kg , usual care group , -0.4 ( 4.7 ) kg , ( P=0.69 ) ; fasting plasma glucose : intervention group , -0.17 ( 0.4 ) mmol/l , usual care group , -0.10 ( 0.5 ) mmol/l , ( P=0.10 ) ] . Differences between groups were significant only for total physical activity and fibre intake . In the intervention group , self-efficacy was significantly higher in individuals successful at losing weight compared with unsuccessful individuals . No significant differences in participant weight loss were found between general practitioners and nurse practitioners with different levels of motivation or self-efficacy . CONCLUSIONS Diabetes risk factors could significantly be reduced by lifestyle counselling in Dutch primary care . However , intervention effects above the effects attributable to usual care were modest . Higher participant self-efficacy seemed to facilitate weight loss . Lack of motivation or self-efficacy of professionals did not negatively influence participant guidance", "Objective : To investigate whether the effects on weight loss and cardiometabolic risk factor reduction of two technology-mediated lifestyle interventions for 15 months in a primary care-based translation trial sustained at 24 months ( that is , 9 months after the end of intervention ) . Design : This study analyzed data from an extended follow-up of participants in the original ‘ E-LITE ’ ( Evaluation of Lifestyle Interventions to Treat Elevated Cardiometabolic Risk in Primary Care)-r and omized controlled trial , which demonstrated the effectiveness of two adapted Diabetes Prevention Program ( DPP ) lifestyle interventions compared with usual primary care . Subjects : E-LITE r and omized 241 overweight or obese participants with pre-diabetes and /or metabolic syndrome to receive usual care alone ( n=81 ) or usual care plus a coach-led ( n=79 ) or self-directed intervention ( n=81 ) . The interventions provided coach-led group behavioral weight-loss treatment or a take-home , self-directed DVD using the same 12-week curriculum , followed by 12 additional months of technology-mediated coach contact and self-monitoring support . Participants received no further intervention after month 15 . A blinded assessor conducted 24-month visits by following the measurement protocol s of the original trial . Measurements include weight and cardiometabolic risk factors ( waist circumference , fasting plasma glucose , resting blood pressure , triglycerides , high- and low-density lipoprotein cholesterol , total cholesterol and triglyceride to high-density lipoprotein cholesterol ratio ) . Results : At month 24 , mean±s.e . changes in body mass index ( trial primary outcome ) and weight ( kg ) from baseline were –1.9±0.3 ( P=0.001 ) and –5.4±0.9 ( P maintaining ⩾7 % weight loss and sustained improvements in waist circumference and fasting plasma glucose levels than usual care . Conclusion : This study shows sustained benefits of the two primary care-based , technology-mediated DPP lifestyle interventions . The findings warrant replication in long-term studies involving diverse population", "OBJECTIVE To pilot test the feasibility and effectiveness of interactive voice response ( IVR ) calls targeting physical activity and healthful eating as strategies for weight loss for patients with pre-diabetes . METHODS Participants ( N=77 ) who engaged in a 90-min diabetes prevention class were r and omly assigned to receive IVR support targeting physical activity and nutrition weight loss strategies or to a no-contact control . Physical activity , dietary intake , and body weight were assessed prior to and following the 3-month intervention . RESULTS Eighty-five percent of the intervention participants completed at least half of the intervention . Participants assigned to receive the intervention lost an average of 2.6 % of body weight during the 3 months while control participants lost an average of 1.6 % . To determine the effect of the calls when used we found that those who used the system lost approximately 3 % of body weight which approached significance when compared to controls ( p IVR holds promise for follow-up encounters with patients with pre-diabetes . PRACTICE IMPLICATION S IVR can be used to provide physical activity and nutrition counseling that can enhance the potential reach and effectiveness of health professionals working with patients who have diabetes while placing a minimal burden on financial re sources and staff time", "AIMS To evaluate the effectiveness and feasibility of implementing a linguistically and culturally tailored Diabetes Prevention Program among Chinese immigrants with prediabetes living in New York City . METHODS A total of 60 Chinese immigrants with prediabetes were r and omized into either a Diabetes Prevention Program lifestyle intervention ( n = 30 ) consisting of 12 bi-weekly core sessions and six monthly post-core sessions or the control intervention ( n = 30 ) , consisting of quarterly mailing of diabetes prevention information . Each Diabetes Prevention Program intervention session lasted 1.5 - 2 h and covered topics such as healthy eating , physical activity , stress reduction and problem-solving skills . Outcomes such as percent change in weight , BMI , and HbA1c concentration were assessed at baseline , 6 and 12 months . A mixed-effects linear regression was applied to test the intervention effect at months 6 and 12 . Data were collected in the period 2012 - 2013 and analysed in 2014 . RESULTS The participant attrition rate was greater percent weight loss in the intervention group ( -3.5 vs. -0.1 % ; P = 0.0001 ) at 6 months , which was largely maintained at 12 months ( -3.3 vs. 0.3 % ; P = 0.0003 ) . CONCLUSIONS Participants in a Diabetes Prevention Program-based intervention achieved greater weight loss and improvements in HbA1c concentration than control participants . Evaluation of the Chinese Diabetes Prevention Program curriculum in a larger trial is warranted", "Objective To investigate the effects of pharmacy based counselling on changes in lifestyle and body weight . Methods Three months after screening a stratified sample of 3,800 r and omly chosen overweight persons were addressed with question naires . Half a year and 1 year later the assessment was repeated . St and ard counselling ( SC ; non-specific recommendations towards lifestyle ) , intensive counselling ( IC ; additional advice to reduce body weight ) and counselling for persons at high risk for type 2 diabetes ( HRC ; recommendation to contact a physician ) were compared . Results All counselling groups ( SC ; n = 557 , IC ; n = 568 , HRC ; n = 245 ) showed significant weight loss three months after screening ( 0.6–1.9 kg ) . A further weight reduction was observed at 1 year follow up ( 1.1–2.4 kg ) . The HRC group showed a higher percentage of weight loss than the IC or SC group after 3 months ( −2.25 % vs. −1.20 % and −0.67 % ; P Lifestyle changes in physical activity and /or nutrition were reported by 81.2 % in the HRC group , 74.1 % in the IC group and 67.0 % in the SC group . Conclusion Immediate counselling in community pharmacies after screening for type 2 diabetes can result in significant lifestyle changes and weight loss in overweight individuals", "OBJECTIVES The purpose of this study was to determine the feasibility of implementing a diabetes prevention program ( DPP ) in a rural African-American church . METHODS A six-session DPP , modeled after the successful National Institutes of Health ( NIH ) DPP , was implemented in a rural African-American church . Adult members of the church identified as high risk for diabetes , based on results of a risk question naire , were screened with a fasting glucose . Persons with prediabetes , a fasting glucose of 100 - 125 mg/dL , participated in the six-session , Lifestyle Balance Church DPP . The primary outcomes were attendance rates and changes in fasting glucose , weight and body mass index measured at baseline , six- and 12-month follow-up . RESULTS Ninety-nine adult church members were screened for diabetes risk . Eleven had impaired fasting glucose . Ten of 11 participated in the six-session intervention , for an attendance rate of 78 % . After the intervention and 12-month follow-up , there was a mean weight loss of 7.9 lbs and 10.6 lbs , respectively . CONCLUSIONS This pilot project suggests that a modified six-session DPP can be translated to a group format and successfully implemented in a church setting . Further r and omized studies are needed to determine the effectiveness of such an intervention", "BACKGROUND The susceptibility to type 2 diabetes of people of south Asian descent is established , but there is little trial-based evidence for interventions to tackle this problem . We assessed a weight control and physical activity intervention in south Asian individuals in the UK . METHODS We did this non-blinded trial in two National Health Service ( NHS ) regions in Scotl and ( UK ) . Between July 1 , 2007 , and Oct 31 , 2009 , we recruited men and women of Indian and Pakistani origin , aged 35 years or older , with waist circumference 90 cm or greater in men or 80 cm or greater in women , and with impaired glucose tolerance or impaired fasting glucose determined by oral glucose tolerance test . Families were r and omised ( using a r and om number generator program , with permuted blocks of r and om size , stratified by location [ Edinburgh or Glasgow ] , ethnic group [ Indian or Pakistani ] , and number of participants in the family [ one vs more than one ] ) to intervention or control . Participants in the same family were not r and omised separately . The intervention group received 15 visits from a dietitian over 3 years and the control group received four visits in the same period . The primary outcome was weight change at 3 years . Analysis was by modified intention to treat , excluding participants who died or were lost to follow-up . We used linear regression models to provide mean differences in baseline-adjusted weight at 3 years . This trial is registered , number IS RCT N25729565 . FINDINGS Of 1319 people who were screened with an oral glucose tolerance test , 196 ( 15 % ) had impaired glucose tolerance or impaired fasting glucose and 171 entered the trial . Participants were in 156 family clusters that were r and omised ( 78 families with 85 participants were allocated to intervention ; 78 families with 86 participants were allocated to control ) . 167 ( 98 % ) participants in 152 families completed the trial . Mean weight loss in the intervention group was 1.13 kg ( SD 4.12 ) , compared with a mean weight gain of 0.51 kg ( 3.65 ) in the control group , an adjusted mean difference of -1.64 kg ( 95 % CI -2.83 to -0.44 ) . INTERPRETATION Modest , medium-term changes in weight are achievable as a component of lifestyle-change strategies , which might control or prevent adiposity-related diseases . FUNDING National Prevention Research Initiative , NHS Research and Development ; NHS National Services Scotl and ; NHS Health Scotl and", "INTRODUCTION Gestational diabetes mellitus ( GDM ) increases risks for type 2 diabetes and cardiovascular diseases . Low glycaemic index ( GI ) diets improve cardio-metabolic outcomes in insulin-resistant individuals . We examined the feasibility of lowering GI through GI-based-education among Asian post-GDM women . METHODS A 3-month investigation was carried out on 60 Malaysian women with a mean age of 31.0 + /- 4.5 years and a history of GDM . Subjects were r and omised into two groups : LGIE and CHDR . The CHDR group received conventional healthy dietary recommendations only . The LGIE group received GI based-education in addition to conventional healthy dietary recommendations . At baseline and after 3-months , dietary intake of energy and macronutrient intakes including GI diet and glycaemic load was assessed using 3-day food records . Diabetes-Diet and GI-concept scores and physical activity levels were assessed using a question naire . Adherence to dietary instructions was measured at the end of 3 months . RESULTS At the end of 3 months , the LGIE group had significant reductions in energy intake ( 241.7 + /- 522.4Kcal , P = 0.037 , ES=0.463 ) , total carbohydrate ( 48.7 + /- 83.5 g , P = 0.010 , ES = 0.583 ) , GI ( 3.9 + /- 7.1 , P = 0.017 , ES = 0.549 ) and GL ( 39.0 + /- 55.3 , P = 0.003 , ES = 0.705 ) and significant increases in protein ( 3.7 + /- 5.4 g , 0.003 , ES = 0.685 ) and diet fibre ( 4.6 + /- 7.3 g , P = 0.06 ) . The CHDR group had a significant reduction in fat only ( 5.7 + /- 9.4 g , P = 0.006 , ES = 0.606 ) . There was a 30 % increase in GI-concept scores in the LGIE group ( p Changes in GI-concept scores correlated significantly to the reduction in dietary GI ( r = -0.642 , P = 0.045 ) . Dietary adherence was comparable in both groups . CONCLUSION GI-education improves GI-concept knowledge and helps lower dietary glycaemic index among women with a history of GDM", "Background / Objectives : To evaluate the effect of a 4.1-year ( range 3–6 years ) lifestyle intervention according to general public health recommendations on glucose tolerance and dropout in a Dutch population with impaired glucose tolerance (IGT).Subjects/ Methods : In the Study on Lifestyle intervention and Impaired glucose tolerance Maastricht , 147 Caucasian IGT subjects were r and omized to an intervention group ( INT : n=74 ; 38 male , 36 female ) and control group ( CON : n=73 ; 37 male , 36 female ) . Annually , subjects underwent measurements of body weight , anthropometry , glucose tolerance ( oral glucose tolerance test ) , insulin resistance ( homeostasis model assessment -insulin resistance ) , maximal aerobic capacity ( VO2 max ) , blood lipids and blood pressure . INT received individual advice regarding a healthy diet and physical activity . Results : INT decreased their saturated fat intake , increased their carbohydrate intake ( P and VO2 max ( P=0.04 ) compared with CON . Body weight did not change significantly ( P=0.20 ) between the groups . After an initial decrease , 2-h glucose levels overall increased in INT ( + 0.11 mmol/l ) , but significantly less than CON ( + 1.18 mmol/l ; P=0.04 ) . Diabetes incidence was lower in INT versus CON ( 30 versus 56 % , P=0.04 ) . Change in body weight was associated with change in 2-h glucose levels ( β=0.399 mmol/l per kg , P=0.02 ) . Dropouts had a lower aerobic fitness and socioeconomic status , and a higher body mass index ( BMI ) and 2-h glucose compared with non-dropouts . Conclusions : Prolonged feasible changes in diet and physical activity prevent deterioration of glucose tolerance and reduce diabetes risk . Low socioeconomic status , low aerobic fitness and high BMI and 2-h glucose are indicative of dropout to the program", "OBJECTIVES We evaluated a community-based , translational lifestyle program to reduce diabetes risk in lower-socioeconomic status ( SES ) and ethnic minority adults . METHODS Through an academic-public health department partnership , community-dwelling adults at risk for diabetes were r and omly assigned to individualized lifestyle counseling delivered primarily via telephone by health department counselors or a wait-list control group . Primary outcomes ( 6 and 12 months ) were fasting glucose level , triglycerides , high- and low-density lipoprotein cholesterol , weight , waist circumference , and systolic blood pressure . Secondary outcomes included diet , physical activity , and health-related quality of life . RESULTS Of the 230 participants , study retention was 92 % . The 6-month group differences for weight and triglycerides were significant . The intervention group lost 2 pounds more than did the control group ( P=.03 ) and had decreased triglyceride levels ( difference in change , 23 mg/dL ; P=.02 ) . At 6 months , the intervention group consumed 7.7 fewer grams per day of fat ( P=.05 ) and more fruits and vegetables ( P=.02 ) than did control participants . CONCLUSIONS Despite challenges design ing effective translational interventions for lower-SES and minority communities , this program modestly improved some diabetes risk factors . Thus , individualized , telephone-based models may be a promising alternative to group-based interventions", "Purpose The purpose of this pilot study was to examine the feasibility and preliminary efficacy of an age-specific diabetes prevention program in young adults with prediabetes . Methods A one-group pretest-posttest design was used . The inclusion criteria were age 18 to 29 years and the presence of prediabetes ( either impaired fasting glucose of 100 - 125 mg/dL [ 5.55 - 6.94 mmol/L ] or A1C of 5.7%-6.4 % ) . Fifteen participants were enrolled in the study . A technology-based lifestyle coaching program focused on diet and physical activity and incorporating a h and held device and digital platforms was developed and tested . Psychosocial factors ( health literacy , illness perception , self-efficacy , therapeutic efficacy ) based on social cognitive theory , changes in diet and physical activity , and cardiometabolic risk factors were assessed at baseline and week 12 after the intervention . A paired- sample s t test was performed to examine changes between baseline and postintervention on each psychosocial and physical variable . Results Participants ’ ( n = 13 completers ) mean age was 24.4 ± 2.2 years , 23.1 % were male , and 53.8 % were African American . Overall , the participants were satisfied with the intervention ( mean score , 4.15 on a 5-point , Likert-type scale ) . Between pre- and posttesting , mean body mass index and mean A1C decreased from 41.0 ± 7.3 kg/m2 and 6.0 ± 0.5 % to 40.1 ± 7.0 kg/m2 and 5.6 ± 0.5 % , respectively , whereas mean fasting glucose did not significantly change ( from 92.6 ± 11 to 97.6 ± 14.3 mg/dL [ 5.14 ± 0.61 to 5.42 ± 0.79 mmol/L ] ) . Conclusions The intervention result ed in reduced A1C and a trend toward decreased body mass index in obese sedentary young adults with prediabetes after 12 weeks . Further study through a r and omized clinical trial with a longer intervention period is warranted", "Summary : Women with impaired glucose tolerance are at high risk of developing noninsulin dependent diabetes mellitus ( NIDDM ) . The Mercy Hospital for Women has a long‐term follow‐up programme for women with gestational diabetes , which identifies many women with impaired glucose tolerance . Two hundred of these women were entered into a r and omized controlled trial of intensive versus routine dietary advice . Seven women were lost to follow‐up . The annual incidence rates of diabetes mellitus for the 2 groups were 6.1 % ( intervention ) and 7.3 % ( control ) , an incident rate ratio of 0.83 , 95 % confidence interval 0.47–1.48 , p = 0.50 . Overall , there was a return to normal glucose tolerance in 44 % of patients . Multivariate analysis showed that body mass index , fasting and 2‐hour plasma glucose levels at trial entry were significantly associated with an increased risk of diabetes mellitus . Impaired glucose tolerance is an important condition that should be treated with advice about lifestyle modification ( diet and /or exercise ) . We consider that future trials in the management of women with previous gestational diabetes who have impaired glucose tolerance should investigate the effect of pharmacological intervention in addition to diet and /or exercise , the latter providing a therapy that it would be unethical to exclude on the evidence presently available", "AIM To evaluate the effectiveness of lifestyle interventions in people with impaired glucose tolerance ( IGT ) . METHODS Participants with IGT ( n=78 ) , diagnosed on two consecutive oral glucose tolerance tests ( OGTTs ) , were r and omly assigned to a 2-year lifestyle intervention or to a control group . Main outcome measures were changes from baseline in : nutrient intake ; physical activity ; anthropometry , glucose tolerance and insulin sensitivity . Measurements were repeated at 6 , 12 and 24 months follow-up . RESULTS After 24 months follow-up , there was a significant fall in total fat consumption ( difference in change between groups ( Delta intervention-Delta control)= -17.9 , 95 % confidence interval ( CI ) -33.6 to -2.1g/day ) as a result of the intervention . Body mass was significantly lower in the intervention group compared with controls after 6 months ( -1.6 , 95 % CI -2.9 to -0.4 kg ) and 24 months ( -3.3 , 95 % CI -5.7 to -0.89 kg ) . Whole body insulin sensitivity , assessed by the short insulin tolerance test ( ITT ) , improved after 12 months in the intervention group ( 0.52 , 95 % CI 0.15 - 0.89%/min ) . CONCLUSIONS These findings complement the findings of the Finnish Diabetes Prevention Study and the American Diabetes Prevention Study , both of which tested intensive interventions , by showing that pragmatic lifestyle interventions result in improvements in obesity and whole body insulin sensitivity in individuals with IGT , without change in other cardiovascular risk factors", "Purpose . The purpose of this study was to provide further information about preferences for types and formats ( e.g. , correspondence vs. face to face ) of eating and exercise programs , actual participation rates in a variety of offered programs , and characteristics of program participants vs. non participants . Design . Over a 3-year period , a large sample of community volunteers was given the opportunity to participate in various forms of diet and exercise programs as part of a weight gain prevention study . Setting . The study was conducted at a university and three local health department sites . Subjects . Subjects in the study were 616 individuals participating in the Pound of Prevention study ( POP ) , a 3-year r and omized evaluation of an intervention for preventing weight gain.1 Measures . The primary outcomes assessed were participation rates for each program offering . Program participants were also compared to those who did not participate on demographic characteristics , smoking , diet behavior , exercise behavior , and weight concern . Results . Survey results indicated that correspondence formats for delivery of health education programs were rated as more desirable than face-to-face formats . Participation for program offerings ranged from 0 to 16 % of the study population . Participation data were consistent with survey results and showed participants ' preference for correspondence formats even more strongly . Program offerings attracted health-conscious participants with higher education and income levels . Conclusions . These data suggest that some community members will get interested and take part in low-cost , minimal contact programs for exercise and weight control . Future research efforts should focus on investigating ways to increase participation in brief or minimal contact programs , particularly among groups that may be difficult to reach and at high risk for the development of obesity", "Some slight departures from the protocol of individual r and omization affecting only a small subset of participants in the Prevencion con Dieta Mediterranea ( PREDIMED ) trial ( at most 14 % ) occurred and prompted a thorough re analysis of data and republication of the main PREDIMED paper ( see Estruch et al. , Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts . N Engl J Med 2018;378:e34 ) . The authors report the", "Purpose With growing numbers of people at risk for diabetes and cardiovascular disease , diabetes educators report increasing referrals for intervention in prevention of these conditions . Diabetes educators have expertise in diabetes self-management education ; however , they are generally not prepared for delivery of chronic disease primary prevention . The purpose of this project was to determine if individuals at risk for diabetes who participate in an intervention delivered by trained diabetes educators in existing diabetes self-management education community-based programs can reduce risk factors for diabetes and cardiovascular disease . Methods Diabetes educators in 3 outpatient-hospital programs ( urban , suburban , and rural ) received training and support for implementation of the Group Lifestyle Balance program , an adaptation of the Diabetes Prevention Program lifestyle intervention , from the Diabetes Prevention Support Center of the University of Pittsburgh . Adults with prediabetes and /or the metabolic syndrome were eligible to enroll in the program with physician referral . With use of existing diabetes educator networks , recruitment was completed via on-site physician in-services , informative letters , and e-mail contact as well as participant-directed newspaper advertisement . Results Eighty-one participants enrolled in the study ( 71 women , 10 men ) . Mean overall weight loss was 11.3 lb ( 5.1 % , P fasting plasma glucose , low-density lipoprotein cholesterol , triglycerides , and blood pressure . Conclusions These results suggest that the Group Lifestyle Balance program delivered by diabetes educators was successful in reducing risk for diabetes and cardiovascular disease in high-risk individuals . Furthermore , diabetes educators , already integrated within the existing health care system , provide yet another re source for delivery of primary prevention programs in the community", "Purpose The purpose of this study is to evaluate the effectiveness of a nutrition-based shared medical appointment ( SMA ) intervention in the treatment of prediabetes compared to the individualized counseling st and ard of care . Methods A r and omized controlled trial design comparing health outcomes in patients with prediabetes attending either an individualized counseling ( control group ) or three 90-minute nutrition SMA ( intervention group ) sessions . Demographic , anthropometric ( weight and body mass index ) , clinical ( blood pressure ) , and biochemical ( lipid profile , fasting blood sugar , glycated hemoglobin , albumin-to-creatinine ratio ) measures were obtained from all participants at baseline , at 3 months , and at 1 year . Results Ninety-four participants were r and omized into the 2 study groups with a 69 % completion rate at 1 year ( n = 34 SMA , n = 31 control ) . The average participant was Caucasian ( 64 % ) , male ( 54 % ) , 58.3 ± 9.6 years , had a BMI of 30.8 ± 4.9 kg/m2 ( obese ) , and fasting blood glucose of 109 ± 9.5 mg/dL. The SMA and control participants lost a mean of 6.6 pounds and 3.6 pound , respectively ; neither group met the 5 % modest weight loss expected . The SMA and control group experienced a mean drop in fasting blood glucose of 6 mg/dL. Conclusions As dem and s on health care providers continue to rise , finding innovative ways to manage the patient load while providing quality health care is increasingly important . SMA health outcomes were equivalent to individual counseling outcomes , while increasing the provider ’s productivity by treating 6 to 8 people with prediabetes in 90 minutes compared to 1 patient in 60 minutes", "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" ]

[ "BACKGROUND Low serum 25-hydroxyvitamin D ( 25-[OH]D ) levels have been associated with lower FEV(1 ) , impaired immunologic control , and increased airway inflammation . Because many patients with chronic obstructive pulmonary disease ( COPD ) have vitamin D deficiency , effects of vitamin D supplementation may extend beyond preventing osteoporosis . OBJECTIVE To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations . DESIGN R and omized , single-center , double-blind , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00666367 ) SETTING University Hospitals Leuven , Leuven , Belgium . PATIENTS 182 patients with moderate to very severe COPD and a history of recent exacerbations . INTERVENTION 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year . MEASUREMENTS The primary outcome was time to first exacerbation . Secondary outcomes were exacerbation rate , time to first hospitalization , time to second exacerbation , FEV(1 ) , quality of life , and death . RESULTS Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group ( mean between-group difference , 30 ng/mL [ 95 % CI , 27 to 33 ng/mL ] ; P median time to first exacerbation did not significantly differ between the groups ( hazard ratio , 1.1 [ CI , 0.82 to 1.56 ] ; P = 0.41 ) , nor did exacerbation rates , FEV(1 ) , hospitalization , quality of life , and death . However , a post hoc analysis in 30 participants with severe vitamin D deficiency ( serum 25-[OH]D levels exacerbations in the vitamin D group ( rate ratio , 0.57 [ CI , 0.33 to 0.98 ] ; P = 0.042 ) . LIMITATION This was a single-center study with a small sample size . CONCLUSION High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations . In participants with severe vitamin D deficiency at baseline , supplementation may reduce exacerbations . PRIMARY FUNDING SOURCE Applied Biomedical Research Program , Agency for Innovation by Science and Technology ( IWT-TBM )", "RATIONALE Restoration of vitamin D sufficiency may reduce asthma exacerbations , events that are often associated with respiratory tract infections and cold symptoms . OBJECTIVES To determine whether vitamin D supplementation reduces cold symptom occurrence and severity in adults with mild to moderate asthma and vitamin D insufficiency . METHODS Colds were assessed in the AsthmaNet VIDA ( Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness ) trial , in which 408 adult patients were r and omized to receive placebo or cholecalciferol ( 100,000 IU load plus 4,000 IU/d ) for 28 weeks as add-on therapy . The primary outcome was cold symptom severity , which was assessed using daily scores on the 21-item Wisconsin Upper Respiratory Symptom Survey . MEASUREMENTS AND MAIN RESULTS A total of 203 participants experienced at least one cold . Despite achieving 25-hydroxyvitamin D levels of 41.9 ng/ml ( 95 % confidence interval [ CI ] , 40.1 - 43.7 ng/ml ) by 12 weeks , vitamin D supplementation had no effect on the primary outcome : the average peak WURSS-21 scores ( 62.0 [ 95 % CI , 55.1 - 68.9 ; placebo ] and 58.7 [ 95 % CI , 52.4 - 65.0 ; vitamin D ] ; P = 0.39 ) . The rate of colds did not differ between groups ( rate ratio [ RR ] , 1.2 ; 95 % CI , 0.9 - 1.5 ) ; however , among African Americans , those receiving vitamin D versus placebo had an increased rate of colds ( RR , 1.7 ; 95 % CI , 1.1 - 2.7 ; P = 0.02 ) . This was also observed in a responder analysis of all subjects achieving vitamin D sufficiency , regardless of treatment assignment ( RR , 1.4 ; 95 % CI , 1.1 - 1.7 ; P = 0.009 ) . CONCLUSIONS Our findings in patients with mild to moderate asthma undergoing an inhaled corticosteroid dose reduction do not support the use of vitamin D supplementation for the purpose of reducing cold severity or frequency", "Background Observational studies suggest high prenatal vitamin D intake may be associated with reduced childhood wheezing . We examined the effect of prenatal vitamin D on childhood wheezing in an interventional study . Methods We r and omised 180 pregnant women at 27 weeks gestation to either no vitamin D , 800 IU ergocalciferol daily until delivery or single oral bolus of 200,000 IU cholecalciferol , in an ethnically stratified , r and omised controlled trial . Supplementation improved but did not optimise vitamin D status . Research ers blind to allocation assessed offspring at 3 years . Primary outcome was any history of wheeze assessed by vali date d question naire . Secondary outcomes included atopy , respiratory infection , impulse oscillometry and exhaled nitric oxide . Primary analyses used logistic and linear regression . Results We evaluated 158 of 180 ( 88 % ) offspring at age 3 years for the primary outcome . Atopy was assessed by skin test for 95 children ( 53 % ) , serum IgE for 86 ( 48 % ) , exhaled nitric oxide for 62 ( 34 % ) and impulse oscillometry of acceptable quality for 51 ( 28 % ) . We found no difference between supplemented and control groups in risk of wheeze [ no vitamin D : 14/50 ( 28 % ) ; any vitamin D : 26/108 ( 24 % ) ( risk ratio 0.86 ; 95 % confidence interval 0.49 , 1.50 ; P = 0.69 ) ] . There was no significant difference in atopy , eczema risk , lung function or exhaled nitric oxide between supplemented groups and controls . Conclusion Prenatal vitamin D supplementation in late pregnancy that had a modest effect on cord blood vitamin D level , was not associated with decreased wheezing in offspring at age three years . Trial Registration Controlled-Trials.com IS RCT", "There is intense interest in the role of vitamin D in the development of asthma and allergies . However , studies differ on whether a higher vitamin D intake or status in pregnancy or at birth is protective against asthma and allergies . To address this uncertainty , the Vitamin D Antenatal Asthma Reduction Trial ( VDAART ) was developed . VDAART is a r and omized , double-blind , placebo-controlled trial of vitamin D supplementation in pregnant women to determine whether prenatal supplementation can prevent the development of asthma and allergies in women 's offspring . A secondary aim is to determine whether vitamin D supplementation can prevent the development of pregnancy complications , such as preeclampsia , preterm birth , and gestational diabetes . Women were r and omized to the treatment arm of 4000IU/day of vitamin D3 plus a daily multivitamin that contained 400IU of vitamin D3 or the placebo arm of placebo plus a multivitamin that contained 400IU daily of vitamin D3 . Women who were between the gestational ages of 10 and 18 weeks were r and omized from three clinical centers across the United States - Boston Medical Center , Washington University in St. Louis , and Kaiser Permanente Southern California Region ( San Diego , CA ) . Supplementation took place throughout pregnancy . Monthly monitoring of urinary calcium to creatinine ratio was performed in addition to medical record review for adverse events . Offspring are being evaluated quarterly through question naires and yearly during in-person visits until the 3rd birthday of the child . Ancillary studies will investigate neonatal T-regulatory cell function , maternal vaginal flora , and maternal and child intestinal flora", "Objective : The aim of this pilot study was to determine the combined effect of vitamin D and omega-3 polyunsaturated fatty acid ( PUFA ) supplementation on airway function and inflammation in recreational athletes with exercise-induced bronchoconstriction ( EIB ) . Methods : Ten recreational athletes with EIB participated in a single-blind , placebo-controlled trial over six consecutive weeks . All subjects attended the laboratory on three occasions . Each visit was separated by a period of 3 weeks : visit 1 ( usual diet ) , visit 2 ( placebo ) and visit 3 ( SMARTFISH ® NutriFriend 2000 ; 30 µg vitamin D3–3000 mg eicosapentaenoic acid , 3000 mg docosahexaenoic acid ) consumed once daily for a period of 3 weeks . Venous blood was collected at the beginning of each trial to determine vitamin D status . Spirometry was performed pre- and post-eucapnic voluntary hyperpnoea ( EVH ) . Results : The Maximum fall in FEV1 ( ΔFEV1max ) post-EVH was not different between visits ( usual diet : −15.9 ± 3.6 % , placebo : −16.1 ± 6.1 % , vitamin D + omega-3 PUFA : −17.8 ± 7.2 % ) . Serum vitamin D remained unchanged between visits . Conclusion : Vitamin D and omega-3 PUFA supplementation does not attenuate the reduction in lung function post-EVH . This finding should be viewed as preliminary until the results of r and omised controlled trials are made available", "BACKGROUND Asthma exacerbations , most often caused by respiratory tract infections , are the leading causes of asthma morbidity and comprise a significant proportion of asthma-related costs . Vitamin D status might play a role in preventing asthma exacerbations . OBJECTIVES We sought to assess the relationship between serum vitamin D levels and subsequent severe asthma exacerbations . METHODS We measured 25-hydroxyvitamin D levels in sera collected from 1024 children with mild-to-moderate persistent asthma at the time of enrollment in a multicenter clinical trial of children r and omized to receive budesonide , nedocromil , or placebo ( as-needed beta-agonists ) : the Childhood Asthma Management Program . Using multivariable modeling , we examined the relationship between baseline vitamin D levels and the odds of any hospitalization or emergency department visit over the 4 years of the trial . RESULTS Thirty-five percent of all subjects were vitamin D insufficient , as defined by a level of 30 ng/mL or less 25-hydroxyvitamin D. Mean vitamin D levels were lowest in African American subjects and highest in white subjects . After adjusting for age , sex , body mass index , income , and treatment group , insufficient vitamin D status was associated with a higher odds of any hospitalization or emergency department visit ( odds ratio , 1.5 ; 95 % CI , 1.1 - 1.9 ; P = .01 ) . CONCLUSION Vitamin D insufficiency is common in this population of North American children with mild-to-moderate persistent asthma and is associated with higher odds of severe exacerbation over a 4-year period", "BACKGROUND The cholecalciferol inputs required to achieve or maintain any given serum 25-hydroxycholecalciferol concentration are not known , particularly within ranges comparable to the probable physiologic supply of the vitamin . OBJECTIVES The objectives were to establish the quantitative relation between steady state cholecalciferol input and the result ing serum 25-hydroxycholecalciferol concentration and to estimate the proportion of the daily requirement during winter that is met by cholecalciferol reserves in body tissue stores . DESIGN Cholecalciferol was administered daily in controlled oral doses labeled at 0 , 25 , 125 , and 250 micro g cholecalciferol for approximately 20 wk during the winter to 67 men living in Omaha ( 41.2 degrees N latitude ) . The time course of serum 25-hydroxycholecalciferol concentration was measured at intervals over the course of treatment . RESULTS From a mean baseline value of 70.3 nmol/L , equilibrium concentrations of serum 25-hydroxycholecalciferol changed during the winter months in direct proportion to the dose , with a slope of approximately 0.70 nmol/L for each additional 1 micro g cholecalciferol input . The calculated oral input required to sustain the serum 25-hydroxycholecalciferol concentration present before the study ( ie , in the autumn ) was 12.5 micro g ( 500 IU)/d , whereas the total amount from all sources ( supplement , food , tissue stores ) needed to sustain the starting 25-hydroxycholecalciferol concentration was estimated at approximately 96 micro g ( approximately 3800 IU)/d . By difference , the tissue stores provided approximately 78 - 82 micro g/d . CONCLUSIONS Healthy men seem to use 3000 - 5000 IU cholecalciferol/d , apparently meeting > 80 % of their winter cholecalciferol need with cutaneously synthesized accumulations from solar sources during the preceding summer months . Current recommended vitamin D inputs are inadequate to maintain serum 25-hydroxycholecalciferol concentration in the absence of substantial cutaneous production of vitamin", "BACKGROUND To our knowledge , no rigorously design ed clinical trials have evaluated the relation between vitamin D and physician-diagnosed seasonal influenza . OBJECTIVE We investigated the effect of vitamin D supplements on the incidence of seasonal influenza A in schoolchildren . DESIGN From December 2008 through March 2009 , we conducted a r and omized , double-blind , placebo-controlled trial comparing vitamin D(3 ) supplements ( 1200 IU/d ) with placebo in schoolchildren . The primary outcome was the incidence of influenza A , diagnosed with influenza antigen testing with a nasopharyngeal swab specimen . RESULTS Influenza A occurred in 18 of 167 ( 10.8 % ) children in the vitamin D(3 ) group compared with 31 of 167 ( 18.6 % ) children in the placebo group [ relative risk ( RR ) , 0.58 ; 95 % CI : 0.34 , 0.99 ; P = 0.04 ] . The reduction in influenza A was more prominent in children who had not been taking other vitamin D supplements ( RR : 0.36 ; 95 % CI : 0.17 , 0.79 ; P = 0.006 ) and who started nursery school after age 3 y ( RR : 0.36 ; 95 % CI : 0.17 , 0.78 ; P = 0.005 ) . In children with a previous diagnosis of asthma , asthma attacks as a secondary outcome occurred in 2 children receiving vitamin D(3 ) compared with 12 children receiving placebo ( RR : 0.17 ; 95 % CI : 0.04 , 0.73 ; P = 0.006 ) . CONCLUSION This study suggests that vitamin D(3 ) supplementation during the winter may reduce the incidence of influenza A , especially in specific subgroups of schoolchildren . This trial was registered at https://center.umin.ac.jp as UMIN000001373", "Background Trials in school-aged children suggest vitamin D supplementation reduces asthma exacerbations . Primary aim : to examine whether vitamin D3 ( 100,000 IU ) rapidly raises serum 25-hydroxyvitamin D ( 25OHD ) ≥75 nmol/L in asthmatic preschoolers . Methods In a double-blind , r and omised , placebo-controlled trial , preschool-aged children with asthma received 100,000 IU vitamin D3 ( intervention ) or placebo ( control ) , followed by 400 IU vitamin D3 daily for 6 months . Serum 25OHD was measured at baseline , 10 days , 3 and 6 months . Outcomes included the group difference in 25OHD change from baseline at 3 months ( Δ25OHD ) ; the proportion of children with 25OHD ≥75 nmol/L at 3 months ; the pattern in serum vitamin D over 6 months ; the proportion of children with hypercalciuria at any time point ( safety ) ; and group rates for oral corticosteroids . Continuous outcomes were analysed using generalised linear mixed models and group rate ratios of events per child were assessed using a Poisson distribution model . Results Twenty-two children were r and omised ( intervention:11 ; control:11 ) during winter . At 3 months , the group difference in Δ25OHD ( 7.2 nmol/L ; 95 % CI : -13.7 , 28.1 ) was not significant ; yet , 100 % versus 54.5 % ( intervention versus control ) had serum 25OHD ≥75 nmol/L. There was a significant group difference in Δ25OHD at 10 days ( 110.3 nmol/L ; 95 % CI : 64.0 , 156.6 ) . One child in each group had transient hypercalciuria at 10 days . Group oral corticosteroids rates were 0.82 and 1.18/child , intervention versus control ( rate ratio = 0.68 ; 95 % CI : 0.30 , 1.62 ; non-significant ) . Conclusions Following 100,000 IU vitamin D3 , all children reached serum 25OHD ≥75 nmol/L , compared with half who received placebo . Daily supplementation , sun exposure and insufficient power may explain the absence of a significant 3-month group difference in Δ25OHD . No clinical ly important alterations in bone metabolism biomarkers occurred . Group oral corticosteroid rates will inform sample size calculations for the larger trial . ( NCT01999907 , 25 November 2013 )", "BACKGROUND Low levels of vitamin D are associated with asthma severity , airway remodeling , and exacerbation rate increase , especially in nonatopic asthma . Reduced steroid responsiveness or impaired antimicrobial defense might be underlying mechanisms . OBJECTIVE We sought to evaluate the effect of vitamin D supplementation on eosinophilic and neutrophilic airway inflammation in patients with nonatopic asthma . METHODS In a double-blind , r and omized , placebo-controlled trial , we investigated the effect of long-acting vitamin D3 ( 400,000 IU ) on sputum neutrophils and eosinophils in 44 patients with nonatopic asthma with neutrophilic ( ≥53 % ) and /or eosinophilic ( ≥3 % ) airway inflammation . Sputum induction was performed at baseline and after 9 weeks . Other measurements included question naires , blood sample s , and pulmonary function . RESULTS Treatment with vitamin D did not significantly affect sputum neutrophils or eosinophils compared with treatment with placebo in the total group . Regarding sputum eosinophils , the effect of vitamin D appeared to be dependent on baseline sputum eosinophil levels ( interaction P = .015 ) . In patients with eosinophil levels of 26.2 % or more ( median in patients with sputum eosinophilia , > 3 % ) , eosinophils decreased from a median of 41.0 % to 11.8 % after vitamin D treatment as compared with an increase from 51.8 % to 63.3 % in patients receiving placebo ( P = .034 ) . Vitamin D treatment also result ed in slightly better Asthma Control Question naire scores ( P = .08 ) . CONCLUSIONS Vitamin D supplementation reduced eosinophilic airway inflammation in patients with nonatopic asthma with severe eosinophilic airway inflammation , but did not affect sputum neutrophils . Also , a small effect on asthma control was observed . These findings suggest that vitamin D might have potential as an add-on treatment option in eosinophilic asthma", "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", "Our objective was to assess whether administration of 25-OH-vitamin D to children with asthma treated with inhaled dry-powder budesonide 400 microg daily affects short-term growth or markers of bone turnover . We utilized a r and omized , double-blind , two-period crossover trial with run-in and washout periods of 2 weeks and treatment periods of 4 weeks duration . The setting was an Outpatient clinic in a secondary referral center . Subjects included 14 boys and 3 girls with a mean age of 11.7 ( range , 6.1 - 14.4 ) years . Interventions included 15 microg ( 600 IU ) 25-OH-vitamin D ( cholecalciferol ) in one tablet ABCDin(R ) once daily in the morning . Primary outcome measures were : lower leg growth rate , serum osteocalcin , and serum markers of type I collagen turnover , i.e. , the amino terminal propeptide of type I procollagen ( PINP ) , the carboxy terminal propeptide of type I procollagen ( PICP ) ( formation markers ) , and the carboxy terminal pyridinoline cross-linked telopeptide of type I collagen ( ICTP ) ( degradation markers ) . Secondary outcome measures were parameters of asthma control and serum 25-OH-vitamin D. Lower leg growth rate was 0.22 mm/week during vitamin D and 0.25 mm/week during placebo treatment ( NS ) . Osteocalcin was 59.9 and 57.8 microg/l during vitamin D and placebo treatment , respectively , PINP 574 and 565 microg/l , PICP 381 and 382 microg/l , and ICTP 11.5 and 11.1 microg/l , respectively ( NS ) . Serum 25-OH-vitamin D was 76.3 nmol/l and 48.2 nmol/l , respectively ( P measures of pulmonary function . In conclusion , administration of 25-OH-vitamin D does not affect short-term growth or markers of bone turnover in children with asthma treated with inhaled dry-powder budesonide 400 microg daily", "BACKGROUND Vitamin D promotes different toleragenic processes of the immune system ; however , its role in allergen specific immunotherapy ( SIT ) is still undefined . OBJECTIVE To determine whether the immunologic and clinical effectiveness of allergen SIT depends on the serum level of 25-hydroxyvitamin D ( 25[OH]D ) and its changes during SIT in asthmatic children . METHODS This is a retrospective secondary analysis of pooled data obtained from our 2 recently published prospect i ve , r and omized , placebo-controlled trials on asthmatic children undergoing allergen immunotherapy . Both trials , which assessed the effect of different pharmacologic modulation of SIT effectiveness , were conducted according to the same study protocol . Children from the placebo arms in these trials were treated with immunotherapy only and were included in the present analysis . The study population consisted of 36 children . Data concerning clinical ( asthma symptoms score and percent change in minimal daily inhaled corticosteroid dose ) and immunologic parameters ( including serum level of 25[OH]D ) were analyzed in all patients . RESULTS Patients with a higher serum level of 25(OH)D experienced more significant reduction in asthma symptoms score and steroid-sparing effect of SIT and had higher transforming growth factor â production and higher Foxp3 induction during SIT . Steroid-sparing effect correlated with 25(OH)D serum level at baseline , after 3 months of SIT , and with the changes in serum level of 25(OH)D during the build-up phase of SIT . Better response to SIT was observed among children with an 25(OH)D serum level higher than 30 ng/mL. CONCLUSION The efficacy of allergen SIT correlates with 25(OH)D serum concentration . It seems that a serum level of 25(OH)D higher than 30 ng/mL facilitates the optimal effect of allergen immunotherapy", "Objective To define the therapeutic role of vitamin D in children with moderate to severe bronchial asthma as an adjunct to st and ard treatment . Methods Hundred asthmatic children of either sex , attending the respiratory and asthma clinic were enroled in the study . Diagnosis was made on the basis of history and clinical examination . R and omization was done using sealed opaque envelop method . In addition to the treatment as per GINA guidelines , one group received oral vitamin D3 ( Cholecalciferol ) 60,000 IU per month for 6 mo and the other group received placebo powder in the form of glucose sachet with a double blinded design . Monthly follow up of every patient was done and during every visit change in severity , level of control , Peak expiratory flow rate ( PEFR ) , steroid dosage , number of exacerbations and number of emergency visits were assessed . Results Monthly doses of 60,000 IU vitamin D significantly reduced the number of exacerbations as compared to placebo ( p = 0.011 ) . PEFR significantly increased in the treatment group ( p = 0.000 ) . Monthly doses of vitamin D significantly reduced the requirement of steroids ( p = 0.013 ) and emergency visits ( p = 0.015 ) . Control of asthma was achieved earlier in patients who received monthly vitamin D. Vitamin D significantly reduced the level of severity of asthma patients over 6 mo of treatment ( p = 0.016 ) . Conclusions Vitamin D has a definite role in the management of moderate to severe persistent bronchial asthma as an adjunct to st and ard treatment", "Background A small population of patients with severe asthma does not respond to glucocorticoids ( steroid resistant [ SR ] ) . They have high morbidity , highlighting an urgent need for strategies to enhance glucocorticoid responsiveness . Objective We investigated the immunologic differences between steroid-sensitive ( SS ) and SR asthmatic patients and the effect on immunophenotype of oral calcitriol treatment because it has been previously shown to beneficially modulate the clinical response to glucocorticoids in patients with SR asthma . Methods CD8-depleted P BMC s were isolated from 12 patients with SS and 23 patients with SR asthma and cultured for 7 days with anti-CD3 and IL-2 with or without dexamethasone . Cytokine production was assessed in supernatants by using the Cytometric Bead Array . Patients with SR asthma were subsequently r and omized to oral calcitriol or placebo therapy , and identical studies were repeated . Results Patients with SR asthma produced significantly increased IL-17A and IFN-γ levels compared with those in patients with SS asthma , although it was evident that cells from individual patients might overproduce one or the other of these cytokines . Production of IL-17A was inversely and production of IL-13 was positively associated with the clinical response to prednisolone . Oral calcitriol , compared with placebo , therapy of the patients with SR asthma significantly improved dexamethasone-induced IL-10 production in vitro while suppressing dexamethasone-induced IL-17A production . This effect mirrored the previously demonstrated improvement in clinical response to oral glucocorticoids in calcitriol-treated patients with SR asthma . Conclusions IL-17Ahigh and IFN-γhigh immunophenotypes exist in patients with SR asthma . These data identify immunologic pathways that likely underpin the beneficial clinical effects of calcitriol in patients with SR asthma by directing the SR cytokine profile toward a more SS immune phenotype , suggesting strategies for identifying vitamin D responder immunophenotypes", "Objective : To assess the pulmonary function and quality of life in asthma patients receiving vitamin D3 supplementation with inhaled budesonide and formoterol . Material s and Methods : This was a double blinded , r and omized , comparative study . Patients were recruited as per the study criteria and r and omized into two groups : usual care group ( n = 69 ) patients received budesonide ( 800 μg ) with formoterol ( 24 μg ) and intervention care group ( n = 72 ) patients received vitamin D3 ( 1000 IU ) supplementation along with budesonide ( 800 μg ) plus formoterol ( 24 μg ) for a period of 6 months . Results : A total of 140 patients completed the study . Significant within-group improvement and non-significant between-group improvement is observed with respect to FEV1 . In terms of health-related quality of life , within-group comparison revealed a significant ( P in all the domains of SGRQ . However , between-group comparisons showed statistically significant ( P improvement in symptom , impact and total scores . Conclusion : On the basis of our findings , we conclude that supplementation of vitamin D3 is effective in improving the quality of life rather than pulmonary function in severe asthmatics . However , further studies are warranted to substantiate the present findings", "Summary We studied the effect of alphacalcidol ( 1-α-hydroxycholecalciferol ) on bone metabolism in patients who were placed on glucocorticoid therapy . We selected 41 women ( age : 32–52 yrs ) who were recently diagnosed with systemic lupus erythematodes , multiple sclerosis , rheumatoid arthritis or asthma bronchiale . Patients did not have other disease or take drugs known to influence bone metabolism . Patients were r and omly enrolled into two groups and were given 5–25 mg prednisone daily . After 4 weeks , group A ( n=21 ) received 0.5–1.0μg ( mean=0.54±0.03μg ) alphacalcidol and group B ( control ; n=20 ) was given 500 mg calcium daily for three years . There were no significant differences in age and steroid doses between groups . Serum calcium ( Ca ) , osteocalcin ( OC ) , collagen I C-terminal propeptide ( PICP ) , parathyroid hormone ( PTH ) , and urinary calcium and deoxypyridinoline crosslink excretion ( DPD ) were measured before corticosteroid administration , and before alphacalcidol or calcium treatment as well as 6 weeks , 6 months , and 1 , 2 , and 3 years later . Bone mineral density ( BMD ) was examined before treatment and 6 months , 1 , 2 , and 3 years later by DEXA and SPA . OC and PICP decreased significantly after 4 weeks on steroid in both groups and increased in group A but not in group B after 6 weeks of treatment with alphacalcidol and remained unchanged for 3 years . Serum PTH increased in both groups after 4 weeks of glucocorticoid treatment and was reduced in group A , but not in group B , after 6 weeks on alphacalcidol . Serum Ca , urinary Ca , and DPD did not change significantly in either group during the study period . Lumbar spine and femoral neck BMD were significantly reduced in group B after 6 months and 1 year , respectively , and continued to decrease during the study , while no significant change in group A was observed . BMD of the radius did not change in either group for 2 years but there was a significant reduction by the third year in group B. Based on these results , alphacalcidol treatment appears to be effective in preventing glucocorticoid-induced bone loss in these patients by reducing secondary hyperparathyroidism and stimulating bone formation", "BACKGROUND Patients with chronic obstructive pulmonary disease ( COPD ) often have vitamin D deficiency , which is associated with increased susceptibility to upper respiratory infection-a major precipitant of exacerbation . Multicentre trials of vitamin D supplementation for prevention of exacerbation and upper respiratory infection in patients with COPD are lacking . We therefore investigated whether vitamin D3 ( colecalciferol ) supplementation would reduce the incidence of moderate or severe COPD exacerbations and upper respiratory infections . METHODS We did a r and omised , double-blind , placebo-controlled trial of vitamin D3 supplementation in adults with COPD in 60 general practice s and four Acute National Health Service Trust clinics in London , UK . Patients were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 or placebo over 1 year in a 1:1 ratio using computer-generated permuted block r and omisation . Participants and study staff were masked to treatment assignment . Co primary outcomes were time to first moderate or severe exacerbation and first upper respiratory infection . Analysis was by intention to treat . A prespecified subgroup analysis was done to assess whether effects of the intervention on the co primary outcomes were modified by baseline vitamin D status . This trial is registered with Clinical Trials.gov , number NCT00977873 . FINDINGS 240 patients were r and omly allocated to the vitamin D3 group ( n=122 ) and placebo group ( n=118 ) . Vitamin D3 compared with placebo did not affect time to first moderate or severe exacerbation ( adjusted hazard ratio 0·86 , 95 % CI 0·60 - 1·24 , p=0·42 ) or time to first upper respiratory infection ( 0·95 , 0·69 - 1·31 , p=0·75 ) . Prespecified subgroup analysis showed that vitamin D3 was protective against moderate or severe exacerbation in participants with baseline serum 25-hydroxyvitamin D concentrations of less than 50 nmol/L ( 0·57 , 0·35 - 0·92 , p=0·021 ) , but not in those with baseline 25-hydroxyvitamin D levels of at least 50 nmol/L ( 1·45 , 0·81 - 2·62 , p=0·21 ; p=0·021 for interaction between allocation and baseline serum 25-hydroxyvitamin D status ) . Baseline vitamin D status did not modify the effect of the intervention on risk of upper respiratory infection ( pinteraction=0·41 ) . INTERPRETATION Vitamin D3 supplementation protected against moderate or severe exacerbation , but not upper respiratory infection , in patients with COPD with baseline 25-hydroxyvitamin D levels of less than 50 nmol/L. Our findings suggest that correction of vitamin D deficiency in patients with COPD reduces the risk of moderate or severe exacerbation . FUNDING UK National Institute for Health Research", "Rationale Asthma exacerbations are commonly precipitated by viral upper respiratory infections ( URIs ) . Vitamin D insufficiency associates with susceptibility to URI in patients with asthma . Trials of vitamin D in adults with asthma with incidence of exacerbation and URI as primary outcome are lacking . Objective To conduct a r and omised controlled trial of vitamin D3 supplementation for the prevention of asthma exacerbation and URI ( co primary outcomes ) . Measurements and methods 250 adults with asthma in London , UK were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 ( n=125 ) or placebo ( n=125 ) over 1 year . Secondary outcomes included asthma control test and St George 's Respiratory Question naire scores , fractional exhaled nitric oxide and concentrations of inflammatory markers in induced sputum . Subgroup analyses were performed to determine whether effects of supplementation were modified by baseline vitamin D status or genotype for 34 single nucleotide polymorphisms in 11 vitamin D pathway genes . Main results 206/250 participants ( 82 % ) were vitamin D insufficient at baseline . Vitamin D3 did not influence time to first severe exacerbation ( adjusted HR 1.02 , 95 % CI 0.69 to 1.53 , p=0.91 ) or first URI ( adjusted HR 0.87 , 95 % CI 0.64 to 1.16 , p=0.34 ) . No clinical ly important effect of vitamin D3 was seen on any of the secondary outcomes listed above . The influence of vitamin D3 on co primary outcomes was not modified by baseline vitamin D status or genotype . Conclusions Bolus-dose vitamin D3 supplementation did not influence time to exacerbation or URI in a population of adults with asthma with a high prevalence of baseline vitamin D insufficiency . Trial registration number NCT00978315 ( Clinical Trials.gov )", "In a prospect i ve , controlled , and r and omized clinical trial , we examined the effects of treatment with vitamin D ( 1,000 IU/d ) , calcium ( 1 g/d ) , and ethane-1-hydroxy-1,1-diphosphonate ( EHDP ; 7.5 mg/kg body weight ) on vertebral bone mass in fourteen asthmatics undergoing long-term treatment with systemically applied corticosteroids . The extent of steroid-induced bone loss was judged by vertebral bone density of the lumbar spine measured by dual-photon absorptiometry as well as by vertebral crush fracture incidence examined by conventional X-ray . Results of the measurements before treatment and after six mo were compared with those of an untreated control group of nineteen asthmatics . Bone density increased during the observation period by 5 % in the treated group , compared with a decrease of 4.3 % in the untreated control group ( p radiologically visible new fractures occurred ; in the control group new fractures were observed in four patients . There were no serious side effects of the applied drugs during the 6-mo period . Therefore , the combination of EHDP , calcium , and vitamin D appears to be a useful regimen for the management of steroid-induced bone loss in adult asthmatics", "BACKGROUND Cross-sectional studies have reported an association of vitamin D deficiency with increased asthma prevalence and severity , and with allergies . The effect of vitamin D as sole therapy on airway hyper-reactivity ( AHR ) and airway inflammation has not been reported . AIM To evaluate the effect of vitamin D therapy on AHR as assessed by methacholine concentration , causing a 20 % reduction in FEV1 ( PC20 -FEV1 ) and fractional exhaled nitric oxide ( FeNO ) , systemic markers of allergy and inflammation , and exhaled breath condensate cytokines . PATIENTS AND METHODS Children aged 6 - 18 years with a clinical diagnosis of mild asthma currently not receiving anti-inflammatory therapy and with low vitamin D levels were included in this r and omized , double-blind , placebo-controlled study assessing the effect of 6 weeks of treatment with oral vitamin D 14,000 units once weekly or placebo . RESULTS Of the 39 patients included , 20 received vitamin D treatment and 19 received a placebo . Vitamin D replacement result ed in a significant increase in vitamin levels , which remained unchanged in the placebo group ( P in IgE , eosinophil count , high sensitivity C-reactive protein , FeNO levels or PC20 -FEV1 following treatment . Similar values of exhaled breath condensate cytokines ( IL4 , IL5 , IL10 , IL17 , and γ interferon ) were observed in both groups . CONCLUSIONS In our small group of children with mild asthma , no difference could be demonstrated between the effect of vitamin D and placebo , despite significant increases in vitamin D blood levels . Larger interventional studies are needed to fully explore the possible effect of vitamin D in asthma", "IMPORTANCE In asthma and other diseases , vitamin D insufficiency is associated with adverse outcomes . It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency . OBJECTIVE To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels . DESIGN , SETTING , AND PARTICIPANTS The VIDA ( Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma ) r and omized , double-blind , parallel , placebo-controlled trial study ing adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart , Lung , and Blood Institute 's AsthmaNet network , with enrollment starting in April 2011 and follow-up complete by January 2014 . After a run-in period that included treatment with an inhaled corticosteroid , 408 patients were r and omized . INTERVENTIONS Oral vitamin D3 ( 100,000 IU once , then 4000 IU/d for 28 weeks ; n = 201 ) or placebo ( n = 207 ) was added to inhaled ciclesonide ( 320 µg/d ) . If asthma control was achieved after 12 weeks , ciclesonide was tapered to 160 µg/d for 8 weeks , then to 80 µg/d for 8 weeks if asthma control was maintained . MAIN OUTCOMES AND MEASURES The primary outcome was time to first asthma treatment failure ( a composite outcome of decline in lung function and increases in use of β-agonists , systemic corticosteroids , and health care ) . RESULTS Treatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks ( 28 % [ 95 % CI , 21%-34 % ] with vitamin D3 vs 29 % [ 95 % CI , 23%-35 % ] with placebo ; adjusted hazard ratio , 0.9 [ 95 % CI , 0.6 - 1.3 ] ) . Of 14 prespecified secondary outcomes , 9 were analyzed , including asthma exacerbation ; of those 9 , the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control ( 111.3 µg/d [ 95 % CI , 102.2 - 120.4 µg/d ] in the vitamin D3 group vs 126.2 µg/d [ 95 % CI , 117.2 - 135.3 µg/d ] in the placebo group ; difference of 14.9 µg/d [ 95 % CI , 2.1 - 27.7 µg/d ] ) . CONCLUSIONS AND RELEVANCE Vitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency . These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01248065", "Introduction Oral glucocorticoid therapy reduces bone mineral density ( BMD ) and increases fracture risk . It is uncertain whether inhaled glucocorticoids , the most commonly used long-term therapy for asthma , have a similar effect . If bone loss does occur , it is unclear whether this is preventable by calcitriol . Patients with asthma receiving inhalational plus intermittent oral glucocorticoids lose bone , and treatment with 0.5 μg/day of calcitriol will prevent bone loss . Methods A 2-year r and omized double-blind placebo-controlled trial . One hundred eight patients with asthma were stratified by gender , age , and inhaled glucocorticoid dose and treated with calcitriol ( n=55 ) or placebo ( n=53 ) . There were 41 men ( mean age 53.2±1.7 years ) and 67 women ( mean age 49.1±1 years ) with moderate to severe asthma ( requiring ≥800 μg/day of beclomethasone dipropionate or equivalent maintenance therapy ) . BMD values at the lumbar spine ( LS ) and femoral neck ( FN ) were measured at baseline and at 6 , 12 , and 24 months using dual x-ray absorptiometry . Results Changes in LS and FN BMD . Bone loss occurred in both groups at the FN ( both p group . Bone loss was not less in the calcitriol group at either site . Conclusion Patients with asthma receiving inhalational plus intermittent short courses of oral glucocorticoids lose bone . Calcitriol is unlikely to be appropriate therapy against this bone loss", "Background Vitamin D levels are alarmingly low ( American children older than 1 year . An increased risk of viral upper respiratory tract infections ( URTI ) , asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations , two of the most common and costly illnesses of early childhood . The objectives of this study are : 1 ) to compare the effect of ‘ high dose ’ ( 2000 IU/day ) vs. ‘ st and ard dose ’ ( 400 IU/day ) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children ; and 2 ) to assess the effect of ‘ high dose ’ vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI . Methods / Design This study is a pragmatic r and omized controlled trial . Over 4 successive winters we will recruit 750 healthy children 1–5 years of age . Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be r and omized to the ‘ st and ard dose ’ or ‘ high dose ’ oral supplemental vitamin D for a minimum of 4 months ( 200 children per group ) . Parents will obtain a nasal swab from their child with each URTI , report the number of asthma exacerbations and complete symptom checklists . Unscheduled physician visits for URTIs and asthma exacerbations will be recorded . By May , a blood sample will be drawn to determine vitamin D serum levels . The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model . Secondary analyses will compare vitamin D serum levels , asthma exacerbations and the frequency of specific viral agents between groups . Discussion Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs . This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers", "BACKGROUND Vitamin D is hypothesized to have some roles in innate and adaptive immunity , inflammation reduction , and remodeling ; therefore , it is supposed to affect the asthma phenotype , severity , and response to inhaled corticosteroid ( ICS ) . OBJECTIVE To explore the synergistic effects of vitamin D supplementation in addition to asthma controllers ( ICS or ICS plus long-acting β-agonist ) on airway functions . METHODS A r and omized clinical trial was conducted in 130 individuals aged 10 to 50 years who lived in Tehran during a 24-week period . Data on age , sex , body mass index , stage of asthma , serum total IgE , history of allergic rhinitis , atopic dermatitis , food allergy , and urticaria were collected . Spirometric parameters ( forced expiratory volume in 1 second [ FEV1 ] and ratio of FEV1 to forced vital capacity ) and serum vitamin D measurement were obtained before and 8 and 24 weeks after the intervention . Patients were divided in 2 groups r and omly . Both groups received asthma controllers ( budesonide or budesonide plus formoterol ) according to their stage , but the intervention group received vitamin D supplementation ( 100,000-U bolus intramuscularly plus 50,000 U orally weekly ) in addition to asthma controllers . RESULTS FEV1 improved significantly in both groups after 8 weeks , but no significant difference was found between the 2 groups at baseline ( P = .20 ) or after 8 weeks ( P = .99 ) ; however , a significant improvement was seen in the intervention group in the last 16 weeks , and FEV1 was significantly better in the intervention group than the other group after 24 weeks ( P . CONCLUSION Vitamin D supplementation associated with asthma controllers could significantly improve FEV1 in mild to moderate persistent asthma after 24 weeks . TRIAL REGISTRATION i rct .ir Identifier : I RCT 201302079608N1", "CONTEXT In humans , few studies have compared the potencies of ergocalciferol and cholecalciferol in improving and maintaining vitamin D status . OBJECTIVE Our objective was to evaluate the effects of a single very large dose of both calciferols on serum changes of 25-hydroxyvitamin D [ 25(OH)D ] , 1,25-dihydroxyvitamin D [ 1,25(OH)(2)D ] , ionized calcium , and parathyroid hormone ( PTH ) at baseline , and at 3 , 7 , 30 , and 60 d. DESIGN This was a prospect i ve r and omized intervention study . SETTING The study was performed in a nursing home residence . PARTICIPANTS A total of 32 elderly female patients ( age range 66 - 97 yr ) , with vitamin D deficiency was included in the study . INTERVENTION Participants were r and omized into four groups of eight to receive a single dose of 300,000 IU ergocalciferol or cholecalciferol by oral ( os ) or i m route . RESULTS 25(OH)D levels sharply increased at d 3 only when vitamins were given os . The 30-d basal difference in serum 25(OH)D was significantly greater after cholecalciferol os administration ( 47.8 + /- 7.3 ng/ml ) compared with other forms ( D(3 ) i m : 15.9 + /- 11.3 ; D(2 ) os : 17.3 + /- 4.7 ; D(2 ) i m : 5 + /- 4.4 ; all P area under the curve ( AUC ) of the serum 25(OH)D against time ( AUC(60 ) ) was : D(3 ) os , 3193 + /- 759 ng x d/ml vs. D(2 ) os , 1820 + /- 512 , P PTH levels at 3 ( P ( cholecalciferol ) significantly lowers PTH levels ( P = 0.037 ) . CONCLUSIONS Cholecalciferol is almost twice as potent as ergocalciferol in increasing serum 25(OH)D , when administered either by mouth or i m . 25(OH)D plays a role in modulating serum PTH", "In our prior r and omized trial on preventing influenza , asthma attacks as a secondary outcome occurred less often in the vitamin D group than in the placebo group . We aim ed to clarify whether low‐dose , short‐term vitamin D supplementation , in addition to st and ard treatments , improves control of childhood asthma", "Background : Asthma is a common chronic inflammatory disease of the bronchial airways . Well defined treatment options for asthma are very few . The role of vitamin D3 on asthma is still baffling . Aim : We have examined the effect of vitamin D3 supplementation in mild to moderate persistent asthma patients . Material s and Methods : We conducted an open labeled , r and omized comparative trial in 48 asthma patients . The study duration was about 90 days . The study had a run-in-period of 2 weeks . At the end of run-in-period , patients were divided into two groups : Usual care group ( n = 31 ) patients received budesonide and formoterol and intervention care group ( n = 32 ) patients received vitamin D3 supplementation along with their regular medicine . Results : The primary outcome of the study was to measure the improvement in forced expiratory volume in 1 second ( FEV1 ) . Patients in both groups had a significant improvement in FEV1 at the end of the study . The mean difference in percentage predicted FEV1 in usual care and intervention care group was 4.95 and 7.07 respectively . Conclusion : The study concluded that adjunctive therapy of vitamin D3 is effective in asthma patients . The present study will be an evidence based report ; however , future studies are warranted in longer duration of time to substantiate the present findings" ]

[ "The purpose of the present study was to determine the reliability and validity of the Functional Rating Index ( FRI ) for athletes with low back pain ( LBP ) . In this cross-sectional and prospect i ve cohort study , the vali date d Persian FRI ( PFRI ) was tested in 100 athletes with LBP and 50 healthy athletes . From the athletes with LBP , data were recollected among 50 athletes with a 7-day interval to examine test-retest reliability . The content validity was excellent , and the athletes with LBP responded to all items with no floor or ceiling effects . The discriminative validity was supported by a statistically significant difference in PFRI total scores between the athletes with LBP and healthy athletes . The concurrent criterion validity was good ( rho = 0.72 ) . The construct , convergent validity was good ( r = 0.83 ) . The internal consistency reliability estimate was high ( Cronbach 's α = 0.90 ) . Factor analysis demonstrated a single-factor structure with an explained variance of 52.22 % . The test-retest reliability was excellent , indicated by an ICC(agreement ) of 0.97 , and the agreement observed in the Bl and and Altman plot demonstrated no systematic bias . It is concluded that the PFRI has excellent psychometric properties for assessing athletes with LBP", "Background The severity and course of spinal pain is poorly understood in adolescents . The study aim ed to determine the prevalence and two-year incidence , as well as the course , frequency , and intensity of pain in the neck , mid back , and low back ( spinal pain ) . Methods This study was a school-based prospect i ve cohort study . All 5th and 6th grade students ( 11–13 years ) at 14 schools in the Region of Southern Denmark were invited to participate ( N = 1,348 ) . Data were collected in 2010 and again two years later , using an e-survey completed during school time . Results The lifetime prevalence of spinal pain was 86 % and 89 % at baseline and follow-up , respectively . A group of 13.6 % ( 95 % CI : 11.8 , 15.6 ) at baseline and 19.5 % ( 95 % CI : 17.1 , 22.0 ) at follow-up reported that they had pain frequently . The frequency of pain was strongly associated with the intensity of pain , i.e. , the majority of the participants reported their pain as relatively infrequent and of low intensity , whereas the participants with frequent pain also experienced pain of higher intensity . The two-year incidence of spinal pain varied between 40 % and 60 % across the physical locations . Progression of pain from one to more locations and from infrequent to more frequent was common over the two-year period . Conclusions Spinal pain is common at the age of 11–15 years , but some have more pain than others . The pain is likely to progress , i.e. , to more locations , higher frequency , and higher pain intensity over a two-year period" ]

[ "Background The increased prevalence of overweight and obesity warrants preventive actions , particularly among people in transitional stages associated with lifestyle changes , such as occupational retirement . The purpose is to investigate the effect of a one year low-intensity computer-tailored energy balance programme among recent retirees on waist circumference , body weight and body composition , blood pressure , physical activity and dietary intake . Methods A r and omised controlled trial was conducted among recent retirees ( N = 413 ; mean age 59.5 years ) . Outcome measures were assessed using anthropometry , bio-impedance , blood pressure measurement and question naires . Results Waist circumference , body weight and blood pressure decreased significantly in men of the intervention and control group , but no significant between-group-differences were observed at 12 or at 24-months follow-up . A significant effect of the programme was only observed on waist circumference ( -1.56 cm ( 95%CI : -2.91 to -0.21 ) ) at 12 month follow up among men with low education ( n = 85 ) . Physical activity and dietary behaviours improved in both the intervention and control group during the intervention period . Although , these behaviours changed more favourably in the intervention group , these between-group-differences were not statistically significant . Conclusions The multifaceted computer-tailored programme for recent retirees did not appear to be effective . Apparently the transition to occupational retirement and /or participation in the study had a greater impact than the intervention programme . Trial registration Clinical Trials NCT00122213", "Objectives To examine the trajectories of physical activity from preretirement to postretirement and to further clarify whether the changes in physical activity are associated with changes in body weight . Design Prospect i ve . Setting French national gas and electricity company ( GAZEL cohort ) . Participants From the original sample of 20 625 employees , only those retiring between 2001 and 2008 on a statutory basis were selected for the analyses ( analysis 1 : n=2711 , 63 % men ; analysis 2 : n=3812 , 75 % men ) . Persons with data on at least one preretirement and postretirement measurement of the outcome were selected . Primary and secondary outcome measures All outcome data were gathered by question naires . In analysis 1 , the annual prevalence of higher physical activity ( walking ≥5 km/week ) 4 years before and after retirement was analysed . In analysis 2 , changes in leisure-time sport activities ( engagement , frequency and manner ) from preretirement to postretirement were analysed with simultaneous changes in body weight ( kilogram ) . Results In analysis 1 ( n=2711 ) , prevalence estimates for 4 years before and 4 years after retirement showed that higher leisure-time physical activity ( walking at least 5 km/week ) increased by 36 % in men and 61 % in women during the transition to retirement . This increase was also observed among people at a higher risk of physical inactivity , such as smokers and those with elevated depressive symptoms . In a separate sample ( analysis 2 , n=3812 ) , change in weight as a function of preretirement and postretirement physical activity was analysed . Weight gain preretirement to postretirement was 0.85 ( 95 % CI 0.48 to 1.21 ) to 1.35 ( 0.79 to 1.90 ) kg greater among physically inactive persons ( decrease in activity or inactive ) compared with those physically active ( p<0.001 ) . Conclusions Retirement transition may be associated with beneficial changes in lifestyle and may thus be a good starting point to preventive interventions in various groups of individuals in order to maintain long-term changes", "Background People in transitional life stages , such as occupational retirement , are likely to gain weight and accumulate abdominal fat mass caused by changes in physical activity and diet . Hence , retirees are an important target group for weight gain prevention programmes , as described in the present paper . Methods / Design A systematic and stepwise approach ( Intervention Mapping ) is used to develop a low-intensity energy balance intervention programme for recent retirees . This one-year , low-intensity multifaceted programme aims to prevent accumulation of abdominal fat mass and general weight gain by increasing awareness of energy balance and influencing related behaviours of participants ' preference . These behaviours are physical activity , fibre intake , portion size and fat consumption . The effectiveness of the intervention programme is tested in a cluster r and omised controlled trial . Measurements of anthropometry , physical activity , energy intake , and related psychosocial determinants are performed at baseline and repeated at 6 months for intermediate effect , at 12 months to evaluate short-term intervention effects and at 24 months to test the sustainability of the effects . Discussion This intervention programme is unique in its focus on retirees and energy balance . It aims at increasing awareness and takes into account personal preferences of the users by offering several options for behaviour change . Moreover , the intervention programme is evaluated at short-term and long-term and includes consecutive outcome measures ( determinants , behaviour and body composition ) ", "OBJECTIVE To evaluate the efficacy at 6- , 12- , and 24-month follow-up of Keep Active Minnesota ( KAM ) , a telephone and mail-based intervention design ed to promote physical activity ( PA ) maintenance among currently active adults age 50 to 70 . METHOD Participants who reported having recently increased their MVPA to a minimum of 2d/wk , 30 min/bout , ( N=1049 ) were recruited in 2004 and 2005 from one large managed care organization in Minnesota , and r and omly assigned to either treatment ( KAM ; N=523 ) , or Usual Care ( UC ; N=526 ) with PA assessed using the CHAMPS question naire , and expressed as kcal/wk energy expenditure . RESULTS We find a sustained , significant benefit of the intervention at 6 , 12 and 24 months . kcal/wk expenditure in moderate or vigorous activities was higher at 6 ( p 's d(6m)=.16 ) , 12 ( p and mail-based PA maintenance intervention was effective at maintaining PA in both the short-term ( 6 months ) and longer-term ( 12 and 24 months ) relative to usual care", "Background Computer tailoring and motivational interviewing show promise in promoting lifestyle change , despite few head-to-head comparative studies . Purpose Vitalum is a r and omized controlled trial in which the efficacy of these methods was compared in changing physical activity and fruit and vegetable consumption in middle-aged Dutch adults . Methods Participants ( n = 1,629 ) were recruited via 23 general practice s and r and omly received either four tailored print letters , four motivational telephone calls , two of each type of intervention , or no information . The primary outcomes were absolute change in self-reported physical activity and fruit and vegetable consumption . Results All three intervention groups ( i.e. , the tailored letters , the motivational calls , and the combined version ) were equally and significantly more effective than the control group in increasing physical activity ( hours/day ) , intake of fruit ( servings/day ) , and consumption of vegetables ( grams/day ) from baseline to the intermediate measurement ( week 25 ) , follow-up 1 ( week 47 ) and 2 ( week 73 ) . Effect sizes ( Cohen ’s d ) ranged from 0.15 to 0.18 . Participants rated the interventions positively ; interviews were more positively evaluated than letters . Conclusions Tailored print communication and telephone motivational interviewing or their combination are equally successful in changing multiple behaviors", "The goal of evidence -based medicine is ultimately to improve patient outcomes and quality of care . Systematic review s of the available published evidence are required to identify interventions that lead to improvements in behavior , health , and well-being . Authoritative literature review s depend on the quality of published research and research reports . The Consoli date d St and ards for Reporting Trials ( CONSORT ) Statement ( www.consort-statement.org ) was developed to improve the design and reporting of interventions involving r and omized clinical trials ( RCTs ) in medical journals . We describe the 22 CONSORT guidelines and explain their application to behavioral medicine research and to evidence -based practice . Additional behavioral medicine-specific guidelines ( e.g. , treatment adherence ) are also presented . Use of these guidelines by clinicians , educators , policymakers , and research ers who design , report , and evaluate or review RCTs will strengthen the research itself and accelerate efforts to apply behavioral medicine research to improve the processes and outcomes of behavioral medicine practice", "Background Important health benefits can be derived when low-cost ( e.g. , computer-tailored ) physical activity interventions for older adults demonstrate sustained effects . Purpose The purpose of the study was to conduct in-depth analysis on the long-term efficacy of two tailored physical activity interventions for older adults . Methods A r and omized controlled trial ( n = 1,971 ) with two computer-tailored interventions and a no-intervention control group was conducted . The two tailored interventions consisted of three tailored letters , delivered during 4 months . The basic tailored intervention targeted psychosocial determinants alone , while the environmentally tailored intervention additionally targeted environmental determinants , by providing tailored environmental information . Self-reported behaviors ( i.e. , total physical activity , transport walking and cycling , leisure walking and cycling , and sports ) were measured at baseline and 12 months . Additionally , potential personal , health-related , and psychosocial moderators of the intervention effects were examined . Results The environmentally tailored intervention was effective in changing total physical activity , leisure cycling , and sports compared with the basic intervention and control group . No intervention effects were found for the basic intervention . Moderation analysis revealed that participants with a higher age , lower body mass index , and higher intention were unresponsive to the interventions . Conclusions Providing environmental information is an effective intervention strategy for increasing physical activity behaviors among older adults , especially among certain “ at-risk ” subgroups such as lower educated , overweight , or insufficiently active participants . Moderation analysis was perceived as a promising method for identifying meaningful subgroups that are unaffected by an intervention , which should receive special attention in future interventions", "Background : Evidence on the association between social support and leisure time physical activity ( LTPA ) is scarce and mostly based on cross-sectional data with different types of social support collapsed into a single index . The aim of this study was to investigate whether social support from the closest person was associated with LTPA . Methods : Prospect i ve cohort study of 5395 adults ( mean age 55.7 years , 3864 men ) participating in the British Whitehall II study . Confiding/emotional support and practical support were assessed at baseline in 1997–99 using the Close Persons Question naire . LTPA was assessed at baseline and follow-up in ( 2002–04 ) . Baseline covariates included socio-demographics , self-rated health , long-st and ing illnesses , physical functioning and common mental disorders . Results : Among participants who reported recommended levels of LTPA at baseline , those who experienced high confiding/emotional support were more likely to report recommended levels of LTPA at follow-up [ odds ratio ( OR ) : 1.39 , 95 % confidence interval ( CI ) : 1.12–1.70 in a model adjusted for baseline covariates ] . Among those participants who did not meet the recommended target of LTPA at baseline , high confiding/emotional support was not associated with improvement in activity levels . High practical support was associated with both maintaining ( OR : 1.34 , 95 % CI : 1.10–1.63 ) and improving ( OR : 1.25 , 95 % CI : 1.02–1.53 ) LTPA levels . Conclusion : These findings suggest that emotional and practical support from the closest person may help the individual to maintain the recommended level of LTPA . Practical support also predicted a change towards a more active lifestyle", "Aims /hypothesis . The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying Type II ( non-insulin-dependent ) diabetes mellitus in subjects with impaired glucose tolerance , to evaluate the effects of the intervention programme on cardiovascular risk factors and to assess the determinants for the progression to diabetes in persons with impaired glucose tolerance . Methods . A total of 523 overweight subjects with impaired glucose tolerance ascertained by two oral glucose tolerance tests were r and omised to either a control or intervention group . The control subjects received general information at the start of the trial about the lifestyle changes necessary to prevent diabetes and about annual follow-up visits . The intervention subjects had seven sessions with a nutritionist during the first year and a visit every 3 months thereafter aim ed at reducing weight , the intake of saturated fat and increasing the intake of dietary fibre . Intervention subjects were also guided individually to increase their physical activity . Results . During the first year , weight loss in the first 212 study subjects was 4.7 ± 5.5 vs 0.9 ± 4.1 kg in the intervention and control group , respectively ( p The plasma glucose concentrations ( fasting : 5.9 ± 0.7 vs 6.4 ± 0.8 mmol/l , p in blood pressure , serum lipids and anthropometric indices in the intervention group . Conclusion /interpretation . The interim results show the efficacy and feasibility of the lifestyle intervention programme . [ Diabetologia ( 1999 ) 42 : 793–801", "Background Physical inactivity is an independent risk factor for diabetes and heart disease . There is evidence that increasing physical activity can reduce the risk of developing these chronic diseases , but less evidence about effective ways to increase adherence to physical activity . Interventions are therefore needed that produce sustained increases in adherence to physical activity , are cost-effective and improve clinical endpoints . Methods The Women 's Lifestyle Study is a two year r and omized controlled trial involving a nurse-led intervention to increase physical activity in 40–74 year old physically inactive women recruited from primary care . Baseline measures were assessed in a face-to-face interview with a primary care nurse . The intervention involved delivery of a ' Lifestyle script ' by a primary care nurse followed by telephone counselling for nine months and a face-to-face nurse visit at six months . Outcome measurements are assessed at 12 and 24 months . The primary outcome is physical activity measured using a vali date d physical activity question naire . Secondary outcomes include blood pressure , weight , waist circumference , physical fitness ( step test ) , serum HbA1c , fasting glucose , lipids , insulin , and quality of life ( SF36 ) . Costs were measured prospect ively to allow a subsequent cost-effectiveness evaluation if the trial is positive . Discussion Due to report in 2008 , the Women 's Lifestyle Study tests the effectiveness of an enhanced low-cost , evidence -based intervention in increasing physical activity , and improving cardiovascular and diabetes risk indicators over two years . If successful in demonstrating improvements in health outcomes , this r and omized controlled trial will be the first to demonstrate long-term cardiovascular and diabetes risk health benefit , in addition to improvements in physical activity , from a sustainable physical activity intervention based in primary care . Trial Registration Australian Clinical Trials Registry ( ACTR ) , ACTRN012605000490673", "BACKGROUND Caloric restriction ( CR ) increases maximal life span in short-lived organisms , and its effects are being explored in nonhuman primates . The objectives of this study were to determine the feasibility of prolonged CR in nonobese adults and to compare the effects of CR- and exercise-induced weight loss on body composition and abdominal adiposity . METHODS A r and omized , controlled trial was conducted with 48 healthy , nonobese women and men , aged 57 + /- 1 ( mean + /- st and ard error [ SE ] ) years , with body mass index 27.3 + /- 0.3 kg/m2 . Participants were r and omly assigned to a 20 % calorically-restricted diet ( CR , n = 19 ) , exercise design ed to produce a similar energy deficit ( EX , n = 19 ) , or a healthy lifestyle control group ( HL , n = 10 ) for 1 year . Assessment s included weight , body composition by dual-energy x-ray absorptiometry , abdominal adipose tissue by magnetic resonance imaging , and energy intake by doubly labeled water . RESULTS The average level of CR achieved by the CR group was 11.5 + /- 2.1 % , and the EX group completed 59 + /- 6.7 % of their prescribed exercise . Weight changes were greater ( p Whole-body fat mass and visceral and subcutaneous abdominal adipose tissue decreased significantly ( p CR and exercise were equally effective in reducing weight and adiposity", "PURPOSE Given the prevalence of physical inactivity among American adults , convenient , low-cost interventions are strongly indicated . This study determined the 6- and 12-month effectiveness of telephone interventions delivered by health educators or by an automated computer system in promoting physical activity . DESIGN Initially inactive men and women age 55 years and older ( N = 218 ) in stable health participated . Participants were r and omly assigned to human advice , automated advice , or health education control . MEASURES The vali date d 7-day physical activity recall interview was used to estimate minutes of moderate to vigorous physical activity . Physical activity differences by experimental arm were verified on a r and om sub sample via accelerometry . RESULTS Using intention-to-treat analysis , at 6 months , participants in both interventions , although not differing from one another , showed significant improvements in weekly physical activity compared with controls . These differences were generally maintained at 12 months , with both intervention arms remaining above the target of 150 min per week of moderate to vigorous physical activity on average . CONCLUSION Automated telephone-linked delivery systems represent an effective alternative for delivering physical activity advice to inactive older adults", "Background A large proportion of adults fail to meet public health guidelines for physical activity as well as fruit , vegetable and fat intake . Interventions are needed to improve these health behaviors . Both computer tailoring and motivational interviewing have shown themselves to be promising techniques for health behavior change . The Vitalum project aims to compare the efficacy of these techniques in improving the health behaviors of adults aged 45–70 . This paper describes the design of the Vitalum study . Methods / Design Dutch general medical practice s ( N = 23 ) were recruited via a registration network or by personal invitation . The participants were then enrolled through these general practice s using an invitational letter . They ( n = 2,881 ) received a written baseline question naire to assess health behaviors , and potential psychosocial and socio-demographic behavioral determinants . A power analysis indicated that 1,600 participants who were failing to meet the guidelines for physical activity and either fruit or vegetable consumption were needed . Eligible participants were stratified based on hypertension status and r and omized into one of four intervention groups : tailored print communication , telephone motivational interviewing , combined , and control . The first two groups either received four letters or took part in four interviews , whereas the combined group received two letters and took part in two interviews in turns at 5 , 13 , 30 and 43 weeks after returning the baseline question naire . Each letter and interview focused on physical activity or nutrition behavior . The participants also took part in a telephone survey 25 weeks after baseline to gather new information for tailoring . There were two follow-up question naires , at 47 and 73 weeks after baseline , to measure short- and long-term effects . The control group received a tailored letter after the last posttest . The process , efficacy and cost-effectiveness of the interventions will be examined by means of multilevel mixed regression , cost-effectiveness analyses and process evaluation . Discussion The Vitalum study simultaneously evaluates the efficacy of tailored print communication and telephone motivational interviewing , and their combined use for multiple behaviors and people with different motivational stages and education levels . The results can be used by policymakers to contribute to evidence -based prevention of chronic diseases . Trial Registration Dutch Trial Register", "BACKGROUND The health benefits of leisure-time physical activity are well known , but whether less exercise than the recommended 150 min a week can have life expectancy benefits is unclear . We assessed the health benefits of a range of volumes of physical activity in a Taiwanese population . METHODS In this prospect i ve cohort study , 416,175 individuals ( 199,265 men and 216,910 women ) participated in a st and ard medical screening programme in Taiwan between 1996 and 2008 , with an average follow-up of 8·05 years ( SD 4·21 ) . On the basis of the amount of weekly exercise indicated in a self-administered question naire , participants were placed into one of five categories of exercise volumes : inactive , or low , medium , high , or very high activity . We calculated hazard ratios ( HR ) for mortality risks for every group compared with the inactive group , and calculated life expectancy for every group . FINDINGS Compared with individuals in the inactive group , those in the low-volume activity group , who exercised for an average of 92 min per week ( 95 % CI 71 - 112 ) or 15 min a day ( SD 1·8 ) , had a 14 % reduced risk of all-cause mortality ( 0·86 , 0·81 - 0·91 ) , and had a 3 year longer life expectancy . Every additional 15 min of daily exercise beyond the minimum amount of 15 min a day further reduced all-cause mortality by 4 % ( 95 % CI 2·5 - 7·0 ) and all-cancer mortality by 1 % ( 0·3 - 4·5 ) . These benefits were applicable to all age groups and both sexes , and to those with cardiovascular disease risks . Individuals who were inactive had a 17 % ( HR 1·17 , 95 % CI 1·10 - 1·24 ) increased risk of mortality compared with individuals in the low-volume group . INTERPRETATION 15 min a day or 90 min a week of moderate-intensity exercise might be of benefit , even for individuals at risk of cardiovascular disease . FUNDING Taiwan Department of Health Clinical Trial and Research Center of Excellence and National Health Research Institutes", "Background Physical activity has been associated with a decreased risk for breast cancer . The biological mechanismn(s ) underlying the association between physical activity and breast cancer is not clear . Most prominent hypothesis is that physical activity may protect against breast cancer through reduced lifetime exposure to endogenous hormones either direct , or indirect by preventing overweight and abdominal adiposity . In order to get more insight in the causal pathway between physical activity and breast cancer risk , we design ed the Sex Hormones and Physical Exercise ( SHAPE ) study . Purpose of SHAPE study is to examine the effects of a 1-year moderate-to-vigorous intensity exercise programme on endogenous hormone levels associated with breast cancer among sedentary postmenopausal women and whether the amount of total body fat or abdominal fat mediates the effects . Methods / Design In the SHAPE study , 189 sedentary postmenopausal women , aged 50–69 years , are r and omly allocated to an intervention or a control group . The intervention consists of an 1-year moderate-to-vigorous intensity aerobic and strenght training exercise programme . Partcipants allocated to the control group are requested to retain their habitual exercise pattern . Primary study parameters measured at baseline , at four months and at 12 months are : serum concentrations of endogenous estrogens , endogenous and rogens , sex hormone binding globuline and insuline . Other study parameters include : amount of total and abdominal fat , weight , BMI , body fat distribution , physical fitness , blood pressure and lifestyle factors . Discussion This study will contribute to the body of evidence relating physical activity and breast cancer risk and will provide insight into possible mechanisms through which physical activity might be associated with reduced risk of breast cancer in postmenopausal women . Trial registration", "OBJECTIVE To describe the 1 ) lifestyle intervention used in the Finnish Diabetes Prevention Study , 2 ) short- and long-term changes in diet and exercise behavior , and 3 ) effect of the intervention on glucose and lipid metabolism . RESEARCH DESIGN AND METHODS There were 522 middle-aged , overweight subjects with impaired glucose tolerance who were r and omized to either a usual care control group or an intensive lifestyle intervention group . The control group received general dietary and exercise advice at baseline and had an annual physician 's examination . The subjects in the intervention group received additional individualized dietary counseling from a nutritionist . They were also offered circuit-type resistance training sessions and advised to increase overall physical activity . The intervention was the most intensive during the first year , followed by a maintenance period . The intervention goals were to reduce body weight , reduce dietary and saturated fat , and increase physical activity and dietary fiber . RESULTS The intervention group showed significantly greater improvement in each intervention goal . After 1 and 3 years , weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control group , respectively . Measures of glycemia and lipemia improved more in the intervention group . CONCLUSIONS The intensive lifestyle intervention produced long-term beneficial changes in diet , physical activity , and clinical and biochemical parameters and reduced diabetes risk . This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system", "Cross-sectional data suggest that leisure-time physical activity may increase during retirement . Prospect i ve population -based studies are necessary to characterize leisure activity patterns through retirement among the same persons to verify this observation . Therefore , the purpose of this study was to describe the influence of retirement on leisure activity using data from Atherosclerosis Risk in Communities Study cohort participants aged 45 - 64 years at baseline . Physical activity was measured by the Baecke question naire in 1,825 African-American and 5,957 White participants who were working at the initial visit ( 1986 - 1989 ) and either retired or working 6 years later ( 1993 - 1995 ) . Participants who retired during follow-up were more likely to increase their sport participation and television watching than those who continued to work over the 6-year period . Among those reporting sport or exercise at baseline , those retiring over follow-up were more likely to maintain their sport and exercise participation than those who continued to work across race-gender groups . Among those not reporting sport or exercise at baseline , those who retired were more likely to adopt activity than those who continued to work except for African-American women . In this study , retirement was associated with gains in sport and exercise participation as well as television watching", "Abstract Objective : To assess the long term effectiveness of the “ green prescription ” programme , a clinician based initiative in general practice that provides counselling on physical activity . Design : Cluster r and omised controlled trial . Practice s were r and omised before systematic screening and recruitment of patients . Setting : 42 rural and urban general practice s in one region of New Zeal and . Subjects : All sedentary 40–79 year old patients visiting their general practitioner during the study 's recruitment period . Intervention : General practitioners were prompted by the patient to give oral and written advice on physical activity during usual consultations . Exercise specialists continued support by telephone and post . Control patients received usual care . Main outcome measures : Change in physical activity , quality of life ( as measured by the “ short form 36 ” ( SF-36 ) question naire ) , cardiovascular risk ( Framingham and D'Agostino equations ) , and blood pressure over a 12 month period . Results : 74 % ( 117/159 ) of general practitioners and 66 % ( 878/1322 ) of screened eligible patients participated in the study . The follow up rate was 85 % ( 750/878 ) . Mean total energy expenditure increased by 9.4 kcal/kg/week ( P=0.001 ) and leisure exercise by 2.7 kcal/kg/week ( P=0.02 ) or 34 minutes/week more in the intervention group than in the control group ( P=0.04 ) . The proportion of the intervention group undertaking 2.5 hours/week of leisure exercise increased by 9.72 % ( P=0.003 ) more than in the control group ( number needed to treat=10.3 ) . SF-36 measures of self rated “ general health , ” “ role physical , ” “ vitality , ” and “ bodily pain ” improved significantly more in the intervention group ( P decreasing blood pressure became apparent but no significant difference in four year risk of coronary heart disease . Conclusion : Counselling patients in general practice on exercise is effective in increasing physical activity and improving quality of life over 12 months . What is already known on this topic Counselling patients in general practice on exercise has result ed in gains in physical fitness and activity , but no health benefits have been found What this study adds Counselling patients in general practice on exercise is effective in increasing physical activity and improving quality of life over 12 months without evidence of adverse effects The intervention may reduce blood pressure by an average of 1–2 mm Hg over 12 months No changes in the risk of coronary heart disease were observed The intervention is sustainable in usual general practice Prompting practice staff to deliver the intervention may have increased its", "Background Since many individuals who initiate physical activity programs are highly likely to return to a sedentary lifestyle , innovative strategies to efforts to increase the number of physically active older adults who successfully maintain beneficial levels of PA for a substantial length of time are needed . Methods / Design The Keep Active Minnesota Trial is a r and omized controlled trial of an interactive phone- and mail-based intervention to help 50–70 year old adults who have recently increased their physical activity level , maintain that activity level over a 24-month period in comparison to usual care . Baseline , 6 , 12 , and 24 month measurement occurred via phone surveys with kilocalories expended per week in total and moderate-to-vigorous physical activity ( CHAMPS Question naire ) as the primary outcome measures . Secondary outcomes include hypothesized mediators of physical activity change ( e.g. , physical activity enjoyment , self-efficacy , physical activity self-concept ) , body mass index , and depression . Seven day accelerometry data were collected on a sub- sample of participants at baseline and 24-month follow-up . Discussion The Keep Active Minnesota study offers an innovative approach to the perennial problem of physical activity relapse ; by focusing explicitly on physical activity maintenance , the intervention holds considerable promise for modifying the typical relapse curve . Moreover , if shown to be efficacious , the use of phone- and mail-based intervention delivery offers potential for widespread dissemination . Trial registration Clinical Trials.gov Identifier : NCT00283452", "Physical inactivity among middle- and older-aged adults is pervasive , and is linked with numerous chronic conditions that diminish health and functioning . Counselor-directed physical activity programs may enhance extrinsic motivation ( reflected in social influence theories , such as self-presentation theory ) and , in turn , physical activity adherence , while the counselor is in charge of program delivery . However , external influences can undermine intrinsic motivation , making it more difficult to maintain physical activity once counselor-initiated contact ends . In contrast , programs that diminish the socially evaluative and controlling aspects of the counseling interchange may promote intrinsic motivation ( described in cognitive evaluation theory ) , and , thus , physical activity maintenance , even when counselor-initiated contact ceases . The objective of the Community Health Advice by Telephone ( CHAT ) project is to compare these two theories by conducting a r and omized controlled trial evaluating the effects of a telephone-administered counseling program delivered by a person ( social influence enhancement ) or computer ( cognitive evaluation enhancement ) on physical activity adoption and maintenance over 18 months . Healthy , sedentary adults ( n = 225 ) aged 55 years and older are r and omized to one of these programs or to a control arm . This study will contribute to advancing motivational theory as well as provide information on the sustained effectiveness of interventions with substantial public health applicability", "Objective To assess the effectiveness of a primary care based programme of exercise on prescription among relatively inactive women over a two year period . Design R and omised controlled trial . Setting 17 primary care practice s in Wellington , New Zeal and Participants 1089 women aged 40 - 74 not undertaking 30 minutes of moderate intensity physical activity on at least five days of the week Intervention Brief physical activity intervention led by nurse with six month follow-up visit and monthly telephone support over nine months . Main outcome measure Physical activity assessed at baseline and 12 and 24 months . Secondary outcomes were quality of life ( SF-36 ) , weight , waist circumference , blood pressure , concentrations of fasting serum lipids , glycated haemoglobin ( HbA1c ) , glucose , insulin , and physical fitness . Results Mean age was 58.9 ( SD 7 ) years . Trial retention rates were 93 % and 89 % at 12 and 24 months , respectively . At baseline , 10 % of intervention participants and 11 % of control participants were achieving 150 minutes of at least moderate intensity physical activity a week . At 12 months rates increased to 43 % and 30 % and at 24 months to 39.3 % and 32.8 % ( P SF-36 physical functioning ( P=0.03 ) and mental health ( P role physical scores were significantly lower ( P falls ( P injuries ( P=0.03 ) were recorded in the intervention group . Conclusions This programme of exercise on prescription increased physical activity and quality of life over two years , although falls and injuries also increased . This finding supports the use of exercise on prescription programmes as part of population strategies to reduce physical inactivity . Trial registration Australian New Zeal and Clinical Trials Registry ( ANZCTR ) ANZCTRN012605000490673", "OBJECTIVE To investigate whether a pragmatic structured education program with and without pedometer use is effective for promoting physical activity and improving glucose tolerance in those with impaired glucose tolerance ( IGT ) . RESEARCH DESIGN AND METHODS Overweight and obese individuals with IGT were recruited from ongoing screening studies at the University Hospitals of Leicester , U.K. Participants were r and omly assigned to one of three groups . Group 1 received a 3-h group-based structured education program design ed to promote walking activity using personalized steps-per-day goals and pedometers . Group 2 received a 3-h group-based structured education program design ed to promote walking activity using generic time-based goals . Group 3 received a brief information leaflet ( control condition ) . Outcomes included an oral glucose tolerance test , st and ard anthropometric measures , ambulatory activity , and psychological variables . Follow-up was conducted at 3 , 6 , and 12 months . RESULTS A total of 87 individuals ( 66 % male , mean age 65 years ) were included in this study . At 12 months , significant decreases in 2-h postchallenge glucose and fasting glucose of −1.31 mmol/l ( 95 % CI −2.20 to −0.43 ) and −0.32 mmol/l ( −0.59 to −0.03 ) , respectively , were seen in the pedometer group compared with the control group . No significant improvements in glucose control were seen in those given the st and ard education program . CONCLUSIONS This study suggests that a pragmatic structured education program that incorporates pedometer use is effective for improving glucose tolerance in those with IGT . This result is likely to have important implication s for future primary care – based diabetes prevention initiatives", "OBJECTIVES In this paper , we present the results of changes in risk factors by use of hormone therapy ( HT ) at 18 months in the Women On the Move through Activity and Nutrition ( WOMAN ) r and omized trial . METHODS The trial was design ed to test the hypothesis that aggressive dietary changes and increased physical activity to reduce weight , waist circumference ( WC ) , glucose , insulin , and lipoproteins would reduce progression of sub clinical atherosclerosis , carotid intimal media thickness and plaque , coronary artery calcification , and pulse wave velocity ( PWV ) . The study focused on postmenopausal women ( n = 508 ) , mean age of 57 , who were r and omized to the Lifestyle Change ( LC ) or Health Education ( HE ) group . RESULTS At 18 months of follow-up , there was significant , 17 lb , weight loss and 10 cm WC decrease in the LC group . There were significant differences in changes in low-density lipoprotein cholesterol ( LDL-C ) , insulin , glucose , large LDL , and LDL particles between the LC and HE groups . Risk factor changes were greater for women in the LC who lost a significant amount of weight ( > or=18.8 lb ) . Participants at 18 months were subdivided into women who had stayed on HT , 125 ( 28 % ) ; stopped HT after r and omization , 145 ( 33 % ) ; and not on HT at baseline but stopped an average of 7 months prior to r and omization , 173 ( 39 % ) . Weight loss in the LC was similar for all three groups , but LDL lipoprotein response was better for women who stopped HT after r and omization or were not on HT at baseline . CONCLUSIONS The trial has been successful in increasing exercise and diet changes and reduction in weight and WC and variables related to metabolic syndrome", "Background : Physical activity ( PA ) is inversely associated with obesity but the effect has been difficult to quantify using question naires . In particular , the shape of the association has not yet been well described . Pedometers provide an opportunity to better characterize the association . Methods : Residents of households over the age of 25 years in r and omly selected census districts in Tasmania were eligible to participate in the AusDiab cross-sectional survey conducted in 1999–2000 . 1848 completed the AusDiab survey and 1126 of these ( 609 women and 517 men ) wore a pedometer for 2-weekdays . Question naire data on recent PA , TV time and other factors were obtained . The outcomes were waist circumference ( in cm ) and body mass index ( BMI ) ( kg/m2 ) . Results : Increasing daily steps were associated with a decline in the obesity measures . The logarithmic nature of the associations was indicated by a sharper decline for those with lower daily steps . For example , an additional 2000 steps for those taking only 2000 steps per day was associated with a reduction of 2.8 ( 95 % confidence interval ( CI ) : 2.1,4.4 ) cm in waist circumference among men ( for women ; 2.2 ( 95 % CI : 0.6 , 3.9 cm ) ) with a baseline of only 2000 , steps compared to a 0.7 ( 95 % CI 0.3 , 1.1 ) cm reduction ( for women ; 0.6 ( 95 % CI : 0.2 , 1.0 ) ) for those already walking 10 000 steps daily . In the multivariable analysis , clearer associations were detected for PA and these obesity measures using daily step number rather than PA time by question naire . Interpretation : Pedometer measures of activity indicate that the inverse association between recent PA and obesity is logarithmic in form with the greatest impact for a given arithmetic step number increase seen at lower levels of baseline activity . The findings from this study need to be examined in prospect i ve setting", "Type 2 diabetes mellitus is increasing worldwide largely as a result from increasing obesity and sedentary lifestyle . The Finnish Diabetes Prevention Study ( DPS ) is the first individually r and omized controlled clinical trial to test the feasibility and efficacy of lifestyle modification in high-risk subjects . We r and omly assigned 522 ( 172 men , 350 women ) middle-aged ( mean age 55 yr ) , overweight ( mean body mass index 31 kg/m(2 ) ) subjects with impaired glucose tolerance either to the lifestyle intervention or control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight and intake of total and saturated fat , and increasing intake of fiber and physical activity . An oral glucose tolerance test was performed annually to detect incident cases of diabetes and to measure changes in metabolic parameters . The mean ( + /- SD ) weight reduction from baseline to year 1 and to year 2 , respectively , was 4.2 + /- 5.1 kg and 3.5 + /- 5.5 in the intervention group and 0.8 + /- 3.7 kg and 0.8 + /- 4.4 in the control group ( P risk of diabetes was reduced by 58 % ( P reduction in the incidence of diabetes was directly associated with number and magnitude of lifestyle changes made . In conclusion , the DPS is the first controlled trial demonstrating that type 2 diabetes can be prevented by changes in lifestyle in high-risk subjects", "BACKGROUND Regular physical activity is known to help prevent chronic disease and promote healthy aging . Yet , most older women are not regularly active . This study attempts to identify objective ly measured attributes of the neighborhood environment that may be associated with physical activity levels in older women . METHODS Sociodemographics and physical activity level , as measured by pedometer , were assessed in 158 overweight Caucasian and African-American postmenopausal women from southwestern Pennsylvania at the baseline evaluation of a r and omized clinical trial in 2002 - 2003 . Geographic information systems technology was used to obtain neighborhood-level data , including neighborhood socioeconomic status ( SES ) indicators , the median year that homes were built ( as a proxy measure for urban form ) , and proximity to businesses and facilities . Multiple linear regression was used to test associations between individuals ' physical activity level and neighborhood characteristics . RESULTS After controlling for individual age , race/ethnicity , education , smoking status , and body mass index , indicators of low neighborhood SES , living in a neighborhood with homes built between 1950 and 1969 ( representing an urban form that is more pedestrian-friendly than after 1969 ) , and living within walking distance ( 1500 m ) of specific types of businesses and facilities were positively associated with individuals ' physical activity level measured by pedometer ( p physical activity levels of postmenopausal women . Results warrant future research to clarify the role of these environmental attributes in other population", "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", "OBJECTIVE To determine whether alterations in diet and /or activity patterns during weekends contribute to weight gain or hinder weight loss . METHODS AND PROCEDURES R and omized , controlled trial comparing 1 year of caloric restriction ( CR ) with 1 year of daily exercise ( EX ) . Subjects included 48 healthy adults ( 30F , 18 M ) aged 50 - 60 years with BMI 23.5 - 29.9 kg/m(2 ) . Body weight was measured on 7 consecutive mornings for a total of 165 weeks at baseline and 437 weeks during the 1-year interventions . Daily weight changes were calculated for weekends ( Friday to Monday ) and weekdays ( Monday to Friday ) . Daily energy intake was estimated using food diaries ; daily physical activity was measured using accelerometers . Both measures were vali date d against doubly labeled water ( DLW ) . RESULTS At baseline , participants consistently gained weight on weekend days ( + 0.06 + /- 0.03 kg/day , ( mean + /- s.e . ) , P = 0.02 ) , but not on weekdays ( -0.02 + /- 0.02 kg/day , P = 0.18 ) . This was attributable to higher dietary intake on Saturdays and lower physical activity on Sundays relative to weekdays ( both P negative energy balance on weekdays ( P losing weight , and EX participants gained weight ( + 0.08 + /- 0.03 kg/day , P of weight loss during the interventions . DISCUSSION Alterations in lifestyle behaviors on weekends contribute to weight gain or cessation of weight loss on weekends . These results provide one explanation for the relatively slow rates of weight loss observed in many studies , and the difficulty with maintaining significant weight loss", "OBJECTIVE To determine the effects of adding stages of change-based counseling to an exercise prescription for older , sedentary adults in family practice . DESIGN The Step Test Exercise Prescription Stages of change counseling study was a 12-month cluster r and omized trial . SETTING Forty family practice s in 4 regions of Canada . PARTICIPANTS Healthy , community-dwelling men ( 48 % ) and women ( 52 % ) with a mean ( SD ) age of 64.9 ( 7.1 ) years ( range 55 to 85 years ) . There were a total of 193 participants in the intervention group and 167 in the control group . INTERVENTION Intervention physicians were trained to deliver a tailored exercise prescription and a transtheoretical behaviour change counseling program . Control physicians were trained to deliver the exercise prescription alone . MAIN OUTCOME MEASURES Predicted cardiorespiratory fitness , measured by predicted maximal oxygen consumption ( pVO2max ) , and energy expenditure , measured by 7-day physical activity recall . RESULTS Mean increase in pVO2max was significant for both the intervention ( 3.02 [ 95 % confidence interval 2.40 to 3.65 ] mL/kg/min ) and control ( 2.21 [ 95 % confidence interval 1.27 to 3.15 ] mL/kg/min ) groups at 12 months ( P fitness significantly more than women in the control group did ( 3.20 vs 1.23 mL/kg/min ) . The intervention group had a 4-mm Hg reduction in systolic blood pressure , while the control group 's mean reduction was 0.4 mm Hg ( P mean ( SD ) energy expended significantly increased and was higher in the intervention group than in the control group ( 69.06 [ 169.87 ] kcal/d vs -6.96 [ 157.06 ] kcal/d , P Step Test Exercise Prescription Stages of change exercise and behavioural intervention improved fitness and activity and lowered systolic blood pressure across a range of Canadian practice s , but this was not significantly different from the control group , which received only the exercise prescription . Women in the intervention group showed higher levels of fitness than women in the control group did ; men in both groups showed similar improvement", "OBJECTIVE To evaluate the effects of a lifestyle intervention and a structured exercise intervention on physical activity in older adults . METHOD Participants were r and omly assigned to a lifestyle intervention ( n=60 ) , including an individualized home-based program supported by phone calls , or to a structured intervention ( n=60 ) consisting of three weekly supervised sessions . Results were compared with a control group ( n=66 ) . Physical activity was measured with self-report question naires , pedometers , and accelerometers before the start ( pretest ) , at the end ( 11 months , posttest ) , and after 23 months ( follow-up ) . The study took place in Belgium from March 2004 until April 2006 . RESULTS At posttest , both intervention groups had significantly increased their total physical activity compared with the control group . At follow-up , the lifestyle group showed significantly larger increases in active transportation and total steps than the control and structured group respectively . There were no longer significant differences between the structured intervention and the control group . CONCLUSIONS The structured and lifestyle interventions were equally effective at the end of the intervention . One year after the intervention the lifestyle group maintained a significant increase in physical activity , which highlights the potential of lifestyle programs in the battle against inactivity in older adults ", "BACKGROUND Although inactivity is an important contributor to impaired functioning and disability with age , little is known concerning how improvements in physical functioning and well-being in older adults vary with the type of physical activity undertaken . METHODS One hundred three adults age 65 years and older , recruited via population -based methods , were r and omized to 12 months of community-based , moderate-intensity endurance and strengthening exercises ( Fit & Firm ) or stretching and flexibility exercises ( Stretch & Flex ) . A combination of class- and home-based exercise formats was used . Measured and self-rated physical performance along with perceived functioning and well-being were assessed pre- and postintervention . RESULTS Fit & Firm subjects showed greater 12-month improvements in both measured and self-rated endurance and strength compared to Stretch & Flex subjects . Stretch & Flex subjects reported greater improvements in bodily pain , and Stretch & Flex men evidence d greater improvements in flexibility relative to Fit & Firm subjects . Although overall exercise adherence was high in both exercise conditions ( approximately 80 % ) , subjects in both conditions showed better adherence to the home- versus class-based portions of their exercise prescriptions . CONCLUSIONS Community-based programs focusing on moderate-intensity endurance and strengthening exercises or flexibility exercises can be delivered through a combination of formats that result in improvement in important functional and well-being outcomes . This represents one of the first studies to report significant improvements in an important quality of life outcome -bodily pain-with a regular regimen of stretching and flexibility exercises in a community-based sample of older adults", "AIM To assess the cost-effectiveness of the ' Green Prescription ' physical activity counselling programme in general practice . METHOD Prospect i ve cost-effectiveness study undertaken as part of a cluster r and omised controlled trial with 12-month follow-up of 878 ' less-active ' patients aged 40 - 79 years in 42 general practice s in the Waikato . The intervention was verbal advice and a written exercise prescription given by general practitioners , with telephone exercise specialist follow-up compared with usual care . Main outcome measures included cost per total and leisure-time physical activity gain from health-funders ' and societal perspectives . RESULTS Significant increases in physical activity were found in the r and omised controlled trial . Programme-cost per patient was NZ170 dollars from a funder 's perspective . The monthly cost-effectiveness ratio for total energy expenditure achieved was 11 dollars per kcal/kg/day . The incremental cost of converting one additional ' sedentary ' adult to an ' active ' state over a twelve-month period was NZ1,756 dollars in programme costs . CONCLUSION Verbal and written physical activity advice given in general practice with telephone follow-up is an inexpensive way of increasing activity for sedentary people , and has the potential to have significant economic impact through reduction in cardiovascular and other morbidity and mortality", "Objective : This paper provides intraclass correlation coefficients ( ICCs ) for estimation of sample size inflation required in future cluster r and omised trials in primary or residential care", "There is increased recognition that determinants of health should be investigated in a life-course perspective . Retirement is a major transition in the life course and offers opportunities for changes in physical activity that may improve health in the aging population . The authors examined the effect of retirement on changes in physical activity in the GLOBE Study , a prospect i ve cohort study known by the Dutch acronym for \" Health and Living Conditions of the Population of Eindhoven and surroundings , \" 1991 - 2004 . They followed respondents ( n = 971 ) by postal question naire who were employed and aged 40 - 65 years in 1991 for 13 years , after which they were still employed ( n = 287 ) or had retired ( n = 684 ) . Physical activity included 1 ) work-related transportation , 2 ) sports participation , and 3 ) nonsports leisure-time physical activity . Multinomial logistic regression analyses indicated that retirement was associated with a significantly higher odds for a decline in physical activity from work-related transportation ( odds ratio ( OR ) = 3.03 , 95 % confidence interval ( CI ) : 1.97 , 4.65 ) , adjusted for sex , age , marital status , chronic diseases , and education , compared with remaining employed . Retirement was not associated with an increase in sports participation ( OR = 1.12 , 95 % CI : 0.71 , 1.75 ) or nonsports leisure-time physical activity ( OR = 0.80 , 95 % CI : 0.54 , 1.19 ) . In conclusion , retirement introduces a reduction in physical activity from work-related transportation that is not compensated for by an increase in sports participation or an increase in nonsports leisure-time physical activity", "OBJECTIVE The PREPARE programme study is a r and omized controlled trial which aims to determine whether structured education can be used to increase physical activity and improve glucose tolerance in individuals with impaired glucose tolerance ( IGT ) . This paper outlines the rationale , design and baseline data from the PREPARE programme study . METHODS Individuals with IGT were recruited from ongoing diabetes screening programmes . Outcomes included an oral glucose tolerance test , physical activity ( piezoelectric pedometer ) and psychological determinants . RESULTS 103 individuals ( male n = 65 ; female n = 38 ) were recruited , 28 % of whom were from a South Asian ethnic background . At baseline the participants ' mean age and BMI were 64 + /- 9 years and 29.4 + /- 4.5 kg/m2 respectively . Steps per day were associated with 2-h glucose ( p = -0.22 , p = 0.03 ) , fasting glucose ( p = 0.22 , p = 0.04 ) , HDL-cholesterol ( p = 0.23 , p = 0.02 ) , triglycerides ( p = -0.22 , p = 0.03 ) and body fat percentage ( p = -0.26 , p = 0.01 ) . Mean self-efficacy scores were significantly ( p concern about their IGT status but were confident that exercise would help treat/control IGT . CONCLUSION This study demonstrates the importance of developing effective physical activity and self-management programmes for individuals with IGT . PRACTICE IMPLICATION S This study provides a detailed framework for the promotion of physical activity in a population identified with an increased risk of developing type 2 diabetes which , if successful , could feasibly be implemented in a primary health care or community setting", "OBJECTIVES The effect of national exercise recommendations on adiposity is unknown and may differ by sex . We examined long-term effects of aerobic exercise on adiposity in women and men . RESEARCH METHODS AND PROCEDURES This was a 12-month r and omized , controlled clinical trial testing exercise effect on weight and body composition in men ( N = 102 ) and women ( N = 100 ) . Sedentary/unfit persons , 40 to 75 years old , were recruited through physician practice s and media . The intervention was facility- and home-based moderate-to-vigorous intensity aerobic activity , 60 min/d , 6 days/wk vs. controls ( no intervention ) . RESULTS Exercisers exercised a mean 370 min/wk ( men ) and 295 min/wk ( women ) , and seven dropped the intervention . Exercisers lost weight ( women , -1.4 vs. + 0.7 kg in controls , p = 0.008 ; men , -1.8 vs. -0.1 kg in controls , p = 0.03 ) , BMI ( women , -0.6 vs. + 0.3 kg/m(2 ) in controls , p = 0.006 ; men , -0.5 kg/m(2 ) vs. no change in controls , p = 0.03 ) , waist circumference ( women , -1.4 vs. + 2.2 cm in controls , p total fat mass ( women , -1.9 vs. + 0.2 kg in controls , p = 0.001 ; men , -3.0 vs. + 0.2 kg in controls , p steps per day had greater decreases in weight , BMI , body fat , and intra-abdominal fat ( all p trend minutes per day of exercise and for increases in maximal oxygen consumption . DISCUSSION These data support the U.S. Department of Agriculture and Institute of Medicine guidelines of 60 min/d of moderate-to-vigorous physical activity", "OBJECTIVES To build upon state-of-the-art theory and empirical data to estimate the strength of multiple mediators of the efficacious Keep Active Minnesota ( KAM ) physical activity ( PA ) maintenance intervention . METHODS The total , direct , and indirect effects through which KAM helped r and omized participants ( KAM n = 523 ; UC n = 526 ) maintain moderate or vigorous PA ( MVPA ) for up to 2 years were estimated using structural equation modeling . RESULTS Multiple mediators explained half ( beta = .052 , P = .13 ) of the effect of KAM on MVPA ( beta = .105 , P = .004 ) . Self-efficacy was the upstream variable in 2 endogenously mediated effects , and the self-concept mediator emerged as the strongest predictor of MVPA . CONCLUSIONS KAM positively impacted self-efficacy , which was associated with PA enjoyment , integration into the self-concept , and PA maintenance . Successful long-term PA maintenance appears to be influenced by multiple small interrelated mediational pathways . Future research evaluating maintenance models should specify recursive relationships among mediators and outcomes", "BACKGROUND This report presents the effectiveness of the Massachusetts Well-Integrated Screening and Evaluation for Women Across the Nation ( WISEWOMAN ) Project ( MWWP ) in reducing the cardiovascular disease ( CVD ) risk of uninsured and underinsured women aged > or = 50 . METHODS Healthcare sites were r and omly assigned to an enhanced intervention ( EI ) or minimum intervention ( MI ) . Women enrolled at all sites received CVD risk factor screening , onsite counseling , education , referral , and follow-up as needed . Women enrolled at EI sites received additional services and specially design ed interventions , including one-on-one nutritional and physical activity counseling and group activities , such as walking groups , nutrition classes , and cultural festivals . We report results for 1443 women who attended the initial screening in 10 study sites . Blood pressure , total cholesterol , number of servings of fruits and vegetables , and level of moderate or vigorous physical activity were assessed at baseline and 12-month follow-up screenings . Baseline data were collected between March and June 1996 ; follow-up data were collected 12 months later . RESULTS The comprehensive screenings significantly lowered the overall prevalence of hypertension , result ing in a 7 % reduction in high blood pressure among women at the EI sites ( p = 0.02 ) and a 9 % reduction at MI sites ( p = 0.009 ) . A significantly greater percentage of women became physically active at the EI sites ( 18 % ) than at the MI sites ( 6 % ) ( p = 0.04 ) . CONCLUSIONS MWWP is a promising model for providing comprehensive preventive healthcare to uninsured and underinsured women", "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", "BACKGROUND This study describes a general- practice -based high-risk cardiovascular prevention approach in Maastricht , The Netherl and s ( 1999 - 2003 ) . The intervention consisted of a complete registration of risk factors , optimization of medical treatment and health counseling on high fat consumption , smoking and physical inactivity . METHODS Behavioral effects were assessed in a trial , r and omization by practice and usual care as control . Vali date d question naires were completed by 1300 patients at baseline , 1174 after 4 months ( 90.3 % ) and 1046 ( 80.5 % ) after 18 months . RESULTS After 4 months , intention-to-treat analyses revealed a decrease in saturated fat intake of 1.3 points ( scale ranging from 7 to 30 points , p=0.000 ) . This was partly sustained after 18 months ( -0.5 points , p=0.014 ) . After 18 months , obese intervention patients were more likely to be sufficiently physically active than their control counterparts ( OR=1.90 , p=0.023 ) . No intervention effects were found for smoking . CONCLUSION Given the multiple factor and multiple component high-risk approach , the intervention had modest effects on only some of the behavioral risk factors addressed . Process data showed that the registration of risk factors and the optimization of medical treatment were only partly implemented , that the health counseling component could be further improved and that the intervention could benefit from additional health promoting strategies", "OBJECTIVE To determine whether provision of individualised physical activity advice by an exercise specialist in general practice is effective in modifying physical activity and cardiovascular risk factors in older adults . DESIGN R and omised controlled trial of individualised physical activity advice , reinforced at three and six months ( intervention ) versus no advice ( control ) . SETTING Two general practice s in Adelaide , South Australia , 1996 . PARTICIPANTS 299 adults aged 60 years or more who were healthy , sedentary and living in the community . MAIN OUTCOME MEASURES Changes to physical activity ( frequency and duration of walking and vigorous exercise ) , selected cardiovascular risk factors ( blood pressure , body weight , serum lipid levels ) and quality of life over 12 months . RESULTS Self-reported physical activity increased over the 12 months in both groups ( P time spent walking ( P intention to exercise ( P Serum levels of total and low-density lipoprotein cholesterol and triglycerides fell significantly over the 12 months to a similar extent in the two groups . No other significant changes in cardiovascular risk factors were seen . Quality -of-life scores decreased over the 12 months . The decrease was significantly greater among intervention than control women , but not men , for emotional well-being ( P = 0.02 ) , physical well-being ( P = 0.04 ) and social functioning ( P = 0.04 ) . DISCUSSION Provision of general practice -based physical activity advice reinforced three-monthly produced a sustained increase in self-reported physical activity . However , there were no associated changes in clinical measures of cardiovascular risk factors and minimal changes in quality -of-life measures" ]

[ "Background — Catheter ablation of ventricular tachycardia ( VT ) is effective and particularly useful in patients with frequent defibrillator interventions . Various substrate modification techniques have been described for unmappable or hemodynamically intolerable VT . Noninducibility is the most frequently used end point but is associated with significant limitations , so the optimal end point remains unclear . We hypothesized that elimination of local abnormal ventricular activities ( LAVAs ) during sinus rhythm or ventricular pacing would be a useful and effective end point for substrate-based VT ablation . As an adjunct to this strategy , we used a new high-density mapping catheter and frequently used epicardial mapping . Methods and Results — Seventy patients ( age , 67±11 years ; 7 female ) with VT and structurally abnormal ventricle(s ) were prospect ively enrolled . Conventional mapping was performed in sinus rhythm in all , and a high-density Pentaray mapping catheter was used in the endocardium ( n=35 ) and epicardially . LAVAs were recorded in 67 patients ( 95.7 % ; 95 % confidence interval , 89.2–98.9 ) . Catheter ablation was performed targeting LAVA with an irrigated-tip catheter placed endocardially via a transseptal or retro grade aortic approach or epicardially via the subxiphoid approach . LAVAs were successfully abolished or dissociated in 47 of 67 patients ( 70.1 % ; 95 % confidence interval , 58.7–80.1 ) . In multivariate analysis , LAVA elimination was independently associated with a reduction in recurrent VT or death ( hazard ratio , 0.49 ; 95 % confidence interval , 0.26–0.95 ; P=0.035 ) during long-term follow-up ( median , 22 months ) . Conclusions — LAVAs can be identified in most patients with scar-related VT . Elimination of LAVAs is feasible and safe and is associated with superior survival free from recurrent VT", "BACKGROUND For patients who have a ventricular tachyarrhythmic event , implantable cardioverter-defibrillators ( ICDs ) are a mainstay of therapy to prevent sudden death . However , ICD shocks are painful , can result in clinical depression , and do not offer complete protection against death from arrhythmia . We design ed this r and omized trial to examine whether prophylactic radiofrequency catheter ablation of arrhythmogenic ventricular tissue would reduce the incidence of ICD therapy . METHODS Eligible patients with a history of a myocardial infa rct ion underwent defibrillator implantation for spontaneous ventricular tachycardia or fibrillation . The patients did not receive antiarrhythmic drugs . Patients were r and omly assigned to defibrillator implantation alone or defibrillator implantation with adjunctive catheter ablation ( 64 patients in each group ) . Ablation was performed with the use of a substrate-based approach in which the myocardial scar is mapped and ablated while the heart remains predominantly in sinus rhythm . The primary end point was survival free from any appropriate ICD therapy . RESULTS The mortality rate 30 days after ablation was zero , and there were no significant changes in ventricular function or functional class during the mean ( + /-SD ) follow-up period of 22.5+/-5.5 months . Twenty-one patients assigned to defibrillator implantation alone ( 33 % ) and eight patients assigned to defibrillator implantation plus ablation ( 12 % ) received appropriate ICD therapy ( antitachycardia pacing or shocks ) ( hazard ratio in the ablation group , 0.35 ; 95 % confidence interval , 0.15 to 0.78 , P=0.007 ) . Among these patients , 20 in the control group ( 31 % ) and 6 in the ablation group ( 9 % ) received shocks ( P=0.003 ) . Mortality was not increased in the group assigned to ablation as compared with the control group ( 9 % vs. 17 % , P=0.29 ) . CONCLUSIONS In this r and omized trial , prophylactic substrate-based catheter ablation reduced the incidence of ICD therapy in patients with a history of myocardial infa rct ion who received ICDs for the secondary prevention of sudden death . ( Current Controlled Trials number , IS RCT N62488166 [ controlled-trials.com ] . )", "One hundred and one patients with sustained unimorphic ventricular tachycardia underwent programmed ventricular stimulation with one of two protocol s. Fifty patients underwent programmed stimulation with protocol A , which consisted of burst overdrive pacing , single , double , and triple extrastimuli at the right ventricular apex , right ventricular outflow tract , or septum , and then at the left ventricular apex . Fifty-one patients underwent programmed stimulation with protocol B , which consisted of burst overdrive pacing , single and double extrastimuli at the right ventricular apex , right ventricular outflow tract or septum , and at the left ventricular apex , followed by triple extrastimuli at these sites . The stimulation protocol was continued until sustained ventricular tachycardia or rapid , polymorphic ventricular tachycardia greater than 10 sec in duration was induced . With protocol A , clinical and non clinical ventricular tachycardia was induced in 76 % and 36 % of patients , respectively ; with protocol B , clinical and non clinical ventricular tachycardia was induced in 85 % and 38 % of patients , respectively . Direct-current countershock for sustained polymorphic ventricular tachycardia was required in 10 % of patients studied under protocol A , compared with in 2 % of patients studied under protocol B. With protocol A , near-maximal yield of induced clinical ( 72 % ) and non clinical ventricular tachycardia ( 30 % ) was attained after the use of triple extrastimuli at the first stimulation site . The yield of stimulation at a second right ventricular site and of left ventricular stimulation was only an additional 2 % each . With protocol B , triple extrastimuli increased the yield of induced clinical ventricular tachycardia from 61 % to 85 % . ( ABSTRACT TRUNCATED AT 250 WORDS", "BACKGROUND Recurrent sustained ventricular tachycardia ( VT ) is not responsive to antiarrhythmic drugs in the majority of patients , who therefore need therapy with nonpharmacological methods . We evaluated prospect ively the feasibility , safety , and efficacy of transcatheter radiofrequency ( RF ) ablation of VT in 21 selected patients with ischemic heart disease and VT . METHODS AND RESULTS Twenty-one patients with ischemic heart disease and recurrent , drug-refractory VT documented by 12-lead ECG were selected who had sufficient hemodynamic tolerance of VT to undergo transcatheter mapping . Documented clinical VT was reproduced by programmed cardiac stimulation ( PCS ) , and the site of origin was localized by a combination of techniques , including pace mapping , activation-sequence mapping , recordings of middiastolic potentials , and application of re setting and entrainment principles . RF current at 55 V was applied ( 3.8 + /- 3.1 applications per patient ) for as long as 30 seconds at a time to target sites . Twenty-four distinct clinical VTs ( mean cycle length , 445 + /- 52 milliseconds ) were mapped and ablated in 21 patients . In 17 of 21 patients ( 81 % ) , the procedure was acutely successful , and the target clinical VT could no longer be induced by PCS after the procedure , whereas in 4 patients , clinical VT remained inducible . By contrast , VTs with shorter cycle length and different QRS morphology than the ablated VT could still be induced by PCS in 12 of 21 patients . One patient died in intractable congestive heart failure 10 days after the procedure , and the remaining 20 are alive at the end of the follow-up period . The majority of the patients continued to be treated with at least one additional mode of antiarrhythmic therapy ; 12 patients were still taking antiarrhythmic drugs , and 9 patients received an implantable cardioverter/defibrillator . During a mean follow-up period of 13.2 + /- 5.0 months , 9 of 20 patients ( 45 % ) had recurrent VT . In 4 patients , the recurrent VT was different than the previously ablated one . Clinical VT recurred in all 4 patients in whom RF ablation had been acutely unsuccessful . Four patients with recurrent VT underwent repeat RF ablation procedures that were acutely successful and had no further recurrence . CONCLUSION Transcatheter RF ablation is feasible but has only moderately high efficacy in a small , selected group of patients with ischemic heart disease and drug-refractory , highly frequent , hemodynamically tolerated , sustained VT . In the majority of the patients , this treatment technique is palliative rather than definitive , and many of the patients continue to require other methods of antiarrhythmic therapy", "BACKGROUND This study evaluated the cost-effectiveness of catheter ablation therapy versus amiodarone for treating ventricular tachycardia ( VT ) in patients with structural heart disease . The analysis used a societal perspective for a hypothetical cohort of VT patients with implantable cardioverter-defibrillators , who were experiencing frequent shocks . METHODS AND RESULTS We calculated incremental cost-effectiveness of ablation relative to amiodarone over 5 years after treatment initiation . Event probabilities were from the Chilli r and omized clinical trial ( Chilli Cooled Ablation System , Cardiac Pathways Corporation , Sunnyvale , Calif ) , the literature , and a consensus panel . Costs were from 1998 national Medicare reimbursement schedules . Quality -of-life weights ( utilities ) were estimated using an established preference measurement technique . In a hypothetical cohort of 10 000 patients , 5-year costs were higher for patients undergoing ablation compared with amiodarone therapy ( $ 21 795 versus $ 19 075 ) . Ablation also produced a greater increase in quality of life ( 2.78 versus 2.65 quality -adjusted life-years [ QALYs ] ) . This yielded a cost-effectiveness ratio of $ 20 923 per QALY gained for ablation compared with amiodarone . Results were relatively insensitive to assumptions about ablation success and durability . In less severe patients with good ejection fractions who suffer their first VT episode , the incremental cost-effectiveness ratio was $ 6028 per QALY gained . These cost-effectiveness ratios are within the range generally thought to warrant technology adoption . CONCLUSIONS This study demonstrates that , from a societal perspective , catheter ablation appears to be a cost-effective alternative to amiodarone for treating VT patients", "Reproduction of spontaneously occurring ventricular tachycardia ( VT ) and induction of previously undocumented VT were studied prospect ively in 98 patients : 48 with documented sustained VT or ventricular fibrillation , 25 with nonsustained or exercise-induced VT , and 25 with no documented VT . Patients received 1 to 4 ventricular extrastimuli and ventricular burst pacing at 2 right ventricular ( RV ) sites , first at twice late diastolic threshold , and then at 10 mA using a prospect i ve , t and em study design . Spontaneously occurring VT was reproduced in 37 of 48 patients ( 77 % ) at twice late diastolic threshold and in 1 other patient ( 2 % ) at 10 mA. VT was reproduced at both RV sites in 17 of 48 patients ( 35 % ) and at 1 site in 20 of 48 patients ( 42 % ) at twice late diastolic threshold . A previously undocumented VT was induced in 7 of 25 patients ( 28 % ) with no documented VT at twice diastolic threshold and 14 of 25 patients ( 56 % ) at 10 mA. A previously undocumented VT was induced in 33 of 73 patients ( 45 % ) with a history of sustained or nonsustained VT at twice late diastolic threshold and in 47 of 73 patients ( 64 % ) at 10 mA. In patients with documented sustained VT , the use of up to 4 ventricular extrastimuli at multiple RV sites increases the sensitivity of the test . In patients without documented VT , the induction of previously undocumented VT with more than 3 ventricular extrastimuli limits the specificity of the test . Increased current provides only a slight advantage over 4 ventricular extrastimuli at twice late diastolic threshold in terms of reproduction of spontaneously occurring VT , but leads to a marked increase in induction of previously undocumented VT", "Background — Electrical storm ( ES ) caused by recurrent episodes of ventricular tachycardia ( VT ) can cause sudden death in patients with implantable cardioverter-defibrillators and adversely affects prognosis in survivors . Catheter ablation has been proposed for treating ES , but its long-term effect in a large population has never been verified . Methods and Results — Ninety-five consecutive patients with coronary artery disease ( 72 patients ) , idiopathic dilated cardiomyopathy ( 10 patients ) , and arrhythmogenic right ventricular dysplasia/cardiomyopathy ( 13 patients ) undergoing catheter ablation for drug-refractory ES were prospect ively evaluated . Short-term efficacy was defined by a complete protocol of programmed electric stimulation and by in-hospital outcome ; long-term analysis addressed ES recurrence , cardiac mortality , and VT recurrence . Pleomorphic/nontolerated VTs required electroanatomic and noncontact mapping in 48 and 22 patients , respectively , and percutaneous cardiopulmonary support in 10 patients . An epicardial approach was used in 10 patients . After 1 to 3 procedures , induction of any clinical VT(s ) by programmed electrical stimulation was prevented in 85 patients ( 89 % ) . ES was acutely suppressed in all patients ; a minimum period of 7 days with stable rhythm was required before hospital discharge . At a median follow-up of 22 months ( range , 1 to 43 months ) , 87 patients ( 92 % ) were free of ES and 63 patients ( 66 % ) were free of VT recurrence . Eight of 10 patients with persistent inducibility of clinical VT(s ) had ES recurrence ; 4 of them died suddenly despite appropriate implantable cardioverter-defibrillator intervention . All together , 11 of 95 patients ( 12 % ) died of cardiac-related reasons . In the group of patients presenting with all clinical VTs acutely abolished , no ES recurrence was documented , and cardiac mortality was significantly lower compared with the group of patients showing ≥1 clinical VT still inducible after catheter ablation . Conclusions — Advanced strategies of catheter ablation applied to a large population of patients are effective in the short-term treatment of ES . By preventing ES recurrence , catheter ablation may play a protective role over the long term and , together with long-term pharmacological therapy , may favorably affect cardiac mortality", "BACKGROUND Lately , the number of systematic review s published has increased substantially . Many systematic review s exclude trials published in language s other than English . However , there is little empirical evidence to support this action . We looked for differences in the completeness of reporting between trials published in other language s and those published in English , to see whether the exclusion of trials published in other language s is justified . METHODS We compared completeness of reporting , design characteristics , and analytical approaches of 133 r and omised controlled trials ( RCTs ) published in English between 1989 and 1994 and 96 published in French , German , Italian , or Spanish during the same time . RCTs were identified by h and search ing of journals ( seven in English and six in the other language s ) . FINDINGS We found no significant differences between trials published in English and other- language trials for any single item in the completeness of reporting scale ( r and omisation , double-blinding , withdrawals ) , or for the overall score ( percentage of maximum possible score 51.0 % for trials in English , 46.2 % for trials in other language s ; 95 % CI for difference -1.1 to 10.5 ) . Other- language trials were more likely than English- language trials to have adult participants , to use two or more interventions , and to compare two or more active treatments without an untreated control group . Trials in other language s were less likely to report a clearly prespecified primary outcome or any rationale for sample size estimation . INTERPRETATION These results provide evidence for inclusion of all trial reports , irrespective of the language in which they are published , in systematic review s. Their inclusion is likely to increase precision and may reduce systematic errors . We hope that our findings will prove useful to those developing guidelines and policies for the conduct of reporting of systematic review", "BACKGROUND In patients with ventricular tachycardia ( VT ) and a history of myocardial infa rct ion , intervention with an implantable cardioverter defibrillator ( ICD ) can prevent sudden cardiac death and thereby reduce total mortality . However , ICD shocks are painful and do not provide complete protection against sudden cardiac death . We assessed the potential benefit of catheter ablation before implantation of a cardioverter defibrillator . METHODS The Ventricular Tachycardia Ablation in Coronary Heart Disease ( VTACH ) study was a prospect i ve , open , r and omised controlled trial , undertaken in 16 centres in four European countries . Patients aged 18 - 80 years were eligible for enrolment if they had stable VT , previous myocardial infa rct ion , and reduced left-ventricular ejection fraction ( LVEF ; to receive catheter ablation and an ICD ( ablation group , n=54 ) or ICD alone ( control group , n=56 ) . R and omisation was done by computer-generated r and omly permuted blocks and stratified by centre and LVEF ( 30 % ) . Patients were followed up for at least 1 year . The primary endpoint was the time to first recurrence of VT or ventricular fibrillation ( VF ) . Analysis was by intention to treat ( ITT ) . This study is registered with Clinical Trials.gov , number NCT00919373 . FINDINGS 107 patients were included in the ITT population ( ablation group , n=52 ; control group , n=55 ) . Two patients ( one in each group ) withdrew consent immediately after r and omisation without any follow-up data and one patient ( ablation group ) was excluded because of a protocol violaton . Mean follow-up was 22.5 months ( SD 9.0 ) . Time to recurrence of VT or VF was longer in the ablation group ( median 18.6 months [ lower quartile 2.4 , upper quartile not determinable ] ) than in the control group ( 5.9 months [ IQR 0.8 - 26.7 ] ) . At 2 years , estimates for survival free from VT or VF were 47 % in the ablation group and 29 % in the control group ( hazard ratio 0.61 ; 95 % CI 0.37 - 0.99 ; p=0.045 ) . Complications related to the ablation procedure occurred in two patients ; no deaths occurred within 30 days after ablation . 15 device-related complications requiring surgical intervention occurred in 13 patients ( ablation group , four ; control group , nine ) . Nine patients died during the study ( ablation group , five ; control group , four ) . INTERPRETATION Prophylactic VT ablation before defibrillator implantation seemed to prolong time to recurrence of VT in patients with stable VT , previous myocardial infa rct ion , and reduced LVEF . Prophylactic catheter ablation should therefore be considered before implantation of a cardioverter defibrillator in such patients . FUNDING St Jude Medical" ]

[ "Background —In patients with paroxysmal atrial fibrillation ( AF ) , catheter ablation maintains sinus rhythm more effectively than antiarrhythmic drugs ( AADs ) , but its effect on symptoms and quality of life ( QOL ) has not been fully characterized . Methods and Results —We evaluated symptoms and QOL in a multicenter , r and omized trial comparing catheter ablation with AADs as second-line treatment for patients with paroxysmal AF . The Short Form (SF)-36 health survey and the AF Symptom Checklist were administered at baseline and 3 , 6 , and 9 months after a blanking or dose-titration period . The primary between-group comparisons were conducted at 3 months because of permitted crossover from AAD to ablation beyond this time . Additional analyses based on subsequent follow-up were performed , including the construction of mixed linear regression models to assess the impact of multiple factors on follow-up QOL scores . At baseline in both the ablation ( n=103 ) and the AAD ( n=56 ) groups , 7 of 8 SF-36 scales were well below population norms , as were the physical ( PCS ) and mental ( MCS ) summary scores . At 3 months , the same 7 SF-36 scales were significantly ( P ablation than in the AAD group , as were the PCS ( 52.0±7.8 versus 47.1±10.6 ; P ) and MCS ( 52.4±8.1 versus 46.6±9.8 ; P whereas symptom frequency ( 9.3±9.2 versus 19.0±12.6 ; P ) and symptom severity ( 7.7±7.2 versus 16.2±10.0 ; P with QOL changes over time . Conclusions —For second-line therapy of paroxysmal AF , ablation is superior to AAD treatment at improving symptoms and QOL . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00116428", "Background In contrast to surveys in cardiologist setting s , presentation and management of atrial fibrillation ( AF ) in primary care patients is less well studied . Methods and results The prospect i ve ATRIUM ( OutpatientRegistry Upon Morbidity of Atrial Fibrillation ) collected data from patients with AF seen by 730 physicians representing a r and om sample of all primary care physicians in Germany . ATRIUM enrolled 3,667 patients ( mean age , 72 ± 9 years ; 58 % male , mean CHADS2 score 2.2 ± 1.3 ) , 994 ( 27.1 % ) with paroxysmal , 944 ( 25.7 % ) with persistent or long-st and ing persistent and 1,525 ( 41.6 % ) with permanent AF ( no AF type was specified in 204 patients ) . Mean duration since initial diagnosis of AF was 61 ± 66 months ( median 42 , interquartile range 14–88 ) . Reported symptoms included palpitations ( 43 % ) , shortness of breath ( 49 % ) , fatigue ( 49 % ) , dizziness ( 37 % ) and angina ( 20 % ) . Most common concomitant conditions were hypertension ( 84 % ) , heart failure ( 43 % ) , coronary artery disease ( 345 % ) , diabetes ( 35 % ) and chronic kidney disease ( 20 % ) . Prior myocardial infa rct ion was present in 11 % of patients , prior stroke in 10 % and prior transient ischemic attack in 10 % . Antithrombotic medication was used by 93 % of the patients ( oral anticoagulants , 83 % ) . Rate control therapy was reported in 75 % and rhythm control therapy in 33 % , often added to rate control . Drugs for rhythm and rate control included ß-blockers ( 75 % ) , calcium antagonists ( 15 % ) , digitalis ( 29 % ) , sodium channel blockers of type IA ( quinidine , 1.0 % ) or IC ( flecainide or propafenone , 5 % ) , and potassium channel blockers including amiodarone ( 11 % ) . In the year prior to enrollment , 46 % of the patients had been cardioverted ( 23 % by drugs , 22 % electrically ) , catheter ablation had been performed in 5 % , and 10 % received a pacemaker or defibrillator . A high proportion ( 44 % ) of the patients were hospitalized in the year prior to enrollment . Conclusions Patients with AF managed in primary care often receive guideline -conforming therapy including antithrombotic therapy , rate control and rhythm control ( numbers given above ) . Despite this apparent adherence , almost half of the patients were hospitalized in the year prior to enrollment , suggesting that the therapies applied do not stabilize patients sufficiently to keep them out of hospital", "BACKGROUND Recent data have shown that the septum and anterior left atrial ( LA ) wall may contain \" rotor \" sites required for AF maintenance . However , whether adding ablation of such sites to st and ard ICE-guided PVAI improves outcome is not well known . OBJECTIVE To determine if adjuvant anterior LA ablation during PVAI improves the cure rate of paroxysmal and permanent AF . METHODS One hundred AF patients ( 60 paroxysmal , 40 persistent/permanent ) undergoing first-time PVAI were enrolled over three months to receive adjuvant anterior LA ablation ( Group I ) . These patients were compared with 100 r and omly selected , matched first-time PVAI controls from the preceding three months who did not receive adjuvant ablation ( Group II ) . All 200 patients underwent ICE-guided PVAI during which all four PV antra and SVC were isolated . In group I , a decapolar lasso catheter was used to map the septum and anterior LA wall during AF ( induced or spontaneous ) for continuous high-frequency , fractionated electrograms ( CFAE ) . Sites where CFAE were identified were ablated until the local EGM was eliminated . A complete anterior line of block was not a requisite endpoint . Patients were followed up for 12 months . Recurrence was assessed post-PVAI by symptoms , clinic visits , and Holter at 3 , 6 , and 12 months . Patients also wore rhythm transmitters for the first 3 months . Recurrence was any AF/AFL > 1 min occurring > 2 months post-PVAI . RESULTS Patients ( age 56 + /- 11 years , 37 % female , EF 53%+/- 11 % ) did not differ in baseline characteristics between group I and II by design . Group I patients had longer procedure time ( 188 + /- 45 min vs 162 + /- 37 min ) and RF duration ( 57 + /- 12 min vs 44 + /- 20 min ) than group II ( P Overall recurrence occurred in 15/100 ( 15 % ) in group I and 20/100 ( 20 % ) in group II ( P = 0.054 ) . Success rates did not differ for paroxysmal patients between group I and II ( 87 % vs 85 % , respectively ) . However , for persistent/permanent patients , group I had a higher success rate compared with group II ( 82 % vs 72 % , P = 0.047 ) . CONCLUSIONS Adjuvant anterior LA ablation does not appear to impact procedural outcome in patients with paroxysmal AF but may offer benefit to patients with persistent/permanent AF", "BACKGROUND The aim of this prospect i ve study was to evaluate the recurrences of atrial fibrillation ( AF ) and flutter ( AFL ) after circumferential pulmonary vein ablation ( CPVA ) using repetitive long-term Holter recordings , and to evaluate the change in quality of life ( QoL ) , especially in patients with asymptomatic AF recurrences . METHODS A total of 149 patients with AF were followed up with 7-day Holter monitoring at 3 , 6 , and 12 months after CPVA . We calculated the burden of AF/AFL defined as the percentage of time in AF/AFL , and patients with documented arrhythmia were divided into isolated symptomatic episodes of arrhythmia , mixed symptomatic/asymptomatic arrhythmia , or isolated asymptomatic arrhythmia . The QoL was analyzed with SF-36 question naires in patients with sinus rhythm after CPVA , and in patients with recurrence of symptomatic and asymptomatic arrhythmia , respectively . RESULTS Asymptomatic arrhythmia was observed in 44 % of the patients with documented arrhythmia at 12 months of follow-up . In patients with persistent AF , 63 % of the documented arrhythmia at 12 months of follow-up was asymptomatic and often persistent . In the subgroup of patients with asymptomatic arrhythmia , the QoL improved significantly in the physical scores , in contrast to patients with symptomatic arrhythmia who had unchanged or worsened QoL scores . CONCLUSIONS Asymptomatic arrhythmia is very common after AF ablation . Our data indicate that these patients improve their physical component of the QoL significantly , which may be considered a palliative success of treatment . We suggest that patients with asymptomatic AF recurrences are carefully evaluated before considering reablation . Repetitive rhythm monitoring after AF ablation is very important considering the postablation management of anticoagulant therapy", "AIMS To investigate the effectiveness of additional substrate modification ( SM ) by left atrial ( LA ) linear lesions as compared with pulmonary vein isolation ( PVI ) alone in patients with persistent atrial fibrillation ( AF ) in a prospect i ve r and omized study . Percutaneous PVI has evolved as an accepted treatment for paroxysmal AF but seemed to be less effective in patients with persistent AF . The benefit of PVI alone and additional linear lesions has not been vali date d in a r and omized study so far . METHODS AND RESULTS Sixty-two patients with persistent AF ( median duration 7 , range 1 - 18 months ) were r and omly assigned to either PVI alone ( n = 30 ) or additional SM ( n = 32 ) consisting of a roof line connecting both left superior and right superior PV and LA isthmus ablation between left inferior PV and mitral annulus . Procedures including SM were performed using a three-dimensional mapping system ( EnSite NavX , St Jude Medical , St Paul , MN , USA ) . Anti-arrhythmic drugs were discontinued within 8 weeks after ablation in both groups . Follow-up included daily trans-telephonic ECG transmitted irrespective of the patient 's symptoms . PVI was successful in 98 % of all targeted veins in both groups . Additional SM did not increase fluoroscopy time ( 72.1+/-18.7 vs. 72.9+/-17.3 min , P=0.92 ) because of the use of three-dimensional navigation in the PVI+SM group . AF recurrences within the first 4 weeks following ablation were more common after PVI alone ( 77 % ) than additional SM ( 44 % , P=0.002 ) . After a follow-up time of 487 ( 429 - 570 ) days , only 20 % of patients undergoing st and alone PVI remained in sinus rhythm when compared with 69 % following PVI combined with SM ( P=0.0001 ) . Two patients assigned to PVI+SM experienced procedure-related complications ( cardiac tamponade and minor stroke ) which resolved without sequelae . CONCLUSION PVI alone is insufficient in the treatment of persistent AF . However , additional left linear lesions increase the success rate significantly . Early AF-relapses are associated with a negative outcome after PVI alone but not following additional SM", "Background —The modification of atrial fibrillation cycle length ( AFCL ) during catheter ablation in humans has not been evaluated . Methods and Results —Seventy patients undergoing ablation of prolonged episodes of AF were r and omized to pulmonary vein ( PV ) isolation or additional ablation of the mitral isthmus . Mean AFCL was determined at a distance from the ablated area ( coronary sinus ) at the following intervals : before ablation , after 2- and 4-PV isolations , and after linear ablation . Inducibility of sustained AF ( ≥10 minutes ) was determined before and after ablation . Spontaneous sustained AF ( 715±845 minutes ) was present in 30 patients and induced in 26 ( AFCL , 186±19 ms ) . PV isolation terminated AF in 75 % , with the number of PVs requiring isolation before termination increasing with AF duration ( P = 0.018 ) . PV isolation result ed in progressive or abrupt AFCL prolongation to various extents , depending on the PV : to 214±24 ms ( P increase in AFCL ( 30±17 versus 14±11 ms ; P = 0.005 ) and the decrease in fragmentation ( 30.0±26.8 % to 10.3±14.5 % ; P prolonged AFCL , with a greater prolongation in patients with AF termination ( 44±13 versus 22±23 ms ; P = 0.08 ) . Sustained AF was noninducible in 57 % after PV isolation and in 77 % after linear ablation . At 7±3 months , 74 % with PV isolation and 83 % with linear ablation were arrhythmia free without antiarrhythmics , which was significantly associated with noninducibility ( P = 0.03 ) with a recurrence rate of 38 % and 13 % in patients with and without inducibility , respectively . Conclusions —AF ablation results in a decline in AF frequency , with a magnitude correlating with termination of AF and prevention of inducibility that is predictive of subsequent clinical outcome", "Background —Atrial flutter ( AFL ) and atrial fibrillation ( AF ) frequently coexist in the same patient . Recently it has been demonstrated that the triggers for both AF and AFL may originate in the pulmonary veins ( PVs ) . We hypothesized that in patients with both AF and typical AFL , pulmonary vein – left atrial junction ( PV-LAJ ) disconnection may eliminate both arrhythmias . Methods and Results —Consecutive patients with documented symptomatic AF and typical AFL were r and omly assigned to have PV-LAJ disconnection combined with cavotricuspid isthmus ( CTI ) ablation ( group 1 , n=49 ) or PV-LAJ disconnection alone ( group 2 , n=59 ) . Within the first 8 weeks after ablation , 32 of the group 2 patients had typical AFL documented , whereas none was seen in group 1 . Twenty of these 32 converted to sinus rhythm after initiating antiarrhythmic drugs ( AADs ) . Twelve were cardioverted , and AADs were started . After 8 weeks , all AADS were stopped , and only 3 patients continued to have recurrent sustained typical AFL that was eliminated by CTI ablation . Beyond 8 weeks of follow-up , 7 patients in group 1 and 6 patients in group 2 ( 14 % and 11 % , respectively ) continued to have AF . Ten of these 13 patients underwent a repeat PV-LAJ disconnection procedure and were cured . The remaining 3 remained in normal sinus rhythm while taking AADs . Conclusions —In patients with both AFL and AF , PV-LAJ disconnection alone may be sufficient to control both arrhythmias . CTI block reduced early postablation recurrence of arrhythmias , which in the majority of patients reflects a short-term clinical problem", "BACKGROUND For patients who have a ventricular tachyarrhythmic event , implantable cardioverter-defibrillators ( ICDs ) are a mainstay of therapy to prevent sudden death . However , ICD shocks are painful , can result in clinical depression , and do not offer complete protection against death from arrhythmia . We design ed this r and omized trial to examine whether prophylactic radiofrequency catheter ablation of arrhythmogenic ventricular tissue would reduce the incidence of ICD therapy . METHODS Eligible patients with a history of a myocardial infa rct ion underwent defibrillator implantation for spontaneous ventricular tachycardia or fibrillation . The patients did not receive antiarrhythmic drugs . Patients were r and omly assigned to defibrillator implantation alone or defibrillator implantation with adjunctive catheter ablation ( 64 patients in each group ) . Ablation was performed with the use of a substrate-based approach in which the myocardial scar is mapped and ablated while the heart remains predominantly in sinus rhythm . The primary end point was survival free from any appropriate ICD therapy . RESULTS The mortality rate 30 days after ablation was zero , and there were no significant changes in ventricular function or functional class during the mean ( + /-SD ) follow-up period of 22.5+/-5.5 months . Twenty-one patients assigned to defibrillator implantation alone ( 33 % ) and eight patients assigned to defibrillator implantation plus ablation ( 12 % ) received appropriate ICD therapy ( antitachycardia pacing or shocks ) ( hazard ratio in the ablation group , 0.35 ; 95 % confidence interval , 0.15 to 0.78 , P=0.007 ) . Among these patients , 20 in the control group ( 31 % ) and 6 in the ablation group ( 9 % ) received shocks ( P=0.003 ) . Mortality was not increased in the group assigned to ablation as compared with the control group ( 9 % vs. 17 % , P=0.29 ) . CONCLUSIONS In this r and omized trial , prophylactic substrate-based catheter ablation reduced the incidence of ICD therapy in patients with a history of myocardial infa rct ion who received ICDs for the secondary prevention of sudden death . ( Current Controlled Trials number , IS RCT N62488166 [ controlled-trials.com ] . )", "BACKGROUND There are no reports describing the technique , electrophysiological evaluation , and clinical consequences of complete linear block at roofline joining the superior pulmonary veins ( PVs ) in patients with paroxysmal atrial fibrillation ( AF ) . METHODS AND RESULTS Ninety patients with drug-refractory paroxysmal AF undergoing radiofrequency ablation were prospect ively r and omized into 2 ablation strategies : ( 1 ) PV isolation ( n=45 ) or ( 2 ) PV isolation in combination with linear ablation joining the 2 superior PVs ( roofline ; n=45 ) . In both groups , the cavotricuspid isthmus , fragmented peri-PV-ostial electrograms , and spontaneous non-PV foci were ablated . Roofline ablation was performed at the most cranial part of the left atrium ( LA ) with complete conduction block demonstrated during LA appendage pacing by the online mapping of continuous double potential and an activation detour propagating around the PVs to activate caudocranially the posterior wall of the LA . The effect of ablation at the LA roof was evaluated by the change in fibrillatory cycle length , termination and noninducibility of AF , and clinical outcome . PV isolation was achieved in all patients with no significant differences in the radiofrequency duration , fluoroscopy , or procedural time between the groups . Roofline ablation required 12+/-6 ( median 11 , range 3 to 25 ) minutes of radiofrequency energy delivery with a fluoroscopic duration of 7+/-2 minutes and was performed in 19+/-7 minutes . Complete block was confirmed in 43 patients ( 96 % ) and result ed in an activation delay that was shorter circumventing the left than the right PVs during LA appendage pacing ( 138+/-15 versus 146+/-25 ms , respectively ; P=0.01 ) . Roofline ablation result ed in a significant increase in the fibrillatory cycle length ( 198+/-38 to 217+/-44 ms ; P=0.0005 ) , termination of arrhythmia in 47 % ( 8/17 ) , and subsequent noninducibility of AF in 59 % ( 10/17 ) of the patients inducible after PV isolation . However , LA flutter , predominantly perimitral , could be induced in 10 patients ( 22 % ) after roofline ablation . At 15+/-4 months , 87 % of the roofline group and 69 % with PV isolation alone are arrhythmia free without antiarrhythmics ( P=0.04 ) . CONCLUSIONS This prospect i ve r and omized study demonstrates the feasibility of achieving complete linear block at the LA roof . Such ablation result ed in the prolongation of the fibrillatory cycle , termination of AF , and subsequent noninducibility and is associated with an improved clinical outcome compared with PV isolation alone", "Background — Pulmonary vein ( PV ) isolation is a promising new treatment for atrial fibrillation ( AF ) . We hypothesized that isolation of large areas around both ipsilateral PVs with verification of conduction block is more effective than the isolation of each individual PV . Methods and Results — A total of 110 patients , 67 with paroxysmal AF and 43 with persistent AF , were r and omly assigned to undergo either isolation of each individual PV or isolation of large areas around both ipsilateral PVs . The isolation of each individual PV was an electrophysiologically guided , ostial segmental ablation with a 64-pole basket catheter or a 20-pole circular mapping catheter ( group I ) . Isolation of large areas was performed around the 2 ipsilateral veins with a nonfluoroscopic navigation system and a circular 20-pole mapping catheter for verification of conduction block ( group II ) . In both groups , an irrigated-tip ablation catheter ( 25 to 35 W ) was used to achieve complete isolation . Procedure and ablation times were longer in group II , whereas fluoroscopic time was significantly shorter ( P≤0.001 ) . After a follow-up period of 15±4 months , 27 patients in group I ( 49 % ) and 37 patients in group II ( 67 % ) remained free of symptoms of AF and had no AF or atrial flutter during repetitive Holter monitoring without antiarrhythmic drug treatment after a single procedure ( P≤0.05 ) . Conclusions — The rate of success was significantly higher and fluoroscopy times were significantly lower in the group with large isolation areas around both ipsilateral PVs than in those who underwent individual PV isolation", "CONTEXT Treatment with antiarrhythmic drugs and anticoagulation is considered first-line therapy in patients with symptomatic atrial fibrillation ( AF ) . Pulmonary vein isolation ( PVI ) with radiofrequency ablation may cure AF , obviating the need for antiarrhythmic drugs and anticoagulation . OBJECTIVE To determine whether PVI is feasible as first-line therapy for treating patients with symptomatic AF . DESIGN , SETTING , AND PARTICIPANTS A multicenter prospect i ve r and omized study conducted from December 31 , 2001 , to July 1 , 2002 , of 70 patients aged 18 to 75 years who experienced monthly symptomatic AF episodes for at least 3 months and had not been treated with antiarrhythmic drugs . INTERVENTION Patients were r and omized to receive either PVI using radiofrequency ablation ( n=33 ) or antiarrhythmic drug treatment ( n=37 ) , with a 1-year follow-up . MAIN OUTCOME MEASURES Recurrence of AF , hospitalization , and quality of life assessment . RESULTS Two patients in the antiarrhythmic drug treatment group and 1 patient in the PVI group were lost to follow-up . At the end of 1-year follow-up , 22 ( 63 % ) of 35 patients who received antiarrhythmic drugs had at least 1 recurrence of symptomatic AF compared with 4 ( 13 % ) of 32 patients who received PVI ( P Hospitalization during 1-year follow-up occurred in 19 ( 54 % ) of 35 patients in the antiarrhythmic drug group compared with 3 ( 9 % ) of 32 in the PVI group ( P antiarrhythmic drug group , the mean ( SD ) number of AF episodes decreased from 12 ( 7 ) to 6 ( 4 ) , after initiating therapy ( P = .01 ) . At 6-month follow-up , the improvement in quality of life of patients in the PVI group was significantly better than the improvement in the antiarrhythmic drug group in 5 subclasses of the Short-Form 36 health survey . There were no thromboembolic events in either group . Asymptomatic mild or moderate pulmonary vein stenosis was documented in 2 ( 6 % ) of 32 patients in the PVI group . CONCLUSION Pulmonary vein isolation appears to be a feasible first-line approach for treating patients with symptomatic AF . Larger studies are needed to confirm its safety and efficacy", "Background —The pulmonary veins ( PVs ) have been demonstrated to often play an important role in generating atrial fibrillation ( AF ) . The purpose of this study was to determine the safety and efficacy of segmental PV isolation in patients with paroxysmal or persistent AF . Methods and Results —In 70 consecutive patients ( mean age , 53±11 years ) with paroxysmal ( 58 ) or persistent ( 12 ) AF , segmental PV isolation guided by ostial PV potentials was performed . The left superior , left inferior , and right superior PVs were targeted for isolation in all patients , and the right inferior PV was isolated in 20 patients . Among the 230 targeted PVs , 217 ( 94 % ) were completely isolated , with a mean of 6.5±4.2 minutes of radiofrequency energy applied at a maximum power setting of 35 W. A second PV isolation procedure was performed in 6 patients ( 9 % ) . At 5 months of follow-up , 70 % of patients with paroxysmal and 22 % of patients with persistent AF were free from recurrent AF ( P free of symptomatic AF or had significant improvement . Among various clinical characteristics , only paroxysmal AF was an independent predictor of freedom from recurrence of AF ( P developed unilateral quadrantopsia after the procedure . There were no other complications . Conclusions —With a segmental isolation approach that targets at least 3 PVs , a clinical ly satisfactory result can be achieved in > 80 % of patients with paroxysmal AF . The clinical efficacy of pulmonary vein isolation is much lower when AF is persistent than when it is paroxysmal", "BACKGROUND Complex fractionated electrograms ( CFEs ) are continuous electrograms ( EGMs ) of very short cycle length ( CL ) representing substrate for atrial fibrillation ( AF ) perpetuation . Ablation of CFEs may result in AF slowing , termination , and prevention , but identifying them can be subjective . OBJECTIVE The purpose of this study was to prospect ively assess ( 1 ) whether an automated algorithm can identify CFE regions , ( 2 ) the acute effects of ablating these regions on AF , and ( 3 ) the long-term efficacy as an adjuvant strategy to pulmonary vein antrum isolation ( PVAI ) . METHODS Thirty-five patients ( three centers , 61 + /- 9 years , left atrium [ LA ] 43 + /- 9 mm , ejection fraction 53 % + /- 7 % ) with symptomatic paroxysmal ( n = 21 ) or persistent ( n = 14 ) AF were studied . A decapolar lasso ( 2-mm spacing ) was used for mapping . A three-dimensional shell of the LA and pulmonary veins ( PVs ) was created . If not already in AF , AF was induced by burst pacing ( with or without isoproterenol ) . Atrial EGMs during AF were mapped/analyzed using an automated CFE algorithm . The algorithm measures the time between discrete deflections in a local EGM over 5 seconds ( based on selectable width and peak-to-peak [ > 0.03 mV ] criteria ) . The mean CL of the local EGM is projected onto the LA shell as a color-coded display . Regions of CL Atrial fibrillation cycle length ( AFCL ) and regularity were measured from the CS . After CFE ablation , further ablation was done to achieve complete PVAI . RESULTS AF was spontaneous ( n = 20 ) or induced ( n = 15 ) in all patients . CFEs were most commonly found along the septum ( 97 % ) , anterior LA ( 97 % ) , PV antra ( 83 % ) , base of appendage ( 83 % ) , and annulus ( 71 % ) . CFE ablation alone prolonged the AFCL ( 171 + /- 27 vs. 304 + /- 41 ms ; P = .03 ) and regularized AF to left/right flutter ( AFL ) in 74 % of patients . CFE ablation terminated AF/AFL in 19 patients (54%)-the other 16 were cardioverted- and AF became noninducible in 77 % . CFE ablation alone did not cause PV isolation ( 0.1 + /- 0.3 PV isolated/patient ) . After combined CFE and PVAI ablation , the single-procedure , off-drug success rate was 83 % ( follow-up 13 + /- 4 months ) versus 71 % in matched controls who had PVAI alone ( P = .045 ) . CONCLUSIONS CFE ablation guided by an automated algorithm result ed in AFCL prolongation , regularization , and noninducibility in most patients . AF terminated in 54 % of cases . PVAI with adjuvant CFE ablation has a high efficacy and may be superior to PVAI alone", "Background —Circumferential pulmonary vein ablation ( CPVA ) is effective in curing atrial fibrillation ( AF ) , but new-onset left atrial tachycardia ( AT ) is a potential complication . We evaluated whether a modified CPVA approach including additional ablation lines on posterior wall and the mitral isthmus would reduce the incidence of AT after PV ablation . Methods and Results —A total of 560 patients ( 291 men , 52 % ; age , 56.5±7.3 years ) entered the study ; 280 were r and omized to CPVA alone ( group 1 ) and 280 to modified CPVA ( group 2 ) . The primary end point was freedom from AT after the procedure . In group 1 , 28 patients ( 10 % ) experienced new-onset AT , and 41 ( 14.3 % ) experienced recurrent AF . In group 2 , 11 patients ( 3.9 % ) experienced AT , and 36 ( 12.9 % ) had recurrent AF . Group 1 was more likely to experience AT than group 2 ( P=0.005 ) . Freedom from AF after ablation was similar in both groups ( P=0.57 ) . Among those in group 1 , gap-related macroreentrant AT was documented in 23 of the 28 patients ( 82 % ) , and focal AT was found in 5 ( 18 % ) . In group 2 , gap-related macroreentrant AT was found in 8 of the 11 patients ( 73 % ) , and focal AT was seen in 3 ( 27 % ) . Two patients in group 1 and 1 patient in group 2 had both AT and AF . The strongest predictor of AT was the presence of gaps ( P —Modified CPVA is as effective as CPVA in preventing AF but is associated with a lower risk of developing incessant AT ", "Background — Atrial fibrillation/flutter ( AF ) and heart failure often coexist ; however , the effect of cardiac resynchronization therapy ( CRT ) on the incidence of AF and on the outcome of patients with new-onset AF remains undefined . Methods and Results — In the CArdiac REsynchronisation in Heart Failure ( CARE-HF ) trial , 813 patients with moderate or severe heart failure were r and omly assigned to pharmacological therapy alone or with the addition of CRT . The incidence of AF was assessed by adverse event reporting and by ECGs during follow-up , and the impact of new-onset AF on the outcome and efficacy of CRT was evaluated . By the end of the study ( mean duration of follow-up 29.4 months ) , AF had been documented in 66 patients in the CRT group compared with 58 who received medical therapy only ( 16.1 % versus 14.4 % ; hazard ratio 1.05 ; 95 % confidence interval , 0.73 to 1.50 ; P=0.79 ) . There was no difference in the time until first onset of AF between groups . Mortality was higher in patients who developed AF , but AF was not a predictor in the multivariable model ( hazard ratio 1.17 ; 95 % confidence interval , 0.82 to 1.67 ; P=0.37 ) . In patients with new-onset AF , CRT significantly reduced the risk for all-cause mortality and all other predefined end points and improved ejection fraction and symptoms ( no interaction between AF and CRT ; all P>0.2 ) . Conclusions — Although CRT did not reduce the incidence of AF , CRT improved the outcome regardless of whether AF developed", "Background Various strategies have been used for atrial fibrillation ( AF ) ablation . It is unclear whether adding linear lesions to pulmonary vein ( PV ) isolation has significant advantages . Objectives We assessed the clinical benefit of adding linear lesions in patients undergoing PV isolation for AF . Methods One hundred patients ( 63 male and 37 female ; mean age of 59 ± 11 years ) with documented paroxysmal AF were included in the study . Patients were r and omized into two groups . The first group underwent PV isolation alone . The second group underwent PV isolation and had two linear lesions created ; one line between the superior PVs , and a second line from the left inferior PV to the mitral valve annulus . Patients ’ clinical progress after the ablation was evaluated and compared at 1 , 3 , and 9 months after their respective ablation procedures . Results The linear lesions group maintained sinus rhythm and had fewer symptoms than the lone PV isolation group ( 86 vs. 58 % , respectively ) ( p to regain sinus rhythm ( 90 vs. 82 % , respectively ) ( p = NS ) , there was no statistical difference between the groups regarding the use of antiarrhythmics , the need for electrical cardioversion , and subjective improvement . Conclusion The addition of linear lesions to PV isolation more effectively achieved sinus rhythm initially and fewer patients required additional management to maintain their rhythm when compared to patients who underwent lone PV isolation . However , at 9 months , the overall results were similar in both groups", "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", "The purpose of this study was to evaluate the effects of atrioventricular junction radiofrequency ablation on the quality of life , exercise performance , and echocardiographic parameters in 23 patients with chronic , severely symptomatic , drug-refractory atrial fibrillation or flutter . Initially , patients were r and omized to receive ablation plus pacemaker therapy ( n = 12 ) or pacemaker therapy alone ( n = 11 ) . After 15 days , palpitations decreased by 92 % and 37 % ( p = 0.004 ) , rest dyspnea by 79 % and 40 % ( p = NS ) , effort dyspnea by 65 % and 30 % ( p = 0.03 ) , exercise intolerance by 54 % and 17 % ( p = 0.005 ) , and asthenia by 67 % and 31 % ( p = 0.02 ) in the 2 groups , respectively . At the end of this short-term study , control patients also underwent ablation therapy , and a 3-month intrapatient follow-up study was performed in 22 patients . New York Heart Association functional class > or = 3 was present in 14 patients ( 64 % ) before , but in only 3 patients ( 14 % ) after ablation therapy ( p = 0.002 ) ; specific activity scale functional class > or = 3 was present in 9 patients ( 41 % ) before , but in only 5 ( 23 % ) after ablation therapy ( p = NS ) . Exercise duration during st and ardized stress testing increased by a mean of 63 + /- 93 seconds ( 15 % increase ) ( p = 0.001 ) . In the 9 patients with depressed left ventricular systolic function , echocardiographic fractional shortening increased by 34 % ( from 23 + /- 5 % to 31 + /- 9 % ) ( p = 0.003 ) . In the remaining 13 patients with normal systolic function , fractional shortening decreased by 10 % ( from 40 + /- 5 % to 36 + /- 6 % ) ( p = 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "Background —Segmental ostial catheter ablation ( SOCA ) to isolate the pulmonary veins ( PVs ) and left atrial catheter ablation ( LACA ) to encircle the PVs both may eliminate paroxysmal atrial fibrillation ( PAF ) . The relative efficacy of these 2 techniques has not been directly compared . Methods and Results —Of 80 consecutive patients with symptomatic PAF ( age , 52±10 years ) , 40 patients underwent PV isolation by SOCA and 40 patients underwent LACA to encircle the PVs . During SOCA , ostial PV potentials recorded with a ring catheter were targeted . LACA was performed by encircling the left- and right-sided PVs 1 to 2 cm from the ostia and was guided by an electroanatomic mapping system ; ablation lines also were created in the mitral isthmus and posterior left atrium . The mean procedure and fluoroscopy times were 156±45 and 50±17 minutes for SOCA and 149±33 and 39±12 minutes for LACA , respectively . At 6 months , 67 % of patients who underwent SOCA and 88 % of patients who underwent LACA were free of symptomatic PAF when not taking antiarrhythmic drug therapy ( P = 0.02 ) . Among the variables of age , sex , duration and frequency of PAF , ejection fraction , left atrial size , structural heart disease , and the ablation technique , only an increased left atrial size and the SOCA technique were independent predictors of recurrent PAF . The only complication was left atrial flutter in a patient who underwent LACA . Conclusions —In patients undergoing catheter ablation for PAF , LACA to encircle the PVs is more effective than SOCA", "BACKGROUND Stepwise segmental pulmonary vein isolation ( SPVI ) and circumferential pulmonary vein isolation ( CPVI ) have been developed to treat patients with atrial fibrillation ( AF ) , but the preferable approach for paroxysmal AF ( PAF ) has not been established . METHODS AND RESULTS One hundred and ten patients with symptomatic PAF were r and omized into a stepwise SPVI group ( n=55 ) or CPVI group ( n=55 ) . Systemic SPVI combined with left atrial linear ablation tailored by inducibility of AF was performed in the stepwise SPVI group . Circumferential linear ablation around the left and right-sided pulmonary veins ( PVs ) guided by 3-dimensional electroanatomic mapping was performed in the CPVI group . The endpoints of ablation are non-induciblity of AF in the stepwise SPVI group and continuity of circular lesions combined with PV isolation in the CPVI group . After the initial procedures , atrial tachyarrhythmis ( ATa ) recurred within the first 3 months in 23 of the 55 patients ( 41.8 % ) who underwent stepwise SPVI and in 20 of the 55 patients ( 36.4 % ) who had CPVI ( p=0.69 ) . Repeat procedures were performed in 7 patients from the stepwise SPVI group and 5 from the CPVI group ( p=0.76 ) . During the 3 - 9 months after the last procedure , 46 patients ( 83.6 % ) from the CPVI group and 43 ( 78.2 % ) from the stepwise SPVI group did not have symptomatic ATa while not taking anti-arrhythmic drugs ( p=0.63 ) . Severe subcutaneous hematoma or PV stenosis occurred in 3 patients . CONCLUSIONS The efficacy of stepwise SPVI is comparable to that of CPVI for patients with PAF", "BACKGROUND Amiodarone is effective in maintaining sinus rhythm in atrial fibrillation but is associated with potentially serious toxic effects . Dronedarone is a new antiarrhythmic agent pharmacologically related to amiodarone but developed to reduce the risk of side effects . METHODS In two identical multicenter , double-blind , r and omized trials , one conducted in Europe ( Clinical Trials.gov number , NCT00259428 [ Clinical Trials.gov ] ) and one conducted in the United States , Canada , Australia , South Africa , and Argentina ( termed the non-European trial , NCT00259376 [ Clinical Trials.gov ] ) , we evaluated the efficacy of dronedarone , with 828 patients receiving 400 mg of the drug twice daily and 409 patients receiving placebo . Rhythm was monitored transtelephonically on days 2 , 3 , and 5 ; at 3 , 5 , 7 , and 10 months ; during recurrence of arrhythmia ; and at nine scheduled visits during a 12-month period . The primary end point was the time to the first recurrence of atrial fibrillation or flutter . RESULTS In the European trial , the median times to the recurrence of arrhythmia were 41 days in the placebo group and 96 days in the dronedarone group ( P=0.01 ) . The corresponding duration s in the non-European trial were 59 and 158 days ( P=0.002 ) . At the recurrence of arrhythmia in the European trial , the mean ( + /-SD ) ventricular rate was 117.5+/-29.1 beats per minute in the placebo group and 102.3+/-24.7 beats per minute in the dronedarone group ( P Rates of pulmonary toxic effects and of thyroid and liver dysfunction were not significantly increased in the dronedarone group . CONCLUSIONS Dronedarone was significantly more effective than placebo in maintaining sinus rhythm and in reducing the ventricular rate during recurrence of arrhythmia", "BACKGROUND Current atrial fibrillation ( AF ) ablation involves isolation of all pulmonary veins ( PVs ) with or without additional linear lesions . However , whether such extensive ablation is necessary is unclear . OBJECTIVE The purpose of this study was to assess the efficacy of different ablation strategies on long-term AF control . METHODS We prospect ively r and omized patients to undergo isolation of all versus arrhythmogenic PVs ( identified by st and ardized stimulation protocol ) . PV isolation was guided by circular mapping catheter . The endpoint was entry/exit block persisting for > or = 20 minutes . Patients were evaluated at three clinic visits ( at 6 weeks , 6 months , and 1 year ) and multiple transtelephonic monitoring periods . Antiarrhythmic drugs were discontinued at 6 weeks . Primary study endpoint was long-term AF control ( freedom or > 90 % reduction in AF burden off or on previously ineffective antiarrhythmic drugs at 1 year after a single ablation procedure ) . RESULTS Over a 20-month period , 105 patients ( 76 men and 29 women , age 57 + /- 9 years ; paroxysmal AF = 77 ) were r and omized , and 103 patients completed 1-year follow-up ( 51 patients in all-PV arm , 52 patients in arrhythmogenic PV arm ) . The primary endpoint was achieved in 75 ( 73 % ) patients and was similar in patients r and omized to all-PV arm versus arrhythmogenic PV arm [ 38 ( 75 % ) patients vs 37 ( 71 % ) patients , respectively ; odds ratio 1.18 , 95 % confidence interval 0.50 , 2.83 , P = .70 ] . Secondary study endpoints , including freedom from AF off antiarrhythmic drugs , total procedure/fluoroscopy times , and occurrence of serious adverse events , were not different between the two groups . CONCLUSION In a r and omized comparison , isolation of arrhythmogenic veins was as efficacious as empiric isolation of all veins in achieving long-term AF control", "INTRODUCTION Right atrial linear lesions ( RALL ) , either alone or in combination with antiarrhythmic drug therapy , may modify the substrate for maintenance of atrial fibrillation ( AF ) . The aim of this prospect i ve r and omized study was to determine whether RALL provides additional benefit to right atrial appendage pacing ( RAAP ) and /or interatrial septum pacing ( IASP ) and drug therapy in patients with symptomatic paroxysmal AF and sinus bradycardia requiring permanent atrial pacing . METHODS AND RESULTS Sixty-four patients ( 33 men and 31 women , mean age 73 + /- 10 years ) completed the 6-month follow-up . Patients were r and omized to either RALL ( n = 33 ) or non-right atrial linear lesions ( NRALL ) , and then to either IASP ( n = 32 ) or RAAP ( n = 32 ) . Fifteen RALL patients were paced at the IAS and 18 at the RAA . Seventeen NRALL patients were paced at the IAS and 14 at the RAA . No statistical difference was observed with regard to the mean atrial tachyarrhythmia ( AT ) burden between NRALL ( 84 + /- 169 min/day ) and RALL patients ( 202 + /- 219 min/day ) . Mean AT burden was significantly lower in the IASP group ( 70 + /- 150 min/day ) than in RAAP group ( 219 + /- 317 min/day ; P mean AT burden was 99 + /- 180 min/day in the IASP patients and 288 + /- 372 min/day in the RAAP patients ( P mean AT burden was observed between IASP patients ( 46 + /- 117 min/day ) and RAAP patients ( 130 + /- 211 min/day ) . CONCLUSION The results of the present study indicate that RALL did not provide any additional therapeutic benefit to combined antiarrhythmic drug therapy and septal or nonseptal atrial pacing in patients with sinus bradycardia and paroxysmal AF", "AIMS Beneficial effects of atrial fibrillation ( AF ) ablation have been demonstrated in patients with congestive heart failure ( CHF ) and significantly impaired left ventricular ejection fraction ( LVEF ) . However , the impact of pulmonary vein isolation ( PVI ) on cardiac function in patients with paroxysmal AF and impaired LVEF remains under discussion . This study aim ed to evaluate the impact of PVI for paroxysmal AF on cardiac function in patients with impaired LVEF using cardiac magnetic resonance imaging ( CMRI ) . METHODS AND RESULTS A total number of 70 patients with paroxysmal AF and episodes scanned on a 1.5-T-CMRI before and 6 months after PVI during sinus rhythm . End-diastolic volume , end-systolic volume , and LVEF were determined by epicardial and endocardial measurements . Patients were categorized into two groups regarding cardiac function as assessed by CMRI : group 1 patients ( n = 18 ) with an LVEF 50 % ( group 2 , n = 52 ) . Group 1 patients demonstrated a significant lower success rate than patients of group 2 after a follow-up of 152 + /- 40 days ( 50 vs. 73 % , P cardiac function after AF ablation ( 41 + /- 6 vs. 51 + /- 12 % , P = 0.004 ) , whereas group 2 patients did not show significant differences ( 60 + /- 6 vs. 59 + /- 9 % , P = 0.22 ) after a 6 months follow-up . CONCLUSION Pulmonary vein isolation improves cardiac function in patients with paroxysmal AF and impaired LVEF . These data suggest that an impaired LV function can be partially attributed to AF with short-lasting paroxysms", "Background —There has been growing concern that linear ablation is associated with an increased risk of iatrogenic arrhythmias in patients undergoing ablation for atrial fibrillation ( AF ) . Therefore , we compared circumferential pulmonary vein ablation plus left atrial linear ablation ( CPVA+LALA ) with segmental pulmonary vein isolation (PVI)in patients with paroxysmal AF . Methods and Results —Sixty-six consecutive patients with paroxysmal AF were prospect ively r and omly assigned to receive PVI versus CPVA+LALA ( consisting of encircling lesions around the pulmonary veins ) , a roof line , and a mitral isthmus line with documentation of bidirectional mitral isthmus block . All patients were seen at 1 , 3 , 6 , and every 12 months after ablation , with 14-day continuous ECG monitoring every 6 months . At 16.4±6.3 months after 1 ablation procedure , 19 patients ( 58 % ) remained free of atrial arrhythmias after PVI versus 17 patients ( 51 % ) after CPVA+LALA ( P=0.62 ) . After PVI , 14 patients had recurrent paroxysmal AF , whereas after CPVA+LALA , 8 patients had recurrent AF , 6 had atypical left atrial flutter ( LAFL ) , and 2 had both AF and LAFL ( P=0.32 between PVI versus CPVA+LALA for AF but P=0.002 for LAFL ) . Twenty-eight patients ( 85 % ) remained arrhythmia-free after 1.3±0.5 PVI procedures versus 28 patients ( 85 % ) after 1.4±0.6 CPVA+LALA procedures ( P = NS ) . Fluoroscopy time was longer after CPVA+LALA versus PVI ( 91 versus 73 minutes , P=0.04 ) . Conclusions —As an initial ablation approach in patients with paroxysmal AF , more LAFL occurred after CPVA+LALA and fluoroscopy times were longer compared with segmental PVI", "Background —Radiofrequency catheter ablation ( RFA ) has emerged as an important treatment strategy for atrial fibrillation ( AF ) . The potential cost-effectiveness of RFA for AF , relative to antiarrhythmic drug ( AAD ) therapy , has not been fully explored from a US perspective . Methods and Results —We constructed a Markov disease simulation model for a hypothetical cohort of patients with drug-refractory paroxysmal AF , treated either with RFA with/without AAD or AAD alone . Costs and quality -adjusted life-years were projected over 5 years . Model inputs were drawn from published clinical trial and registry data , from new registry and trial data analysis , and from data prospect ively collected from patients with AF treated with RFA at our institution . We assumed no benefit from ablation on stroke , heart failure or death , but did estimate changes in quality -adjusted life expectancy using data from several AF cohorts . In the base case scenario , cumulative costs with the RFA and AAD strategies were $ 26 584 and $ 19 898 , respectively . Over 5 years , quality -adjusted life expectancy was 3.51 quality -adjusted life-years with RFA versus 3.38 for the AAD group . The incremental cost-effectiveness ratio for RFA versus AAD was thus $ 51 431 per quality -adjusted life-year . Model results were most sensitive to time horizon , the relative utility weights of successful ablation versus unsuccessful drug therapy , and to the cost of an ablation procedure . Conclusions —RFA with/without AAD for symptomatic , drug-refractory paroxysmal AF appears to be reasonably cost-effective compared with AAD therapy alone from the perspective of the US health care system , based on improved quality of life and avoidance of future health care costs", "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", "Background —An anatomic approach of left atrial radiofrequency circumferential ablation ( LACA ) to encircle the pulmonary veins is often effective in eliminating paroxysmal atrial fibrillation ( AF ) . However , no electrophysiological end points other than voltage abatement and /or conduction slowing or block across ablation lines have been used . It has been unclear whether noninducibility of AF is a clinical ly useful end point . Methods and Results —In 100 patients with paroxysmal AF ( mean age , 55±10 years ) , LACA to encircle the left- and right-sided pulmonary veins was performed during AF , with additional ablation lines in the posterior left atrium and mitral isthmus , with an 8-mm-tip catheter . After completion of this lesion set , sinus rhythm was present , and AF lasting > 60 seconds was not inducible in 40 patients ( 40 % ; group 1 ) . The 60 patients in whom AF was still present or who still had inducible AF were r and omly assigned to no further ablation ( group 2 ; 30 patients ) or to additional ablation lines along the left atrial septum , roof , and /or anterior wall where there were fractionated electrograms ( group 3 ; 30 patients ) . In group 3 , AF was rendered noninducible in 27 of 30 patients ( 90 % ) . At a 6-month follow-up , 67 % of patients in group 2 were free of AF without drug therapy compared with 86 % of patients in group 3 . ( P=0.05 , log-rank test ) . Left atrial flutter occurred in 17 % and 27 % of patients in each group , respectively ( P=0.3 ) . Conclusions —After LACA in patients with paroxysmal AF , AF usually can be rendered noninducible by additional ablation at sites of fractionated electrograms . Noninducibility of AF attained by additional electrogram-guided left atrial ablation may be associated with a better midterm clinical outcome than when AF is still inducible after LACA alone", "Background — Data on the comparative value of the circumferential pulmonary vein and the segmental pulmonary vein ablation for interventional treatment of atrial fibrillation are limited . We hypothesized that the circumferential pulmonary vein ablation approach was superior to the segmental pulmonary vein ablation approach . Methods and Results —One hundred patients with highly symptomatic atrial fibrillation were r and omly assigned to undergo either circumferential ( n=50 ) or segmental pulmonary vein ablation ( n=50 ) . Freedom from atrial tachyarrhythmias in a 7-day Holter monitoring at 6 months was the primary end point . Secondary end points were freedom of arrhythmia-related symptoms and a composite of pericardial tamponade , thromboembolic complications , and pulmonary vein stenosis ( safety end point ) . On the basis of the results of the 7-day Holter monitoring at 6 months , 21 patients ( 42 % ) after circumferential pulmonary vein ablation and 33 patients ( 66 % ) after segmental pulmonary vein ablation ( P=0.02 ) were free of atrial tachyarrhythmia episodes . During the 6-month follow-up period , 27 patients ( 54 % ) after circumferential pulmonary vein ablation and 41 patients ( 82 % ) after segmental pulmonary vein ablation remained free of arrhythmia-related symptoms ( P safety end point ( 6 versus 7 events ; P=0.77 ) in the circumferential versus segmental pulmonary vein ablation group , respectively . Conclusions —This study demonstrates no superiority of the circumferential pulmonary vein ablation over segmental pulmonary vein ablation for treatment of atrial fibrillation in terms of efficacy and safety", "OBJECTIVE To determine whether clinical trials originating in certain countries always have positive results . DATA SOURCES Abstract s of trials from Medline ( January 1966-June 1995 ) . STUDY SELECTION Two separate studies were conducted . The first included trials in which the clinical outcome of a group of subjects receiving acupuncture was compared to that of a group receiving placebo , no treatment , or a nonacupuncture intervention . In the second study , r and omized or controlled trials of interventions other than acupuncture that were published in China , Japan , Russia/USSR , or Taiwan were compared to those published in Engl and . DATA EXTRACTION Blinded review ers determined inclusion and outcome and separately classified each trial by country of origin . DATA SYNTHESIS In the study of acupuncture trials , 252 of 1085 abstract s met the inclusion criteria . Research conducted in certain countries was uniformly favorable to acupuncture ; all trials originating in China , Japan , Hong Kong , and Taiwan were positive , as were 10 out of 11 of those published in Russia/USSR . In studies that examined interventions other than acupuncture , 405 of 1100 abstract s met the inclusion criteria . Of trials published in Engl and , 75 % gave the test treatment as superior to control . The results for China , Japan , Russia/USSR , and Taiwan were 99 % , 89 % , 97 % , and 95 % , respectively . No trial published in China or Russia/USSR found a test treatment to be ineffective . CONCLUSIONS Some countries publish unusually high proportions of positive results . Publication bias is a possible explanation . Research ers undertaking systematic review s should consider carefully how to manage data from these countries", "OBJECTIVES This study sought to determine whether ablation of complex fractionated atrial electrograms ( CFAEs ) after antral pulmonary vein isolation ( APVI ) further improves the clinical outcome of APVI in patients with long-lasting persistent atrial fibrillation ( AF ) . BACKGROUND Ablation of CFAEs has been reported to eliminate persistent AF . However , residual pulmonary vein arrhythmogenicity is a common mechanism of recurrence . METHODS In this r and omized study , 119 consecutive patients ( mean age 60 + /- 9 years ) with long-lasting persistent AF underwent APVI with an irrigated-tip radiofrequency ablation catheter . Antral pulmonary vein isolation result ed in termination of AF in 19 of 119 patients ( Group A , 16 % ) . The remaining 100 patients who still were in AF were r and omized to no further ablation and underwent cardioversion ( Group B , n = 50 ) or to ablation of CFAEs in the left atrium or coronary sinus for up to 2 additional hours of procedure duration ( Group C , n = 50 ) . RESULTS Atrial fibrillation terminated during ablation of CFAEs in 9 of 50 patients ( 18 % ) in Group C. At 10 + /- 3 months after a single ablation procedure , 18 of 50 ( 36 % ) in Group B and 17 of 50 ( 34 % ) in Group C were in sinus rhythm without antiarrhythmic drugs ( p = 0.84 ) . In Group A , 15 of 19 patients ( 79 % ) were in sinus rhythm . A repeat ablation procedure was performed in 34 of 100 r and omized patients ( for AF in 30 and atrial flutter in 4 ) . At 9 + /- 4 months after the final procedure , 34 of 50 ( 68 % ) in Group B and 30 of 50 ( 60 % ) in Group C were in sinus rhythm without antiarrhythmic drugs ( p = 0.40 ) . CONCLUSIONS Up to 2 h of additional ablation of CFAEs after APVI does not appear to improve clinical outcomes in patients with long-lasting persistent AF ", "BACKGROUND The deployment of an ablation line connecting the left inferior PV to the mitral annulus ( mitral isthmus line [ MIL ] ) enhances the efficacy of pulmonary vein disconnection ( PVD ) in preventing atrial fibrillation ( AF ) recurrences . OBJECTIVES To investigate the long-term effect of the additional linear lesion in a prospect i ve r and omized study . METHODS One hundred and eighty-seven patients ( 37 females , mean age : 55 + /- 11 years ) with paroxysmal ( 126 ) or persistent ( 61 patients ) AF , were prospect ively r and omized into two groups : PVD ( group A , 92 patients ) or PVD combined with MIL ( group B , 95 patients ) , performed by means of an irrigated-tip ablation catheter . RESULTS Successful disconnection of all PVs was achieved in all patients . A bidirectional block ( BB ) along the left atrial isthmus was obtained in 72 of 95 ( 76 % ) patients in group B , most of whom required additional RF pulses from within the distal CS . A transient ischemic attack occurred in 1 patient of group A , and a cardiac tamponade occurred in 1 patient of group B. At 1 year , 53 + /- 5 % ( group A ) and 71 + /- 5 % ( group B ) remained arrhythmia free ( P = 0.01 ) ; subgroup analysis highlights a higher improvement among patients with persistent AF ( 74 + /- 9 % vs 36 + /- 9 % ; P sinus rhythm maintenance rate , particularly in patients with persistent AF , without the risk for major complications", "Purpose We tested the hypothesis that electroanatomic pulmonary vein ( PV ) antra encircling for the PV isolation will improve the outcome in treatment of paroxysmal atrial fibrillation ( PAF ) , compared with segmental PV isolation . Methods Fifty-four patients underwent segmental PV isolation ( group 1 ) and 56 patients circumferential PV isolation ( group 2 ) for symptomatic PAF in a r and omized study . Results Following single ablation procedure , at the 48 ± 8 month follow-up , 30 ( 56 % ) and 32 ( 57 % ) patients in groups 1 and 2 remained free of arrhythmia ( P = 0.41 ) . After repeat ablation , 43 ( 80 % ) and 45 ( 80 % ) patients in groups 1 and 2 were free of arrhythmia without antiarrhythmic drugs ( AADs ) ; 48 ( 89 % ) and 51 ( 91 % ) patients in groups 1 and 2 did not have arrhythmia recurrences without or with AADs . Conclusion This study demonstrates no advantage in long-term arrhythmia-free clinical outcome after circumferential PV isolation in patients with frequent PAF", "AIMS We conducted a multi-centre , prospect i ve , controlled , r and omized trial to investigate the adjunctive role of ablation therapy to antiarrhythmic drug therapy in preventing atrial fibrillation ( AF ) relapses in patients with paroxysmal or persistent AF in whom antiarrhythmic drug therapy had already failed . METHODS AND RESULTS One hundred and thirty seven patients were r and omized to ablation and antiarrhythmic drug therapy ( ablation group ) or antiarrhythmic drug therapy alone ( control group ) . In the ablation group , patients underwent cavo-tricuspid and left inferior pulmonary vein (PV)-mitral isthmus ablation plus circumferential PV ablation . The primary end-point of the study was the absence of any recurrence of atrial arrhythmia lasting > 30 s in the 1-year follow-up period , after 1-month blanking period . Three ( 4.4 % ) major complications were related to ablation : one patient had a stroke during left atrium ablation , another suffered transient phrenic paralysis , and the third had a pericardial effusion which required pericardiocentesis . After 12 months of follow-up , 63/69 ( 91.3 % ) control group patients had at least one AF recurrence , whereas 30/68 ( 44.1 % ) ( P atrial arrhythmia recurrence ( four patients had atrial flutter , 26 patients AF ) . CONCLUSION Ablation therapy combined with antiarrhythmic drug therapy is superior to antiarrhythmic drug therapy alone in preventing atrial arrhythmia recurrences in patients with paroxysmal or persistent AF in whom antiarrhythmic drug therapy has already failed", "BACKGROUND Left atrial tachycardia ( AT ) is a complication of left atrial catheter ablation ( LACA ) of atrial fibrillation ( AF ) . However , its prevalence and characteristics have not been sufficiently clarified . METHODS We divided 121 patients who underwent LACA into 2 groups based on the results of AT occurrence after LACA ( follow-up period ; 12 + /- 7 months ) : an AT+ group and AT- group . RESULTS New-onset left AT occurred in 30 patients ( 25 % ) 31 + /- 51 days after LACA . Among the 26 patients with an early onset of AT , 4 underwent a second ablation for AT , and 21 became free of AT within 6 months without a repeat ablation procedure . Among the 4 patients with a late onset of AT ( > 2 months after the LACA ) , the tachycardia remitted without a repeat ablation procedure in a single patient within 6 months . Among 71 patients who underwent LACA with additional ablation lines , 22 ( 31 % ) developed new-onset left AT . Among 50 patients who underwent LACA alone , 8 ( 16 % ) developed new-onset left AT ( P = 0.02 ) . CONCLUSIONS New-onset left AT is a frequent complication of LACA for AF , especially in men and in patients with a low left ventricular ejection fraction . Early ( < 2 months ) onset AT does not require a repeat ablation because it often represents a transient phenomenon and disappears spontaneously", "BACKGROUND Radiofrequency ( RF ) ablation procedures for atrial fibrillation ( AF ) are associated with potential risks of thromboembolism , which may be minimized by the use of cryoablation that preserves the integrity of endocardium . The objective of this study was to compare the thrombogenic potential of transvenous cryoablation versus RF ablation during pulmonary vein ( PV ) isolation . METHODS AND RESULTS Thirty consecutive patients with paroxysmal AF were r and omized to undergo segmental PV isolation procedure using 4-mm tip RF ablation ( n = 15 ) or cryoablation ( CryoCor , San Diego , CA , USA ) ( n = 15 ) . Blood sample s were drawn after sheath insertion ( baseline ) , after transseptal puncture , before ablation ( after heparin administration ) , and after isolation of a superior PV . Activation of coagulation was measured with plasma levels of prothrombin fragment 1 + 2 ( F1 + 2 ) and thrombin-antithrombin III complex ( TAT ) , and platelets by plasma level of beta-thromboglobulin ( beta-TG ) and flow cytometric enumerating of P-selectin (CD62)-positive platelets . In both groups , the plasma level of beta-TG , F1 + 2 , and TAT were elevated after sheath insertion . The percentage changes in plasma level of beta-TG , F1 + 2 , and TAT and CD41/62-positive platelets from baseline after transseptal puncture and before ablation were similar ( P > 0.05 ) . However , the percentage changes in CD62-positive platelets from baseline were significantly higher in patients treated with RF ablation ( 82 + /- 20 % ) than with cryoablation ( 22 + /- 14 % , P = 0.02 ) , although their plasma levels of beta-TG , F1 + 2 , and TAT were not different ( P > 0.05 ) . CONCLUSIONS Significant platelet and coagulation activations were observed during PV ablation procedures , and heparin administration only prevented activation of coagulation but not platelets . Persistent platelets activation was observed during RF energy application , but not during cryoablation", "BACKGROUND Circumferential and segmental pulmonary vein ablations are two established treatment strategies for ablation of atrial fibrillation . Both techniques require the application of radiofrequency current at anatomical sites that are close to autonomic ganglia . However , the effects of current pulmonary vein ablation techniques on cardiac autonomic function are unknown . OBJECTIVE The purpose of this study was to analyze the short- and long-term effects of circumferential and segmental pulmonary vein ablation on cardiac autonomic function . METHODS One hundred patients with highly symptomatic atrial fibrillation were r and omly assigned to undergo either circumferential or segmental pulmonary vein ablation . Holter recordings were recorded at baseline and at regular intervals for up to 1 year after ablation . Autonomic function was assessed by deceleration capacity and acceleration capacity of heart rate as well as by st and ard measures of heart rate variability . RESULTS In the circumferential pulmonary vein ablation group , deceleration capacity and acceleration capacity decreased highly significantly from 5.7 + /- 2.1 ms and -8.0 + /- 1.9 ms at baseline to 3.3 + /- 1.8 ms and -5.5 + /- 2.3 ms directly after ablation , respectively ( P deceleration capacity and acceleration capacity was present up to 1 year after ablation . In the segmental pulmonary vein ablation group , deceleration capacity and acceleration capacity decreased from 5.8 + /- 2.0 ms and -7.8 + /- 1.6 ms at baseline to 3.4 + /- 1.2 ms and -6.0 + /- 2.4 ms directly after ablation ( P deceleration capacity and acceleration capacity returned to baseline values within 1 month . CONCLUSIONS Circumferential and segmental pulmonary vein ablations induce an immediate decrease of autonomic function . However , while this decrease is only transient with segmental pulmonary vein ablation , it persists with circumferential pulmonary vein ablation for at least 1 year", "BACKGROUND Postoperative arrhythmias are among the most common complications of cardiac surgery . Total serum magnesium concentration will change after coronary bypass surgery but compensatory prophylactic administration of magnesium has remained a controversial issue . We studied whether prophylactic administration of magnesium could prevent post-coronary artery bypass grafting ( CABG ) arrhythmias and evaluated the effects of diabetes mellitus on prophylactic magnesium administration . METHODS In a clinical trial , 345 consecutive CABG c and i date s were r and omly assigned to study ( n = 166 , 48.1 % ) and control groups . Patients in study group received supplemental magnesium infusion as following : 2 g [ corrected ] after induction of anesthesia until cardio-pulmonary bypass and then 8 g upon arrival in Intensive Care Unit ( ICU ) until 24 hr . Total serum magnesium concentration was measured at four design ated time points : onset of induction , and 0 , 24 and 48 hr after ICU admission . Cardiac arrhythmias were sought with a 12-lead electrocardiogram ( ECG ) from the end of surgery up till discharge . RESULTS Atrial Fibrillation ( Af ) occurred in 34 patients ( 9.9 % ) . Total serum magnesium concentration was significantly higher in patients who received supplemental magnesium ( P non-diabetics , Af incidence was significantly lower in study group compared with control group . CONCLUSIONS The occurrence of atrial fibrillation correlates with serum magnesium level . Diabetes mellitus probably hampers prophylactic effect of supplemental magnesium in preventing the occurrence of Af", "Atrial fibrillation is the most common type of arrhythmia in adults . It is more common as patients age ; the prevalence is 1 % among those younger than age 60 years and increases to more than 8 % in those older than age 80 years . When data are adjusted for age , men are affected more often than women . Cardiac conditions associated with the development of atrial fibrillation are hypertension , rheumatic mitral valve disease , coronary artery disease , and congestive heart failure . Noncardiac causes include hyperthyroidism , hypoxic pulmonary conditions , surgery , and alcohol intoxication . Patients with atrial fibrillation may have symptoms of hemodynamic compromise , such as irregular palpitations and lightheadedness , or more vague symptoms , such as malaise , but may be asymptomatic . Patients with atrial fibrillation are at increased risk for thromboembolic disease . The purpose of this guideline is to make recommendations on the pharmacologic management of newly detected atrial fibrillation in primary care . The target patient population is adult patients with first-detected atrial fibrillation , defined as the presence of symptoms or electrocardiographic evidence of atrial fibrillation . The American College of Cardiology/American Heart Association has recommended using first-detected atrial fibrillation regardless of whether it is symptomatic or self-limited , recognizing that there can be uncertainty about the duration of the episode and about previous undetected episodes ( 1 ) . This guideline does not apply to patients with postoperative or postmyocardial infa rct ion atrial fibrillation , patients with class IV heart failure , patients already taking antiarrhythmic drugs , or patients with valvular disease . The target physician audience is internists and family physicians dedicated to primary care . This guideline is based on the accompanying background paper by McNamara and colleagues ( 2 ) and on the evidence report Management of New-Onset Atrial Fibrillation ( 3 ) , which was produced by the Johns Hopkins Evidence -based Practice Center under contract to the Agency for Healthcare Research and Quality ( AHRQ ) , Rockville , Maryl and . The American Academy of Family Physicians ( AAFP ) and the American College of Physicians ( ACP ) created this guideline in collaboration . The Joint AAFP/ACP Panel review ed the evidence and developed and grade d the recommendations ( Table 1 ) . The guideline was then approved by both organizations . The guideline makes recommendations in the following areas : rate control versus rhythm control , stroke prevention and anticoagulation , electrical cardioversion versus pharmacologic cardioversion , the role of transesophageal echocardiography in guiding therapy , and maintenance therapy . Table 1 . The Guyatt Approach to Grading Recommendations * Section 1 : Rate Control versus Rhythm Control One of the fundamental questions in the management of atrial fibrillation is whether to attempt cardioversion . The answer to this question depends on whether rate control or rhythm control provides more effective protection from thromboembolic events , improved mortality , better relief of symptoms , or improved quality of life . Another significant clinical question is whether certain population s , such as women , patients with hypertension or congestive heart failure , or young people with structurally healthy hearts , have better outcomes with one or the other strategy . Four studies have compared rate control with rhythm control . The study sample s have generally involved older patients ( > 65 years of age ) , and women and younger patients with healthy hearts and paroxysmal atrial fibrillation have not been well represented ( 5 ) . The Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) trial compared rhythm control versus rate control , and use of anticoagulation was recommended in both arms ( 6 ) . More than 4000 patients who were at least 65 years of age or who had at least 1 risk factor for stroke or death , such as hypertension , diabetes , previous stroke , or poor ventricular function , were followed for a mean of 3.5 years . Slightly more than one third of the patients were enrolled after their first episode of atrial fibrillation , and more than 90 % had had their qualifying episode within the previous 6 weeks . In more than two thirds of patients , the qualifying episode lasted at least 2 days . The average patient age was 70 years . Sixty-one percent of patients were men , and 89 % were white . Seventy-one percent of patients had hypertension , 38 % had coronary heart disease , 18 % had previously had failure of antiarrhythmic therapy , and 12 % had no apparent heart disease ( lone atrial fibrillation ) . Patients were r and omly assigned to rate or rhythm control , and their physicians chose the specific therapies ( pharmacologic first , then nonpharmacologic if needed ) . Anticoagulation was continued indefinitely in the rate-control group and was encouraged in the rhythm-control group but could be stopped at the physician 's discretion if sinus rhythm had been maintained for at least 4 , and preferably 12 , consecutive weeks with antiarrhythmic therapy . The prevalence of sinus rhythm in the rhythm-control group was 82 % , 73 % , and 63 % at 1 , 3 , and 5 years , respectively . The prevalence of sinus rhythm in the rate-control group was 34.6 % at 5 years . The primary end point in the AFFIRM trial , overall mortality , was not statistically significantly different between the groups . However , the rhythm-control strategy was associated with a higher risk for death than the rate-control strategy among older patients , those without congestive heart failure , and those with coronary disease . Rates of stroke also did not differ between groups ; 70 % of all strokes occurred in patients who had stopped receiving anticoagulation or who had subtherapeutic international normalized ratios ( hospitalizations were reported in the rhythm-control group ( P aggressive rhythm control or rate control ( 7 ) . This was a smaller study , involving 522 patients ( mean age , 68 years ) . Sixty-four percent of patients were men , 49 % had hypertension , and 27 % had coronary artery disease . All patients had persistent atrial fibrillation lasting less than 1 year and had had at least 1 previous electrical cardioversion ( a maximum of 2 previous cardioversions was permitted for study inclusion ) . The primary end point was a composite of cardiovascular mortality , heart failure , thromboembolic complications , bleeding , pacemaker implantation , and severe side effects of antiarrhythmic drugs . Again , no difference was seen between groups in the primary composite end point . As in the AFFIRM study , most of the strokes occurred in patients whose anticoagulation had been halted or patients whose international normalized ratio was subtherapeutic ( patients with hypertension and in women . Since this was a post hoc analysis , these results will need to be confirmed by further studies . Of note , despite an aggressive treatment protocol , at the end of follow-up only 39 % of the patients in the rhythm-control group were in sinus rhythm . The Pharmacological Intervention in Atrial Fibrillation ( PIAF ) trial r and omly assigned 252 patients 18 to 75 years of age with new-onset or permanent symptomatic atrial fibrillation ( mean duration of atrial fibrillation , approximately 4 months ) to rate control with diltiazem or aggressive conversion ( many times if necessary ) and maintenance therapy with amiodarone ( 8) . The primary end point of the study was improvement in symptoms related to atrial fibrillation . After 1 year of follow-up , relief of symptoms was similar in both groups , as were quality -of-life measures . Walking distance was improved in the rhythm-control group , but hospital admissions were more frequent in this group . Although final results are not yet available , preliminary reports of the Strategies of Treatment of Atrial Fibrillation ( STAF ) trial have been presented ( 9 ) . Patients were r and omly assigned to receive anticoagulation for 3 weeks before conversion and for 4 weeks after attempted conversion , with antiarrhythmic therapy to maintain sinus rhythm , or to long-term anticoagulation and rate control . ( Patients included in this study had at least 1 previous conversion attempt . ) After more than 1.5 years of follow-up , no difference was seen between the groups in rates of the primary end points of death , stroke , transient ischemic attacks , cardiopulmonary resuscitation , or thromboembolism . Of interest , only 40 % of patients in the rhythm-control group were still in sinus rhythm at 1 year , and all primary end points occurred in patients in atrial fibrillation , even in the rhythm-control group . This result has created speculation about whether fewer events would have occurred if anticoagulation had been continued indefinitely in the conversion group . It also suggests that despite aggressive rhythm management , a substantial number of patients can not maintain sinus rhythm . In general , the trial sample s were older and male and had risk factors for stroke , such as hypertension , congestive heart failure , and coronary disease . Certain subgroups of patients with atrial fibrillation , such as younger patients with healthy hearts or paroxysmal atrial fibrillation , were not well represented in the trials . Therefore , it is not certain whether these subgroups of patients may benefit from more aggressive rhythm control or rate control . Recommendation 1 : Rate control with chronic anticoagulation is the recommended strategy for the majority of patients with atrial fibrillation . Rhythm control has not been shown to be superior to rate control ( with chronic anticoagulation ) in reducing morbidity and mortality and may be inferior in some patient subgroups to rate control . Rhythm", "Intracranial hemorrhage is the most feared complication of anticoagulant therapy . Outcomes are frequently catastrophic , often result ing in death or severe neurologic disability . The effect of intracranial hemorrhage is as great as that of the thromboembolic events warfarin is used to prevent . As a result , the risk for intracranial hemorrhage is a critical feature of the decision to use anticoagulation [ 1 ] . The indications for use of anticoagulants are exp and ing , particularly among older patients . For example , anticoagulant therapy is now recommended to prevent stroke in patients with atrial fibrillation [ 2 - 6 ] , and it has been found to significantly improve outcome in patients after myocardial infa rct ion [ 7 ] . Clinical trials of warfarin as primary preventive therapy for ischemic heart disease are ongoing [ 8 ] . With this increase in the use of long-term warfarin therapy , there is a pressing need to identify clinical features that raise the risk of its most severe bleeding complications . No previous study has identified independent risk factors for intracranial hemorrhage among patients taking warfarin . Previous prospect i ve analytic studies that focused on the entire spectrum of major bleeding complications have contained few cases of intracranial hemorrhage [ 9 - 11 ] . We design ed a casecontrol study focused exclusively on intracranial hemorrhage occurring among out patients taking warfarin . We drew on an 11-year experience of one general hospital to provide case- patients and used the same hospital 's large anticoagulant therapy unit to provide contemporaneous controls who were also taking warfarin . This design was chosen to increase statistical power for detecting risk factors for intracranial hemorrhage while reducing possible bias . Methods Case-Patient Identification and Eligibility Using a discharge log of consecutive admissions to the Massachusetts General Hospital during the period from 1 January 1981 through 31 December 1991 , we identified 1881 patients with a principal diagnosis of intracranial hemorrhage ( ICD-9 codes 430 , 431 , 432.0 , 432.1 , and 432.9 ) . Forty-one ( 2 % ) medical records for these patients could not be located . In the remaining 1840 case- patients , warfarin use was determined from review of the neurologist , neurosurgery resident , and attending staff physician admission notes . Intracranial hemorrhage was verified by computed tomographic ( CT ) scanning , lumbar puncture , or postmortem examination in all but one case-patient . In this latter case-patient , the diagnosis was based on clinical grounds because the patient died before diagnostic studies were done and no autopsy was performed . To be eligible for the study , patients had to be at least 18 years old and taking warfarin as an outpatient . Patients with an anatomic abnormality or underlying bleeding diathesis predisposing to intracranial hemorrhage , regardless of anticoagulant therapy , were not included . Hemorrhages sustained as a result of major head trauma ( with skull fracture and loss of consciousness ) also were not eligible . Of 131 patients with intracranial hemorrhage identified , 10 were excluded as ineligible : Four patients had subarachnoid hemorrhage result ing from angiographically identified intracranial aneurysms ; 2 had hemorrhage into primary or metastatic tumors ; 2 had acute subdural hemorrhage after major head trauma ; 1 bled after multiple craniotomies and radiation therapy for a recurrent craniopharyngioma ; and another patient had aplastic anemia . Controls : Source and Matching Controls were selected from the registry of the Massachusetts General Hospital 's anticoagulant therapy unit . During the study period , this unit managed warfarin dosing for approximately 8000 patients referred from all hospital clinical services . The most common indications for anticoagulation were atrial fibrillation , previous stroke , presence of prosthetic heart valves , and venous thromboembolism . Approximately 40 % of the patients managed by the anticoagulant therapy unit have prothrombin time tests done at the Massachusetts General Hospital . An additional 20 % have their prothrombin times measured at one large commercial laboratory ( via home phlebotomy services ) . The remaining 40 % have their tests done at various local laboratories . Each case-patient was matched to three r and omly selected controls taking warfarin at the time of the case-patient 's intracranial hemorrhage . Matching was accomplished by first identifying all patients managed by the anticoagulant therapy unit at the date of hospital admission for the given case-patient . Each potential control was assigned a r and om number . The three controls with the lowest r and om numbers were selected . No control was used more than once . Three controls subsequently became case- patients . Matching was done to control for any change in background risk over the 11-year study period ( for example , from changes in prothrombin time targets or technique of measuring the prothrombin time ) . Data Collected Clinical features of case- patients and controls were extracted primarily from hospital records , with supplementation in a few instances from physician office records . Variables were entered on a pre design ed data form and included indication for anticoagulant therapy ; race ; sex ; age ; prothrombin time ratio ( PTR ) ; duration of warfarin therapy ; history of diagnosed hypertension , stroke , transient ischemic attack , diabetes mellitus , myocardial infa rct ion , atrial fibrillation , and congestive heart failure ; and medications . Clinical features of the intracranial hemorrhages were also recorded . Clinical data for the controls were current at the admission date of the matched case-patient with intracranial hemorrhage . The prothrombin time ratio was expressed as the ratio of the patient 's value divided by the simultaneously reported control value . For case- patients , we used the PTR on admission , or , if available , the PTR closest to the reported onset of symptoms . For controls , the PTR closest to that of the case-patient admission date was recorded from the anticoagulant therapy unit data base . Because values for the international sensitivity index ( ISI ) for thromboplastins were not universally reported before 1988 , we analyzed our data using the PTR rather than the international normalized ratio ( INR ) . Since 1988 , Massachusetts General Hospital 's hematology laboratory has used Simplastin Automated ( Organon Teknika Corporation , Durham , North Carolina ) , with values for the ISI ranging from 1.9 to 2.0 . During the study period , this company ( previously General Diagnostics ) supplied the thromboplastin and assisted our laboratory in selecting lots of comparable sensitivity . Studies were routinely done to minimize year-to-year variation in thromboplastin sensitivity . Since 1988 , the most frequently used commercial laboratory has used thromboplastins with ISI values ranging from 1.9 to 2.1 . The PTR was missing for four case- patients ; the data for case- patients and controls were otherwise complete . Selected Relevant Definitions Hypertension was defined as probable if the patient had such a diagnosis listed in the medical record and as definite if the patient was receiving antihypertensive medication . When hypertension was diagnosed , it was classified as definite 97 % of the time for case- patients and 93 % of the time for controls . All diagnoses of hypertension are used in the analyses . Patients with documented carotid or vertebrobasilar disease and those with a history of previous stroke were defined as having cerebrovascular disease . Diagnoses of carotid or vertebrobasilar disease or both were confirmed by angiography in 71 % of case- patients and 93 % of controls , by Doppler studies in 17 % of case- patients and 2 % of controls , and solely by assessment by a neurologist in 12 % of case- patients and 5 % of controls . Statistical Analysis Case- patients and controls were compared using chi-square tests and the Fisher exact test , where appropriate , for categorical variables and using the Student t-test for continuous variables . Univariate odds ratios were calculated using unmatched and matched techniques . The matched odds ratios were provided by the Mantel-Haenszel [ 12 ] summary statistic across matched sets . The unmatched and matched techniques provided very similar estimates of odds ratios . We report the unmatched results . Confidence intervals for odds ratios were calculated using the Taylor series method [ 13 ] . The test of trend was done using the Cochran-Mantel-Haenszel test [ 14 ] . Logistic regression models assessed the independent effect of multiple clinical features and the significance of interaction terms . Conditional logistic models [ 15 ] accounting for matching provided estimates similar to those of the unmatched logistic regression analyses . The estimates from the unmatched analyses are reported . Data were recorded in R : BASE ( Microrim , Bellevue , Washington ) from the paper data forms . Statistical analyses were done using SAS ( SAS Institute Inc. , Cary , North Carolina ) and GLIM ( Numerical Algorithms Group Limited , Oxford , United Kingdom ) . Results Clinical Course of Case- Patients During the 11-year study period , 121 patients with intracranial hemorrhage were eligible ; 77 hemorrhages were intracerebral and 44 were subdural ( Table 1 ) . Three of the patients with subdural hemorrhage had a history of trivial head trauma ; the others had no known antecedent head trauma . For the patients with intracerebral hemorrhages , headache was the most common presenting feature ( 53 % ) , followed by nausea and vomiting ( 40 % ) and unresponsiveness ( 36 % ) . Seventy-eight percent of the case- patients presented to the emergency department within 24 hours of the onset of symptoms and 87 % within 48 hours . In contrast , only 36 % of the patients with subdural bleeding came to medical attention within this same period . Forty-six percent of patients with intracerebral bleeding died , and 17 % survived with major neurologic deficits that prevented subsequent independent living . Table 1 .", "INTRODUCTION Atrial fibrillation ( AF ) and diabetes mellitus type 2 ( DM2 ) often coexist ; however , a small number of patients with DM2 undergoing catheter ablation ( CA ) of AF have been included in previous studies . The aim of this study was to evaluate safety and efficacy of ablation therapy in DM2 patients with drug refractory AF . METHODS AND RESULTS From January 2005 to September 2006 , 70 patients with a diagnosis of DM2 and paroxysmal ( n = 29 ) or persistent ( n = 41 ) AF were r and omized to receive either pulmonary vein isolation or a new antiarrhythmic drug treatment ( ADT ) with a 1-year follow-up . The primary endpoint was the time to first AF recurrence . By Kaplan-Meier analysis , at the end of follow-up , 42.9 % of patients in the ADT group and 80 % of patients who received a single ablation procedure and were without medications were free of AF ( P = 0.001 ) . In the ablation group , a significant improvement in quality -of-life ( QoL ) scores as compared with ADT group was observed . Six patients in the ADT group ( 17.1 % ) developed significant adverse drug effects . Hospitalization rate during follow-up was higher in the ADT group ( P = 0.01 ) . The only complication attributable to ablation was one significant access-site hematoma . CONCLUSION In patients with DM2 , CA of AF provides significant clinical benefits over the ADT and appears to be a reasonable approach regarding feasibility , effectiveness , and low procedural risk", "BACKGROUND In the elderly the impact of atrial fibrillation on mortality and morbidity is substantial . Oral anticoagulant therapy reduces the risk of stroke by 70 % ; nevertheless , it remains largely underused . We evaluated , in a community prospect i ve study , the factors associated with embolic events and death and the feasibility of oral anticoagulant therapy managed by general practitioners . METHODS We enrolled at the Trieste Cardiovascular Center 229 patients aged > or = 65 years with non-rheumatic atrial fibrillation . At baseline , each patient underwent a transesophageal echocardiography and received instructions about oral anticoagulation . Patients were regularly followed by their general practitioner and finally evaluated at the Center . RESULTS At baseline , the mean age was 73 years , 14 % of patients were free of heart disease , 27 % had had a previous embolic event , and 33 % had an atrial thrombus . After a 5-year follow-up , 85 % of the patients had been admitted to hospital , 17 % had suffered an embolic event , and 35 % were dead . Diabetes and the presence of a low flow in the left atrial appendage were predictive of embolic events . Heart failure , spontaneous echocontrast and aortic plaques were predictive of death . Anticoagulant therapy increased from 14 to 34 % but the incidence of major bleeding did not change . The patients on anticoagulant therapy at follow-up constituted the group with the worst cardiovascular profile and embolic rate , but had a lower death rate ( 19 % ) compared with those on antiplatelet therapy ( 32 % ) and with those without antithrombotic therapy ( 67 % ) . The hospitalization rates were respectively 78 , 83 and 100 % . CONCLUSIONS In a group of elderly patients followed by their general practitioner with the support of a specialized cardiologic unit , oral anticoagulant therapy was well tolerated and associated with a significant decrease in mortality and hospitalization", "OBJECTIVES We assessed feasibility of magnetic catheter guidance in patients with atrial fibrillation ( AF ) undergoing circumferential pulmonary vein ablation ( CPVA ) . BACKGROUND No data are available on feasibility of remote navigation for AF ablation . METHODS Forty patients underwent CPVA for symptomatic AF using the NIOBE II remote magnetic system ( Stereotaxis Inc. , St. Louis , Missouri ) . Ablation was performed with a 4-mm tip , magnetic catheter ( 65 degrees C , maximum 50 W , 15 s ) . The catheter tip was guided by a uniform magnetic field ( 0.08-T ) , and a motor drive ( Cardiodrive unit , Stereotaxis Inc. ) . Left atrium maps were created using an integrated CARTO RMT system ( Stereotaxis Inc. ) . End point of ablation was voltage abatement > 90 % of bipolar electrogram amplitude . RESULTS Remote ablation was successful in 38 of 40 patients without complications . The median mapping and ablation time was 152.5 min ( range , 90 to 380 min ) but was much longer in the first 12 patients ( 192.5 min vs. 148 min ; p = 0.012 ) . Median ablation time was 49.5 min ( range , 17 to 154 min ) , but it was much shorter in the last 28 patients than in the first 12 patients ( 49 min vs. 70 min ; p = 0.021 ) . Patients receiving remote ablation had longer procedure times than control patients ( p mapping time but shorter ablation time on right-sided pulmonary veins . Many more mapping points regardless of their location were collected remotely ( p Remote magnetic navigation for AF ablation is safe and feasible with a short learning curve . Although all procedures were performed by a highly experienced operator , remote AF ablation can be performed even by less experienced operators", "AIMS Catheter positioning and stability are recognized challenges in catheter ablation of atrial fibrillation ( AF ) . This prospect i ve r and omized study assessed whether routinely using a steerable sheath affects procedure outcomes . METHODS AND RESULTS Fifty-six AF patients were r and omized to ablation using either an Agilis NXT ( St Jude Medical , St Paul , MN , USA ) steerable sheath or a fixed-curve Mullins sheath ( Cook Medical Inc. , Bloomington , IN , USA ) for the ablation catheter . A mapping system with CT integration was used to isolate the pulmonary veins ( PVs ) in pairs and further ablation performed if AF persisted . There was no significant difference in time to gain trans-septal access , CT registration time , time to isolate PVs , fluoroscopy time for PV isolation , total procedure time , or total fluoroscopy time . A learning curve was seen for the steerable sheath , and after correcting for this , CT registration time and right PV isolation were quicker in this group . One patient crossed over from fixed-curve to steerable . Acute , 3- , and 6-month single procedure success were similar in both groups . CONCLUSION Allowing for the usage learning curve , a steerable sheath reduced time for some elements of AF ablation . Although this did not result in improved success , it may be useful for inexperienced operators , but at increased procedure cost", "INTRODUCTION We performed a prospect i ve study to compare efficacy and safety of both open irrigation tip ( OIT ) technology with intracardiac echo (ICE)-guided energy delivery in patients presenting for PVAI . METHODS AND RESULTS Fifty-three patients presenting for PVAI were r and omized to ablation using an OIT catheter ( Group 1 , 26 patients ; temperature and power were set at 50 degrees and 50 W , respectively , with a saline pump flow rate of 30 mL/min ) or radiofrequency ( RF ) energy delivery under ICE guidance ( Group 2 , 27 patients ; energy was titrated based on microbubbles formation ) . The mean procedure time and fluoroscopy exposure were lower in Group 1 ( 164 + /- 42 min and 7,560 + /- 2,298 microGray m2 vs 204 + /- 47 min and 12,240 + /- 4,356 microGray m2 ; P = 0.005 and 0.008 , respectively ) . Moreover , the duration s of RF lesions applied per PV antrum was lower in Group 1 compared with Group 2 ( 5.1 + /- 2.2 min vs 9.2 + /- 3.2 min , P = 0.03 , respectively ) . Within 24 hours after PVAI in 35.7 % ( all erythema ) of Group 1 and 57.1 % ( 21.4 % erythema and 35.7 % necrosis ) of Group 2 , patients ' esophageal wall changes were documented . After 14 + /- 2 months of follow up , recurrences were documented in 19.2 % of Group 1 and 22.2 % of Group 2 patients . CONCLUSION Although both OIT and ICE-guided energy delivery possess a similar effect in treating AF , OIT seems to be superior in terms of achieving isolation and shortening fluoroscopy exposure . Moreover , a lower incidence of esophageal wall injury was observed utilizing OIT for PVAI", "OBJECTIVES The aim of this study was to compare -- in patients with persistent and permanent atrial fibrillation (AF)--the efficacy and safety of left atrial ablation with that of a biatrial approach . BACKGROUND Left atrium-based catheter ablation of AF , although very effective in the paroxysmal form of the arrhythmia , has an insufficient efficacy in patients with persistent and permanent AF . METHODS Eighty highly symptomatic patients ( age , 58.6 + /- 8.9 years ) with persistent ( n = 43 ) and permanent AF ( n = 37 ) , refractory to antiarrhythmic drugs , were r and omized to two different ablation approaches guided by electroanatomical mapping . A procedure including circumferential pulmonary vein , mitral isthmus , and cavotricuspid isthmus ablation was performed in 41 cases ( left atrial ablation group ) . In the remaining 39 patients ( biatrial ablation group ) , the aforementioned approach was integrated by the following lesions in the right atrium : intercaval posterior line , intercaval septal line , and electrical disconnection of the superior vena cava . RESULTS During follow-up ( mean duration 14 + /- 5 months ) , AF recurred in 39 % of patients in the left atrial ablation group and in 15 % of patients in the biatrial ablation group ( p = 0.022 ) . Multivariable Cox regression analysis showed that ablation technique was an independent predictor of AF recurrence during follow-up . CONCLUSIONS In patients with persistent and permanent AF , circumferential pulmonary vein ablation , combined with linear lesions in the right atrium , is feasible , safe , and has a significantly higher success rate than left atrial and cavotricuspid ablation alone", "OBJECTIVES We compared ablation strategy with antiarrhythmic drug therapy ( ADT ) in patients with paroxysmal atrial fibrillation ( PAF ) . BACKGROUND Atrial fibrillation ( AF ) ablation strategy is superior to ADT in patients with an initial history of PAF , but its role in patients with a long history of AF as compared with ADT remains a challenge . METHODS One hundred ninety-eight patients ( age , 56 + /- 10 years ) with PAF of 6 + /- 5 years ' duration ( mean AF episodes 3.4/month ) who had failed ADT were r and omized to AF ablation by circumferential pulmonary vein ablation ( CPVA ) or to the maximum tolerable doses of another ADT , which included flecainide , sotalol , and amiodarone . Crossover to CPVA was allowed after 3 months of ADT . RESULTS By Kaplan-Meier analysis , 86 % of patients in the CPVA group and 22 % of those in the ADT group who did not require a second ADT were free from recurrent atrial tachyarrhythmias ( AT ) ( p CPVA and ADT groups , respectively , were AT-free . Ejection fraction , hypertension , and age independently predicted AF recurrences in the ADT group . Circumferential pulmonary vein ablation was associated with fewer cardiovascular hospitalizations ( p transient ischemic attack and 1 pericardial effusion occurred in the CPVA group ; side effects of ADT were observed in 23 patients . CONCLUSIONS Circumferential pulmonary vein ablation is more successful than ADT for prevention of PAF with few complications . Atrial fibrillation ablation warrants consideration in selected patients in whom ADT had already failed and maintenance of sinus rhythm is desired . ( A Controlled R and omized Trial of CPVA Versus Antiarrhythmic Drug Therapy in for Paroxysmal AF : APAF/01 ; http:// clinical trials.gov/ct/show ; NCT00340314 )", "BACKGROUND Multiple cardiac ganglia are present in the left atrial ( LA ) region , and marked changes in autonomic nervous activity can occur after left atrial catheter ablation ( CA ) for atrial fibrillation ( AF ) . Vasospastic angina involving the inferior wall of the left ventricle has been reported as a complication shortly after LACA . METHODS We studied 20 patients with drug-refractory AF who underwent LACA , performed to encircle the left- and right-sided pulmonary veins , 1 to 2 cm from their ostia under fluoroscopic guidance . Quantitative coronary angiography was performed before and after LACA , and we analyzed the minimal lesion diameter ( MLD ) of the proximal segment of the coronary arteries , and the basal tone , the baseline percent constriction versus maximal dilation after nitroglycerin administration . RESULTS No significant difference was observed in MLD or basal tone of the left coronary arteries after LACA . However , in the right coronary artery ( RCA ) , the basal MLD was smaller ( P basal tone was greater ( P the baseline MLD or tone of the RCA and total amount of radiofrequency energy delivered or procedure duration . In 75 % of RCA , the baseline MLD was smaller after than before LACA , which was significantly higher ( P Vasoconstriction was promoted in the RCA shortly after LACA , which may explain the variant angina reported after LACA", "Chronic atrial fibrillation ( AF ) is a common arrhythmia with significant morbidity and mortality . AF has been the subject of considerable attention and intensive clinical research in recent years . Current opinion on the management of AF favors the restoration and maintenance of normal ventricular rhythm . This has several potential benefits , including the alleviation of arrhythmia-associated symptoms and hemodynamic improvements . Maintenance of frequents normalization of ventricular rhythm ( NVR ) can be achieved with antiarrhythmic drug therapy or with AV node radiofrequency ablation ( RFA ) and permanent ventricular pacing . Recent interest has focused on the use of class III antiarrhythmic agents , such as amiodarone hydrochloride . This investigation compared amiodarone to AV node RFA and permanent pacing of the His-bundle area in maintaining NVR in patients with resistant chronic AF . After 12 months of treatment with amiodarone ( 200 to 400 mg/d ) 30 % of patients remained in NVR , 30 % were in transitional phase of improvement , and 40 % showed negative effect . Only a few patients in this group developed ocular or hepatic side effects . On one year follow-up was achieved in 100 % of cases without any clinical ly significant side effects being seen . In conclusion , analysis of the results of this study suggests that low-dose amiodarone is well tolerated in the management of chronic AF in a selected patient population . The more aggressive interventional radiofrequency ablation technique is significantly more effective and more reliable in the long-term clinical treatment of drug-resistant AF", "BACKGROUND Data on the procedural safety of pulmonary vein radiofrequency catheter ablation for atrial fibrillation ( AF ) are as yet scant . OBJECTIVE The aims of the present study were to prospect ively evaluate the incidence of early complications of pulmonary vein ablation for AF in an unselected population of consecutive patients , and to identify possible predictors . METHODS From April 2005 to October 2006 , data from 1,011 consecutive patients who were undergoing radiofrequency catheter ablation for every type of AF in 10 Italian centers were collected . All complications occurring from the admission of the patient up to the 30th day were considered . RESULTS No procedure-related death was observed . Complications occurred in 40 patients ( 3.9 % ) : 12 ( 1.2 % ) had peripheral vascular complications , 8 ( 0.8 % ) had conservatively treated pericardial effusion , 6 ( 0.6 % ) had cardiac tamponade ( successfully drained ) , 5 ( 0.5 % ) had cerebral embolisms , 4 ( 0.4 % ) presented pulmonary vein stenosis > 50 % , and 5 ( 0.5 % ) presented other isolated adverse events . History of coronary artery disease ( odds ratio 5,603 , 95 % confidence interval 1,559 to 20,139 , P hemorrhagic complications . CONCLUSION Early complications of pulmonary vein catheter ablation seem to be fewer than in the early years of AF ablation , but still occur in 3.9 % of procedures", "OBJECTIVES The purpose of this study was to determine the long-term clinical outcomes of catheter ablation of atrial fibrillation ( AF ) substrate for high-risk patients with AF . BACKGROUND The benefits of catheter ablation for high-risk AF patients with respect to mortality and stroke reductions remain unclear . METHODS We performed AF substrate ablation guided by complex fractionated atrial electrogram ( CFAE ) mapping in 674 high-risk AF patients . The clinical end points were sinus rhythm ( SR ) , death , stroke , or bleeding . Of these 674 patients , 635 were available for follow-up and made up the study cohort . The patients were relatively old ( mean age 67 + /- 12 years ) and 129 had an ejection fraction ( EF ) RESULTS After the mean follow-up period of 836 + /- 605 days , 517 were in SR ( 81.4 % ) . There were 15 deaths among the patients who stayed in SR compared with 14 deaths among those who remained in AF ( 5-year survival rate , 92 % vs. 64 % , respectively ; p SR was the most important independent favorable parameter for survival ( hazard ratio 0.14 , 95 % confidence interval 0.06 to 0.36 , p Warfarin therapy was discontinued in 434 of the 517 patients in SR post-ablation ( 84 % ) whose annual stroke rate was only 0.4 % compared with 2 % in those with continuing warfarin treatment ( p = 0.004 ) . CONCLUSIONS CFAE-targeted ablation of AF is effective in maintaining SR in selected high-risk AF patients and might allow patients to stop warfarin therapy . SR after AF ablation is a marker of relatively low mortality and stroke risk . Our findings support conducting further r and omized studies to determine whether AF ablation is associated with mortality and /or stroke reduction", "INTRODUCTION Pulmonary vein isolation ( PVI ) is an established treatment for paroxysmal atrial fibrillation ( AF ) . The ablation of complex fractionated atrial electrograms ( CFAE ) has emerged as a novel treatment approach . We sought to evaluate the additional effect of CFAE ablation to PVI in paroxysmal AF . METHODS AND RESULTS Ninety-eight patients with paroxysmal AF ( 57 + /- 10 years , 74 male ) were r and omized to the PVI ( n = 48 ) or PVI + CFAE group ( n = 50 ) . After PVI , CFAE ablation was performed in patients with inducible AF in the PVI + CFAE group . The primary endpoint was combined objective ( 7-day Holter ECG ) and subjective ( symptoms ) freedom of atrial tachyarrhythmia 3 months after ablation . Long-term follow-up ( 19 + /- 8 months ) was available in 94 of 98 patients . CFAE ablation was performed in 30 of 50 patients of the PVI + CFAE group . After 3 months , 36 of 48 patients ( 75 % ) in the PVI group and 38 of 50 patients ( 76 % ) in the PVI + CFAE group were in stable sinus rhythm ( P = NS ) . During long-term follow-up ( 19 + /- 8 months ) , 34 of 46 patients ( 74 % ) in the PVI group and 40 of 48 patients ( 83 % ) in the PVI + CFAE group were in sinus rhythm ( P = 0.08 ) . In a subgroup analysis , a significantly better long-term outcome was achieved if inducible AF after PVI had been treated by additional CFAE ablation as compared with PVI only ( sinus rhythm in 25/28 patients ; 89 % vs 22/30 patients 73 % ; P = 0.003 ) . CONCLUSION In the intention-to-treat analysis , additional CFAE ablation did not improve the success rate of PVI in patients with paroxysmal AF . However , during long-term follow-up , patients with still inducible AF after PVI seemed to profit from additional CFAE ablation", "INTRODUCTION Circumferential pulmonary vein ablation ( CPVA ) with the endpoint of pulmonary vein ( PV ) isolation has been developed as an effective therapy for atrial fibrillation ( AF ) . This endpoint can be achieved either by closing gaps along circular lines or by segmental PV isolation inside the circular lines after creation of initial CPVA lesions . We investigated whether the clinical outcome depends on the PV isolation approach used during the first-time CPVA procedure . METHODS AND RESULTS One hundred consecutive patients ( 69 male ; age , 56.7 + /- 11.6 years ) who underwent first-time CPVA for treatment of symptomatic AF were enrolled . PV isolation was r and omly achieved either by CPVA alone ( aggressive CPVA [ A-CPVA ] group , n = 50 ) or by a combination of CPVA with segmental PV ostia ablation ( modified CPVA [ M-CPVA ] group , n = 50 ) . Recurrence of atrial tachyarrhythmias ( ATa ) within 3 months after the initial procedure occurred in 30 patients ( 60 % ) in the M-CPVA group and in only 15 patients ( 30 % ) in the A-CPVA group ( P ATa relapse after the first 3 months was detected in 21 patients ( 42 % ) in the M-CPVA group , compared with 9 patients ( 18 % ) in the A-CPVA group ( P = 0.01 ) . At 13 + /- 4 months , patients treated by the A-CPVA approach had greater freedom from ATa recurrence than patients who underwent M-CPVA ( P = 0.01 ) . The M-CPVA approach was the only independent predictor associated with procedural failure ( RR 0.318 ; 95 % CI 0.123 - 0.821 ; P = 0.02 ) . CONCLUSIONS When PV isolation is the endpoint of CPVA , the efficacy of the A-CPVA approach is better than that of M-CPVA", "Objectives : This r and omised trial evaluated if patients with atrial fibrillation ( AF ) and no history of atrial flutter ( AFL ) had any benefit of prophylactic cavotricuspid isthmus block ( CTIB ) in addition to circumferential pulmonary vein ablation ( CPVA ) . Methods : 149 patients with AF ( 54 % paroxysmal ) were r and omised to CPVA and CTIB ( group CTIB+ , n = 73 ) or CPVA alone ( group CTIB− , n = 76 ) . Patients were followed for 12 months with repetitive 7-day Holter monitoring after 3 , 6 and 12 months . Results : Six patients ( 4 % ) had cardiac tamponade , and one patient had a stroke . No difference was found in the cumulative AFL-free rate between the two treatment groups ( CTIB+ : 88 % vs CTIB− : 84 % , hazard ratio ( HR ) 0.80 , 95 % CI ( 0.34 to 1.90 ) , p = 0.61 ) . There was no difference in the cumulative AF-free rate between the groups ( CTIB+ : 34 % vs CTIB− : 32 % , HR 0.93 , 95 % CI ( 0.63 to 1.38 ) , p = 0.71 ) . Overall , 33 % of the patients were free of AF after a single procedure . Including re procedures , a complete or partial beneficial effect was noted in 62 % of the patients at 12 months . At 12-month follow-up , 24 ( 50 % ) patients with documented AF or AFL in the Holter recordings were asymptomatic . Conclusions : It was not possible to demonstrate any beneficial effect of CTIB in addition to CPVA with regard to AFL or AF recurrences during follow-up . Repetitive long-term Holter monitoring demonstrated a 33 % rate of freedom from AF during a 1-year follow-up . Including additional CPVA procedures , a clinical effect was noted in 62 % of the patients at 12 months . Patients with AF or AFL recurrences were often asymptomatic", "BACKGROUND Atrial fibrillation is the most commonly encountered sustained cardiac arrhythmia . Restoration and maintenance of sinus rhythm is believed by many physicians to be superior to rate control only . However , there are no prospect i ve data that compare both therapeutic strategies . METHODS The Pharmacological Intervention in Atrial Fibrillation ( PIAF ) trial was a r and omised trial in 252 patients with atrial fibrillation of between 7 days and 360 days duration , which compared rate ( group A , 125 patients ) with rhythm control ( group B , 127 patients ) . In group A , diltiazem was used as first-line therapy and amiodarone was used in group B. The primary study endpoint was improvement in symptoms related to atrial fibrillation . FINDINGS Over the entire observation period of 1 year , a similar proportion of patients reported improvement in symptoms in both groups ( 76 responders at 12 months in group A vs 70 responders in group B , p=0.317 ) . Amiodarone administration result ed in pharmacological restoration of sinus rhythm in 23 % of patients . Walking distance in a 6 min walk test was better in group B compared with group A , but assessment of quality of life showed no differences between groups . The incidence of hospital admission was higher in group B ( 87 [ 69 % ] out of 127 vs 30 [ 24 % ] out of 125 in group A , p=0.001 ) . Adverse drug effects more frequently led to a change in therapy in group B ( 31 [ 25 % ] patients compared with 17 [ 14 % ] in group A , p=0.036 ) . INTERPRETATION With respect to symptomatic improvement in patients with atrial fibrillation , the therapeutic strategies of rate versus rhythm control yielded similar clinical results overall . However , exercise tolerance is better with rhythm control , although hospital admission is more frequent . These data may serve as a basis to select therapy in individual patients", "STUDY OBJECTIVES The relative risks and benefits of strategies of rate control vs rhythm control in patients with atrial fibrillation ( AF ) remain to be fully explored . DESIGN The How to Treat Chronic Atrial Fibrillation ( HOT CAFE ) Polish trial was design ed to evaluate in a r and omized , multicenter , and prospect i ve manner the feasibility and long-term outcomes of rate control vs rhythm control strategies in patients with persistent AF . PATIENTS Our study population comprised 205 patients ( 134 men and 71 women ; mean [ + /- SD ] age , 60.8 + /- 11.2 years ) with a mean AF duration of 273.7 + /- 112.4 days . The mean observation period was 1.7 + /- 0.4 years . One hundred one patients were r and omly assigned to the rate control group and received rate-slowing therapy guided by repeated 24-h Holter monitoring . Direct current cardioversion and atrioventricular junctional ablation with pacemaker placement were alternative nonpharmacologic strategies for patients with tachycardia that was resistant to medical therapy . One hundred four patients were r and omized to sinus rhythm restoration and maintenance using serial cardioversion supported by a predefined stepwise antiarrhythmic drug regimen ( ie , disopyramide , propafenone , sotalol , and amiodarone ) . In both groups , thromboembolic prophylaxis followed current guidelines . MEASUREMENTS AND RESULTS At the end of follow-up , 63.5 % of patients in the rhythm control arm remained in sinus rhythm . No significant differences in the composite end point ( ie , all-cause mortality , number of thromboembolic events , or major bleeding ) were found between the rate control group and the rhythm control group ( odds ratio , 1.98 ; 95 % confidence interval , 0.28 to 22.3 ; p > 0.71 ) . The incidence of hospital admissions was much lower in the rate control arm ( 12 % vs 74 % , respectively ; p New York Heart Association functional class improved in both study groups , while mean exercise tolerance , as measured by the maximal treadmill workload , improved only in the rhythm control group ( 5.2 + /- 5.1 vs 7.6 + /- 3.3 metabolic equivalents , respectively ; p mean left ventricular fractional shortening ( 29 + /- 7 % vs 31 + /- 7 % , respectively ; p pulmonary embolism occurred in the rate control group despite oral anticoagulation therapy , while three patients in the rhythm control arm of the study experienced ischemic strokes ( not significant ) . CONCLUSIONS The Polish HOT CAFE study revealed no significant differences in major end points between the rate control group and the rhythm control group", "OBJECTIVES This study was design ed to compare two treatment strategies in patients with atrial fibrillation(AF ) : rhythm-control ( restoration and maintenance of sinus rhythm ) and rate-control ( pharmacologic or invasive rate-control and anticoagulation ) . BACKGROUND Atrial fibrillation is the most common arrhythmia . It is unclear whether a strategy of rhythm- or rate-control is better in terms of mortality , morbidity , and quality of life . METHODS The Strategies of Treatment of Atrial Fibrillation ( STAF ) multicenter pilot trial r and omized 200 patients ( 100 per group ) with persistent AF to rhythm- or rate-control . The combined primary end point was a combination of death , cardiopulmonary resuscitation , cerebrovascular event , and systemic embolism . RESULTS After 19.6 + /- 8.9 months ( range 0 to 36 months ) there was no difference in the primary end point between rhythm-control ( 9/100 ; 5.54%/year ) and rate-control ( 10/100 ; 6.09%/year ; p = 0.99 ) . The percentage of patients in sinus rhythm in the rhythm-control group after up to four cardioversions during the follow-up period ( rate-control group ) was 23 % ( 0 % ) at 36 months . Eighteen primary end points occurred in atrial fibrillation ; only one occurred in sinus rhythm ( p = 0.049 ) . CONCLUSIONS The STAF pilot study showed no differences between the two treatment strategies in all end points except hospitalizations . These data suggest that there was no benefit in attempting rhythm-control in these patients with a high risk of arrhythmia recurrence . It remains unclear whether the results in the rhythm-control group would have been better if sinus rhythm had been maintained in a higher proportion of patients , as all but one end point occurred during AF", "Context The appropriate level of warfarin anticoagulation in elderly patients with atrial fibrillation has been debated because of an age-associated increase in intracerebral hemorrhage . Contribution Patients with atrial fibrillation and intracerebral hemorrhage who were receiving anticoagulation were matched with similar patients who did not develop intracerebral hemorrhage . Although intracerebral hemorrhage was associated with increasing age ( especially > 85 years ) and increasing international normalized ratios ( INRs ) ( especially > 3.5 ) , the incidence of intracerebral hemorrhage was not statistically different in patients with INRs less than 2.0 and those with INRs between 2.0 and 3.0 . This was true even among those older than 75 years of age . Implication s Risk for intracerebral hemorrhage is not diminished in elderly patients with atrial fibrillation when anticoagulation is maintained below an INR of 2.0 . The Editors Intracranial hemorrhage is the most dangerous complication of warfarin anticoagulant therapy because of its high short-term risk for death and severe neurologic deficit ( 1 - 5 ) . Warfarin is extremely effective in reducing the risk for ischemic stroke associated with atrial fibrillation ( 6 , 7 ) . However , fear of hemorrhage may prompt some physicians to avoid prescribing anticoagulation ( 8) , especially in elderly patients , who appear to have a higher risk for hemorrhage ( 8 - 13 ) . Prominent recent guidelines recommend using lower-intensity anticoagulation for the primary prevention of stroke in patients older than 75 years of age who have atrial fibrillation ( 14 ) and suggest a target international normalized ratio ( INR ) range of 1.6 to 2.5 , despite evidence that the risk for ischemic stroke increases sharply at INRs less than 2.0 ( 15 , 16 ) . Previous studies have not thoroughly addressed the relationship of age and anticoagulation intensity to the risk for intracranial hemorrhage among patients with atrial fibrillation ( 1 , 2 ) . A study of 121 patients with warfarin-associated intracranial hemorrhage used the now-out date d prothrombin time ratio as a measure of anticoagulation intensity and did not specifically address risk in patients with atrial fibrillation ( 1 ) . Earlier studies also included patients receiving anticoagulation for mechanical valves , whose risk-to-benefit ratio is different from that of patients with atrial fibrillation ( 1 , 2 , 17 ) . As the number of individuals with atrial fibrillation increases ( 18 - 21 ) and as a greater proportion of older adults receive anticoagulant therapy ( 22 ) , more precise data are needed about the association of age , INR , and risk for intracranial hemorrhage . Intracranial hemorrhage , although critically important , is an uncommon complication among patients with atrial fibrillation who are receiving anticoagulation . As a result , r and omized trials and cohort studies have difficulty accumulating enough hemorrhage events to powerfully assess risk factors . To address these limitations , we performed a large casecontrol study to evaluate the relationship of increasing age and INR to the risk for intracranial hemorrhage among patients with nonvalvular atrial fibrillation . Methods Case- Patients We performed a casecontrol study comparing 2 groups : 1 ) case- patients with nonvalvular atrial fibrillation who developed intracranial hemorrhage while taking warfarin and 2 ) controls who were receiving anticoagulation for nonvalvular atrial fibrillation but did not develop intracranial hemorrhage . We found potential case- patients using the Partners HealthCare System Research Patient Data Registry , which can identify patients with specific International Classification of Diseases , Ninth Revision , Clinical Modification ( ICD-9-CM ) diagnoses by search ing the Massachusetts General Hospital billing system . We search ed for patients 18 years of age or older who had diagnoses of atrial fibrillation ( ICD-9-CM code 427.31 ) and intracranial hemorrhage ( ICD-9-CM codes 430 , 431 , 432.0 , 432.1 , 432.9 ) at any time from October 1993 to June 2002 . By 1993 , nearly all prothrombin time ratios at the hospital were reported as INRs . We review ed medical records to confirm whether patients were eligible , that is , whether they had intracranial hemorrhage documented by computed tomography or magnetic resonance imaging and documentation of warfarin therapy for atrial fibrillation at the time of the event . We excluded patients who were not taking warfarin at the time of hemorrhage ; those who were receiving anticoagulation for rheumatic heart disease , mitral stenosis , or mechanical valve placement ; those whose event was an ischemic stroke with hemorrhagic conversion ; or those in whom clinical factors may have led to hemorrhage independent of warfarin therapy . These factors included underlying anatomic brain abnormalities ( such as tumors or aneurysms ) , antecedent major head trauma ( skull fracture , trauma with loss of consciousness , motor vehicle injury , or neurosurgical procedures ) , or platelet count less than 50 109 cells/L. Starting in July 1994 , consecutive patients with intracerebral hemorrhage have been enrolled through the Massachusetts General Hospital emergency department as part of a longitudinal cohort study ( 23 ) . To vali date our automated search strategy , we compared our case-patient list with the list of patients identified through the cohort study and found that our search strategy missed only 4 patients with intracerebral hemorrhage . We obtained data on patient date of birth , sex , and ethnicity from computerized records . The type of hemorrhage ( intracerebral , subdural , subarachnoid , intraventricular , or epidural ) was determined through review of radiology reports . Data on presenting symptoms , history of minor head trauma , concomitant aspirin use , and disposition status were obtained from review of the admission medical record and were recorded on a st and ardized data collection form . We recorded the INR measurement obtained closest to the onset of symptoms . If an INR was not available or fresh frozen plasma or vitamin K was administered before the measurement , we considered INR data missing . We review ed medical charts for documentation of the following comorbid conditions : history of cerebrovascular disease ( defined as previous ischemic stroke or carotid artery disease ) , hypertension , congestive heart failure , coronary artery disease , diabetes mellitus , and cancer ( excluding nonmelanoma skin cancer ) . Controls Controls were sample d from patients managed by the Massachusetts General Hospital Anticoagulation Management Services clinic , which followed approximately 1000 patients receiving anticoagulation for atrial fibrillation at any given time during the study period . All patients who were followed in the anticoagulation clinic , received anticoagulation for atrial fibrillation , and had an INR measurement obtained in the same month and year as the given case date were assigned a r and om number . Six controls per case-patient were then r and omly selected . We matched case- patients to controls by INR date to account for any technical changes in INR testing that may have occurred over time . Because of this sampling method , an individual patient could potentially serve as a control for more than 1 case-patient ( 24 ) . Like case- patients , controls were 18 years of age or older ; were receiving anticoagulation for atrial fibrillation ; and had no documented rheumatic heart disease , mitral stenosis , or valve replacement . We sought data on potential confounders of the association of age , INR , and risk for intracranial hemorrhage , focusing on relevant comorbid conditions and combined use of aspirin with warfarin . We review ed available computerized discharge summaries , outpatient clinic notes , and medication lists from up to 2 years before the admission date . If combination warfarin and aspirin use was not documented , patients were considered to not be taking aspirin . Statistical Analysis Case- patients were categorized by type of hemorrhage : intracerebral , subdural , and other ( subarachnoid , intraventricular , or epidural ) . Clinical differences between types of hemorrhage were compared by using the KruskalWallis test for continuous variables ( age and INR ) and chi-square tests for categorical variables . We compared case- patients with controls by using multivariable conditional logistic regression , matching on INR date . Patient age was divided into 5-year intervals that were coded as indicator variables , and the odds of intracranial hemorrhage for each interval were compared with the odds of hemorrhage at a referent age of 70 to 74 years . The INR was divided into a set of ordered intervals that were coded as indicator variables . The relative odds for intracranial hemorrhage at each interval were calculated by using an INR of 2.0 to 3.0 as the referent category . In addition to age , INR , sex , and ethnicity , the following variables were included in the multivariable models to control for potential confounding effects of clinical factors and aspirin use : cerebrovascular disease , hypertension , congestive heart failure , coronary artery disease , diabetes mellitus , cancer , and concomitant aspirin use . If no records were available for review , comorbid conditions and aspirin use were coded as missing . We used multiple imputations for missing data on ethnicity , comorbid conditions , and aspirin use ( 25 ) . We tested for interactions between age and INR and comorbid conditions using 2-way interactions . None of the interaction terms were included in the model if they were not statistically significant when tested collectively . We tested the model 's goodness of fit using the HosmerLemeshow method ( 26 ) . Because the hospital 's anticoagulation clinic did not follow some case- patients before the event , and since factors relating to differences in outpatient care and monitoring could have confounded our analyses , we repeated these analyses in the subgroup of case- patients managed by the anticoagulation clinic . These restricted analyses", "INTRODUCTION Isolation of all pulmonary veins ( PV ) is advocated for treatment of paroxysmal atrial fibrillation ( PAF ) . However , the superior PVs are responsible for most AF triggers , whereas the inferior PVs carry the higher risk for ablation-induced ostial stenosis . The aim of this study was to compare a superior PV isolation approach with isolation of all PVs for treatment of PAF . METHODS AND RESULTS Fifty-two patients with PAF were r and omized to either left superior pulmonary vein ( LSPV ) isolation followed by additional isolation of the right superior pulmonary vein ( RSPV ) in case of AF recurrence ( group A , n = 27 ) or isolation of all four PVs followed by a repeat procedure in case of recurrence ( group B , n = 25 ) . At 1-year follow-up , 11 patients ( 41 % ) in group A and 8 patients ( 32 % ) in group B had AF relapse ( P = 0.55 ) . No significant differences in AF relapse were detected between groups at 3 and 12 months ( log rank = 0.36 , P = 0.54 ) and by Cox proportional hazards model analysis ( P = 0.62 ) . Nonsignificant PV stenosis was detected in two patients from group B. Total radiofrequency energy delivery and fluoroscopy and procedure times were lower in group A : 8.9 + /- 1.4 minutes vs 25.6 + /- 3.7 minutes ( P superior PVs isolation approach confers equal success rates but with reduced radiofrequency energy delivery and fluoroscopy and procedure times compared to isolation of all PVs at the initial ablation attempt ", "AIMS Direct current cardioversion of persistent atrial fibrillation is one of the most widely used and effective treatments for the restoration of sinus rhythm , but may be hampered by a low success rate and a high percentage of early recurrence . Pre-treatment with amiodarone or a glucose-insulin-potassium solution could improve the efficacy of electrical cardioversion by reversing the partially depolarized diastolic potential of the subsidiary pacemakers in atrial fibrillation . In a controlled r and omized study , we assessed the effectiveness of electrical cardioversion in patients with persistent atrial fibrillation after pre-treatment with amiodarone or potassium infusion and the efficacy of amiodarone in maintaining sinus rhythm after electrical cardioversion . METHODS AND RESULTS Ninety-two patients with persistent atrial fibrillation ( > 2 weeks duration ) were prospect ively r and omized into three matched groups : A ( n=31 , oral amiodarone 400 mg . day(-1)1 month before and 200 mg . day(-1)2 months after cardioversion ) , B ( n=31 , 180 mg . day(-1)oral diltiazem 1 month before and 2 months after cardioversion and 80 mmol potassium , 50 UI insulin in 500 ml 30 % glucose solution 24 h before cardioversion ) and C ( n=30 , control patients , 180 mg . day(-1)oral diltiazem 1 month before and 2 months after cardioversion ) . Before cardioversion all patients were under 4 weeks effective oral anticoagulant therapy ( warfarin ) . Before electrical cardioversion , the rate of spontaneous conversion to sinus rhythm was higher in group A ( 25 % ) than groups B ( 6 % ) or C ( 3 % ) ( P Electrical cardioversion was more successful in group A ( 88 % ) than groups B ( 56 % ) or C ( 65 % ) ( P electrical thresholds for effective cardioversion were lower in group B than the other groups ( P early recurrence of atrial fibrillation was similar in the three groups ( P = ns ) , while at 2 months the recurrence rate was lower in group A ( 32 % ) than groups B ( 56 % ) or C ( 52 % ) ( P amiodarone , compared with oral diltiazem or glucose-insulin-potassium treatments , induces a significantly high percentage of instances of spontaneous conversion , increases electrical cardioversion efficacy and reduces atrial fibrillation recurrence", "BACKGROUND Maintenance of sinus rhythm is the main therapeutic goal in patients with atrial fibrillation . However , recurrences of atrial fibrillation and side effects of antiarrhythmic drugs offset the benefits of sinus rhythm . We hypothesized that ventricular rate control is not inferior to the maintenance of sinus rhythm for the treatment of atrial fibrillation . METHODS We r and omly assigned 522 patients who had persistent atrial fibrillation after a previous electrical cardioversion to receive treatment aim ed at rate control or rhythm control . Patients in the rate-control group received oral anticoagulant drugs and rate-slowing medication . Patients in the rhythm-control group underwent serial cardioversions and received antiarrhythmic drugs and oral anticoagulant drugs . The end point was a composite of death from cardiovascular causes , heart failure , thromboembolic complications , bleeding , implantation of a pacemaker , and severe adverse effects of drugs . RESULTS After a mean ( + /-SD ) of 2.3+/-0.6 years , 39 percent of the 266 patients in the rhythm-control group had sinus rhythm , as compared with 10 percent of the 256 patients in the rate-control group . The primary end point occurred in 44 patients ( 17.2 percent ) in the rate-control group and in 60 ( 22.6 percent ) in the rhythm-control group . The 90 percent ( two-sided ) upper boundary of the absolute difference in the primary end point was 0.4 percent ( the prespecified criterion for noninferiority was 10 percent or less ) . The distribution of the various components of the primary end point was similar in the rate-control and rhythm-control groups . CONCLUSIONS Rate control is not inferior to rhythm control for the prevention of death and morbidity from cardiovascular causes and may be appropriate therapy in patients with a recurrence of persistent atrial fibrillation after electrical cardioversion", "BACKGROUND There are two approaches to the treatment of atrial fibrillation : one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm , and the other is the use of rate-controlling drugs , allowing atrial fibrillation to persist . In both approaches , the use of anticoagulant drugs is recommended . METHODS We conducted a r and omized , multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death . The primary end point was overall mortality . RESULTS A total of 4060 patients ( mean [ + /-SD ] age , 69.7+/-9.0 years ) were enrolled in the study ; 70.8 percent had a history of hypertension , and 38.2 percent had coronary artery disease . Of the 3311 patients with echocardiograms , the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent . There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy ( mortality at five years , 23.8 percent and 21.3 percent , respectively ; hazard ratio , 1.15 [ 95 percent confidence interval , 0.99 to 1.34 ] ; P=0.08 ) . More patients in the rhythm-control group than in the rate-control group were hospitalized , and there were more adverse drug effects in the rhythm-control group as well . In both groups , the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic . CONCLUSIONS Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy , and there are potential advantages , such as a lower risk of adverse drug effects , with the rate-control strategy . Anticoagulation should be continued in this group of high-risk patients", "AIMS Circumferential pulmonary vein isolation ( CPVI ) is an established strategy for atrial fibrillation ( AF ) ablation . Superior vena cava ( SVC ) , by harbouring the majority of non-pulmonary vein ( PV ) foci , is the most common non-PV origin for AF . However , it is unknown whether CPVI combined with SVC isolation ( SVCI ) could improve clinical results and whether SVCI is technically safe and feasible . METHODS AND RESULTS A total of 106 cases ( 58 males , average age 66.0 + /- 8.8 years ) with paroxysmal AF were included for ablation . They were allocated r and omly to two groups : CPVI group ( n = 54 ) and CPVI + SVCI group ( n = 52 ) . All cases underwent the procedure successfully . Pulmonary vein isolation was achieved in all cases . The procedural time and fluoroscopic time were comparable between the two groups . The mean ablation time for SVC was 7.8 + /- 2.7 min . Superior vena cava isolation was obtained in 50/52 cases . In the remaining two cases , SVCI was not achieved because of obviating diaphragmatic nerve injury . During a mean follow-up of 4 + /- 2 months , 12 ( 22.2 % ) cases in the CPVI group and 10 ( 19.2 % ) cases in the CPVI + SVCI group had atrial tachyarrhythmias ( ATa ) recurrence ( P = 0.70 ) . Nine of 12 cases in the CPVI group and 8/10 cases in the CPVI + SVCI group underwent reablation ( P = 0.86 ) , and PV reconnection occurred in 7/9 cases in the CPVI group and in 8/8 cases in the CPVI + SVCI group . All PV reconnection was reisolated by gaps ablation . There was no SVC reconnection in the CPVI + SVCI group . In two cases without PV reconnection from the CPVI group , SVC-originated short run of atrial tachycardia was identified and eliminated by the SVCI . At the end of 12 months of follow-up , 50 cases ( 92.6 % ) in the CPVI group and 49 ( 94.2 % ) in the CPVI + SVC group were free of ATa recurrence ( P = 0.73 ) . CONCLUSION In our series of paroxysmal AF patients , empirically adding SVCI to CPVI did not significantly reduce the AF recurrence after ablation . Superior vena cava isolation may be useful , however , in selected patients in whom the SVC is identified as a trigger for AF . However , because of the preliminary property of the study and its relatively small sample size , the impact of SVCI on clinical results should be evaluated in a large series of patients", "BACKGROUND Both segmental ostial and circumferential extraostial pulmonary vein ( PV ) isolation have been proven effective in the treatment of atrial fibrillation ( AF ) . However , the recurrence of AF and PV conduction after the 2 ablation strategies has never been compared in a r and omized study . METHODS A total of 100 consecutive patients ( age 56 + /- 10 ; 71 men ) with symptomatic AF ( paroxysmal , 51 ; persistent , 49 ) were r and omized to segmental ostial ( n = 54 ) or circumferential extraostial ( n = 46 ) PV isolation . A circular catheter positioned at the ostium of each target PV guided the ostial PV isolation . Extraostial PV isolation was performed by encircling the paired left and right PVs , respectively , guided by an electroanatomic mapping system . RESULTS A total of 84 % of the patients had recurrent AF after the first PV isolation procedure , showing 72 % with AF and 12 % with organized left atrial tachycardia . In patients undergoing reablation , all but 2 patients had recurrence of left atrium PV conduction ( > 95 % ) . During a mean follow-up of 12 months without antiarrhythmic medication , 57 % of patients who underwent extraostial PV isolation were free of arrhythmia symptoms compared with 31 % of patients who underwent ostial PV isolation ( P success rate between the 2 ablation strategies was mainly seen in patients known with persistent AF ( 52 % and 15 % , respectively ; P = .02 ) as opposed to patients with paroxysmal AF ( 65 % and 46 % , respectively ; P = .26 ) . CONCLUSIONS Overall , the more proximal , extraostial PV isolation was found to be superior to ostial PV isolation , especially in patients known with persistent AF . A high recurrence rate of 84 % after a single complete PV isolation procedure was seen . At reablation , more than 95 % had recurrence of left atrium PV conduction regardless of the procedure used , supporting the idea that complete PV isolation seems essential to prevent arrhythmia recurrences", "The limited efficacy and proarrhythmic risks of antiarrhythmia agents have result ed in alternative therapeutic approaches . Radiofrequency ablation has been reported to be an effective treatment of patients with atrial fibrillation . However , there is no r and omized clinical trial comparing drug and radiofrequency ablation . The authors r and omized 30 patients with chronic atrial fibrillation refractory to medication into amiodarone and radiofrequency ablation . The primary objective of this study was to compare the efficacy of amiodarone and radiofrequency ablation in the maintenance of sinus rhythm at 1 year after r and omization . Pulmonary vein isolation and linear ablation of right atrium was the technique used for radiofrequency ablation . There were no significant differences in baseline patient characteristics between the 2 groups . The results of this study showed that the probability of free from atrial fibrillation was better in the radiofrequency ablation group compared to amiodarone ( 78.6 % in the ablation group and 40 % in the amiodarone group , p = 0.018 ) . Radiofrequency ablation results in a significant reduction in symptoms relating to atrial fibrillation and a significant improvement in quality of life , whereas amiodarone had no significant effect on symptoms and quality of life . There was an ischemic stroke as a major complication related to radiofrequency ablation . Amiodarone was associated with adverse effects in 46.7 per cent of patients and needed discontinuation in 1 patient . In conclusion , radiofrequency ablation is an effective alternative treatment in patients with atrial fibrillation refractory to medication", "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" ]

[ "OBJECTIVE To study the effects of varicocele treatment on testicular function in adolescents . DESIGN A prospect i ve controlled study in 88 r and omly selected adolescents . SETTING All participants were referred to the fertility outpatient clinic of our university hospital . PARTICIPANTS All participants with a varicocele were r and omly assigned into two groups . Group 1 ( n = 33 ) was not treated , whereas group 2 ( n = 34 ) was treated . A similar group of healthy volunteers without a varicocele served as a control group ( group 3 , n = 21 ) . INTERVENTIONS Testes volumes were measured at intake and during follow-up using an orchiometer . Semen analysis was performed according to st and ard procedures both at intake and after 1 year of follow-up . Serum hormone levels were determined at intake using a radioimmunoassay . Treatment was performed by means of transcatheter embolization of the left testicular vein . MAIN OUTCOME MEASURES Testes volumes and semen quality at intake and after 1 year of follow-up were compared within and between the three groups . Hormonal parameters were determined at intake only . RESULTS Before treatment , the mean left testis volume in groups 1 ( n = 26 ) and 2 ( n = 27 ) ( 20.0 mL ; 95 % confidence interval [ CI ] : 18.2 to 21.8 and 21.6 mL ; 95 % CI : 19.4 to 23.8 , respectively ) were significantly smaller than those in the control group ( n = 19 ) ( 24.5 mL ; 95 % CI : 22.7 to 26.4 ) . During follow-up , left testis volumes of the treated group were comparable with those in the control group ( 24.2 mL ; 95 % CI : 22.2 to 26.1 and 24.8 mL ; 95 % CI : 23.0 to 26.7 respectively ) and significantly ( P ( P was observed after treatment . Semen parameters before treatment were not significantly different between the three groups . Sperm concentration increased significantly ( P semen quality in the untreated and control groups did not change . Although both testes volumes and sperm concentration improved in the treated group , these phenomena were not consistently correlated to each other . CONCLUSIONS Although not apparent in all adolescents , varicocele correction result ed in an increase in left testis volume and sperm concentration . At this moment , it is not clear if early preventive treatment of varicocele in adolescents , in time , will have a positive effect on testicular function", "INTRODUCTION Adolescent males with varicoceles present a dilemma for surveillance and treatment . Testicular volumetrics have not been shown to predict SA outcomes . Serial SAs are thus recommended in asymptomatic adolescent males with varicoceles and normal testicular development , but the natural history of semen parameters is unknown . OBJECTIVE To explore the natural history of semen parameters in adolescent boys with a left varicocele under active surveillance . STUDY DESIGN Adolescents with an asymptomatic unilateral left varicocele , Tanner V development , normal testicular volumes , and an initial SA were retrospectively review ed in a single-institution prospect ively followed cohort . Total motile count ( TMC ) was calculated . A cutoff of TMC Z 20 million was used to dichotomize SA results into \" normal \" or \" poor . \" Those with poor SA were offered repeat SA . Cumulative probabilities of normal TMC over successive rounds of SA were calculated . Bivariate models were used to explore associations of a second consecutive poor TMC with age and varicocele grade . RESULTS A total of 216 patients provided an initial SA between 1992 and 2015 . We excluded 17 for a history of cryptorchidism or incomplete SA data for a final cohort of 199 patients with median follow-up of 3.3 years ( interquartile range 1.5 - 5.6 years ) . The mean age at initial SA was 17.9 years ( range 14.8 - 21.8 years ) . One hundred and nine out of 199 had an initial normal TMC . Of the 90 out of 199 with an initially poor TMC , 51 had repeat SA and 24 of the 51 patients improved to normal TMC . Of the 27 patients with two consecutive poor TMCs , 15 had a third SA and five out of 15 improved to normal TMC . Thus , cumulatively , 55 % , 67 % , and 69 % of all patients had a normal TMC after an initial , second , and third SA , respectively . However , fewer patients in each round of SA normalized their TMC ( Figure ) . Neither age nor varicocele grade was associated with a second consecutive poor TMC . DISCUSSION Two-thirds of Tanner V boys with an uncorrected varicocele and normal testicular volumes achieve a normal TMC regardless of varicocele grade or age . Despite Tanner V development , 47 % with an initial \" poor \" SA will improve to normal status without surgery . However , a small subgroup of patients will have persistently poor TMC and thus should be targeted in future research for timely intervention . CONCLUSION Semen parameters improve over time . SA should be followed and repeated at least once in symptomatic Tanner V boys with varicoceles", "The aim of this prospect i ve study was to assess long-term functional results ( spermiograms ) in subjects who underwent laparoscopic varicocelectomy via either of 2 procedures ( ligation or preservation of testicular artery ) . A total of 122 patients underwent laparoscopic varicocelectomy performed via either of the 2 different procedures : complete ligation of the spermatic vessels or preservation of the spermatic artery . After surgery when patients achieved 18 years , they were asked to undergo semen analysis . Spermiogram results were divided into 2 subgroups : \" normal \" and \" abnormal . \" We analyzed volume , sperm count per mL , percentage of motile spermatozoa , percentage of normal spermatozoa , and percentage of vitality for each group . Both groups showed the same results in terms of \" normal \" and \" abnormal \" spermiograms ( World Health Organization criteria ) , but analysis showed higher sperm concentration per mL , sperm motility , volume , vitality , and rate of morphologically normal sperm for the group with arteries preserved and \" normal \" spermiograms ( P semen quality . Therefore , we believe that surgical treatment of varicocele should be carried out using procedures involving artery preservation", "OBJECTIVE To compare the effect of transumbilical single-site single-port with that of transumbilical single-site double-port laparoscopic varicocelectomy in the treatment of varicocele in adolescents . METHODS We r and omly assigned 80 varicocele patients aged 10 - 16 years to two groups of equal number to receive transumbilical single-site single-port and single-site double-port laparoscopic varicocelectomy , respectively . We compared the operation time , postoperative hospital stay , incisional pain , complications and satisfaction with the abdominal cosmetic outcomes between the two groups . RESULTS All the operations were successfully performed . The double-port group showed a significantly higher score on the Visual Analogue Scale than the single-port group ( 4.8 + /- 1.4 vs 3.6 + /- 1.1 , t = -4.986 , P operation time ( [ 29.8 + /- 4.2 ] vs [ 31.2 + /- 4.6 ] min , t = 1.383 , P = 0.171 ) , postoperative hospital stay ( [ 1.95 + /- 0.7 ] vs [ 1.82 + /- 0.8 ] d , t = -0.784 , P = 0.436 ) , complications ( 0 vs 0 ) and scores on the satisfaction with abdominal cosmetic outcomes ( 4.6 + /- 0.6 vs 4.8 + /- 0.5 , t = 1.253 , P = 0.214 ) . No recurrence , umbilical hernia , hydrocele and orchiatrophy were found in the two groups of patients at 6 months after operation , and no visible scar was observed on the abdominal surface . CONCLUSION With strict surgical indications , single-site single-port and single-site double-port laparoscopic varicocelectomies have similar clinical effects in the treatment of varicocele , which leave no scar on the abdominal surface . Single-site double-port laparoscopy needs no special instruments and therefore is worthier of wide clinical application", "BACKGROUND / PURPOSE The purpose of this investigation was to evaluate the advantages and the shortcomings of laparoscopic varicocelectomy compared with open traditional treatment of varicoceles . METHODS A total of 654 patients were operated on for left-sided varicoceles over 5 years from 1995 to 2000 . To evaluate the clinical efficiency of the treatment , the patients were divided r and omly into 2 groups . Laparoscopic varicocelectomy ( LV ) was performed on 434 patients , and open varicocelectomy ( OV ) in 220 patients . Outcome data looked at relapse rate , presence of hydrocele , wound complications , and testicular or scrotal edema . Operating time , postoperative length of stay , and pain control also were compared . In both groups , the operations were performed by Palomo 's technique with preservation of lymphatics and mass ligation of the artery and veins in the retroperitoneum above the internal inguinal ring . RESULTS In LV versus OV , relapse rates were 1.84 % versus 1.36 ( P hydrocele occurrence was 0.23 % versus 1.82 % ( P wound complication was 0.23 % versus 7.73 % , and testicular or scrotal edema was 3.9 % versus 13.1 % . LV hospital stay was an average of 3 days versus 7 days for OV . Operating time was 15 minutes for LV versus 26 minutes in open . Postoperative analgesic use was almost cut in half with LV . CONCLUSION The clinical efficacy of LV is superior to traditional OV", "OBJECTIVE Hydrocele , the main complication of laparoscopic varicocelectomy , is thought to result from a disruption of gonadal lymphatics . The aim of this study was to evaluate the effectiveness of patent blue V dyeing to identify and preserve lymphatic vessels and to assess whether the lymphatic sparing technique avoids postoperative hydrocele in adolescent boys undergoing a laparoscopic procedure . MATERIAL S AND METHODS Fifty-two ( 52 ) boys affected by varicocele Grade III ( range , 12 - 16 years ) underwent a left-sided laparoscopic varicocelectomy . Twenty-six ( 26 ) boys were r and omly assigned to a lymphatic nonsparing ( LNS ) group , and the others to a lymphatic sparing ( LS ) group . Before surgery in the LS group , 2 mL of patent blue V was injected under the tunica dartos on the left side . RESULTS All varicocelectomies were performed laparoscopically . Lymphatic vessels were identified in 23 ( 88.5 % ) boys of the LS group . In the remaining three ( 11.5 % ) , the lymphatics could not be identified clearly . No adverse local or generalized reactions were noted . At a mean follow-up of 14 months , no recurrent varicocele or testicular volume reduction were detected . Hydrocele developed in 4 LNS patients and 1 was operated on . No patient from the LS group developed a hydrocele . CONCLUSIONS Staining gonadal lymph vessels with patent blue V is an effective and simple method of visualization of the lymphatic drainage from the testis . Blue-stained lymph vessels could be readily distinguished and preserved during a laparoscopic varicocelectomy , which results in a decrease of hydrocele development . To vali date an efficacy of vital staining of lymphatic vessels in avoiding hydrocele formation , a larger series and longer follow-up are necessary", "Because the treatment of a varicocele in adolescents remains controversial , we undertook a prospect i ve study in 51 male adolescents , aged 15 - 21 years , who were referred for a varicocele . Twenty-nine patients were treated with high retroperitoneal ligation of the left spermatic vein , and 22 were untreated . Eighteen healthy adolescent volunteers without a varicocele were also assessed . Testicular volume was measured using an orchiometer , and semen analyses were carried out at referral and after 1 year of follow-up . In addition , serum luteinizing hormone ( LH ) , follicle-stimulating hormone ( FSH ) and testosterone levels were estimated by radioimmunoassay . Both patient groups had significantly smaller testis volumes than the controls at the outset . In the follow-up , the treated patients had testis volumes similar to those of the controls . Both testes increased significantly in volume after treatment . Although semen parameters were comparable in all groups initially , sperm concentration increased significantly after treatment of the varicocele . We concluded that varicocele treatment in adolescents leads to increased testis volume and a higher sperm concentration ; however , whether early treatment will improve testicular function remains to be eluci date", "PURPOSE We design ed a r and omized prospect i ve study of male adolescents with moderate and severe varicoceles to determine whether prophylactic varicocele repair is beneficial . MATERIAL S AND METHODS We evaluated 2,100 boys ( 10 to 20 years old ) for genitourinary abnormalities . From this population 2 groups of adolescents 15 to 19 years old with grade 2 or 3 varicoceles were created , including 88 who underwent varicocele repair and 36 controls . Testicular volume and pampiniform vein diameter were measured , and Doppler ultrasound was performed . RESULTS After 12 months volume of the involved left testis increased to almost normal in treated boys ( mean atrophy index 12.7 % at surgery and 3 % 12 months later ) . In controls the corresponding atrophy indexes were 10 and 9 % , respectively . The relative increase in left testicular volume was 26 % in the surgery group and 11 % in controls . In the surgery group mean pampiniform vein diameter decreased from 2.8 preoperatively to 2 mm . postoperatively but there was no change in controls . CONCLUSIONS Varicocele repair in adolescents with moderate and severe varicocele reversed testicular growth arrest and result ed in catch-up growth within 12 month of surgery", "OBJECTIVE To compare the surgical outcomes of subinguinal and high inguinal approaches for microsurgical varicocelectomy . METHODS A total of 81 patients with left varicocele were r and omly assigned to undergo microsurgical left varicocelectomy by the subinguinal ( n = 41 ) or high inguinal ( n = 40 ) approach . These two techniques were compared with regard to the operative parameters , complications and testicular growth . Anatomical parameters , including the numbers and diameters of internal spermatic arteries , veins and lymphatic vessels , were recorded . RESULTS The microsurgical step was significantly shorter for the high inguinal approach compared with the subinguinal approach ( 25.5 vs 33.3 min , respectively , P numbers of preserved arteries and ligated veins were significantly greater and the artery size was significantly smaller for the subinguinal ( 1.6 arteries , 11.5 veins and 1.1 mm , respectively ) compared with the high inguinal approach ( 1.2 arteries , 7.3 veins and 1.3 mm ; P postoperative hydrocele , and three with persistent scrotal pain after treatment with the subinguinal approach . The postoperative catch-up growth rates at 24 months were 70 % and 78 % for the subinguinal and high inguinal approaches , respectively . CONCLUSIONS The microsurgical subinguinal and high inguinal approaches seem to yield similar success rates in terms of testicular growth . However , the high inguinal approach is easier to carry out , as it requires fewer divisions of veins and is associated with a larger diameter of the spermatic artery", "OBJECTIVE To investigate different varicocele hemodynamic patterns ( shunt type vs. stop type ) as predictors of new-onset testicular hypotrophy or recurrence after varicocelectomy . DESIGN Prospect i ve clinical study . SETTING Department of pediatric urology , children 's hospital medical center . PATIENT(S ) Seventy-four children and adolescents with varicocele . INTERVENTION(S ) Based on ultrasound findings , patients were classified into shunt-type or stop-type varicocele groups . All patients with stop-type varicocele and testicular volume discrepancy of ≥20 % underwent retroperitoneal varicocelectomy and internal spermatic vein ligation . Patients with shunt-type varicocele and ≥20 % testicular asymmetry were r and omly divided to undergo either retroperitoneal varicocelectomy ( ligation of internal spermatic vein ) or inguinal varicocelectomy with ligation of both internal and external spermatic veins . Patients with testicular volume discrepancy of 20 % were put on conservative management . MAIN OUTCOME MEASURE(S ) Occurrence of new-onset asymmetry among untreated patients and recurrence rate among operated patients . RESULT ( S ) Patients with shunt-type varicocele who did not undergo surgery revealed a higher risk of developing asymmetry during follow-up ( odds ratio 10.5 ) . Ligation of both internal and external spermatic veins in shunt-type patients was associated with significantly decreased rate of recurrence ( 6.3 % ) compared with retroperitoneal approach ( 30.8 % ) . CONCLUSION ( S ) Shunt-type varicocele is associated with a higher risk of testicular hypotrophy among untreated patients . In addition , recurrence rate in shunt-type patients who underwent inguinal varicocelectomy was lower compared with retroperitoneal approach" ]

[ "Background — Physical activity ( PA ) is well known to reduce the risk of cardiovascular disease . We hypothesized that regular PA , possibly acting through reductions in blood pressure and body mass index ( BMI ) , would reduce the risk of incident atrial fibrillation ( AF ) in women . Methods and Results — We prospect ively followed 34 759 women who reported their leisure-time PA levels for the occurrence of AF . We estimated energy expenditure in metabolic equivalent (MET)-h/wk and vali date d self-reported AF with medical records . The mean ( SD ) age of the 34 759 participants was 54.6 ( 7.0 ) years , the mean BMI was 26.0 ( 5.0 ) kg/m2 , 26.5 % had hypertension , and the median ( IQR ) PA was 8.4 ( 2.8 , 20.4 ) MET-h/wk . After a median of 14.4 years of observation , 968 women had development of AF . In age- , cholesterol- , smoking- , alcohol- , diabetes- , and race-adjusted models , increasing quintiles of PA were associated with reduced risks of AF ( hazard ratio for extreme quintiles , 0.82 ; 0.66 to 1.01 ; P trend=0.007 over quintiles ) . Although this association was not substantially different after adjusting for hypertension ( 0.87 ; 0.70 to 1.07 ; P trend 0.02 ) , it was attenuated after adjustment for BMI ( 0.99 ; 0.80 to 1.23 ; P trend=0.22 ) . Women who achieved the federal government 's recommendation of 7.5 MET-h/wk of PA were at reduced risk of AF compared with those who did not ( 0.86 ; 0.75 to 0.98 ; P=0.03 ) . This association was also attenuated by BMI ( 0.96 ; 0.84 to 1.10 ; P=0.57 ) . Conclusions — In middle-aged women , physical activity was associated with a modestly reduced risk of AF . However , this relationship was no longer significant after controlling for body mass index", "Background No previous studies have examined the interplay among socioeconomic status , sex , and race with the risk of atrial fibrillation ( AF ) . Methods and Results We prospect ively followed 14 352 persons ( 25 % black , 75 % white , 55 % women , mean age 54 years ) who were free of AF and participating in the Atherosclerosis Risk in Communities ( ARIC ) study . Socioeconomic status was assessed at baseline ( 1987–1989 ) through educational level and total family income . Incident AF through 2009 was ascertained from electrocardiograms , hospitalizations , and death certificates . Cox regression was used to estimate hazard ratios and 95 % CIs of AF for education and family income . Interactions were tested between socioeconomic status and age , race , or sex . Over a median follow‐up of 20.6 years , 1794 AF cases occurred . Lower family income was associated with higher AF risk ( hazard ratio 1.45 , 95 % CI 1.27 to 1.67 in those with income less than $ 25 000 per year compared with those with $ 50 000 or more per year ) . The association between education and AF risk varied by sex ( P=0.01 ) , with the lowest education group associated with higher AF risk in women ( hazard ratio 1.88 , 95 % CI 1.55 to 2.28 ) but not in men ( hazard ratio 1.15 , 95 % CI 0.97 to 1.36 ) compared with the highest education group . Adjustment for cardiovascular risk factors attenuated the associations . There were no interactions with race or age . Blacks had lower AF risk than whites in all income and education groups . Conclusions Lower family income was associated with a higher AF risk overall , whereas the impact of education on AF risk was present only in women . Differences in socioeconomic status do not explain the lower risk of AF in blacks compared with whites", "Background —Low-density lipoprotein ( LDL ) cholesterol is a strong risk factor for atherosclerosis but has an inverse association with atrial fibrillation ( AF ) . We aim ed to provide insight into the paradoxical association of LDL cholesterol with AF by evaluating the relationship of various lipoprotein measures and incident AF . Methods and Results —We prospect ively evaluated lipoprotein measures among 23 738 healthy middle-aged and older women ( median follow-up 16.4 years ; N=795 incident AF events ) . Baseline LDL cholesterol was directly measured , lipoprotein particle concentrations and size were measured by nuclear magnetic resonance spectroscopy , and apolipoproteins were measured by immunoassay . Cox regression models were adjusted for age , AF risk factors , inflammatory , and dysglycemic biomarkers . After multivariable adjustment , inverse associations with AF were observed ( hazard ratio , 95 % confidence interval for top versus bottom quintile , P value ) for LDL cholesterol ( 0.72 , 0.56–0.92 , P=0.009 ) , the total number of LDL particles ( 0.77 , 0.60–0.99 , P=0.045 ) , and very-low-density lipoprotein particles ( 0.78 , 0.61–0.99 , P=0.04 ) , which was driven by the number of cholesterol-poor small LDL ( 0.78 , 0.61–1.00 , P=0.05 ) and small very-low-density lipoprotein particles ( 0.78 , 0.62–0.99 , P=0.04 ) . By contrast , the larger cholesterol-rich LDL particles and all high-density lipoprotein measures were not associated with AF in multivariable models . Adjustment for inflammatory and dysglycemic biomarkers had minimal impact on these associations . Conclusions —In this prospect i ve study , the inverse association between LDL cholesterol and AF extended to several other atherogenic lipoproteins , and these associations are unlikely to be mediated by direct cholesterol effects . Clinical Trial Registration — Clinical Trials.gov ; Unique Identifier : NCT00000479", "Summary Background The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared . In this study , we aim ed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease . Methods We used linked electronic health records from 1997 to 2010 in the CALIBER ( CArdiovascular research using LInked Bespoke studies and Electronic health Records ) programme to assemble a cohort of 1·25 million patients , 30 years of age or older and initially free from cardiovascular disease , a fifth of whom received blood pressure-lowering treatments . We studied the heterogeneity in the age-specific associations of clinical ly measured blood pressure with 12 acute and chronic cardiovascular diseases , and estimated the lifetime risks ( up to 95 years of age ) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30 , 60 , and 80 years . This study is registered at Clinical Trials.gov , number NCT01164371 . Findings During 5·2 years median follow-up , we recorded 83 098 initial cardiovascular disease presentations . In each age group , the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90–114 mm Hg and diastolic blood pressure of 60–74 mm Hg , with no evidence of a J-shaped increased risk at lower blood pressures . The effect of high blood pressure varied by cardiovascular disease endpoint , from strongly positive to no effect . Associations with high systolic blood pressure were strongest for intracerebral haemorrhage ( hazard ratio 1·44 [ 95 % CI 1·32–1·58 ] ) , subarachnoid haemorrhage ( 1·43 [ 1·25–1·63 ] ) , and stable angina ( 1·41 [ 1·36–1·46 ] ) , and weakest for abdominal aortic aneurysm ( 1·08 [ 1·00–1·17 ] ) . Compared with diastolic blood pressure , raised systolic blood pressure had a greater effect on angina , myocardial infa rct ion , and peripheral arterial disease , whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure . Pulse pressure associations were inverse for abdominal aortic aneurysm ( HR per 10 mm Hg 0·91 [ 95 % CI 0·86–0·98 ] ) and strongest for peripheral arterial disease ( 1·23 [ 1·20–1·27 ] ) . People with hypertension ( blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs ) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3 % ( 95 % CI 62·9–63·8 ) compared with 46·1 % ( 45·5–46·8 ) for those with normal blood pressure , and developed cardiovascular disease 5·0 years earlier ( 95 % CI 4·8–5·2 ) . Stable and unstable angina accounted for most ( 43 % ) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years , whereas heart failure and stable angina accounted for the largest proportion ( 19 % each ) of years of life lost from index age 80 years . Interpretation The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range , and that diastolic and systolic associations are concordant , are not supported by the findings of this high-resolution study . Despite modern treatments , the lifetime burden of hypertension is substantial . These findings emphasise the need for new blood pressure-lowering strategies , and will help to inform the design of r and omised trials to assess them . Funding Medical Research Council , National Institute for Health Research , and Wellcome Trust", "Background Atrial fibrillation ( AF ) is the most common cardiac arrhythmia and is associated with increased risk of stroke and death . Obesity is an independent risk factor for AF , but modifiers of this risk are not well known . We studied the roles of obesity , physical activity , and their interaction in conferring risk of incident AF . Methods and Results The Women 's Health Initiative ( WHI ) Observational Study was a prospect i ve observational study of 93 676 postmenopausal women followed for an average of 11.5 years . Incident AF was identified using WHI‐ascertained hospitalization records and diagnostic codes from Medicare cl aims . A multivariate Cox 's hazard regression model adjusted for demographic and clinical risk factors was used to evaluate the interaction between obesity and physical activity and its association with incident AF . After exclusion of women with prevalent AF , incomplete data , or underweight body mass index ( BMI ) , 9792 of the remaining 81 317 women developed AF . Women were , on average , 63.4 years old , 7.8 % were African American , and 3.6 % were Hispanic . Increased BMI ( hazard ratio [ HR ] , 1.12 per 5‐kg/m2 increase ; 95 % confidence interval [ CI ] , 1.10 to 1.14 ) and reduced physical activity ( > 9 vs. 0 metabolic equivalent task hours per week ; HR , 0.90 ; 95 % CI , 0.85 to 0.96 ) were independently associated with higher rates of AF after multivariate adjustment . Higher levels of physical activity reduced the AF risk conferred by obesity ( interaction P=0.033 ) . Conclusions Greater physical activity is associated with lower rates of incident AF and modifies the association between obesity and incident AF", "Background — Vigorous exertion and endurance training have been reported to increase atrial fibrillation ( AF ) . Associations of habitual light or moderate activity with AF incidence have not been evaluated . Methods and Results — We prospect ively investigated associations of leisure-time activity , exercise intensity , and walking habits , assessed at baseline and up date d during follow-up visits , with incident AF , diagnosed by annual 12-lead ECGs and hospital discharge records , from 1989 to 2001 among 5446 adults ≥65 years of age in the Cardiovascular Health Study . During 47 280 person-years of follow-up , 1061 new AF cases occurred ( incidence 22.4/1000 person-years ) . In multivariable-adjusted analyses , leisure-time activity was associated with lower AF incidence in a grade d manner , with 25 % ( hazard ratio [ HR ] 0.75 , 95 % confidence interval [ CI ] 0.61 to 0.90 ) , 22 % ( HR 0.78 , 95 % CI 0.65 to 0.95 ) , and 36 % ( HR 0.64 , 95 % CI 0.52 to 0.79 ) lower risk in quintiles 3 , 4 , and 5 versus quintile 1 ( P for trend . Exercise intensity had a U-shaped relationship with AF ( quadratic P=0.02 ) : Versus no exercise , AF incidence was lower with moderate-intensity exercise ( HR 0.72 , 95 % CI 0.58 to 0.89 ) but not with high-intensity exercise ( HR 0.87 , 95 % CI 0.64 to 1.19 ) . Walking distance and pace were each associated with lower AF risk in a grade d manner ( P for trend lower AF incidence than individuals in quartile 1 . Findings appeared unrelated to confounding by comorbidity or indication . After evaluation of cut points of moderate leisure-time activity ( ≈600 kcal/week ) , walking distance ( 12 blocks per week ) , and pace ( 2 mph ) , 26 % of all new AF cases ( 95 % CI 7 % to 43 % ) appeared attributable to absence of these activities . Conclusions — Light to moderate physical activities , particularly leisure-time activity and walking , are associated with significantly lower AF incidence in older adults", "BACKGROUND Evidence regarding the relationship between different levels of alcohol consumption and the risk of atrial fibrillation ( AF ) is currently limited in Asian population s. METHODS AND RESULTS Between 1991 and 1995 , a total of 8,602 Japanese men and women aged 30 - 80 years took part in the first examination of the Circulatory Risk in Communities Study ( CIRCS ) , a population -based cohort study in Japanese communities . An interviewer obtained detailed information on weekly alcohol intake . During the follow-up period , the incidence of AF was ascertained from annual ECG records , the subject 's medical history of AF , and cardiovascular disease surveillance . The hazard ratios ( HRs ) of incident AF and the 95 % confidence intervals ( CIs ) relative to the never-drinking group were calculated with adjustment for potential confounding factors by using the Cox proportional hazard model . During a median follow-up period of 6.4 years , 296 incidents of AF occurred . A higher incidence of AF was observed among participants with an ethanol intake > 69g/day , compared with never-drinkers . Compared with the never-drinkers , the multivariable-adjusted HRs ( CIs ) of past , light ( 69g/day ) drinkers were 1.30 ( 0.68 - 2.49 ) , 0.89 ( 0.60 - 1.32 ) , 1.19 ( 0.73 - 1.95 ) , 1.36 ( 0.79 - 2.35 ) , and 2.90 ( 1.61 - 5.23 ) , respectively . CONCLUSIONS Heavy alcohol consumption is associated with a higher risk of AF", "Purpose — The aim of this guideline is to provide a focused up date of the current recommendations for the endovascular treatment of acute ischemic stroke . When there is overlap , the recommendations made here supersede those of previous guidelines . Methods — This focused up date analyzes results from 8 r and omized , clinical trials of endovascular treatment and other relevant data published since 2013 . It is not intended to be a complete literature review from the date of the previous guideline publication but rather to include pivotal new evidence that justifies changes in current recommendations . Members of the writing committee were appointed by the American Heart Association/American Stroke Association Stroke Council ’s Scientific Statement Oversight Committee and the American Heart Association/American Stroke Association Manuscript Oversight Committee . Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process . Recommendations follow the American Heart Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence . Prerelease review of the draft guideline was performed by 6 expert peer review ers and by the members of the Stroke Council Scientific Statement Oversight Committee and Stroke Council Leadership Committee . Results — Evidence -based guidelines are presented for the selection of patients with acute ischemic stroke for endovascular treatment , for the endovascular procedure , and for systems of care to facilitate endovascular treatment . Conclusions — Certain endovascular procedures have been demonstrated to provide clinical benefit in selected patients with acute ischemic stroke . Systems of care should be organized to facilitate the delivery of this care", "The validity of atrial fibrillation ( AF ) diagnoses in national registers for use as endpoints in prospect i ve studies has not been evaluated . We studied the validity of AF diagnoses in Swedish national hospital discharge and cause of death registers and the occurrence of and risk factors for AF in a middle-aged Swedish population using these registers . Our study included the 30,447 individuals ( age 44–73 ) who attended baseline visits in 1991–1996 of the Malmö Diet and Cancer study . Individuals with a first AF diagnosis were identified by record linkage with national registers . A subset of cases was r and omly selected for validation by examination of electrocardiograms and patient records . Electrocardiograms were available in 98 % of the validation sample ( 95 % definitive AF , 3 % no AF ) . The 2 % with ECGs unavailable had probable AF . Baseline AF prevalence was 1.3 % , higher in men and increased with age . During 11.2 years of follow-up 1430 first AF diagnoses occurred . Risk factors were age , hypertension , BMI , diabetes , history of heart failure , history of myocardial infa rct ion and , in men but not women , current smoking . The strongest risk factors were history of heart failure ( hazard ratio men 4.5 , women 8.7 ) and myocardial infa rct ion ( hazard ratio men 2.0 , women 1.8 ) . The largest population attributable risks were observed for hypertension ( men 38 % , women 34 % ) and obesity ( men 11 % , women 10 % ) . In conclusion , case misclassification of AF in national registers is small , indicating feasibility of use in prospect i ve studies . Hypertension and obesity account for large portions of population risk in middle-aged individuals with low prevalence of manifest cardiac disease", "Background —Physical activity ( PA ) has previously been suggested to attenuate the risk of atrial fibrillation ( AF ) conferred by excess body weight and weight gain . We prospect ively examined the relationship between body size , weight change , and level of PA in a biracial cohort of middle-aged men and women . Methods and Results —Baseline characteristics on risk factor levels were obtained on 14 219 participants from the Atherosclerosis Risk in Communities Study . AF incidence was ascertained from 1987 to 2009 . Adjusted Cox proportional hazards models were used to estimate the associations between body mass index , waist circumference , relative weight change , and PA level with incident AF . During follow-up , there were 1775 cases of incident AF . Body mass index and waist circumference were positively associated with AF as was weight loss/gain of > 5 % initial body weight . An ideal level of PA had a small protective effect on AF risk and partially attenuated the risk of AF associated with excess weight in men but not women : compared with men with a normal body mass index , the risk of AF in obese men with an ideal , intermediate , and poor level of PA at baseline was increased by 37 % , 129 % , and 156 % ( Pinteraction=0.04 ) . During follow-up , PA did not modify the association between weight gain and risk of AF . Conclusions —Obesity and extreme weight change are risk factors for incident AF , whereas being physically active is associated with a small reduction in risk . In men only , being physically active offset some , but not all , of the risk incurred with excess body weight", "CONTEXT Atrial fibrillation ( AF ) is responsible for considerable morbidity and mortality , making identification of modifiable risk factors a priority . Increased pulse pressure , a reflection of aortic stiffness , increases cardiac load and may increase AF risk . OBJECTIVE To examine relations between pulse pressure and incident AF . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve , community-based observational cohort in Framingham , Mass , including 5331 Framingham Heart Study participants aged 35 years and older and initially free from AF ( median age , 57 years ; 55 % women ) . MAIN OUTCOME MEASURES Incident AF . RESULTS AF developed in 698 participants ( 13.1 % ) a median of 12 years after pulse pressure assessment . Cumulative 20-year AF incidence rates were 5.6 % for pulse pressure of 40 mm Hg or less ( 25th percentile ) and 23.3 % for pulse pressure greater than 61 mm Hg ( 75th percentile ) . In models adjusted for age , sex , baseline and time-dependent change in mean arterial pressure , and clinical risk factors for AF ( body mass index , smoking , valvular disease , diabetes , electrocardiographic left ventricular hypertrophy , hypertension treatment , and prevalent myocardial infa rct ion or heart failure ) , pulse pressure was associated with increased risk for AF ( adjusted hazard ratio [ HR ] , 1.26 per 20-mm Hg increment ; 95 % confidence interval [ CI ] , 1.12 - 1.43 ; P mean arterial pressure was unrelated to incident AF ( adjusted HR , 0.96 per 10-mm Hg increment ; 95 % CI , 0.88 - 1.05 ; P = .39 ) . Systolic pressure was related to AF ( HR , 1.14 per 20-mm Hg increment ; 95 % CI , 1.04 - 1.25 ; P = .006 ) ; however , if diastolic pressure was added , model fit improved and the diastolic relation was inverse ( adjusted HR , 0.87 per 10-mm Hg increment ; 95 % CI , 0.78 - 0.96 ; P = .01 ) , consistent with a pulse pressure effect . Among patients with interpretable echocardiographic images , the association between pulse pressure and AF persisted in models that adjusted for baseline left atrial dimension , left ventricular mass , and left ventricular fractional shortening ( adjusted HR , 1.23 ; 95 % CI , 1.09 - 1.39 ; P = .001 ) . CONCLUSION Pulse pressure is an important risk factor for incident AF in a community-based sample . Further research is needed to determine whether interventions that reduce pulse pressure will limit the growing incidence of AF", "PURPOSE We studied incident atrial fibrillation ( AF ) in the prospect i ve community-based Multi-Ethnic Study of Atherosclerosis ( MESA ) . Reportedly , non-Hispanic blacks ( NHBs ) have a lower AF burden compared with their non-Hispanic white ( NHW ) counterparts . Information on the epidemiology of AF in Hispanic and Asian population s is much more limited . METHODS We excluded participants with a history of AF at enrollment . A total of 6721 MESA participants were monitored for the first AF event ascertained according to hospital discharge International Classification of Diseases , Ninth Revision , codes . Age- and sex-adjusted incidence rates ( IRs ) of AF were calculated per 1000 person-years of observation . IR ratios were calculated using NHWs as the reference group . Age- and sex-adjusted population attributable fractions ( PAFs ) of established modifiable AF risk factors were ascertained . RESULTS In the MESA cohort , 47.2 % was male ; at baseline , 25.7 % had hypertension ; 12.5 % had diabetes . Three hundred five incident hospitalized AF events occurred over a mean follow-up of 7.3 years . Age- and sex-adjusted IRs and IR ratios showed that overall AF incidence was significantly lower among Hispanics , NHBs and Chinese compared with NHWs ( all P participants 65 years of age or greater , Hispanics , Chinese , and blacks had significantly lower AF incidence than NHWs ( all P ≤ .01 ) , but IRs were similar among participants under age 65 years . The PAF for smoking was 27 % among NHBs but lower among other race-ethnic groups . Among NHWs , the PAF for hypertension was 22.2 % , but this was higher among NHBs ( 33.1 % ) , Chinese ( 46.3 % ) , and Hispanics ( 43.9 % ) . CONCLUSIONS Overall , the incidence of hospitalized AF was significantly lower in Hispanics , NHBs , and Chinese than in NHWs . A larger proportion of AF events appear to be attributable to hypertension among nonwhite population s compared with NHWs", "Objective Atrial fibrillation ( AF ) is the most common arrhythmia in women . Large studies evaluating key AF risk factors in older women are lacking . We aim ed to identify risk factors for AF in postmenopausal women and measure population burden of modifiable risk factors . Design Prospect i ve observational study . Setting The Women 's Health Initiative ( WHI ) Observational Study . Patients 93 676 postmenopausal women were followed for an average of 9.8 years for cardiovascular outcomes . After exclusion of women with prevalent AF or incomplete data , 8252 of the remaining 81 892 women developed incident AF . Main outcome measures Incident AF was identified by WHI-ascertained hospitalisation records and diagnosis codes from Medicare cl aims . Multivariate Cox hazard regression analysis identified independent risk factors for incident AF . Results Age , hypertension , obesity , diabetes , myocardial infa rct ion and heart failure were independently associated with incident AF . Hypertension and overweight status accounted for 28.3 % and 12.1 % , respectively , of the population attributable risk . Hispanic and African – American participants had lower rates of incident AF ( HR 0.58 , 95 % CI 0.47 to 0.70 and HR 0.59 , 95 % CI 0.53 to 0.65 , respectively ) than Caucasians . Conclusions Caucasian ethnicity , traditional cardiovascular risk factors and peripheral arterial disease were independently associated with higher rates of incident AF in postmenopausal women . Hypertension and overweight status accounted for a large proportion of population attributable risk . Measuring burden of modifiable AF risk factors in older women may help target interventions", "AIMS Psoriasis is a chronic inflammatory disease and inflammation contributes to the pathogenesis of atrial fibrillation ( AF ) and ischaemic stroke . We therefore investigated the risk of these endpoints in patients with psoriasis . METHODS AND RESULTS Cohort study of the entire Danish population followed from 1997 to 2006 by individual-level-linkage of nationwide prospect ively recorded registers . Multivariable Poisson 's regression and sensitivity analyses were used to assess the psoriasis-related risk of AF and ischaemic stroke . A total of 36 765 patients with mild psoriasis and 2793 with severe psoriasis were compared with 4 478 926 individuals , i.e. , the reference population . In patients with mild psoriasis , the adjusted rate ratios ( RRs ) for AF were 1.50 ( 1.21 - 1.86 ) and 1.16 ( 1.08 - 1.24 ) in patients aged higher risk of AF with RRs 2.98 ( 1.80 - 4.92 ) in patients aged disease severity-dependent increased risk of ischaemic stroke , i.e. RRs 1.97 ( 1.66 - 2.34 ) and 2.80 ( 1.81 - 4.34 ) in patients aged with increased risk of AF and ischaemic stroke . These novel results add to a growing body of evidence , suggesting that patients with psoriasis could be considered at increased cardiovascular risk ", "BACKGROUND AND PURPOSE To prevent stroke , strategies for atrial fibrillation ( AF ) prevention and an early detection of AF by electrocardiogram are essential . However , only a limited prospect i ve studies have examined the risk factors for AF , even in blood pressure ( BP ) and body mass index ( BMI ) , which are not clear among general population s. We investigated the impacts of BP and BMI on the risk of incident AF in a general population . METHODS A total of 6,906 participants ( 30 - 84 years ) in the Suita Study were prospect ively followed up for incident AF . Participants were diagnosed with AF if AF or atrial flutter was present on an electrocardiogram from a routine health examination ( every 2 years ) or if AF was indicated as a present illness from health examinations and /or medical records during follow-up . Adjusted Cox proportional hazard ratios ( HRs ) were calculated . RESULTS During the 12.8-year follow-up , 253 incident AF events occurred . Compared with the systolic BP ( SBP ) of incident AF in the systolic hypertension and the overweight ( BMI ≥ 25kg/m(2 ) ) groups were 1.74 ( 1.22 - 2.49 ) and 1.35 ( 1.01 - 1.80 ) , respectively . Compared with SBP of incident AF in the SBP = 120 - 139 mm Hg with overweight and the systolic hypertension with normal or overweight were 1.72 ( 1.01 - 2.91 ) , 1.66 ( 1.10 - 2.50 ) , and 2.31 ( 1.47 - 3.65 ) , respectively ( P for interaction = 0.04 ) . CONCLUSIONS Systolic prehypertension and overweight are associated with incident AF in Japanese population . The association between SBP and AF may be evident by overweight", "Background : Atrial fibrillation is a common arrhythmia associated with excess morbidity and mortality . We studied temporal changes in hospital admission rates for atrial fibrillation using data from a prospect i ve population -based cohort study spanning 2 decades ( the Copenhagen City Heart Study ) . Methods : The study included baseline data collected in 1981 through 1983 on 10,955 persons age 40 to 79 years and baseline data collected in 1991 through 1994 on 7212 persons age 40 to 79 years . We used hospital diagnosis data from the Danish National Hospital Discharge Register to determine the rate of first hospital admission for atrial fibrillation during 7 years following each of the 2 baseline data collecting periods . Changes in admission rates were analyzed using Cox proportional hazard models . Results : During the 2 7-year periods , 379 subjects were admitted with a hospital diagnosis of atrial fibrillation . The rate of hospital admissions for atrial fibrillation increased among both men and women from the first to the second period ( relative risk = 1.6 ; 95 % confidence interval = 1.3–1.9 [ adjusted for age , sex , prior myocardial infa rct ion , arterial hypertension , diabetes mellitus , electrocardiographic left ventricular hypertrophy , decreased lung function , smoking , height , and weight ] ) . Conclusion : During the latest 10 to 20 years , there has been a 60 % increase in hospital admissions for atrial fibrillation independent of changes in known risk factors . This increase could result from changes in admission threshold or coding practice s , or it could reflect a genuine increase in the population incidence of atrial fibrillation", "Background : Atrial fibrillation ( AF ) is a common cardiac arrhythmia which increases morbidity and mortality . Identification of risk factors is therefore important . We examined the impact of palpitations and cardiovascular risk factors in prediction of AF ( all types ) and lone AF in a large population -based cohort . Design : We carried out a prospect i ve population -based cohort study . Methods : A total of 22,815 participants from a population survey in 1994–1995 were followed-up for a mean of 11.1 years . Mean age at baseline was 46 years . Measurements of height , weight , blood pressure , heart rate , total cholesterol and high-density lipoprotein (HDL)-cholesterol , and information on palpitations , diabetes , angina , myocardial infa rct ion , and antihypertensive treatment were obtained at baseline . The outcome measure was first-ever AF , documented on an electrocardiogram . Cox proportional hazards regression model was used to estimate hazard ratios ( HRs ) for AF . Results : Palpitations were associated with increased risk of AF in both women ( HR 1.62 , 95 % confidence interval [ CI ] 1.29–2.02 ) and men ( HR 1.91 , 95 % CI 1.54–2.35 ) . For hypertension the HR for AF was 1.98 ( 1.46 - 2.69 ) in women and 1.40 ( 1.13 - 1.74 ) in men . The HR for 1 SD increase in body mass index ( BMI ) was 1.16 ( 1.06–1.27 ) in women and 1.47 ( 1.32–1.63 ) in men . Body height and BMI were associated with increased risk for lone AF in men . Conclusion : Palpitations , hypertension and BMI were predictive of future atrial fibrillation in both sexes", "OBJECTIVES Orthostatic hypotension ( OH ) , a common manifestation of autonomic dysfunction , has been identified as an independent risk factor for all-cause mortality and incident cardiovascular disease . However , the role of OH in the development of atrial fibrillation has not been studied . DESIGN We investigated the incidence of atrial fibrillation in relation to baseline presence of OH according to international consensus criteria in the Swedish population -based prospect i ve cohort of the Malmö Preventive Project . The study sample consisted of 33,346 individuals ( 67.3 % men ; mean age , 45.6 ± 7.4 years ; range , 26 - 61 years ) . The association between OH and incidence of atrial fibrillation during follow-up was assessed using the Kaplan-Meier method and multivariable Cox proportional hazard models , taking into account conventional risk factors for atrial fibrillation . RESULTS At baseline , 1987 participants ( 6.1 % ) met the diagnostic criteria for OH . Over a follow-up period of approximately 24 years , 2312 individuals ( 3.0 events/1000 person-years ) were diagnosed with new-onset atrial fibrillation . Of these , 196 had OH at baseline ( 4.6 events/1000 person-years amongst all OH-positive individuals ) . In a multivariable Cox regression analysis , OH predicted incidence of atrial fibrillation independently of other risk factors ( hazard ratio [ HR ] : 1.30 ; 95 % confidence interval [ CI ] : 1.05 - 1.61 ; P = 0.016 ) , and this association was significant in hypertensive ( HR : 1.44 ; 95%CI : 1.10 - 1.88 ; P = 0.008 ) , but not in normotensive participants ( HR : 1.10 ; 95%CI : 0.77 - 1.58 ; P = 0.60 ) . CONCLUSIONS The presence of OH predicts the incidence of atrial fibrillation in middle-aged hypertensive individuals , independently of conventional risk factors . Further studies of the association of autonomic dysfunction and OH with atrial fibrillation are needed", "BACKGROUND Cigarette smoking is an important risk factor for cardiovascular disease , but it is unknown whether it also contributes to the risk of atrial fibrillation . METHODS AND RESULTS The study is part of the Rotterdam Study , a population -based cohort study among subjects aged > or = 55 years . The association between cigarette smoking and the risk of atrial fibrillation was examined in 5,668 subjects without atrial fibrillation at baseline . During a median follow-up of 7.2 years , 371 cases of atrial fibrillation were identified . Relative risks ( RR ) were calculated with 95 % CIs using the Cox proportional hazards model , adjusted for age , gender , body mass index , hypertension , systolic blood pressure , serum cholesterol level , diabetes mellitus , left ventricular hypertrophy on the electrocardiogram , prevalent and incident myocardial infa rct ion , prevalent heart failure , and the use of pulmonary medication . After multivariate adjustment , current smokers and former smokers had increased risks of atrial fibrillation as compared to never smokers ( RR 1.51 , 95 % CI 1.07 - 2.12 ; and RR 1.49 , 95 % CI 1.14 - 1.97 , respectively ) . No differences were found between men and women . CONCLUSIONS The results of this prospect i ve , population -based study show that current and former smoking of cigarettes are associated with increased risk of atrial fibrillation", "AIMS Obesity is a recognized risk factor for atrial fibrillation ( AF ) , partly because of the association between body mass index ( BMI ) and atrial volume . We aim ed to determine whether other factors relating to body size were related to AF . METHODS AND RESULTS Data were derived from a r and om population sample of 6903 men ( mean age 51.5 years ) who underwent a single midlife evaluation as part of the multifactor Swedish Primary Prevention Study . A total of 1253 men ( 18.2 % ) had a subsequent hospital discharge diagnosis ( principal or secondary ) of AF during a maximum follow-up of 34.3 years . Body surface area ( BSA ) at age 20 ( calculated from recalled weight and measured height ) was strongly related to subsequent AF ( P BMI and weight gain from age 20 to midlife ( P midlife BMI , weight gain and other risk factors , hazard ratios ( HR ) [ 95 % confidence intervals ( CI ) ] for AF for the second , third , and fourth quartile of BSA at age 20 , compared with the lowest quartile , were 1.47 ( 95 % CI , 1.22 - 1.76 ) , 1.66 ( 95 % CI , 1.38 - 2.00 ) , and 2.22 ( 95 % CI , 1.82 - 2.70 ) ( P for trend AF . Given the current trends not only for obesity but also for height , a substantial increase in the incidence of AF is likely", "OBJECTIVE It is recognized that higher height and weight are associated with higher risk of atrial fibrillation or flutter ( AF ) but it is unclear whether risk of AF is related to body fat , body fat location , or lean body mass . METHODS This article reports the Danish population -based prospect i ve cohort Diet , Cancer and Health study conducted among 55,273 men and women 50 - 64 years of age at recruitment . The associations between bioelectrical impedance derived measures of body composition and combinations of anthropometric measures of body fat distribution and risk of an incident record of AF in the Danish Registry of Patients were investigated . RESULTS During follow-up ( median 13.5 years ) AF developed in 1,669 men and 912 women . Higher body fat at any measured location was associated with higher risk of AF . The adjusted hazard ratio ( HR ) per 1 sex-specific st and ard deviation ( SD ) increment in body fat mass was 1.29 ( 95 % confidence interval [ CI ] , 1.24 - 1.33 ) . Higher lean body mass was also associated with a higher risk of AF . The adjusted HR for 1 sex-specific SD increment was 1.40 ( 95 % CI , 1.35 - 1.45 ) . CONCLUSION Higher body fat and higher lean body mass were both associated with higher risk of AF", "Background and Aims : Excessive sporting activities have been associated with risk of atrial fibrillation . To study if work related physical activity also confers risk of atrial fibrillation or flutter , the association between work related physical strain and the risk of a hospital discharge diagnosis ( inpatient as well as outpatient ) of atrial fibrillation or flutter was examined . Methods : A population based prospect i ve cohort study was conducted from December 1993 to December 2001 among 19 593 men and 18 807 women with a mean age at baseline of 56 years ( range 50–65 years ) in the Danish Diet , Cancer , and Health Study . The physical strain during working hours was categorised as sedentary , light , or heavy , and analysed using proportional hazard models . Subjects were followed up in the Danish National Registry of Patients and in the Danish Civil Registration System . Results : During follow up ( mean 5.7 years ) a hospital discharge diagnosis of atrial fibrillation or flutter occurred in 305 men and 113 women . When using the risk of atrial fibrillation or flutter associated with sedentary work at a sitting position as a reference , no excess risk ( unadjusted as well as adjusted ) was found of atrial fibrillation or flutter associated with sedentary work in a st and ing position , light workload , or heavy workload in men or women . Conclusion : No evidence was found of an association between physical activities during working hours and risk of a hospital discharge diagnosis of atrial fibrillation or flutter for men and women in the age group of 50–65 years", "AIMS To assess the joint influence of inflammatory biomarkers on the risk of incident atrial fibrillation ( AF ) in women . METHODS AND RESULTS We performed a prospect i ve cohort study among women participating in the Women 's Health Study . All women were free of AF at study entry and provided a baseline blood sample assayed for high-sensitivity C-reactive protein , soluble intercellular adhesion molecule-1 , and fibrinogen . To evaluate the joint effect of these three biomarkers , an inflammation score was created that ranged from 0 to 3 and reflected the number of biomarkers in the highest tertile per individual . During a median follow-up of 14.4 years , 747 of 24,734 women ( 3.0 % ) experienced a first AF event . Assessed individually , all three biomarkers were associated with incident AF , even after adjustment for traditional risk factors . When combined into an inflammation score , a strong and independent relationship between inflammation and incident AF emerged . Across increasing inflammation score categories , there were 1.66 , 2.22 , 2.73 , and 3.25 AF events per 1000 person-years of follow-up . The corresponding hazard ratios ( 95 % confidence intervals ) across inflammation score categories were 1.0 , 1.22 ( 1.00 - 1.49 ) , 1.32 ( 1.06 - 1.65 ) , and 1.59 ( 1.22 - 2.06 ) ( P for linear trend 0.0006 ) after multivariable adjustment . CONCLUSION In this large-scale prospect i ve study among women without a history of cardiovascular disease , markers of systemic inflammation were significantly related to AF even after controlling for traditional risk factors", "OBJECTIVES The purpose of this study was to characterize the relationship between changes in body mass index ( BMI ) and incident atrial fibrillation ( AF ) in a large cohort of women . BACKGROUND Obesity and AF are increasing public health problems . The importance of dynamic obesity-associated AF risk is uncertain , and mediators are not well characterized . METHODS Cases of AF were confirmed by medical record review in 34,309 participants in the Women 's Health Study . Baseline and up date d measures of BMI were obtained from periodic question naires . RESULTS During 12.9 + /- 1.9 years of follow-up , 834 AF events were confirmed . BMI was linearly associated with AF risk , with a 4.7 % ( 95 % confidence interval [ CI ] : 3.4 to 6.1 , p BMI were used to estimate dynamic risk , overweight ( hazard ratio [ HR ] : 1.22 ; 95 % CI : 1.02 to 1.45 , p = 0.03 ) , and obesity ( HR : 1.65 ; 95 % CI : 1.36 to 2.00 ; p development of AF ( p = 0.02 ) compared with those maintaining BMI overweight and obesity increased over time . The adjusted proportion of incident AF attributable to short-term elevations in BMI was substantial ( 18.3 % ) . CONCLUSIONS In this population of apparently healthy women , BMI was associated with short- and long-term increases in AF risk , accounting for a large proportion of incident AF independent of traditional risk factors . A strategy of weight control may reduce the increasing incidence of AF . ( Women 's Health Study [ WHS ] : A R and omized Trial of Low-Dose Aspirin and Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer ; NCT00000479 )", "BACKGROUND Atrial fibrillation ( AF ) and chronic kidney disease share risk factors and pathophysiologic mechanisms , suggesting that two conditions have close relationships . METHODS This is a prospect i ve community-based observational cohort study including 235,818 subjects based upon a voluntary annual health check-up program in Japan . We studied the association of kidney dysfunction at entry with subsequent new-onset AF and the association of AF at entry with the development of kidney disease . RESULTS During a follow-up of 5.9 + /- 2.4 years , AF developed in 2947 subjects ( 1.3 % ) . Baseline serum creatinine and estimated glomerular filtration rate ( GFR ) were associated with risk of subsequent AF . The HRs ( 95 % CI ) for AF were 1.32 ( 1.08 - 1.62 ) and 1.57 ( 0.89 - 2.77 ) for GFR 30 to 59 and effect of kidney disease on risk of new-onset AF remained significant in subjects without treated hypertension or diabetes . During the follow-up , 7791 subjects ( 3.3 % ) developed kidney dysfunction ( GFR proteinuria . Atrial fibrillation at entry was associated with development of kidney dysfunction ( HRs [ 95 % CI ] , 1.77 [ 1.50 - 2.10 ] ) and proteinuria ( HR [ 95 % CI ] , 2.20 [ 1.92 - 2.52 ] ) . The association persisted in subjects without treated hypertension or diabetes . CONCLUSIONS Kidney dysfunction increased the risk of new onset of AF , and AF increased the risk of development of kidney disease . This finding supports the concept that the two conditions share common abnormal molecular signaling pathways contributing to their pathogenesis", "A risk score for atrial fibrillation ( AF ) has been developed by the Framingham Heart Study ; however , the applicability of this risk score , derived using data from white patients , to predict new-onset AF in nonwhites is uncertain . Therefore , we developed a 10-year risk score for new-onset AF from risk factors commonly measured in clinical practice using 14,546 subjects from the Atherosclerosis Risk In Communities ( ARIC ) study , a prospect i ve community-based cohort of blacks and whites in the United States . During 10 years of follow-up , 515 incident AF events occurred . The following variables were included in the AF risk score : age , race , height , smoking status , systolic blood pressure , hypertension medication use , precordial murmur , left ventricular hypertrophy , left atrial enlargement , diabetes , coronary heart disease , and heart failure . The area under the receiver operating characteristics curve ( AUC ) of a Cox regression model that included the previous variables was 0.78 , suggesting moderately good discrimination . The point-based score developed from the coefficients in the Cox model had an AUC of 0.76 . This clinical risk score for AF in the Atherosclerosis Risk In Communities cohort compared favorably with the Framingham Heart Study 's AF ( AUC 0.68 ) , coronary heart disease ( CHD ) ( AUC 0.63 ) , and hard CHD ( AUC 0.59 ) risk scores and the Atherosclerosis Risk In Communities CHD risk score ( AUC 0.58 ) . In conclusion , we have developed a risk score for AF and have shown that the different pathophysiologies of AF and CHD limit the usefulness of a CHD risk score in identifying subjects at greater risk of AF", "PURPOSE We examined the association between the body mass index analyzed as a continuous variable and by categorization according to World Health Organization criteria ( normal weight , overweight and obesity ) and the risk of a hospital ( inpatient as well as outpatient ) diagnosis of atrial fibrillation or flutter . METHODS Population -based prospect i ve cohort study conducted from December 1993 to December 2001 among 47589 participants ( 22482 men and 25107 women ) without preexisting cardiovascular or endocrine disease and with a mean age at baseline of 56 years ( range 50 - 64 years ) in the Danish Diet , Cancer , and Health Study . Subjects were followed up in the Danish National Registry of Patients and in the Danish Civil Registration System . RESULTS During follow-up ( mean , 5.7 years ) atrial fibrillation or flutter developed in 553 subjects ( 372 men and 181 women ) . The adjusted hazard ratio for atrial fibrillation or flutter per unit of increase in the body mass index was 1.08 ( 95 % confidence interval [ CI ] : 1.05 to 1.11 ) in men and 1.06 ( 95 % CI : 1.03 to 1.09 ) in women . When using normal weight as a reference , the adjusted hazard ratio for atrial fibrillation or flutter by overweight was 1.75 ( 95 % CI : 1.35 to 2.27 ) in men and 1.39 ( 95 % CI : 0.99 to 1.94 ) in women . The adjusted hazard ratio by obesity was 2.35 ( 95 % CI : 1.70 to 3.25 ) in men and 1.99 ( 95 % CI : 1.31 to 3.02 ) in women . CONCLUSION Overweight and obesity are associated with an increased risk of a diagnosis of atrial fibrillation or flutter", "CONTEXT Hyperthyroidism is an established risk factor for atrial fibrillation ( AF ) , but information concerning the association with variations within the normal range of thyroid function and subgroups at risk is lacking . OBJECTIVE This study aim ed to investigate the association between normal thyroid function and AF prospect ively and explore potential differential risk patterns . DESIGN , SETTING , AND PARTICIPANTS From the Rotterdam Study we included 9166 participants ≥ 45 y with TSH and /or free T4 ( FT4 ) measurements and AF assessment ( 1997 - 2012 median followup , 6.8 y ) , with 399 prevalent and 403 incident AF cases . MAIN OUTCOME MEASURES Outcome measures were 3-fold : 1 ) hazard ratios ( HRs ) for the risk of incident AF by Cox proportional-hazards models , 2 ) 10-year absolute risks taking competing risk of death into account , and 3 ) discrimination ability of adding FT4 to the CHARGE-AF simple model , an established prediction model for AF . RESULTS Higher FT4 levels were associated with higher risks of AF ( HR 1.63 , 95 % confidence interval , 1.19 - 2.22 ) , when comparing those in the highest quartile to those in lowest quartile . Absolute 10-year risks increased with higher FT4 in participants ≤ 65 y from 1 - 9 % and from 6 - 12 % in subjects ≥ 65 y. Discrimination of the prediction model improved when adding FT4 to the simple model ( c-statistic , 0.722 vs 0.729 ; P = .039 ) . TSH levels were not associated with AF . CONCLUSIONS There is an increased risk of AF with higher FT4 levels within the normal range , especially in younger subjects . Adding FT4 to the simple model slightly improved discrimination of risk prediction ", "Few prospect i ve studies have explored the association between renal function and risk for incident atrial fibrillation ( AF ) in apparently healthy population s. A total of 24,746 women participating in the Women 's Health Study who were free of cardiovascular disease and AF and provided blood sample s at baseline were prospect ively followed for incident AF from 1993 to 2010 . AF events were confirmed by medical chart review . Estimated glomerular filtration rate ( eGFR ) was calculated from baseline creatinine using the Chronic Kidney Disease Epidemiology ( CKD-EPI ) equation . Cox models were used to estimate hazard ratios and 95 % confidence intervals ( CIs ) for incident AF across eGFR categories controlling for AF risk factors . During a median of 15.4 years of follow-up , 786 incident AF events occurred . The multivariate-adjusted hazard ratios for incident AF across eGFR categories ( the 1,008 women with eGFRs multivariate-adjusted hazard ratio for AF of 1.39 ( 95 % CI 1.04 to 1.86 , p = 0.03 ) . In conclusion , no significant linear or curvilinear relation was observed between incident AF and less severe impairment of renal function in this large prospect i ve cohort of women . However , a significant elevation in AF risk was observed at a threshold eGFR of < 60 ml/min/1.73 m(2 )", "AIMS Since atrial fibrillation ( AF ) is associated with increased risks of cardiovascular and cerebrovascular complications , estimations on the number of individuals with AF are relevant to healthcare planning . We aim ed to project the number of individuals with AF in the Netherl and s and in the European Union from 2000 to 2060 . METHODS AND RESULTS Age- and sex-specific AF prevalence estimates were obtained from the prospect i ve community-based Rotterdam Study . Population projections for the Netherl and s and the European Union were obtained from the European Union 's statistics office . In the age stratum of 55 - 59 years , the prevalence of AF was 1.3 % in men ( 95 % CI : 0.4 - 3.6 % ) and 1.7 % in women ( 95 % CI : 0.7 - 4.0 % ) . The prevalence of AF increased to 24.2 % in men ( 95 % CI : 18.5 - 30.7 % ) , and 16.1 % in women ( 95 % CI : 13.1 - 19.4 % ) , for those > 85 years of age . This age- and sex-specific prevalence remained stable during the years of follow-up . Furthermore , we estimate that in the European Union , 8.8 million adults over 55 years had AF in 2010 ( 95 % CI : 6.5 - 12.3 million ) . We project that this number will double by 2060 to 17.9 million ( 95 % CI : 13.6 - 23.7 million ) if the age- and sex-specific prevalence remains stable . CONCLUSION We estimate that from 2010 to 2060 , the number of adults 55 years and over with AF in the European Union will more than double . As AF is associated with significant morbidities and mortality , this increasing number of individuals with AF may have major public health implication", "Cross-sectional and limited prospect i ve evidence has suggested that inflammatory markers may predict for the risk of atrial fibrillation ( AF ) . In a prospect i ve cohort study , we studied the risk of incident AF among 8,870 women and men free of cardiovascular disease enrolled in the Copenhagen City Heart Study . We measured plasma fibrinogen and serum albumin levels at a study visit from 1991 to 1994 . We identified 286 subsequent cases of AF during a mean of 7.5 years of follow-up by a vali date d nationwide registry of all hospitalizations . The fibrinogen levels at baseline were associated with a higher risk of AF , with a multivariate-adjusted hazard ratio for the highest versus lowest quartiles of 1.98 ( 95 % confidence interval [ CI ] 0.94 to 4.17 ) among men and 2.14 ( 95 % CI 1.15 to 3.96 ) among women . The albumin levels were inversely associated with the risk of AF among women ( hazard ratio 0.47 , 95 % CI 0.28 to 0.77 ) but not among men ( hazard ratio 1.01 , 95 % CI 0.56 to 1.84 ) . Additional adjustment for cases of coronary heart disease , congestive heart failure , and stroke that occurred during follow-up did not attenuate these associations . In conclusion , higher levels of fibrinogen and lower levels of albumin were prospect ively associated with a higher risk of AF , even accounting for their relation with the risk of cardiovascular disease . These findings support the hypothesis that inflammation contributes to the etiology of AF", "Background — The influence of systolic and diastolic blood pressure ( BP ) on incident atrial fibrillation ( AF ) is not well studied among initially healthy , middle-aged women . Methods and Results — A total of 34 221 women participating in the Women 's Health Study were prospect ively followed up for incident AF . The risk of AF across categories of systolic and diastolic BP was compared by use of Cox proportional-hazards models . During 12.4 years of follow-up , 644 incident AF events occurred . Using BP measurements at baseline , we discovered that the long-term risk of AF was significantly increased across categories of systolic and diastolic BP . Multivariable-adjusted hazard ratios for systolic BP categories ( 0.0001 ) . Adjusted hazard ratios across baseline diastolic BP categories ( BP changes over time were accounted for in up date d models , multivariable-adjusted hazard ratios were 1.0 , 1.14 ( 95 % CI , 0.89 to 1.46 ) , 1.37 ( 95 % CI , 1.07 to 1.76 ) , 1.71 ( 95 % CI , 1.33 to 2.21 ) , and 2.21 ( 95 % CI , 1.45 to 3.36 ) ( P for trend for systolic BP categories and 1.0 , 1.12 ( 95 % CI , 0.82 to 1.52 ) , 1.13 ( 95 % CI , 0.83 to 1.52 ) , 1.30 ( 95 % CI , 0.89 to 1.88 ) , 1.50 ( 95 % CI , 1.01 to 1.88 ) , and 1.54 ( 95 % CI , 0.75 to 3.14 ) ( P for trend=0.026 ) for diastolic BP categories . Conclusions — In this large cohort of initially healthy women , BP was strongly associated with incident AF , and systolic BP was a better predictor than diastolic BP . Systolic BP levels within the nonhypertensive range were independently associated with incident AF even after BP changes over time were taken into account", "CONTEXT Previous studies suggest that consuming moderate to high amounts of alcohol on a regular basis might increase the risk of developing atrial fibrillation in men but not in women . However , these studies were not powered to investigate the association of alcohol consumption and atrial fibrillation among women . OBJECTIVE To prospect ively assess the association between regular alcohol consumption and incident atrial fibrillation among women . DESIGN , SETTING , AND PARTICIPANTS Participants were 34 715 initially healthy women participating in the Women 's Health Study , a completed r and omized controlled trial conducted in the United States . Participants were older than 45 years and free of atrial fibrillation at baseline and underwent prospect i ve follow-up from 1993 to October 31 , 2006 . Alcohol consumption was assessed via question naires at baseline and at 48 months of follow-up and was grouped into 4 categories ( 0 , > 0 and or = 1 and or = 2 drinks per day ) . Atrial fibrillation was self-reported on the yearly question naires and subsequently confirmed by electrocardiogram and medical record review . MAIN OUTCOME MEASURE Time to first episode of atrial fibrillation . RESULTS Over a median follow-up of 12.4 years , 653 cases of incident atrial fibrillation were confirmed . Age-adjusted incidences among women consuming 0 ( n = 15,370 ) , more than 0 and less than 1 ( n = 15,758 ) , 1 or more and less than 2 ( n = 2228 ) , and 2 or more ( n = 1359 ) drinks per day were 1.59 , 1.55 , 1.27 , and 2.25 events/1000 person-years of follow-up . Thus , compared with nondrinking women , women consuming 2 or more drinks per day had an absolute risk increase of 0.66 events/1000 person-years . The corresponding multivariate-adjusted hazard ratios ( HRs ) for incident atrial fibrillation were 1 , 1.05 ( 95 % CI , 0.88 - 1.25 ) , 0.84 ( 95 % CI , 0.58 - 1.22 ) , and 1.60 ( 95 % CI , 1.13 - 2.25 ) , respectively . The increased hazard in the small group of women consuming 2 or more drinks per day persisted when alcohol intake was up date d at 48 months ( HR , 1.49 ; 95 % CI , 1.05 - 2.11 ) or when women were censored at their first cardiovascular event ( HR , 1.68 ; 95 % CI , 1.18 - 2.39 ) . CONCLUSIONS Among healthy middle-aged women , consumption of up to 2 alcoholic beverages per day was not associated with an increased risk of incident atrial fibrillation . Heavier consumption of 2 or more drinks per day , however , was associated with a small but statistically significant increased risk of atrial fibrillation", "Chronic kidney disease ( CKD ) is a potential independent risk factor for atrial fibrillation ( AF ) . It remains unclear whether anemia is synergistically associated with increased risk of AF onset in subjects with CKD . We evaluated the association of kidney function , hemoglobin ( Hb ) , and their combination with new-onset AF in a population -based cohort study . We conducted a 15-year prospect i ve cohort study of 132,250 Japanese subjects aged 40 to 79 years who participated in annual health checkups from 1993 . Kaplan-Meier survival analysis was used to compare freedom from new-onset AF between groups classified by estimated glomerular filtration rate grade , Hb grade , and their combination . Cox proportional hazard model analysis was used to estimate hazard ratios ( HRs ) for new-onset AF . During a 13.8-year mean follow-up period , 1,232 ( 0.93 % ) subjects with new-onset AF were identified . Lower estimated glomerular filtration rate and lower Hb grade s were significantly associated with a higher incidence of new-onset AF . Multivariate HRs and 95 % confidence intervals ( CIs ) of new-onset AF were 1.38 ( 1.21 to 1.56 ) for mild CKD group , 2.56 ( 2.09 to 3.13 ) for CKD group , and 1.50 ( 1.24 to 1.83 ) for anemia group . Borderline Hb level was not significantly associated with increased risk for new-onset AF ( HR 1.07 , CI 0.91 to 1.25 , p = 0.4284 ) . In the model with interaction term between CKD and anemia , the risk was significantly higher ( p = 0.0343 for the interaction ) than that predicted by each factor independently . In conclusion , decreased kidney function and lower Hb level are associated with increased risk for new-onset AF , especially when both are present" ]

[ "BACKGROUND The role of weight training in the primary prevention of type 2 diabetes mellitus ( T2DM ) is largely unknown . METHODS To examine the association of weight training with risk of T2DM in US men and to assess the influence of combining weight training and aerobic exercise , we performed a prospect i ve cohort study of 32 002 men from the Health Professionals Follow-up Study observed from 1990 to 2008 . Weekly time spent on weight training and aerobic exercise ( including brisk walking , jogging , running , bicycling , swimming , tennis , squash , and calisthenics/rowing ) was obtained from question naires at baseline and biennially during follow-up . RESULTS During 508 332 person-years of follow-up ( 18 years ) , we documented 2278 new cases of T2DM . In multivariable-adjusted models , we observed a dose-response relationship between an increasing amount of time spent on weight training or aerobic exercise and lower risk of T2DM ( P weight training or aerobic exercise for at least 150 minutes per week was independently associated with a lower risk of T2DM of 34 % ( 95 % CI , 7%-54 % ) and 52 % ( 95 % CI , 45%-58 % ) , respectively . Men who engaged in aerobic exercise and weight training for at least 150 minutes per week had the greatest reduction in T2DM risk ( 59 % ; 95 % CI , 39%-73 % ) . CONCLUSIONS Weight training was associated with a significantly lower risk of T2DM , independent of aerobic exercise . Combined weight training and aerobic exercise conferred a greater benefit", "OBJECTIVE Changing dietary and physical activity habits has the potential to postpone or prevent the development of type 2 diabetes . However , it needs to be assessed whether moderate interventions , in agreement with current guidelines for the general population , are effective . We evaluated the impact of a 2-year combined diet and physical activity intervention program on glucose tolerance in Dutch subjects at increased risk for developing diabetes . RESEARCH METHODS AND PROCEDURES Subjects with glucose intolerance were r and omly assigned to either the lifestyle intervention group ( INT ) or control group ( CON ) . The INT received regular dietary advice and was stimulated to increase their physical activity . The CON received a brief leaflet about healthy diet and increased physical activity . Primary outcome measure was the change in glucose tolerance . RESULTS In total , 88 subjects completed 2 years of intervention ( 40 subjects in the INT , 48 subjects in the CON , mean BMI 29.4 kg/m2 ) . Subjects in the INT reduced their body weight , waist circumference , and ( saturated ) fat intake and improved their aerobic capacity . Two-hour plasma glucose concentration declined from 8.7 to 8.0 mM in the INT and rose from 8.6 to 9.4 mM in the CON ( p diet and exercise intervention showed the largest reduction in 2-hour glucose levels . DISCUSSION Our results showed that a lifestyle intervention program according to general recommendations improves glucose tolerance , even in a less obese and more physical active population . Furthermore , our results underscore the importance of combining diet and physical activity to improve glucose tolerance and insulin resistance", "Thirty obese women were r and omly assigned to either 40 % [ severe energy restriction ( SER ) ] or 70 % [ moderate energy restriction ( MER ) ] of their maintenance energy requirements and to no exercise , aerobic exercise ( walking ) , or aerobic exercise plus circuit weight training . Body composition by hydrostatic weighing and energy expenditure by indirect calorimetry were measured at 0 , 3 , and 6 mo . In addition , we developed a deficit-efficiency factor ( DEF ) , calculated as body energy loss/dietary energy deficit , to attempt to quantify the effectiveness of the weight-reduction interventions . Subjects in the SER group lost more weight ( mean + /- SE : 15.1 + /- 1.4 vs 10.8 + /- 1.0 kg ) , fat ( 11.7 + /- 1.1 vs 8.3 + /- 0.6 kg ) , and fat-free mass ( 2.8 + /- 0.3 vs 1.8 + /- 0.3 kg ) than the MER group ( P overall DEF was greatest in the MER group ( 0.80 + /- 0.07 ) compared with the SER group ( 0.52 + /- 0.05 ; P Exercise had no significant effect . This study demonstrates that MER may offer an advantage over SER because it produces a greater energy loss relative to energy deficit", "Aims /hypothesis . The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying Type II ( non-insulin-dependent ) diabetes mellitus in subjects with impaired glucose tolerance , to evaluate the effects of the intervention programme on cardiovascular risk factors and to assess the determinants for the progression to diabetes in persons with impaired glucose tolerance . Methods . A total of 523 overweight subjects with impaired glucose tolerance ascertained by two oral glucose tolerance tests were r and omised to either a control or intervention group . The control subjects received general information at the start of the trial about the lifestyle changes necessary to prevent diabetes and about annual follow-up visits . The intervention subjects had seven sessions with a nutritionist during the first year and a visit every 3 months thereafter aim ed at reducing weight , the intake of saturated fat and increasing the intake of dietary fibre . Intervention subjects were also guided individually to increase their physical activity . Results . During the first year , weight loss in the first 212 study subjects was 4.7 ± 5.5 vs 0.9 ± 4.1 kg in the intervention and control group , respectively ( p The plasma glucose concentrations ( fasting : 5.9 ± 0.7 vs 6.4 ± 0.8 mmol/l , p in blood pressure , serum lipids and anthropometric indices in the intervention group . Conclusion /interpretation . The interim results show the efficacy and feasibility of the lifestyle intervention programme . [ Diabetologia ( 1999 ) 42 : 793–801", "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", "CONTEXT Exercise guidelines for individuals with diabetes include both aerobic and resistance training although few studies have directly examined this exercise combination . OBJECTIVE To examine the benefits of aerobic training alone , resistance training alone , and a combination of both on hemoglobin A(1c ) ( HbA(1c ) ) in individuals with type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled trial in which 262 sedentary men and women in Louisiana with type 2 diabetes and HbA(1c ) levels of 6.5 % or higher were enrolled in the 9-month exercise program between April 2007 and August 2009 . INTERVENTION Forty-one participants were assigned to the nonexercise control group , 73 to resistance training 3 days a week , 72 to aerobic exercise in which they expended 12 kcal/kg per week ; and 76 to combined aerobic and resistance training in which they expended 10 kcal/kg per week and engaged in resistance training twice a week . Main Outcome Change in HbA(1c ) level . Secondary outcomes included measures of anthropometry and fitness . RESULTS The study included 63.0 % women and 47.3 % nonwhite participants who were a mean ( SD ) age of 55.8 years ( 8.7 years ) with a baseline HbA(1c ) level of 7.7 % ( 1.0 % ) . Compared with the control group , the absolute mean change in HbA(1c ) in the combination training exercise group was -0.34 % ( 95 % confidence interval [ CI ] , -0.64 % to -0.03 % ; P = .03 ) . The mean changes in HbA(1c ) were not statistically significant in either the resistance training ( -0.16 % ; 95 % CI , -0.46 % to 0.15 % ; P = .32 ) or the aerobic ( -0.24 % ; 95 % CI , -0.55 % to 0.07 % ; P = .14 ) groups compared with the control group . Only the combination exercise group improved maximum oxygen consumption ( mean , 1.0 mL/kg per min ; 95 % CI , 0.5 - 1.5 , P reduced waist circumference from -1.9 to -2.8 cm compared with the control group . The resistance training group lost a mean of -1.4 kg fat mass ( 95 % CI , -2.0 to -0.7 kg ; P combination training group lost a mean of -1.7 ( -2.3 to -1.1 kg ; P patients with type 2 diabetes mellitus , a combination of aerobic and resistance training compared with the nonexercise control group improved HbA(1c ) levels . This was not achieved by aerobic or resistance training alone . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00458133", "OBJECTIVE —The purpose of this study was to assess the effectiveness of a low – re source -intensive lifestyle modification program incorporating resistance training and to compare a gymnasium-based with a home-based resistance training program on diabetes diagnosis status and risk . RESEARCH DESIGN AND METHODS —A quasi-experimental two-group study was undertaken with 122 participants with diabetes risk factors ; 36.9 % had impaired glucose tolerance ( IGT ) or impaired fasting glucose ( IFG ) at baseline . The intervention included a 6-week group self-management education program , a gymnasium-based or home-based 12-week resistance training program , and a 34-week maintenance program . Fasting plasma glucose ( FPG ) and 2-h plasma glucose , blood lipids , blood pressure , body composition , physical activity , and diet were assessed at baseline and week 52 . RESULTS —Mean 2-h plasma glucose and FPG fell by 0.34 mmol/l ( 95 % CI −0.60 to −0.08 ) and 0.15 mmol/l ( −0.23 to −0.07 ) , respectively . The proportion of participants with IFG or IGT decreased from 36.9 to 23.0 % ( P = 0.006 ) . Mean weight loss was 4.07 kg ( −4.99 to −3.15 ) . The only significant difference between resistance training groups was a greater reduction in systolic blood pressure for the gymnasium-based group ( P = 0.008 ) . CONCLUSIONS —This intervention significantly improved diabetes diagnostic status and reduced diabetes risk to a degree comparable to that of other low – re source -intensive lifestyle modification programs and more intensive interventions applied to individuals with IGT . The effects of home-based and gymnasium-based resistance training did not differ significantly", "OBJECTIVE To describe the 1 ) lifestyle intervention used in the Finnish Diabetes Prevention Study , 2 ) short- and long-term changes in diet and exercise behavior , and 3 ) effect of the intervention on glucose and lipid metabolism . RESEARCH DESIGN AND METHODS There were 522 middle-aged , overweight subjects with impaired glucose tolerance who were r and omized to either a usual care control group or an intensive lifestyle intervention group . The control group received general dietary and exercise advice at baseline and had an annual physician 's examination . The subjects in the intervention group received additional individualized dietary counseling from a nutritionist . They were also offered circuit-type resistance training sessions and advised to increase overall physical activity . The intervention was the most intensive during the first year , followed by a maintenance period . The intervention goals were to reduce body weight , reduce dietary and saturated fat , and increase physical activity and dietary fiber . RESULTS The intervention group showed significantly greater improvement in each intervention goal . After 1 and 3 years , weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control group , respectively . Measures of glycemia and lipemia improved more in the intervention group . CONCLUSIONS The intensive lifestyle intervention produced long-term beneficial changes in diet , physical activity , and clinical and biochemical parameters and reduced diabetes risk . This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system", "OBJECTIVE To determine the efficacy of high-intensity progressive resistance training ( PRT ) on glycemic control in older adults with type 2 diabetes . RESEARCH DESIGN AND METHODS We performed a 16-week r and omized controlled trial in 62 Latino older adults ( 40 women and 22 men ; mean + /- SE age 66 + /- 8 years ) with type 2 diabetes r and omly assigned to supervised PRT or a control group . Glycemic control , metabolic syndrome abnormalities , body composition , and muscle glycogen stores were determined before and after the intervention . RESULTS Sixteen weeks of PRT ( three times per week ) result ed in reduced plasma glycosylated hemoglobin levels ( from 8.7 + /- 0.3 to 7.6 + /- 0.2 % ) , increased muscle glycogen stores ( from 60.3 + /- 3.9 to 79.1 + /- 5.0 mmol glucose/kg muscle ) , and reduced the dose of prescribed diabetes medication in 72 % of exercisers compared with the control group , P = 0.004 - 0.05 . Control subjects showed no change in glycosylated hemoglobin , a reduction in muscle glycogen ( from 61.4 + /- 7.7 to 47.2 + /- 6.7 mmol glucose/kg muscle ) , and a 42 % increase in diabetes medications . PRT subjects versus control subjects also increased lean mass ( + 1.2 + /- 0.2 vs. -0.1 + /- 0.1 kg ) , reduced systolic blood pressure ( -9.7 + /- 1.6 vs. + 7.7 + /- 1.9 mmHg ) , and decreased trunk fat mass ( -0.7 + /- 0.1 vs. + 0.8 + /- 0.1 kg ; P = 0.01 - 0.05 ) . CONCLUSIONS PRT as an adjunct to st and ard of care is feasible and effective in improving glycemic control and some of the abnormalities associated with the metabolic syndrome among high-risk older adults with type 2 diabetes", "OBJECTIVE To examine the effect of high-intensity progressive resistance training combined with moderate weight loss on glycemic control and body composition in older patients with type 2 diabetes . RESEARCH DESIGN AND METHODS Sedentary , overweight men and women with type 2 diabetes , aged 60 - 80 years ( n = 36 ) , were r and omized to high-intensity progressive resistance training plus moderate weight loss ( RT & WL group ) or moderate weight loss plus a control program ( WL group ) . Clinical and laboratory measurements were assessed at 0 , 3 , and 6 months . RESULTS HbA(1c ) fell significantly more in RT & WL than WL at 3 months ( 0.6 + /- 0.7 vs. 0.07 + /- 0.8 % , P body weight ( RT & WL 2.5 + /- 2.9 vs. WL 3.1 + /- 2.1 kg ) and fat mass ( RT & WL 2.4 + /- 2.7 vs. WL 2.7 + /- 2.5 kg ) were observed after 6 months . In contrast , lean body mass ( LBM ) increased in the RT & WL group ( 0.5 + /- 1.1 kg ) and decreased in the WL group ( 0.4 + /- 1.0 ) after 6 months ( P fasting glucose , insulin , serum lipids and lipoproteins , or resting blood pressure . CONCLUSIONS High-intensity progressive resistance training , in combination with moderate weight loss , was effective in improving glycemic control in older patients with type 2 diabetes . Additional benefits of improved muscular strength and LBM identify high-intensity resistance training as a feasible and effective component in the management program for older patients with type 2 diabetes", "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", "OBJECTIVE The purpose of this study was to evaluate whether a combined resistance and aerobic training program would improve insulin sensitivity compared with aerobic training alone in postmenopausal women with type 2 diabetes . A second objective was to relate the improved insulin sensitivity to changes in abdominal adipose tissue ( AT ) and thigh muscle density . RESEARCH DESIGN AND METHODS A total of 28 obese postmenopausal women with type 2 diabetes were r and omly assigned to one of three 16-week treatments : control , aerobic only training ( Ae only ) , or aerobic plus resistance training ( Ae+RT ) . Pre- and posttreatment outcome measures included glucose disposal by hyperinsulinemic-euglycemic clamp and computed tomography scans of abdominal AT and mid-thigh skeletal muscle . RESULTS Glucose infusion rates increased significantly ( P abdominal subcutaneous and visceral AT and increased muscle density . The Ae+RT training group exhibited a significantly greater increase in muscle density than the Ae only group . Improved glucose disposal was independently associated with changes in subcutaneous AT , visceral AT , and muscle density . Muscle density retained a relationship with glucose disposal after controlling for abdominal AT . CONCLUSIONS Adding resistance training to aerobic training enhanced glucose disposal in postmenopausal women with type 2 diabetes . The improved insulin sensitivity is related to loss of abdominal subcutaneous and visceral AT and to increased muscle density", "Objective : To compare the effects of counseling alone with that of additional participation in supervised training courses on exercise capacity in patients with impaired fasting glucose . Design : R and omized , controlled intervention trial using a nested cohort approach . Setting : Primary care centers in western Austria . Patients : Thirty-six patients with impaired fasting glucose ( 16 males , 20 females ; mean age , 57.5 ± 6.9 years ) . Interventions : Participants of both groups were instructed about the preventive effectiveness of changing their lifestyle , especially losing weight and increasing physical activity . One group had additionally been offered supervised , progressive , individually tailored aerobic exercise programs for 1 hour twice a week . Main Outcome Measures : Changes in the levels of exercise capacity , body mass , and fasting blood glucose . Results : The subjects with supervised exercise participated in this program for 1.8 hours ( ± 0.3 ) per week over 12 months . Supervised exercise was sufficient to maintain exercise capacity , whereas counseling alone was not ( + 4.4 % versus -6.9 % ; P = 0.01 ) . After the 12-month intervention period , body mass was reduced in the supervised exercise group ( -3.0 % ) compared with the counseling alone group ( + 1.0 % ) ( P = 0.03 ) and fasting plasma glucose levels had similarly improved by counseling for adequate lifestyle changes alone ( -8.2 % ) and in combination with supervised exercise ( -6.0 % ) . Conclusion : In contrast to counseling alone , 2 sessions of supervised training per week , besides the self-chosen physical activity and nutritional measures , are sufficient to maintain exercise capacity in patients with impaired fasting glucose", "Type 2 diabetes mellitus is increasing worldwide largely as a result from increasing obesity and sedentary lifestyle . The Finnish Diabetes Prevention Study ( DPS ) is the first individually r and omized controlled clinical trial to test the feasibility and efficacy of lifestyle modification in high-risk subjects . We r and omly assigned 522 ( 172 men , 350 women ) middle-aged ( mean age 55 yr ) , overweight ( mean body mass index 31 kg/m(2 ) ) subjects with impaired glucose tolerance either to the lifestyle intervention or control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight and intake of total and saturated fat , and increasing intake of fiber and physical activity . An oral glucose tolerance test was performed annually to detect incident cases of diabetes and to measure changes in metabolic parameters . The mean ( + /- SD ) weight reduction from baseline to year 1 and to year 2 , respectively , was 4.2 + /- 5.1 kg and 3.5 + /- 5.5 in the intervention group and 0.8 + /- 3.7 kg and 0.8 + /- 4.4 in the control group ( P risk of diabetes was reduced by 58 % ( P reduction in the incidence of diabetes was directly associated with number and magnitude of lifestyle changes made . In conclusion , the DPS is the first controlled trial demonstrating that type 2 diabetes can be prevented by changes in lifestyle in high-risk subjects", "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", "This study was undertaken to determine whether impaired glucose tolerance and associated risk factors for cardiovascular disease can be improved with ' healthy living ' by diet and exercise or with sulphonylurea therapy . Patients were recruited by screening subjects with either a family history of type II diabetes , previous gestational diabetes , or a previously raised plasma glucose ( 5.6 - 6.6 mmol/l ) . Impaired glucose tolerance was defined as hyperglycaemia on two separate tests , an achieved glucose level after a glucose infusion test above the 90th percentile of an age-matched normal population ( > 9.3 mmol/l ) or a fasting plasma glucose above the 95th percentile ( > 5.6 mmol/l ) . Thirty-seven subjects with impaired glucose tolerance were entered into a r and omized , prospect i ve study for 6 months with allocations to healthy living or double blind to sulphonylurea ( gliclazide 40 mg twice daily ) or placebo tablets . The study took place in an out-patient setting , with three times weekly exercise sessions at a Sports Centre . After 6 months the placebo group showed no change in plasma glucose , cholesterol and blood pressure . The subjects receiving gliclazide showed improved glucose levels ( mean fasting plasma glucose levels fell from 5.8 to 5.1 mmol/l , p plasma cholesterol or blood pressure . The healthy living group , after exclusion of four non-compliant subjects , showed no change in glucose levels , but a decreased systolic blood pressure ( fall in mean from 124 to 116 mmHg , p plasma cholesterol levels ( fall in mean from 5.2 to 4.5 mmol/l , p HDL : LDL ratio ( rise in mean from 0.39 to 0.46 , p impaired glucose tolerance may benefit in different ways from gliclazide and healthy living . The metabolic responses to each therapy may help to decrease the risk of developing diabetes and cardiovascular disease", "The Diabetes Prevention Program is a r and omized clinical trial testing strategies to prevent or delay the development of type 2 diabetes in high-risk individuals with elevated fasting plasma glucose concentrations and impaired glucose tolerance . The 27 clinical centers in the U.S. are recruiting at least 3,000 participants of both sexes , approximately 50 % of whom are minority patients and 20 % of whom are > or = 65 years old , to be assigned at r and om to one of three intervention groups : an intensive lifestyle intervention focusing on a healthy diet and exercise and two masked medication treatment groups -- metformin or placebo -- combined with st and ard diet and exercise recommendations . Participants are being recruited during a 2 2/3-year period , and all will be followed for an additional 3 1/3 to 5 years after the close of recruitment to a common closing date in 2002 . The primary outcome is the development of diabetes , diagnosed by fasting or post-challenge plasma glucose concentrations meeting the 1997 American Diabetes Association criteria . The 3,000 participants will provide 90 % power to detect a 33 % reduction in an expected diabetes incidence rate of at least 6.5 % per year in the placebo group . Secondary outcomes include cardiovascular disease and its risk factors ; changes in glycemia , beta-cell function , insulin sensitivity , obesity , diet , physical activity , and health-related quality of life ; and occurrence of adverse events . A fourth treatment group -- troglitazone combined with st and ard diet and exercise recommendations --was included initially but discontinued because of the liver toxicity of the drug . This r and omized clinical trial will test the possibility of preventing or delaying the onset of type 2 diabetes in individuals at high risk", "The purpose of this investigation was to determine whether moderate intensity resistance training ( RT ) improves glycaemic control in obese , type 2 diabetic men . Eighteen subjects were r and omly assigned to a 10-week RT program , or a non-training control group ( C ) . Glycosylated haemoglobin ( HbA 1c ) , fasting glucose and insulin , glucose and insulin 120 minutes ( 2h ) after a 75 g oral glucose load , body composition and muscular strength and endurance were measured before and after the 10-week experimental period . In the RT group fasting glucose and insulin decreased with training ( p 2-h glucose and insulin did not change in either group . Fat free mass ( FFM ) increased by 3.5 % after RT but was unchanged in the controls . Fat mass ( FM ) increased 6.9 % in C but was unchanged in RT . Percent body fat was unchanged in both groups . Muscular strength and endurance increased by 25 to 52 % in the RT group but was unchanged in controls . Changes in fasting glucose and HbA 1c were inversely related to changes in FFM . These results suggest that RT is an effective form of exercise training which modestly improves glycaemic control and lowers fasting insulin levels in obese type 2 diabetics", "The study on lifestyle-intervention and impaired glucose tolerance Maastricht ( SLIM ) is a 3 years r and omised clinical trial design ed to evaluate the effect of a combined diet and physical activity intervention program on glucose tolerance in a Dutch population at increased risk for developing type 2 diabetes . Here the design of the lifestyle-intervention study is described and results are presented from the preliminary population screening , conducted between March 1999 and June 2000 . In total , 2,820 subjects with an increased risk of having disturbances in glucose homeostasis ( i.e. age > 40 years and BMI > 25 kg/m(2 ) or a family history of diabetes ) underwent a first oral glucose tolerance test ( OGTT ) . Abnormal glucose homeostasis was detected in 826 subjects ( 30.4 % ) : 226 type 2 diabetes ( type 2DM , 8.3 % ) , 215 impaired fasting glucose ( IFG , 7.9 % ) and 385 impaired glucose tolerance ( IGT , 14.2 % ) . Both increasing age and BMI were strongly related to the prevalence of IGT and diabetes . After a second OGTT , 114 subjects with glucose intolerance and in otherwise good health were eligible for participation in the intervention study ( SLIM ) . The high prevalence of disturbances in glucose homeostasis observed in the preliminary screening underscore the importance of early ( lifestyle ) interventions in those at risk for developing diabetes . SLIM will address this topic in the Dutch population", "OBJECTIVE To evaluate the influence of a twice-weekly progressive resistance training ( PRT ) program , without a concomitant weight loss diet , on abdominal fat and insulin sensitivity in older men with type 2 diabetes . RESEARCH DESIGN AND METHODS Nine older men ( aged 66.6 + /- 3.1 ) with type 2 diabetes participated in a 16-week PRT supervised program ( 50 - 80 % of the one repetition maximum ) , for all main muscle groups . Basal glycemia , HbA(1c ) , diet , habitual physical activity , body composition , and upper/lower maximal strength were measured . Insulin sensitivity was determined according to Bergman 's minimal model procedure and abdominal fat was obtained by computed tomography . The measurements were taken 4 weeks before training ( -4 ) , immediately before training ( 0 ) , and at 8-week intervals ( i.e. , weeks 8 and 16 ) during the 16-week training period . RESULTS No significant variation was observed in any of the above selected parameters during the 4-week control period . After PRT , both leg and arm maximal strength increased significantly by 17.1 and 18.2 % , respectively . Visceral and subcutaneous abdominal fat decreased significantly by 10.3 % ( from 249.5 + /- 97.9 to 225.6 + /- 96.6 cm(3 ) , P body mass . PRT significantly increased insulin sensitivity by 46.3 % ( from 2.0 + /- 1.2 to 2.8 + /- 1.6 . 10(4 ) . min(-1 ) . muU(-1 ) . ml(-1 ) , P fasting blood glucose ( from 146.6 + /- 28.3 to 135.0 + /- 29.3 mg/dl ) . Finally , a 15.5 % increase in energy intake ( from 2,287.1 + /- 354.7 to 2,619.0 + /- 472.1 kcal/day , P insulin sensitivity and fasting glycemia and decreases abdominal fat in older men with type 2 diabetes", "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", "OBJECTIVE The extent to which lifestyle must be altered to improve insulin sensitivity has not been established . This study compares the effect on insulin sensitivity of current dietary and exercise recommendations with a more intensive intervention in normoglycemic insulin-resistant individuals . RESEARCH DESIGN AND METHODS Seventy-nine normoglycemic insulin-resistant ( determined by the euglycemic insulin clamp ) men and women were r and omized to either a control group or one of two combined dietary and exercise programs . One group ( modest level ) was based on current recommendations and the other on a more intensive dietary and exercise program . Insulin sensitivity was measured using a euglycemic insulin clamp , body composition was measured using dual-energy X-ray absorptiometry , and anthropometry and aerobic fitness were assessed before and after a 4-month intervention period . Four-day dietary intakes were recorded , and fasting glucose , insulin , and lipids were measured . RESULTS Only the intensive group showed a significant improvement in insulin sensitivity ( 23 % increase , P=0.006 vs. 9 % in the modest group , P=0.23 ) . This was associated with a significant improvement in aerobic fitness ( 11 % increase in the intensive group , P=0.02 vs. 1 % in the modest group , P=0.94 ) and a greater fiber intake , but no difference in reported total or saturated dietary fat . CONCLUSIONS Current clinical dietary and exercise recommendations , even when vigorously implemented , did not significantly improve insulin sensitivity ; however , a more intensive program did . Improved aerobic fitness appeared to be the major difference between the two intervention groups , although weight loss and diet composition may have also played an important role in determining insulin sensitivity", "The objective of this study was to determine whether overweight insulin resistant individuals who lost weight and improved cardiovascular risk factors during a 4-month lifestyle intervention could sustain these lifestyle changes in the long-term . Seventy-nine insulin resistant adults were r and omised to a control group or either a modest or intensive lifestyle intervention group for 4-months . Thereafter the two intervention groups were combined and all participants were followed-up at 8 , 12 and 24 months . Anthropometry , blood pressure , fasting glucose , lipids , insulin and aerobic fitness were measured and dietary intake was assessed . An interview was conducted to determine factors which participants perceived facilitated or hindered maintenance of healthy lifestyle habits . Seventy-two ( 91.1 % ) , sixty-nine ( 87.3 % ) and sixty-two ( 78.5 % ) participants were retained at 8 , 12 and 24-month respectively . At 4-months the adjusted difference in weight between the modest and control groups was -3.4 kg ( 95 % CI -5.4 , -1.3 ) p=0.002 and intensive and control groups was -4.7 kg ( -6.9 , -2.4 ) p=0.0001 respectively . At 2-years there were no significant differences for weight when the initial 3 groups were compared or when the combined intervention group was compared with the control group . At 2-years , 64 % of participants reported that more frequent follow-up would have helped them to maintain healthy lifestyle habits . Even intensive counselling for 4-months with 4-monthly and then yearly monitoring were not enough for maintaining lifestyle changes sufficient to sustain weight loss . More frequent monitoring for an indefinite period was perceived by two-thirds of participants as necessary for them to maintain their initial lifestyle changes", "Thirty-one subjects with impaired glucose tolerance were r and omly allocated to a group receiving advice to improve their diet and physical activity levels over 6 months ( n = 23 ) or to a control group ( n = 8) . At 6 months , 18 of the 23 subjects receiving ' healthy living ' advice were re-examined ( five subjects had withdrawn ) . Fourteen of the 18 subjects showed an alteration in diet or an increase in exercise . The 18 subjects re-evaluated showed a reduction in systolic blood pressure ( 118 + /- 15 vs 124 + /- 15 mmHg , p less than 0.05 ) and decrease in total plasma cholesterol ( 4.5 + /- 1 vs 5.2 + /- 1 mmol l-1 , p less than 0.01 ) and LDL-cholesterol levels ( 2.8 + /- 0.9 vs 3.2 + /- 0.9 mmol l-1 , p less than 0.05 ) . Plasma glucose levels were unchanged . One subject withdrew from the control group . At 6 months , the seven control subjects examined showed no significant change in metabolic parameters , with little measurable change in diet or exercise . At 2 years , 17 of the 23 ' healthy living ' subjects were reassessed . Nine of the subjects had continued to exercise or maintained a decreased weight compared to baseline . Fasting plasma glucose levels had increased ( 6.0 + /- 1.2 vs 5.5 + /- 0.6 mmol l-1 , p less than 0.05 ) , with the only continued improvement being a reduced LDL level ( 2.8 + /- 0.7 vs 3.1 + /- 0.9 mmol l-1 , p less than 0.05 ) . At 2 years , a similar proportion of the control group were taking regular exercise compared with the ' healthy living ' group . ( ABSTRACT TRUNCATED AT 250 WORDS", "BACKGROUND Obesity exacerbates the age-related decline in physical function and causes frailty in older persons . However , appropriate treatment for obese older persons is unknown . We evaluated the effects of weight loss and exercise therapy on physical function and body composition in obese older persons . METHODS We screened 40 obese older volunteers and eventually r and omized 27 frail obese older volunteers to treatment or control groups . Treatment consisted of 6 months of weekly behavioral therapy for weight loss in conjunction with exercise training 3 times per week . Physical function was evaluated with measurements of frailty ( Physical Performance Test , peak oxygen consumption , and Functional Status Question naire ) ; strength , gait , and balance tests ; body composition with dual-energy x-ray absorptiometry ; and quality of life using the Medical Outcomes Survey 36-Item Short-Form Health Survey . Results are reported as mean + /- SD . RESULTS Two subjects in the treatment group did not comply with the intervention , and 1 subject in the control group withdrew . Analyses included all 27 subjects originally r and omized to the treatment and control groups . The treatment group lost 8.4 % + /- 5.6 % of body weight , whereas weight did not change in the control group ( + 0.5 % + /- 2.8 % ; P fat mass decreased ( -6.6 + /- 3.4 vs + 1.7 + /- 4.1 kg ; P fat-free mass ( -1.2 + /- 2.1 vs -1.0 + /- 3.5 kg ; P = .75 ) in the treatment group . The Physical Performance Test score ( 2.6 + /- 2.5 vs 0.1 + /- 1.0 ; P = .001 ) , peak oxygen consumption ( 1.7 + /- 1.6 vs 0.3 + /- 1.1 mL/min per kilogram ; P = .02 ) , and Functional Status Question naire score ( 2.9 + /- 3.7 vs -0.2 + /- 3.9 ; P = .02 ) improved in treated subjects compared with control subjects . Treatment also improved strength , walking speed , obstacle course , 1-leg limb stance time , and health survey physical subscale scores ( all P in obese older adults . Trial Registration clinical trials.gov Identifier : NCT00146133", "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", "This study assessed the effects of short-term circuit weight training ( CWT ) on glycaemic control in NIDDM . Twenty-seven untrained , sedentary subjects ( mean age , 51 ) with NIDDM participated in an 8-week r and omised , controlled study , involving either CWT 3 days/week ( n = 15 ) or no formal exercise ( control ) ( n = 12 ) . All subjects performed regular self-blood glucose monitoring throughout . Fasting serum glucose and insulin were measured following a 12-h fast and during an oral glucose tolerance test ( 75 g ) before and after 8 weeks . Twenty-one subjects completed the study ( CWT , n = 11 ) ( Control , n = 10 ) . Strength for all exercises improved significantly after CWT . Pooled time-series analysis , using a r and om effects model , revealed an overall decrease in self-monitored glucose levels with CWT compared to controls . Significant reductions from baseline values were observed in both the glucose ( -213 mmol l-1 per 120 min , P insulin ( -6130 pmol l-1 per 120 min , P change in self-monitored glucose levels and insulin area under the curve , but not glucose area under the curve , remained significant . Short-term CWT therefore may provide a practical exercise alternative in the lifestyle management of this condition", "Aims /hypothesisThe aim of this study was to investigate whether lifestyle intervention-induced changes in serum fatty acid profile of cholesteryl esters and estimated desaturase activities are related to improvements in insulin sensitivity in subjects at risk of type 2 diabetes . Material s and methods In the Study on Lifestyle Intervention and Impaired Glucose Tolerance Maastricht ( SLIM ) , 97 men and women with IGT were r and omised to a combined diet and exercise programme ( 47 intervention ) or a control group ( 50 control subjects ) . At baseline and after 1 year the following assessment s were made : an OGTT , an exercise test to determine maximal aerobic capacity , anthropometry , and analysis of the serum fatty acid profile of cholesteryl esters . Results The lifestyle programme was effective in reducing the intake of total and saturated fat , increasing physical activity , reducing obesity and improving insulin sensitivity and glucose tolerance . Regression analysis of the total population showed that an increase in the C20:4 n-6/C20:3 n-6 ratio ( estimated Δ5-desaturase activity ) and reductions in the C18:3 n-6/C18:2 n-6 ratio ( estimated Δ6-desaturase activity ) and the C16:1 n-7/C16:0 ratio ( estimated Δ9-desaturase activity or stearoyl-CoA desaturase-1 ) were significantly associated with a decrease in homeostasis model assessment for insulin resistance . After adjustment for lifestyle changes ( change in percentage body fat , aerobic capacity and saturated fat intake ) , these associations were partly reduced , but remained statistically significant . Conclusions /interpretationLifestyle-induced changes in fatty acid profile of cholesteryl esters and desaturase activities were independently related to changes in insulin sensitivity in subjects at risk of type 2 diabetes", "Background / Objectives : To evaluate the effect of a 4.1-year ( range 3–6 years ) lifestyle intervention according to general public health recommendations on glucose tolerance and dropout in a Dutch population with impaired glucose tolerance (IGT).Subjects/ Methods : In the Study on Lifestyle intervention and Impaired glucose tolerance Maastricht , 147 Caucasian IGT subjects were r and omized to an intervention group ( INT : n=74 ; 38 male , 36 female ) and control group ( CON : n=73 ; 37 male , 36 female ) . Annually , subjects underwent measurements of body weight , anthropometry , glucose tolerance ( oral glucose tolerance test ) , insulin resistance ( homeostasis model assessment -insulin resistance ) , maximal aerobic capacity ( VO2 max ) , blood lipids and blood pressure . INT received individual advice regarding a healthy diet and physical activity . Results : INT decreased their saturated fat intake , increased their carbohydrate intake ( P and VO2 max ( P=0.04 ) compared with CON . Body weight did not change significantly ( P=0.20 ) between the groups . After an initial decrease , 2-h glucose levels overall increased in INT ( + 0.11 mmol/l ) , but significantly less than CON ( + 1.18 mmol/l ; P=0.04 ) . Diabetes incidence was lower in INT versus CON ( 30 versus 56 % , P=0.04 ) . Change in body weight was associated with change in 2-h glucose levels ( β=0.399 mmol/l per kg , P=0.02 ) . Dropouts had a lower aerobic fitness and socioeconomic status , and a higher body mass index ( BMI ) and 2-h glucose compared with non-dropouts . Conclusions : Prolonged feasible changes in diet and physical activity prevent deterioration of glucose tolerance and reduce diabetes risk . Low socioeconomic status , low aerobic fitness and high BMI and 2-h glucose are indicative of dropout to the program", "OBJECTIVE Obesity and aging increase the risk of type 2 diabetes ( T2D ) . We evaluated whether weight loss therapy improves pancreatic endocrine function and insulin sensitivity in obese older adults . METHODS AND PROCEDURES Twenty-four obese ( BMI : 38 + /- 2 kg/m(2 ) ) older ( age : 70 + /- 2 years ) adults completed a 6-month r and omized , controlled trial . Participants were r and omized to diet and exercise ( treatment group ) or no therapy ( control group ) . beta-Cell function ( assessed using the C-peptide minimal model ) , alpha-cell function ( assessed by the glucagon response to an oral glucose load ) , insulin sensitivity ( assessed using the glucose minimal model ) , and insulin clearance rate were evaluated using a 5-h modified oral glucose tolerance test . RESULTS Body weight decreased in the treatment group , but did not change in the control group ( -9 + /- 1 % vs. 0 + /- 1 % ; P Insulin sensitivity doubled in the treatment group and did not change in the control group ( 116 + /- 49 % vs. -11 + /- 13 % ; P of beta-cell responsivity to glucose did not change ( P > 0.05 ) , the disposition index ( DI ) , which adjusts beta-cell insulin response to changes in insulin sensitivity , improved in the treatment group compared with the control group ( 100 + /- 47 % vs. -22 + /- 9 % ; P glucagon response decreased in the treatment but not in the control group ( -5 + /- 2 % vs. 4 + /- 4 % ; P Insulin secretion rate did not change ( P > 0.05 ) , but insulin clearance rate increased ( 51 + /- 25 % ; P plasma insulin concentrations . DISCUSSION Weight loss therapy concomitantly improves beta-cell function , lowers plasma glucagon concentrations , and improves insulin action in obese older adults . These metabolic effects are likely to reduce the risk of developing T2D in this population" ]

[ "Background : Exercise can be beneficial for cardiopulmonary , musculoskeletal or neurological systems , and other factors including mood , and may be beneficial in reducing fall risks , dementia and variables associated with quality of life ( QOL ) . Parkinson 's disease ( PD ) produces progressive motor and cognitive deterioration that may leave those inflicted unable to participate in st and ard exercise programs . Alternative forms of exercise such as yoga may be successful in improving physical function , QOL and physiological variables for overall well-being . Aim : This r and omized controlled pilot study investigated the effectiveness of yoga intervention on physiological and health-related QOL measures in people with PD . Methods and Material s : Thirteen people with stage 1 - 2 PD were r and omized to either a yoga ( n = 8) or a control group ( n = 5 ) . The yoga group participated in twice-weekly yoga sessions for 12 weeks . Participants were tested at baseline , and at 6 and 12 weeks using the Unified Parkinson 's Disease Rating Scale ( UPDRS ) , clinical measures of health-related QOL and physiological measures . Results : Significant improvement in UPDRS scores ( P = .006 ) , diastolic blood pressure ( P = 0.036 ) and average forced vital capacity ( P = 0.03 ) was noted in the yoga group over time . Changes between groups were also noted in two SF-36 subscales . Positive trends of improvement were noted in depression scores ( P = 0.056 ) , body weight ( P = 0.056 ) and forced expiratory volume ( P = 0.059 ) . Yoga participants reported more positive symptom changes including immediate tremor reduction . Conclusions : The results suggest that yoga may improve aspects of QOL and physiological functions in stages 1 - 2 PD . Future larger studies are needed to confirm and extend our findings of the effects of yoga in PD", "Objectives : Published preliminary findings from a r and omized-controlled trial suggest that an 8-week Yoga of Awareness intervention may be effective for improving symptoms , functional deficits , and coping abilities in fibromyalgia . The primary aims of this study were to evaluate the same intervention ’s posttreatment effects in a wait-list group and to test the intervention ’s effects at 3-month follow-up in the immediate treatment group . Methods : Unpaired t tests were used to compare data from a per protocol sample of 21 women in the immediate treatment group who had completed treatment and 18 women in the wait-list group who had completed treatment . Within-group paired t tests were performed to compare posttreatment data with 3-month follow-up data in the immediate treatment group . The primary outcome measure was the Fibromyalgia Impact Question naire Revised ( FIQR ) . Multilevel r and om-effects models were also used to examine associations between yoga practice rates and outcomes . Results : Posttreatment results in the wait-list group largely mirrored results seen at posttreatment in the immediate treatment group , with the FIQR Total Score improving by 31.9 % across the 2 groups . Follow-up results showed that patients sustained most of their posttreatment gains , with the FIQR Total Score remaining 21.9 % improved at 3 months . Yoga practice rates were good , and more practice was associated with more benefit for a variety of outcomes . Discussion : These findings indicate that the benefits of Yoga of Awareness in fibromyalgia are replicable and can be maintained", "Fibromyalgia is a chronic syndrome characterized by widespread pain , sleep disturbance , stiffness , fatigue , headache , and mood disorders . Recent research has result ed in an improved underst and ing of fibromyalgia and its possible causes . This article highlights some of the current research , discusses a strategy for using yoga and meditation as a therapy for fibromyalgia sufferers , and presents the results of a preliminary 8-week study using yoga and meditation to help manage fibromyalgia symptoms . The study of 11 participants found significant improvement in the overall health status of the participants and in symptoms of stiffness , anxiety , and depression . Significant improvements were also seen in the reported number of days \" felt good \" and number of days \" missed work \" because of fibromyalgia . Nonsignificant improvements were seen in measures of pain , fatigue , and how one felt in the morning . Effect sizes were medium to large for most tested areas . This study supports the benefits of yoga and meditation for individuals with fibromyalgia and encourages further research to explore their use as st and ard therapies for fibromyalgia", "Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field", "Background There is evidence for augmented processing of pain and impaired endogenous pain inhibition in Fibromyalgia syndrome ( FM ) . In order to fully underst and the mechanisms involved in FM pathology , there is a need for closer investigation of endogenous pain modulation . In the present study , we compared the functional connectivity of the descending pain inhibitory network in age-matched FM patients and healthy controls (HC).We performed functional magnetic resonance imaging ( fMRI ) in 42 subjects ; 14 healthy and 28 age-matched FM patients ( 2 patients per HC ) , during r and omly presented , subjectively calibrated pressure pain stimuli . A seed-based functional connectivity analysis of brain activity was performed . The seed coordinates were based on the findings from our previous study , comparing the fMRI signal during calibrated pressure pain in FM and HC : the rostral anterior cingulate cortex ( rACC ) and thalamus . Results FM patients required significantly less pressure ( kPa ) to reach calibrated pain at 50 mm on a 0–100 visual analogue scale ( p higher connectivity to the amygdala , hippocampus , and brainstem in healthy controls , compared to FM patients . There were no regions where FM patients showed higher rACC connectivity . Thalamus showed significantly higher connectivity to the orbitofrontal cortex in healthy controls but no regions showed higher thalamic connectivity in FM patients . Conclusion Patients with FM displayed less connectivity within the brain ’s pain inhibitory network during calibrated pressure pain , compared to healthy controls . The present study provides brain-imaging evidence on how brain regions involved in homeostatic control of pain are less connected in FM patients . It is possible that the dysfunction of the descending pain modulatory network plays an important role in maintenance of FM pain and our results may translate into clinical implication s by using the functional connectivity of the pain modulatory network as an objective measure of pain dysregulation", "& NA ; A mounting body of literature recommends that treatment for fibromyalgia ( FM ) encompass medications , exercise and improvement of coping skills . However , there is a significant gap in determining an effective counterpart to pharmacotherapy that incorporates both exercise and coping . The aim of this r and omized controlled trial was to evaluate the effects of a comprehensive yoga intervention on FM symptoms and coping . A sample of 53 female FM patients were r and omized to the 8‐week Yoga of Awareness program ( gentle poses , meditation , breathing exercises , yoga‐based coping instructions , group discussion s ) or to wait‐listed st and ard care . Data were analyzed by intention to treat . At post‐treatment , women assigned to the yoga program showed significantly greater improvements on st and ardized measures of FM symptoms and functioning , including pain , fatigue , and mood , and in pain catastrophizing , acceptance , and other coping strategies . This pilot study provides promising support for the potential benefits of a yoga program for women with FM", "OBJECTIVES This study aim ed to verify whether techniques of yoga with and without the addition of Tui Na might improve pain and the negative impact of fibromyalgia ( FMS ) on patients ' daily life . DESIGN Forty ( 40 ) FMS women were r and omized into two groups , Relaxing Yoga ( RY ) and Relaxing Yoga plus Touch ( RYT ) , for eight weekly sessions of stretching , breathing , and relaxing yogic techniques . RYT patients were further su bmi tted to manipulative techniques of Tui Na . OUTCOME MEASURE Outcome measures comprised the Fibromyalgia Impact Question naire ( FIQ ) , pain threshold at the 18 FMS tender points , and a verbal graduation of pain assessed before treatment and on the followup . The visual analog scale ( VAS ) for pain was assessed before and after each session and on the follow-up . RESULTS Seventeen ( 17 ) RYT and 16 RY patients completed the study . Both RY and RYT groups showed improvement in the FIQ and VAS scores , which decreased on all sessions . The RYT group showed lower VAS and verbal scores for pain on the eighth session , but this difference was not maintained on the follow-up . Conversely , RY VAS and verbal scores were significantly lower just on the follow-up . CONCLUSIONS These study results showed that yogic techniques are valid therapeutic methods for FMS . Touch addition yielded greater improvement during the treatment . Over time , however , RY patients reported less pain than RYT . These results suggest that a passive therapy may possibly decrease control over FMS symptoms", "OBJECTIVES Restorative yoga ( RY ) is a gentle type of yoga that may be beneficial for cancer patients and post-treatment survivors . Study goals were : to determine the feasibility of implementing a RY intervention for women with breast cancer ; and to examine group differences in self-reported emotional , health-related quality of life , and symptom outcomes . METHODS Women with breast cancer ( n=44 ; mean age 55.8 years ) enrolled in this study ; 34 % were actively undergoing cancer treatment . Study participants were r and omized to the intervention ( 10 weekly 75-minute RY classes ) or a waitlist control group . Participants completed question naires at Week 0 ( baseline ) and Week 10 ( immediately post-intervention for the yoga group ) . RESULTS Group differences favoring the yoga group were seen for mental health , depression , positive affect , and spirituality ( peace/meaning ) . Significant baseline*group interactions were observed for negative affect and emotional well-being . Women with higher negative affect and lower emotional well-being at baseline derived greater benefit from the yoga intervention compared to those with similar values at baseline in the control group . The yoga group demonstrated a significant within-group improvement in fatigue ; no significant difference was noted for the control group . CONCLUSIONS Although limited by sample size , these pilot data suggest potential benefit of RY on emotional outcomes and fatigue in cancer patients . This study demonstrates that a RY intervention is feasible for women with breast cancer ; implication s for study design and implementation are noted with an emphasis on program adoption and participant adherence", "OBJECTIVES To develop and vali date a new risk-of-bias tool for nonr and omized studies ( NRSs ) . STUDY DESIGN AND SETTING We developed the Risk of Bias Assessment Tool for Nonr and omized Studies ( RoBANS ) . A validation process with 39 NRSs examined the reliability ( interrater agreement ) , validity ( the degree of correlation between the overall assessment s of RoBANS and Method ological Index for Nonr and omized Studies [ MINORS ] , obtained by plotting the overall risk of bias relative to effect size and funding source ) , face validity with eight experts , and completion time for the RoBANS approach . RESULTS RoBANS contains six domains : the selection of participants , confounding variables , the measurement of exposure , the blinding of the outcome assessment s , incomplete outcome data , and selective outcome reporting . The interrater agreement of the RoBANS tool except the measurement of exposure and selective outcome reporting domains ranged from fair to substantial . There was a moderate correlation between the overall risks of bias determined using RoBANS and MINORS . The observed differences in effect sizes and funding sources among the assessed studies were not correlated with the overall risk of bias in these studies . The mean time required to complete RoBANS was approximately 10 min . The external experts who were interviewed evaluated RoBANS as a \" fair \" assessment tool . CONCLUSIONS RoBANS shows moderate reliability , promising feasibility , and validity . The further refinement of this tool and larger validation studies are required", "OBJECTIVES AND METHODS This study examined whether gentle Hatha yoga reduced fibromyalgia-related symptoms for a convenience sample of 10 participants ranging in age from 39 to 64 years who received yoga instruction 2 times per week for 8 weeks . METHODS Respondents completed the Fibromyalgia Impact Question naire 1 time per week and provided weekly journal reports regarding their health status . Pre- and post-intervention manual tender point evaluations were also conducted . RESULTS Findings provide evidence of association between participating in gentle Hatha yoga classes and reduced fibromyalgia - related symptoms . CONCLUSIONS Additional r and omized controlled trials with larger sample sizes and greater empirical rigor are needed to more fully underst and this relationship", "The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials" ]

[ "Background Children with attention deficit hyperactivity disorder ( ADHD ) are characterised by developmentally inappropriate levels of hyperactivity , impulsivity and /or inattention and are particularly impaired when performing tasks that require a high level of cognitive control . Methylpheni date ( MPH ) and motivational incentives may help improve cognitive control by enhancing the ability to monitor response accuracy and regulate performance accordingly . Methods Twenty-eight children with DSM-IV ADHD ( combined type ) aged 9–15 years and pairwise-matched typically developing children ( CTRL ) performed a go/no-go task in which the incentives attached to performance on no-go trials were manipulated . The ADHD group performed the task off and on their usual dose of MPH . CTRL children performed the task twice but were never medicated . EEG data were recorded simultaneously and two electrophysiological indices of error monitoring , the error-related negativity ( ERN ) and error positivity ( Pe ) were measured . Amplitudes of each ERP were compared between diagnostic groups ( CTRL , ADHD ) , medication days ( Off MPH , On MPH ) and motivational conditions ( baseline – low incentive , reward , response cost ) . Results Error rates were lower in the reward and response cost conditions compared with baseline across diagnostic groups and medication days . ERN and Pe amplitudes were significantly reduced in ADHD compared with CTRL , and were significantly enhanced by MPH . Incentives significantly increased ERN and Pe amplitudes in the ADHD group but had no effect in CTRL . The effects of incentives did not interact with the effects of MPH on either ERP . Effect sizes were computed and revealed larger effects of MPH than incentives on ERN and Pe amplitudes . Conclusions The findings reveal independent effects of motivational incentives and MPH on two electrophysiological markers of error monitoring in children with ADHD , suggesting that each may be important tools for enhancing or restoring cognitive control in these children", "The effect of a single oral dose of caffeine was examined in a r and omised double-blind placebo-controlled repeated- measures cross-over study . Eighteen children with AD/HD , aged between 8 and 13 years , were individually age- and gender-matched with a control group . All children participated in two sessions , one week apart . Skin conductance level ( SCL ) from a 3 min eyes-closed epoch , commencing 30 min after ingestion of caffeine or placebo , was examined . Across conditions , mean SCL was lower in the AD/HD group than controls , confirming hypoarousal in AD/HD . Caffeine produced an increase in SCL , and this increase did not differ between the groups . However , arousal increases were dose-dependent in controls , but not in AD/HD . Rather , caffeine-induced arousal increases in the AD/HD group were positively related to their hyperactivity/impulsivity levels . This suggests an anomalous arousal mechanism in AD/HD functionally related to impairment in one symptom dimension", "The timing of caffeine effects on arousal levels was examined . From previous work in our laboratory , an increase in skin conductance level ( SCL ) was used as the marker of arousal increase , and we sought to identify the timing of this and related effects following caffeine ingestion . A single oral dose of caffeine ( 250 mg ) was used in a r and omised double-blind placebo-controlled repeated- measures cross-over study . Eyes-closed resting electroencephalogram ( EEG ) and autonomic data ( SCL , heart rate , respiration rate , and systolic and diastolic blood pressure ) during 2 min epochs that commenced every 4 min after ingestion , were analysed . The SCL placebo data were used to identify potential arousal measures prior to examining caffeine effects . Caffeine was associated with increased SCL , increased respiratory rate and a global reduction in alpha power . There were no significant cardiovascular effects of caffeine-induced arousal . These caffeine results are consistent with our recent electrodermal and EEG studies of arousal , and confirm the potential use of caffeine as a simple means of experimentally modifying arousal levels without task-related confounds", "Rationale Previous research investigating the effects of stimulants , such as methylpheni date ( MPH ) , on children with attention deficit/hyperactivity disorder ( AD/HD ) has rarely included autonomic measures of arousal . Objective Our aim was to clarify the effects of MPH on central and autonomic measures in AD/HD children during a continuous performance task ( CPT ) using a naturalistic open-label study . Method Thirty-six boys ( 18 AD/HD and 18 control ) participated in a CPT over two trial periods , allowing a more valid estimate of the effects of medication , rather than assuming that retesting per se has no substantial impact . MPH was administered to the AD/HD group 1 h prior to the second trial . Errors and reaction time ( RT ) were recorded as measures of performance , electrodermal activity as an autonomic nervous system measure and event-related potentials ( ERPs ) as an index of central nervous system activity . Results AD/HD children made more errors than controls in the first session , but no group differences were found after medication . No significant differences were observed for RT . Skin conductance level was found to be lower in AD/HD children than controls , but this difference was also ameliorated after medication . Conversely , mean skin conductance response to target stimuli was found not to differ between groups during the initial test phase but became significantly different in phase 2 . ERP data showed topographic differences between groups in N1 , P2 , N2 and P3 at the initial test phase , which were reduced at the second test . ConclusionS timulant medication ameliorated some of the dysfunctions in AD/HD children , which are reflected in behavioural and ERP measures . These results , in combination with general differences in electrodermal activity , support a hypoarousal model of AD/HD , which can explain the action of MPH in these children", "Attention Deficit Hyperactivity Disorder ( ADHD ) is a developmental disorder that has previously been related to a decreased sensitivity to errors and feedback . Supplementary to the traditional performance measures , this study uses autonomic measures to study this decreased sensitivity in ADHD and the modulating effects of medication . Children with ADHD , on and off Methylpheni date ( Mph ) , and typically developing ( TD ) children performed a selective attention task with three feedback conditions : reward , punishment and no feedback . Evoked Heart Rate ( EHR ) responses were computed for correct and error trials . All groups performed more efficiently with performance feedback than without . EHR analyses , however , showed that enhanced EHR decelerations on error trials seen in TD children , were absent in the medication-free ADHD group for all feedback conditions . The Mph-treated ADHD group showed ' normalised ' EHR decelerations to errors and error feedback , depending on the feedback condition . This study provides further evidence for a decreased physiological responsiveness to errors and error feedback in children with ADHD and for a modulating effect of Mph", "OBJECTIVE This study examined the use of caffeine to manipulate arousal level without the confounds associated with task-related activation . From previous work in our laboratory , an increase in skin conductance level ( SCL ) and EEG alpha frequency , together with a global decrease in alpha power , were used as markers of arousal increase , and we sought to identify these effects with caffeine ingestion . METHODS We examined the effect of a single oral dose of caffeine ( 250 mg ) in a r and omised double-blind placebo-controlled repeated- measures cross-over study . Eighteen healthy university students ( mean age 21 years ; 13/18 females ) participated in two sessions 1 week apart . EEG and autonomic data ( SCL , heart rate , systolic and diastolic blood pressure , and respiration rate ) from a 2 min eyes-closed epoch , commencing approximately 30 min after ingestion of caffeine or placebo , were examined . RESULTS Caffeine was associated with increased SCL , a global reduction in EEG power in the alpha b and , and a global increase in alpha frequency . There were no cardiovascular effects . CONCLUSIONS The positive results are consistent with recent electrodermal and EEG studies of arousal and suggest that caffeine may be utilised as a task-free means of manipulating arousal in future investigations . Further work is necessary to clarify the absence of cardiovascular effects , and to integrate those data with emerging conceptualisations of arousal and activation . SIGNIFICANCE The present data support the use of caffeine as a simple tool to explore the role of arousal in both normal and atypical functioning , and this may be useful in determining the validity and importance of supposed hyper- or hypo-arousal in such syndromes as attention-deficit/hyperactivity disorder ( AD/HD )", "This paper aims to examine the effects of methylpheni date ( MPH ) on integrated baseline and event-related psychophysiological measures in AD/HD . Thirty-four unmedicated AD/HD adolescents ( 11 - 17 years ; 6 females ) were first compared to 34 age- and sex-matched controls , and then re-tested at least 4 weeks after methylpheni date ( MPH ) medication . In each testing session , EDA was recorded simultaneously with EEG during a resting eyes open condition , and with ERPs during an auditory oddball task . Unmedicated AD/HD subjects were compared to controls and then AD/HD subjects were compared pre- and post-medication . Correlations between the change in EEG theta and the remaining psychophysiological variables were undertaken to provide information about post MPH treatment changes . In the unmedicated state , AD/HD was characterized by abnormally enhanced theta , across fronto- central sites , generally reduced P2 responses , with larger non-specific and oddball-elicited SCRs and poor behavioural performance on the oddball task . Following treatment , AD/HD showed a ' normalization ' of theta activity ( particularly in the right hemisphere ) , a reduction in the rate of decrement of EDA and a general increase in P3 amplitude . These findings suggest that methylpheni date is associated with a robust ' normalization ' of low frequency EEG activity during the resting brain state , but has less impact on task-related brain activity or phasic changes in autonomic function . This dissociation of resting and task-related activity may prove to be useful in elucidating the effects of stimulant versus new non-stimulant medications in AD/HD" ]

[ "To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results", "The aim of the present study was to compare intraindividually a type III fissure-sealant , glass ionomer cement with a resin-based sealant . One hundred and forty-eight first permanent molars were sealed in forty-seven children . After three years 20.8 percent of the resin and 34.7 percent of the glass ionomer cement sealants were partially lost , and 0 percent and 37.5 percent , respectively , were totally lost . One tooth ( 1.4 percent ) in the glass ionomer cement group and three teeth ( 4.2 percent ) in the resin group developed caries", "Context Clinicians rely on systematic review s for current , evidence -based information . Contribution This survival analysis of 100 meta-analyses indexed in ACP Journal Club from 1995 to 2005 found that new evidence that substantively changed conclusions about the effectiveness or harms of therapies arose frequently and within relatively short time periods . The median survival time without substantive new evidence for the meta-analyses was 5.5 years . Significant new evidence was already available for 7 % of the review s at the time of publication and became available for 23 % within 2 years . Implication Clinical ly important evidence that alters conclusions about the effectiveness and harms of treatments can accumulate rapidly . The Editors Systematic review s have become increasingly common in recent years ( 1 ) and are recommended by many as the best sources of evidence to guide both clinical decisions ( 2 ) and health care policy ( 3 ) . For systematic review s to fulfill these roles , their findings must remain relatively stable for at least several years or effective mechanisms must exist for alerting end users to important changes in evidence . Yet , surprisingly little research has assessed the extent to which systematic review s become out of date or the rate at which this occurs ( 47 ) . Some organizations , such as the Cochrane Collaboration , recommend updating systematic review s every 2 years , but few empirical data guide this or other recommendations about updating . We sought to determine how quickly systematic review s meet explicitly defined criteria for changes in evidence of sufficient importance to warrant updating . We also sought to identify predictors of survival time , the time to such important changes in evidence . Survival time might vary depending on many factors , including the type of question posed by the original review ( for example , therapeutic or diagnostic ) , the types of studies included ( for example , r and omized trials or observational studies ) , and whether the systematic review provided quantitative synthesis . To limit such variation , we focused on systematic review s of r and omized , controlled trials that evaluated therapeutic benefit or harm by providing quantitative synthesis ( meta- analysis ) for at least 1 outcome . Methods Study Design and Sample We used a quasi-r and om process ( alphabetical sort order by author ) to select 100 systematic review s that were indexed in ACP Journal Club with an accompanying commentary between January 1995 and December 2005 ( with a search date no later than 31 December 2004 to ensure at least 1 full year for new evidence to appear ) . We chose this sampling frame because ACP Journal Club selects systematic review s that meet explicit quality st and ards and are deemed directly relevant to clinical practice ( 8) . We regarded the sample size of 100 as sufficiently large to achieve suitably narrow confidence intervals and to permit evaluation of up to 5 potential predictors of survival . Eligibility Criteria Eligible review s evaluated the benefit or harm of a specific drug , class of drug , device , or procedure ( invasive procedure or surgery ) and included r and omized or quasi-r and omized , controlled trials . We excluded evaluations of alternative and complementary medicines because the stability of review s of such therapies might differ substantially from review s of conventional therapies . We required that review s provide a point estimate and 95 % confidence interval for at least 1 outcome in the form of a relative risk , odds ratio , or absolute risk difference for binary outcomes and weighted mean differences for continuous outcomes . We excluded meta-analyses of individual-patient data , meta-regressions , and indirect meta-analyses because of the difficulty of determining whether new data would alter previous quantitative results . Two team members independently assessed eligibility , with disagreements resolved by consensus involving a third review er . When more than 1 review on the same topic was identified , only the earliest was included . Search ing For each review , search es for new trials included identifying new systematic review s on the same topic , su bmi tting relevant content terms to the Clinical Queries function in Ovid , applying the Related Articles function in PubMed to the 3 largest and the 3 most recent trials in the original review ( up to 6 trials in total ) , and using Scopus ( www . scopus .com/ scopus /home.url ) to identify new r and omized trials that cited the original review . When these search strategies yielded no eligible new trials , we conducted more comprehensive electronic search es and review ed relevant chapters in such sources as Clinical Evidence and UpTo Date to ensure that we had not missed new trials . Team members who had background s in both medicine and clinical research screened citations retrieved by the preceding methods to identify trials that would have met the inclusion criteria in the original review . Retrieved articles were screened in chronological order to ascertain quantitative or qualitative signals for the need for updating . The review protocol stopped when any criteria for updating were met . Each systematic review was discussed in detail , with the final statussignal for updating was or was not detectedadjudicated by consensus ( Figure 1 ) . Figure 1 . Overall process for determining updating status . ACP Journal Club Signals for the Need to Up date Systematic Review s In design ing criteria for comparing new findings with those in a previous review , we adapted methods used by other investigators to address similar problems with comparing 2 sets of results relating to the same question ( 913 ) , such as r and omized and nonr and omized studies of the same intervention . These investigators identified conflicting findings among different publications using a combination of quantitative thresholds for differences in effect magnitude and qualitative judgments about the language used to describe the results . We have similarly conceptualized quantitative and qualitative signals of potential changes in evidence that are sufficiently important to warrant updating previous systematic review s. Quantitative Signals Quantitative signals consisted of a change in statistical significance or relative change in effect magnitude of at least 50 % . We restricted these changes to those involving 1 of the primary outcomes of the original review or any mortality outcome . We also ignored trivial changes in statistical significance when the original and up date d meta-analytic results both had P values between 0.04 and 0.06so that quantitative signals of changes in evidence would represent robust indicators of the need to up date previous review s. Quantitative signals were detected by combining data from eligible new trials with the previous results using a fixed-effects approach . Use of fixed-effect models allowed pooling of the new trials with the previous meta-analytic result , as opposed to having to obtain original data from all of the included trials in each of 100 systematic review s. Although r and om-effects models are usually preferred to avoid spurious precision in the face of heterogeneity , our goal was to detect potential changes in evidence that would warrant a formal up date , not produce exact estimates of the up date d results . Qualitative Signals Qualitative signals included new information about harm sufficient to affect clinical decision making , important caveats to the original results , emergence of a superior alternate therapy , and important changes in certainty or direction of effect . Qualitative signals were detected by using explicit criteria for comparing the language in the original review with descriptions of findings in new systematic review s that addressed the same topic , pivotal trials , clinical practice guidelines , or recent editions of major textbooks ( for example , UpTo Date ) . Pivotal trials were defined as trials that had a sample size at least 3 times larger than that of the previous largest trial or were published in 1 of the 5 highest-impact general medical journals ( The New Engl and Journal of Medicine , Lancet , Journal of the American Medical Association , Annals of Internal Medicine , and the British Medical Journal ) . We defined 2 levels of importance for qualitative signals : potentially invalidating changes in evidence , which would make one no longer want clinicians or policymakers to base decisions on the original findings ( such as a pivotal trial that characterized treatment effectiveness in terms opposite of those in the original systematic review ) , and major changes in evidence , which would affect clinical decision making in important ways without invalidating the previous results ( such as the identification of patient population s for whom treatment is more or less beneficial ) . Major changes also included differing characterizations of effectiveness that were less extreme than those for potentially invalidating signals but that would still affect clinical decision making ( for example , a change from possibly beneficial to definitely beneficial ) . Of importance , such characterizations as possibly effective , probably effective , and promising , were all categorized as possibly effective . Thus , qualitative signals for changes in evidence captured substantive differences in the characterization of treatment effects , not merely semantic differences . Full definitions for each of the specific signals can be found at www.ohri.ca/UpdatingSystRevs . Data Collection For each review , we characterized the clinical content area , eligibility criteria for included trials , definitions of reported outcomes , number of included trials and participants , meta-analytic result for each outcome , identification of statistical heterogeneity , and excerpted quotations of the authors ' characterizations of the main results . We also abstract ed whether a given outcome was explicitly identified as 1 of the primary or main outcomes . We discounted identification of more than 3 such outcomes as inconsistent with the", "The aim of the present trial was to ( 1 ) compare the caries-preventive effect of glass ionomer sealants , placed according to the atraumatic restorative treatment ( ART ) procedure , with composite resin sealants over time and ( 2 ) investigate the caries-preventive effect after complete disappearance of sealant material . Forty-six boys and 57 girls , mean age 7.8 years , were r and omly divided into two treatment groups in a parallel-group study design . A light-polymerized composite resin sealant material and a high-viscosity glass ionomer were each placed in 180 fully erupted first molars in their respective treatment groups . Evaluation took place annually for 5 years by calibrated examiners . After 5 years , 86 % composite resin and 88 % glass ionomer sealants did not survive . Three categories of re-exposure periods for caries development in pits and fissures after complete loss of sealants were distinguished : 0–1 , 1–2 and 2–3 years . In the 2- to 3-year group , 13 and 3 % of pits and fissures previously sealed with composite resin and glass ionomer , respectively , were diagnosed as having developed a dentine lesion . The relative risks ( 95 % CI ) of dentine lesion development in surfaces sealed with glass ionomer compared to those sealed with composite resin after 3 , 4 and 5 years were 0.22 ( 0.06–0.82 ) , 0.32 ( 0.14–0.73 ) and 0.28 ( 0.13–0.61 ) , respectively . The relative risks of dentine lesion development in pits and fissures previously sealed with glass ionomer compared with composite resin over re-exposure periods of 1–2 and 2–3 years were 0.26 ( 0.14–0.48 ) and 0.25 ( 0.09–0.68 ) , respectively . We conclude that the caries-preventive effect of high-viscosity glass ionomer sealants , placed using the ART procedure , was between 3.1 and 4.5 times higher than that of composite resin sealants after 3–5 years . Furthermore , high-viscosity ( ART ) glass ionomer sealants appear to have a four times higher chance of preventing caries development in re-exposed pits and fissures of occlusal surfaces in first molars than light-cured composite resin sealant material over a 1- to 3-year period . A well- design ed clinical trial using different types of oral health personnel should be implemented to confirm these initial results", "OBJECTIVE To compare the retention and the caries preventive effect of a glass-ionomer developed for fissure sealing ( Fuji III ) and a chemically polymerized resin-based fissure sealant ( Delton ) . DESIGN A split mouth r and omized design using contralateral teeth . SETTING WHO Regional Demonstration , Training and Research Center for Oral Health , Damascus , Syrian Arab Republic . SAMPLE AND METHODS 179 children , 7 years old at the start of the study , were recruited from schools close to the Center . Only children with at least one pair of permanent first molars that were caries free or only had incipient lesions were included in the study . Follow-up examinations for sealant retention were done after 6 months , 1 year , 2 years and 3 years . The number of children available for reexamination was 129 ( after 6 months ) ; 121 ( after 1 year ) ; 115 ( after 2 years ) and 116 ( after 3 years ) . Four dental hygienists were trained in the sealant procedures and did approximately one fourth of the sealants each . RESULTS After 3 years the glass-ionomer sealant was completely lost in almost 90 % of the teeth compared to less than 10 % of the resin sealed teeth . After 3 years the relative risk of a tooth sealed with glass-ionomer over that of a tooth sealed with resin was 3.38 ( 95 % CL : 1.98 ; 5.79 ) . This finding was consistent over type of tooth . CONCLUSIONS The glass-ionomer sealant tested in the present study had poorer retention and less caries protective effect than the resin-based sealant used", "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 This article presents evidence -based clinical recommendations for the use of pit- and -fissure sealants on the occlusal surfaces of primary and permanent molars in children and adolescents . A guideline panel convened by the American Dental Association ( ADA ) Council on Scientific Affairs and the American Academy of Pediatric Dentistry conducted a systematic review and formulated recommendations to address clinical questions in relation to the efficacy , retention , and potential side effects of sealants to prevent dental caries ; their efficacy compared with fluoride varnishes ; and a head-to-head comparison of the different types of sealant material used to prevent caries on pits- and -fissures of occlusal surfaces . TYPES OF STUDIES REVIEW ED This is an up date of the ADA 2008 recommendations on the use of pit- and -fissure sealants on the occlusal surfaces of primary and permanent molars . The authors conducted a systematic search in MEDLINE , Embase , Cochrane Central Register of Controlled Trials , and other sources to identify r and omized controlled trials reporting on the effect of sealants ( available on the U.S. market ) when applied to the occlusal surfaces of primary and permanent molars . The authors used the Grading of Recommendations Assessment , Development , and Evaluation approach to assess the quality of the evidence and to move from the evidence to the decisions . RESULTS The guideline panel formulated 3 main recommendations . They concluded that sealants are effective in preventing and arresting pit- and -fissure occlusal carious lesions of primary and permanent molars in children and adolescents compared with the nonuse of sealants or use of fluoride varnishes . They also concluded that sealants could minimize the progression of non-cavitated occlusal carious lesions ( also referred to as initial lesions ) that receive a sealant . Finally , based on the available limited evidence , the panel was unable to provide specific recommendations on the relative merits of 1 type of sealant material over the others . Conclusions and practical implication s : These recommendations are design ed to inform practitioners during the clinical decision-making process in relation to the prevention of occlusal carious lesions in children and adolescents . Clinicians are encouraged to discuss the information in this guideline with patients or the parents of patients . The authors recommend that clinicians re-orient their efforts toward increasing the use of sealants on the occlusal surfaces of primary and permanent molars in children and adolescents", "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", "The usefulness of fluoride-releasing restorations in secondary caries prevention may be question ed because of the presence of other common sources of fluoride and because of ageing of the restorations . This study tested the hypothesis that glass-ionomer cement restorations , either aged or unaged , do not prevent secondary root caries , when fluoride dentifrice is frequently used . Sixteen volunteers wore palatal appliances in two phases of 14 days , according to a 2 × 2 crossover design . In each phase the appliance was loaded with bovine root dentine slabs restored with either glass-ionomer or resin composite , either aged or unaged . Specimens were exposed to cariogenic challenge 4 times/day and to fluori date d dentifrice 3 times/day . The fluoride content in the biofilm ( FB ) formed on slabs and the mineral loss ( ΔZ ) around the restorations were analysed . No differences were found between restorative material s regarding the FB and the ΔZ , for either aged ( p = 0.792 and p = 0.645 , respectively ) or unaged ( p = 1.00 and p = 0.278 , respectively ) groups . Under the cariogenic and fluoride dentifrice exposure conditions of this study , the glass-ionomer restoration , either aged or unaged , did not provide additional protection against secondary root caries ", "PURPOSE This study 's purpose was to evaluate the caries-preventive effect of a glass ionomer cement ( GIC ) used as an occlusal sealant on recently erupted permanent first molars . METHODS A double-blind , r and omized , controlled , clinical trial was undertaken that included 36 5- to 8-year-olds ( and 92 permanent first molars ) who were r and omly allocated to the test group ( GIC ) or the control group ( auto-polymerized resin-based sealant [ RBS ] ) . The Mann-Whitney test was used to compare the number of new carious or filled occlusal surfaces in the 2 groups . RESULTS After 6 months , 1 occlusal surface in the test group and 2 occlusal surfaces in the control group showed carious lesions ( P=.15 ) . In the fifth year of follow-up , 2 occlusal surfaces in the test group and 7 occlusal surfaces in the control group were filled or carious ( P=.42 ) , and the mean number of sealed surfaces that became carious or filled was 0.2 ( 95 % confidence interval [CI]=0.02 - 0.70 ) for the GIC-sealed teeth and 0.6 ( 95 % CI=0.20 - 1.30 ) for the RBS-sealed teeth ( P=.30 ) . CONCLUSION High-viscosity glass ionomer cement can provide some level of protection against dental caries when used as a dental sealant in newly erupted permanent first molars", "Since the last comprehensive review of anticoagulation in acute myocardial infa rct ion four additional r and omized control trials have been reported . The overwhelming majority of all trials favored anticoagulation . Rates of thromboembolism were higher in the control , and hemorrhagic complications in the anticoagulated group . Pooling of all r and omized control trials gives mean case fatality rates of 19.6 % for the control and 15.4 % for the anticoagulated group , a relative reduction of 21 % ( P less than 0.05 or less than 0.001 , depending on the analytic method ) . Five of six r and omized control trials reported \" no effect \" because the difference favoring anticoagulation was not statistically significant . However , sample sizes in these \" negative \" papers were too small to protect against missing a 21 % reduction in true case fatality rate due to anticoagulation ( beta greater than 0.10 ) . All patients who present no specific contraindication should receive anticoagulants during hospitalization for infa rct ion ", "In recent years , the interest in the use of glass-ionomer material s as fissure sealants has increased . The aim of this study was to compare the retention and caries-preventive effect of glass-ionomer ( Fuji III ) and resin-based light-cured ( Delton ) fissure sealants . Three health center dentists applied the sealants to 166 children ; glass-ionomer sealants on one side and resin-based sealants on the contralateral side of the mouth . After 2 yr , one pair of molar teeth in the mouths of 151 children was compared . Twenty-six percent of glass-ionomer and 82 % of resin-based sealants were totally present ( P carious . The results show that the retention of glass-ionomer sealants is markedly inferior to the resin-based sealants . In this study , however , no difference in caries increment on the sealed surfaces was observed . This may be due to the different mechanism of caries prevention for the sealant material s , or to the overall low caries activity of the participants", "Abstract Fissure sealing using partially filled resins is an established caries preventive practice . Glass ionomer cement ( GIC ) sealants may offer additional advantages due to their ability to bond chemically to enamel and release fluoride . The aim of this study was to compare the caries preventive effect and retention of a GIC and a resin-based sealant . Ketac-fil ® was tested against a chemically cured resin-based material ( Delton ® ) using a split mouth design . Perth ( Western Australia ) schoolchildren ( n= 465 ) , mean age 7 yr±0.72 ( S.D. ) , received sealants on the occlusal surfaces of sound homologous permanent first molar pairs . Test ( GIC ) and control ( resin ) sealants were systematic ally allocated to left and right sides based on the child 's month of birth , and were placed by dental therapists . After 3.64±0.11 yr , 415 children were examined by different clinicians , and the clinical status of the teeth and the extent of sealant retention recorded . Sealants were deemed retained when at least 2/3 of the fissure pattern was still sealed . In 252 tooth pairs , neither sealant was retained to this extent . In 71 pairs , the GIC was not retained and the resin sealant retained . In 40 pairs the reverse occurred ( McNemar 's test , χ2= 8.66 , P ( additional lesions prevented by the test agent per 100 treatments ) was 6.1%(95 % CI 3.3 % , 8.9 % ) . Effectiveness of the GIC was 80.6 % ( 95 % CI 59.6 % , 90.7 % ) . The relative risk of caries in test teeth was 0.19 ( 95 % CI 0.09 , 0.40 ) . The study suggests that complete retention of GIC sealant is not necessary for caries prevention in newly erupted permanent first molars", "OBJECTIVES The objectives of the study were to investigate the clinical use of two fluoride-releasing fissure sealants and to study fluoride release under laboratory conditions . METHODS In the clinical part of the study the two material s , FluroShield and Baseline , were applied to matched contralateral caries-free first permanent molars in 86 children aged 7 - 8 years . In the laboratory study fluoride release from each material was measured using a model cavity system . RESULTS After 3 years FluroShield was intact on 70 % of teeth . Retention was significantly better on lower molars than upper molars . Baseline was lost from all except two teeth within 6 months . After 3 years , caries had affected four teeth sealed with FluroShield and 24 teeth sealed with Baseline ; this difference was highly significant . The laboratory study showed that FluroShield released twice as much fluoride over 9 days than did Baseline . Long term studies using FluroShield showed a small steady fluoride release over 6 months . CONCLUSIONS The conclusion of the study was that FluroShield was a much more effective fissure sealant than Baseline . The clinical performance of FluroShield was comparable to that of other inert composite resin sealants and superior to that of fluoride-releasing sealants used previously", "The aim of this community-oriented study was to evaluate different methods to prevent fissure caries . The following products and measures were tested : 1 ) glass ionomer cement ( GIC ) applied by dentist ; 2 ) same material applied by short term ( 3 days ) trained personnel ( teachers ) ; 3 ) application of a 0.5 % HF solution three times ; 4 ) an established autopolymerized resin based sealant ( Delton ) . The study was performed in Bangkok , Thail and , a city in a developing country experiencing increasing caries prevalence . Children with at least three sound permanent molars from two age groups , 7 - 8 and 12 - 13-yr-olds respectively were chosen from very low to medium socioeconomic level families . 1264 children were systematic ally assigned to experiment or control groups based on school and DMFT . For the younger age group , the 2 yr mean DFS occlusal increment in the Control group was 0.66 surfaces . Significantly lower increments were observed in the GIC experimental group : 0.17 surfaces applied by the teachers and 0.32 applied by dentist , corresponding to 74 % and 52 % reductions , respectively . The mean increment in the HF group was 0.44 surfaces , a 33 % reduction in relation to the Control group . For the 12 - 13-yr-olds , the mean occlusal surface DF increment was 0.70 surfaces in the Control group . Almost no occlusal increment was found in the Delton group , 0.05 DFS , a 93 % reduction . In the GIC Dentist group , the DFS increment was 0.48 and in the Teacher group 0.56 , corresponding to 31 % and 20 % reduction , respectively . A slight and nonsignificant increase of caries in relation to the Control group was observed in the HF group . ( ABSTRACT TRUNCATED AT 250 WORDS", "The aim of this study was to compare the retention and caries preventive efficacy of glass ionomer ( Fuji III ; GIC ) and light-cured resin-based ( Delton ; LCR ) fissure sealants . One hundred and sixty-six 5 - 14-year-old schoolchildren received sealants on their newly erupted first or second molars ; a split mouth design was used . Previously reported 2-year results showed low retention rates for GIC sealants , but no difference in the caries increment between the groups . The same persons were invited to a dental check-up 6.1 to 7.8 ( mean 7.1 ) years after the application of sealants ; 111 persons ( 66.8 % of the original group ) participated in the study . The retention of sealants , and the caries status of occlusal surfaces and adjacent proximal surfaces was recorded . On the sealed occlusal surfaces , 10 % of GIC and 45 % of LCR sealants were totally and 9 % of GIC and 20 % of LCR sealants partially present . Twenty-three ( 23.5 % ) of the occlusal surfaces sealed with GIC and 16 ( 16.5 % ) of those sealed with LCR were carious or filled . Compared to LCR sealants , the effectiveness of GIC sealants was -44 % ( 95 % CI -71 % , -16 % ) and net gain -7 % ( 95 % CI -18 % , 4 % ) . The relative risk of caries occurring was 1.44 ( 95 % CI 0.96 , 2.14 )", "The 4-year results of a fissure sealant trial are reported . Glass polyalkenoate and bis GMA sealant were applied to 590 first permanent molar teeth using a half mouth study design in a group of 228 6 - 8-year-old children . Similar cariostasis was observed for the two material s at the end of 4 years despite marked differences in retention . Polyalkenoate cements probably should be regarded as ' fluoride depot ' material s rather than fissure sealants when used in this", "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" ]

[ "Background : The evidence stemming from trials on restorative material s is shaped not only by trial findings , but also trial design and validity . We aim ed to evaluate both aspects in r and omized controlled dental restorative trials published from 2005–2015 . Methods : Using systematic review methodology , we retrieved trials comparing restorative or adhesive dental material s. Two authors independently assessed design , risk of bias , registration status , and findings of trials . Descriptive and regression analyses were performed . Results : 114 studies on 15,321 restorations placed mainly in permanent teeth of 5232 patients were included . Per trial , the median number of patients was 37 ( 25th/75th percentiles : 30/51 ) . Follow-up was 24 ( 20/48 ) months . Seventeen percent of trials reported on sample size calculations , 2 % had been registered . Most trials ( 90 % ) used US Public Health Service ( USPHS ) criteria , and had a high risk of bias . More recent trials were more likely to have been registered , to have reported on sample size calculations , to be of low risk of bias , and to use other than USPHS- criteria . Twenty-three percent of trials yielded significant differences between groups . The likelihood of such differences was significantly increased in older studies , studies with potential reporting bias , published in journals with high impact factor ( > 2 ) , longer follow-up periods , and not using USPHS- criteria . Conclusions : The majority of dental restorative trials published from 2005–2015 had limited validity . Risk of bias decreased in more recent trials . Future trials should aim for high validity , be registered , and use defined and appropriate sample sizes , follow-up periods , and outcome measures", "PURPOSE This longitudinal r and omized controlled clinical trial evaluated direct composite restorations for clinical acceptability as posterior restoratives in single- or multi-surface cavities and provides a survey of the 4-year results . MATERIAL S AND METHODS Three dentists placed 46 Quixfil ( Xeno III ) and 50 Tetric Ceram ( Syntac Classic ) composite restorations in stress-bearing Class I and II cavities in first or second molars ( 43 adult patients ) . Clinical evaluation was performed at baseline and after 4 years by 2 other dentists using modified USPHS criteria . At the last recall period , 37 Quixfil and 46 Tetric Ceram restorations were assessed . RESULTS A total of 89.2 % of Quixfil and 97.8 % of Tetric Ceram posterior composites were assessed to be clinical ly excellent or acceptable with predominating alfa scores . Up to the 4-year recall , four Quixfil restorations failed because of bulk fracture , partial tooth fracture ( 2x ) and postoperative symptoms . One Tetric Ceram restoration was lost due to problems with tooth integrity . No significant differences between the two composites could be detected at 4 years for any of the evaluated clinical criteria ( p > 0.05 ) . The comparison of restoration performance with time within both groups yielded a significant increase in marginal discoloration and decrease in marginal integrity for both material s. After 4 years , small restorations exhibited significantly less marginal discoloration than large restorations . CONCLUSION Clinical assessment of stress-bearing Quixfil and Tetric Ceram posterior composite restorations showed good clinical results with predominantly alfa scores for both material", "OBJECTIVES To analyze the relationship between the cavity depth and liners with postoperative sensitivity of resin composite restorations . METHODS A clinical follow-up was conducted on 319 resin composite restorations made in the final year of an undergraduate program over a 3-year period . Along with the analyses of cavity type , cavity depth , type of pulpal protection and the material s used , the postoperative sensitivity was also examined on each restoration . RESULTS Thirty-nine percent of the restorations had no protective layer ( Group 1 ) . As the depth of the prepared cavities increased , the restorations received one of the three pulpal protection methods ; a calcium hydroxide base ( Group 2 ) , glass ionomer cement ( Group 3 ) , or protection with a calcium hydroxide base in combination with glass ionomer cement ( Group 4 ) . The incidence of postoperative sensitivity showed no significant difference among Groups 1 , 2 and 3 , but was significantly lower in Group 1 than in Group 4 . The restorations made in shallow and medium depth cavities demonstrated significantly less-postoperative sensitivity than those made in deep cavities . The newer generation dentine-bonding agents showed a significantly lower incidence of postoperative sensitivity than the early generation group . CONCLUSIONS Postoperative sensitivity in resin composite restorations was not related to the absence of protective layers but increased with the depth of cavities restored with the resin composite . The type of dentine-bonding agents could also be responsible for postoperative sensitivity", "PURPOSE To evaluate the 3-year clinical durability of the flowable bulk-fill resin composite SDR in Class I and Class II restorations . MATERIAL S AND METHODS Thirty-eight pairs of Class I and 62 pairs of Class II restorations were placed in 44 male and 42 female patients ( mean age 52.4 years ) . Each patient received at least two extended Class I or Class II restorations that were as similar as possible . In all cavities , a one-step self-etching adhesive ( XenoV+ ) was applied . One of the cavities of each pair was r and omly assigned to receive the flowable bulk-fill resin composite SDR in increments up to 4 mm as needed to fill the cavity 2 mm short of the occlusal cavosurface . The occlusal part was completed with an ormocer-based nanohybrid resin composite ( Ceram X mono+ ) . In the other cavity , only the resin composite CeramX mono+ was placed in 2 mm increments . The restorations were evaluated using slightly modified USPHS criteria at baseline and then annually for 3 years . Caries risk and bruxing habits of the participants were estimated . RESULTS No post-operative sensitivity was reported . At the 3-year follow-up , 196 restorations - 74 Class I and 122 Class II - were evaluated . Seven restorations failed ( 3.6 % ) , 4 SDR-CeramX mono+ and 3 CeramX mono+ only restorations , all of which were Class II . The main reason for failure was tooth fracture , followed by resin composite fracture . The annual failure rate ( AFR ) for all restorations ( Class I and II ) was 1.2 % for the bulkfilled restorations and 1.0 % for the resin composite-only restorations ( p > 0.05 ) . For the Class II restorations , the AFR was 2.2 % and 1.6 % , respectively . CONCLUSION The 4-mm bulk-fill technique showed good clinical effectiveness during the 3-year follow-up", "OBJECTIVE The objective of this split-mouth r and omized controlled study was to compare the 2-year clinical performance of two restorative techniques and material s for posterior permanent carious teeth . METHOD AND MATERIAL S After signing informed consent , 30 patients aged between 7 and 16 received two Class 1 restorations on cavities on permanent first or second molar teeth performed with one of two systems : incrementally placed conventional posterior composite resin ( Herculite Ultra , Kerr ) , and sonic-resin placement system ( SonicFill , Kerr ) with single-component self-etch adhesive system ( Kerr ) according to the manufacturers ' directions . Two blinded observers evaluated the restorations at three times ( baseline , and after 1 and 2 years ) according to the US Public Health Service modified criteria . Kruskal-Wallis test and Mann-Whitney U-test were used to compare the clinical performance of the restorative systems . RESULTS The restorative systems showed similar clinical performance at 2 years . At the end of 2 years in both groups , one restoration 's marginal staining Alpha ratings decreased . In the same period , two restorations in the conventional group and one in the SonicFill group received Bravo ratings for color match and surface roughness scorings . CONCLUSION The sonic-resin placement system demonstrated similar results to incrementally placed conventional composite resin in terms of clinical success . Considering the advantages of providing up to 5 mm in a single layer , and the adjustability of the viscosity , bulk-fill composite restorations seem to be a good alternative to posterior Class 1 composite restorations . CLINICAL RELEVANCE This study suggests that a new dental material for bulk-fill technology exhibits similar clinical success to incrementally placed composite resin", "OBJECTIVE The aim of this study was to evaluate the morphology of the resin-dentin interface formed in vivo with two posterior resin composite placement techniques ( incremental and bulk ) . METHOD AND MATERIAL S After approval from the patients , 12 Class II cavities with margins in enamel ( 2.5 x 2.5 x 4.5 mm ) were prepared in caries-free premolars scheduled to be extracted for orthodontic reasons ( n = 6 ) . The cavities were restored with Single Bond + Filtek P60 as a bulk condensable technique or Single Bond + Filtek Z250 as an oblique incremental technique . After 1 week , the teeth were extracted with minimal trauma to the restored area . After the teeth were sectioned , a polyvinyl siloxane impression was taken from the resin-dentin interface to control for artifacts created during preparation for scanning electron microscopy . The specimens were subsequently processed for and observed under a scanning electron microscope to assess gap formation . RESULTS The mean percentage of gap formation was 6.1 % for teeth restored with the incremental placement technique and 18.7 % for teeth restored with the bulk placement technique . The difference was statistically significant . CONCLUSION The incremental placement of posterior resin composites may still provide better seal than the new bulk condensable technique", "The objective of this longitudinal clinical r and omized trial was to evaluate the clinical performance of a nanofilled and a nanohybrid resin composite in Class I occlusal restorations of posterior teeth over the course of 54 months . Forty-one adolescents participated in the study . The teeth were restored with Adper Single Bond 2 ( 3 M ESPE ) and nanofilled ( Filtek Z350 , 3 M ESPE ) , nanohybrid ( Esthet-X , Dentsply ) and microhybrid Filtek Z250 ( 3 M ESPE ) used as a control . After 54 months , the restorations were evaluated in accordance with the modified United States Public Health Service criteria . The McNemar and Friedman tests were used for statistical analysis , at a level of significance of 5 % . Five failed restorations were observed during the follow-up . A change to unacceptable restoration occurred for one Esthet-X , two Filtek Z350 , and two Filtek Z250 restorations , which received the clinical ly unacceptable score , Charlie , for both anatomic form and marginal adaptation . Secondary caries and postoperative sensitivity occurred in one Filtek Z250 and one Filtek Z350 restoration . When the five evaluation periods ( baseline and six , 12 , 30 , and 54 months ) were compared , significant differences were found in the marginal adaptation of Filtek Z250 and Filtek Z350 . Significant differences in the roughness criteria ( p=0.005 ) were also observed when the three composites were compared after 54 months ( Filtek Z350 > Filtek Z250 > Esthet-X ) , always within clinical ly acceptable limits . The material s investigated showed acceptable clinical performance for Class I restoration after 54 months . Long-term reevaluations are necessary for a more detailed analysis of these composites", "Background : Recently , manufacturers have introduced bulk-fill composite resins that reportedly can be placed in increments of 4 mm or greater . Objective : The purpose of this article was to report the results of 12 months prospect i ve r and omized clinical trial that evaluated the clinical performance of one high-viscosity bulk-fill composite resin in Class II cavities of posterior teeth . Material s and Methods : Thirty-four participants had at least two Class II cavities included the study . Class II cavities restored with either a Tetric EvoCeram bulk-fi fill or universal nano-hybrid resin composite ( Tetric EvoCeram ) . A total of 74 restorations ( 37 with each material ) on 34 patients were placed according to the manufacturers ' instructions by one calibrated operator . Results : Seventy restorations were evaluated after 12 months evaluation period . No postoperative sensitivity , anatomic form , retention , and secondary caries were observed after 6 and 12 months . Regarding the items color match , marginal discoloration , and marginal adaptation , the statistical analysis did not detect any statistical significance between two material s ( P > 0.05 ) . Conclusion : After 12 months of clinical service , all restorations evaluated for both material s were classified as ideal , receiving predominantly Alfa scores for all parameters analyzed . Clinical Relevance : This study presents that high-viscosity bulk-fill resin composites ( RCs ) perform just as well as nano-hybrid RCs with the 2 mm RC layering technique , therefore could be alternative to conventional nano-hybrid RCs", "OBJECTIVE The objective of this 6 year prospect i ve r and omized equivalence trial was to evaluate the long-term clinical performance of a new nano-hybrid resin composite ( RC ) in Class II restorations in an intraindividual comparison with its well-established conventional hybrid RC predecessor . METHODS Each of 52 participants received at least two , as similar as possible , Class II restorations . The cavities were chosen at r and om to be restored with an experimental nano-hybrid RC ( Exite/Tetric EvoCeram ( TEC ) ; n=61 ) and a conventional hybrid RC ( Exite/Tetric Ceram ( TC ) ; n=61 ) . The restorations were evaluated with slightly modified USPHS criteria at baseline and then annually during 6 years . RESULTS Two patient drop outs with 4 restorations ( 2TEC , 2TC ) were registered during the follow-up . A prediction of the caries risk showed that 16 of the evaluated 52 patients were considered as high risk patients . Eight TEC ( 2 P , 6 M ) and 6 TC ( 2P , 4 M ) restorations failed during the 6 years . The main reason of failure was secondary caries ( 43 % ; including the failure fracture+ secondary caries it increases to 57.1 % ) . 63 % of the recurrent caries lesions were found in high caries risk participants . The overall success rate at six years was 88.1 % . No statistical significant difference was found in the overall survival rate between the two investigated RC . SIGNIFICANCE The nano-hybrid RC showed good clinical performance during the 6 year evaluation , comparable to the well-established conventional hybrid RC", "OBJECTIVE This longitudinal r and omized controlled clinical trial evaluated direct composite restorations for clinical acceptability of posterior restoratives in single- or multisurface cavities and provided a preliminary survey of the 3- , 6- , and 18-month results . METHOD AND MATERIAL S Three clinicians placed 46 QuiXfil ( Xeno III ; Dentsply DeTrey ) and 50 Tetric Ceram ( Syntac Classic ; Vivadent ) composite restorations in stress-bearing Class 1 and 2 cavities in first or second molars ( 43 adult patients ) . Clinical evaluation was performed at baseline and after 3 , 6 , and 18 months by 2 other clinicians using modified US Public Health Service criteria . At the final recall period , 45 QuiXfil and 49 Tetric Ceram restorations were assessed . RESULTS A total of 97.8 % of QuiXfil and 100 % of Tetric Ceram posterior composites were assessed to be clinical ly excellent or acceptable with predominating Alpha scores . At the 18-month recall , 1 QuiXfil restoration had failed because of bulk fracture . No significant differences between either composite could be detected at 18 months for all evaluated clinical criteria ( P > .05 ) . Small QuiXfil restorations exhibited significantly less marginal discoloration ( P = .003 ) and better restoration integrity ( P = .008 ) than large restorations . The comparison of restoration performance with time within both groups yielded a significant increase in marginal discoloration for QuiXfil ( P = .011 ) and significant deterioration for anatomic form at the marginal step for Tetric Ceram ( P = .011 ) . However , both changes were only effects of scoring shifts from Alpha to Bravo . CONCLUSION Clinical assessment of stress-bearing QuiXfil and Tetric Ceram posterior composite restorations exhibited for both material s good clinical results with predominating Alpha scores", "The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials", "This longitudinal r and omized controlled clinical trial evaluated direct composite restorations for clinical acceptability as posterior restoratives in single- or multi-surface cavities and provides a survey of the 3-year results . Three dentists placed 46 QuiXfil ( Xeno III ) and 50 Tetric Ceram ( Syntac Classic ) composite restorations in stress-bearing class I and II cavities in first or second molars ( 43 adult patients ) . Clinical evaluation was performed at baseline and after 3 years by two other dentists using modified US Public Health Service criteria . At the last recall period , 40 QuiXfil and 46 Tetric Ceram restorations were assessed . A total of 92.5 % of QuiXfil and 97.8 % of Tetric Ceram posterior composites were assessed to be clinical ly excellent or acceptable with predominating alpha scores . Up to the 3-year recall , three QuiXfil restorations failed because of bulk fracture , partial tooth fracture , and postoperative symptoms . One Tetric Ceram restoration was lost due to problems with tooth integrity . No significant differences between both composites could be detected at 3 years for all evaluated clinical criteria ( p > 0.05 ) . The comparison of restoration performance with time within both groups yielded a significant increase in marginal discoloration ( p = 0.007 ) and deterioration of marginal integrity ( p = 0.029 ) for QuiXfil and significant increase in marginal discoloration ( p = 0.009 ) for Tetric Ceram . However , both changes were mainly effects of scoring shifts from alpha to bravo . Clinical assessment of stress-bearing QuiXfil and Tetric Ceram posterior composite restorations exhibited for both material s good clinical results with predominating alpha scores", "This study evaluated the performance of a low-shrinking resin composite compared with an amalgam for restoration of Class I and II cavities of moderate size in posterior teeth in a general practice setting . Fifty-two pairs of test and control restorations were placed in 49 patients . Clinical evaluations and assessment s of replica models were carried out at baseline , six months and one year . Patients recorded their level of satisfaction with the restorations by means of visual analog scales . Apart from one control restoration that failed due to a fractured cusp , all of the restorations review ed at six months and one year were intact with no unacceptable scores for any of the evaluation criteria . It was concluded that the resin composite evaluated , when used in conjunction with the recommended adhesive system , may be an appropriate alternative to amalgam in the restoration of posterior teeth over one year in clinical service", "This r and omized study evaluated a flowable resin composite bulk-fill technique in posterior restorations and compared it intraindividually with a conventional 2-mm resin composite layering technique over a 6-yr follow-up period . Thirty-eight pairs of Class II restorations and 15 pairs of Class I restorations were placed in 38 adults . In all cavities a single-step self-etch adhesive ( Xeno V ) was applied . In the first cavity of each pair , the flowable resin composite ( SDR ) was placed , in bulk increments of up to 4 mm . The occlusal part was completed with a layer of nanohybrid resin composite ( Ceram X mono ) . In the second cavity of each pair , the hybrid resin composite was placed in 2-mm increments . The restorations were evaluated using slightly modified US Public Health Service ( USPHS ) criteria at baseline and then annually for a time period of 6 yr . After 6 yr , 72 Class II restorations and 26 Class I restorations could be evaluated . Six failed Class II molar restorations , three in each group , were observed , result ing in a success rate of 93.9 % for all restorations and an annual failure rate ( AFR ) of 1.0 % for both groups . The AFR for Class II and Class I restorations in both groups was 1.4 % and 0 % , respectively . The main reason for failure was resin composite fracture", "OBJECTIVE This r and omized controlled clinical trial compared two techniques and material s for restoring carious teeth-Bulk dentine replacement versus incremental placement of a hybrid posterior resin composite material in terms of patient comfort ( post operative sensitivity and tenderness on biting ) . MATERIAL AND METHODS Seventy-two carious teeth were r and omized to one of two treatment groups : Group A-were restored with a bulk dentine replacement material or Group B-restored with incrementally placed hybrid composite . Patients were followed up by way of a structured phone call at day 2 and day 7 post-operatively . Patients reporting discomfort at day 7 were subsequently followed up on days 14 , and 30 . RESULTS All patients were followed up . At day 2 , 18/72 restored teeth had post-operative sensitivity ; this figure fell to 10/72 at day 7 . A Chi squared test revealed that at day 2 a greater level of sensitivity was reported by patients in Group A ( P=0.029 ) . However , at day 7 there was no statistically significant difference between the two groups in terms of sensitivity ( P=0.453 ) . 8/72 and 6 /72 teeth had tenderness to biting at days 2 and 7 respectively . A Chi squared test revealed no statistically significant difference between the two groups in terms of tenderness on biting at any time period ( P=0.722 ) . Interestingly , Class I cavities were found to be more tender on biting than Class II cavities . At day 30 2/72 teeth exhibited sensitivity and none of the teeth exhibiting tenderness on biting . CONCLUSION At day 7 there was no significant difference between the two groups in terms of postoperative sensitivity and tenderness on biting", "PURPOSE This double blind , r and omized clinical trial compared the postoperative sensitivity of the placement technique ( incremental and bulk fill ) in posterior composite resin restorations bonded with two different adhesive strategies ( self-etch and etch- and -rinse ) . METHODS Posterior dental cavities of 72 participants ( n=236 ) , with a cavity depth of at least 3 mm , were r and omly divided into four groups . The restorations were bonded using either the etch- and -rinse Tetric N-Bond ( Ivoclar Vivadent ) or the self-etch Tetric N-Bond SE ( Ivoclar Vivadent ) . The composite resin Tetric N-Ceram Bulk Fill ( Ivoclar Vivadent ) was placed either incrementally or using the bulk-fill technique . Two experienced and calibrated examiners evaluated the restorations using World Dental Federation criteria after one week of clinical service . Spontaneous postoperative sensitivity was assessed using a 0 - 4 numerical rating scale and a 0 - 10 and 0 - 100 visual analog scale up to 48 h after the restorative procedure and after one week . RESULTS The risk ( p>0.49 ) and intensity of spontaneous postoperative sensitivity ( p>0.38 ) was not affected by the adhesive strategy or the filling technique . The overall risk of postoperative sensitivity was 20.3 % ( 95 % confidence interval 15.7 - 25.9 ) and typically occurred within 48 hours after the restorative procedure . CONCLUSIONS The overall risk of immediate postoperative sensitivity was 20.3 % and was not affected by either the adhesive strategy ( etch- and -rinse/self-etch ) or the filling technique ( incremental/ bulk )" ]

[ "The number of published systematic review s of studies of healthcare interventions has increased rapidly and these are used extensively for clinical and policy decisions . Systematic review s are subject to a range of biases and increasingly include non-r and omised studies of interventions . It is important that users can distinguish high quality review s. Many instruments have been design ed to evaluate different aspects of review s , but there are few comprehensive critical appraisal instruments . AMSTAR was developed to evaluate systematic review s of r and omised trials . In this paper , we report on the updating of AMSTAR and its adaptation to enable more detailed assessment of systematic review s that include r and omised or non-r and omised studies of healthcare interventions , or both . With moves to base more decisions on real world observational evidence we believe that AMSTAR 2 will assist decision makers in the identification of high quality systematic review s , including those based on non-r and omised studies of healthcare interventions", "OBJECTIVE To evaluate efficacy , safety , and tolerability of long-acting injectable antipsychotic aripiprazole once-monthly 400 mg ( AOM 400 ) as maintenance treatment for bipolar I disorder ( BP-I ) . METHODS In a double-blind , placebo-controlled , 52-week r and omized withdrawal study conducted from August 2012 to April 2016 , patients with a DSM-IV-TR diagnosis of BP-I currently experiencing a manic episode were stabilized sequentially on oral aripiprazole and AOM 400 and then r and omized to AOM 400 or placebo . The primary end point was time from r and omization to recurrence of any mood episode . Other end points included proportion of patients with recurrence of any mood episode and recurrence by mood episode type . RESULTS Of 266 r and omized patients , 64 ( 48.1 % ) of 133 in the AOM 400 group and 38 ( 28.6 % ) of 133 in the placebo group completed the study . AOM 400 significantly delayed the time to recurrence of any mood episode compared with placebo ( hazard ratio : 0.45 ; 95 % CI , 0.30 to 0.68 ; P recurrence of any mood episode with AOM 400 ( 35/132 ; 26.5 % ) compared with placebo ( 68/133 ; 51.1 % ) , with the effects observed predominantly on manic episodes ( P . Patients were not depressed at study entry , and between-group differences in depressive episodes were not significant ( P adverse events ( incidence > 5 % ) that were reported at higher rates with AOM 400 than placebo were weight increase , akathisia , insomnia , and anxiety . CONCLUSIONS AOM 400 delayed the time to and reduced the rate of recurrence of mood episodes and was generally safe and well tolerated . These findings support the use of AOM 400 for maintenance treatment of BP-I. TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01567527", "A double-blind cross-over trial of depot flupenthixol in recurrent manic depressive psychosis was carried out . All patients continued on lithium . Eleven patients completed the two-year trial . Flupenthixol appeared to have no prophylactic effect", "Background : Risperidone is the first atypical antipsychotic to become available in a long-acting , injectable formulation . This is the first prospect i ve study to assess the effectiveness of long-acting risperidone in a cohort of bipolar patients . Methods : Twenty-nine DSM-IV acutely manic bipolar in patients with a history of poor or partial adherence to medication entered the mirror- design observational study . They received naturalistic treatment for a manic episode plus long-acting , injectable risperidone for a mean period of 2 years . The following measures were used to assess the effectiveness of risperidone : the number of hospitalizations , the number of manic , mixed , and depressive episodes leading to hospitalization , the mean duration of hospitalizations , time to relapse , treatment adherence , aggression and suicide attempts . The Clinical Global Impressions ( CGI ) was used for clinical relevance as well . Results : During the follow-up , there was a significant decrease in the number of hospitalizations per patient ( Z−2.72 P the number of manic or mixed episodes leading to hospitalization ( Z−2.68 P the hospitalizations due to depressive episodes , a decrease in the average length of hospitalization per patient ( Z−3.27 P increase in the time to any new episode ( first relapse ) ( Z−3.28 , P significant improvements in treatment adherence ( P ) and hetero-aggressive episodes ( P ) , but not suicide attempts ( P = NS ) . At study endpoint 14 patients ( 48 % ) were very much improved according to the CGI . Discussion : This observational long-term study provides support to long-acting injectable risperidone being effective for the maintenance treatment of mania and improving treatment adherence , reducing relapses and re-hospitalization rates ", "In an open , prospect i ve 12 month study of perphenazine decanoate ( PD ) , 42 psyhchotic patients diagnosed according to DSM‐III were treated with a fixed depot interval and an individual dose , guided by gas chromatographic perphenazine plasma concentration monitoring combined with clinical evaluation . Degree of illness was rated using a social‐psychiatric CGI‐scale and extrapyramidal side effects were evaluated by means of a modified Simpson and Angus rating scale . After six months of treatment , a statistically significant improvement was found ( p reduction in mean CGI‐scores was observed . Mild to moderate extrapyramidal side effects occurred in 9 patients ( 21 % ) principally during the initial phase of therapy . No other side effects or changes in blood chemistry were found during the study . Plasma concentrations of perphenazine increased during the initial 3 months and stabilized hereafter . There were however , large intra‐ and inter‐individual variations in the perphenazine plasma concentration/dose ratio . In addition , it was observed that plasma concentrations of perphenazine were significantly higher in patients who had been treated with neuroleptics for more than 10 years compared to those who had been treted 5 years or less . This observation indicates gradual development of tolerance to neuroleptic treatment ", "OBJECTIVE No large controlled trials have evaluated adjunctive maintenance treatment with long-acting injectable antipsychotics in patients with bipolar disorder . This study assessed whether adjunctive maintenance treatment with risperidone long-acting therapy ( RLAT ) , added to treatment-as-usual ( TAU ) medications for bipolar disorder , delays relapse in patients with bipolar disorder type I. METHODS This study included patients with bipolar disorder type I with > or = four mood episodes in the 12 months prior to study entry . Following a 16-week , open-label stabilization phase with RLAT plus TAU , remitted patients entered a 52-week , double-blind , placebo-controlled , relapse-prevention phase . R and omized patients continued treatment with adjunctive RLAT ( 25 - 50 mg every two weeks ) plus TAU ( n = 65 ) or switched to adjunctive placebo injection plus TAU ( n = 59 ) . The primary outcome measure was time to relapse to any mood episode . RESULTS Of 240 enrolled patients , 124 entered double-blind treatment . Time to relapse was longer in patients receiving adjunctive RLAT ( p = 0.010 ) . Relapse rates were 23.1 % ( n = 15 ) with adjunctive RLAT versus 45.8 % ( n = 27 ) with adjunctive placebo ; relative relapse risk was 2.3-fold higher with adjunctive placebo ( p = 0.011 ) . Completion rates were : adjunctive RLAT , 60.0 % ( n = 39 ) and adjunctive placebo , 42.4 % ( n = 25 ; p = 0.050 ) . Adverse event (AE)-related discontinuations were 4.6 % ( n = 3 ) and 1.7 % ( n = 1 ) , respectively . Common AEs ( adjunctive RLAT versus adjunctive placebo ) were : tremor ( 24.6 % versus 10.2 % ) , insomnia ( 20.0 % versus 18.6 % ) , muscle rigidity ( 12.3 % versus 5.1 % ) , weight increased ( 6.2 % versus 1.7 % ) , and hypokinesia ( 7.7 % versus 0.0 % ) . CONCLUSIONS Adjunctive RLAT significantly delayed time to relapse in patients with bipolar disorder type I who relapse frequently . Safety and tolerability of RLAT were generally consistent with that previously observed", "BACKGROUND Poor medication adherence is common among bipolar patients . METHOD We examined prospect i ve data from 2 cohorts of individuals from the Systematic Treatment Enhancement Program for Bipolar Disorder ( STEP-BD ) study ( 1999 - 2005 ) with bipolar disorder . Clinical and sociodemographic features associated with missing at least 25 % of doses of at least 1 medication were assessed using logistic regression , and a risk stratification model was developed and vali date d. RESULTS Of 3,640 subjects with 48,287 follow-up visits , 871 ( 24 % ) reported nonadherence on 20 % or more study visits . Clinical features significantly associated ( P adherence included rapid cycling , suicide attempts , earlier onset of illness , and current anxiety or alcohol use disorder . Nonadherence during the first 3 months of follow-up was associated with less improvement in functioning at 12-month follow-up ( P medication adherence can be estimated and may be useful in targeting interventions", "The hypothesis that flupenthixol decanoate may serve as an alter‐native to prophylactically administered lithium in recurrent manicdepressive illness , bipolar and unipolar type , was tested in two groups of patients . In Group I the patients were allocated r and omly to maintenance treatment with either lithium or flupenthixol decanoate . The patients in Group II had previously been given lithium and were switched to flupenthixol decanoate because of unsatisfactory prophylactic effect of lithium , doubtful tablet compliance , troublesome side effects , or fear of later harmful effects . The flupenthixol decanoate dosage was 20 mg every 2–3 weeks . The study was not blind", "OBJECTIVE Schizoaffective disorder is a complex illness for which optimal treatment is not well established . Results of the first controlled , relapse-prevention study of paliperidone palmitate once-monthly injectable ( paliperidone monthly ) in schizoaffective disorder are presented . METHOD The study was conducted between September 20 , 2010 , and October 22 , 2013 . Patients with schizoaffective disorder ( confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders ) experiencing acute exacerbation of psychotic and depressive/manic symptoms were stabilized with paliperidone monthly as monotherapy or as adjunctive therapy to mood stabilizers or antidepressants and r and omly assigned ( 1:1 ) to paliperidone monthly or placebo in a 15-month , double-blind , relapse-prevention phase . R and omization was stratified by administration as monotherapy or adjunctive therapy and by study center . The primary endpoint was time to relapse . RESULTS 334 patients were evaluated . Paliperidone monthly significantly delayed time to relapse for psychotic , depressive , and manic symptoms compared with placebo ( P Relapse risk was 2.49 times greater for placebo ( hazard ratio = 2.49 ; 95 % CI , 1.55 to 3.99 ; P Overall relapse rates were 33.5 % for placebo and 15.2 % for paliperidone monthly . For monotherapy , relapse risk was 3.38 times greater with placebo ( P = .002 ) , and for adjunctive treatment it was 2.03 times greater with placebo ( P = .021 ) . Paliperidone monthly was superior to placebo in maintaining functioning as measured by the Personal and Social Performance scale ( P = .014 , mixed-model repeated- measures analysis ) . The most common adverse events ( placebo , paliperidone monthly ) were increased weight ( 4.7 % , 8.5 % ) , insomnia ( 7.1 % , 4.9 % ) , schizoaffective disorder ( 5.9 % , 3.0 % ) , headache ( 3.5 % , 5.5 % ) , and nasopharyngitis ( 3.5 % , 5.5 % ) . Incidence of any extrapyramidal-related adverse event was 7.1 % for placebo and 8.5 % for paliperidone monthly . CONCLUSIONS Paliperidone monthly as monotherapy or adjunctive therapy significantly delayed psychotic , depressive , and /or manic relapses ; reduced their risk ; and better maintained functioning in patients with schizoaffective disorder . Results support the value of maintenance treatment with paliperidone monthly in schizoaffective disorder . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01193153", "BACKGROUND Treatment adherence is a significant problem in patients with bipolar disorder . This study was design ed to determine the efficacy of risperidone long-acting injectable ( LAI ) in the maintenance treatment of bipolar I disorder . METHODS Eligible patients with current or recent manic or mixed episodes ( n = 559 , aged 18 - 65 years ) were treated with open-label oral risperidone for 3 weeks ( period II ) and open-label risperidone LAI for 26 weeks ( n = 501 ; period III ) . Patients who maintained response ( n = 303 ) were r and omly allocated 1:1 to placebo injections ( n = 149 ) or to continue risperidone LAI ( n = 154 ) for up to 24 months ( period IV ) . RESULTS Most ( 77 % ) patients on risperidone LAI received a dose of 25 mg every 2 weeks during period IV . Time to recurrence for any mood episode ( primary outcome variable ) was significantly longer in the risperidone LAI group versus placebo ( p time to recurrence of elevated-mood episode ( p to recurrence of depressive episode ( p = .805 ) . Weight gains > or = 7 % ( compared with the period 's baseline ) occurred in 15 % of patients in period III ; in 12 % of patients on risperidone LAI and 3 % of patients on placebo in period IV . CONCLUSIONS Risperidone LAI monotherapy significantly delayed the time to recurrence of mood episodes , versus placebo , in this controlled , r and omized study in patients with bipolar I disorder . Risperidone LAI was tolerable and no new safety concerns emerged compared with previous studies of risperidone LAI", "BACKGROUND Noncompliance with medication is a very common feature among bipolar patients . Rates of poor compliance may reach 64 % for bipolar disorders , and noncompliance is the most frequent cause of recurrence . Knowledge of the clinical factors associated with noncompliance would enhance clinical management and the design of strategies to achieve a better outcome for bipolar patients . Although most patients withdraw from medication during maintenance treatment , compliance studies in euthymic bipolar sample s are scarce . METHOD Compliance treatment and its clinical correlates were assessed at the end of 2-year follow-up in 200 patients meeting Research Diagnostic Criteria for bipolar I or bipolar II disorder by means of compliance-focused interviews , measurements of plasma concentrations of mood stabilizers , and 2 structured interviews : the Schedule for Affective Disorders and Schizophrenia and the Structured Clinical Interview for DSM-III-R Axis II disorders . Well-compliant patients and poorly compliant patients were compared with respect to several clinical and treatment variables . RESULTS The rate of mildly and poorly compliant patients was close to 40 % . Comorbidity with personality disorders was strongly associated with poor compliance . Poorly compliant patients had a higher number of previous hospitalizations , but reported fewer previous episodes . The type of treatment was not associated with compliance . CONCLUSION Clinical factors , especially comorbidity with personality disorders , are more relevant for treatment compliance than other issues such as the nature of pharmacologic treatment . Compliant patients may have a better outcome in terms of number of hospitalizations , but not necessarily with respect to the number of episodes . Bipolar patients , especially those with personality disorders , should be monitored for treatment compliance", "Background To overcome nonadherence in patients with psychosis switch to long-acting injectable ( LAI ) antipsychotic formulations is adopted . Most oral versus LAI comparisons showed similar antipsychotic responses . Psychoses often overlap with substance use disorder ( SUD ) . Head-to-head LAI comparisons have hitherto focused only on non-comorbid population s. Objective The objective of this study was to compare two LAIs , administered for 12 months , in initially hospitalized patients with psychosis comorbid with SUD in their clinical and quality of life ( QoL ) outcomes . Patients and methods In patients were recruited during 2016 and switched r and omly to 400 mg intramuscular aripiprazole monohydrate ( AM ) ( N=50 ) or to 100 mg intramuscular paliperidone palmitate ( PP ) once-monthly ( N=51 ) ; patients were discharged and followed up for 12 months . Patients were rated at baseline and after 1 year through the Clinical Global Impression scale – severity ( CGIs ) , substance craving intensity was rated through a visual analog scale for substance craving , and QoL through the World Health Organization ( WHOQOL-BREF ) scale . We addressed confounders with backward stepwise logistic regression and three-way analysis of variance . Results PP were older and had more cases of schizophrenia spectrum and less bipolar disorders than AM , but AM had a stronger craving for substances at baseline . Both LAIs were associated with significant improvements in all outcomes , with AM displaying stronger effect sizes than PP . The two groups did not differ on baseline WHOQOL-BREF scores in any domain , but at the 1-year follow-up , AM fared better on all domains . The two groups did not differ in final severity , but PP scored higher than AM in craving at the 1-year endpoint . Limitation : The CGIs is not a refined tool for severity and the substance craving may be subject to recall bias . Conclusion 1-year AM and PP was followed by improved clinical status and QoL and reduced substance craving in a population with psychosis and SUD comorbidity . AM , compared to PP , improved craving and QoL at the 1-year follow-up", "BACKGROUND Despite the longer duration of the depressive phase in bipolar disorder and the frequent clinical use of antidepressants combined with antipsychotics or mood stabilizers , relatively few controlled studies have examined treatment strategies for bipolar depression . OBJECTIVE To examine the use of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression . DESIGN Double-blind , 8-week , r and omized controlled trial . SETTING Eighty-four sites ( inpatient and outpatient ) in 13 countries . Patients A total of 833 r and omized adults with bipolar I depression with a Montgomery-Asberg Depression Rating Scale ( MADRS ) score of at least 20 . Intervention Patients were r and omly assigned to receive placebo ( n = 377 ) ; olanzapine , 5 to 20 mg/d ( n = 370 ) ; or olanzapine-fluoxetine combination , 6 and 25 , 6 and 50 , or 12 and 50 mg/d ( n = 86 ) . MAIN OUTCOME MEASURE Changes in MADRS total scores using mixed-effects model repeated- measures analyses . RESULTS During all 8 study weeks , the olanzapine and olanzapine-fluoxetine groups showed statistically significant improvement in depressive symptoms vs the placebo group ( P olanzapine-fluoxetine group also showed statistically greater improvement than the olanzapine group at weeks 4 through 8 . At week 8 , MADRS total scores were lower than at baseline by 11.9 , 15.0 , and 18.5 points in the placebo , olanzapine , and olanzapine-fluoxetine groups , respectively . Remission criteria were met by 24.5 % ( 87/355 ) of the placebo group , 32.8 % ( 115/351 ) of the olanzapine group , and 48.8 % ( 40/82 ) of the olanzapine-fluoxetine group . Treatment-emergent mania ( Young Mania Rating Scale score or = 15 subsequently ) did not differ among groups ( placebo , 6.7 % [ 23/345 ] ; olanzapine , 5.7 % [ 19/335 ] ; and olanzapine-fluoxetine , 6.4 % [ 5/78 ] ) . Adverse events for olanzapine-fluoxetine therapy were similar to those for olanzapine therapy but also included higher rates of nausea and diarrhea . CONCLUSIONS Olanzapine is more effective than placebo , and combined olanzapine-fluoxetine is more effective than olanzapine and placebo in the treatment of bipolar I depression without increased risk of developing manic symptoms", "UNLABELLED Chengappa KNR , Turkin SR , Schlicht PJ , Murphy SL , Brar JS , Fagiolini A , Houck PR , Garbutt RG , Fredrick N. A Pilot , 15-month , r and omised effectiveness trial of Risperidone long acting injection ( RLAI ) versus oral atypical antipsychotic agents ( AAP ) in persons with bipolar disorder . OBJECTIVE Long-acting injectible antipsychotic agents are rarely considered in the treatment of bipolar patients [ bipolar disorder ( BPD ) ] . We posited that BPD patients receiving risperidone long-acting injections [ Risperidone long-acting injections ( RLAIs ) ] would experience fewer negative clinical events than those receiving oral atypical antipsychotic agents ( AAP ) . METHODS Adult BPD patients in a hypomanic , manic or mixed episode were r and omised to either oral risperdone followed by RLAI ( n = 23 ) or an AAP ( n = 25 ) for 15 months . Any mood stabilizers were continued . An independent clinician board declared any clinical events that occurred but the treatment assignment was concealed . RESULTS Nine of the 48 patients who participated in this study did not improve , leaving 39 patients in 1-year extension . RLAI patients received the following bi-weekly dosages : 25 mg ( n = 9 ) , 37.5 mg ( n = 8) , and 50 mg ( n = 6 ) . The AAP group included aripiprazole ( n = 11 , 15 - 30 mg/day ) , quetiapine ( n = 8 , 300 - 700 mg/day ) , olanzapine ( n = 5 , 15 - 25 mg/day ) , and ziprasidone , ( n = 1 , 160 mg/day ) . In total , 47 clinical events were declared . The RLAI-treated group experienced significantly fewer clinical events ( mean : 0.86 ± 0.73 ) compared with the AAP group ( 1.61 ± 1.29 ) , t = 2.29 , d.f . = 37 , p = 0.028 ( 95 % CI = 0.087 - 1.421 ) . Of all , 50 % of the AAP subjects gained ≥ 7 % of their baseline body weight as did 38 % of the RLAI-treated patients . CONCLUSIONS RLAI-treated patients experienced significantly fewer negative clinical events . Further exploration should focus on which subtypes of BPD patients might benefit from RLAI treatment . Weight gain in BPD subjects requires clinical attention . Limitations include an open design , small sample size and the inability to conclude on whether this strategy is useful for depressive episodes " ]

[ "BACKGROUND tibolone at usual doses of 2.5 mg/day in postmenopausal women has been shown to improve climacteric complaints , without affecting endometrial thickness and lipid profile or blood glucose . However , the potentially similar efficacy , but better tolerability , of a low dose of this drug ( 1.25 mg ) has never been established . METHODS 162 healthy , non-obese , post-menopausal women , aged 40 - 65 years , with an intact uterus were enrolled in a national , single centre , r and omised , double blind , placebo controlled , parallel group trial . After 1 week of runin , patients were treated for 24 weeks with placebo , tibolone 1.25 mg or 2.5 mg/day . During the study laboratory tests , endometrial ultrasound scans and mammography were performed . Occurrence of menopausal signs and symptoms , including vaginal bleeding , and quality of sexual life were also checked . RESULTS in the 120 patients terminating the study without major protocol violations , climacteric symptoms were similarly improved by tibolone 1.25 and 2.5 mg ( 78 % and 90 % reduction at week 24 for hot flushes , 36 % and 34 % for sweating episodes and 44 % and 51 % for vaginal dryness ) , but not by placebo . Benefits occurred earlier in the group treated with tibolone 2.5 mg . Quality of sexual life was almost invariably improved by tibolone as compared to placebo , but improvement occurred earlier in the tibolone 1.25 mg group . Severity of vaginal bleeding was not different between placebo and active treatment groups , except at week 12 when was higher . At the end of treatment vaginal bleeding occurred in 15 % of patients treated with placebo , 14 % treated with tibolone 1.25 mg and 12 % treated with tibolone 2.5 mg . Endometrial thickness and breast density were not changed by treatment , as well as FSH , 17-beta-estradiol , total cholesterol , HDL and LDL cholesterol , triglycerides and blood glucose . Adverse events were reported by 14.7 % , 26.7 % and 24.4 % of patients treated with placebo , tibolone 1.25 mg and tibolone 2.5 mg/day , respectively . CONCLUSIONS tibolone at doses of 1.25 or 2.5 mg/day given for 24 weeks to postmenopausal women displayed similar efficacy and safety profiles , though were more effective than placebo . Tibolone 1.25 mg induced a more gradual relief from climacteric symptoms and a more prompt improvement of sexual function", "In this report we evaluated the action of conjugated equine estrogens ( CEE ) on vaginal symptoms , cytology , pH , and flora in late postmenopausal women without any previous hormone therapy . The study was a r and omized , double-blind , placebo-controlled trial with 48 late postmenopausal women who received placebo or unopposed CEE ( 0.625mg/day of CEE orally ) during three months of treatment . Vaginal and sexual complaints were evaluated through daily diary cards . We analyzed vaginal changes through cytology and pH measurements . After three months of treatment , 20 % of placebo-treated patients and 80 % of the CEE-treated patients reported improvement in vaginal dryness and irritation . In the latter group , the vaginal cells and Lactobacillus increased and the vaginal pH decreased , without other changes in sexual complaints . We concluded that estrogen ameliorated the genital tract of late postmenopausal women without any previous hormone therapy", "OBJECTIVE In some women , hot flashes and other symptoms attributed to menopause persist for many years after the cessation of menses . The frequency and severity of such symptoms and response to hormone therapy in older women have not been well documented . METHODS We used data from the Heart and Estrogen/Progestin Replacement Study , a blinded , clinical trial among 2763 women with documented coronary disease and a uterus who were r and omized to receive either conjugated estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg in one tablet or placebo . Participants were queried at baseline and annually regarding menopausal symptoms . Breast symptoms were self‐reported , and uterine bleeding was recorded on a daily diary . RESULTS Symptoms associated with menopause were relatively common among Heart and Estrogen/Progestin Replacement Study participants , whose average age was 67 years and who averaged 18 years since menopause . At baseline , 16 % of women reported frequent hot flashes , 26 % vaginal dryness , 10 % genital irritation , 55 % trouble sleeping , and 53 % early awakening . Women assigned to hormone therapy reported less frequent hot flashes , vaginal dryness , and trouble sleeping compared with women assigned to placebo , but more frequent vaginal discharge , genital irritation , uterine bleeding , and breast symptoms . The reporting of breast symptoms among women in the hormone group decreased from 40 % at 1 year to 13 % by the 4th year . Uterine bleeding was reported by 31 % and spotting by an additional 33 % of women in the hormone group during the 1st year of treatment ; by the 4th year , these proportions had fallen to 11 % and 20 % , respectively . CONCLUSION Symptoms typically attributed to menopause are common in elderly women . Postmenopausal hormone therapy reduces hot flashes , trouble sleeping , and vaginal dryness , but at st and ard doses in elderly women is associated with vaginal discharge , genital irritation , uterine bleeding , and breast symptoms", "Objective : To determine the effects of raloxifene on sexual function in postmenopausal women with pre-existing vaginal atrophy treated with vaginal estrogen cream . Methods : A total of 187 naturally postmenopausal women , 42 - 80 years of age , with signs of genitourinary atrophy were enrolled in this 6-month , multicenter , parallel-group study . Subjects were r and omized to oral raloxifene HCl 60 mg daily or matching placebo ; the same subjects were also r and omized to receive one application of either vaginal conjugated estrogen cream 0.5 g twice weekly for 6 months or non-hormonal vaginal moisturizer twice weekly for 3 months , followed by conjugated estrogen cream for 3 months . Both investigators and subjects were masked to the identity of the oral medication . The vaginal preparations were administered in an open-label fashion . The Sexual Activity Question naire ( SAQ ) was administered at baseline and at 3 and 6 months . Safety was assessed throughout the study . Results : A total of 102 women were sexually active at baseline and , of these , 82 were also sexually active at the 6-month end-point . At 6 months , raloxifene and placebo , in the presence of vaginal conjugated estrogen cream , were both associated with improvement from baseline in vaginal dryness and reduced discomfort during sexual activity . There were no significant differences between raloxifene and placebo groups in any SAQ item . Enjoyment of sexual activity significantly increased from baseline with raloxifene but not with placebo . No difference in adverse events was observed between groups . Conclusion : Raloxifene had no negative effects on sexual function in postmenopausal women with vaginal atrophy who were treated concomitantly with vaginal estrogen cream", " The women in this study were either post-menopausal or ovariectomised for at least 1 yr prior to the study . They had also been treated for cancer of the cervix ( 27 women ) , endometrium ( 5 ) , ovaries ( 5 ) or breast ( 1 ) . All women presented with sexual troubles , mainly genital discomfort ( dyspareunia or vaginism ) . In a double-blind fashion , gynaecological capsules containing either an oestradiol diether ( ICD : promestriene ) or only the excipient were administered for 40 consecutive days . At the end of the treatment , the FSH , LH , oestrone ( E1 ) and oestradiol ( E2 ) plasma levels were not found to be significantly different from the pre-therapeutic values . These results suggest that promestriene acts on the vaginal mucosa , therefore not being converted back into the hormone from which it was derived . Also , in its dietheroxide form , promestriene is incapable of crossing the malpighian ( vaginal or epidermal ) epithelium and of reaching the general blood circulation . This discrepancy between the local anti-atrophic effects and the inability to exert systemic oestrogen activities singles out promestriene and justifies its therapeutic use when hormonally active oestrogens are contra-indicated , as in patients who have an oestrogen-sensitive cancer in their medical history", "Objective To assess the effect of combined hormone replacement therapy ( HRT ) on health related quality of life . Design R and omised placebo controlled double blind trial . Setting General practice s in United Kingdom ( 384 ) , Australia ( 94 ) , and New Zeal and ( 24 ) . Participants Postmenopausal women aged 50 - 69 at r and omisation ; 3721 women with a uterus were r and omised to combined oestrogen and progestogen ( n=1862 ) or placebo ( n=1859 ) . Data on health related quality of life at one year were available from 1043 and 1087 women , respectively . Interventions Conjugated equine oestrogen 0.625 mg plus medroxyprogesterone acetate 2.5/5.0 mg or matched placebo orally daily for one year . Main outcome measures Health related quality of life and psychological wellbeing as measured by the women ’s health question naire . Changes in emotional and physical menopausal symptoms as measured by a symptoms question naire and depression by the Centre for Epidemiological Studies depression scale ( CES-D ) . Overall health related quality of life and overall quality of life as measured by the European quality of life instrument ( EuroQol ) and visual analogue scale , respectively . Results After one year small but significant improvements were observed in three of nine components of the women ’s health question naire for those taking combined HRT compared with those taking placebo : vasomotor symptoms ( P sexual functioning ( P sleep problems ( P combined HRT group reported hot flushes ( P night sweats ( P aching joints and muscles ( P=0.001 ) , insomnia ( P vaginal dryness ( P placebo group , but greater proportions reported breast tenderness ( P vaginal discharge ( P Hot flushes were experienced in the combined HRT and placebo groups by 30 % and 29 % at trial entry and 9 % and 25 % at one year , respectively . No significant differences in other menopausal symptoms , depression , or overall quality of life were observed at one year . Conclusions Combined HRT started many years after the menopause can improve health related quality of life . Trial registration IS RCT N 63718836", "Aim . To evaluate with vali date d instruments changes in quality of life and sexuality in women receiving hormonal replacement therapy ( AHT ) . Design . R and omised , double-blind , double-dummy study with two parallel treatment arms . Patients and methods . Forty-seven healthy post-menopausal women , aged 45–64 years , were evaluated using the Female Sexual Function Index ( FSFI ) and the menopause-specific quality of life question naire ( MENQOL ) . Of them , 40 diagnosed with sexual dysfunction were r and omised ( 1:1 ) to receive daily 0.625 mg of conjugated estrogens plus 1.25 mg of methyl-testosterone and 100 mg of micronised progesterone or placebo . After 3 months follow-up , FSFI and MENQOL question naires were administered for a second time . Results . Quality of life was unchanged in the placebo group whereas AHT significantly improved scores of vasomotor , psychological , physical and sexual symptoms . As expected , FSFI was not modified in the placebo group while in AHT group the FSFI score improved significantly . In addition , at the end of the study , 68.7 % of subjects of the AHT group did not fit did not fit the criteria for sexual dysfunction as per the FSFI ( p methyl-testosterone to hormone therapy improves quality of life and sexuality in post-menopausal women with sexual dysfunction", "OBJECTIVES Guidelines recommend using the lowest effective dose of oestrogen for the management of vasomotor symptoms in postmenopausal women . The primary aim of this double-blind , multi-centre , r and omised study was to assess the efficacy of oral ultra-low dose continuous combined hormone replacement therapy with 17β-oestradiol and dydrogesterone . STUDY DESIGN 313 women with ≥50 moderate to severe hot flushes during the previous week were r and omised to 0.5 mg 17β-oestradiol/2.5 mg dydrogesterone ( E 0.5 mg/D 2.5 mg ) , 1 mg 17β-oestradiol/5 mg dydrogesterone ( E 1mg/D 5 mg ) or placebo for 13 weeks . The placebo group then switched to E 0.5 mg/D 2.5 mg for a further 39 weeks , whilst the other groups continued on the same treatment . RESULTS After 13 weeks , the reduction in the number of moderate to severe hot flushes/day in the E 0.5 mg/D 2.5 mg group was greater than in the placebo group ( -6.4 vs. -4.9 , p improved the total Menopause Rating Scale score . The number of bleeding/spotting days was lower with E 0.5 mg/D 2.5 mg than with E 1 mg/D 5 mg . The overall amenorrhoea rate with E 0.5 mg/D 2.5 mg was 81 % ; this increased to 91 % in months 10 - 12 . CONCLUSIONS Continuous combined 0.5 mg 17β-oestradiol and 2.5 mg dydrogesterone was effective in alleviating vasomotor symptoms and improving quality of life , and was associated with a high amenorrhoea rate and a good tolerability profile", "Background With the exception of sexual functioning and weight , social and behavioural effects of postmenopausal hormone therapy ( HT ) have not been reported from trials . This paper reports such results from the EPHT-trial in Estonia . Methods A r and omized trial , with a blind and non-blind sub-trial in Estonia . From 1999–2001 , 1778 women were recruited . The mean follow-up was 3.6 years . Women 's experiences were asked in the first and final study year by mailed question naires ( 74 and 81 % response rates ) . Comparisons of the groups were made by cross-tabulation and logistic regression , adjusting for age . Results There were no differences between the HT and non-HT groups in regard to being employed , the extent of social involvement or marital status or opinions on aging . There was no difference in the frequency of free-time exercise , or overweight . Some of the indicators suggested less sexual inactivity , but the differences were small . Conclusion In a trial setting , postmenopausal hormone therapy did not influence work or social involvement or health behaviour . Trial registration IS RCT", "OBJECTIVE : To evaluate the efficacy of two vaginal doses of estradiol ( E2 ) compared with placebo in the treatment of atrophic vaginitis . METHODS : In a multi-center , r and omized , double-blind , parallel-group study , 230 postmenopausal women received treatment with 25 mcg or 10 mcg E2 or placebo for 12 weeks . Efficacy was measured through composite score of three vaginal symptoms and grading of vaginal health . Additional analyses included maturation of vaginal and urethral mucosa . Safety assessment s included endometrial biopsy , adverse events , changes in laboratory tests , and physical examinations . After 12 weeks of treatment , all patients were switched to the open-label extension and received treatment with 25 mcg E2 up to week 52 . RESULTS : Vaginal tablets with 25 mcg and 10 mcg E2 showed significant ( P composite score of vaginal health . Other results with 10 mcg E2 were not entirely consistent with those for 25 mcg E2 . Over 12 weeks , both active treatments result ed in greater decreases in vaginal pH than placebo . There were no significant differences between the 25 mcg and 10 mcg E2 groups in terms of improvements in maturation value or composite score of three vaginal symptoms . The efficacy was maintained to week 52 with 25 mcg E2 . CONCLUSION : Vaginal tablets with 25 mcg and 10 mcg E2 provided relief of vaginal symptoms , improved urogenital atrophy , decreased vaginal pH , and increased maturation of the vaginal and urethral epithelium . Those improvements were greater with 25 mcg than with 10 mcg E2 . Both doses were effective in the treatment of atrophic vaginitis . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00465192 and NCT00464971 LEVEL OF EVIDENCE :", "BACKGROUND To compare the metabolic effects on lipids and acceptability and safety of , and compliance with , a continuous administration of conjugated estrogen plus medroxyprogesterone acetate ( Premelle ) versus a placebo in non-hysterectomized postmenopausal women . METHODS Sixty-six generally healthy , female , early post-menopausal women , from 45 - 60 years of age , were r and omized for an administration of conjugated estrogen plus medroxyprogesterone acetate ( Premelle , Premarin 0.625 mg plus medroxyprogesterone acetate 2.5 mg/tablet orally ) or a placebo for 6 months . The changes in each patient 's lipid profiles from baseline , the frequency of hot flushes , bleeding occurrences , and climacteric symptoms , were evaluated . Safety was monitored by means of physical examination , Papanicolau smear , transvaginal ultrasonography , and laboratory check-up . Adverse events were also recorded . RESULTS The difference before and after treatment in serum LDL-C and total cholesterol ( TC ) was statistically significant in the Premelle group ( LDL-C , p = 0.006 , TC , p = 0.040 ) . No statistically significant difference in the change from baseline was observed in the levels of LDL-C and TC in the placebo treatment group . There was a statistically significant change from baseline in menopausal symptoms , which were evaluated by the Greene Climacteric Scales in the Premelle group . There was no clinical ly significant finding in the physical examination , vital signs , laboratory data , or endometrial thickness in either treatment group . The difference in the number of patients who reported an adverse event was not statistically significant between the 2 treatment groups . CONCLUSIONS This study demonstrated that Premelle was effective in decreasing LDL-C and total cholesterol levels , and also showed an improvement in some menopausal symptoms , such as vasomotor and sexual dysfunction symptoms . No significant bleeding was observed with Premelle , which was well tolerated in this study . The results of this study could support the use of Premelle tablets as a convenient alternative hormone therapy", "Objective : The aim of this study was to study the efficacy and safety of ospemifene , a new selective estrogen receptor modulator , in the treatment of vulvovaginal atrophy in postmenopausal women . Methods : A r and omized , double-blind phase 3 study in which 826 postmenopausal women were r and omized 1:1:1 to receive treatment with ospemifene 30 or 60 mg/day or placebo orally for 12 weeks was conducted . The primary inclusion criteria were having 5 % or less superficial cells on the vaginal smear ( maturation index ) , vaginal pH greater than 5.0 , and at least one moderate or severe symptom of vulvovaginal atrophy . The four co primary endpoints were the change from baseline to 12 weeks in the percentage of superficial and parabasal cells on the vaginal smear , change in vaginal pH , and change in severity of most bothersome symptom ( vaginal dryness or dyspareunia ) compared with placebo . All participants were given a nonhormonal vaginal lubricant for use as needed . Results : Ospemifene was statistically significantly superior to placebo in each of the co primary endpoints at the 60-mg dose . Statistically significant results were achieved for all co primary endpoints with the 30-mg dose except for dyspareunia . Ospemifene was well tolerated at both doses and demonstrated a favorable safety profile . Conclusions : Ospemifene was shown to be effective and well tolerated for the treatment of the symptoms of vaginal dryness and dyspareunia associated with vulvovaginal atrophy over and above the use of provided lubricants", "Objective To assess the efficacy and safety of intravaginal estriol administration on urinary incontinence , urogenital atrophy , and recurrent urinary tract infections in postmenopausal women . Design Eighty-eight postmenopausal women with urogenital aging symptoms were enrolled in this prospect i ve , r and omized , placebo-controlled study . Participants were r and omly divided into two groups , with each group consisting of 44 women . Women in the treatment group received intravaginal estriol ovules : 1 ovule ( 1 mg ) once daily for 2 weeks and then 2 ovules once weekly for a total of 6 months as maintenance therapy . Women in the control group received inert placebo vaginal suppositories in a similar regimen . We evaluated urogenital symptomatology , urine cultures , colposcopic findings , urethral cytologic findings , urethral pressure profiles , and urethrocystometry before as well as after 6 months of treatment . Results After therapy , the symptoms and signs of urogenital atrophy significantly improved in the treatment group in comparison with the control group . Thirty ( 68 % ) of the treated participants , and only seven ( 16 % ) of the control participants registered a subjective improvement of their incontinence . In the treated participants , we observed significant improvements of colposcopic findings , and there were statistically significant increases in mean maximum urethral pressure , in mean urethral closure pressure as well as in the abdominal pressure transmission ratio to the proximal urethra . Urethrocystometry showed positive but not statistically significant modifications . Conclusions Our results show that intravaginal administration of estriol may represent a satisfactory therapeutic choice for those postmenopausal women with urogenital tract disturbances who have contraindications or refuse to undergo st and ard hormone therapy", "CONTEXT Menopausal hormone therapy has long been credited with many benefits beyond the indications of relieving hot flashes , night sweats , and vaginal dryness , and it is often prescribed to treat urinary incontinence ( UI ) . OBJECTIVE To assess the effects of menopausal hormone therapy on the incidence and severity of symptoms of stress , urge , and mixed UI in healthy postmenopausal women . DESIGN , SETTING , AND PARTICIPANTS Women 's Health Initiative multicenter double-blind , placebo-controlled , r and omized clinical trials of menopausal hormone therapy in 27,347 postmenopausal women aged 50 to 79 years enrolled between 1993 and 1998 , for whom UI symptoms were known in 23,296 participants at baseline and 1 year . INTERVENTIONS Women were r and omized based on hysterectomy status to active treatment or placebo in either the estrogen plus progestin ( E + P ) or estrogen alone trials . The E + P hormones were 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate ( CEE + MPA ) ; estrogen alone consisted of 0.625 mg/d of conjugated equine estrogen ( CEE ) . There were 8506 participants who received CEE + MPA ( 8102 who received placebo ) and 5310 who received CEE alone ( 5429 who received placebo ) . MAIN OUTCOME MEASURES Incident UI at 1 year among women without UI at baseline and severity of UI at 1 year among women who had UI at baseline . RESULTS Menopausal hormone therapy increased the incidence of all types of UI at 1 year among women who were continent at baseline . The risk was highest for stress UI ( CEE + MPA : relative risk [ RR ] , 1.87 [ 95 % confidence interval { CI } , 1.61 - 2.18 ] ; CEE alone : RR , 2.15 [ 95 % CI , 1.77 - 2.62 ] ) , followed by mixed UI ( CEE + MPA : RR , 1.49 [ 95 % CI , 1.10 - 2.01 ] ; CEE alone : RR , 1.79 [ 95 % CI , 1.26 - 2.53 ] ) . The combination of CEE + MPA had no significant effect on developing urge UI ( RR , 1.15 ; 95 % CI , 0.99 - 1.34 ) , but CEE alone increased the risk ( RR , 1.32 ; 95 % CI , 1.10 - 1.58 ) . Among women experiencing UI at baseline , frequency worsened in both trials ( CEE + MPA : RR , 1.38 [ 95 % CI , 1.28 - 1.49 ] ; CEE alone : RR , 1.47 [ 95 % CI , 1.35 - 1.61 ] ) . Amount of UI worsened at 1 year in both trials ( CEE + MPA : RR , 1.20 [ 95 % CI , 1.06 - 1.36 ] ; CEE alone : RR , 1.59 [ 95 % CI , 1.39 - 1.82 ] ) . Women receiving menopausal hormone therapy were more likely to report that UI limited their daily activities ( CEE + MPA : RR , 1.18 [ 95 % CI , 1.06 - 1.32 ] ; CEE alone : RR , 1.29 [ 95 % CI , 1.15 - 1.45 ] ) and bothered or disturbed them ( CEE + MPA : RR , 1.22 [ 95 % CI , 1.13 - 1.32 ] ; CEE alone : RR , 1.50 [ 95 % CI , 1.37 - 1.65 ] ) at 1 year . CONCLUSIONS Conjugated equine estrogen alone and CEE + MPA increased the risk of UI among continent women and worsened the characteristics of UI among symptomatic women after 1 year . Conjugated equine estrogen with or without progestin should not be prescribed for the prevention or relief of UI", "Objectives Drospirenone is a novel progestogen that , combined with 17β-estradiol , reduces the frequency and severity of menopausal vasomotor symptoms ( VMS ) in different population s. This double-blind , multicenter study compared the efficacy , safety and tolerability of 2 mg drospirenone/1 mg estradiol ( DRSP/E2 ) vs. placebo in Chinese postmenopausal women with moderate to severe VMS . Methods Women , aged 45–65 years , were r and omized to DRSP/E2 ( n = 183 ) or placebo ( n = 61 ) once daily for four 28-day cycles . Changes in the frequency and severity of hot flushes were analyzed as primary variables , together with other climacteric and urogenital symptoms , clinical global improvement , adverse events and physical/gynecological parameters . Results Relative changes in numbers of hot flushes/week were −80.4 % for DRSP/E2 vs. −51.9 % for placebo ( treatment difference −28.5 % , p reduction in severity of hot flushes with DRSP/E2 treatment . Patients treated with DRSP/E2 were more often free from sweating episodes ( p and vaginal dryness ( p = 0.0008 ) . Other climacteric symptoms , including nervousness and pollakisuria , followed a trend of greater response with DRSP/E2 . Similar to other combination HRT regimens , DRSP/E2 increased occurrences of bleeding , but these decreased over time . Adverse events in patients treated with DRSP/E2 were mostly mild to moderate and withdrawal rates were low . Conclusions Daily treatment of postmenopausal Chinese women with DRSP/E2 for 16 weeks significantly reduced the incidence of hot flushes and demonstrated advantages vs. placebo for other climacteric symptoms . These results indicate that DRSP/E2 is effective , safe and well tolerated in postmenopausal Chinese women", "Introduction Menopausal hot flushes may affect the responses of various vascular risk factors to hormone therapy ( HT ) . We compared the responses of biochemical markers for cardiovascular diseases to HT in recently postmenopausal women with tolerable or intolerable hot flushes . Methods Healthy , non-smoking freshly postmenopausal women ( n = 150 ) with no previous HT use were studied . Seventy-two women reported intolerable hot flushes ( ≥7 moderate/severe episodes/day ) and 78 women tolerable hot flushes ( ≤3 mild episodes/day ) . The participants were treated in r and omized order with either transdermal estradiol gel ( 1 mg ) , oral estradiol valerate ( 2 mg ) with or without medroxyprogesterone acetate ( 5 mg ) , or placebo for 6 months . Treatment-induced changes in lipids , lipoproteins , apolipoproteins , sex hormone binding globulin ( SHBG ) and high-sensitivity C-reactive protein were compared . The trial is registered in the US National Institutes of Health Clinical Research Registry ( no. NCT00668603 ) . Results Pretreatment hot flush status was not related to the responses of these markers to different forms of HT . However , when all active regimens were evaluated together as a post-hoc analysis , 7/10 markers showed a tendency toward greater beneficial changes in women with intolerable hot flushes . Furthermore , in women with intolerable hot flushes and with HT use , the increases in SHBG ( Spearman 's rho = − 0.570 , p in hot flushes during the use of HT . Conclusions Hot flushes appear to be no significant determinant for the responses of vascular markers to HT use", "BACKGROUND When genital atrophy exists , systemic hormone therapy ( HT ) has a timing until to induce vaginal proliferation and symptomatic relieve . Thus , in order to obtain a prompt improvement , the association of local therapy acting on the genital epithelium to the systemic treatment should be considered . OBJECTIVE To evaluate the effects of a combined therapy consisting of vaginal estriol with transdermal 17-beta-estradiol ( 50 microg/day ) plus medroxyprogesterone acetate ( 5 mg/day ) per os in shortening the period of uro-genital symptoms . SUBJECTS AND METHODS In a r and omized , double blind , controlled with placebo study , 27 women with climacteric symptoms and atrophic vaginitis were treated for 4 months with HT plus vaginal estriol 0.5 mg/day ( group E ) or placebo ( group P ) . Patients use the local medication daily for the first 3 weeks and twice-weekly thereafter . Before entering in the study , patients were asked about HT and selected for inclusion . In the first visit , electible patients after written informed consent were r and omized to receive HT plus local estriol or placebo . All the subjects had baseline studies , including medical history , physical examination , blood and urine analysis . In order to evaluate the effect of local treatment on urinary and genital symptoms , a score for genital , urinary and colposcopic complaints ( 0 minimum-100 maximum ) was developed . This score and Blatt-Kuperman were recorded and performed in every control . RESULTS There were no differences on climacteric symptoms relief between the two groups . Additionally , the improvement in urinary symptoms at the end of the study was similar for both groups ( from 16.5 + /- 6.1 to 8.5 + /- 2.4 for E group and from 15.8 + /- 7.8 to 8.8 + /- 2.7 for P group ; P reached significant improvement on urinary complaints since the first month of treatment . Additionally , a significant difference between E and P was observed at months 2 and 3 , although no differences were detected at the end of the study . Papanicolaou smear showed reactive or reparative changes and karyopyknotic index exhibited a significant increase in superficial cells in both groups and at the end of the study . CONCLUSIONS Adding vaginal estriol to HRT may shorten the latency period for urinary symptoms", "Objectives To compare the effect of micro-dose transdermal estradiol and placebo on the incidence and severity of menopausal symptoms and well-being in postmenopausal Asian women with vasomotor symptoms . Design Multicenter , double-blind , r and omized , placebo-controlled study . Results Of 165 subjects r and omized to estradiol 0.014 mg/day or placebo for 12 weeks , 80 per group were included in the analysis . Groups were comparable at baseline , although time since menopause was slightly shorter in the estradiol group . There was a greater reduction in mean weekly hot flushes at week 12 in the estradiol group ( 55 % ) than the placebo group ( 40 % ; p moderate and severe hot flushes ( −58 % vs. −39 % , respectively ) . Reductions were statistically significant at weeks 4 , 8 , and 12 . Vaginal pH fell significantly in the estradiol group by week 4 and then remained stable throughout the treatment period , but there were no significant changes in the placebo group . Vaginal maturation value increased more in the estradiol than the placebo group ( p had vaginal bleeding or spotting . Quality of life improved similarly in both groups . Urogenital symptoms improved considerably from baseline in both treatment groups , with no significant differences . Eight subjects experienced treatment-related adverse events ( seven in the estradiol group ) . Conclusions In Asian women , micro-dose estradiol was significantly superior to placebo in improving vasomotor symptoms . The bleeding profile was comparable with that of placebo . Micro-dose estradiol was safe and well tolerated in Asian women", "Introduction The Livial Intervention Following Breast Cancer : Efficacy , Recurrence and Tolerability Endpoints ( LIBERATE : Clinical http://Trials.gov number NCT00408863 ) , a r and omized , placebo-controlled , double-blind trial that demonstrated that tibolone ( Livial ) , a tissue-selective hormone-replacement therapy ( HRT ) , increased breast cancer ( BC ) recurrence HR 1.40 ( 95 % CI , 1.14 to 1.70 ; P = 0.001 ) . A subgroup of women was entered into a study of bone mineral density ( BMD ) . Methods Women with surgically excised primary BC ( T1 - 3 , N0 - 2 , M-0 ) within the last 5 years , complaining of vasomotor symptoms , were assigned to tibolone , 2.5 mg daily , or placebo treatment for a maximum of 5 years . The BMD sub study enrolled 763 patients , using dual-energy X-ray absorptiometry ( DXA ) scanning at baseline and at 2 years . Results In the bone sub study , 699 of 763 women were eligible ( 345 allocated to tibolone , and 354 , to placebo ) . After undergoing DXA scans , 300 ( 43 % ) women had normal BMD ; 317 ( 45 % ) , osteopenia ; and 82 ( 11.7 % ) , osteoporosis . Low body-mass index ( P Tibolone increased BMD by 3.2 % at the lumbar spine and 2.9 % at the hip compared with placebo ( both P fractures ( 55 % ) occurred in osteopenic patients . Women with normal BMD had increased recurrence with tibolone , 22 ( 15.6 % ) of 141 compared with placebo , 11 ( 6.9 % ) of 159 ( P = 0.016 ) , whereas no increased BC recurrence was seen in women with low BMD ; 15 ( 7.4 % ) of 204 taking tibolone versus 13 ( 6.7 % ) of 195 taking placebo . Conclusions Tibolone is contraindicated after BC treatment , as it increases BMD and BC recurrence . Risk of BC recurrence was elevated in BC women with normal BMD ( compared with low ) who took tibolone", "Objective To compare the effects of tibolone and continuous combined hormone therapy on circulating sex steroids and their binding proteins and their relationship to mammographic density . Study design A prospect i ve , double-blind placebo-controlled study . A total of 166 postmenopausal women were equally r and omized to receive tibolone 2.5 mg , estradiol 2 mg/norethisterone acetate 1 mg ( E2/NETA ) or placebo . Serum analyses of sex steroids , insulin-like growth factor ( IGF-I ) and binding proteins and assessment of mammographic breast density were performed at baseline and after 6 months of treatment . Results Estrogens were markedly increased and and rogens decreased by E2/NETA . In contrast , tibolone had only a minor influence on circulating estrogens . Sex hormone binding globulin ( SHBG ) levels were reduced by 50 % , while levels of and rogens increased . Baseline values of estrone sulfate ( E1S ) , around 1.0–1.1 nmol/l , were increased to 44.7 nmol/l by E2/NETA and to only 1.7 nmol/l by tibolone ( p Mammographic breast density displayed a negative correlation with age and body mass index and a positive association with SHBG . After 6 months there was also a negative correlation with levels of free testosterone . Conclusion We found that tibolone and E2/NETA caused distinct differences in estrogen/ and rogen status and blood levels of possible breast mitogens . The negative association between free testosterone and mammographic density could be a possible explanation for tibolone having less influence on the breast", "OBJECTIVE To study the efficacy and safety of estradiol and drospirenone tablets ( Angeliq ) in treatment of menopausal symptoms among postmenopausal Chinese healthy women . METHODS Total 244 postmenopausal Chinese healthy women who had moderate to severe hot flushes were r and omly assigned into estradiol and drospirenone ( observation group , n = 183 ) or placebo group ( n = 61 ) by the ratio of 3:1 for 16 weeks in this r and omized multi-center double-blind placebo-controlled study . During the trial , the follow-up visits were conducted at week 4 , 8 , 12 , 16 of treatment and 2 weeks after treatment respectively . Height , weight , vital signs , hot flushes , other relevant menopausal symptoms and vaginal bleeding were observed in each follow-up visit , while the clinical global impression scale was assessed at 16 weeks as well . RESULTS It showed that hot flushes were reduced significantly more in observation group than that in placebo group ( P . The absolute values of mean severity index of total hot flushes decreased by -0.6 ± 0.5 in observation group and -0.4 ± 0.4 in placebo group from baseline respectively , which reached significant difference ( P the absolute values of mean severity index of moderate to severe hot flushes decreased by -0.6 ± 0.8 in observation group and -0.3 ± 0.6 in placebo group from baseline respectively , which had no significant difference ( P > 0.05 ) . After 16 weeks treatment , it also showed that estradiol and drospirenone had significant better efficacy than placebo on moderate to severe sweating , vaginal dryness and clinical global impression scale ( P trial , blood pressure in observation group was stable . The rate of vaginal bleeding in observation group was higher than that in the placebo group , especially during the week 4 to week 8 when 48.9 % ( 87/178 ) in observation group and 10.7 % ( 6/56 ) in placebo group of patients bled . Although the cumulative amenorrhea rate of observation group was lower than that of placebo group in each cycle ( 28 days ) , it increased gradually along with duration of the treatment . The commonest adverse event in observation group was breast tenderness which accounted for 12.0 % ( 22/183 ) . The level of serum potassium was in the normal range in observation group mostly . Meanwhile , the other adverse events rate was low . Serious adverse events reported in this trial were assessed as not study drug related or as unlikely study drug related . CONCLUSION Estradiol and drospirenone tablets which could effectively alleviate menopausal symptoms in postmenopausal Chinese healthy women is a novel hormone replacement therapy regimen with high safety and efficacy", "UNLABELLED The aim of the double-blind , placebo-controlled study was to investigate the effects of a continuous combined estrogen-progestogen treatment ( Climodien , Lafamme ) as compared with estrogen alone on vigilance in insomniac postmenopausal syndrome patients , objectified by EEG mapping . METHODS In a 3-arm , 2-month parallel group design phase , patients received a combination of estradiol valerate 2 mg and the novel progestogen dienogest 3 mg ( Climodien 2/3 ) or estradiol valerate 2 mg alone or placebo . In a subsequent open-label phase , all patients received estradiol valerate 2 mg+dienogest 2 mg ( Climodien 2/2 ) . EEG mapping was carried out before and after the 2-month double-blind phase as well as after the 2-month open-label treatment . RESULTS As compared with placebo , Climodien 2/3 induced a marked and highly significant increase in absolute power in all frequency b and s , specifically in alpha-2 activity . Moreover , a significant increase in relative alpha-2 power , a decrease in relative delta and beta power as well as an acceleration of the dominant frequency and of the delta and alpha centroids suggested a marked improvement in vigilance . In contrast , under estradiol valerate 2 mg alone , only a slight augmentation of alpha and attenuation of relative delta and beta power occurred , suggesting only a slight vigilance improvement as compared with placebo . Thus , dienogest 2 mg increased the estrogen effect , which was also confirmed by a statistical evaluation of the differences between Climodien 2/3 and estradiol valerate alone ( augmentation of alpha-2 , attenuation of relative beta , acceleration of the dominant frequency ) . Moreover , Climodien 2/2 also markedly increased alpha-2 power , decreased relative beta-2 power and accelerated the alpha centroid . Finally , comparing Climodien 2/3 with Climodien 2/2 , there was even a dose-efficacy relation . CONCLUSIONS Estradiol valerate 2 mg improves vigilance slightly , thereby confirming previous findings . The additional administration of dienogest does not minimize the effect of estrogen , but on the contrary increases it , which makes the combination superior to both placebo and estradiol valerate alone . Vigilance improvement may be of great therapeutic benefit to menopausal syndrome patients at a time when increased adaptability is needed to adjust to increasing sexual , marital , occupational and social difficulties known to occur specifically in this period of life", "OBJECTIVE To assess the efficacy , tolerability , and acceptance of a vaginal ring delivering the equivalent of 50 or 100 microg per day of estradiol ( E2 ) , compared with placebo , for relief of moderate to severe vasomotor symptoms and urogenital symptoms in postmenopausal women . METHODS Women with moderate to severe vasomotor symptoms ( seven or more per day or 56 per week average ) received 13 weeks of treatment with a vaginal ring delivering 50 microg per day E2 ( n = 113 ) or 100 microg per day E2 ( n = 112 ) , or a placebo vaginal ring ( n = 108 ) . Severity of vasomotor symptoms was assessed by a daily diary card and the Greene Climacteric Scale . Urogenital signs and symptoms were evaluated via patient and physician assessment and vaginal cytology . Participant satisfaction with the vaginal ring was evaluated via question naire . RESULTS Vasomotor symptoms significantly improved in both treatment groups , compared with placebo ( P patient assessment of urogenital signs with active rings compared with placebo . For women with vaginal atrophy at baseline ( n = 60 ) , the maturation index improved significantly in both treatment groups compared with placebo . Total Greene Climacteric Scale scores significantly improved for both E2 vaginal ring groups ( P tolerated . Most adverse events were mild or moderate and consistent with estrogen therapy . CONCLUSION A novel vaginal ring delivering the equivalent of 50 or 100 microg per day of E2 significantly reduced the number and severity of vasomotor symptoms and improved urogenital symptoms , compared with placebo . The E2 vaginal ring was well tolerated", "Background At the time of feasibility work and final design of the trial there was no r and omised control trial evidence for the long-term risks and benefits of hormone replacement therapy . Observational studies had suggested that long term use of estrogen was likely to be associated , amongst other things , with reduced risks of osteoporosis and ischaemic heart disease and increased risks of breast and endometrial cancer . Concomitant use of progestogens had been shown to protect against endometrial cancer , but there were few data showing how progestogen might affect estrogen actions on other conditions . Disease specific risks from observational studies suggested that , overall , long-term HRT was likely to be beneficial . Several studies showed that mortality from all causes was lower in HRT users than in non-users . Some secondary cardiovascular prevention trials were ongoing but evidence was also required for a range of outcomes in healthy women . The WISDOM trial was design ed to compare combined estrogen and progestogen versus placebo , and estrogen alone versus combined estrogen and progestogen . During the development of WISDOM the Women 's Health Initiative trial was design ed , funded and started in the US . Design R and omised , placebo , controlled , trial . Methods The trial was set in general practice s in the UK ( 384 ) , Australia ( 94 ) , and New Zeal and ( 24 ) . In these practice s 284175 women aged 50–69 years were registered with 226282 potentially eligible . We sought to r and omise 22300 postmenopausal women aged 50 – 69 and treat for ten years . The interventions were : conjugated equine estrogens , 0.625 mg orally daily ; conjugated equine estrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily ; matched placebo . Primary outcome measures were : major cardiovascular disease , osteoporotic fractures , breast cancer and dementia . Secondary outcomes were : other cancers , all cause death , venous thromboembolism and cerebro-vascular disease . Results The trial was prematurely closed during recruitment following publication of early results from the Women 's Health Initiative . At the time of closure , 56583 had been screened , 8980 entered run-in , and 5694 ( 26 % of target of 22,300 ) r and omised . Those women r and omised had received a mean of one year of therapy , mean age was 62.8 years and total follow-up time was 6491 person years . Discussion The WISDOM experience leads to some simple messages . The larger a trial is the more simple it needs to be to ensure cost effective and timely delivery . When a trial is very costly and beyond the re sources of one country , funders and investigators should make every effort to develop international collaboration with joint funding", "OBJECTIVE To evaluate the safety and efficacy of synthetic conjugated estrogens B ( SCE-B ; 0.3 mg/d ) for 12 weeks in the treatment of vulvovaginal atrophy in symptomatic , postmenopausal women . DESIGN Prospect i ve , r and omized , multicenter , double-blind , placebo-controlled trial . SETTING Forty-two participating sites in the United States . PATIENT(S ) Postmenopausal women with at least one moderate to severe symptom of vaginal atrophy . INTERVENTION(S ) Daily oral administration , in a r and omized , placebo-controlled setting , of SCE-B ( 0.3 mg ) or of placebo for 12 weeks . MAIN OUTCOME MEASURE(S ) Mean changes in vaginal maturation index , percentage of parabasal and superficial cells , vaginal pH , and severity of the most bothersome symptom ( MBS ) between baseline and predetermined time points were assessed . Safety and tolerability were evaluated . RESULT ( S ) A total of 310 women ( mean age , 58.6 y ) were enrolled . Synthetic conjugated estrogens B yielded statistically significantly greater differences in vaginal maturation index and vaginal pH from baseline to the end of treatment . Vaginal dryness ( 44.4 % ) and pain during intercourse ( 30.2 % ) were the symptoms most commonly identified as the MBS . A statistically significant mean reduction in the severity of the MBS was noted for SCE-B. There were no clinical ly significant differences observed between the two groups for findings related to safety . CONCLUSION ( S ) Synthetic conjugated estrogens B ( 0.3 mg/d ) was effective in treating vulvovaginal atrophy in symptomatic postmenopausal women . Significant improvement was seen in vaginal maturation index , vaginal pH , and severity of MBS from baseline to the end of treatment", "A prospect i ve r and omised double-blind placebo-controlled trial of 17-beta oestradiol 25-mg vaginal tablets or placebo daily for 12 weeks was undertaken in 110 postmenopausal women with urinary frequency , urgency and /or urge incontinence recruited from a tertiary referral urogynaecology clinic . After 3 months the only statistically significant difference was a greater reduction in urinary urgency in those women with sensory urgency treated with 17-beta oestradiol compared to placebo . This may be due to the effective treatment of local vaginal atrophy by low-dose oestrogen rather than any effect on the lower urinary tract", "Objective : The aim of this study was to determine the patterns and predictors of sexual activity in the Hormone Therapy ( HT ) Trials of the Women 's Health Initiative ( WHI ) . Methods : Sexual activity questions were administered to 27,347 women ages 50 to 79 years at baseline and at year 1 and to a r and om 8.6 % sub sample at years 3 and 6 . The associations with demographic and health characteristics were determined . Results : Sexual activity at baseline was 60.7 % , 44.9 % , and 28.2 % in the 50- to 59- , 60- to 69- , and 70- to 79-year-old age groups , respectively . Most of the participants were satisfied with their current sexual activity ( 63.2 % ) . Of those dissatisfied , 57 % preferred more sexual activity . Vaginal atrophy correlated with sexual inactivity at baseline ( P poor/fair self-rated health , lack of satisfaction with quality of life , depression , and loss of partner ( P sexual activity at year 1 was sexual activity at baseline ( odds ratio , 96.71 ; 95 % CI , 81.90 - 114.20 ) . A subset analysis of women adherent with HT or placebo at years 3 and 6 suggested that HT was associated with a higher percentage of participants reporting sexual activity ( P = 0.01 ) . Conclusions : Most women in the WHI HT Trials were satisfied with their sexual activity . Of those who were dissatisfied , the majority preferred more , rather than less , sexual activity . Vaginal atrophy at baseline correlated with sexual inactivity , and sexual activity at baseline was the strongest identified predictor of sexual activity at year 1 . HT use was not predictive of ongoing sexual activity in the intent-to-treat analysis . This report further characterizes the participants in the WHI HT trials and reveals the complexity of factors related to the prevalence of sexual activity and satisfaction", "Objectives : To evaluate the efficacy and safety of different doses of 17&bgr;‐estradiol for the treatment of vasomotor and vulvovaginal symptoms . Design : This was a r and omized , double‐blind , multicenter , parallel‐group study . One hundred forty‐five subjects , including naturally postmenopausal women aged 40‐60 ( who had not experienced menses for at least 12 months ) , women who had undergone hysterectomy , and women aged 25‐60 who had undergone bilateral oophorectomy with or without hysterectomy were studied . Either placebo or 17&bgr;‐estradiol ( 1 mg or 0.5 mg ) was given orally every day for 12 weeks , and vasomotor symptoms and vaginal epithelial cytology were evaluated . Results : There were significant differences between placebo and the active treatments in the percentage change from baseline in the number of hot flushes ( all hot flushes , 1 mg vs. placebo , p mean number of hot flushes of 83.2 % ) . Both doses were also more effective than placebo in increasing the proportion of mature vaginal cells ( end‐of‐treatment mean values of 0 % , 78.5 % , and 21.5 % for parabasal , intermediate , and superficial cells , respectively , in the 1‐mg group ; mean values of 0.3 % , 80.8 % , and 18.9 % in the 0.5‐mg group ; and mean values of 15.2 % , 74.7 % , and 10.2 % in the placebo group ) . The proportion of subjects reporting no vaginal dryness was greatest in the 1‐mg group ( mean percentage of days without dryness of 86.1 % at weeks 9‐12 ) . Conclusions : For the relief of vasomotor and vulvovaginal symptoms , 17&bgr;‐estradiol 1 mg is effective and has an excellent safety profile . ( Menopause 2000;7:310‐317 . © 2000 , The North American Menopause Society .", "Objective To evaluate the effects of the tissue selective estrogen complex ( TSEC ) pairing bazedoxifene ( BZA ) with conjugated estrogens ( CE ) on sexual function and quality of life in postmenopausal women . Methods In this 12-week , double-blind , placebo-controlled study , postmenopausal , non-hysterectomized women ( n = 652 ) with symptoms of moderate to severe vulvar/vaginal atrophy were r and omized to once-daily treatment with BZA 20 mg/CE 0.45 or 0.625 mg , BZA 20 mg , or placebo . The Arizona Sexual Experiences ( ASEX ) Scale , Menopause-Specific Quality of Life ( MENQOL ) question naire , and Menopause Symptoms Treatment Satisfaction Question naire ( MS-TSQ ) were secondary measures used to assess the effects of BZA/CE on sexual function , menopausal symptoms , and satisfaction with treatment , respectively . Results At week 12 , both BZA/CE doses were associated with significant improvement in ease of lubrication score from baseline compared with placebo ( p MENQOL question naire results at week 12 showed significant improvements in vasomotor function , sexual function and total scores with both BZA/CE doses vs. placebo or BZA 20 mg ( p overall satisfaction with treatment , as well as satisfaction with control of hot flushes during the day and night , effect on quality of sleep , and effect on mood or emotions , compared with subjects treated with placebo or BZA 20 mg ( all p BZA/CE for 12 weeks was shown to significantly improve sexual function and quality -of-life measures in symptomatic postmenopausal women", "AIMS --To study the effects of ovarian hormone replacement therapy ( HRT ) on bone mineral density and disease activity in postmenopausal women with rheumatoid arthritis ( RA ) . METHOD --A placebo controlled double-blind study was carried out on 62 patients with RA , 22 on placebo and 40 on HRT ( transdermal oestradiol patches twice weekly for 48 weeks plus norithisterone tablets when clinical ly indicated ) . Bone mineral density of spine , hip and wrist was measured at 0 and 48 weeks and clinical and laboratory measures of general well-being and disease activity at 0 , 12 , 24 and 48 weeks . RESULTS --Thirteen of 22 ( 59 % ) of placebo and 31 of 40 ( 78 % ) of the HRT group completed 48 weeks in the study . At entry , bone mineral density ( BMD ) values in the lumbar spine and femoral neck were similar to those in age and sex matched controls in both treatment groups , whereas at the distal radius , BMD was significantly reduced to approximately 50 % of control values ( both p HRT group , spine BMD increased significantly by a median of + 0.94 % at 48 weeks ( p = 0.024 ) , but did not change significantly in the placebo group . BMD at the femoral neck and distal radius did not change in either group . In the HRT group , there was significant improvement in well being as assessed by the Nottingham Health Care Profile ( p ESR or CRP in either group . CONCLUSION --Transdermal HRT was well tolerated , increased well being , reduced articular index and increased lumbar spine bone density over a one year period in postmenopausal women with RA . Although no laboratory evidence was found of a disease modifying effect , the symptomatic benefits and improvements in bone density indicate that HRT may be a valuable adjunct to conventional antirheumatic therapy in RA", "OBJECTIVE To evaluate the feasibility of conducting a large r and omized trial of HRT in symptomatic women with early-stage breast cancer . DESIGN Open r and omized study . SETTING Outpatient clinics at The Royal Marsden and St. George 's Hospitals , London . PATIENT(S ) One hundred postmenopausal women with early-stage breast cancer , experiencing vasomotor symptoms and /or vaginal dryness . INTERVENTION(S ) R and omization ( 1:1 ) to HRT or no HRT for 6 months . MAIN OUTCOME MEASURE(S ) Acceptance , continuance rates , and the reasons eligible women declined study entry . RESULT ( S ) Acceptance ( 38.8 % ) and continuance rates ( > 80 % ) were encouraging . The efficacy of HRT did not appear to be antagonized with concomitant tamoxifen . Seventy-five percent of women continued HRT after the study ended . Three women developed metastatic disease . Two used HRT . CONCLUSION ( S ) Despite informed consent , a national UK r and omized trial of HRT should be feasible and has now been planned . Successful implementation necessitates the provision of information about HRT and the estrogen deficiency side effects of breast cancer therapy to health professionals and women with breast cancer", "OBJECTIVES FM is a condition that preferentially affects women . Sex hormones , and in particular oestrogens , have been shown to affect pain processing and pain sensitivity , and oestrogen deficit has been considered a potentially promoting factor for FM . However , the effects of oestrogen treatment in patients suffering from FM have not been studied . Here , we examined the effect of transdermal oestrogen substitution treatment on experimental as well as self-estimated pain in women suffering from FM . METHODS Twenty-nine post-menopausal women were r and omized to either 8 weeks of treatment with transdermal 17β-oestradiol ( 50 µg/day ) or placebo according to a double-blind protocol . A self-estimation of pain , a set of quantitative sensory tests measuring thresholds to temperature , thermal pain , cold pain and pressure pain , and a cold pressor test were performed on three occasions : before treatment , after 8 weeks of treatment and 20 weeks after cessation of treatment . RESULTS Hormonal replacement treatment significantly increased serum oestradiol levels as expected ( P in self-estimated pain were seen between treatment and placebo groups , nor were there any differences between the two groups regarding the results of the quantitative sensory tests or the cold pressor test at any of the examined time points . CONCLUSION Eight weeks of transdermal oestradiol treatment does not influence perceived pain , pain thresholds or pain tolerance as compared with placebo treatment in post-menopausal women suffering from FM . TRIAL REGISTRATION Clinical Trials.gov Registration ; http://www . clinical trials.gov ; NCT01087593", "OBJECTIVE To investigate the effects of estrogen and progesterone on sleep in postmenopausal women . METHOD The 33 participants were r and omly assigned to an estrogen or placebo group after undergoing clinical and hormonal assessment s and a polysomnogram , and they underwent the same tests again after 12 weeks . Then , while still taking estrogen or placebo , they all received progesterone for another 12 weeks and underwent a final polysomnogram . RESULTS Estrogen plus progesterone was more effective than estrogen alone in decreasing the prevalence of periodic limb movement ( PLM ) ( 8.1 % vs 2.8 % ) , hot flashes ( 14.2 % vs 0 % ) , and bruxism ( 11.1 % vs 0 % ) at night , or somnolence and attention difficulty during the day . The prevalences of breathing irregularities , arousal from sleep , anxiety , and memory impairment were decreased in both groups following progesterone treatment . CONCLUSION While not significantly affecting sleep quality , hormone therapy decreased the prevalence of arousal in both groups and that of PLM in the group treated with estrogen plus progesterone", "Objective Pueraria lobata ( PL ) is used as a traditional Chinese herbal remedy for menopausal symptoms , as well as an ingredient in preparations for conditions affecting menopausal women , such as osteoporosis , coronary heart disease , and some hormone-dependent cancers . The scientific basis for its action may be its action as a phytoestrogen . Design To examine the effects of PL in comparison with hormone replacement therapy ( HRT ) on lipid profile , sex hormone levels , bone turnover markers , and indices of cognitive function . For the study , 127 community-living , postmenopausal women aged 50 to 65 years were r and omized to receive HRT ( n = 43 ) , PL ( equivalent to 100 mg isoflavone ; n = 45 ) , or no treatment ( n = 39 ) for 3 months . The following measurements were carried out at baseline and after 3 months for all participants : menopausal symptoms question naire ; neuropsychological tests covering memory , attention , motor speed , and word-finding ability ; quality of life ( SF36 ) ; lipid profile ; urinary deoxypyridinoline ; dietary phytoestrogen intake and urinary phytoestrogen ; estradiol ; follicle-stimulating hormone ; and luteinizing hormone . Results Only participants in the HRT group showed a mean reduction in cholesterol and low-density lipoprotein cholesterol that was significantly different from that of the control group . No significant changes in lipid profile or follicle-stimulating hormone and luteinizing hormone were observed in the PL group compared with the controls . However , both the HRT and PL groups showed an improvement in Mini-Mental State Examination score and attention span compared with the case of participants receiving no treatment . HRT and PL had different effects on cognitive function ; HRT improved delayed recall , whereas flexible thinking seemed improved in the PL group . Conclusions This study was unable to demonstrate a scientific basis for the use of PL for improving the health of postmenopausal women in general . However , the effect of PL on cognitive function deserves further study", "OBJECTIVE The primary objective was to detect a difference in time until the first recurrence of urinary tract infection during treatment with an estradiol-releasing silicone vaginal ring ( Estring ; Pharmacia & Upjohn , Inc , Uppsala , Sweden ) compared with no estrogen treatment . The secondary objective was to detect any differences in improvement of urethral and vaginal mucosal atrophy and in the subjective assessment of urogenital symptoms . The study also sought to detect a difference in decrease of vaginal pH to Postmenopausal women with recurrent symptomatic , bacteriologically confirmed urinary tract infections were r and omly assigned to receive either Estring ( 2 mg estradiol ) or no estrogen treatment . One ring was carried vaginally for 12 weeks . The duration of treatment was 36 weeks for the Estring group and either 36 weeks or until the first recurrence for the control group . Both intent-to-treat and per- protocol analyses were performed to evaluate efficacy , whereas the safety analysis was limited to the intent-to-treat group . The primary variable was analyzed by survival analysis with the Kaplan-Meier method for estimating the survival density function . To compare the survival curves for the 2 treatment groups a log-rank test was performed for time until first recurrence . RESULTS A total of 108 women were r and omly assigned , 53 to the Estring group and 55 to the control group . The cumulative proportion of women remaining free of urinary tract infection was significantly higher in the Estring group than in the control group ( P = .008 ) . After 36 weeks of study the cumulative likelihood of remaining free of disease was approximately 45 % in the women with the vaginal ring compared with approximately 20 % in the control group . Estring lowered vaginal pH , and the time to first recurrence was effectively prolonged by Estring treatment . Vaginal and , to a lesser extent , urethral mucosal cells were significantly more mature in the Estring group . No unexpected adverse events were found . CONCLUSION Estring is useful to prolong the time to next recurrence among postmenopausal women with recurrent urinary tract infection and to decrease the number of recurrences per year . The silicone vaginal ring also has a clinical ly significant ability to alleviate other postmenopausal urogenital symptoms . Estring is safe and well tolerated", "Objective : To determine the efficacy of three doses of a new , oral formulation of estradiol acetate ( EA ) for alleviation of vasomotor and urogenital symptoms in postmenopausal women . Design : Two separate 12-week studies were undertaken in postmenopausal women with moderate to severe vasomotor symptoms . In the first study , women were r and omly assigned to EA 0.9 mg/day , EA 1.8 mg/day , or placebo ( study 1 ; N = 293 ) , and in the second study to oral EA 0.45 mg/day or placebo ( study 2 ; N = 259 ) . Women recorded the frequency and severity of vasomotor symptoms daily and urogenital symptoms weekly on diary cards . Investigators assessed signs of vaginal atrophy . Results : Frequency of moderate to severe vasomotor symptoms decreased significantly versus placebo , starting at week 2 in the EA 1.8-mg group ( P = 0.005 ) , week 3 in the EA 0.9-mg group ( P = 0.003 ) , and week 6 in the EA 0.45-mg group ( P vasomotor-symptom frequency was 91 % , 78 % , and 61 % , respectively . Vasomotor-symptom severity decreased significantly versus placebo , starting at weeks 2 and 3 with EA 1.8 mg and 0.9 mg , respectively , and at week 5 with EA 0.45 mg . Vaginal pH and maturation index improved significantly in all EA groups versus placebo , and some signs and symptoms of vaginal atrophy improved at the EA 0.9- and 1.8-mg doses . Side effects were mild to moderate and consistent with estrogen therapy . Conclusions : Oral EA at all doses was well tolerated and significantly reduced the frequency and severity of postmenopause symptoms versus placebo", "OBJECTIVE : To evaluate two doses of oral synthetic conjugated estrogens-B tablets compared with placebo on the frequency of awakenings result ing from nocturnal vasomotor symptoms in postmenopausal women over a 12-week treatment period . METHODS : A double-blind , r and omized , placebo-controlled multicenter study enrolled a total of 157 women who were experiencing daytime vasomotor symptoms and a minimum of at least three nocturnal awakenings per night as a result of hot flushes . Participants were evenly r and omized to one of three treatment groups ( 0.3 mg , 0.625 mg , or matching placebo ) and treated for up to 12 weeks . Subjective sleep quality also was assessed . RESULTS : Significantly greater reductions from baseline in the weekly mean frequency of awakenings result ing from hot flushes occurred for participants r and omized to either synthetic conjugated estrogens-B dose relative to placebo ( mean reductions , 3.55 , P=.004 , and 4.65 , P elimination of nocturnal awakenings ( 36.5 % for 0.3 mg , 34 % for 0.625 mg compared with 9.8 % for placebo ; P⩽.002 ) with a general finding of improved sleep based on actigraphy data . No differences were observed in measures of sleep quality or daytime sleepiness . CONCLUSION : In this symptomatic postmenopausal population of women experiencing sleep disruption result ing from nocturnal vasomotor symptoms , a daily dose of synthetic conjugated estrogens-B as low as 0.3 mg appears to be effective in treating nocturnal hot flushes that lead to unwanted awakenings . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00592839 . LEVEL OF EVIDENCE :", "OBJECTIVE Estrogen or combined hormone ( estrogen-progestin ) therapy is highly efficacious for managing the signs and symptoms of urogenital atrophy . A low , effective estrogen dose may enhance patient acceptance and reduce side effects . METHODS In this r and omized , double-blind , multicenter clinical trial , 71 healthy postmenopausal women with vaginal atrophy ( Vaginal Maturation Index received either low-dose synthetic conjugated estrogens , A tablets ( Cenestin ) ( SCE-A ) , 0.3 mg once daily , or placebo for 16 weeks . RESULTS Treatment with SCE-A for 16 weeks result ed in a highly significant ( P Vaginal Maturation Index compared to a mean increase of 4.1 with placebo treatment . A significant estrogenic improvement was detected as early as 4 weeks ( mean increase 14.6 ) . Superficial cells were significantly increased from 2.1 % at baseline to 15.9 % at week 16 with SCE-A , and parabasal cells were significantly reduced from 23.0 % at baseline to 1.6 % at week 16 ( P Vaginal pH was significantly decreased from 6.2 at week -2 to 5.2 at week 16 with SCE-A compared to placebo ( P treatment-emergent side effects or other measures of safety , except for urinary tract infection , which occurred more frequently in the placebo group . CONCLUSIONS These results confirm the relatively rapid estrogenic effect and safety of a low-dose ( 0.3 mg/day ) of slow-release SCE-A ( Cenestin ) in the treatment of vaginal atrophy in postmenopausal women", "OBJECTIVES To determine the effects of ultra-low-dose hormone therapy on muscle mass and physical function in community-dwelling women . DESIGN Double-blind , placebo-controlled trial . SETTING Clinical research center in Connecticut . PARTICIPANTS Healthy , community-dwelling women aged 65 and older ( n=167 ) . INTERVENTION Eligible women were r and omly assigned to treatment with 0.25 mg 17-beta estradiol or placebo for 36 months . All women ( estradiol or placebo ) with an intact uterus received micronized progesterone 100 mg/d for 2 weeks every 6 months . All participants received 1,300 mg elemental calcium with 1,000 IU vitamin D per day . MEASUREMENTS Appendicular skeletal muscle mass ( ASM ) , lean body mass ( LBM ) , and percentage body fat were measured using dual x-ray absorptiometry . Sarcopenia was defined as skeletal muscle mass ( ASM/height2 ) 2 st and ard deviations or less than young , healthy reference population mean . Physical activity ( Physical Activity Scale in the Elderly ( PASE ) ) and performance were measured . Serum estrone , estradiol , and sex hormone-binding globulin were measured . RESULTS The prevalence of sarcopenia at baseline was 13 % . There were no baseline differences between groups except for PASE score and chair rise time , in which the estrogen group had better performance . No changes in ASM , LBM , percentage of body fat , or physical performance were found after 3 years of estrogen therapy . CONCLUSION Sarcopenia was present in 13 % of this group of community-dwelling , postmenopausal older women . Ultra-low-dose estrogen therapy neither improves nor harms ASM . Similarly , no changes in body fat or physical performance were detected", "Two hundred and forty‐two postmenopausal women between 35 and 65 years of age requiring hormone replacement therapy for climacteric symptoms were blindly and r and omly allocated to treatment either with transdermal estradiol therapy ( Estraderm * 50 μg/24 h ) ( E ) or placebo ( P ) . The patches were changed twice a week and treatment continued for 12 weeks . No progestogen supplement therapy was given during the study . No previous hormone replacement therapy had been given for the last six months and the women had had their last menstruation more than sin months ago . As a part of a larger study assessing women 's quality of life , a Swedish version of ‘ McCoy 's Sex Scale Question naire ’ was administered at the start of treatment and after 12 weeks . This question naire contains nine items regarding different aspects of sexual life . The difference between the scorings at the start of treatment and after 12 weeks were calculated for each item and the values of the E and the P groups were compared . Items regarding ‘ satisfaction with frequency of sexual activity , sexual fantasies . degree of enjoyment . vaginal lubrication and pain during intercourse ’ were positively influenced in the E group compared to the P group . Items not affected were ‘ frequency of orgasm and sexual arousal ’ . A correlation between improved sexual life and quality of life was also found when the results from the McCoy scale were compared with a battery of quality of life question naires", "OBJECTIVE To test the causal relationship between sex hormones and cognitive skills in postmenopausal women . We hypothesized that testosterone would decrease verbal memory and verbal fluency and increase spatial ability compared with a placebo . For estrogen , we conversely hypothesized that the treatment would increase verbal fluency and verbal memory and decrease spatial ability . DESIGN R and omized , double-blind , placebo-controlled , parallel-group trial . SETTING Women 's health clinical research unit at a university hospital . PATIENT(S ) Two-hundred healthy , naturally postmenopausal women aged 50 - 65 years . INTERVENTION(S ) R and omization to 4 weeks ' treatment with testosterone ( testosterone undecanoate , 40 mg/day ) , estrogen ( oral E2 2 mg/day ) or placebo . MAIN OUTCOME MEASURE(S ) Comparisons in verbal fluency , verbal memory , and spatial ability between the three treatment groups . RESULT ( S ) We found no significant effects of testosterone or estrogen on verbal fluency , verbal memory , or spatial ability . CONCLUSION ( S ) Our results give no support for short-term testosterone or estrogen treatment having any substantial effect on verbal fluency , verbal memory , or spatial ability in healthy postmenopausal women", "The results of several observational studies suggest that the use of estrogen replacement is associated with better mood , cognitive function and quality of life . Such findings are consistent with those of laboratory-based research showing that estrogen promotes neuronal sprouting , enhances cholinergic activity in the brain , decreases brain and plasma levels of beta-amyloid , increases serotonin postsynaptic responsivity and the turnover of noradrenaline , and inhibits monoamine oxidase activity . However , the findings from the Women 's Health Initiative controlled trial showed that hormone replacement ( estrogen plus progestin ) not only failed to improve mood , cognition and quality of life but also increased the risk of dementia . At present , there is limited information about the effect of unopposed estradiol replacement therapy ( ERT ) on the mental health outcomes of women at increased risk of cognitive decline ( aged 70 years and over ) . We design ed the present r and omized , double-blind , placebo-controlled trial to clarify this issue . One hundred and fifteen women were r and omized to treatment with estradiol ( n=58 ; 2 mg per day ) or placebo for a total period of 20 weeks . The outcomes of interest in this study included changes in the Beck Depression Inventory ( BDI ) scores between baseline and week 20 , as well as changes in quality of life scores ( as measured by the SF-36 ) and cognitive function ( CAMCOG , Block Design , Memory for Faces , California Verbal Learning Test ( CVLT ) and verbal fluency ( VF ) ) . Nineteen women treated with estradiol and 10 of those treated with placebo discontinued the use of the medication during trial , most frequently due to adverse reactions ( OR=4.11 , 95 % CI=1.29 - 15.37 ) . Intention-to-treat analysis showed that the active and placebo groups did not differ in their response to treatment in any of the outcome measures ( p>0.05 ) . A separate analysis restricted to women who completed the 20-week-trial produced similar negative results . The results of this trial indicate that the use of a relatively high dosage of unopposed estrogen replacement for 20 weeks is not associated with significant changes in cognitive function , mood and quality of life . Other more efficacious and safer interventions need to be devised with the aim of improving the mental state and quality of life of older women", "BACKGROUND The main goals of estrogen replacement therapy ( ERT ) are the prevention of osteoporosis and cardioprotection and the improvement of quality of life ( QL ) . And rogens and tibolone therapy may increase bone mineral density ( BMD ) to a greater extent than ERT and offer an increase in QL . Lipid and cardiovascular effects , however , are still a major concern . AIM To evaluate whether the addition of a weak and rogen to ERT may improve postmenopausal bone loss and sexual activity without adverse effects on lipid pattern and to compare these effects with those observed after tibolone therapy . SUBJECTS AND METHODS This prospect i ve study enrolled 120 surgical postmenopausal women ; of these , 96 completed the 1-year follow-up . Patients were allocated to one of four groups . The first group ( A ; n = 23 ) received 4 mg of estradiol valerate plus 200 mg of enanthate of dihydro and rosterone i m monthly . The second group ( E ; n = 26 ) received 50 microg/day of transdermal 17-b-estradiol continuously ; the third ( T ; n = 23 ) received 2.5 mg of tibolone every day ; and finally , the fourth group ( C ; n = 24 ) constituted a treatment-free control group . Bone mass ( dual X-ray absorptiometry ) , serum total cholesterol , HDL , LDL , triglycerides , apolipoproteins A1 and B and sexual activity were evaluated before starting therapy and at the end of follow-up . RESULTS All active treatment groups showed an increase in BMD . This increase was higher in the A treatment group ( 4.08 % P Sexuality improved significantly with therapy ; however , tibolone and and rogens increased scores to a greater extent than ERT . And rogen therapy was associated with significant increases in total cholesterol , LDL and triglycerides . Cholesterol and LDL fall into groups E and T , HDL into groups A and T and triglycerides in group T only . CONCLUSION The combined regimen of and rogens and ERT increased vertebral bone mass and enhance sexual activity in postmenopausal women equal to that of tibolone and to a greater extent than ERT alone ; its effects on lipids , however , are clearly adverse", "OBJECTIVE The effect of transdermal estradiol and placebo therapy on the quality of life of postmenopausal women was compared in a r and omized trial over 12 weeks . STUDY DESIGN Two hundred forty-two women were r and omized , and 223 were analyzed for efficacy ( n = 112 for estradiol and n = 111 for placebo ) . The quality of life was assessed by means of a battery of st and ard question naires . RESULTS Quality of life improved after both therapies , but health-related quality of life ( p = 0.0003 ) and well being ( p = 0.003 ) improved more after transdermal estradiol therapy than after placebo . This was also the case for all specific climacteric aspects , including sexual problems ( p dysfunction ( p = 0.01 ) , at comparison with placebo . Self-rated symptom relief was more pronounced with estrogen therapy than with placebo ( p estradiol therapy was superior to placebo in relieving symptoms and improving quality of life", "Background Since sex hormones are reported to have important roles in the regulation of immune function , this study was design ed to investigate the effects hormone replacement therapy ( HRT ) and raloxifene ( RAL ) on serum cytokine concentrations in healthy postmenopausal women . Methods Fifty-three healthy postmenopausal women were r and omly assigned and treated by RAL ( Group I , [ RAL 60 mg daily and continuously ] , n = 16 ) , HRT ( Group II , [ 2 mg estradiol valerat + 2 mg dienogest , continuously ] n = 18 ) or placebo ( Group III , n = 19 ) . Two fasting morning blood sample s were obtained from each participant before and 3 months after the treatments . Serum concentration of interleukin (IL)-4 ( as a Th2 cytokine ) and transforming growth factor-beta (TGF-β)1 ( as a Th3 cytokine ) , were measured by using commercially available enzyme-linked immunosorbent assay kits . Kruskal – Wallis analysis of variance , Mann – Whitney U , and Wilcoxon Signed-Ranks Tests were used as necessary . Results At the beginning of the study , the chronological ages , menopausal ages , years of amenorrhea , weights , body mass indexes , and blood pressures were not significantly different between groups ( P 0.05 ) . RAL treatment caused a significant decrease on serum IL-4 concentration ( P in serum IL-4 concentration , this decrease was not statistically significant ( P > 0.05 ) . Serum TGF-β1 concentrations were significantly decreased by HRT when compared to basal value ( P 0.05 ) . RAL treatment has no significant effect on serum TGF-β1 concentration ( P > 0.05 ) . Conclusion It seems that RAL treatment might cause a decrease in serum IL-4 concentration while valerate plus dienogest treatment as HRT seems to cause a Th3 tendency in healthy postmenopausal women", "Objective : To explore whether inhibition of the conversion of testosterone to estradiol modifies the effects of testosterone on cognition in 61 healthy , estrogen-treated postmenopausal women . Design : Seventy-six postmenopausal women using transdermal estrogen for at least 8 weeks , with a serum total testosterone less than 1.2 nmol/L participated in a single-center , double-blind , r and omized , placebo-controlled study . All participants received transdermal testosterone , 400 & mgr;L of a 0.5 % testosterone gel , daily and were r and omized to receive either letrozole 2.5 mg/day or an identical placebo tablet . The main outcome measure was cognition , evaluated using a comprehensive battery of st and ardized neuropsychological tests , at baseline and week 16 . Results : Thirty women in each group completed the study . Free testosterone increased from baseline in both groups , with no difference between groups . Free testosterone levels achieved were below the 90th centile for young women in 80 % of the participants at week 16 . Serum estradiol and sex hormone-binding globulin levels did not differ from baseline or between groups during the study . No clinical ly significant effects of testosterone treatment were seen for attention and working memory , psychomotor speed , or executive function . Significant improvements were seen for immediate and delayed visual and verbal memory and for simple concentration with testosterone therapy , all of which were unaffected by the aromatase inhibitor . Conclusions : We did not observe any effects of aromatase inhibition on cognition in healthy , estrogen-treated postmenopausal women treated with testosterone . This may be due to insufficient study power or a true lack of effect . However , our findings highlight that the detection of subtle changes in cognition in well women require the development of sensitive instruments and large r and omized , controlled trials", "Females are disproportionately affected by constipation , which is often aggravated during pregnancy . Bowel function also changes during the luteal phase of the menstrual cycle . The aim was to compare the effects of acute administration of female sex steroids on gastric emptying , small bowel transit and colonic transit in healthy postmenopausal subjects . A second aim was to determine whether withdrawal of the hormones was associated with a change in transit . Forty-nine postmenopausal females were r and omized to receive for 7 days 400 mg day(-1 ) micronized progesterone , 0.2 mg day(-1 ) oestradiol , combination of the two , or placebo . Treatment groups were balanced on age . Participants underwent whole gut transit measurement by scintigraphy using a 99m-labeled technetium-egg meal and 111-labeled indium-charcoal via a delayed-release capsule . Transit measurement was repeated after withdrawal of the study medications . The primary endpoints were ascending colon ( AC ) emptying half-life time ( t1/2 ) and colonic geometric centre ( GC ) at 24 h. Secondary analysis variables were GC at 4 and 48 h , gastric emptying t1/2 and colonic filling at 6 h. There was a significant overall effect of progesterone on colonic transit with shorter AC emptying t1/2 and significantly greater colonic GC at 48 h. No transit endpoints were altered by oestradiol or combined hormonal treatment relative to placebo . Oestradiol and progesterone result ed in looser stool consistency . Withdrawal of the hormone supplement was not associated with significant alteration in transit . Micronized progesterone does not retard colonic transit in postmenopausal females", "Abstract : Local estrogen substitution has been shown to be more appropriate than any systemic application for the treatment of urogenital symptoms of hormone defiency . The efficacy , safety and acceptability of a new low-dose drug delivery system consisting of an estradiol-releasing silicone vaginal ring was studied in two multicenter trials . In an open-label comparative trial a total of 219 postmenopausal women were r and omized to the estradiol-releasing vaginal ring or to estriol suppositories . In terms of efficacy both treatment arms were shown to be equivalent ; however , significantly higher rates of acceptability were found for the vaginal ring . In a double-blinded placebo-controlled study a total of 84 patients were r and omized to either treatment arm for a period of 24 weeks . The statistically significant improvement of the vaginal epithelial pH and maturation values demonstrated the efficacy of the estradiol-releasing vaginal ring compared to the placebo ring", "OBJECTIVE To investigate the effect of pulsed estrogen therapy S21400 ( intranasal 17 beta-estradiol ) on different quality of life ( QoL ) dimensions in early postmenopausal women treated with S21400 150 microg per day , S21400 300 microg per day , or placebo in a double blind , r and omized , controlled 2-year study . STUDY DESIGN QoL was assessed based on the vali date d Women 's Health Question naire design ed for peri- and post-menopausal women . Three hundred and thirty-five healthy , early postmenopausal Danish women , 53 years of age in average , who completed one question naire at baseline and one under study treatment were included in the analysis set . All analyses were performed on an intention-to-treat basis . RESULTS QoL improved significantly in both S21400 groups compared to placebo in the dimensions ' memory/concentration ' , ' vasomotor symptoms ' , ' sleep problems ' and ' sexual behavior ' ( difference in mean change scores being respectively + 7.9 , + 28.3 , + 9.9 and + 10.8 % , p ' anxiety/depressed mood ' and ' well-being ' . CONCLUSION Pulsed estradiol therapy had a pronounced effect not only on vasomotor symptoms but also a significant and clinical ly relevant improvement in several other QoL dimensions ", "Objective : More than 50 % of all fractures occur in people without osteoporosis . Hormone therapy increases bone density , improves postural balance , and reduces fracture risk in postmenopausal women . It is unclear whether tibolone , a synthetic steroid hormone drug , can improve muscle strength . Thus , the aim of this study was to study the effects of low-dose tibolone therapy on muscle strength in older women . Methods : Eighty healthy women ( 69 completed the study ) 60 years or older were recruited through advertising in the local media . They were r and omly allocated to receive either tibolone 1.25 mg/day or placebo for 6 months . The st and -up test was used to assess leg muscle strength and balance . H and grip and leg muscle strength were measured using JAMAR and modified Cybex dynamometers . Results : Baseline characteristics , including serum estradiol values and muscle strength , were similar in the two groups . Compliance with the therapy regimen was very high , averaging more than 97 % in both groups . After 6 months , mean values for h and grip strength , knee extensor strength , and average time to perform 10 st and s were improved numerically in both groups compared with values during baseline . However , there were no significant differences in these parameters within or between groups , and differences remained nonsignificant after adjustment for age , serum estradiol , and baseline value . Conclusions : Short-term treatment with low-dose tibolone ( 1.25 mg/d ) seems not to affect muscle strength in older women", "OBJECTIVE To determine the effects of raloxifene hydrochloride , 60 mg/d , on serum levels of E(2 ) , estrone , sex steroid-binding globulin , thyroxine-binding globulin , and follicle-stimulating hormone ( FSH ) in postmenopausal women . DESIGN R and omized placebo-controlled study at 16 centers in the United States . PATIENT(S ) Ninety three women 42 to 80 years of age who were at least 2 years postmenopausal . INTERVENTION(S ) Raloxifene ( n = 47 ) or placebo ( n = 46 ) for 3 months . MAIN OUTCOME MEASURE(S ) Levels of E(2 ) , estrone , sex steroid-binding globulin , thyroxine-binding globulin , and FSH were measured at baseline and after 3 months of therapy . RESULT ( S ) Raloxifene increased serum levels of sex steroid-binding globulin and thyroxine-binding globulin and decreased FSH levels compared with placebo . Levels of E(2 ) and estrone were unaffected . CONCLUSION ( S ) In postmenopausal women , raloxifene ( 60 mg/d ) did not increase serum estrogen levels ; however , it increased levels of sex steroid-binding globulin and thyroxine-binding globulin and decreased FSH levels", "OBJECTIVE To evaluate clinical efficacy of multiple regimen combination in treatment of osteoporosis of perimenopausal or postmenopausal women . METHODS From Jul. 2008 to Dec. 2009 , 109 women with low bone mineral density ( BMD ) or osteoporosis treated in Department of Obstetrics and Gynecology , Affiliated Second Hospital , Wenzhou Medical College were enrolled r and omly into 3 group , including 36 women in Group A managed by osteoform 1000 mg/d + alfacalcidol 0.25 µg/bid orally , 40 women in group B managed by osteoform 1000 mg/d + alfacalcidol 0.25 µg/bid + tibolone 1.25 mg/d orally and 33 women in group C managed by osteoform 1000 mg/d + alfacalcidol 0.25 µg/bid + bisphosphonates 70 mg/w orally . After 48 weeks BMD on lumbar 1 - 4 ( L₁₋₄ ) and left femur were detected by X-ray . Bone alkaline phosphatase(BALP ) , cross linked clelopeptide of type I collagen ( CTX ) and 25-hydroxychole calciferol [ 25(OH)D₃ ] was measured by enzyme linked immunosorbent assay ( ELISA ) . RESULT Seven women ( 6.4 % , 7/109 ) were withdrawed form this study , including 2 cases losing follow up in group A , 3 cases stopping treatment in group B , 2 cases giving up treatment due to severe adverse effect ( burning in upper abdomen ) in group C. ( 1 ) Pain relieve : after 48 weeks treatment , women in 3 groups improved symptom of pain significantly , the rates of pain relieve were 85 % ( 29/34 ) in group A , 92 % ( 34/37 ) in group B and 94 % ( 29/31 ) in group C. ( 2 ) BMD : BMD was improved significantly in women in 3 groups after treatment . BMD of L₁₋₄ were ( 0.88 ± 0.15 ) g/cm² in group A , ( 0.89 ± 0.18 ) g/cm² in group B and ( 0.87 ± 0.10 ) g/cm² in group C before treatment , and converted to ( 0.90 ± 0.01 ) g/cm² in group A , ( 0.93 ± 0.09 ) g/cm² in group B and ( 0.91 ± 0.11 ) g/cm² in group C after treatment . BMD of left femur were ( 0.87 ± 0.07 ) g/cm² in group A , ( 0.87 ± 0.07 ) g/cm² in group B and ( 0.85 ± 0.12 ) g/cm² in group C before treatment and converted to ( 0.90 ± 0.03 ) g/cm² in group A , ( 0.91 ± 0.08 ) g/cm² in group B and ( 0.89 ± 0.12 ) g/cm² in group C after treatment . It was shown significantly different BMD between group B or C and group A ( P 0.05 ) . ( 3 ) Index of bone metabolism : BALP were ( 26 ± 6 ) µg/L in group A , ( 26 ± 9 ) µg/L in group B and ( 28 ± 7 ) µg/L in group C before treatment and converted to ( 22 ± 5 ) µg/L in group A , ( 20 ± 9 ) µg/L in group B and ( 22 ± 8) µg/L in group C after treatment , which showed statistical difference ( P 0.05 ) . CTX were ( 0.85 ± 0.20 ) ng/L in group A , ( 0.84 ± 0.47 ) ng/L in group B , and ( 0.88 ± 0.11 ) ng/L in group C before treatment and converted to ( 0.81 ± 0.19 ) ng/L in group A , ( 0.77 ± 0.33 ) ng/L in group B , and ( 0.82 ± 0.14 ) ng/L in group C after treatment , which showed statistical difference ( P of osteoporosis by decreasing bone conversion , increasing bone density , decreasing bone absorption . Regimen A was only suitable for basic therapy , the other two regimens could provide better treatment", "Abstract Rationale : Estrogen concentrations decline with age and menopause is often followed by an acceleration of the age effects on cognition . It is suggested that replacement of estrogen would reinstate , at least in part , cognitive abilities . Effects of estrogens on memory have been reported in studies with women in a clinical setting who either needed or wished to have the estrogen replacement and are mostly in the perimenopausal age-b and . Objective : The present study investigated the effects of estradiol on memory and on frontal lobe function in elderly female subjects who did not suffer any of the postmenopausal symptoms and had never taken estrogen hormone replacement ( EHR ) previously . Methods : EHR ( Progynova TS , transdermal estradiol ; n=19 ) or placebo ( n=18 ) was given for a period of 3 weeks to elderly healthy female subjects . Memory , frontal lobe functions ( inhibition and planning ) and visuospatial abilities ( mental rotation ) were tested before and after treatment . Estrogen plasma levels were measured to confirm the result of EHR . Cortisol plasma levels were also measured before and after cognitive performance in order to evaluate the effects of EHR on the sensitivity of the hypothalamo- pituitary-adrenal ( HPA ) axis to mild mental stress . Results : Plasma estradiol levels in the drug group increased to levels equivalent to that of a fertile woman ( 0.21± 0.5 nmol/l ) . Memory function as well as visuospatial abilities as measured by a mental rotation task improved significantly with EHR . However , there was no effect of EHR on frontal lobe functions . The cognitive effects were not dependent on an improvement in mood or general well-being as may be the case with EHR in women at peri- or post-menopausal stage . EHR was found to increase the HPA response to task-induced stress , as indicated by an increase in cortisol plasma levels . Conclusions : The present study has provided evidence of a beneficial effect of EHR on cognitive abilities given for first time to healthy elderly women . Furthermore , the present study has demonstrated a differential effect of EHR on memory , visuospatial abilities and frontal lobe function ", "Objective : To demonstrate the safety and efficacy of tibolone ( 1.25 and 2.5 mg ) in the treatment of moderate to severe vasomotor symptoms and symptoms associated with vaginal atrophy . Design : A placebo-controlled , double-blind , r and omized , multicenter study was conducted on 396 healthy postmenopausal women experiencing a minimum of 7 moderate to severe hot flashes per day ( 60 per week ) . Participants were r and omized to receive tibolone 1.25 or 2.5 mg or placebo once daily for 12 weeks . Assessment s were done at weeks 4 , 8 , and 12 . The severity and frequency of hot flashes were recorded in patient diaries on a daily basis . Results : Tibolone 2.5 mg significantly ( P the average number of hot flashes compared with placebo at week 4 ( −7.82 vs −5.27 ) , week 8 ( −9.71 vs −5.86 ) , and week 12 ( −10.14 vs −5.85 ) . The difference between tibolone 1.25 mg and placebo was significant ( P the average daily severity of hot flashes were similar , with significantly greater reductions at week 4 ( P that tibolone 2.5 mg significantly ( P reduced nocturia compared with placebo at weeks 4 , 8 , and 12 and urinary urgency at week 4 . Compared with placebo , both doses of tibolone also significantly ( P increased the vaginal maturation value from baseline . The overall incidence of adverse events was similar in all treatment groups . Conclusions : Tibolone is effective and well tolerated for the treatment of moderate to severe vasomotor symptoms and the effects of vaginal atrophy associated with menopause", "OBJECTIVES Determination of the efficacy and safety of vaginally administered low dose ( 25 microg ) micronized 17beta-estradiol in the management of patients with urogenital symptoms . METHODS A total of 1612 patients with urogenital complaints were r and omized to receive 25 microg of micronized 17beta-estradiol ( n=828 ) or placebo ( n=784 ) in a multicenter double-blind placebo-controlled study running for 12 months . Female patients were treated once a day over a period of 2 weeks , and then twice a week for the remaining of the 12 months with an active or placebo tablet . The assessment included full history- question naire , micturition diary , gynecologic and cystometric examination , transvaginal ultrasound , and serum 17beta-estradiol level determination . It was carried out at the beginning , and after 4 and 12 months of treatment . RESULTS The overall success rate of micronized 17beta-estradiol and placebo on subjective and objective symptoms of postmenopausal women with vaginal atrophy was 85.5 % , and 41.4 % , respectively . A significant improvement of urinary atrophy symptoms was determined in vaginal ERT group as compared with the beginning of the study ( 51.9 % vs. 15.5 % , P=0.001 ) . The maximal cystometric capacity ( 290 ml vs. 200 ml , P=0.023 ) , the volume of the urinary bladder at which patients first felt urgency ( 180 vs. 140 , P=0.048 ) , and strong desire to void ( 170 ml vs. 130 ml , P=0.045 ) were significantly increased subsequent to the micronized 17beta-estradiol treatment . The number of patients with uninhibited bladder contractions significantly decreased following micronized 17beta-estradiol as compared with pretreatment values ( 17/30 , P=0.013 ) . Side effects were observed in 61 ( 7.8 % ) patients treated with low dose micronized 17beta-estradiol . Therapy with 25 microg of micronized 17beta-estradiol did not raise serum estrogen level nor stimulated endometrial growth . CONCLUSIONS Local administration of 25 microg of micronized 17beta-estradiol is an effective and a safe treatment option in the management of women with urogenital complaints", "OBJECTIVES At present the Women 's Health Initiative trial is the only reported r and omised controlled trial study ing the effects of hormone therapy among healthy postmenopausal women . The Women 's Health Initiative reports have been criticized for lacking in generalisability , due to the characteristics of the trial population . We aim ed to compare the health effects of oral continuous combined hormone therapy with a placebo and non-treatment among healthy Estonian women . METHODS Eligible women were r and omised into a blind group of hormone therapy versus placebo and into a non-blind group of open label hormone therapy versus non-treatment . One thous and seven hundred and seventy-eight postmenopausal women aged 50 - 64 at the time of sampling were recruited in 1999 - 2001 at three clinical centers in Estonia . Participants received conjugated equine oestrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5mg/d , or conjugated equine oestrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 5mg/d , if less than 3 years had passed since menopause at recruitment , or matched placebo or non-treatment . Trial treatment was stopped gradually from 1 January 2004 to 31 May 2004 . RESULTS After a follow-up period from 2.0 to 5.0 years the combined hazard ratio , stratified by blinding and adjusted for age at recruitment and former oral contraceptive use was 1.12 ( 95 % confidence interval [ CI ] : 0.90 - 1.40 ) for coronary heart disease , 1.24 ( 95 % CI : 0.85 - 1.82 ) for cerebrovascular disease , 1.36 ( 95 % CI : 0.73 - 2.52 ) for total cancer , and 0.61 ( 95 % CI : 0.42 to 0.89 ) for bone fractures . CONCLUSIONS The results from the Estonian Postmenopausal Hormone Therapy r and omised trial are consistent with the Women 's Health Initiative findings", "To test the postulate that sex difference , sex steroids , and peptidyl secretagogues control GH autofeedback , 11 healthy postmenopausal women and 14 older men were each given 1 ) a single iv pulse of GH to enforce negative feedback and 2 ) continuous iv infusion of saline vs. combined GHRH/GHRP-2 to drive feedback escape during pharmacological estradiol ( E(2 ) ; women ) or testosterone ( T ; men ) supplementation vs. placebo in a double-blind , prospect ively r and omized crossover design . By three-way ANCOVA , sex difference , sex hormone treatment , peptide stimulation , and placebo/saline responses ( covariate ) controlled total ( integrated ) GH recovery during feedback ( each P nadir ( maximally feedback-suppressed ) GH concentrations . E(2)/T exposure elevated nadir GH concentrations during saline infusion ( P = 0.003 ) , whereas dual-peptide infusion did so independently of T/E(2 ) and sex difference ( P = 0.001 ) . All three of sex difference ( P = 0.001 ) , sex steroid treatment ( P = 0.005 ) , and double-peptide stimulation ( P recovery of peak ( maximally feedback-escaped ) GH concentrations . Peak GH responses to dual-peptidyl agonists were greater in women than in men ( P = 0.016 ) . E(2)/T augmented peak GH recovery during saline infusion ( P Approximate entropy analysis corroborated independent effects of sex steroid treatment ( P = 0.012 ) and peptide infusion ( P nadir , peak , and entropic measurements of GH release under controlled negative feedback . To the degree that the pharmacological sex steroid , GH , and dual-peptide clamps provide prephysiological regulatory insights , these outcomes suggest major determinants of pulsatile GH secretion in the feedback domain", "Method Twenty-three patients with acroparesthesia were su bmi tted to clinical evaluation and color Doppler analysis of the uterine artery and palmaris superficial branch of the radial artery . Thirteen women ( Group I ) were su bmi tted to hormone treatment with drospirenone 2 mg + + estradiol emidrate 1 mg . Ten patients refused the treatment and served as controls ( Group II ) . The patients were studied at baseline and after 6 months ' therapy . Results After 6 months of hormone therapy , the resistances of the uterine artery and palmaris superficial branch of the radial artery significantly decreased in Group I patients . This was associated with the complete disappearance of paresthesic symptoms in 12/13 ( 92%% ) of the treated patients . In patients belonging to Group II , the paresthesia remained unchanged . Conclusion Hormone therapy with drospirenone may increase the forearm/h and blood flow , and favor the amelioration of paresthesia", "Objective To assess the effects of raloxifene , estrogen , and placebo on quality of life in healthy , asymptomatic , postmenopausal women . Methods In a multicenter , double-blind , 12-month study , 398 women were assigned r and omly to one of four groups : raloxifene HCl , 60 ( n = 97 ) or 150 mg/day ( n = 100 ) ; conjugated equine estrogens , 0.625 mg/day ( n = 96 ) ; or placebo ( n = 105 ) . The Women 's Health Question naire , a vali date d quality -of-life instrument for perimenopausal and postmenopausal women , was administered at baseline and 3-month intervals . Results Overall , quality of life from baseline to end point was preserved equally in all treatment groups . Six domains ( depressed mood , somatic symptoms , memory/ concentration , sexual behavior , sleep problems , and perceived attractiveness ) were unchanged in all groups . Three domains ( menstrual symptoms , vasomotor symptoms , and anxiety/fears ) were statistically significantly different among groups . Mean scores for menstrual symptoms significantly worsened and vasomotor symptoms significantly improved from baseline to end point in the estrogen group . Mean scores for vasomotor symptoms did not worsen at any point in the raloxifene 60 mg/day group . Mean anxiety/fears scores improved significantly during raloxifene 60 mg/day administration throughout treatment ( P quality -of-life domains were not affected by treatment with estrogen or raloxifene . Estrogen provided relief from vasomotor symptoms but caused menstrual symptoms . Raloxifene 60 mg/day improved anxiety levels in postmenopausal women", "Aim : This multicenter , open-label , single-arm study evaluated subject satisfaction and improvements in menopausal quality of life among menopausal women using the CombiPatch ® transdermal system consisting of 17β-estradiol 0.05 mg plus norethindrone acetate 0.14 mg in a matrix patch formulation . Methods : The 193 postmenopausal women between the ages of 45 and 65 years who comprised the modified intent-to-treat population ( at least one patch and one efficacy assessment ) were required to have reported at least five daily moderate-to-severe hot flashes and episodes of nocturnal sweating upon study entry for at least 1 month and applied one patch twice a week for 12 weeks . At weeks 0 , 6 , and 12 , the women completed the Menopause-Specific Quality of Life ( MENQOL ) Question naire and , as a secondary study outcome , reported the scale of their application site discomfort . During weeks 1–12 , they also kept diary records of number and severity of hot flashes and four other menopausal symptoms . Skin tolerance and adherence of the transdermal system were evaluated at weeks 6 and 12 by qualified evaluators . At week 6 and the end of the study , both subjects and physicians rated their satisfaction with the system . Results : Among women in the modified intent-to-treat population , transdermal 17β-estradiol plus norethindrone acetate significantly reduced the mean daily number of moderate-to-severe hot flashes experienced by women from 4.1 at week 1 to 0.6 at week 12 ( p The mean ratings of headache severity , insomnia , and vaginal irritation/dryness also improved significantly by week 6 and were maintained at week 12 . At week 12 , 92.4 % of the subjects and 97.3 % of the physicians reported that they were ‘ satisfied ’ or ‘ very satisfied ’ with the transdermal hormone delivery system . Conclusions : The results of this study compare favorably with previous placebo-controlled studies of transdermal hormone therapy in managing menopausal signs and symptoms . Furthermore , quality of life was significantly improved by the transdermal hormone therapy system , and both subjects and physicians reported high levels of satisfaction ", "BACKGROUND The Women 's Health Initiative ( WHI ) clinical trial of conjugated equine estrogens ( CEEs ) , involving 10,739 postmenopausal women with hysterectomy , aged 50 to 79 years , was stopped early owing to lack of overall health benefit and increased risk of stroke . Because CEE is still prescribed for treatment of menopausal symptoms and prevention of osteoporosis , it is important to underst and the overall impact of this therapy on health-related quality of life ( HRQOL ) . METHODS All participants completed 6 specific measures of quality of life at baseline and 1 year , and a sub sample ( n = 1189 ) also completed the questions 3 years after r and omization . Changes in scores were analyzed for treatment effect . RESULTS R and omization to CEE was associated with a statistically significant but small reduction in sleep disturbance at year 1 compared with baseline ( mean benefit , 0.4 points on a 20-point scale ) and a statistically significant but small negative effect on social functioning ( mean effect , -1.3 points on a 100-point scale ) . There were no significant improvements due to CEE in the areas of general health , physical functioning , pain , vitality , role functioning , mental health , depressive symptoms , cognitive function , or sexual satisfaction at year 1 . A subgroup examined 3 years after baseline had no significant benefits for any HRQOL outcomes . Among women aged 50 to 54 years with moderate to severe vasomotor symptoms at baseline , CEE did not improve any of the HRQOL variables at year 1 . CONCLUSION In this trial of postmenopausal women with prior hysterectomy , oral CEE did not have a clinical ly meaningful effect on HRQOL", "Summary In this 2-year extension of a 3-year study , bazedoxifene showed sustained efficacy in preventing new vertebral fractures in postmenopausal women with osteoporosis and in preventing non-vertebral fractures in higher-risk women . Bazedoxifene significantly increased bone mineral density and reduced bone turnover versus placebo and was generally safe and well tolerated . Introduction This study evaluated the efficacy and safety of bazedoxifene for the treatment of postmenopausal osteoporosis over 5 years . Methods A total of 4,216 postmenopausal women with osteoporosis were enrolled in this 2-year extension of a 3-year , r and omized , double-blind , placebo-controlled , phase 3 trial . In the core study ( N = 7,492 ) , subjects received bazedoxifene 20 or 40 mg/day , raloxifene 60 mg/day , or placebo . The raloxifene arm was discontinued after 3 years ; subjects receiving bazedoxifene 40 mg were transitioned to bazedoxifene 20 mg after 4 years . Five-year findings are reported for bazedoxifene 20 and 40/20 mg and placebo . Endpoints included incidence of new vertebral fractures ( primary ) and non-vertebral fractures , and changes in bone mineral density ( BMD ) and bone turnover markers . Results At 5 years , the incidence of new vertebral fractures in the intent-to-treat population was significantly lower with bazedoxifene 20 mg ( 4.5 % ) and 40/20 mg ( 3.9 % ) versus placebo ( 6.8 % ; P respectively . Non-vertebral fracture incidence was similar among groups . In a subgroup of higher-risk women ( n = 1,324 ; femoral neck T-score ≤−3.0 and /or ≥1 moderate or severe or ≥2 mild vertebral fracture[s ] ) , bazedoxifene 20 mg reduced non-vertebral fracture risk versus placebo ( 37 % ; P = 0.06 ) ; combined data for bazedoxifene 20 and 40/20 mg reached statistical significance ( 34 % reduction ; P 0.05 ) . Bazedoxifene significantly increased BMD and reduced bone turnover versus placebo ( P safe and well tolerated . Conclusions The findings support a sustained anti-fracture effect of bazedoxifene on new vertebral fractures in postmenopausal osteoporotic women and on non-vertebral fractures in the higher-risk subgroup of women", "OBJECTIVE To evaluate the effects of combination estrogen/ and rogen therapy on muscle mass , strength and endurance , serum hormone and lipid profiles , and quality of life measures in postmenopausal women . METHODS Prospect i ve , r and omized , placebo-controlled pilot study at a tertiary care medical center . Fifty postmenopausal women were r and omized to a 12-week course of ( 1 ) dehydroepi and rostenedione ( DHEA ) 50 mg daily , ( 2 ) conjugated equine estrogen ( CEE ) 0.625 mg daily , ( 3 ) DHEA 50 mg+CEE 0.625 mg daily , or ( 4 ) placebo . Main outcome measures of lower extremity muscle ( calf ) mass , functional muscle parameters , serum hormone and lipid levels , and quality of life ( QOL ) were obtained at baseline and after treatment . Statistical analysis compared percent change from baseline values and treatment differences among outcomes . RESULTS Significant increases in mean DHEA , DHEA sulfate ( DHEA-S ) , testosterone , and and rostenedione levels were noted with DHEA alone or combined DHEA/CEE treatments when compared with placebo . Compared with no hormone therapy , none of the supplemental hormone groups caused significant changes in muscle mass , muscle strength , muscle endurance , feelings of well-being , sleep , or sexual function . CONCLUSIONS And rogen replacement therapy , with DHEA , to menopausal women increases serum and rogen levels without any appreciable effect on muscle cross-sectional area , muscle strength , muscle function , or improvement in health-related QOL", "OBJECTIVE To determine the effects of 9 months of hormone replacement therapy ( HRT ) on cognitive performance in women aged 75 years and older . METHODS A 9-month r and omized , double-blinded , placebo-controlled parallel trial . Fifty-two elderly postmenopausal women ( age range 75 - 91 years ) without known contraindications to HRT or evidence of dementia or depression were enrolled . Participants were r and omly assigned in a 1:2 ratio to placebo or conjugated estrogens at 0.625 mg/d plus trimonthly medroxyprogesterone acetate at 5 mg/d for 13 days ( HRT ) . Main outcome measures were change from baseline and rate of change from baseline for the following psychometric tests : Verbal Fluency Test , Weschler Paired Associate Learning and 20 min Delayed Recall , Trailmaking A and B Tests , Cancellation R and om Letter and R and om Form Tests . RESULTS At baseline , women in the HRT group reported a younger age of onset of menopause and a higher prevalence of hysterectomy , but otherwise did not differ from women in the placebo group . After 9 months of treatment , there were no significant group differences for any of the cognitive performance measures . The lack of an observed group-by-time difference for all cognitive tests remained after controlling for age of onset of menopause , education , and previous hysterectomy . CONCLUSIONS Although conclusions are limited by small sample size and the relatively short duration of treatment , results suggest that 9 months of estrogen replacement in combination with trimonthly progestin does not improve cognitive performance in women over 75 years who do not have dementia or depression", "OBJECTIVE Menopause is linked to an increase in fat mass and a decrease in lean mass exceeding age-related changes , possibly related to reduced output of ovarian steroids . In this study we examined the effect of combined postmenopausal hormone replacement therapy ( HRT ) on the total and regional distribution of fat and lean body mass . RESEARCH METHODS AND PROCEDURES Sixteen healthy postmenopausal women ( age : 55 + /- 3 years ) were studied in a placebo-controlled , crossover study and were r and omized to 17beta estradiol plus cyclic norethisterone acetate ( HRT ) or placebo in two 12-week periods separated by a 3-month washout . Total and regional body composition was measured by DXA at baseline and in the 10th treatment week in both periods . Changes were compared by a paired Student 's t test . RESULTS The change in body weight during HRT was equal to the change during placebo ( -24.6 g vs. -164 g , p = 0.42 ) , but relative fat mass was significantly reduced ( -0.5 % vs. + 1.24 % , p HRT , compared with during placebo , lean body mass increased ( + 347 g vs. -996 g , p total fat mass decreased ( -400 g vs. + 836 g , p = 0.06 ) . Total bone mineral content increased ( + 28.9 g vs. -4.4 g , p = 0.04 ) and abdominal fat decreased ( -185 g vs. + 253 g , p = 0.04 ) during HRT compared with placebo . DISCUSSION HRT is linked to the reversal of both menopause-related obesity and loss of lean mass , without overall change in body weight . The increase in lean body mass during HRT is likely explained by muscle anabolism , which in turn , prevents disease in the elderly", "OBJECTIVE Two prospect i ve multicenter , double-blind , r and omized , controlled trials were conducted to examine the safety and efficacy of three once-a-week continuous combined 17beta-estradiol/levonorgestrel ( E2/LNG ) transdermal systems ( E2 0.045 mg/day with 0.015 , 0.030 , and 0.040 mg/day LNG ) for the treatment of vasomotor symptoms and prevention of estrogen-induced endometrial hyperplasia in healthy , postmenopausal women . DESIGN In study 1 , performed in 293 hysterectomized and nonhysterectomized women with moderate to severe hot flushes , transdermal E2/LNG ( E2 0.045 mg/day with 0.030 and 0.040 mg/day LNG ) was compared with placebo for three 28-day treatment cycles . The frequency and severity of hot flushes were recorded daily . In study 2 , performed in 845 women with intact uteri , transdermal E2/LNG ( E2 0.045 mg/day with 0.015 , 0.030 , and 0.040 mg/day LNG ) was compared with transdermal E2 0.045 mg/day monotherapy for thirteen 28-day treatment cycles . Women with endometrial tissue sufficient for evaluation underwent endometrial biopsy assessment at the end of cycle 13 . Bleeding patterns were assessed throughout the study , and the Women 's Health Question naire was used to assess well-being . RESULTS In study 1 , transdermal E2/LNG ( E2 0.045 mg/day with 0.030 and 0.040 mg/day LNG ) significantly decreased the number and severity of hot flushes when compared with placebo . Symptom relief was seen as early as 2 weeks posttreatment . Similarly , in study 2 , all three doses of transdermal E2/LNG and E2 controlled hot flushes with no differences between groups . In study 2 , no women receiving transdermal E2/LNG developed endometrial hyperplasia compared with 19 ( 12.8 % ) who received transdermal E2 0.045 mg/day ( p Women 's Health Question naire for vasomotor symptoms , sleep problems , sexual function , cognitive difficulties , and total score were noted at all or most time points with both transdermal E2/LNG and E2 . Application-site reactions , vaginal hemorrhage , and breast pain were the most common adverse events reported with transdermal E2/LNG . The proportion of women with amenorrhea increased over time in all treatment groups in study 2 . CONCLUSIONS All three doses of this once-a-week combined E2/LNG transdermal system rapidly and effectively control vasomotor symptoms in postmenopausal women while protecting against endometrial hyperplasia . Amelioration of vasomotor symptoms also is accompanied by improvements in aspects of subjective well-being . Once-a-week transdermal E2/LNG , therefore , offers an effective and convenient formulation , the dosing of which can be individualized according to the needs of each patient", "OBJECTIVE The aim of the study was to confirm the superior efficacy of estriol containing pessaries compared to placebo in the treatment of vaginal atrophy . STUDY DESIGN In a prospect i ve , multicenter , r and omized , placebo-controlled , double-blind study , 436 postmenopausal women with vaginal atrophy ( vaginal maturation index , VMI5 ; most bothersome symptom , MBS≥65 on visual analogue scale , VAS ) were treated with pessaries containing either 0.2 mg estriol ( N=142 ) or 0.03 mg estriol ( N=147 ) or with a matching placebo ( N=147 ) for 12 weeks . MAIN OUTCOME MEASURES Primary efficacy endpoints included increase in VMI , decrease of the vaginal pH value and decrease in intensity of MBS after 12 weeks of treatment . RESULTS The increase in VMI was significantly greater under 0.2 mg estriol and 0.03 mg estriol ( 46.3±17.0 and 38.4±19.4 , respectively ) compared to placebo ( 23.9±21.5 ; p values decreased significantly more ( -1.6±0.8 and -1.4±0.9 , respectively ) compared to placebo ( -0.6±0.8 ; p values VAS ) declined significantly more ( -52.2±23.7 and -47.1±23.4 , respectively ) compared to placebo ( -31.8±26.3 ; p values events were rare and occurred at similar rates in all three groups . CONCLUSIONS Superiority of estriol containing pessaries over placebo was shown in the local treatment of vaginal atrophy . Even a very low dose of 0.03 mg estriol proved sufficient for local treatment of vaginal atrophy with excellent tolerability", "The aim of the study was to investigate the effect of 25 micrograms 17 beta-estradiol administered as a small vaginal tablet ( Vagifem , Novo Nordisk A/S ) on the symptoms of the vagina related to atrophy . The study was design ed as a double-blind r and omized placebo controlled study running for 12 weeks . The women were treated once daily for 2 weeks with the active or the placebo tablet . During the subsequent 10 weeks the women were treated twice a week . One hundred and sixty-four women were included . Ten dropped out for minor reasons , most of these due to lack of effect in the placebo group . In the Vagifem group 78.8 % were suffering from moderate to severe atrophy of the vagina , compared with 81.9 % in the placebo group . After 2 weeks the percentages were 14.3 and 35.3 , respectively . After 12 weeks of treatment , 10.7 % in the Vagifem group compared with 29.9 % in the placebo group had moderate to severe atrophy ( P less than 0.0001 ) . A substantial part of the women complained about subjective symptoms such as vaginal dryness and dyspareunia . After 12 weeks of treatment , a significant improvement was found in the Vagifem group ( P less than 0.002 ) . Before treatment 53.1 % in the treatment group and 41.0 % in the placebo group were suffering from urological symptoms . After 2 weeks , 60.5 % of the women in the Vagifem group underwent a change for the better compared to 35.3 % in the placebo group . After 12 weeks of treatment the percentages in the two groups feeling an improvement were 62.8 % and 32.4 % . In this study local low-dose treatment with 25 micrograms 17 beta-estradiol was found to have a significant effect on the postmenopausal urogenital symptoms related to atrophy", "BACKGROUND In perimenopause many women complain of psychogenic and organic disorders often connected with initial and increasing levels of hypoestrogenism . In this study we evaluated the effects of hormone replacement therapy ( HRT ) in symptomatic women in perimenopause . METHODS We enrolled 100 healthy and symptomatic women who were r and omly distributed to two groups for a 12-month study . Group A : 50 patients received HRT with estradiol valerate and cyproterone acetate ( Pausene(R ) ) ; Group B : 50 patients were used as a control group ( treated with Cacit Vitamin D30(R ) ) . A number of clinical and instrumental tests were performed at 0 , 6 and 12 months to evaluate any changes in vasomotor and urogenital symptoms , bone and serum homeostasis and possible sexual disorders . The statistical analysis was performed using the c2 test . RESULTS The group of women receiving HRT showed a significant reduction in vasomotor clinical symptoms ( p sexual disorders ( p libido decreased steadily with apparent slight improvements only at the end of the study . The urogenital disorders disappeared almost completely in Group A , whereas they diminished in Group B. HRT patients also showed a slight increase ( p BMD ( bone mineral density ) , a reduction in the marker for bone turnover and an improved lipid profile ( p HRT appeared to have a beneficial effect on perimenopausal clinical symptoms over the 12-month period , leading to marked improvements in the psychophysical wellbeing of symptomatic women in perimenopause", "OBJECTIVE : To investigate safety and efficacy and identify the lowest effective dose of a new transdermal estradiol ( E2 ) gel for relief of menopausal symptoms in a population of postmenopausal women . METHODS : This study was a r and omized , double-blind , placebo-controlled , multicenter , parallel-group study . Postmenopausal women with at least 60 hot flushes per week applied 0.87 g/d ( n=136 ) , 1.7 g/d ( n=142 ) , or 2.6 g/d ( n=69 ) E2 gel or placebo gel ( n=137 ) topically for 12 weeks . The changes from baseline in hot flush frequency and severity at 4 and 12 weeks and changes from baseline in vaginal atrophy symptoms at 12 weeks were examined . RESULTS : With increasing E2 doses , mean trough serum E2 increased from 17 to 29 pg/mL. By weeks 3–5 , E2 gel reduced moderate-to-severe hot flush rate by at least seven hot flushes per day ( P in hot flush number were 3.2 and 6.3 for the 0.87-g/d group and 1.3 and 2.3 for the 2.6-g/d group . At week 12 , vaginal pH was more acidic and vaginal maturation index more mature compared with placebo ( P most bothersome vulvovaginal atrophy symptoms ( P well tolerated at the site of application and produced no unexpected adverse effects . The 0.87 g/d dose produced fewest adverse events . CONCLUSION : The 0.87 g/d dose of this new transdermal E2 gel , which delivers an estimated 0.0125 mg E2 daily , delivered the lowest effective dose for treatment of vasomotor symptoms and vulvovaginal atrophy in a population of postmenopausal women . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00391417 LEVEL OF EVIDENCE :", "OBJECTIVE To assess the effect of raloxifene compared with placebo on sexual function in older postmenopausal women undergoing therapy for the treatment of osteoporosis . METHODS A subset ( 12 % ) of English-speaking women in the United States and Canada participating in the Multiple Outcomes of Raloxifene Evaluation Trial were asked to complete a sexual function question naire at baseline and after 36 months of treatment . The Multiple Outcomes of Raloxifene Evaluation Trial is a multicenter , r and omized , blinded , placebo-controlled clinical trial , in which 7705 postmenopausal women with osteoporosis were r and omly assigned to one of three groups : raloxifene hydrochloride 60 mg per day or 120 mg per day or placebo . In this sub study , 943 women completed the sexual function question naire at both visits . Because preliminary analyses showed no differences by raloxifene dose ( n = 302 for 60 mg per day ; n = 322 for 120 mg/day ) , the two groups were combined and compared with the placebo group ( n = 319 ) . For the given sample size , we had 80 % power ( & agr ; = .05 , two-sided , ratio of raloxifene to placebo = 2:1 ) to detect a 10%–16 % difference in the proportion of women experiencing no change in sexual function between placebo and treatment groups . RESULTS Overall , sexual function and changes in sexual function from baseline to study end between the raloxifene and placebo groups did not differ . In particular , there were no differences in sexual desire or frequency of sexual activity between the groups . Among sexually active women , there were no differences in enjoyment , satisfaction , orgasm , or reported sexual problems . CONCLUSION Sexual function in older postmenopausal women with osteoporosis is not affected by treatment with raloxifene", "Objective : To determine the effects of lower doses of conjugated estrogens ( CE ) alone or in combination with medroxyprogesterone acetate ( MPA ) on body weight and to evaluate the influence of body mass index ( BMI ) on the effect of lower-dose CE or CE/MPA on vasomotor symptoms , vaginal atrophy , bone mineral density ( BMD ) , endometrial safety , and side effects such as endometrial bleeding and breast pain . Design : In this large clinical trial [ the Women 's Health , Osteoporosis , Progestin , Estrogen ( Women 's HOPE ) study ] , 2,673 healthy , postmenopausal women with intact uteri were r and omized for 1 year of CE 0.625 , CE 0.625/MPA 2.5 , CE 0.45 , CE 0.45/MPA 2.5 , CE 0.45/MPA 1.5 , CE 0.3 , CE 0.3/MPA 1.5 ( all doses mg/d ) , or placebo . Weight , BMI , number and severity of hot flushes , vaginal atrophy ( as determined by the vaginal maturation index ) , bleeding profiles , breast pain , and endometrial biopsies were evaluated . A subset of 822 women was r and omized into a 2-year sub study to evaluate changes in BMD with lower-dose CE or CE/MPA regimens . Results : After 1 year of treatment , a small but significant ( P gain in body weight from baseline was observed in all arms of the study , the largest increase in body weight occurring in the placebo group [ 1.15 ± 0.21 ( SE ) kg ] . Body mass index had no significant effect on changes from baseline for vasomotor symptoms , bleeding patterns , vaginal atrophy , BMD , endometrial safety , or breast pain when analyzed both by analysis of covariance with baseline BMI as covariate or when participants were grouped into BMI less than 25 kg/m2 and BMI of 25 kg/m2 or greater . In placebo-treated women , vaginal atrophy was significantly greater ( P of CE or CE/MPA are not associated with greater weight gain than placebo . In addition , BMI does not seem to influence effects of these regimens on vasomotor symptoms , vaginal atrophy , bleeding profiles , BMD , endometrial safety , or breast pain", "Aims : To compare the effects of 3 months ' tibolone treatment with the effects of placebo on sexual function ( in particular , vaginal blood flow , and sexual desire and arousability ) and climacteric symptoms in postmenopausal women . Methods : A r and omized , double-blind , cross-over study was conducted in 38 postmenopausal women who received tibolone 2.5 mg/day and placebo . Vaginal blood flow during erotic stimulation by fantasy and film was measured using a vaginal photoplethysmograph and subjects completed sexual function question naires and daily diaries . Results : Tibolone significantly increased baseline vaginal pulse amplitude ( VPA ) levels compared with placebo . There were significant treatment differences in VPA in favor of tibolone during fantasy periods but not during erotic film stimulation . Tibolone was associated with significant increases in sexual desire , and the frequency of arousability and of sexual fantasies compared with those with placebo . Vaginal lubrication was significantly improved on tibolone . Twenty-five of 38 ( 66 % ) subjects correctly guessed when they were on active treatment . Tibolone was well tolerated . Conclusions : Tibolone was associated with significant improvements in sexual function in postmenopausal women , reflecting both its estrogenic and and rogenic properties . There were significantly greater increases in vaginal blood flow with tibolone in response to erotic fantasy but not film , suggesting two possible pathways of female sexual response", "Objective The aim of this study was to determine the efficacy , safety , and lowest practical dose of a transdermal estradiol gel in the treatment of symptomatic postmenopausal women . Methods Healthy postmenopausal women with seven or more moderate to severe hot flushes per day or 50 to 60 or more per week were r and omized to transdermal gel containing 1.5 mg ( n = 73 ) or 0.75 mg ( n = 75 ) estradiol ( EstroGel 0.06 % ) or placebo ( n = 73 ) in a phase 3 study , or to 0.375 mg ( n = 119 ) or 0.27 mg ( n = 118 ) estradiol ( 0.03 % gel ) or placebo ( n = 114 ) in a phase 4 study . Results The frequency of moderate to severe hot flushes and severity of all hot flushes significantly decreased versus placebo at weeks 4 and 12 with 1.5 , 0.75 , and 0.375 mg estradiol . Overall participant responder rates were generally lower in the phase 4 study than those in the phase 3 study with the approved 0.75-mg estradiol dose . Vaginal maturation index ( VMI ) shifts from baseline to week 12 were significant ( P estradiol versus placebo ; VMI improved ( P superficial cells increased ( P = 0.005 ) , and parabasal cells decreased ( P = 0.002 ) with 0.375 mg estradiol vs placebo but not with 0.27 mg estradiol . The most frequently reported treatment-emergent adverse events , although not necessarily treatment related , were headache , infection , breast pain , and nausea ( phase 3 study ) and insomnia and headache ( phase 4 study ) . No serious adverse events were related to treatment ; no deaths occurred . Conclusion A transdermal gel with 0.75 mg estradiol was the lowest practical dose that effectively reduced the frequency and severity of moderate to severe hot flushes , improved VMI , and was well tolerated", "ABSTRACT Objectives To determine the efficacy and safety of low-dose maintenance therapy with transdermal estradiol ( E2 ) gel in Japanese women with climacteric disorder and estrogen deficiency symptoms . Methods Women ( n = 209 ) aged 37–59 years who had climacteric disorder or estrogen deficiency symptoms received a st and ard dose of transdermal E2 gel ( 1.8 g/day , containing E2 1.08 mg/day ) for 8 weeks as induction treatment . A total of 177 women in whom the number of daily hot flushes had decreased to less than one-third of the baseline value ( marked improvement ) at week 8 were double-blindly r and omized to receive low-dose E2 ( n = 88 , 0.9 g/day , containing E2 0.54 mg/day ) or E2-free placebo ( n = 89 ) for 16 weeks . Results Improvement rates in the number of daily hot flushes at the final evaluation ( primary endpoint ) in the low-dose E2 group ( marked 90.8 % , moderate 6.9 % , mild 1.1 % , no change 1.1 % , worsening 0 % ) were significantly greater than in the placebo group ( marked 77.0 % , moderate 10.3 % , mild 4.6 % , no change 2.3 % , worsening 5.7 % ) ( p = 0.0097 ) , showing an inhibitive effect on the flare-up of climacteric symptoms . The incidence of treatment-related adverse events in the low-dose group ( 21.6 % ) was similar to that in the placebo ( 22.5 % ) but was lower than that in the st and ard-dose treatment ( 32.5 % ) . Conclusions Low-dose maintenance therapy that was half the st and ard dose of transdermal E2 gel ( 0.9 g/day ) applied to women who had achieved marked improvement in the number of hot flushes at the st and ard dose ( 1.8 g/day ) was demonstrated to be effective ( inhibition of recurrence ) and safe for the treatment of climacteric disorder and estrogen deficiency symptoms", "Objective : To evaluate the effects of combined vaginal and oral low-dose estrogen plus progestogen therapy ( EPT ) on the frequency and severity of dyspareunia , sexual function , and quality of life in recently postmenopausal women . Methods : This outpatient , double-blind , r and omized , placebo-controlled trial enrolled 285 healthy , sexually active postmenopausal women aged 45 to 65 years . Women received either one daily oral low-dose conjugated estrogens ( 0.45 mg)/medroxyprogesterone ( 1.5 mg ) tablet for six 28-day cycles along with 1 g conjugated estrogens vaginal cream ( 0.625 mg ) , intravaginally for the first 6 weeks of the trial or a placebo cream and placebo tablet . Efficacy was evaluated using the McCoy Female Sexuality Question naire , self-reported daily diary cards , the Brief Index of Sexual Functioning-Women ( BISF-W ) , and the Women 's Health Question naire . Results : The EPT group had a significant decrease in the frequency of dyspareunia compared with baseline and placebo in an analysis of responses to the McCoy Female Sexuality Question naire . Also , EPT was associated with a significant improvement in a woman 's level of sexual interest , frequency of orgasm , and pleasure of orgasm . There was no effect of EPT use on coital frequency . The EPT group had significant improvement in receptivity/initiation and relationship satisfaction , although not in other BISF-W domains , versus placebo ( BISF-W analysis ) and significant improvement versus placebo on most Women 's Health Question naire responses . Conclusions : EPT provided a statistically significant improvement compared with placebo in dyspareunia , sexual experience , and quality of life as measured in this study . In general , EPT also improved self-reported sexual perception and enjoyment significantly compared with placebo", "OBJECTIVE : To evaluate the efficacy of ultra – low-dose 10-microgram 17&bgr;-estradiol ( E2 ) vaginal tablets for treatment of vaginal atrophy . METHODS : Postmenopausal women ( N=309 ) were r and omly assigned to 10-microgram E2 or placebo vaginal tablets for 52 weeks in a multicenter , double-blind study . Primary efficacy endpoints included change from baseline to week 12 in vaginal cytology , vaginal pH , and most bothersome urogenital symptoms score . Grading of vaginal health was a secondary efficacy assessment . Safety assessment s included endometrial biopsy , physical and gynecologic examinations , and recording adverse events . RESULTS : At week 12 , the change from baseline for 10 micrograms E2 compared with placebo demonstrated significant improvement in vaginal Maturation Index ( proportion of parabasal cells : –37 % compared with –9 % ; superficial cells : 13 % compared with 4 % ; intermediate cells : 24 % compared with 5 % ; P each ) , Maturation Value ( 25.0 compared with 6.5 , P grading of vaginal health ( –0.91 compared with –0.51 , P vaginal pH grade ( –1.3 compared with –0.4 , P and most bothersome symptoms score ( –1.23 compared with –0.87 , P=.003 ) . For each component of vaginal Maturation Index , vaginal Maturation Value , grading of vaginal health , and vaginal pH , treatment effects were statistically different from placebo after 2 weeks of treatment . For most bothersome symptoms , treatment effect became apparent after 4 weeks and reached statistical significance at week 8 of therapy . All treatment effects were statistically significant at week 52 . There were no major safety findings regarding physical , gynecologic , or laboratory assessment s. CONCLUSION : After 12 weeks of treatment , an ultra – low-dose 10-microgram E2 vaginal tablet , compared with placebo , demonstrated significant improvement for the primary endpoints : vaginal cytology and pH and most bothersome urogenital symptoms score . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , http:// clinical trials.gov , NCT00108849 LEVEL OF EVIDENCE :", "OBJECTIVE Selective estrogen receptor modulators ( SERMs ) are drugs that exhibit both estrogen agonistic and antagonistic effects that are tissue-specific . Ospemifene ( FC-1271a ) is a novel SERM compound , which has been shown in animal models to have estrogen-like effects on bone and the cardiovascular system , while having antiestrogen-like effects in uterus and breast . In this study , we investigated the effects of ospemifene on the uterine endometrium , vaginal maturation index and hormonal status in healthy postmenopausal women . METHODS The study was conducted as a double-blind , placebo-controlled phase I study , where 40 healthy postmenopausal women volunteers were r and omized to receive daily oral doses of ospemifene either 25 , 50 , 100 or 200 mg or placebo for 12 weeks . Vaginal ultrasonography and endometrial biopsy were performed and vaginal maturation index determined at baseline and at 12 weeks ' visit . Serum concentrations of estradiol , luteinizing hormone , follicle stimulating hormone ( FSH ) , sex-hormone binding globulin ( SHBG ) , parathyroid hormone and prolactin were determined from sample s taken at baseline , at 4 days and at 4 , 12 , and 16 weeks ' visits . Climacteric symptoms were assessed using 12 visual analogue scales ( VAS ) at baseline and at the end of the study . RESULTS No clinical ly significant changes were seen in endometrial thickness at any dose level . Ospemifene exerted a very weak estrogenic effect on endometrial histology . On the other h and , it induced a clear estrogenic effect on vaginal epithelium . Among the endocrine parameters only FSH and SHBG showed significant dose dependent changes ; FSH decreased and SHBG increased during the treatment . In general , ospemifene was well tolerated . The 25 and 50 mg doses tended to reduce climacteric symptoms , but no statistically significant differences were observed between different doses of ospemifene and placebo . The highest dose level ( 200 mg ) induced more subjective adverse reactions , especially hot flushes , than lower doses . CONCLUSION Our study suggests that a safe and well tolerated dose of ospemifene for potential clinical use may be between 25 and 100 mg . Further studies are needed to substantiate the results of this Phase I pilot study", "BACKGROUND Vasomotor symptoms and bone loss are complications frequently induced by adjuvant treatment for breast cancer . Tibolone prevents both side-effects , but its effect on cancer recurrence is unknown . The aim of this study was to show non-inferiority of tibolone to placebo regarding risk of recurrence in breast-cancer patients with climacteric complaints . METHODS Between July 11 , 2002 , and Dec 20 , 2004 , women surgically treated for a histologically confirmed breast cancer ( T(1 - 3)N(0 - 2)M(0 ) ) with vasomotor symptoms were r and omly assigned to either tibolone 2.5 mg daily or placebo at 245 centres in 31 countries . R and omisation was done by use of a central ised interactive voice response system , stratified by centre , with a block size of four . The primary endpoint was breast-cancer recurrence , including contralateral breast cancer , and was analysed in the intention-to-treat ( ITT ) and per- protocol population s ; the margin for non-inferiority was set as a hazard ratio of 1.278 . This study is registered with Clinical Trials.gov , number NCT00408863 . FINDINGS Of the 3148 women r and omised , 3098 were included in the ITT analysis ( 1556 in the tibolone group and 1542 in the placebo group ) . Mean age at r and omisation was 52.7 years ( SD 7.3 ) and mean time since surgery was 2.1 years ( SD 1.3 ) . 1792 of 3098 ( 58 % ) women were node positive and 2185 of 3098 ( 71 % ) were oestrogen-receptor positive . At study entry , 2068 of 3098 ( 67 % ) women used tamoxifen and 202 of 3098 ( 6.5 % ) women used aromatase inhibitors . The mean daily number of hot flushes was 6.4 ( SD 5.1 ) . After a median follow-up of 3.1 years ( range 0.01 - 4.99 ) , 237 of 1556 ( 15.2 % ) women on tibolone had a cancer recurrence , compared with 165 of 1542 ( 10.7 % ) on placebo ( HR 1.40 [ 95 % CI 1.14 - 1.70 ] ; p=0.001 ) . Results in the per- protocol population were similar ( 209 of 1254 [ 16.7 % ] women in the tibolone group had a recurrence vs 138 of 1213 [ 11.4 % ] women in the placebo group ; HR 1.44 [ 95 % CI 1.16 - 1.79 ] ; p=0.0009 ) . Tibolone was not different from placebo with regard to other safety outcomes , such as mortality ( 72 patients vs 63 patients , respectively ) , cardiovascular events ( 14 vs 10 , respectively ) , or gynaecological cancers ( 10 vs 10 , respectively ) . Vasomotor symptoms and bone-mineral density improved significantly with tibolone , compared with placebo . INTERPRETATION Tibolone increases the risk of recurrence in breast cancer patients , while relieving vasomotor symptoms and preventing bone loss . FUNDING Schering-Plough ( formerly NV Organon , Oss , Netherl and s )", "This study reports some of the effects of oestrogen and progestogen therapy . forty-nine women who had undergone hysterectomy and bilateral salpingo-oophorectomy took part in a double blind crossover study during which they received ethinyl oestradiol 50 micrograms/day , norgestrel 250 micrograms/day , the combination of these substances \" Nordiol \" and placebo . Somatic complaints were assessed at monthly interviews and weight and blood pressure recorded . The addition of norgestrel to ethinyl oestradiol therapy result ed in less dryness of skin but significantly increased mastalgia and breast size . There were no significant differences between drugs on amount of facial hair , acne , arthralgia , pruritus vulvae , vaginal discharge , vaginal odour , dyspareunia , weight or blood pressure . There was a significant reduction of diastolic blood pressure with the time duration of the study", "Abstract Objective : This study aim ed to evaluate the effects of monophasic estrogen-progestogen therapy on the sexuality and climacteric symptoms of postmenopausal women . Patients and methods : A prospect i ve , r and omised , double-blind , crossover , placebo-controlled , single-centre study was carried out over a total of 12 consecutive months in 40 postmenopausal women with an intact uterus who had no contraindications to hormone therapy . Patients received 17β-estradiol 2 mg in combination with norethisterone acetate 1 mg ( Cliane ® ) daily for 6 months or one placebo tablet daily for 6 months . The tablets were identical in appearance . After 6 months , the groups were crossed over and the patients were followed up for another 6 months . The groups were homogenous with respect to age , height , bodyweight , body mass index and race . For the statistical analysis , the group receiving hormone therapy was referred to as group A and the placebo group was design ated group B , irrespective of the placebo/hormone therapy sequence . Results : In group A there were fewer hot flashes ( F = 22.85 , p improvement in sexual interest ( F = 5.55 , p respect to dyspareunia ( F = 9.65 , p and satisfaction with the duration of penetration ( F = 6.58 , p to orgasmic capability and the presence of dialogue with partner regarding the couple ’s sexual life , whether the placebo was taken prior to or following hormone therapy was significant ( F = 17.12 , p Conclusions : Monophasic estrogen-progestogen therapy has a beneficial effect on sexuality and on hot flashes in postmenopausal women", "OBJECTIVES To study the effects of hormonal replacement on hot flushes , other symptoms linked to menopause , and blood pressure . METHODS The study included 1006 early postmenopausal women aged 45 - 58 years , participating in the Danish Osteoporosis Prevention Study ( DOPS ) r and omised to Hormonal replacement therapy ( HRT ) ( n=502 ) or no HRT ( n=504 ) in an open label trial . Symptom scores were recorded at baseline , after 6 month , 1 , 2 , and 5 years on a modified Greene scale ( range 0 - 4 with 0 equalling no symptoms , and 4 maximal symptoms ) . RESULTS HRT efficiently alleviated hot flushes ( mean+/-S.E.M. score 0.48+/-0.04 in HRT vs. 0.83+/-0.05 in no HRT after 5 years , P sleeping difficulties associated with hot flushes ( 0.21+/-0.60 vs. 0.37+/-0.86 , P vaginal dryness ( 0.45+/-0.04 vs. 0.73+/-0.05 , P dyspareunia ( 0.27+/-0.04 vs. 0.39+/-0.04 , P libido ( 0.48+/-0.05 vs. 0.59+/-0.05 , P=0.08 ) . In the untreated group the occurrence of mood swings ( from 0.77+/-0.05 at baseline to 0.45+/-0.04 after 5 years , 2P oedemas ( from 0.59+/-0.04 to 0.43+/-0.04 , 2P=0.02 ) decreased with age while the occurrence of incontinence increased ( from 0.43+/-0.03 to 0.52+/-0.04 , 2P HRT . Furthermore , HRT had no influence on presence of headache ( 0.54+/-0.05 vs. 0.58+/-0.05 after 5 years ) , voiding pattern ( 0.49+/-0.04 vs. 0.53+/-0.04 ) , or blood pressure ( mean systolic pressure 123+/-18 vs. 123+/-19 , diastolic pressure 77+/-10 vs. 77+/-11 ) . CONCLUSIONS HRT is efficient in controlling hot flushes and vaginal dryness , and symptoms related to these conditions . However , no effect on blood pressure or other menopause symptoms was recorded", "Objective To determine the prevalence of endometrial hyperplasia and endometrial cancer in postmenopausal women with endometrial thickness of 4.1–8 mm on transvaginal ultrasound scan . Design Prospect i ve observational study carried out in the Heart of Engl and NHS Trust Teaching Hospital in the West Midl and s , UK , in a population of 58 women with postmenopausal bleeding . Method Prospect i ve analysis of all women referred to the Rapid Access Clinic in the Heart of Engl and Hospital with a history of postmenopausal bleeding over a 12-month period ( April 2007–April 2008 ) . Endometrial histology was taken as the final diagnosis . The main outcome measure was endometrial histology in women with postmenopausal bleeding with endometrial thickness of 4.1–8 mm . Results All women ( n = = 58 ) diagnosed with endometrial thickness of 4.1–8 mm on transvaginal sonography were included in the analysis . Pipelle endometrial biopsy could only be performed in 22 women ( 37.9%% ) . Hysteroscopy was performed in 45 women ( 77.5%% ) . Out of these , a histological diagnosis was available in 28 women ( 62.2%% ) . In the remaining 17 women , the endometrium was observed as atrophic on hysteroscopy . In these 17 cases , either no or insufficient endometrial sample was obtained . In total , two ( 3.4%% ) women were diagnosed with complex endometrial hyperplasia and two ( 3.4%% ) women were diagnosed with endometrial carcinoma . Conclusion There was a significant prevalence of endometrial hyperplasia and endometrial cancer in postmenopausal women with a history of postmenopausal bleeding and who had endometrial thickness of 4.1–8 mm . Therefore , the current recommendation of histological assessment on all women with endometrial thickness > 4 mm should remain unchanged", "Objective : To evaluate the effects of hormone therapy ( HT ) on cognition and subjective quality of life ( QoL ) in recently postmenopausal women with cognitive complaints . Methods : Cognitive Complaints in Early Menopause Trial ( COGENT ) was a r and omized , double-blind , placebo-controlled , multicenter , pilot study of 180 healthy postmenopausal women aged 45 to 55 years , r and omly assigned to receive either placebo or conjugated equine estrogen 0.625 mg/medroxyprogesterone acetate 2.5 mg for 4 months . Outcome measures included memory , subjective cognition , QoL , sexuality , and sleep , which were assessed at baseline and month 4 . Results : The study was terminated before the expected final sample size of 275 due to a decrease in enrollment coinciding with the publication of findings from the Women ’s Health Initiative . There were no differences between groups on any cognitive or QoL measures , except for an increase in sexual interest and thoughts with HT . Modest negative effects on short- and long-term verbal memory approached significance ( p baseline vasomotor symptoms ( VMS ) showed a decrease in VMS and an improvement in general QoL , but no cognitive benefit vs placebo . Conclusions : With the power to detect an effect size of ≥0.45 , this study suggests potential modest negative effects on verbal memory that are consistent with previous hormone therapy trials in older women . GLOSSARY : BTA = Brief Test of Attention ; BVRT = Benton Visual Retention Test ; COGENT = Cognitive Complaints in Early Menopause Trial ; CRT = Educational Testing Service Card Rotation Test ; CVLT = California Verbal Learning ; FAS = Letter Fluency Test ; HERS = Heart and Estrogen/progestin Replacement Study ; HT = hormone therapy ; MFSQ = McCoy Female Sexuality Scale Question naire ; MFQ = The Memory Functioning Question naire ; PANAS = Positive and Negative Affect Scale ; PSQI = The Pittsburgh Sleep Quality Index ; QoL = subjective quality of life ; SWAN = Study of Women ’s Health Across the Nation ; UQoL = Utian Quality of Life ; VMS = vasomotor symptoms Test ; WHI = Women ’s Health Initiative ; WHISCA = WHI Study of Cognitive Aging ; WMS-R/DGT-F , MS-R/DGT-B = Digit Span Forward and Backward Subtests of the Wechsler Memory Scale – Revised", "Objective : To investigate the effect of ultralow-dose transdermal estradiol on postmenopausal symptoms and side effects in a cohort of largely asymptomatic postmenopausal women aged 60 to 80 years . Design : This secondary analysis used data from the UltraLow-dose Transdermal estRogen Assessment trial , a r and omized , placebo-controlled , double-blind trial in postmenopausal women to determine the skeletal effects and safety of ultralow-dose transdermal estradiol . Four hundred seventeen postmenopausal women , aged 60 to 80 years , were r and omly assigned to receive either unopposed transdermal estradiol at 0.014 mg/d ( n = 208 ) or placebo ( n = 209 ) . Participants were queried at each clinic visit about postmenopausal symptoms and side effects purported to be associated with estrogen therapy using a st and ardized question naire . Results : At baseline , 16 % of women reported hot flashes , 32 % reported vaginal dryness , and 35 % reported trouble sleeping . Women who received ultralow-dose estradiol were no more likely to report improvement of hot flashes , vaginal dryness , or sleep difficulties than those who received placebo . Treatment with ultralow-dose estradiol did not cause breast tenderness , uterine bleeding , or other symptoms often attributed to estrogen , but vaginal discharge was more common in women who received estradiol compared with those who received placebo . Conclusion : In this population of older , largely asymptomatic women , ultralow-dose transdermal estradiol did not improve postmenopausal symptoms and did not cause side effects other than vaginal discharge . Further study is needed to determine whether this dose of transdermal estradiol is effective in treating symptoms of postmenopause in younger , more symptomatic women", "Objective : To evaluate whether the frequency of overactive bladder ( OAB ) symptoms increases in menopause patients after a tension-free vaginal tape ( TVT ) procedure , and to determine if topical estrogen therapy can help prevent these symptoms . Design : After undergoing a preoperative assessment , enrolled patients were r and omly allocated to receive TVT plus postoperative vaginal estrogen therapy ( ET group ) or TVT without adjunctive medical treatment ( No ET group ) . The pre- and postoperative assessment s included : acquisition of a urogynecologic history with st and ardized questions regarding urinary function ( including a 10- grade visual analogue scale score ) , urogynecologic clinical examination , and urodynamic assessment . Follow-up assessment s were performed at 1 , 3 , and 6 months after surgery . Results : Fifty-six of 59 patients were evaluable ; 28 received topic vaginal estrogen after surgery ( ET group ) and 28 did not receive adjunctive medical treatment ( No ET group ) . The overall OAB syndrome rate in menopause patients ( No ET group ) was 7 % ( 2 of 28 patients ) at baseline and 32 % ( 9 of 28 patients ) 6 months after surgery ( P = 0.04 ) . At the 6-month follow-up assessment , the incidence of urinary urgency was 4 % ( 1 of 28 patients ) and 29 % ( 8 of 28 patients ) in the ET and No ET groups , respectively ( P = 0.01 ) . Differences in frequency and nocturia were not statistically significant . Analysis of the visual analogue scale scores revealed that at the 6-month follow-up assessment , urgency significantly improved in the ET group compared with the No ET group ( 0.23 ± 1.0 vs 2.30 ± 3.7 , respectively ; P = 0.02 ) . Conclusions : The TVT procedure seems to increase the frequency of OAB syndrome in menopause patients . Vaginal estriol therapy significantly reduces symptoms of urinary urgency , has a high rate of patient satisfaction , and can be used to treat postmenopausal women for at least 6 months after a TVT procedure ", "CONTEXT GH negatively regulates its own secretion . How gender , sex steroids , and secretagogues modulate GH autofeedback is not known . HYPOTHESIS/ OBJECTIVE Supplementation with sex steroids and /or a peptidyl secretagogue will enhance the escape of GH from autoinhibition , thus framing a mechanism for amplifying pulsatile GH secretion . SUBJECTS AND SETTING Ten healthy postmenopausal women and 10 comparably aged men participated at the Clinical -Translational Science Unit . DESIGN / INTERVENTIONS R and omly ordered , double-blind , prospect i ve crossover treatment with placebo vs. testosterone ( men ) or placebo vs. estradiol ( women ) . Autofeedback was imposed by an iv pulse of GH . Recovery of feedback inhibition was quantified during constant infusion of saline , GHRH , or GH-releasing peptide-2 ( three peptide categories ) . OUTCOMES / RESULTS During negative feedback , total ( integrated ) GH recovery depended upon gender ( P = 0.017 ) , sex hormone ( P feedback-suppressed nadir GH concentrations were determined by sex-steroid treatment ( P = 0.018 ) but not by gender ( P = 0.444 ) . Peak GH escape was controlled by both treatment ( P = 0.004 ) and gender ( P = 0.003 ) . Nadir GH and peak GH during feedback were enhanced by GHRH or GHRP-2 ( P nadir GH ) regulated GH recovery interactively . CONCLUSION Gender , sex-steroid supplementation , and secretagogue type confer distinct feedback-rescuing effects , introducing a new level of complexity in the control of pulsatile GH regulation", "Objective To study the impact of low-dose unopposed esterified estrogens on menopausal symptoms and quality of life . Methods In a long-term , 2-year , r and omized , double-blind , placebo-controlled study , 204 postmenopausal women were treated with esterified estrogens 0.3 mg daily or placebo . Menopausal symptoms were assessed with a modified Kupperman index at baseline , 3 , 6 and thereafter every 6 months . In a second 12-week , open-label , short-term pilot study , 25 postmenopausal women with moderate to severe vasomotor symptoms were treated with esterified estrogens 0.3 mg daily for 12 weeks . Vasomotor symptoms and quality of life were assessed using the Greene scale and Quality of Life Menopause Scale ( QUALMS ) . Results In the long-term study , significant ( p total symptom scores were observed at each time point with esterified estrogens compared with placebo . Somatic symptom scores ( hot flushes , night sweats , vaginal dryness ) decreased significantly ( p esterified estrogens 0.3 mg compared to baseline and placebo . In the short-term , open-label pilot study , the incidence of vasomotor symptoms was significantly ( p esterified estrogens 0.3 mg from week 4 until the study end . Significant ( p somatic and vasomotor/sleep domains and in the total quality -of-life score . Conclusions Esterified estrogens 0.3 mg given daily provide adequate menopausal symptom relief and improved quality of life in postmenopausal women", "Summary A double-blind cross-over study with Org OD 14 was done in 35 post-menopausal patients aged 48–69 years who had hot flushes and other associated symptoms . Patients were r and omly allocated to Org OD 14 or to placebo as first treatment . Each period of treatment lasted for 6 weeks and there were no intervals between treatments . Tablets containing 2.5 mg of Org OD 14 or placebo tablets of identical appearance were supplied . Patients took one Org OD 14 tablet or one placebo tablet per day . Data on the following variables were obtained and analyzed statistically : hot flushes , sweating , dizziness , palpitation , tiredness , headache , insomnia , irritability , breathlessness , backache , loss of libido , and mood . Assessment was daily in the case of hot flushes and weekly for the other variables . Org OD 14 was statistically significantly more effective in controlling hot flushes , sweating and headache and tended to be better than the placebo tablets for the other variables", "Estrogen treatment of postmenopausal women has been suggested to improve mood and psychological function . However , this remains controversial because previous studies involved heterogeneous groups , were not double blind , and included women who were also experiencing somatic symptoms that were relieved by estrogen . A r and omized double-blind study was carried out comparing the effects of placebo and conjugated equine estrogens ( 0.625 and 1.25 mg ) on psychological function over 3 months in 36 asymptomatic women , aged 45 - 60 . The tests included the Minnesota Multiphasic Personality Inventory-168 , the Profile of Adaptation to Life , and the Beck Depression Inventory . Memory was assessed directly by the Wechsler Adult Intelligence Scales , measuring both digit span and digit symbol . All women were well-adjusted psychologically . The income management scale of the Profile of Adaptation to Life improved ( P Beck Depression Inventory ( P Memory assessed prospect ively by the Wechsler Adult Intelligence Scales was not affected significantly . These results suggest that estrogen use may improve the overall quality of life in postmenopausal women", "AIM The effect of hormone replacement therapy ( HRT ) on the quality of life in women with hypertension is still not clear . Thus , the aim of the study was to assess the effect of hormone replacement therapy on quality of life in postmenopausal women with essential hypertension by using a battery of st and ardized question naires . MATERIAL AND METHODS The study population consisted of 53 women ( mean age 50.9 + /- 6.3 years ) with mild and moderate essential hypertension ( mean duration 6.4 + /- 6.4 years ) . The postmenopausal status was defined as the absence of menstrual blood loss during > 6 months and blood estradiol concentration 21 U/I. Twenty seven women were blindly r and omised to transdermal hormone replacement therapy ( HRT ) and received 17-beta-estradiol and noretisterone acetate , TTS . Twenty six women were r and omly selected as controls . The subjects were evaluated at baseline ( after 2 weeks ' wash-out from hypotensive drug period ) and after three months of HRT using self-administered st and ardized quality of life question naires : the Psychological General Well-being Index ( PGWB ) and the Subjective Symptoms Assessment Profile ( SSA-P ) . RESULTS No differences were found in blood pressure values , heart rate , body mass index and distribution of body fat tissue between women receiving HRT and controls at baseline and after 3 months of follow-up . There were no significant differences in the baseline total PGWB score as well as in its subscale between two groups . Similarly , the frequency and intensity of subjective symptoms assessed by SSA-profile were the same in both groups at baseline . After 3 months , a significant improvement in PGWB total score was observed in women receiving HRT . This effect was due to improvement in anxiety , positive well-being and vitality . Moreover , emotional distress , symptoms of flushing , sweating and trembling h and s also diminished and sexual capacity improved in women treated with HRT . CONCLUSION A three-month hormone replacement therapy in hypertensive postmenopausal women slightly improves the general well-being , seems to decrease emotional tension , increase sexual capacity and markedly relieves some vasomotor symptoms", "CONTEXT Lower-than-commonly-prescribed doses of conjugated equine estrogens ( CEEs ) with medroxyprogesterone acetate ( MPA ) improve vasomotor symptoms and vaginal atrophy , provide acceptable bleeding and lipid profiles , and afford endometrial protection . This lower-dose therapy 's protection against loss of bone mineral density ( BMD ) associated with menopause has not been thoroughly investigated . OBJECTIVE To determine the effects of lower doses of CEEs only or CEEs-MPA on spine and hip BMD , total body bone mineral content ( BMC ) , and biochemical markers of bone turnover in postmenopausal women . DESIGN AND SETTING Two-year r and omized , double-blind , placebo-controlled sub study of the Women 's Health , Osteoporosis , Progestin , Estrogen trial , conducted at 19 US centers between August 1995 and October 2000 . PARTICIPANTS Eight hundred twenty-two healthy postmenopausal women aged 40 to 65 years who were within 4 years of their last menstrual period . INTERVENTIONS Patients were r and omly assigned to receive CEEs , 0.625 ; CEEs , 0.625 and MPA , 2.5 ; CEEs , 0.45 ; CEEs , 0.45 and MPA , 2.5 ; CEEs , 0.45 and MPA , 1.5 ; CEEs , 0.3 ; CEEs 0.3 and MPA , 1.5 ( all doses in mg/d ) ; or placebo for 2 years . All participants also received elemental calcium at 600 mg/d . MAIN OUTCOME MEASURES Changes from baseline in spine and total hip BMD , total body BMC , and biochemical markers of bone turnover ( serum osteocalcin and urinary cross-linked N-telopeptides of type I collagen ) , assessed at 6-month intervals and compared among treatment groups with a modified intention-to-treat approach . RESULTS At 24 months , women assigned to all of the active treatment groups had significant gains from baseline ( P spine and hip BMD and total body BMC ( except total body BMC in the group receiving CEEs , 0.3 mg/d ) . These changes were significantly different from those in the placebo group , in which losses of bone mass in spine and total body were evident over the course of the study ( P loss in hip BMD from baseline in the placebo group was significant at 18 ( P = .02 ) but not at 24 months ( P = .06 ) . Osteocalcin and N-telopeptides of type I collagen were significantly reduced from baseline ( P placebo group . For women treated with CEEs alone , the gains in spine BMD for the group taking CEEs , 0.625 mg/d , were significantly higher than those of the group taking CEEs , 0.3 mg/d ( P = .02 ) , but not the group treated with CEEs , 0.45 mg/d ( P = .48 ) . CONCLUSIONS Doses of CEEs or CEEs-MPA lower than 0.625 mg/d effectively increase BMD and BMC in early postmenopausal women", "OBJECTIVE This study was undertaken to examine the effect of ultralow-dose transdermal estradiol on sexual function in postmenopausal women . STUDY DESIGN Analysis of data from a multicenter , r and omized , double-blind , placebo-controlled trial of a 0.014 mg/day transdermal estradiol patch in 417 women aged 60 to 80 years . Sexual function was assessed by self-administered question naires at baseline and 4 , 12 , and 24 months . A linear effects model was used to assess treatment effects using data from all on- study assessment s. RESULTS Women r and omly assigned to estradiol had a 4.3 point greater improvement in the vaginal pain/dryness domain relative to placebo ( 95 % CI = 0.3 - 8.4 , P = .04 ) . No significant differences in frequency of sexual activity or other sexual function domains ( desire , satisfaction , problems , or orgasm ) were observed between treatment groups ( P > or = .10 for all ) . CONCLUSIONS Ultralow-dose estradiol result ed in modest improvement in sexual function related to vaginal pain and dryness , but not in other domains of sexual function", "OBJECTIVE To investigate somatic symptom relief , gonadotropin secretion , and endogenous and rogen bioavailability ( protein-bound and free ) during 3 months of estrogen- and rogen therapy or matched estrogen-only replacement therapy . DESIGN Ninety-three naturally menopausal out patients with 6 or more months of amenorrhea , who were experiencing mild-to-moderate vasomotor symptoms , were r and omized to receive one of five treatments : oral esterified estrogens ( 0.625 mg or 1.25 mg ) , oral esterified estrogens combined with methyltestosterone ( 0.625 mg combined with 1.25 mg methyltestosterone or esterified estrogens 1.25 mg combined with 2.5 mg methyltestosterone ) , or placebo for 12 weeks . All treatments were preceded by a 4-week placebo lead-in period . RESULTS Patients receiving the lower dose of estrogen- and rogen therapy had fewer somatic menopausal symptoms than patients receiving the lower dose estrogen ( 0.625 mg ) , and they experienced somatic symptom relief similar to those patients receiving the higher dose of estrogen ( 1.25 mg ) . Significantly greater luteinizing hormone suppression ( p Sex hormone-binding globulin increased significantly in both estrogen-treated groups ( p estrogen-only preparation significantly reduced and rostenedione ( p dehydroepi and rosterone sulfate ( p estrogen- and rogen therapy was similar to higher dose estrogen-only treatment . The greater efficacy of combination therapy on somatic symptoms could be mediated by the same mechanism responsible for the suppressive effects of estrogen- and rogen therapy on luteinizing hormone secretion . The marked differences in circulating levels of sex hormone building globulin , which were increased by estrogen and decreased by estrogen- and rogen , and the result ing impact on bioavailable and rogens and estrogens could also explain the differential somatic relief with both treatments . Endogenous adrenal and rogens were lower in women treated with esterified estrogens 1.25 mg/day , suggesting that estrogen therapy can produce a significant hypo and rogenic state by inhibiting production or accelerating clearance of adrenal and rogens", "Out of a sample of 162 early post-menopausal women , aged 45 - 54 yr , 131 completed a placebo-controlled study to investigate the effect of sex hormones on mild climacteric symptoms with special reference to the dose-response relationship and withdrawal effects . The women were followed up for 42 mth under four different study programmes . All the women were examined every 3 mth and a blind assessment made of the menopausal index estimated according to Kupperman et al. The data revealed a highly significant reduction in climacteric symptoms in the hormone-treated women as compared with the placebo group ( P less than 0.001 ) , a highly significant dose relationship between climacteric symptoms and treatment with 4 , 2 and 1 mg oestradiol , respectively ( P less than 0.001 ) , a highly significant and dose-dependent rebound phenomenon after withdrawal of hormone treatment ( P less than 0.001)--which levelled off after 6 mth following withdrawal-- and complete relief of hot flushes with the two highest doses of oestradiol ( 4 and 2 mg oestradiol ) . It is concluded that sex hormones have a beneficial effect in post-menopausal women with even mild symptoms", "Objective : Phase 3 studies of postmenopausal women with or at risk for osteoporosis reported that , compared with placebo , bazedoxifene increased the incidence of hot flushes . The current study evaluated the vasomotor effects of bazedoxifene in healthy nonflushing postmenopausal women . Methods : In this phase 2 study , nonflushing postmenopausal women ( n = 494 ) were r and omized to daily treatment with bazedoxifene 5 , 10 , or 20 mg ; raloxifene 60 mg ; or placebo for 12 weeks . The primary endpoint was the percentage of women reporting hot flushes at any time during the study ; secondary endpoints included the mean number and severity of hot flushes and the mean number of days with hot flushes . Effects on bone turnover markers and lipid parameters were also evaluated . Results : Over the 12-week study , 25.5 % of placebo-treated women reported hot flushes . The incidence of hot flushes with bazedoxifene 5 , 10 , and 20 mg and raloxifene 60 mg was 26.0 % , 33.7 % , 27.6 % , and 21.4 % , respectively , with no significant differences from that with placebo . The active treatment groups showed no significant differences from placebo in the mean number or severity of hot flushes during week 12 or any 4-week period . Bazedoxifene and raloxifene showed beneficial effects on lipid parameters and markers of bone turnover . All doses of bazedoxifene were generally well tolerated and did not increase endometrial thickness , vaginal bleeding , or breast pain compared with placebo over 12 weeks of therapy . Conclusions : Data from this phase 2 clinical trial suggest that bazedoxifene does not increase the incidence of hot flushes relative to placebo in nonflushing postmenopausal women", "In order to analyse both sexual desire after menopause and its response to treatment with tibolone , a r and omized placebo/tibolone trial has been design ed with 28 postmenopausal patients . They were asked to answer a question naire design ed by us to obtain quantitative measurements to describe changes in sexual desire . After selection , the patients were r and omly assigned to two groups as follows : 14 in the group treated with 2.5 mg/day of tibolone and 14 in the placebo group treated with 500 mg/day of calcium . The patients were monitored after 3 , 6 and 12 months . Before joining this study , they had signed a written consent . It was observed that the sexual desire after menopause underwent a significant fall , with decline in arousability and intercourse . The comparative results show that the patients treated with tibolone experience an improvement after the third month of treatment and this improvement was maintained until the end of treatment . We conclude that the question naire proposed here is a useful non-parametric method to diagnose a patient 's sexuality status at the baseline assessment and a valuable tool for monitoring various therapies . Furthermore , tibolone proved to be effective in managing reduced sexual desire which appears in postmenopausal patients", "BACKGROUND This study focus on the effect of 6 months transdermal estradiol therapy ( TTS ) on the sexual behaviour and the quality of life in early menopausal women , complaining of uncomfortable menopausal symptoms . METHODS Three hundred and sixty-two postmenopausal women , aged 48 - 56 , participated in this study . One hundred and seventy-one of them were given continuous solid matrix patch TTS 50 mg/day for 6 months . Sexual behaviour , menopausal symptoms and well-being were evaluated through a self-rating method . We used a structured question naire with three obligatory answers ( less/same/more ) for each question --sexual life , hot flushes , touchiness , insomnia , blood pressure , work willing , memory loss , well-being -- filled in by the women themselves or by the medical equipe after a telephone interview . RESULTS Seventy five per cent of women aged 51 - 53 and 84 % aged 54 - 56 , who had been treated for 6 months with TTS showed a fall of sexual drive , if compared with , respectively , 62 % and 48 % of untreated subjects . Relief of hot flushes , touchiness and insomnia occurred in 80 % of treated women , with slight differences among the various groups while 61 % showed increase of well-being . CONCLUSIONS The results of our study demonstrate that continuous TTS for 6 months decreased sexual drive in 69 % of women , improved menopausal symptoms in 80 % women but increased well-being only in 61 % of women . These differences suggest that women 's well-being does not seem linked only to the relief of menopausal symptoms and the impairment of their sexual life can play a negative role", "The purpose of this study was to investigate the value of tibolone in the treatment of psychosomatic symptoms in menopause . Forty-two menopausal women ( aged 46 - 63 , mean 53.9 ) with nightly perspiration , vasomotor flushes , disturbance of libido , dyspnea and other psychosomatic symptoms were assigned to one of two treatment groups for three months : 1st group ) 21 users of tibolone ; 2nd group ) 21 users of placebo . At the end of the trial disturbance of libido was observed in 4 ( 19.0 % ) cases tin the 1st group and 11 ( 52.4 % ) cases in the 2nd ( p nightly perspiration was observed in 3 cases ( 14.3 % ) in the 1st group and 9 cases ( 42.9 % ) in the 2nd ( p vasomotor flushes were observed in only 3 ( 14.3 % ) cases in the 1st group and 7 cases ( 33.3 % ) in the 2nd group , this difference was not significant ( p > 0.05 ) . There was no significant effect of tibolone or placebo in dyspnea , vertigo and headache . From the results it can be concluded that tibolone can have a beneficial effect on some psychosomatic symptoms in postmenopausal women", "Objectives : The primary objective of the Selective estrogen Menopause And Response to Therapy 3 ( SMART-3 ) trial was to compare the efficacy and safety of two doses of bazedoxifene (BZA)/conjugated estrogens ( CE ) versus placebo for the treatment of moderate to severe vulvar/vaginal atrophy ( VVA ) associated with menopause . Methods : This was a phase 3 , multicenter , double-blind , r and omized , placebo-controlled , and active comparator-controlled study . Healthy postmenopausal women ( n = 664 ; aged 40 - 65 y ) were r and omized to BZA 20 mg/CE 0.625 mg , BZA 20 mg/CE 0.45 mg , BZA 20 mg , or placebo once daily for 12 weeks . Changes in vaginal maturation , vaginal pH , and severity of the most bothersome symptom of VVA from baseline were assessed at screening and at weeks 4 and 12 . Adverse events were recorded throughout the study . Results : BZA 20 mg/CE 0.625 or CE 0.45 mg significantly ( P superficial cells and decreased parabasal cells compared with placebo . Vaginal pH and most bothersome symptom significantly improved with BZA 20 mg/CE 0.625 mg compared with placebo ( P vaginal dryness were also observed with both BZA/CE doses ( P adverse events were similar across treatment groups . Conclusions : BZA/CE is effective in treating moderate to severe VVA and vaginal symptoms . These data further support the use of a tissue-selective estrogen complex containing BZA/CE as a new menopausal therapy for postmenopausal women", "OBJECTIVE The purpose of this study was to assess the urogenital effects of raloxifene , tamoxifen , conjugated equine estrogen , and placebo in healthy postmenopausal women . STUDY DESIGN This r and omized , double-blind , placebo-controlled study compared the urogenital effects of 0.625 mg of conjugated equine estrogen ( n = 15 women ) , 20 mg of tamoxifen ( n = 14 women ) , 60 mg of raloxifene , ( n = 15 women ) , and placebo ( n = 13 women ) . Evaluations at baseline and evaluations after 20 weeks receiving the drug included a pelvic examination with cytologic evaluation of vagina and urethra , pelvic organ prolapse quantitation , and urethral axis deflection by cotton swab test ( only in patients with incontinence [ 33 % ] ) . RESULTS Conjugated equine estrogen increased the maturation value of both urethral and vaginal cytologic condition ( P = .002 , P = .032 , respectively ) . There was a decrease in vaginal maturation value in the raloxifene group ( not significant ) . Two of 8 women in the conjugated equine estrogen group showed evidence of worsening prolapse by pelvic organ prolapse quantitation ; the condition of 2 of 8 women improved . In the raloxifene , tamoxifen , and placebo groups 8 of 12 women , 4 of 13 women , and 2 of 11 women had worsening in prolapse scores , respectively , whereas none of the women had improvement . Increased cotton swab deflection was found in 3 of 5 women in the raloxifene group , in 5 of 8 women in the tamoxifen group , in 0 of 4 women in the placebo group , and in 0 of 2 women in the conjugated equine estrogen group . Seventy-five percent of the patients who received raloxifene and 60 % of the patients who received tamoxifen had increases in prolapse by any measure ( ie , pelvic organ prolapse quantitation or cotton swab or clinical assessment ) compared with 18 % of the patients in the placebo group and 22 % of the patients in the conjugated equine estrogen group ( P = .015 ) , although symptoms did not differ among groups . CONCLUSION Neither raloxifene nor tamoxifen improve cytohormonal effects in the vagina or urethra , whereas conjugated equine estrogen does . Raloxifene and tamoxifen appear to show worsening prolapse compared with conjugated equine estrogen and placebo . The clinical relevance of these effects is unknown and requires investigation", "Objective The aim of this study was to assess the safety of ospemifene , a novel selective estrogen receptor modulator , for the treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus . Methods In this multicenter , r and omized , double-blind , placebo-controlled , long-term safety extension study , nonhysterectomized women aged 40 to 80 years ( n = 180 ) received daily oral doses of placebo , ospemifene 30 mg/day , or ospemifene 60 mg/day for 40 weeks ( continued as blinded treatments from the initial 12-week pivotal efficacy study of ospemifene ) . The total treatment period was 52 weeks . Safety assessment s included adverse events , cervical Papanicolaou tests , endometrial histology , endometrial thickness , gynecological examination , breast palpation , mammography , physical examination , and clinical safety laboratory assessment s. Results No clinical ly significant adverse changes in safety assessment s were observed in any treatment group . Most treatment-emergent adverse events were mild or moderate in severity . Hot flushes , the most frequently occurring treatment-emergent adverse event related to the study drug , had a low discontinuation rate ( 1.6 % ) . No study participants discontinued because of endometrial or cervical pathology ; no endometrial findings were clinical ly meaningful . On week 52 , more than 95 % of endometrial biopsy sample s either were classified as atrophic or inactive or had insufficient tissue for diagnosis . There were no treatment-emergent adverse events of pelvic organ prolapse or venous thromboembolism . No cases of endometrial hyperplasia or carcinoma were observed . Only three participants ( 1.7 % ) taking ospemifene experienced vaginal bleeding or spotting , which was self-limiting . Conclusions Daily doses of ospemifene 30 mg and ospemifene 60 mg yielded few treatment-emergent adverse events and demonstrated no significant endometrial changes during the 1-year treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus", "INTRODUCTION Sexual dysfunction is more prevalent in postmenopausal women . AIMS To prospect ively evaluate and compare the effects of hormone therapy ( HT ) regimens , oral and vaginal estradiol , estradiol + drospirenone and tibolone , on sexual function in healthy postmenopausal women . METHODS The study included 169 consecutive healthy postmenopausal women , and the women were divided into two groups : 111 women received HT , and 58 women received no treatment and served as a control group . As an HT , 23 women with surgically induced menopause received oral 17-beta estradiol . The rest of the women with natural menopause were prospect ively r and omized : 22 received oral 17-beta estradiol + drospirenone daily , 42 received oral tibolone , and 24 received vaginal 17-beta estradiol . Sexual function was evaluated with a detailed 19-item question naire , the female sexual function index , including sexual desire , arousal , lubrication , orgasm , satisfaction , and pain . MAIN OUTCOME MEASURES The differences in sexual function were compared before and 6 months after the treatment in all women . RESULTS Total sexual function score increased from 19.81 + /- 7.15 to 22.9 + /- 6.44 in the HT group and decreased from 21.6 + /- 8.69 to 17.6 + /- 5.7 in the control group , revealing a significant difference from baseline to post-treatment between the two groups ( P = 0.000 ) . The highest improvement in total score and arousal was achieved with the oral 17-beta estradiol ( P = 0.000 and P = 0.000 , respectively ) . The highest improvement in lubrication was achieved with the oral and vaginal 17-beta estradiol groups ( P = 0.000 ) . The highest improvement in orgasm was achieved with the tibolone group ( P = 0.000 ) . The highest improvement in pain was achieved with the oral and vaginal 17-beta estradiol groups ( P = 0.000 ) . CONCLUSIONS HT provided significant improvement in sexual function compared to women receiving no treatment , and therefore , HT regimens should be suggested for improvement in sexual functioning of postmenopausal women", "Objective To evaluate the effect of estrogen replacement therapy on cognitive functioning . Methods The study consisted of two 3-month treatment periods , one with estrogen and one with the placebo , in r and om order , separated by a 1-month wash-out period . The study group comprised 70 healthy postmenopausal women , aged 47–65 years , with previous hysterectomy . Sixty-two women completed the study . Cognitive speed and accuracy , attention , and memory were evaluated . Serum estradiol ( E2 ) and FSH levels were controlled at the end of the estrogen , placebo , and wash-out periods . Results Most of the cognitive tests correlated with age : older women were slower and made errors than younger women . Estrogen replacement therapy was not superior to the placebo in any test of cognitive performance . In two out of ten visual detection tasks , recognition thresholds were longer with estrogen than with the placebo ( P working memory , the reaction times ( P = .045 ) and error rates ( P = .043 ) differed between treatments , yet this finding proved to be an effect of learning rather than treatment . There was no correlation between cognitive performance and serum E2 levels . Conclusion Cognitive performance decreased with age . Short-term estrogen replacement therapy did not provide any advantage over the placebo in terms of improving the performance", "Objective To compare the effect of different formulations of continuous combined hormone therapy on sexual performance in naturally postmenopausal women . Material and methods A total of 158 postmenopausal women were enrolled and prospect ively r and omized to the single-blind study . Fifty-four women received tibolone 2.5 mg , 53 received 2 mg estradiol and 2 mg dienogest ( E2/dienogest ) , and 51 did not receive any menopausal therapy . The patients were monitored after 6 months . Attitudes of sexuality were evaluated by using the Rosen 's female sexual function index . Results Compared with E2/dienogest and the control group , tibolone treatment was associated with more improvement of sexual performance , including sexual desire , sexual arousal and satisfaction . Both of the hormone therapies decreased frequencies of vaginal dryness and painful intercourse . Conclusions Tibolone has more positive effects on the sexual dysfunction of postmenopausal women and may be an alternative to the E2/dienogest preparation in postmenopausal women with sexual dysfunction", "OBJECTIVE The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized . Raloxifene , a selective estrogen receptor modulator , appears to act similarly to conjugated estrogens on dopamine and serotonin brain systems and may be a better option since it lacks the possible negative effects of estrogen on breast and uterine tissue . In this study , we assess the utility of raloxifene as an adjunctive treatment for negative symptoms and other psychotic symptoms in postmenopausal women with schizophrenia . METHOD This was a 12-week , double-blind , r and omized , placebo-controlled study . Patients were recruited from both the inpatient and outpatient departments of Parc Sanitari Sant Joan de Déu , Barcelona , Spain , and Corporació Sanitària Parc Taulí , Sabadell , Spain . Thirty-three postmenopausal women with schizophrenia ( DSM-IV criteria ) who exhibited prominent negative symptoms were r and omized to either adjunctive raloxifene ( 16 women ; mean age = 60.14 years , SD = 6.41 years ) or adjunctive placebo ( 17 women ; mean age = 62.66 years , SD = 4.54 years ) for 12 weeks . The period of recruitment lasted from January 2005 through June 2009 . Psychopathological symptoms were assessed at baseline and weeks 4 , 8 , and 12 by means of the Positive and Negative Syndrome Scale . RESULTS The addition of raloxifene ( 60 mg/d ) to regular antipsychotic treatment significantly reduced negative ( P = .044 ) , positive ( P = .031 ) , and general psychopathological ( P = .045 ) symptoms during the 12-week trial as compared with women receiving placebo . CONCLUSIONS Raloxifene as an adjuvant treatment in postmenopausal women with schizophrenia who exhibit prominent negative symptoms appears to be useful in improving negative , positive , and general psychopathological symptoms . If more extensive and longer-term studies confirm and exp and upon these positive results , the use of raloxifene could be recommended in postmenopausal patients with schizophrenia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01041092", "Objective The aim of this study was to evaluate the efficacy and safety of a new low-concentration estriol formulation ( 0.005 % estriol vaginal gel ) , providing an ultra low dose of estriol per application ( 50 & mgr;g ) , for the local treatment of postmenopausal vaginal atrophy . Methods Postmenopausal women with symptoms and signs of vaginal atrophy were enrolled in a prospect i ve , double-blind , placebo-controlled study . Women received either 1 g of vaginal gel containing 50 & mgr;g of estriol or placebo gel , daily for 3 weeks and then twice weekly up to 12 weeks . A cytological vaginal study , evaluation of vaginal pH , and assessment of symptoms and signs of vaginal atrophy were performed , and changes between baseline and weeks 3 and 12 were assessed . Adverse events were recorded . Results A total of 167 women were included ( 114 received estriol and 53 received placebo ) . After 12 weeks of therapy , a superiority of estriol compared with placebo gel was shown in the change in maturation value and vaginal pH ( P estriol was well demonstrated in improvement of vaginal dryness ( P = 0.001 ) and the Global Symptom Score ( P = 0.018 ) . Estriol gel proved also superior in the improvement of several of the most outst and ing vaginal signs of vaginal atrophy evaluated . After 3 weeks , estriol gel also showed a superiority over the placebo gel in most symptoms and signs evaluated . Treatment-related adverse events were similar among groups . Conclusions 0.005 % Estriol vaginal gel , a new formulation providing an ultra low dose of estriol per application , was shown to be safe and effective in the treatment of postmenopausal vaginal atrophy", "Objective : The objective of this study was to evaluate the efficacy and safety of three doses of estradiol gel 0.1 % ( Divigel , a novel formulation consisting of 1 mg estradiol per 1 g transdermal gel ) to reduce the frequency and severity of vasomotor symptoms and signs of vulvar and vaginal atrophy associated with menopause . Design : A total of 488 postmenopausal women were evaluated in a 12-week study comparing placebo with estradiol gel 0.1 % at doses of 1.0 , 0.5 , and 0.25 mg/day , with estimated daily deliveries of 0.027 , 0.009 , and 0.003 mg of estradiol , respectively . Primary endpoints were the change from baseline in daily frequency and severity of moderate to severe vasomotor symptoms . Change from baseline in the signs of vulvar and vaginal atrophy ( vaginal pH and percentage of superficial cells ) was also assessed . Results : Treatment with estradiol gel 0.1 % showed statistically significant reductions in frequency and severity of vasomotor symptoms from baseline compared with placebo as early as Week 2 that were maintained throughout treatment . Signs of vulvar and vaginal atrophy were also significantly improved from baseline with all three doses of estradiol gel 0.1 % compared with placebo . Conclusions : Low-dose transdermal estradiol gel 0.1 % is an effective treatment for relief of vasomotor symptoms , as well as signs of vulvar and vaginal atrophy , associated with menopause . Estradiol gel 0.1 % offers multiple dosing options to individualize patient therapy , including the lowest available effective dose ( 0.25 mg estradiol , delivering 0.003 mg/d estradiol ) to treat the vasomotor symptoms of menopause", "Objective : The aim of this study was to investigate the effectiveness of microdose transdermal 17&bgr;-estradiol ( E2 ) therapy in postmenopausal women with moderate to severe vulvovaginal symptoms . Methods : This report is based on a subset of 121 women who reported most bothersome moderate or severe vulvovaginal symptoms at baseline , from a previous r and omized , double-blind , placebo-controlled , multicenter study of 425 healthy , symptomatic , postmenopausal women . Recruits had experienced at least 7 moderate or severe hot flushes daily for at least 1 week or at least 50 moderate or severe hot flushes per week for at least 1 week . Effects on co primary efficacy variables have been reported previously . Participants received low-dose transdermal E2 plus levonorgestrel ( n = 43 ; nominal delivery 0.023 mg/d E2/0.0075 mg/d levonorgestrel ) , microdose E2 ( n = 42 ; nominal delivery 0.014 mg/d ) , or placebo ( n = 36 ) for 12 weeks . Secondary efficacy variables reported herein include mean change from baseline in vaginal pH and vaginal maturation index , the proportion of women with symptoms of vulvar and vaginal atrophy at baseline and week 12 , and the proportion of women with moderate-to-severe symptoms of vulvar and vaginal atrophy . Results : Microdose transdermal E2 treatment was associated with a consistent benefit versus placebo in women with vulvovaginal atrophy . There was a statistically significant difference between both E2 versus placebo for changes in vaginal pH and vaginal maturation index . Conclusions : Microdose transdermal E2 offers a useful addition to the therapeutic armamentarium for postmenopausal women in whom vulvovaginal symptoms are particularly troublesome", "Objective : The aim of this study was to evaluate low-dose synthetic conjugated estrogens A ( SCE-A ) cream administered twice weekly for the treatment of moderate to severe vulvovaginal atrophy ( VVA ) in a symptomatic postmenopausal population . Methods : In a multicenter , double-blind , r and omized , placebo-controlled study , 305 women with symptoms of VVA were treated with either 1 g SCE-A cream ( n = 150 ) or matching placebo ( n = 155 ) for a period of up to 12 weeks . Participants had to have a vaginal pH of greater than 5 , less than or equal to 5 % superficial cells on a vaginal smear , and at least one of five symptoms of VVA ( dryness , soreness , irritation , pain with intercourse , and bleeding after intercourse ) that was moderate or severe in intensity . Women had to select one moderate or severe symptom as the most bothersome . Results : Efficacy was assessed at 2 , 3 , 4 , 8 , and 12 weeks and included the change from baseline in the severity of the most bothersome symptom ( MBS ) , maturation index , and pH. Most women identified vaginal dryness as the MBS ( 48 % ) followed by pain with intercourse ( 31.3 % ) . A statistically significant increase in the maturation index and significant decreases in pH and severity of the MBS were observed for those treated with SCE-A vaginal cream compared with placebo . Conclusions : A low dose ( 1 g = 0.625 mg ) of SCE-A vaginal cream administered twice weekly was shown to be effective compared with placebo in treating VVA in postmenopausal women for the three co primary efficacy measures of maturation index , pH , and severity of the MBS" ]

[ "BACKGROUND Very little work on alcohol consumption patterns in older people has been undertaken . As a result , knowledge about the prevalence and characteristics of regular drinkers and heavy drinkers in this age group remains limited . OBJECTIVE To determine the socio-economic and health characteristics associated with different levels of alcohol intake in older people . DESIGN Detailed screening of patients in one arm of a cluster r and omised trial . SETTING 53 UK general practice s drawn from the Medical Research Council General Practice Research Framework . SUBJECTS All patients aged 75 and over on the GP lists ( excluding those in nursing homes or other long stay care ) were invited to participate in the study . Of the 15358 people who received a detailed assessment in the ' universal ' arm , 14962 ( 97 % ) of these answered questions on alcohol consumption . Of these , 62 % were female and the median age was 80.3 years . METHODS Associations between reported alcohol intake and various socio-economic and health variables were investigated , first in univariate analyses and then controlling for other variables in logistic regression models . RESULTS 5 % of men and 2.5 % of women exceeded the Royal College of Physicians , Psychiatrists and General Practitioners ' recommended drinking limits of 21 and 14 units a week respectively ; 17 % of subjects had never had a drink . Women and the very elderly were less likely to be drinkers . Those that drank were more likely to be people who still had a fairly active and sociable lifestyle , and with a better self-perceived health status compared with non-drinkers . Moderate drinkers were also less likely to be severely cognitively impaired compared with non-drinkers : adjusted odds ratio 0.69 ( 95 % CI 0.57 , 0.85 ) ; but more likely to report symptoms of anxiety : 1.31 ( 1.07 , 1.61 ) . CONCLUSIONS Our results suggest that moderate alcohol consumption is associated with relative financial security and good health with the exception of higher levels of anxiety amongst drinkers", "Background : light-to-moderate drinking is apparently associated with a decreased risk of physical limitations in middle-aged and older adults . Objective : to investigate the association between alcohol consumption and physical limitations in Eastern European population s. Study design : a cross-sectional survey of 28,783 r and omly selected residents ( 45–69 years ) in Novosibirsk ( Russia ) , Krakow ( Pol and ) and seven towns of Czech Republic . Methods : physical limitations were defined as Alcohol consumption was assessed by a graduated frequency question naire , and problem drinking was defined as ≥2 positive responses on the CAGE question naire . In the Russian sample , past drinking was also assessed . Results : the odds of physical limitations were highest among non-drinkers , decreased with increasing drinking frequency , annual consumption and average drinking quantity and were not associated with problem drinking . The adjusted odds ratio ( OR ) of physical limitations in non-drinkers versus regular moderate drinkers was 1.61 ( 95 % confidence interval : 1.48–1.75 ) . In the Russian sample with past drinking available , the adjusted OR in those who stopped drinking for health reasons versus continuing drinkers was 3.19 ( 2.58–3.95 ) ; ORs in lifetime abstainers , former drinkers for non-health reasons and reduced drinkers for health reasons were 1.27 ( 1.02–1.57 ) , 1.48 ( 1.18–1.85 ) and 2.40 ( 2.05–2.81 ) , respectively . Conclusion : this study found an inverse association between alcohol consumption and physical limitations . The high odds of physical limitations in non-drinkers can be largely explained by poor health of former drinkers . The apparently protective effect of heavier drinking was partly due to less healthy former heavy drinkers who moved to lower drinking categories", "Abstract Objectives . The aim of this study was to assess the possibility of clinical ly significant drug – alcohol interactions among home-dwelling older adults aged ≥ 65 years . Design . This study was a cross-sectional assessment of a stratified r and om sample of 2100 elderly people ( ≥ 65 years ) in Espoo , Finl and . The response rate was 71.6 % from the community-dwelling sample . The drugs were coded according to their Anatomical Therapeutic Chemical ( ATC ) classification index ( ATC DDD 2012 ) . Significant alcohol interactive ( AI ) drugs were examined according to the Swedish , Finnish , INteraction X-referencing ( SFINX ) interaction data base , as well as concomitant use of central nervous system drugs , hypoglycaemics , and warfarin with alcohol . “ At-risk alcohol users ” were defined consuming > 7 drinks/week , or ≥ 5 drinks on a typical drinking day , or using ≥ 3 drinks several times/week , “ moderate users ” as consuming at least one drink/month , but less than 7 drinks/week , and “ minimal/non-users ” less than one drink/month . Results . Of the total sample ( n = 1395 ) , 1142 respondents responded as using at least one drug . Of the drug users , 715 ( 62.6 % ) persons used alcohol . The mean number of medications was 4.2 ( SD 2.5 ) among “ at-risk users ” , 4.0 ( SD 2.6 ) among “ moderate users ” , and 5.4 ( SD 3.4 ) among “ minimal/non-users ” ( p The concomitant use of AI drugs was widespread . Among the “ at-risk users ” , “ moderate users ” , and “ minimal/nonusers ” 42.2 % , 34.9 % , and 52.7 % , respectively , were on AI drugs ( p used warfarin , hypnotics/sedatives , or metformin . Conclusions . Use of AI drugs is common among older adults , and this increases the potential risks related to the use of alcohol", "Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies", "BACKGROUND A major issue in any systematic review is deciding which trials or studies to include and which to exclude . The Cochrane Collaboration and similar respected organizations have traditionally viewed the r and omized trial ( RCT ) as the only acceptable evidence on treatment outcome . However , many systematic review s are indeterminate because they include insufficient RCTs whilst they reject large numbers of non-r and omized controlled studies . This is particularly true in forensic mental health , a domain where RCT methodology can be problematic . Systematic review s could become more informative if review ers knew when , and under what circumstances , non-r and omized design s are acceptable for inclusion alongside RCTs . METHOD This pilot study explores whether good- quality , controlled , non-r and omized studies can be reliable surrogates for RCTs . We examined two published review s from the Cochrane Schizophrenia Group . We compared outcomes between ( a ) r and omized trials ( that had been included ) and non-r and omized studies ( that had been excluded ) , and ( b ) between high- and low- quality studies using an established quality checklist . RESULTS In the first review , effect scores were similar for r and omized and non-r and omized studies and relatively insensitive to study quality . In the second review , the treatment effect was considerably lower for the RCT group - here , however , studies of high- quality showed much smaller effect scores than those of low- quality on two separate outcomes . CONCLUSIONS Non-r and omized controlled studies of high quality can produce outcomes that approximate to those found in RCTs . Trial quality may have a greater impact on treatment effect size than r and omization alone , suggesting that r and omization should not be seen as a reliable proxy for overall quality . The problems and issues still to be resolved are discussed with recommendations for future research", "AIMS To explore alcohol use and concomitant use of prescription and over the counter ( OTC ) medicines in people aged 75 years or over . DESIGN Community-based r and omized survey of home-dwelling elderly persons , Setting : the City of Kuopio , Finl and . PARTICIPANTS Population -based r and om sample of 700 persons aged 75 years or over , of whom 601 participated ( 86 % ) . Only home-dwellers ( n = 523 ) were included in this study . MEASUREMENTS Alcohol use based on responses to questions concerning quantity and frequency , and CAGE questions . Use of prescription and non-prescription medicines . Mean corpuscular volume . RESULTS Of the participants , 44 % used alcohol . Most alcohol drinkers used medications on a regular basis ( 86.9 % ) or as needed ( 87.8 % ) , among them medicines known to have some potential interactions with alcohol . Elevated mean corpuscular volume was more widespread among alcohol drinkers than non drinkers . CONCLUSION Theoretical risks posed by alcohol use are not minimal in the older elderly , though the quantity of alcohol use is not considerable . Physicians and nurses should pay attention to chronic diseases and medications when counselling aged people about alcohol consumption . The question of clinical importance of alcohol-medication interactions needs to be studied further", "BACKGROUND Consumption of moderate-to-heavy amounts of alcohol has been associated with lower risk of cardiovascular disease and diabetes . Although both diseases are main causes of the frailty syndrome , no previous study has assessed the association between alcohol-drinking patterns and risk of frailty in older adults . METHODS A prospect i ve cohort study of 2,086 community-dwelling individuals aged 60 and older , recruited in 2008 - 2010 , and followed through 2012 , was carried out . Drinking patterns were self-reported at baseline . Moderate drinking was defined as alcohol intake less than 40 g/day for men and less than 24 g/day for women . A Mediterranean drinking pattern was defined as moderate alcohol intake , with wine preference ( ≥80 % of alcohol proceeds from wine ) and drinking only with meals . Study participants were followed through 2012 to ascertain incident frailty , defined as ≥2 of the following 4 Fried criteria : exhaustion , muscle weakness , low physical activity , and slow walking speed . Analyses were performed with logistic regression and adjusted for the main confounders . RESULTS After a mean follow-up of 3.3 ( SD = 0.6 ) years , 292 participants with incident frailty were identified . Compared with nondrinkers , the odds ratio and its 95 % confidence interval of frailty was 0.90 ( 0.65 - 1.25 ) for moderate drinkers . The corresponding results were 0.74 ( 0.48 - 1.16 ) for wine versus other beverage preference and 0.53 ( 0.31 - 0.92 ) for drinking only with meals versus only outside meals . Finally , compared with nondrinkers , the odds ratio ( 95 % confidence interval ) of frailty was 0.68 ( 0.47 - 0.99 ) for those adhering to the Mediterranean drinking pattern . CONCLUSIONS Certain drinking patterns , in particular drinking only with meals and the Mediterranean drinking pattern , are associated with a lower risk of frailty in older adults", "Research ers investigated whether a low cost public campaign by local health authorities reduced antibiotic prescribing for out patients . A non-r and omised controlled trial study design was used . The intervention was multifaceted and included posters , brochures , and advertisements on local media , plus a newsletter on local antibiotic resistance targeted at doctors and pharmacists . The campaign focused primarily on the prescription of antibiotics for upper respiratory tract infections . The trial was based in Emilia-Romagna in northern Italy . The provinces of Modena and Parma ( about 1 150 000 residents ) were chosen for implementation of the intervention between November 2011 and February 2012 . The provinces where the campaign was not implemented , with no information provided to doctors and pharmacists , formed the control group ( about 3 250 000 residents ) . The primary outcome was the change in prescribing rates of antibiotics for out patients over five months.1 The research ers reported that a low cost community based public campaign targeted at residents , combined with a newsletter on local antibiotic resistance for doctors and pharmacists , was associated with a significantly decreased total rate of antibiotic prescribing . However , the campaign did not affect the participants ’ knowledge and attitudes about antibiotic resistance . Which of the following statements , if any , are true", "OBJECTIVE To determine if alcohol use is a risk factor for fall injury events among community-dwelling older persons . DESIGN Case-control study . SETTING South Miami Beach , Florida . PARTICIPANTS 320 persons 65 or older who sought treatment at six area hospitals for injuries result ing from falls ; 609 controls , matched for sex and age , selected r and omly from Health Care Financing Administration ( Medicare ) files . MAIN INDEPENDENT VARIABLES Self-reported current alcohol use . RESULTS No association was found between fall injury events and average weekly alcohol use . CONCLUSIONS Further efforts at reducing injuries to older persons from falls should concentrate on other modifiable risk factors , including adequate treatment of underlying medical conditions , reducing inappropriate psychotropic medication use , and installing safety devices in the home", "Purpose : The aim of this study was to determine the association between alcohol intake and risk of dementia related death , taking into account relevant confounding and mediating factors . Material s and Methods : Data was obtained from a Norwegian prospect i ve study with a 17-year follow-up . The study population comprised 25,635 participants aged between 60 and 80 years at the time of examination from the Cohort of Norway ( CONOR ) . Cox regression was used to investigate the association between alcohol use and dementia related death . Results : Nearly half ( 12,139 ) of the study population died during follow-up , of which 1,224 had a diagnosis of dementia on their death certificate . The risk of dementia related death was significantly higher among abstainers than among individuals that drank alcohol once per month ( HR = 1.33 , 95 % CI = 1.14–1.56 , p risk of dementia related death ( HR = 1.60 , 95 % CI = 1.28–2.00 , p higher mortality rates due to alcohol-related causes ( HR = 1.41 , 95 % CI = 1.03–1.93 , p = 0.031 ) and other causes ( HR = 1.32 , 95 % CI = 1.21–1.43 , p the risk of dementia related death is significantly higher among elderly abstainers than among those who drink alcohol , after adjusting for relevant confounders . However , care should be taken in interpretation of data due to missing information on drinking frequency , as this missing-group might have a large share of the heavy drinkers in the study cohort" ]

[ "Although resveratrol has widely been studied for its potential health benefits , little is known about its metabolic effects in humans . Our aims were to determine whether the polyphenol resveratrol improves insulin sensitivity in type 2 diabetic patients and to gain some insight into the mechanism of its action . After an initial general examination ( including blood chemistry ) , nineteen patients enrolled in the 4-week-long double-blind study were r and omly assigned into two groups : a resveratrol group receiving oral 2 × 5 mg resveratrol and a control group receiving placebo . Before and after the second and fourth weeks of the trial , insulin resistance/sensitivity , creatinine-normalised ortho-tyrosine level in urine sample s ( as a measure of oxidative stress ) , incretin levels and phosphorylated protein kinase B (pAkt):protein kinase B ( Akt ) ratio in platelets were assessed and statistically analysed . After the fourth week , resveratrol significantly decreased insulin resistance ( homeostasis model of assessment for insulin resistance ) and urinary ortho-tyrosine excretion , while it increased the pAkt : Akt ratio in platelets . On the other h and , it had no effect on parameters that relate to β-cell function ( i.e. homeostasis model of assessment of β-cell function ) . The present study shows for the first time that resveratrol improves insulin sensitivity in humans , which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin signalling via the Akt pathway", "In healthy older adults , resveratrol supplementation has been shown to improve long-term glucose control , resting-state functional connectivity ( RSFC ) of the hippocampus , and memory function . Here , we aim ed to investigate if these beneficial effects extend to individuals at high-risk for dementia , i.e. , patients with mild cognitive impairment ( MCI ) . In a r and omized , double-blind interventional study , 40 well-characterized patients with MCI ( 21 females ; 50–80 years ) completed 26 weeks of resveratrol ( 200 mg/d ; n = 18 ) or placebo ( 1,015 mg/d olive oil ; n = 22 ) intake . Serum levels of glucose , glycated hemoglobin A1c and insulin were determined before and after intervention . Moreover , cerebral magnetic resonance imaging ( MRI ) ( 3 T ) ( n = 14 vs. 16 ) was conducted to analyze hippocampus volume , microstructure and RSFC , and neuropsychological testing was conducted to assess learning and memory ( primary endpoint ) at both time points . In comparison to the control group , resveratrol supplementation result ed in lower glycated hemoglobin A1c concentration with a moderate effect size ( ANOVARM p = 0.059 , Cohen 's d = 0.66 ) , higher RSFC between right anterior hippocampus and right angular cortex ( p preservation of left anterior hippocampus volume ( ANOVARM p = 0.061 , Cohen 's d = 0.68 ) . No significant differences in memory performance emerged between groups . This proof-of-concept study indicates for the first-time that resveratrol intake may reduce glycated hemoglobin A1c , preserves hippocampus volume , and improves hippocampus RSFC in at-risk patients for dementia . Larger trials with longer intervention time should now determine if these benefits can be vali date d and extended to cognitive function", "BACKGROUND The many putative beneficial effects of the polyphenol resveratrol include an ability to bolster endogenous antioxidant defenses , modulate nitric oxide synthesis , and promote vasodilation , which thereby improves blood flow . Resveratrol may therefore modulate aspects of brain function in humans . OBJECTIVE The current study assessed the effects of oral resveratrol on cognitive performance and localized cerebral blood flow variables in healthy human adults . DESIGN In this r and omized , double-blind , placebo-controlled , crossover study , 22 healthy adults received placebo and 2 doses ( 250 and 500 mg ) of trans-resveratrol in counterbalanced order on separate days . After a 45-min resting absorption period , the participants performed a selection of cognitive tasks that activate the frontal cortex for an additional 36 min . Cerebral blood flow and hemodynamics , as indexed by concentration changes in oxygenated and deoxygenated hemoglobin , were assessed in the frontal cortex throughout the posttreatment period with the use of near-infrared spectroscopy . The presence of resveratrol and its conjugates in plasma was confirmed by HPLC after the same doses in a separate cohort ( n = 9 ) . RESULTS Resveratrol administration result ed in dose-dependent increases in cerebral blood flow during task performance , as indexed by total concentrations of hemoglobin . There was also an increase in deoxyhemoglobin after both doses of resveratrol , which suggested enhanced oxygen extraction , that became apparent toward the end of the 45-min absorption phase and was sustained throughout task performance . Cognitive function was not affected . Resveratrol metabolites were present in plasma throughout the cognitive task period . CONCLUSION These results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables", "Background Schizophrenia ( SZ ) is associated with psychotic experiences and cognitive deficits . Therefore , cognitive function is one of the most critical determinants of quality of life in this pathology . Resveratrol has been related to neuroprotective action , but there are no studies evaluating resveratrol in SZ . The objective of this study was to determine the efficacy of resveratrol supplementation on cognition in individuals with SZ . Methods This is a 1-month r and omized , double-blind , and controlled trial ( NCT 02062190 ) , in which 19 men with diagnosis of SZ , aged 18–65 years , were assigned to a resveratrol supplementation group ( 200 mg ) or placebo group ( 200 mg ) , with a 1-month follow-up . Applying a series of cognitive tests assessed neuropsychology performance ( Hopkins Verbal Learning Test , Stroop Color and Word Test , and Weschler Adult Intelligence Scale ) and Brief Psychiatric Rating Scale assessed psychopathology severity . Results There were no significant improvement in neuropsychology performance ( episodic memory , working memory , attention and concentration capacity , inhibitory control , interference measures , selective attention , and mental flexibility ) and psychopathology severity after 1 month of resveratrol supplementation ( P > 0.05 ) . Conclusion In conclusion , we have shown that 1 month of a resveratrol supplementation ( 200 mg/day ) did not improve episodic memory , working memory , attention and concentration capacity , inhibitory control , interference measures , selective attention , and mental flexibility as compared with placebo in patients with SZ", "Previous research has shown that resveratrol can increase cerebral blood flow ( CBF ) in the absence of improved cognitive performance in healthy , young human subjects during the performance of cognitively dem and ing tasks . This lack of cognitive effects may be due to low bioavailability and , in turn , reduced bioefficacy of resveratrol in vivo . Piperine can alter polyphenol pharmacokinetics , but previous studies have not investigated whether this affects the efficacy of the target compound . Therefore , the objective of the present study was to ascertain whether co-supplementation of piperine with resveratrol affects the bioavailability and efficacy of resveratrol with regard to cognition and CBF . The present study utilised a r and omised , double-blind , placebo-controlled , within-subjects design , where twenty-three adults were given placebo , trans-resveratrol ( 250 mg ) and trans-resveratrol with 20 mg piperine on separate days at least a week apart . After a 40 min rest/absorption period , the participants performed a selection of cognitive tasks and CBF was assessed throughout the period , in the frontal cortex , using near-IR spectroscopy . The presence of resveratrol and its conjugates in the plasma was confirmed by liquid chromatography-MS analysis carried out following the administration of the same doses in a separate cohort ( n 6 ) . The results indicated that when co-supplemented , piperine and resveratrol significantly augmented CBF during task performance in comparison with placebo and resveratrol alone . Cognitive function , mood and blood pressure were not affected . The plasma concentrations of resveratrol and its metabolites were not significantly different between the treatments , which indicates that co-supplementation of piperine with resveratrol enhances the bioefficacy of resveratrol with regard to CBF effects , but not cognitive performance , and does this without altering bioavailability", "We tested whether chronic supplementation with resveratrol ( a phytoestrogen ) could improve cerebrovascular function , cognition and mood in post-menopausal women . Eighty post-menopausal women aged 45–85 years were r and omised to take trans-resveratrol or placebo for 14 weeks and the effects on cognitive performance , cerebral blood flow velocity and pulsatility index ( a measure of arterial stiffness ) in the middle cerebral artery ( using transcranial Doppler ultrasound ) , and cerebrovascular responsiveness ( CVR ) to both cognitive testing and hypercapnia were assessed . Mood question naires were also administered . Compared to placebo , resveratrol elicited 17 % increases in CVR to both hypercapnic ( p = 0.010 ) and cognitive stimuli ( p = 0.002 ) . Significant improvements were observed in the performance of cognitive tasks in the domain of verbal memory ( p = 0.041 ) and in overall cognitive performance ( p = 0.020 ) , which correlated with the increase in CVR ( r = 0.327 ; p = 0.048 ) . Mood tended to improve in multiple measures , although not significantly . These results indicate that regular consumption of a modest dose of resveratrol can enhance both cerebrovascular function and cognition in post-menopausal women , potentially reducing their heightened risk of accelerated cognitive decline and offering a promising therapeutic treatment for menopause-related cognitive decline", "Background : Poor cerebral perfusion may contribute to cognitive impairment in type 2 diabetes mellitus ( T2DM ) . We conducted a r and omized controlled trial to test the hypothesis that resveratrol can enhance cerebral vasodilator function and thereby alleviate the cognitive deficits in T2DM . We have already reported that acute resveratrol consumption improved cerebrovascular responsiveness ( CVR ) to hypercapnia . We now report the effects of resveratrol on neurovascular coupling capacity ( CVR to cognitive stimuli ) , cognitive performance and correlations with plasma resveratrol concentrations . Methods : Thirty-six T2DM adults aged 40–80 years were r and omized to consume single doses of resveratrol ( 0 , 75 , 150 and 300 mg ) at weekly intervals . Transcranial Doppler ultrasound was used to monitor changes in blood flow velocity ( BFV ) during a cognitive test battery . The battery consisted of dual-tasking ( finger tapping with both Trail Making task and Serial Subtraction 3 task ) and a computerized multi-tasking test that required attending to four tasks simultaneously . CVR to cognitive tasks was calculated as the per cent increase in BFV from pre-test basal to peak mean blood flow velocity and also as the area under the curve for BFV . Results : Compared to placebo , 75 mg resveratrol significantly improved neurovascular coupling capacity , which correlated with plasma total resveratrol levels . Enhanced performance on the multi-tasking test battery was also evident following 75 mg and 300 mg of resveratrol . Conclusion : a single 75 mg dose of resveratrol was able to improve neurovascular coupling and cognitive performance in T2DM . Evaluation of benefits of chronic resveratrol supplementation is now warranted", "Single doses of resveratrol have previously been shown to increase cerebral blood flow ( CBF ) with no clear effect on cognitive function or mood in healthy adults . Chronic resveratrol consumption may increase the poor bioavailability of resveratrol or otherwise potentiate its psychological effects . In this r and omised , double-blind , placebo-controlled , parallel-groups study , a total of sixty adults aged between 18 and 30 years received either placebo or resveratrol for 28 d. On the 1st and 28th day of treatment , the performance of cognitively dem and ing tasks ( serial subtractions , rapid visual information processing and 3-Back ) ( n 41 complete data sets ) was assessed , alongside blood pressure ( n 26 ) and acute ( near-IR spectroscopy ( NIRS ) ) and chronic ( transcranial Doppler ) measures of CBF ( n 46 ) . Subjective mood , sleep quality and health question naires were completed at weekly intervals ( n 53/54 ) . The results showed that the cognitive effects of resveratrol on day 1 were restricted to more accurate but slower serial subtraction task performance . The only cognitive finding on day 28 was a beneficial effect of resveratrol on the accuracy of the 3-Back task before treatment consumption . Subjective ratings of ' fatigue ' were significantly lower across the entire 28 d in the resveratrol condition . Resveratrol also result ed in modulation of CBF parameters on day 1 , as assessed by NIRS , and significantly increased diastolic blood pressure on day 28 . Levels of resveratrol metabolites were significantly higher both before and after the day 's treatment on day 28 , in comparison with day 1 . These results confirm the acute CBF effects of resveratrol and the lack of interpretable cognitive effects", "Background : We have previously demonstrated acute dose-dependent increases of flow-mediated dilatation ( FMD ) in the brachial artery after resveratrol consumption in mildly hypertensive , overweight/obese adults . Resveratrol supplementation has also been shown to increase cerebral blood flow acutely , without affecting cognition . Objectives : To evaluate the effects of chronic resveratrol supplementation on both FMD and cognitive performance . Method : Twenty-eight obese but otherwise healthy adults ( BMI : 33.3 ± 0.6 kg/m2 ) were r and omized to take a single 75 mg capsule of trans-resveratrol ( Resvida ) or placebo daily for 6 weeks each in a double-blind crossover supplementation trial . Blood pressure , arterial compliance , FMD , and performance on the Stroop Color-Word Test were assessed at the end of each 6-week intervention period while fasted and at least 18 h after taking the last daily capsule . An additional capsule of the same supplement was then taken . FMD assessment was repeated 1 h later . Results : Chronic resveratrol supplementation for 6 weeks was well tolerated and result ed in a 23 % increase in FMD compared with placebo ( P = 0.021 , paired t-test ) . The extent of increase correlated negatively with baseline FMD ( r = −0.47 , P = 0.01 ) . A single dose of resveratrol ( 75 mg ) following chronic resveratrol supplementation result ed in a 35 % greater acute FMD response than the equivalent placebo supplementation . These FMD improvements remained significant after adjusting for baseline FMD . Blood pressure , arterial compliance , and all components of the Stroop Color-Word Test were unaffected by chronic resveratrol supplementation . Conclusion : Daily resveratrol consumption was well tolerated and has the potential to maintain healthy circulatory function in obese adults" ]

[ "OBJECTIVE --To compare the effects of uteroplacental circulation of two beta adrenoceptor blockers , atenolol ( cardioselective ) and pindolol ( non-selective with intrinsic sympathomimetic activity ) . DESIGN --Controlled double blind double dummy study . SETTING --Departments of obstetrics and gynaecology in two Swedish university hospitals . SUBJECTS--29 women with pregnancy induced hypertension in the third trimester , 13 r and omised to atenolol and 16 to pindolol . MAIN OUTCOME MEASURES --Pulsatility index in fetal aorta , umbilical artery , and maternal arcuate artery . Volumetric blood flow in fetal aorta and umbilical vein . RESULTS --Mean arterial blood pressure decreased by 9.0 ( 95 % confidence interval -13.0 to -5.0 ) mm Hg in the atenolol group and by 7.8 ( -11.4 to -4.2 ) mm Hg in the pindolol group . During atenolol treatment the pulsatility index increased significantly from 1.82 ( SD 0.20 ) to 2.07 ( 0.32 ) in the fetal thoracic descending aorta , from 1.44 ( 0.28 ) to 1.79 ( 0.27 ) in the abdominal aorta , and from 0.93 ( 0.17 ) to 1.05 ( 0.19 ) in the umbilical artery ; the volumetric blood flow in the umbilical vein decreased from 106 ( 28.8 ) to 84 ( 22.6 ) ml/min/kg . No such changes were seen after treatment with pindolol . Birth weight was similar in the two groups but placental weight was significantly different ( 529 ( 122 ) g in atenolol group v 653 ( 136 ) g in pindolol group ; p = 0.03 ) . CONCLUSION --The hypotensive effect was similar with both drugs , but only the beta 1 blocker atenolol had significant effects on fetal haemodynamics , although within normal ranges . The implication s of these findings can be only speculative , but negative fetal consequences of beta 1 adrenoceptor blockade can not be excluded", "One hundred and eighty three hypertensive pregnant women were r and omly assigned to antihypertensive treatment with oxprenolol ( 96 women ) or methyldopa ( 87 women ) . Control of hypertension was equivalent in both treatment groups , and in 64 ( 35 % ) cases hydralazine had to be added to the treatment to achieve the therapeutic goal ( diastolic blood pressure below 85 mm Hg ) . Five perinatal deaths occurred , one in the oxprenolol group and four in the methyldopa group . Detailed analysis confirmed a previous report of greater fetal growth in the group treated with oxprenolol ; this trend was present regardless of severity of hypertension and parity . With increasing duration of treatment the differences between the two groups diminished , and there was no difference after 10 weeks of treatment , a finding that may explain some of the reported discrepancies among therapeutic studies . As hypertension in pregnancy may pursue an accelerated course , necessitating urgent delivery , and there is no satisfactory method of predicting the duration of treatment in individual patients fetal benefit is most likely to be achieved by treatment with oxprenolol , provided that there is no maternal contraindication to treatment with beta blockers", "PURPOSE To evaluate the evolution of glycemic levels in newborns of hypertensive mothers according to maternal treatment . METHODS Prospect i ve r and omized study , including 93 newborns of mothers treated with isradipine ( n = 39 ) , atenolol ( n = 40 ) , or low sodium diet ( control group - n=14 ) . Glycemia was determined at birth ( mother and newborn by the oxidase glucose method ) and in the 1st , 3rd , 6th , 12th , and 24th hours after birth ( newborn by a test strip method ) . The evolution of glycemia was analyzed in each group ( Friedman test ) . The groups were compared regarding glycemia ( Kruskall-Wallis test ) , and linear regression models were constructed for the analyses ( independent variable = maternal glycemia ; dependent variables = umbilical cord , 3rd , and 6th hour glycemia ) . RESULTS There were no statistically significant differences among the mean blood glucose levels of the 3 groups in any of the assessment s. There was a correlation between maternal and umbilical cord blood glucose in the isradipine ( r = 0.61 ; P glycemia levels of the mothers and newborns in the third and sixth hours postpartum , this correlation was present only in the control group ( maternal x third hour : r = 0.65 ; P atenolol group . Hypoglycemia was detected in 51.3 % of the isradipine group , 60 % of the atenolol group , and 35.7 % of the control group , and it was more frequent in the first hour postpartum in all groups . CONCLUSIONS The results suggest a similar effect of the 3 types of treatment upon newborn glycemia . The correlation analysis suggests that isradipine could have effects upon newborn glycemia only after birth ( correlation only in umbilical cord blood ) , whereas atenolol could act earlier ( there was no correlation at any moment ) . The results also point to the need for glycemic control from the first hour postpartum of newborns of hypertensive mothers whether they have or have not undergone treatment with antihypertensive drugs", "OBJECTIVE --To determine the effect of atenolol on the outcome of pregnancy in women with essential hypertension . DESIGN -- Prospect i ve , r and omised , double blind , placebo controlled study . SETTING --Hospital clinic . PATIENTS --33 Women with mild essential hypertension ( systolic blood pressure 140 - 170 mm Hg or diastolic pressure 90 - 110 mm Hg on two occasions at least 24 hours apart ) consecutively referred to two obstetric medical clinics . Four patients in the placebo group were withdrawn from the study : control of blood pressure was inadequate in two , one developed breathlessness , and one changed her mind about participating . The mean gestation in the 29 remaining women on entry to the study was 15.9 weeks . MAIN OUTCOME MEASURES --Blood pressure and birth weight . INTERVENTION--14 Women received placebo . 15 Women received atenolol 50 mg daily initially , increasing until either the blood pressure was less than 140/90 mm Hg or a dose of 200 micrograms daily was reached . RESULTS --The mean blood pressure on entry was 148/86 mm Hg in the group given atenolol and 144/86 mm Hg in the group given placebo . During treatment the mean diastolic pressure was significantly reduced by atenolol compared with placebo ( to 74 v 81 mm Hg ; difference in means ( 95 % confidence interval ) 7.0 ( 2.9 to 10.0 ) mm Hg ) but the effect on systolic pressure was marginal ( 132 v 136 mm Hg ; 4.0 ( -1.4 to 8.6 ) mm Hg ) . Babies in the atenolol group had a significantly lower birth weight than those in the placebo group ( 2620 g v 3530 g ; 910 ( 440 to 1380)g ) . CONCLUSION --Atenolol given from the end of the first trimester in patients with mild hypertension is associated with intrauterine growth retardation . When taken in conjunction with the results of a previous study in which methyldopa was given these findings indicate that benefit is unlikely to result from treating mild essential hypertension in pregnancy", "OBJECTIVE To determine the haemostatic status in preeclampsia and to investigate the effects of short-term use of anti-hypertensive drugs , methyldopa and isradipine . METHODS Thirty preeclamptic ( PE ) women admitted to the hospital for observation and treatment were r and omized to receive either methyldopa or isradipine for 2 weeks . Their blood pressure were monitored for 24 h before treatment and again at 7 days and 14 days after treatment using the programmable automated ambulatory blood pressure ( ABP ) monitoring system . Blood sampling was performed before commencement of anti-hypertensive treatment , 7 days and 14 days after treatment and the haemostatic parameters studied was compared before treatment with normal pregnancy and the effect of anti-hypertensive treatment . Nineteen normal pregnant subjects with a total of 30 blood sampling at various gestation and good pregnancy outcome served as controls . The following haemostatic parameters were determined ; thrombelastography , fibrinogen , antithrombin III ( ATIII ) , thrombin-antithrombin (TAT)-complex , beta-thromboglobulin ( beta-TG ) , plasminogen activators ( t-PA , u-PA ) , plasminogen activator inhibitors ( PAI-1 , PAI-2 ) , and plasminogen . RESULTS Significant lowering of blood pressure was evident at Days 7 and 14 of therapy with either methyldopa or isradipine . Increased mean plasma fibrinogen and decreased ATIII levels were seen in preeclampsia together with decreased u-PA and t-PA activity levels in contrast to increased t-PA antigen and beta-TG . No significant differences were seen for TAT-complex , PAI-1 , plasminogen and D-dimer levels although their mean levels were higher than observed in non-pregnant subject except for PAI-2 , the level was significantly reduced when compared with normal pregnancy . Two-way analysis of variance showed no significant alteration on all haemostatic parameters studied in preeclamptic women receiving either methyldopa or isradipine after 7 and 14 days of therapy . CONCLUSION Enhance activation of coagulation was observed together with raised fibrinolysis in normal pregnancy and PE . However , in PE a further reduction in ATIII , u-PA and PAI-2 with increased fibrinogen and platelet activation could lead to an imbalance in the coagulation/fibrinolysis equilibrium which favours fibrin deposition . All these changes seen in PE including the coagulation kinetics were not altered by the short term effects of methyldopa and isradipine even though significantly lowered blood pressure were observed during therapy", "OBJECTIVE To assess the efficacy and safety of labetalol compared with methyldopa in the management of mild and moderate cases of pregnancy-induced hypertension ( PIH ) . METHODS One hundred four primigravidas with PIH were r and omly allocated to receive either labetalol ( group A ) or methyldopa ( group B ) . The dose of the drugs was doubled every 48 h to maintain a mean arterial blood pressure Clinico-biochemical effects and frequency of side effects were studied . The statistical level of significance was taken at P significant proteinuria ( > 30 mg/dl ) whereas none developed proteinuria in group A. Labetalol was quicker and more efficient at controlling blood pressure , having a beneficial effect on renal functions and causing fewer side effects compared with methyldopa . The rate of induction of labor and rate of cesarean section for uncontrolled PIH was less in group A ( 48 % and 1 % , respectively ) compared with group B ( 63.0 % and 5.6 % , respectively ) . Moreover a higher Bishop score at induction of labor was noticed in group A. CONCLUSIONS Labetalol is better tolerated than methyldopa , gives more efficient control of blood pressure and may have a ripening effect on the uterine cervix", "Summary . Intravenous treatment with 10 mg of hydralazine or 100 mg of labetalol was r and omly allocated to 30 hypertensive pregnant women . Umbilical artery flow velocity waveforms were recorded using a pulsed Doppler duplex scanner ( ATL Mk V ) and umbilical artery pulsatility index ( PI ) and fetal heart rate ( FHR ) were derived from these recordings . Maternal blood pressure decreased significantly after both drugs . Maternal pulse rate increased after hydralazine but did not change significantly after labetalol . FHR did not change significantly after hydralazine but decreased after labetalol . PI decreased after hydralazine and increased after labetalol‐most fetuses showed little change but a few in each group showed large changes in PI , as did two of five additional patients studied . We attributed the decrease in PI in some fetuses after hydralazine to vasodilation , and the increase in PI in some fetuses after labetalol to vasoconstriction in the fetoplacental circulation , suggesting that fetal beta‐blockade may occur after maternal treatment with labetalol ", "Atenolol was compared with placebo in a r and omised and double-blind prospect i ve study of 120 women with mild to moderate pregnancy-associated hypertension who were also initially managed conventionally by bed rest . Atenolol given once daily significantly reduced blood-pressure , prevented proteinuria , and reduced the number of hospital admissions . Loss of blood-pressure control leading to withdrawal from the study was commoner among the placebo group , whose babies had a high morbidity . Respiratory distress syndrome occurred only in the placebo group . Intrauterine growth retardation , neonatal hypoglycaemia , and hyperbilirubinaemia occurred with the same frequency in the two groups . Neonatal bradycardia was more common after atenolol but the systolic blood-pressure of the babies was the same in both groups . There was no difference between the groups in maternal symptoms which could have been attributed to beta-blocker therapy . Thus atenolol is more effective than conventional obstetric management in this form of hypertension and does not adversely affect mother or baby", "Ninety‐seven women with moderate to severe preeclampsia ( PE ) were allocated at r and om to labetalol or hydralazine treatment . Of these , 22 women with severe PE gave birth to neonates with VLBW ( very low birth weight ≥ 1500 g ) . Seven were allocated to labetalol treatment ( Group A ) , eight to hydralazine treatment ( Group B ) and seven women received both drugs due to poor blood pressure control with a single drug therapy ( Group C ) . No difference in cesarean section rate or in the indication for operative delivery could be seen . Gestational age was 29.9 weeks ( 25.4–32.5 ) in Group A. 28.6 weeks ( 26.6–33.4 ) in Group B and 27.3 weeks ( 26.7–31.1 ) in Group C ( median and range ) . Birth weight did not differ between groups and 13 of the 22 infants weighed below 1000 g. There was a tendency to lower Apgar scores at five minutes in the hydralazine group . Time spent in the neonatal intensive care unit did not differ between groups . Five of the 11 neonates with gestational age (GA)≥28 weeks and three of the seven neonates in GA 29–30 weeks died . Neither the number of infants requiring intermittent positive pressure ventilation or duration of O2‐treatment , nor number of infants with respiratory distress syndrome differed between groups . We did not find any difference in the outcome of the VLBW infants when the hypertensive mother had been treated with either hydralazine or labetalol ", "Fifty-one women with pregnancy-induced hypertension ( PIH ) were r and omly allocated to one of three treatment groups : A : hydralazine ( 13 ) ; B : hydralazine and propranolol ( 17 ) ; and C : hydralazine and pindolol ( 19 ) . All women fulfilled the pretreatment criteria and were of similar age , numbers of previous pregnancies and had systolic blood pressure ( SBP ) of between 140 and 160 mmHg and diastolic blood pressure ( DBP ) of between 95 and 110 mmHg . Hypertension was treated equally well by all three regimens ( mean SBP was 133.6 , 130 and 134 mmHg , respectively ) . Heart rate was significantly higher than baseline in group A and lower in groups B and C , as is to be expected with beta-blocker treatment . Side-effects were more frequent in group A than in groups B and C , 62 % of the patients on hydralazine monotherapy complained of palpitations compared to 35 % on combination treatment . Fetal outcome differed in the various groups . Birth weight was significantly lower in group B , where regimen included propranolol , compared to that of group C , for whom the regimen included pindolol ( 3,044.7 + /- 443.8 and 2,709.6 + /- 485.5 gm , p Mean blood glucose of the newborns were similar in groups A and C ( 76.5 + /- 16.5 and 78.6 + /- 15 gm% ) and significantly lower in group B ( 62.6 + /- 14 gm% , p blood pressure was equally well treated in all three treatment groups . However , more maternal side-effects occurred in group A , the group treated with hydralazine monotherapy , while propranolol in combination with hydrazaline ( group B ) had some negative effects on fetal development which did not occur in pindolol/hydrazaline combination", "Three hundred women with mild chronic hypertension at 6 to 13 weeks ' gestation were r and omly allocated to receive either methyldopa or labetalol or be in the control group . Thirty-seven women ( 12 % ) were excluded for various reasons . Of the remaining 263 patients , 90 received no drug , 87 received methyldopa , and 86 received labetalol . All 263 were followed throughout pregnancy with serial renal function tests and serial assessment of fetal status . There were no differences among the three groups in mean systolic or diastolic blood pressures , mean gestational age , or initial laboratory findings at time of entry . Patients treated with medications had significantly lower ( p less than 0.0001 ) systolic and diastolic blood pressures throughout gestation compared with the no-medication group . Among the control group there was a spontaneously significant lowering ( p less than 0.0001 ) of both systolic and diastolic blood pressures at 14 to 26 weeks ' gestation . However , there were no differences among the three groups regarding the incidences of either superimposed preeclampsia ( 15.6 % , 18.4 % , and 16.3 % , respectively ) , abruptio placentae ( 2.2 % , 1.1 % , and 2.3 % , respectively ) , or preterm delivery ( 10 % , 12.5 % , and 11.6 % , respectively ) . In addition , there were no differences among the groups regarding gestational age at delivery , birth weight , incidence of fetal growth retardation , or neonatal head circumference . There was one midtrimester loss in the methyldopa group and one stillbirth in each of the other groups . We conclude that treatment of maternal blood pressure in mild chronic hypertension during pregnancy did not improve perinatal outcome", "The obstetric implication s of the use of the beta-adrenoceptor antagonist atenolol have been evaluated in a prospect i ve , r and omized , double-blind , and placebo-controlled study involving 120 women with pregnancy-associated hypertension . The clinical interpretation of antenatal and intrapartum cardiotocographs was uninfluenced by atenolol . Human placental lactogen concentration fell in the atenolol group , but this was not an indicator of subsequent fetal distress . Other obstetric indices , such as urinary estriol excretion , were the same in both groups . Spontaneous premature labor occurred in five women receiving placebo but in none who received atenolol . Together with previously reported findings on pregnancy outcome , our study leads us to conclude that beta-blockers such as atenolol can appropriately be used in the management of hypertension during pregnancy", "We compared propranolol with methyldopa in a r and omized prospect i ve study of 28 women with pregnancy associated hypertension . Both drugs were equally effective in controlling maternal hypertension . There was no significant difference in the birthweights of the babies in each group . However one infant born to a mother receiving propranolol had symptomatic hypoglycaemia . The mean peak levels of propranolol , propranolol glucuronide , 4-hydroxypropranolol , and 4-hydroxypropranolol glucuronide were not significantly different in the first , second , third trimesters and at least 3 months post partum . The mean peak plasma level of naphthoxylactic acid however was significantly less in the third trimester compared with post partum levels . Propranolol and its metabolites were found to cross into breast milk with the maximum dose likely to be ingested by the infant as either propranolol or propranolol glucuronide being 7 micrograms of propranolol per 100 g of breast milk , being approximately 0.1 % of the maternal dose", "A controlled prospect i ve evaluation of pregnancy complicated by chronic hypertension is proposed and preliminary data on population selection and pregnancy outcome are presented . Sixty-three women with evidence of underlying hypertensive disease were followed prospect ively throughout pregnancy . Twenty-three patients were followed in a protocol of intensified prenatal care and r and omized assignment of antihypertensive agents : placebo , hydralazine , or methyldopa . Forty patients were followed in the high-risk pregnancy clinics at Duke University . The incidence of preeclampsia in the r and omized prophylactic antihypertensive group was statistically lower than that in the nonr and omized group ( 8.7 versus 32.5 % ; P 63 hypertensive women had a high incidence of diabetes mellitus diagnosed during pregnancy ( 49.2 % ) as compared to the authors ' general obstetric population ( 8.1 % )", "In a double blind study , 20 gravidas with pre-eclampsia were r and omly allocated to treatment with either propranolol 120 mg/day or pindolol 15 mg/day for 7 days . Flow velocimetry was performed before and after treatment to assess the influence of these two regimens of beta blocker on the feto-placental circulation . A continuous wave Doppler unit was used to measure umbilical and uterine artery flow velocity waveforms . The systolic/diastolic ( A/B ) ratio and the systolic minus diastolic divided by systolic (A-B)/A ratio ( resistance index ) were used as indexes of blood flow resistance in the umbilical and uterine arteries , respectively . A resistance to flow in the uteroplacental circulation was significantly less in patients treated with pindolol compared to those treated with propranolol ( P less than 0.01 ) . The same pattern was also found in umbilical velocimetry , although the statistical significance was borderline ( P = 0.06 ) . Although both drugs were equally effective in reducing blood pressure at rest , their effect on the peripheral resistance was different . Pindolol appears to act in part through a peripheral vascular mechanism . Our data support this assumption because the flow in the uteroplacental bed , as reflected by a decrease in resistance index , improved when patients were treated with the drug pindolol", "Atenolol use may be associated with growth retardation when given in pregnancy , although the relationship to trimester of initiation , duration of treatment , and its use as monotherapy is still uncertain . To compare the obstetric and fetal outcome between women receiving atenolol ( as monotherapy ) and other antihypertensive drug monotherapies , and also to investigate the effect of duration of treatment on fetal growth , we performed a retrospective cohort study of 312 pregnancies in 223 women attending an Antenatal Hypertension Clinic . Atenolol ( as monotherapy ) was given in 78 pregnancies ( 25.0 % ) , other types of antihypertensive drugs as monotherapy were given in 53 pregnancies ( 17.0 % ) , and multiple drug combinations were given in 90 pregnancies ( 28.8 % ) . In 91 pregnancies ( 29.2 % ) no antihypertensive drugs were given . Atenolol was found to be associated with lower birth weight and ponderal index values , with a trend toward a higher prevalence of preterm ( when compared to other antihypertensive drugs as monotherapy , or to no treatment . The adverse effect of atenolol was more pronounced in women receiving the drug earlier in their pregnancy , and continuing the drug for a longer duration . In conclusion , atenolol should be avoided in the early stages of pregnancy and given with caution at the later stages , as it is associated with fetal growth retardation , which is related to duration of treatment", "Two hundred primigravid women with mild preeclampsia at 26 - 35 weeks ' gestation were r and omly allocated to treatment with hospitalization alone or combined with labetalol . There were no differences between the two groups in mean systolic or diastolic pressures , mean gestational age , or initial laboratory findings at time of entry . Patients in the labetalol group demonstrated a statistically significant ( P less than .005 ) decrease in blood pressure during treatment . No such decrease occurred in the hospitalization-alone group . Both groups exhibited significant deterioration in proteinuria , creatinine , and uric acid . The average days of pregnancy prolongation ( mean + /- SD ) were 21.3 + /- 13 and 20.1 + /- 14 days in the hospitalization and labetalol groups , respectively . There were no differences between the groups regarding any of the following : gestational age at delivery , birth weight , number of infants admitted to the special care unit , or cord blood gas measurements . However , the incidence of small-for-gestational-age infants was significantly higher in the labetalol group ( 19 versus 9 % , P less than .05 ) . There were no stillbirths , but one neonatal death in the labetalol group . Treatment of maternal blood pressure in preeclamptic pregnancies with labetalol did not improve perinatal outcome , and was associated with a higher frequency of fetal growth retardation", "Abstract . in an open , controlled trial , treatment with a combination of metoprolol and hydralazine was compared with non‐pharmacological management of mild and moderate hypertension in pregnancy . One hundred and sixty‐one women participated in the study . the drug‐treated group showed significantly better blood pressure control than the group not given antihypertensives . Induction of labor before term , because of maternal or fetal complications , was somewhat more frequent in the control group . Nine women in the treatment group and 5 in the control group developed albuminuria . Three infants in the drug‐treated group died perinatally , and one in the control group . the outcome for the newborns was similar in both groups concerning birth weight , head circumference and Apgar score and in the frequencies of respiratory distress , bradycardia and hypoglycemia . the better blood pressure control achieved with these drugs makes it possible to treat the patient at home and reduce the risk of emergency delivery , but treatment does not seem to be m and atory for a good outcome of the pregnancy in cases of mild and moderate hypertension during pregnancy", "Forty-four consecutive patients referred for treatment because of hypertension ( greater than 150/90 mmHg ) occurring during pregnancy were r and omly allocated to one of two treatment groups , hydralazine alone ( n = 21 ) or hydralazine combined with pindolol ( n = 23 ) . Satisfactory blood pressure control ( diastolic pressure less than 90 mmHg ) was achieved in 86 % of patients receiving hydralazine alone and 91 % of those on combined therapy . Although the treatment did not lower the overall incidence of hypertensive complications it appeared to delay the onset of such complications until successful surgical intervention was possible . Fetal outcome was similar in both groups and there was no perinatal mortality in this high-risk population . Although blood pressure control was similar in both groups of patients , combined therapy with hydralazine and pindolol can be considered to be superior to hydralazine monotherapy , since in patients treated with the combination the incidence and intensity of troublesome side-effects was markedly lower", "Summary . Two treatment strategies were compared in 155 women with pregnancy‐induced hypertension who were also given comprehensive non‐pharmacological care . The mean gestation at entry was 28 weeks . As long as the diastolic blood pressure ( DBP ) remained below 106 mmHg , oxprenolol , or oxprenolol plus dihydralazine , were given to the early treatment group , and matching placebos to the control group . Open antihypertensive treatment was provided for patients whose DBP rose above 105 mmHg . Proteinuria occurred in seven women in each group . In the early treatment group , 13 of the 78 women were delivered by caesarean section ; the corresponding numbers in the control group were 27 of 76 ( 17 vs 36 % , 95 % confidence interval ( CI ) of difference : 5‐33 % ) ; the sections included seven and 16 in the early treatment and control groups , respectively , for severe hypertension and /or fetal distress . There were five perinatal deaths , two in the early treatment group and three in the control group . Early treatment did not influence gestational age at birth or birthweight . Respiratory distress syndrome occurred in four infants in the early treated group and in 10 in the control group ; 14 infants in the former group and 26 in the latter were in hospital for more than 10 days ( 18 vs 35 % ; 95 % CI of difference 4.32 % ) . These results indicate that early antihypertensive treatment with oxprenolol is safe for the fetus and newborn in pregnancy‐induced hypertension , but has no advantage over non‐pharmacological care in terms of fetal growth . However , it may prevent acute hypertension in late pregnancy and associated fetal distress , and thus reduce the number of caesarean sections", "Twentysix women with pregnancy-induced hypertension have been r and omly treated with either labetalol or Aldomet . A more satisfactory control of blood pressure was obtained with labetalol with minimal side-effects . After two weeks of treatment with labetalol renal function had significantly improved with a markedly lower incidence of proteinuria . More patients went into spontaneous labour following labetalol than following Aldomet ; the Bishop score was also higher in this group . No adverse effects attributable to labetalol were noted in the baby either ante- or post-natally", "It is the development of proteinuria in pregnancy-induced hypertension which is associated with an increased perinatal mortality . There is some evidence to suggest that labetalol may diminish the amount of proteinuria in patients who have already developed proteinuric pre-eclampsia . A r and omised controlled study design was used to investigate whether labetalol treatment , started when a persistent diastolic blood pressure greater than 90 mmHg was observed , influenced the subsequent development of proteinuria . One hundred and fourteen women with singleton pregnancies and hypertension in the absence of proteinuria were r and omised to receive either labetalol or no antihypertensive therapy . At recruitment maternal age , blood pressure and gestation were similar in both the labetalol and control groups . There was no difference in the frequency , quantity or timing of subsequent proteinuria between treatment and control groups . Overall 34 % of primigravidae and 10 % of parous women developed proteinuria . Labetalol did , however , control the blood pressure in 45 of the 51 treated women ( 88 % ) within 24 h. This effect was often shortlived requiring dose escalation after 3 to 5 days in the majority of cases . Labetalol was well tolerated and no significant maternal toxicity was noted", "Objective To compare the effects of treatment with nicardipine and metoprolol in patients with hypertension during pregnancy", "Thirty patients matched for age , parity , socioeconomic status and severity of pregnancy induced hypertension ( PIH ) were r and omly allocated to treatment with metoprolol or methyldopa . The average fall in diastolic blood pressure was significant in the group treated with metoprolol as compared with the methyldopa group ( p less than 0.01 ) . There were 3 perinatal deaths in the methyldopa group and 1 in the metoprolol group ; the mean birth weight of the babies was higher in cases treated with metoprolol . The results suggest metoprolol to be more efficacious with regard to control of hypertension and fetal outcome in cases of pregnancy induced hypertension", "One hundred pregnant women with hypertension ( defined as diastolic blood pressure at or above 95 mm Hg ) were allocated at r and om to treatment with methyldopa or oxprenolol and were compared with nonhypertensive controls matched according to parity and gestation at delivery . The patients were also stratified into those entering the study early ( before 32 weeks ' gestation ) and those entering late ( after 32 weeks ' gestation ) . Although there were no differences in diastolic blood pressure between the hypertensive groups before or during treatment , in the early entry group the systolic blood pressure at entry of those allocated to oxprenolol was significantly higher than that of those receiving methyldopa ; this difference remained throughout the treatment period . Also in the early entry group further increments of drug treatment were required to control blood pressure of patients receiving oxprenolol than in those receiving methyldopa . The eventual fetal outcome for all patients treated with methyldopa was the same as that for those treated with oxprenolol ; birth weight , placental weight , head circumference , and Apgar score were not significantly different and there were no stillbirths in either group", "Abstract . A review is presented as regards the neonatal effects of beta‐blocking agents in hypertension during pregnancy . Experience points to low fetal and neonatal risks , but firmly based data concerning the neonates are very scanty . An on‐going double‐blind study is presented in which pregnant women with hypertension are r and omly allocated to either metoprolol or placebo treatment . One of the aims is to study the postnatal adaptation of the infants . The following measurements , recordings and examinations are performed : anthropometric measurements , Apgar score , blood gases and acid‐base status in umbilical ( venous and arterial ) blood , lactate and hypoxanthine in umbilical venous blood , catecholamines in umbilical arterial blood , pulse rate , blood glucose and a quantitative neurobehavioral assessment in the neonatal period", "Labetalol was compared with methyldopa in a r and omised trial involving 176 pregnant women with mild to moderate hypertension . Effective blood pressure control ( diastolic pressure below 86 mmHg ) was obtained in a similar proportion of mothers given labetalol or methyldopa , but the addition of a complementary treatment to achieve control was less frequently needed in the labetalol than in the methyldopa group ( 12/91 vs 22/85 p less than 0.05 ) . Side effects were mild and result ed in discontinuation of the r and omised treatment in 1 mother given labetalol . Pregnancy was terminated by intrauterine death in 4 mothers given methyldopa , and one neonate born to a patient allocated to labetalol died at day 1 . The average birthweight and the proportion of premature delivery or of small for gestational age newborns were similar in both treatment groups . Heart rate , blood pressure , respiratory rate and blood glucose did not differ between infants born to the mothers of the labetalol and the methyldopa groups , irrespective of gestational age at birth or birthweight . Blood pressure control is more frequently achieved in hypertensive pregnancies with labetalol than with methyldopa as a first line treatment . Labetalol is safe to the fetus and newborn and might offer a better prevention of intrauterine death than methyldopa", "Cord blood IgE levels and the development of allergy were studied in 29 children born by mothers who had been treated with the beta-adrenergic receptor blocking agent , metoprolol , during the pregnancy and in 23 children of placebo-treated mothers . In 13 ( 45 % ) of the former and 3 ( 15 % ) of the placebo group elevated cord blood IgE levels , i.e. more than 0.9 kU/l and /or obvious or probable allergy developed ( p = 0.03 ) . The findings support previous experimental observations that beta-blocking agents may enhance IgE antibody formation . It also adds to the number of environmental factors that may increase the risk for atopic disease in children", "Objective To determine the need for , and efficacy of , treatment with labetalol in women with mild‐to‐moderate pregnancy induced hypertension ( PIH )", "We describe the results of a prospect i ve study in which 120 women who developed hypertension in the last trimester of pregnancy were r and omly allocated in double blind manner to atenolol or placebo . The mean duration of treatment was five weeks . The only difference between groups during the neonatal period was in respiratory distress syndrome , mainly related to spontaneous premature labour , which occurred in six placebo group babies but in none from the atenolol group . Fifty five children from each group have been followed to 1 year of age . All in the atenolol group are developing normally but one child from the placebo group is brain damaged . These findings do not suggest any short or medium term paediatric complications after the use of beta blockers in pregnancy", "OBJECTIVE To evaluate the short-term effects of intravenously given atenolol and pindolol on utero- and umbilicoplacental vascular impedance , fetal hemodynamics and cardiac function in patients suffering from pregnancy-induced hypertension . STUDY DESIGN A total of 24 women were r and omized to receive atenolol or pindolol infusion . By using pulsed color Doppler techniques , uterine , placental arcuate , umbilical fetal middle cerebral and renal arteries were examined before , at the end and 30 min after the end of infusion . Pulsatility indices ( PI ) were calculated to assess vascular impedance . Fetal myocardial function was evaluated by using pulsed Doppler and M-mode echocardiography . Peak systolic velocities from the ascending aorta and pulmonary trunk , and also inner diameters and fractional shortenings of both ventricles were measured . RESULTS Both drugs significantly decreased maternal blood pressure . Immediately after the infusion , maternal heart rate was significantly decreased in both groups ; but the decrease was clearer and lasted longer in the atenolol group . Pindolol caused no changes in utero- or umbilicoplacental vascular impedance , while atenolol increased it in the nonplacental uterine artery . After atenolol infusion , PI in the umbilical artery was higher than after pindolol . Pindolol had no effects on fetal hemodynamics , while atenolol decreased PI value in the fetal renal artery . Peak systolic velocity in the pulmonary trunk was decreased after atenolol . Pindolol did not affect the fetal cardiac function . In subgroups with originally increased utero- or umbilicoplacental vascular impedance , the responses in uterine and umbilical vascular impedance and in fetal hemodynamics and cardiac function after atenolol and pindolol were different compared to whole groups . CONCLUSION Differently acting antihypertensive agents seem to affect differently uteroplacental vascular impedance . Atenolol may have some direct effects on fetal hemodynamics and cardiac function . According to our results , pindolol seems to be more preferable in the treatment of pregnancy-induced hypertension than atenolol", "OBJECTIVE To determine if assessment of maternal hemodynamics could predict women at risk for the development of preeclampsia , if treatment directed at hemodynamic abnormalities before the onset of hypertension could prevent preeclampsia , and if mothers could be treated in a way that protects fetal growth . METHODS A double-blinded , r and omized controlled trial was conducted . Subjects were considered to be at risk for preeclampsia if their cardiac output was greater than 7.4 L/min before 24 weeks ' gestation . Nulliparous and diabetic subjects at risk were treated with 100 mg of atenolol or placebo . Cardiac output was measured by Doppler technique . Inulin and para-aminohippurate clearances were performed . RESULTS Treatment with atenolol reduced the incidence of preeclampsia from 5 of 28 ( 18 % ) to 1 of 28 ( 3.8 % ) , ( P = .04 ) . Nulliparous women determined to be at risk for preeclampsia were similar to diabetic women at risk . Each was significantly heavier and had inulin and para-aminohippurate clearances greater than the control group . Treatment with atenolol was associated with infants weighing 440 g less than infants in the Noneiparous placebo group , ( P = .02 ) . No effect on birth weight was seen in the diabetic patients . Mothers of the smallest infants who were treated with atenolol could be identified by unexpectedly large reductions in cardiac output . CONCLUSION Measurement of cardiac output in the second trimester identified women at risk for preeclampsia . Treatment with atenolol decreased the incidence of preeclampsia . Nulliparous and diabetic women at risk for preeclampsia were similar with regard to maternal hemodynamics , maternal weight , and renal function . Treatment with atenolol was associated with reduced infant birth weight", "Eclampsia remains a rare , but serious , complication of pregnancy , estimated to complicate around 1 in 2000 deliveries in Europe and other developed countries ( Douglas & Redman 1992 ) , and from 1 in 100 to 1700 deliveries in developing countries ( Crowther 1985 ; WHO lnternational Collaborative Study of Hypertensive Disorders of Pregnancy 1988 ) ; eclampsia is associated with 10 % of maternal deaths and approximately 50000 women die each year having had an eclamptic convulsion ( Duley 1992 ) . Much of the recent debate about management of women with eclampsia has focused on control of convulsions . Anticonvulsants are given to prevent the first fit in women who have fulminating pre-eclampsia and to prevent further convulsions in women who already have had an eclamptic fit . Although these indications are related , women who have pre-eclampsia are likely to be less sick than those with eclampsia . The potential for benefit or for harm will , therefore , be different , and the effectiveness of anticonvulsants should be evaluated separately for these two situations . For well over half a century , magnesium sulphate has been advocated for the care of women with pre-eclampsia and eclampsia , yet its use remains controversial ( Donaldson 1992 ) . In the past , the lack of a sound hypothesis for the mechanism by which magnesium sulphate might act as an anticonvulsant has contributed to this . Recent plausible suggestions are that it may act by vasodilatation and subsequent reduction of cerebral ischaemia ( Belfort & Moise 1992 ) ; an alternative is by blocking some of the neuronal damage associated with cerebral ischaemia ( Goldman & Finkbeiner 1988 ) . Reflecting ongoing uncertainty about its role , use of magnesium sulphate continues to vary enormously . In the United States , for example , magnesium sulphate is the anticonvulsant of choice for women with either eclampsia or pre-eclampsia ( Consensus Report 1990 ) , while in the United Kingdom it is used by only 2 % of obstetricians ( Hutton et al. 1992 ) . What is the evidence that magnesium sulphate given to women with either pre-eclampsia or eclampsia does more good than harm ? The popularity of . magnesium sulphate in North America ( and elsewhere ) is largely based on reports of a few hundred women with eclampsia who were treated with magnesium sulphate ( Pritchard et al. 1984 ) . Whilst sometimes impressive in the number of women included , none of these reports included any form of comparison or control group . Without comparison , it is impossible to know whether the good or bad outcome for the women was due to magnesium sulphate or to a combination of other factors , such as the severity of disease , health status of the women , or to additional interventions . The effectiveness of an intervention , such as magnesium sulphate , is best evaluated by systematic review of all relevant r and omised trials . In the perinatal field , a system for preparing and maintaining review s of the effects of health care already exists ( Cochrane Pregnancy and Childbirth Data base 1993 ) . The evidence presented here is derived from review s published on this data base", "Thirty-two consecutive women with pregnancy-induced hypertension of early onset were r and omly allocated to treatment with pindolol or methyldopa . There was no difference between the groups in regard to the average time of delivery ( 36.33 vs. 36.6 weeks ) and weight of the newborn ( 2850 vs. 2870 g ) . A significant drop in systolic ( P less than 0.005 ) and diastolic ( P less than 0.05 ) blood pressure was observed in the group of patients treated with pindolol as compared with the methyldopa group . In the pindolol group an improvement in renal function was observed as determined by CCT and serum creatinine . There were no side effects from the drugs in the mother or in the newborn", "Fifty-three pregnant women with moderately severe hypertension were r and omly allocated to treatment with methyldopa or oxprenolol . There were no significant differences between the groups in age , height , weight , parity , or stage of gestation at the start of treatment . The outcome of pregnancy was better in the group treated with oxprenolol , with greater maternal plasma volume expansion and placental and fetal growth . No intrauterine deaths occurred in either group , and antepartum fetal distress , detected by oxytocin challenge testing , was evident in only one patient , who received methyldopa . This infant , and one other in the methyldopa group , died in the neonatal period . No neonatal deaths occurred in the oxprenolol-treated group . Even in this small number of patients these results were considerably better than those in untreated women with hypertension of similar severity . Apgar scores in both groups were equivalent at birth , while blood sugar concentrations were higher in the oxprenolol group . Oxprenolol appears to be safe and effective in controlling hypertension during pregnancy . There was no evidence of harmful effects on the fetus , and oxprenolol may offer a selective advantage over methyldopa for fetal growth and wellbeing in utero" ]

[ "Aim The aim of this study was to evaluate the benefits and safety of long-term i.v . iron therapy in iron-deficient patients with heart failure ( HF ) . Methods and results CONFIRM-HF was a multi-centre , double-blind , placebo-controlled trial that enrolled 304 ambulatory symptomatic HF patients with left ventricular ejection fraction ≤45 % , elevated natriuretic peptides , and iron deficiency ( ferritin Patients were r and omized 1 : 1 to treatment with i.v . iron , as ferric carboxymaltose ( FCM , n = 152 ) or placebo ( saline , n = 152 ) for 52 weeks . The primary end-point was the change in 6-min-walk-test ( 6MWT ) distance from baseline to Week 24 . Secondary end-points included changes in New York Heart Association ( NYHA ) class , Patient Global Assessment ( PGA ) , 6MWT distance , health-related quality of life ( QoL ) , Fatigue Score at Weeks 6 , 12 , 24 , 36 , and 52 and the effect of FCM on the rate of hospitalization for worsening HF . Treatment with FCM significantly prolonged 6MWT distance at Week 24 ( difference FCM vs. placebo : 33 ± 11 m , P = 0.002 ) . The treatment effect of FCM was consistent in all subgroups and was sustained to Week 52 ( difference FCM vs. placebo : 36 ± 11 m , P improvement in NYHA class , PGA , QoL , and Fatigue Score in patients treated with FCM was detected with statistical significance observed from Week 24 onwards . Treatment with FCM was associated with a significant reduction in the risk of hospitalizations for worsening HF [ hazard ratio ( 95 % confidence interval ) : 0.39 ( 0.19–0.82 ) , P = 0.009 ] . The number of deaths ( FCM : 12 , placebo : 14 deaths ) and the incidence of adverse events were comparable between both groups . Conclusion Treatment of symptomatic , iron-deficient HF patients with FCM over a 1-year period result ed in sustainable improvement in functional capacity , symptoms , and QoL and may be associated with risk reduction of hospitalization for worsening HF ( Clinical Trials.gov number NCT01453608 )", "Aims Therapy with i.v . iron in patients with chronic heart failure ( CHF ) and iron deficiency ( ID ) improves symptoms , functional capacity , and quality of life . We sought to investigate whether these beneficial outcomes are independent of anaemia . Methods and results FAIR-HF r and omized 459 patients with CHF [ NYHA class II or III , LVEF ≤40 % ( NYHA II ) or ≤45 % ( NYHA III ) ] and ID to i.v . iron as ferric carboxymaltose ( FCM ) or placebo in a 2:1 ratio . We analysed the efficacy and safety according to the presence or absence of anaemia ( haemoglobin ≤120 g/L ) at baseline . Of 459 patients , 232 had anaemia at baseline ( 51 % ) . The effect of FCM on the primary endpoints of self-reported Patient Global Assessment ( PGA ) and NYHA class at week 24 was similar in patients with and without anaemia [ odds ratio ( OR ) for improvement , 2.48 vs. 2.60 , P = 0.97 for PGA and 1.90 vs. 3.39 , P = 0.51 for NYHA ) . Results were also similar for the secondary endpoints , including PGA and NYHA at weeks 4 and 12 , 6 min walk test distance , Kansas City Cardiomyopathy Question naire overall score , and European Quality of Life-5 Dimensions Visual Analogue Scale at most time points . Regarding safety , no differences were noticed in the rates of death or first hospitalization between FCM and placebo both in anaemic and in non-anaemic patients . Conclusions Treatment of ID with FCM in patients with CHF is equally efficacious and shows a similar favourable safety profile irrespective of anaemia . Iron status should be assessed in symptomatic CHF patients both with and without anaemia and treatment of ID should be considered", "BACKGROUND Iron deficiency may impair aerobic performance . This study aim ed to determine whether treatment with intravenous iron ( ferric carboxymaltose ) would improve symptoms in patients who had heart failure , reduced left ventricular ejection fraction , and iron deficiency , either with or without anemia . METHODS We enrolled 459 patients with chronic heart failure of New York Heart Association ( NYHA ) functional class II or III , a left ventricular ejection fraction of 40 % or less ( for patients with NYHA class II ) or 45 % or less ( for NYHA class III ) , iron deficiency ( ferritin level were r and omly assigned , in a 2:1 ratio , to receive 200 mg of intravenous iron ( ferric carboxymaltose ) or saline ( placebo ) . The primary end points were the self-reported Patient Global Assessment and NYHA functional class , both at week 24 . Secondary end points included the distance walked in 6 minutes and the health-related quality of life . RESULTS Among the patients receiving ferric carboxymaltose , 50 % reported being much or moderately improved , as compared with 28 % of patients receiving placebo , according to the Patient Global Assessment ( odds ratio for improvement , 2.51 ; 95 % confidence interval [ CI ] , 1.75 to 3.61 ) . Among the patients assigned to ferric carboxymaltose , 47 % had an NYHA functional class I or II at week 24 , as compared with 30 % of patients assigned to placebo ( odds ratio for improvement by one class , 2.40 ; 95 % CI , 1.55 to 3.71 ) . Results were similar in patients with anemia and those without anemia . Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality -of-life assessment s. The rates of death , adverse events , and serious adverse events were similar in the two study groups . CONCLUSIONS Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency , with or without anemia , improves symptoms , functional capacity , and quality of life ; the side-effect profile is acceptable . ( Clinical Trials.gov number , NCT00520780 )", "Abstract Aims Iron deficiency is highly prevalent in Southeast Asians with heart failure ( HF ) and associated with worse outcomes . This trial aim ed to assess the effect of intravenous iron in Southeast Asians hospitalized with decompensated HF . Methods and results Fifty patients hospitalized for acute decompensated HF , regardless of ejection fraction , with iron deficiency ( defined as serum ferritin to receive either one dose of intravenous ferric carboxymaltose ( FCM ) 1000 mg or placebo ( 0.9 % saline ) following HF stabilization and before discharge in two Singapore tertiary centres . The primary endpoint was difference in 6‐min walk test ( 6MWT ) distance over 12 weeks , while secondary endpoints were quality of life assessed using vali date d Kansas City Cardiomyopathy Question naire ( KCCQ ) and Visual Analogue Scale ( VAS ) . Improvement in 6MWT distance at Week 12 was observed in both FCM and placebo groups ( from 252 ± 123 to 334 ± 128 m and from 243 ± 67 to 301 ± 83 m , respectively ) . Unadjusted analysis showed 6MWT distance for FCM exceeded that for placebo , but adjustment for baseline covariates and time attenuated this effect { adjusted mean difference between groups : 0.88 m [ 95 % confidence interval ( CI ) −30.2 to 32.0 , P = 0.956]}. KCCQ overall summary and VAS were similar in both groups [ adjusted mean difference : KCCQ −1.48 ( 95 % CI −8.27 to 5.31 , P = 0.670 ) and VAS 0.26 ( 95 % CI −0.33 to 0.86 , P = 0.386 ) ] . FCM was well tolerated with no serious treatment‐related adverse events . Conclusions Intravenous FCM administered pre‐discharge in Southeast Asians hospitalized with decompensated HF is clinical ly feasible . Changes in 6MWT distance should be measured beyond Week 12 to account for background therapy effects", "Objective Iron supplementation in iron-deficiency anaemia is st and ard practice , but the benefits of iron supplementation in iron-deficient non-anaemic ( IDNA ) individuals remains controversial . Our objective is to identify the effects of iron therapy on fatigue and physical capacity in IDNA adults . Design Systematic review and meta- analysis of r and omised controlled trials ( RCTs ) . Setting Primary care . Participants Adults ( ≥18 years ) who were iron deficient but non-anaemic . Interventions Oral , intramuscular or intravenous iron supplementation ; all therapy doses , frequencies and duration s were included . Comparators Placebo or active therapy . Results We identified RCTs in Medline , Embase , Cochrane Central Register of Controlled Trials , Cumulative Index of Nursing and Allied Health , SportD iscus and CAB Abstract s from inception to 31 October 2016 . We search ed the WHO ’s International Clinical Trials Registry Platform for relevant ongoing trials and performed forward search es of included trials and relevant review s in Web of Science . We assessed internal validity of included trials using the Cochrane Risk of Bias tool and the external validity using the Grading of Recommendations Assessment , Development and Evaluation methodology . From 11 580 citations , we included 18 unique trials and 2 companion papers enrolling 1170 patients . Using a Mantel-Haenszel r and om-effects model , iron supplementation was associated with reduced self-reported fatigue ( st and ardised mean difference ( SMD ) −0.38 ; 95 % CI −0.52 to −0.23 ; I2 0 % ; 4 trials ; 714 participants ) but was not associated with differences in objective measures of physical capacity , including maximal oxygen consumption ( SMD 0.11 ; 95 % CI −0.15 to 0.37 ; I2 0 % ; 9 trials ; 235 participants ) and timed methods of exercise testing . Iron supplementation significantly increased serum haemoglobin concentration ( MD 4.01 g/L ; 95 % CI 1.22 to 6.81 ; I2 48 % ; 12 trials ; 298 participants ) and serum ferritin ( MD 9.23 µmol/L ; 95 % CI 6.48 to 11.97 ; I2 58 % ; 14 trials ; 616 participants ) . Conclusion In IDNA adults , iron supplementation is associated with reduced subjective measures of fatigue but not with objective improvements in physical capacity . Given the global prevalence of both iron deficiency and fatigue , patients and practitioners could consider consumption of iron-rich foods or iron supplementation to improve symptoms of fatigue in the absence of documented anaemia . PROSPERO registration number CRD42014007085", "Purpose To determine the effect of intravenous iron supplementation on performance , fatigue and overall mood in runners without clinical iron deficiency . Methods Fourteen distance runners with serum ferritin 30–100 µg·L−1 were r and omly assigned to receive three blinded injections of intravenous ferric-carboxymaltose ( 2 ml , 100 mg , IRON ) or normal saline ( PLACEBO ) over four weeks ( weeks 0 , 2 , 4 ) . Athletes performed a 3,000 m time trial and 10 × 400 m monitored training session on consecutive days at week 0 and again following each injection . Hemoglobin mass ( Hbmass ) was assessed via carbon monoxide rebreathing at weeks 0 and 6 . Fatigue and mood were determined bi-weekly until week 6 via Total Fatigue Score ( TFS ) and Total Mood Disturbance ( TMD ) using the Brief Fatigue Inventory and Brunel Mood Scale . Data were analyzed using magnitude-based inferences , based on the unequal variances t-statistic and Cohen 's Effect sizes ( ES ) . Results Serum ferritin increased in IRON only ( Week 0 : 62.8±21.9 , Week 4 : 128.1±46.6 µg·L−1 ; p = 0.002 ) and remained elevated two weeks after the final injection ( 127.0±66.3 µg·L−1 , p = 0.01 ) , without significant changes in Hbmass . Supplementation had a moderate effect on TMD of IRON ( ES -0.77 ) with scores at week 6 lower than PLACEBO ( ES -1.58 , p = 0.02 ) . Similarly , at week 6 , TFS was significantly improved in IRON vs. PLACEBO ( ES –1.54 , p = 0.05 ) . There were no significant improvements in 3,000 m time in either group ( Week 0 vs. Week 4 ; Iron : 625.6±55.5 s vs. 625.4±52.7 s ; PLACEBO : 624.8±47.2 s vs. 639.1±59.7 s ) ; but IRON reduced their average time for the 10 × 400 m training session at week 2 ( Week 0 : 78.0±6.6 s , Week 2 : 77.2±6.3 ; ES–0.20 , p = 0.004 ) . Conclusion During 6 weeks of training , intravenous iron supplementation improved perceived fatigue and mood of trained athletes with no clinical iron deficiency , without concurrent improvements in oxygen transport capacity or performance", "BACKGROUND This trial evaluated the efficacy and safety of intravenous ( IV ) iron isomaltoside ( Monofer ) in comparison with placebo in first-time female blood donors . STUDY DESIGN AND METHODS The trial was a prospect i ve , double blind , placebo-controlled , r and omized , comparative , single-center trial of 85 first-time female blood donors . The subjects were r and omly assigned 1:1 to either 1000 mg IV iron isomaltoside infusion or placebo . The primary endpoint of the trial was change in hemoglobin ( Hb ) from baseline to right before the third blood donation . RESULTS The increase in Hb was significantly higher for iron isomaltoside compared with placebo right before both the second blood donation ( p = 0.0327 ) and the third blood donation ( primary endpoint , p iron-related variables ( plasma iron , plasma ferritin , transferrin saturation , and reticulocyte count ) in favor of iron isomaltoside were also observed . The trial was not powered on patient-reported outcomes . However , improvements in iron stores and Hb levels after iron isomaltoside administration were supported by the fact that several of the fatigue symptoms scores showed numerical differences in favor of iron isomaltoside . There were no differences in side effects between the groups . CONCLUSION In iron-deficient female blood donors a single IV iron isomaltoside administration result ed in an improvement in Hb concentration and iron stores and demonstrated a favorable safety profile comparable to placebo", "Objective : To determine if preoperative intravenous ( IV ) iron improves outcomes in abdominal surgery patients . Summary Background Data : Preoperative iron deficiency anemia ( IDA ) occurs frequently ; however if left untreated , increases the risk of blood transfusion allogeneic blood transfusion ( ABT ) . Limited evidence supports IDA treatment with preoperative IV iron . This r and omized controlled trial aim ed to determine whether perioperative IV iron reduced the need for ABT . Methods : Between August 2011 and November 2014 , 72 patients with IDA were assigned to receive either IV iron or usual care . The primary endpoint was incidence of ABT . Secondary endpoints were various hemoglobin ( Hb ) levels , change in Hb between time points , length of stay , iron status , morbidity , mortality , and quality of life 4 weeks postsurgery . Results : A 60 % reduction in ABT was observed in the IV iron group compared with the usual care group ( 31.25 % vs 12.5 % ) . Hb values , although similar at r and omization , improved by 0.8 g/dL with IV iron compared with 0.1 g/dL with usual care ( P = 0.01 ) by the day of admission . The IV iron group had higher Hb 4 weeks after discharge compared with the usual care group ( 1.9 vs 0.9 g/dL , P = 0.01 ) , and a shorter length of stay ( 7.0 vs 9.7 d , P = 0.026 ) . There was no difference in discharge Hb levels , morbidity , mortality , or quality of life . Conclusions : Administration of perioperative IV iron reduces the need for blood transfusion , and is associated with a shorter hospital stay , enhanced restoration of iron stores , and a higher mean Hb concentration 4 weeks after surgery", "OBJECTIVE There have been three r and omized , placebo-controlled , double-blind studies of intravenous iron in restless legs syndrome ( RLS ) , with differing outcomes . The one positive study used ferric carboxymaltose ( FCM ) at a total dose of 1000 mg . The purpose of this study was to replicate and extend the findings from the prior FCM study . METHODS Non-anemic , idiopathic RLS patients were enrolled in a r and omized , double-blinded , placebo-controlled study and received either 1000 mg FCM or placebo as a single infusion ( phase I ) . Subjects were off any RLS medications for at least two weeks prior to baseline assessment . The primary outcome variable was change from baseline at week 6 on the International Restless Legs Syndrome Severity ( IRLSS ) scale and a subject-completed , visual analog scale ( VAS ) of severity . Phase II of the study involved long-term ( 30 weeks ) follow-up after completion of the six-week efficacy phase . RESULTS At week 6 postinfusion , FCM compared to placebo recipients showed significantly greater change from baseline for both primary outcome measures ( IRLSS scale , -11.9 ± 8.04 vs -7.88 ± 5.89 , p = 0.03 ; VAS , -40.6 ± 22.7 vs -21.3 ± 20.0 , p = 0.001 ) . None of the secondary outcome variables showed a significant difference at week 6 . After six weeks of treatment , the FCM group had 19 ( 59.4 % ) responders , of which 12 had IRLSS scores 32 subjects treated with iron in phase I remained free of further RLS medications at 30 weeks . There were no serious adverse events observed in this study . CONCLUSION Two studies now support the value of FCM treatment both in the short term ( six weeks ) and long term ( 30 weeks ) for improving RLS symptoms ", "This is the first study to investigate the efficacy of intravenous iron in treating fatigue in nonanemic patients with low serum ferritin concentration . In a r and omized , double-blinded , placebo-controlled study , 90 premenopausal women presenting with fatigue , serum ferritin ≤ 50 ng/mL , and hemoglobin ≥ 120 g/L were r and omized to receive either 800 mg of intravenous iron (III)-hydroxide sucrose or intravenous placebo . Fatigue and serum iron status were assessed at baseline and after 6 and 12 weeks . Median fatigue at baseline was 4.5 ( on a 0 - 10 scale ) . Fatigue decreased during the initial 6 weeks by 1.1 in the iron group compared with 0.7 in the placebo group ( P = .07 ) . Efficacy of iron was bound to depleted iron stores : In patients with baseline serum ferritin ≤ 15 ng/mL , fatigue decreased by 1.8 in the iron group compared with 0.4 in the placebo group ( P = .005 ) , and 82 % of iron-treated compared with 47 % of placebo-treated patients reported improved fatigue ( P = .03 ) . Drug-associated adverse events were observed in 21 % of iron-treated patients and in 7 % of placebo-treated patients ( P = .05 ) ; none of these events was serious . Intravenous administration of iron improved fatigue in iron-deficient , nonanemic women with a good safety and tolerability profile . The efficacy of intravenous iron was bound to a serum ferritin concentration ≤ 15 ng/mL. This study was registered at the International St and ard R and omized Controlled Trial Number Register ( www.is rct n.org ) as IS RCT N78430425", "Background Unexplained fatigue is often left untreated or treated with antidepressants . This r and omized , placebo-controlled , single-blinded study evaluated the efficacy and tolerability of single-dose intravenous ferric carboxymaltose ( FCM ) in iron-deficient , premenopausal women with symptomatic , unexplained fatigue . Methods Fatigued women ( Piper Fatigue Scale [ PFS ] score ≥5 ) with iron deficiency ( ferritin and , blinded to the study drug and r and omized ( computer-generated r and omization sequence ) to a single FCM ( 1000 mg iron ) or saline ( placebo ) infusion . Primary endpoint was the proportion of patients with reduced fatigue ( ≥1 point decrease in PFS score from baseline to Day 56 ) . Results The full analysis included 290 women ( FCM 144 , placebo 146 ) . Fatigue was reduced in 65.3 % ( FCM ) and 52.7 % ( placebo ) of patients ( OR 1.68 , 95%CI 1.05–2.70 ; p = 0.03 ) . A 50 % reduction of PFS score was achieved in 33.3 % FCM- vs. 16.4 % placebo-treated patients ( p had hemoglobin levels ≥120 g/L ( vs. 87 % at baseline ) ; with placebo , the proportion decreased from 86 % to 81 % . Mental quality -of-life ( SF-12 ) and the cognitive function scores improved better with FCM . ‘ Power of attention ’ improved better in FCM-treated patients with ferritin µg/L. Treatment-emergent adverse events ( placebo 114 , FCM 209 ; most frequently headache , nasopharyngitis , pyrexia and nausea ) were mainly mild or moderate . Conclusion A single infusion of FCM improved fatigue , mental quality -of-life , cognitive function and erythropoiesis in iron-deficient women with normal or borderline hemoglobin . Although more side effects were reported compared to placebo , FCM can be an effective alternative in patients who can not tolerate or use oral iron , the common treatment of iron deficiency . Overall , the results support the hypothesis that iron deficiency can affect women ’s health , and a normal iron status should be maintained independent of hemoglobin levels . Trial Registration Clinical Trials.gov", "Background : Secondary thrombocytosis is a common clinical feature . In patients with cancer , it is a risk factor for venous thromboembolic events . In inflammatory bowel disease ( IBD ) , thrombocytosis is so far considered a marker of active disease and may contribute to the increased thromboembolic risk in this population . Observed effects of iron therapy on normalization of platelet counts led us to hypothesize that iron itself may regulate megakaryopoiesis . Here , we want to test the effect of iron replacement on platelet count and activity in IBD-associated thrombocytosis . Methods : We performed a r and omized , single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose ( FCM ) in patients with IBD with secondary thrombocytosis ( platelets > 450 G/L ) . Changes in platelet counts , hemoglobin , iron parameters , disease activity , megakaryopoietic growth factors , erythropoietin , and platelet activity were assessed . Patients received placebo or up to 1500 mg iron as FCM . Endpoints were evaluated at week 6 . Results : A total of 26 patients were included in the study , 15 patients were available for the per protocol analysis . A drop in platelets > 25 % ( primary endpoint ) was observed in 4 of 8 ( 50 % , iron group ) and 1 of 7 patients ( 14 % , placebo group , P = 0.143 ) . Mean platelet counts dropped on FCM but not on placebo ( 536 G/L to 411 G/L versus 580 G/L to 559 G/L ; P = 0.002 ) . Disease activity and megakaryopoietic growth factors remained unchanged and hemoglobin and iron parameters increased on FCM . The normalization of platelet counts was associated with a decrease in platelet aggregation and P-selectin expression . Conclusion : FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis", "CONTEXT Hypoxia is a major cause of pulmonary hypertension in respiratory disease and at high altitude . Recent work has established that the effect of hypoxia on pulmonary arterial pressure may depend on iron status , possibly acting through the transcription factor hypoxia-inducible factor , but the pathophysiological and clinical importance of this interaction is unknown . OBJECTIVE To determine whether increasing or decreasing iron availability modifies altitude-induced hypoxic pulmonary hypertension . DESIGN , SETTING , AND PARTICIPANTS Two r and omized , double-blind , placebo-controlled protocol s conducted in October-November 2008 . In the first protocol , 22 healthy sea-level resident men ( aged 19 - 60 years ) were studied over 1 week of hypoxia at Cerro de Pasco , Peru ( altitude 4340 m ) . In the second protocol , 11 high-altitude resident men ( aged 30 - 59 years ) diagnosed with chronic mountain sickness were studied over 1 month of hypoxia at Cerro de Pasco , Peru . INTERVENTION In the first protocol , participants received intravenous infusions of Fe(III)-hydroxide sucrose ( 200 mg ) or placebo on the third day of hypoxia . In the second protocol , patients underwent staged isovolemic venesection of 2 L of blood . Two weeks later , patients received intravenous infusions of Fe(III)-hydroxide sucrose ( 400 mg ) or placebo , which were subsequently crossed over . MAIN OUTCOME MEASURE Effect of varying iron availability on pulmonary artery systolic pressure ( PASP ) assessed by Doppler echocardiography . RESULTS In the sea-level resident protocol , approximately 40 % of the pulmonary hypertensive response to hypoxia was reversed by infusion of iron , which reduced PASP by 6 mm Hg ( 95 % confidence interval [ CI ] , 4 - 8 mm Hg ) , from 37 mm Hg ( 95 % CI , 34 - 40 mm Hg ) to 31 mm Hg ( 95 % CI , 29 - 33 mm Hg ; P = .01 ) . In the chronic mountain sickness protocol , progressive iron deficiency induced by venesection was associated with an approximately 25 % increase in PASP of 9 mm Hg ( 95 % CI , 4 - 14 mm Hg ) , from 37 mm Hg ( 95 % CI , 30 - 44 mm Hg ) to 46 mm Hg ( 95 % CI , 40 - 52 mm Hg ; P = .003 ) . During the subsequent crossover period , no acute effect of iron replacement on PASP was detected . CONCLUSION Hypoxic pulmonary hypertension may be attenuated by iron supplementation and exacerbated by iron depletion . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00952302", "Abstract Objective . Iron isomaltoside 1000 ( Monofer ® ) is a high-dose intravenous ( IV ) iron , which in a recent 8 weeks trial in inflammatory bowel disease ( IBD ) subjects with iron deficiency anemia ( IDA ) demonstrated good tolerability and efficacy . The present trial is an extension to this trial , which evaluates the need for additional high IV iron doses to maintain a stable hemoglobin ( Hb ) ≥12.0 g/dl . Material and methods . This was a prospect i ve , open-label , 12 months trial of European IBD subjects willing to participate after completing the lead-in trial . Subjects were allowed re-dosing with 500–2000 mg single doses of iron isomaltoside 1000 infused over ∼15 min at 3 months intervals depending on a predefined algorithm . Outcome measures included Hb , safety parameters and need for additional iron dosing . Results . A total of 39 subjects were enrolled of which 34 subjects required re-dosing with a median cumulative 1-year dose of 1.8 g ( mean cumulative dose 2.2 g ) . The mean ( SD ) Hb was 12.3 ( 1.5 ) g/dl at baseline , 12.8 ( 1.6 ) g/dl at 3 months , 12.8 ( 1.6 ) g/dl at 6 months , 12.9 ( 1.4 ) g/dl at 9 months and 12.9 ( 1.6 ) g/dl at 12 months . Seventy-four percent of subjects who had an Hb ≥12.0 g/dl at baseline were able to maintain Hb ≥12.0 g/dl till the end of the trial at 12 months . Nonserious probably related hypersensitivity reactions without significant hypotension were reported at the beginning of the infusion in two subjects , who recovered without sequelae . Conclusion . Repeated treatment of iron deficiency with iron isomaltoside 1000 could avoid episodes of IDA without major safety issues . Trial registration : Clinical Trial.gov identifier : NCT01410435", "Background Restless legs syndrome ( RLS ) is a common disorder in hemodialysis ( HD ) patients that causes sleep disturbances and diminished quality of life . Because iron deficiency has been implicated in the pathogenesis of RLS , we sought to investigate the effects of intravenous ( IV ) iron sucrose on symptoms of RLS in HD patients . Material / Methods The study was a r and omized , placebo-controlled study of 1000 mg iron sucrose versus normal saline as placebo . Patients were evaluated at baseline and 2 weeks after the last injection . The severity of RLS was assessed using the International RLS Study Group rating scale ( IRLS ) . Blood sample s were taken to measure iron parameters reflecting the iron status , including serum ferritin ( SF ) concentration , percentage transferrin saturation ( TSAT% ) and hemoglobin ( Hb ) , and other biochemical parameters as safety assessment s , including creatinine ( Cr ) , urea , intact parathyroid hormone ( iPTH ) , and the index of urea clearance ( Kt/V ) . Adverse events were monitored in all subjects during the period of infusion . Results After 2 weeks , IRLS scores decreased more in the IV-iron group ( −7.38±2.03 ) than in the placebo group ( −0.81±2.61 ) ( P=0.000 ) . Serum ferritin , TSAT , and hemoglobin increased more in the IV-iron group ( 227.63±77.64 μg/L ; 26.06±7.77 % ; 13.98±3.62g/L , respectively ) than in the placebo group ( SF , p=0.000 ; TSAT , p=0.000 ; Hb , p=0.000 , respectively ) . There were no significant differences between IV-iron and placebo groups in Cr , urea , iPTH , and Kt/V. No adverse effects were observed in the study . Conclusions IV iron sucrose is a safe and effective treatment for reducing RLS symptoms in HD patients over the short-term", "Background : It is intriguing and imperative that the comparison of the iron preparations in hemodialysis ( HD ) patients . This study aim ed to observe the short-term efficacy of parenteral iron sucrose and ferric chloride in HD patients . Material s and Methods : This was a consecutive 10-week single-blind study in Taiwan . An intravenous iron supplement of 100 mg/week was administered as an infusion in 100 ml of normal saline , until a total dose of 1000 mg was achieved . The primary outcome was evaluated by the changes in serum hematocrit ( Hct ) levels . The changes in serum Hct and iron indices were evaluated every 2 weeks for 10 weeks . The results were collected from 21 April to 4 July 2013 . Results : A total of 56 HD patients completed the study . Subjects were r and omized into an iron sucrose group ( 26 patients ) and a ferric chloride group ( 30 patients ) . Between the two treatment groups , there were no statistically significant differences in the change in serum Hct , ferritin , iron , or total iron binding capacity ( P > 0.05 ) . In the iron sucrose group , the increase in Hct levels was statistically significant at weeks 4 , 8 , and 10 . In the ferric chloride group , the increase in Hct levels was statistically significant at week 8 . No obvious major side effects were observed in both groups . Conclusion : In the study subjects , parenteral iron sucrose was as effective and safe as ferric chloride for treating anemia in HD patients", "Aims Patients with chronic heart failure ( CHF ) show impaired health-related quality of life ( HRQoL ) , an important target for therapeutic intervention . Impaired iron homeostasis may be one mechanism underlying the poor physical condition of CHF patients . This detailed sub analysis of the previously published FAIR-HF study evaluated baseline HRQoL in iron-deficient patients with CHF and the effect of intravenous ferric carboxymaltose ( FCM ) on HRQoL. Methods and results FAIR-HF r and omized 459 patients with reduced left ventricular ejection fraction and iron deficiency , with or without anaemia , to FCM or placebo ( 2:1 ) . Health-related quality of life was assessed at baseline and after 4 , 12 , and 24 weeks of therapy using the generic EQ-5D question naire and disease-specific Kansas City Cardiomyopathy Question naire ( KCCQ ) . Baseline mean Visual Analogue Scale ( VAS ) score was 54.3 ± 16.4 and KCCQ overall summary score was 52.4 ± 18.8 . Ferric carboxymaltose significantly improved VAS and KCCQ ( mean differences from baseline in KCCQ overall , clinical and total symptom scores , P 0.001 vs. placebo ) at all time points . At Week 24 , significant improvement vs. placebo was observed in four of the five EQ-5D dimensions : mobility ( P= 0.004 ) , self-care ( P , pain/discomfort ( P= 0.006 ) , anxiety/depression ( P= 0.012 ) , and usual activity ( P= 0.035 ) . Ferric carboxymaltose improved all KCCQ domain mean scores from Week 4 onward ( P≤ 0.05 ) , except for self-efficacy and social limitation . Effects were present in both anaemic and non-anaemic patients . Conclusions HRQoL is impaired in iron-deficient patients with CHF . Intravenous FCM significantly improved HRQoL after 4 weeks , and throughout the remaining study period . The positive effects of FCM were independent of anaemia status", "Background and Objectives This trial explores whether intravenous iron isomaltoside 1000 ( Monofer ® ) results in a better regeneration of haemoglobin levels and prevents anaemia compared to placebo in preoperative non-anaemic patients undergoing cardiac surgery . Study Design and Methods The trial is a prospect i ve , double-blind , comparative , placebo-controlled trial of 60 non-anaemic patients undergoing cardiac surgery . The patients were r and omized 1:1 to either 1000 mg intravenous iron isomaltoside 1000 administered perioperatively by infusion or placebo . Results Mean preoperative haemoglobin in the active treatment group was 14·3 g/dl vs. 14·0 g/dl in the placebo group . At discharge 5 days after surgery , haemoglobin levels were reduced to 10·7 and 10·5 g/dl , respectively . One month after surgery , haemoglobin concentration had increased to an average of 12·6 g/dl vs. 11·8 g/dl ( p = 0·012 ) and significantly more patients were non-anaemic in the intravenous iron isomaltoside 1000-treated group compared to the placebo group ( 38·5 % vs. 8·0 % ; p = 0·019 ) . There were no differences in side-effects between the groups . Conclusion A single perioperative 1000 mg dose of intravenous iron isomaltoside 1000 significantly increased the haemoglobin level and prevented anaemia 4 weeks after surgery , with a short-term safety profile similar to placebo . Future trials on potential clinical benefits of preoperative treatment with intravenous iron in non-anaemic patients are needed", "BACKGROUND Diagnosis of iron deficiency in hemodialysis patients is limited by the inaccuracy of commonly used tests . Reticulocyte hemoglobin content ( CHr ) is a test that has shown promise for improved diagnosis in preliminary studies . The purpose of this study was to compare iron management guided by serum ferritin and transferrin saturation to management guided by CHr . METHODS A total of 157 hemodialysis patients from three centers were r and omized to iron management based on ( group 1 ) serum ferritin and transferrin saturation , or ( group 2 ) CHr . Patients were followed for six months . Treatment with intravenous iron dextran , 100 mg for 10 consecutive treatments was initiated if ( group 1 ) serum ferritin final mean hematocrit or epoetin dose . The mean weekly dose of iron dextran was 47.7 + /- 35.5 mg in group 1 compared to 22.9 + /- 20.5 mg in group 2 ( P = 0.02 ) . The final mean serum ferritin was 399.5 + /- 247.6 ng/mL in group 1 compared to 304.7 + /- 290.6 ng/mL in group 2 ( P final TSAT or CHr . Coefficient of variation was significantly lower for CHr than serum ferritin and transferrin saturation ( 3.4 % vs. 43.6 % and 39.5 % , respectively ) . CONCLUSIONS CHr is a markedly more stable analyte than serum ferritin or transferrin saturation , and iron management based on CHr results in similar hematocrit and epoetin dosing while significantly reducing IV iron exposure", "Background Intravenous iron therapy is a treatment option for iron deficient patients who are intolerant to oral iron or where oral iron is ineffective , but with possible adverse effects . Currently , prospect i ve studies comparing different intravenous iron formulations are needed to determine safety and efficacy of these agents . Methods We conducted a prospect i ve , double-blind , r and omized controlled trial ( RCT ) to assess the feasibility of a trial comparing the safety of high molecular weight intravenous iron dextran , Infufer ® , with intravenous iron sucrose , Venofer ® , in non-hemodialysis adult out patients . Primary outcome was the occurrence of immediate severe drug reactions . Results We enrolled 143 patients in a one-year period . Overall , 45/143 ( 31.5 % ) patients ( 20 iron dextran , 25 iron sucrose ) developed 48 infusion reactions ( 14 immediate , 28 delayed , and 3 both ) . The risk of an immediate reaction was similar in both groups , 9/73 ( 12.3 % ) iron dextran versus 8/70 ( 11.4 % ) iron sucrose , RR = 0.93 ( 95 % CI ; 0.38 to 2.27 ) . The risk of a delayed reaction was significantly higher in the iron sucrose group 22/70 ( 31.4 % ) versus the iron dextran group 9/73 ( 12.3 % ) , RR = 2.55 ( 95 % CI ; 1.26 to 5.15 ; p = 0.0078 ) . Conclusion In this limited feasibility study , no major differences in immediate reactions were seen , but a significantly higher number of delayed reactions were seen in the iron sucrose group . Further , under our assumptions and design a full RCT to evaluate the safety of different intravenous iron preparations is not feasible . Future studies should consider modifying the clinical outcomes , utilize multiple centers , and consider other emerging parenteral iron formulations . ( Clinical Trials.gov NCT005936197 January 3 , 2008 )", "OBJECTIVE Intravenous ( IV ) iron has been used as a treatment to reduce Restless Legs Syndrome ( RLS ) symptoms , but two double-blinded trials of a frequently prescribed IV iron formulation , iron sucrose , failed to show lasting efficacy . This study evaluates efficacy and safety of a new IV iron formulation ( ferric carboxymaltose , FCM ) with molecular properties that may make iron more available for uptake to the brain than iron sucrose does . METHODS In this 28-day , multi-centre , r and omised , placebo-controlled trial 46 RLS patients were discontinued from all RLS treatment . Twenty-four received 500 mg FCM in two doses 5 days apart and 22 received a matching placebo . At day 28 , those on placebo were given a single 1000 mg IV FCM and those not responding to initial treatment were given a third dose of 500 mg FCM . Patients were followed up for 24 weeks or until needing added RLS treatment . RESULTS FCM significantly improved primary and secondary outcomes compared to placebo : International Restless Legs Syndrome study group severity scale ( IRLS ) average ( SD ) decrease of 8.9 ( 8.52 ) versus 4.0 ( 6.11 ) , p=0.040 ; Clinical Global Inventory of Change ( CGI-1 ) very much or much improved 48.3 % versus 14.3 % , p=0.004 . Quality of life was also significantly improved . Of the 24 with initial iron treatment 45 % responded and 29 % remitted ( IRLS ≤ 10 ) at day 28 , and 25 % continued free of other RLS medications at 24 weeks after treatment . The single 1000 mg dose on day 28 produced the same degree of treatment response as the divided dose , but the added 500 mg dose for those not responding to the initial treatment showed little benefit . There were no significant adverse events . CONCLUSIONS IV FCM provided a safe and effective treatment for RLS that lasted for at least 24 weeks for some patients . Larger studies are needed to confirm these results", "BACKGROUND Anemia in heart failure patients and has been associated with increased morbi-mortality . Previous studies have treated anemia in heart failure patients with either erythropoietin alone or combination of erythropoietin and intravenous ( i.v . ) iron . However , the effect of i.v . or oral ( p.o . ) iron supplementation alone in heart failure patients with anemia was virtually unknown . AIM To compare , in a double-blind design , the effects of i.v . iron versus p.o . iron in anemic heart failure patients . METHODS IRON-HF study was a multicenter , investigator initiated , r and omized , double-blind , placebo controlled trial that enrolled anemic heart failure patients with preserved renal function , low transferrin saturation ( TSat ) and low-to-moderately elevated ferritin levels . Interventions were Iron Sucrose i.v . 200 mg , once a week , for 5 weeks , ferrous sulfate 200 mg p.o . TID , for 8 weeks , or placebo . Primary endpoint was variation of peak oxygen consumption ( peak VO2 ) assessed by ergospirometry over 3 month follow-up . RESULTS Eighteen patients had full follow-up data . There was an increment of 3.5 ml/kg/min in peak VO2 in the i.v . iron group . There was no increment in peak VO2 in the p.o . iron group . Patients ' ferritin and TSat increased significantly in both treated groups . Hemoglobin increased similarly in all groups . CONCLUSION I.v . iron seems to be superior in improving functional capacity of heart failure patients . However , correction of anemia seems to be at least similar between p.o . iron and i.v . iron supplementation", "Iron deficiency may exacerbate symptoms in the Restless Legs Syndrome ( RLS ) . We investigated the effect of intravenous iron sucrose or placebo on symptoms in patients with RLS and mild to moderate iron deficit . Sixty patients with primary RLS ( seven males , age 46 ( 9 ) years , S-ferritin r and omly assigned in a 12-months double-blind , multi-centre study of iron sucrose 1000 mg ( n = 29 ) or saline ( n = 31 ) . The primary efficacy variable was the RLS severity scale ( IRLS ) score at week 11 . Median IRLS score decreased from 24 to 7 ( week 11 ) after iron sucrose and from 26 to 17 after placebo ( P = 0.123 , N.S. for between treatment comparison ) . The corresponding scores at week 7 were 12 and 20 in the two groups ( P = 0.017 ) . Drop out rate because of lack of efficacy at 12 months was 19/31 after placebo and 5/29 patients after iron sucrose ( Kaplan-Meier estimate , log rank test P = 0.0006 ) suggesting an iron induced superior long term RLS symptom control . Iron sucrose was well tolerated . This study showed a lack of superiority of iron sucrose at 11 weeks but found evidence that iron sucrose reduced RLS symptoms both in the acute phase ( 7 weeks ) and during long-term follow up in patients with variable degree of iron deficiency . Further studies on target patient groups , dosing and dosing intervals are warranted before iron sucrose could be considered for treatment of iron deficient patients with RLS", "BACKGROUND AND OBJECTIVE Non-anaemic iron deficiency ( NAID ) might alter the oxygen pathway in health and disease . The current study aims at assessing the impact of NAID on aerobic capacity in patients with chronic obstructive pulmonary disease ( COPD ) . METHODS A prospect i ve sample of 70 non-anaemic COPD patients c and i date to participate in an 8-week pulmonary rehabilitation ( PR ) programme was studied . Incremental cycling exercise to peak oxygen uptake ( V'O2peak ) and constant work-rate exercise at 80 % V'O2peak to exhaustion were assessed pre- and post-PR . Training-induced increase of endurance time ( ET ) ≥33 % , which represented the minimal clinical ly important difference , classified patients as responders to exercise training . RESULTS The prevalence of NAID was 48 % ( n = 34 ) showing no relationship with the Global Initiative for Chronic Obstructive Lung Disease stages ( P = 0.209 ) . Patients with NAID showed lower pre-training ET ( P = 0.033 ) and V'O2peak ( P = 0.007 ) than normal iron status ( NIS ) patients after adjustment for potential covariates . Significant training-induced physiological changes were seen in the NIS group ( ΔV'O2peak 68(132 ) mL/min ; P = 0.009 ) , but not in the NAID group ( ΔV'O2peak 26 ( 126 ) mL/min ; P = 0.269 ) . The NAID group showed lower percentage of responders to training ( 56 % ) than the NIS group ( 78 % ) ( P = 0.041 ) . CONCLUSIONS COPD patients with NAID showed lower pre-training aerobic capacity and reduced training-induced response than NIS patients after adjusting for potential confounding variables", "Abstract Objective : Parenteral sodium ferric gluconate in complex ( Ferrlecit [ br and ed SFG ] ) is used to treat patients with iron deficiency anemia undergoing chronic hemodialysis and receiving supplemental epoetin . This comparative pharmacokinetic study ( GeneraMedix , Inc. , Study 17909 ) evaluates whether the recently approved generic product Nulecit ( generic SFG ) and the br and ed product Ferrlecit ( br and ed SFG ) are bioequivalent . Methods : In this open-label study , 240 healthy volunteers in a fasting state were assigned r and omly to a single 10-min intravenous ( IV ) infusion of 125 mg of generic or br and ed SFG . Total and transferrin-bound iron concentrations were determined for the 36-h period after infusion and corrected for pretreatment levels . Maximum concentration ( Cmax ) and area under the concentration – time curve of 0 to 36 h ( AUC[0–36 ] ) were compared between the two products . Demonstration of bioequivalence required that the 90 % confidence intervals of each parameter evaluated for generic SFG were within 80 % to 125 % of the corresponding values for br and ed SFG . Results : Uncorrected and baseline-corrected mean serum concentrations of total serum iron during the 36-h assessment period were similar for generic and br and ed SFG . For total serum iron , the geometric mean ratios of corrected Cmax and AUC[0–36 ] were 100 % . For transferrin-bound iron , the geometric mean ratios were 87 % for corrected Cmax and 92 % for corrected AUC[0–36 ] . All associated 90 % confidence intervals were within the range of 80 % to 125 % . Conclusions : A new generic SFG in complex for IV infusion is bioequivalent to the br and ed SFG in complex for IV infusion . The generic SFG is AB rated by the FDA and considered therapeutically equivalent to the br and ed product", "Purpose Both anaemia and allogenic red blood cell transfusion are common and potentially harmful in patients admitted to the intensive care unit . Whilst intravenous iron may decrease anaemia and RBC transfusion requirement , the safety and efficacy of administering iron intravenously to critically ill patients is uncertain . Methods The multicentre , r and omized , placebo-controlled , blinded Intravenous Iron or Placebo for Anaemia in Intensive Care ( IRONMAN ) study was design ed to test the hypothesis that , in anaemic critically ill patients admitted to the intensive care unit , early administration of intravenous iron , compared with placebo , reduces allogeneic red blood cell transfusion during hospital stay and increases the haemoglobin level at the time of hospital discharge . Results Of 140 patients enrolled , 70 were assigned to intravenous iron and 70 to placebo . The iron group received 97 red blood cell units versus 136 red blood cell units in the placebo group , yielding an incidence rate ratio of 0.71 [ 95 % confidence interval ( 0.43–1.18 ) , P = 0.19 ] . Overall , median haemoglobin at hospital discharge was significantly higher in the intravenous iron group than in the placebo group [ 107 ( interquartile ratio IQR 97–115 ) vs. 100 g/L ( IQR 89–111 ) , P = 0.02 ] . There was no significant difference between the groups in any safety outcome . Conclusions In patients admitted to the intensive care unit who were anaemic , intravenous iron , compared with placebo , did not result in a significant lowering of red blood cell transfusion requirement during hospital stay . Patients who received intravenous iron had a significantly higher haemoglobin concentration at hospital discharge . The trial was registered at http://www.anzctr.org.au as # ACTRN12612001249842", "This investigation examined the effect of intramuscular iron injections on aerobic-exercise performance in iron-deficient women . Sixteen athletes performed a 10-min steady-state submaximal economy test , a VO2max test , and a timed test to exhaustion at VO2max workload . Subjects were r and omly assigned to an iron-supplemented group ( IG ) receiving intramuscular iron injections or to a placebo group ( PG ) . Twenty days after the first injection , exercise and blood testing were repeated . A final blood test occurred on Day 28 . Post supplementation , no differences were found between the groups ' submaximal or maximal VO2 , heart rate , or blood lactate ( P > 0.05 ) . Time to exhaustion was increased in the IG ( P 0.05 ) . The IG 's serum ferritin ( SF ) was significantly increased on Days 20 and 28 ( mean + /- st and ard error : 19 + /- 3 to 65 + /- 11 to 57 + /- 12 microg/L ; P SF without enhancing submaximal or maximal aerobic-exercise performance in iron-depleted female athletes", "BACKGROUND Restless legs syndrome ( RLS ) is a common disorder in patients with end-stage renal disease ( ESRD ) that causes motor agitation and insomnia . Because RLS has been associated with iron deficiency , we sought to investigate the effects of intravenous ( IV ) iron dextran on symptoms of RLS in a double-blind placebo-controlled trial . METHODS Patients determined to have RLS by International RLS Study Group criteria were administered either iron dextran , 1,000 mg , or normal saline IV in a blinded fashion . Patient demographic data were collected , and blood chemistry tests , liver function studies , serum iron levels , ferritin levels , and total iron-binding capacity were obtained at baseline and 1 , 2 , and 4 weeks postinfusion . Side effects or adverse events to interventions were monitored , and RLS symptoms were assessed by a rating scale at the same intervals . RESULTS Eleven patients were r and omly assigned to the administration of iron dextran , and 14 patients to the administration of saline . RLS severity scores were slightly higher in the placebo group at baseline , but hemoglobin levels , iron stores , and other biochemical parameters did not differ . Although no change in symptoms were seen in the placebo-treated group , significant improvement in RLS symptom scores in response to iron dextran was seen 1 week after infusion ( -2 ; interquartile range [ IQR ] , -6 to -1 ; P = 0.03 , Wilcoxon 's rank sums ) , but was greatest at 2 weeks ( -3 ; IQR , -5 to -2 compared with -1 to 0 ; P = 0.01 ) . Salutary effects of iron persisted at 4 weeks , but were no longer statistically significant . The significant increase in serum ferritin levels and iron saturation observed in the iron dextran-treated group was not seen in the placebo-treated group . No differences in adverse events were noted between groups . CONCLUSION High-dose iron dextran infusion is associated with a significant , but transient , reduction in symptoms of RLS in patients with ESRD", "Abstract Background : Compromised iron status is important in restless legs syndrome pathophysiology . We compared the efficacy and tolerability of ferric carboxymaltose ( single intravenous dose ) versus placebo for restless legs syndrome treatment in iron‐deficient nonanemic patients . Methods : Patients with moderate to severe restless legs syndrome and serum ferritin were r and omized to ferric carboxymaltose ( 1000 mg iron ) or placebo . Mean change difference between ferric carboxymaltose and placebo in International Restless Legs Syndrome Severity Scale score from baseline to week 4 was the primary end point ; week 12 was a secondary end point . Results : Ferric carboxymaltose treatment ( n = 59 ) led to nonsignificant improvement over placebo ( n = 51 ) in International Restless Legs Syndrome Severity Scale score at week 4 ( difference [ 95 % confidence interval ] , ‐2.5 [ ‐5.93 to 1.02 ] , P = 0.163 ) , reaching significance by week 12 ( ‐4.66 [ ‐8.59 to ‐0.73 ] , P = 0.021 ) . Conclusions : In patients who responded to treatment , ferric carboxymaltose may require more time to stabilize restless legs syndrome than previously assumed . © 2017 The Authors . Movement Disorders published by Wiley Periodicals , Inc. on behalf of International Parkinson and Movement Disorder Society", "BACKGROUND Current guidelines to treat iron deficiency recommend daily provision of ferrous iron divided through the day to increase absorption . However , daily dosing and split dosing might increase serum hepcidin and decrease iron absorption from subsequent doses . Our study aim was to compare iron absorption from oral iron supplements given on consecutive versus alternate days and given as single morning doses versus twice-daily split dosing . METHODS We did two prospect i ve , open-label , r and omised controlled trials assessing iron absorption using (54Fe)-labelled , (57Fe)-labelled , or (58Fe)-labelled ferrous sulfate in iron-depleted ( serum ferritin ≤25 μg/L ) women aged 18 - 40 years recruited from ETH Zurich and the University of Zurich , Switzerl and . In study 1 , women were r and omly assigned ( 1:1 ) to two groups . One group was given 60 mg iron at 0800 h ( ±1 h ) on consecutive days for 14 days , and the other group was given the same doses on alternate days for 28 days . In study 2 , women were assigned to two groups , stratified by serum ferritin so that two groups with similar iron statuses could be formed . One group was given 120 mg iron at 0800 h ( ±1 h ) and the other was given the dose split into two divided doses of 60 mg at 0800 h ( ±1 h ) and 1700 h ( ±1 h ) for three consecutive days . 14 days after the final dose , the groups were each crossed over to the other regimen . Within-individual comparisons were done . The co- primary outcomes in both studies were iron bioavailability ( total and fractional iron absorption ) , assessed by measuring the isotopic label abundance in erythrocytes 14 days after administration , and serum hepcidin . Group allocations in both studies were not masked and primary and safety analyses were done on an intention-to-treat basis . The studies were registered at Clinical Trials.gov , numbers NCT02175888 ( study 1 ) and NCT02177851 ( study 2 ) and are complete . FINDINGS For study 1 , 40 women were enrolled on Oct 15 - 29 , 2015 . 21 women were assigned to the consecutive-day group and 19 to the alternate-day group . At the end of treatment ( 14 days for the consecutive-day group and 28 days for the alternate-day group ) , geometric mean ( -SD , + SD ) cumulative fractional iron absorptions were 16·3 % ( 9·3 , 28·8 ) in the consecutive-day group versus 21·8 % ( 13·7 , 34·6 ) in the alternate-day group ( p=0·0013 ) , and cumulative total iron absorption was 131·0 mg ( 71·4 , 240·5 ) versus 175·3 mg ( 110·3 , 278·5 ; p=0·0010 ) . During the first 14 days of supplementation in both groups , serum hepcidin was higher in the consecutive-day group than the alternate-day group ( p=0·0031 ) . In study 2 , 20 women were enrolled between Aug 13 and 18 , 2015 . Ten women were assigned to receive once-daily dosing and ten were assigned to receive twice-daily divided dosing . No significant differences were seen in fractional ( day 1 - 3 geometric mean : 11·8 % [ 7·1 , 19·4 ] once daily vs 13·1 % [ 8·2 , 20·7 ] twice daily ; p=0·33 ) or total iron absorption ( day 1 - 3 : 44·3 mg [ 29·4 , 66·7 ] once daily vs 49·4 [ 35·2 , 69·4 ] twice daily ; p=0·33 ) between the two dosing regimens . Twice-daily divided doses result ed in a higher serum hepcidin concentration than once-daily dosing ( p=0·013 ) . No grade 3 or 4 adverse events were reported in either study . INTERPRETATION In iron-depleted women , providing iron supplements daily as divided doses increases serum hepcidin and reduces iron absorption . Providing iron supplements on alternate days and in single doses optimises iron absorption and might be a preferable dosing regimen . These findings should be confirmed in iron-deficient anaemic patients . FUNDING Swiss National Science Foundation , Bern , Switzerl and", "Introduction This study sought to compare efficacy and safety of ferric carboxymaltose vs. placebo in iron-deficient patients with fibromyalgia . Methods This blinded , placebo-controlled , phase 2 study r and omized adults with fibromyalgia and Revised Fibromyalgia Impact Question naire ( FIQR ) scores ≥ 60 , ferritin levels receive ferric carboxymaltose [ 15 mg/kg ( up to 750 mg ) ] , or placebo ( 15 cc normal saline ) intravenously on study days 0 and 5 . Patients visited the clinic on days 14 , 28 , and 42 for efficacy and safety assessment s. The primary efficacy endpoint was proportion of patients with a ≥ 13-point improvement from baseline to day 42 in FIQR scale score . Secondary endpoints included changes from baseline in FIQR scale , Brief Pain Inventory ( BPI ) total score , Medical Outcomes Study ( MOS ) Sleep scale , Fatigue Visual Numeric Scale ( VNS ) , iron indices ( transferrin saturation and ferritin ) , and safety . Results The efficacy analysis group comprised 80 patients , and the safety analysis group comprised 81 . More ferric carboxymaltose patients ( 77 % ) vs. placebo patients ( 67 % ) achieved the primary endpoint , but the difference was not significant . Greater improvements from baseline to day 42 were observed for ferric carboxymaltose vs. placebo in FIQR total score , BPI total score , Fatigue VNS score , and iron indices . Mean changes in MOS Sleep scale scores were similar between groups . Ferric carboxymaltose was safe and well tolerated . Conclusions Compared with placebo , ferric carboxymaltose improved measures of fibromyalgia severity and was well tolerated . The current results suggest that ferric carboxymaltose shows benefit in iron-deficient patients with concurrent fibromyalgia . Funding Luitpold Pharmaceuticals , Inc . Trial Registration Clinical Trials.gov identifier , NCT02409459", "Intravenous ( iv ) iron administration is typically indicated in individuals who have iron deficiency refractory to oral iron . However , in certain chronic disease states , it may be beneficial to administer iv iron to individuals who are not strictly iron deficient . The purpose of this study was to define a dose-response relationship between clinical indices of iron status and modest loading with iv iron in healthy , iron-replete participants . This was a double-blind , controlled study involving 18 male participants . Participants were block r and omised 2:1 to the iron and saline ( control ) groups . Participants in the iron group received 250 mg of iv iron , once a month for six months , provided that their ferritin remained saline infusion , as did the control participants . Iron indices were measured monthly during the study . The pulmonary vascular response to sustained hypoxia and total hemoglobin mass were measured before , at three months ( hemoglobin mass only ) and at six months , as variables that may be affected by iron loading . Serum ferritin was robustly elevated by iv iron by 0.21 µg/L/mg of iron delivered ( 95 % CI : 0.15 - 0.26 µg/L/mg ) , but the effects on all other iron indices did not reach statistical significance . The pulmonary vascular response to sustained hypoxia was significantly suppressed by iron loading at six months , but the hemoglobin mass was unaffected . We conclude that the robust effect on ferritin provides a quantitative measure for the degree of iron loading in iron-replete individuals", "BACKGROUND Iron repletion augments exercise capacity in chronic heart failure ( HF ) , but there is a lack of mechanistic data explaining how iron could augment exercise performance despite minimal changes in hemoglobin ( Hb ) . Besides Hb , iron is an obligate component of mitochondrial enzymes that generate cellular energy in the form of adenosine triphosphate and phosphocreatine ( PCr ) . Dynamic phosphorus magnetic resonance spectroscopy is a noninvasive tool that quantifies in vivo muscle energetics by measuring the kinetics of PCr recovery after exertion . We tested the hypothesis that intravenous iron repletion in chronic HF enhances skeletal muscle energetics as reflected by shorter PCr recovery half-times ( PCr t1/2 ) on phosphorus magnetic resonance spectroscopy . METHODS We enrolled 40 patients ( 50 % anemic ) with chronic HF , New York Heart Association class ≥II , left ventricular ejection fraction ≤45 % , and iron deficiency ( ferritin Subjects underwent stratified ( anemic versus nonanemic ) r and omization ( 1:1 ) to a single , double-blinded , total dose infusion of iron isomaltoside or saline placebo with end points reassessed early at 2 weeks posttreatment to minimize confounding from exercise adaptation . The primary end point was PCr t1/2 at 2 weeks . Secondary end points included ADP recovery half-time ( ADP t1/2 ; energetic marker ) , iron status , symptoms , Hb , exercise capacity , and safety . RESULTS In the total population , treatment groups were similar at baseline . At 2 weeks , iron isomaltoside improved PCr t1/2 ( adjusted difference , -6.8 s ; 95 % CI , 11.5 to -2.1 ; P=0.006 ) , ADP t1/2 ( -5.3 s ; 95 % CI , -9.7 to -0.9 ; P=0.02 ) , ferritin ( 304 ng/mL ; 95 % CI , 217 - 391 ; P ) , transferrin saturation ( 6.8 % ; 95 % CI , 2.7 - 10.8 ; P=0.002 ) , New York Heart Association class ( -0.23 ; 95 % CI , -0.46 to -0.01 ; P=0.04 ) , resting respiratory rate ( -0.7 breaths/min ; 95 % CI , -1.2 to -0.2 ; P=0.009 ) , and postexercise Borg dyspnea score ( -2.0 ; 95 % CI , -3.7 to -0.3 ; P=0.04 ) , but not Hb ( 2.4 g/L ; 95 % CI , -3.5 to 8.4 ; P=0.41 ) . Adverse events were similar between groups . In subgroup analyses , iron isomaltoside improved PCr t1/2 in anemic ( -8.4 s ; 95 % CI , -16.7 to -0.2 ; P=0.04 ) and nonanemic ( -5.2 s ; 95 % CI , -10.6 to 0.2 ; P=0.06 ) cohorts . CONCLUSIONS In patients with chronic HF and iron deficiency , a total repletion dose of iron isomaltoside given at a single sitting is well tolerated and associated with faster skeletal muscle PCr t1/2 at 2 weeks , implying better mitochondrial function . Augmented skeletal muscle energetics might therefore be an important mechanism via which iron repletion confers benefits in chronic HF despite minimal Hb changes . CLINICAL TRIAL REGISTRATION URL : https://www . clinical trialsregister.eu/ctr- search /trial/2012 - 005592 - 13/GB . Unique identifier : EudraCT 2012 - 005592 - 13", "Iron deficiency is common in colorectal cancer . Despite perioperative guidelines advocating for the correction of non-anaemic iron deficiency prior to major surgery , the impact of this pathology on postoperative outcome is unclear . We conducted a single-centre , historical cohort study of 141 elective resections for colorectal cancer . We stratified non-anaemic patients into iron deficient and iron replete groups , and collected data on baseline characteristics , preoperative laboratory results , intraoperative events and postoperative outcomes . As this study was an exploratory work for future research , a P-value of 0.25 was considered relevant . Patients in the deficient group demonstrated lower baseline ferritin ( median ( interquartile range , IQR ) 76 ( 41–141 ) µg/L versus 207 ( 140–334 ) µg/L , P ) and transferrin saturation ( mean ( st and ard deviation , SD ) 18 % ( 8 % ) versus 32 % ( 12 % ) , P lower starting haemoglobin ( mean ( SD ) 138 ( 10 ) g/L versus 144 ( 12 ) g/L , P = 0.01 ) . The deficient group had increased re-admission ( 25 % ( 24 % ) versus 4 % ( 11 % ) , P = 0.15 ) and all-cause infection ( 25 % ( 24 % ) versus 5 % ( 14 % ) , P = 0.24 ) . A decrease of two days in days alive and out of hospital at postoperative day 90 was seen in the deficient group on univariate analysis ( median ( IQR ) 81 ( 75–84 ) versus 83 ( 78–84 ) , P = 0.25 ) . This reduced to 1.24 days in multivariate adjusted quantile regression analysis ( P = 0.22 ) . Days alive and out of hospital at day 90 , postoperative re-admission and postoperative infection may be meaningful outcome measures for future prospect i ve observational work examining non-anaemic iron deficiency in patients undergoing major surgery for colorectal cancer", "BACKGROUND Iron deficiency is frequent in patients undergoing cardiac surgery . The relevance of iron deficiency , however , is ill defined . Therefore , our study aim ed to investigate the impact of iron deficiency ( ferritin 730 patients undergoing elective cardiac surgery were assigned into four groups according to their iron status and anaemia . Mortality , serious adverse events ( SAEs ) , major cardiac and cerebrovascular events ( MACCEs ) , allogenic blood transfusion requirements , and length of hospital stay were assessed during a 90-day follow-up period . The effect of iron deficiency on these outcomes was first calculated in models adjusting for anaemia only , followed by two multivariate models adjusting for anaemia and either the EuroSCORE II or any possible confounders . RESULTS The presence of iron deficiency ( ferritin in 90-day mortality from 2 % to 5 % in patients without anaemia , and from 4 % to 14 % in patients with anaemia . Logistic regression result ed in an odds ratio of 3.5 ( 95 % confidence interval : 1.5 - 8.4 ) ; P=0.004 . The effect persisted in both multivariate models . Moreover , iron deficiency was associated with an increased incidence of SAEs , MACCEs , transfusion , and prolonged hospital stay . CONCLUSIONS Preoperative iron deficiency ( ferritin increased mortality , more SAEs , and prolonged hospital stay after cardiac surgery . These findings underline the importance of preoperative iron deficiency screening in the context of a comprehensive patient blood management programme , and highlight its importance as a research topic in cardiac surgery . CLINICAL TRIAL REGISTRATION NCT02031289", "OBJECTIVES We tested the hypothesis that intravenous iron improves exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure ( CHF ) and iron deficiency . BACKGROUND Anemia is common in heart failure . Iron metabolism is disturbed , and administration of iron might improve both symptoms and exercise tolerance . METHODS We r and omized 35 patients with CHF ( age 64 + /- 13 years , peak oxygen consumption [ pVO2 ] 14.0 + /- 2.7 ml/kg/min ) to 16 weeks of intravenous iron ( 200 mg weekly until ferritin > 500 ng/ml , 200 mg monthly thereafter ) or no treatment in a 2:1 ratio . Ferritin was required to be change in absolute pVO2 . RESULTS The difference ( 95 % confidence interval [ CI ] ) in the mean changes from baseline to end of study between the iron and control groups was 273 ( 151 to 396 ) ng/ml for ferritin ( p hemoglobin ( p = 0.9 ) , 96 ( -12 to 205 ) ml/min for absolute pVO2 ( p = 0.08 ) , 2.2 ( 0.5 to 4.0 ) ml/kg/min for pVO2/kg ( p = 0.01 ) , 60 ( -6 to 126 ) s for treadmill exercise duration ( p = 0.08 ) , -0.6 ( -0.9 to -0.2 ) for New York Heart Association ( NYHA ) functional class ( p = 0.007 ) , and 1.7 ( 0.7 to 2.6 ) for patient global assessment ( p = 0.002 ) . In anemic patients ( n = 18 ) , the difference ( 95 % CI ) was 204 ( 31 to 378 ) ml/min for absolute pVO2 ( p = 0.02 ) , and 3.9 ( 1.1 to 6.8 ) ml/kg/min for pVO2/kg ( p = 0.01 ) . In nonanemic patients , NYHA functional class improved ( p = 0.06 ) . Adverse events were similar . CONCLUSIONS Intravenous iron loading improved exercise capacity and symptoms in patients with CHF and evidence of abnormal iron metabolism . Benefits were more evident in anemic patients . ( Effect of Intravenous Ferrous Sucrose on Exercise Capacity in Chronic Heart Failure ; http://www . clinical trials.gov/ct/show/NCT00125996 ; NCT00125996 )", "Background : Iron deficiency is common in patients with heart failure ( HF ) and is associated with reduced exercise capacity and poor outcomes . Whether correction of iron deficiency with ( intravenous ) ferric carboxymaltose ( FCM ) affects peak oxygen consumption [ peak VO2 ] , an objective measure of exercise intolerance in HF , has not been examined . Methods : We studied patients with systolic HF ( left ventricular ejection fraction ⩽45 % ) and mild to moderate symptoms despite optimal HF medication . Patients were r and omized 1:1 to treatment with FCM for 24 weeks or st and ard of care . The primary end point was the change in peak VO2 from baseline to 24 weeks . Secondary end points included the effect on hematinic and cardiac biomarkers , quality of life , and safety . For the primary analysis , patients who died had a value of 0 imputed for 24-week peak VO2 . Additional sensitivity analyses were performed to determine the impact of imputation of missing peak VO2 data . Results : A total of 172 patients with HF were studied and received FCM ( n=86 ) or st and ard of care ( control group , n=86 ) . At baseline , the groups were well matched ; mean age was 64 years , 75 % were male , mean left ventricular ejection fraction was 32 % , and peak VO2 was 13.5 mL/min/kg . FCM significantly increased serum ferritin and transferrin saturation . At 24 weeks , peak VO2 had decreased in the control group ( least square means −1.19±0.389 mL/min/kg ) but was maintained on FCM ( −0.16±0.387 mL/min/kg ; P=0.020 between groups ) . In a sensitivity analysis , in which missing data were not imputed , peak VO2 at 24 weeks decreased by −0.63±0.375 mL/min/kg in the control group and by −0.16±0.373 mL/min/kg in the FCM group ; P=0.23 between groups ) . Patients ’ global assessment and functional class as assessed by the New York Heart Association improved on FCM versus st and ard of care . Conclusions : Treatment with intravenous FCM in patients with HF and iron deficiency improves iron stores . Although a favorable effect on peak VO2 was observed on FCM , compared with st and ard of care in the primary analysis , this effect was highly sensitive to the imputation strategy for peak VO2 among patients who died . Whether FCM is associated with an improved outcome in these high-risk patients needs further study . Clinical Trial Registration : URL : http://www . clinical trials.gov . Unique identifier : NCT01394562" ]

[ "AIMS Hydrotherapy , i.e. exercise in warm water , as a rehabilitation program has been considered potentially dangerous in patients with chronic heart failure ( CHF ) due to the increased venous return caused by the hydrostatic pressure . However , hydrotherapy has advantages compared to conventional training . We studied the applicability of an exercise programme in a temperature-controlled swimming pool , with specific reference to exercise capacity , muscle function , quality of life and safety . METHODS AND RESULTS Twenty-five patients with CHF ( NYHA II-III , age 72.1+/-6.1 ) were r and omised into either 8 weeks of hydrotherapy ( n=15 ) , or into a control group ( n=10 ) . The training program was well tolerated with no adverse events . Patients in the hydrotherapy group improved their maximal exercise capacity ( + 6.5 vs.-5.9 W , P=0.001 ) , isometric endurance in knee extension ( + 4 vs.-9 s , P=0.01 ) together with an improvement in the performance of heel-lift ( + 4 vs. -3 n.o . , P= shoulder abduction ( + 12 vs. -8 s , P=0.01 ) and shoulder flexion ( + 6 vs. + 4 , P=0.01 ) in comparison to patients in the control group . CONCLUSION Physical training in warm water was well tolerated and seems to improve exercise capacity as well as muscle function in small muscle groups in patients with CHF . This new approach broadens the variety of training regimes for older patients with CHF", "Abstract Background : No controlled studies have investigated whether balneotherapy is effective in atopic dermatitis ( AD ) . Objectives : To investigate the efficacy and safety of balneotherapy performed at Comano spa ( Trentino , Italy ) compared to topical corticosteroids ( TCS ) in the treatment of AD . Methods : This was an open , r and omized , clinical trial including 104 children ( aged 1–14 years ) with mild to moderate AD who were assigned either to balneotherapy ( n = 54 ) or TCS ( n = 50 ) once daily for 2 weeks . AD severity and quality of life were measured using the SCORAD , investigator global assessment ( IGA ) , patients ' self global assessment ( PSGA ) , children 's dermatology life quality index ( CDLQI ) and family dermatitis impact question naire ( FDIQ ) . Subjective measures were re-evaluated 4 months after the end of therapy . Results : Balneotherapy and TCS result ed in a significant reduction of all parameters at week 2 . TCS were more effective than balneotherapy regarding SCORAD ( 46 % ± 7.71 vs 26 % ± 9.4 , mean ± SD ; p contrast , IGA , PSGA , CDLQI and FDIQ improvement was similar . At month 4 , the number and duration of relapses were less in patients treated with balneotherapy compared to those treated with TCS ( p : Balneotherapy at Comano spa appears to be beneficial in children with mild to moderate AD", "Thermal water inhalations have been traditionally used in the treatment of upper and lower chronic airway diseases . However , the benefit and the mechanism of this treatment have not been properly assessed . To determine whether inhaled salt-bromide-iodine thermal water improves lung function , quality of life and airway inflammation , 39 patients with chronic obstructive pulmonary disease ( COPD ) were r and omly assigned to receive 2-weeks inhalation treatment with thermal water ( active , no. = 20 ) or normal saline ( control , no. = 19 ) in single blind . Lung volumes were measured , Saint George 's respiratory question naire ( SGRQ ) was administered and induced sputum was performed before and after treatment . No changes in pre- and post-salbutamol lung volumes was observed after inhalation treatment in both groups . SGRQ score showed a significant improvement in active group compared with control group at the end of the trial . The concentration of total cells in induced sputum increased significantly in both active ( P percentages of sputum neutrophils ( P macrophages ( P differential sputum cell counts . In conclusion , treatment with inhaled salt-bromide-iodine thermal water in COPD is associated with a reduced proportion of neutrophils in induced sputum suggesting that thermal water may have a mild anti-inflammatory effect on the airways . However , the short-term improvement in some components health-related quality of life was not related with changes in lung function or with the degree of airway inflammation", "The upper airway respiratory diseases ( i.e. common cold , allergic rhinitis , nonallergic/vasomotor rhinitis , acute and chronic rhinosinusitis and nasal polyposis ) in which nasal congestion is a common symptom are often undertreated due to the frequent inadequate efficacy and safety concern with current therapies . In scientific literature , few studies seem to support the hypothesis that nasal inhalatory treatment with thermal water promotes the improvement of nasal symptoms , even if the mechanisms by which the improvement from SPA therapy can be expected remain debated . A prospect i ve comparative study with a pre – post design has been performed consecutively enrolling 33 ( males 70 % ) patients of both genders older than 12 years of age , affected by chronic sinonasal inflammation . All patients underwent a 14-days course of radioactive water warm vapour inhalations followed by nasal aerosol of the same thermal water 10 min each once/day at Merano Therme . At the beginning and end of the study , in all the subjects , nasal function evaluation by active anterior rhinomanometry , mucociliary transport time ( MCTt ) determination and nasal cytology were performed . After the inhalatory treatment , the mucociliary function was improved and the pathologic mucociliary transport times recorded at the beginning of the study being significantly reduced to physiologic ones . Besides , before treatment , the cytologic picture showed an inflammatory cell infiltration ( eosinophils , neutrophils with/without bacteria , mast cells ) in 37 % of patients ; after therapy in 66 % of these patients , the rhinocytogram was normal . Our results suggest , according to the literature data , that SPA therapy with radioactive water could represent an alternative choice in chronic inflammatory diseases of the upper airways , nonresponsive to pharmacological therapy", "Bathing in water ( balneotherapy or spa therapy ) has been frequently and widely used in classical medicine as a cure for diseases . This paper review s the present literature on the use of balneotherapy in dermatologic , chronic musculoskeletal ( inflammatory and non-inflammatory ) , metabolic and psychological conditions . We performed a systematic review on related papers appearing in the Medline and Cochrane Library data base from 1966 to 2003 that included r and omized controlled and non-r and omized clinical trials using balneotherapy . We also determined to reflect where possible the chemical compositions of spas . The major dermatologic and musculoskeletal diseases that are frequently treated by balneotherapy with a remarkable rate of success are atopic dermatitis , psoriasis , rheumatoid arthritis ( RA ) , ankylosing spondylitis , osteoarthritis and low back pain . Moreover , the effects of spa therapy on several metabolic conditions are discussed . The mechanisms by which broad spectrums of diseases respond to spa therapy probably incorporate chemical , thermal and mechanical effects . The importance of balneotherapy either alone or as complement to other therapies should be considered after , or accompanying , orthodox medical treatments", "Objective . To assess the one-year effectiveness on weight loss of a 3-week balneotherapy program ( BT ) . Method . A Zelen double consent r and omised controlled trial to compare one-year BMI loss between a 3-week BT program versus usual care ( UC ) for overweight or obese patients ( BMI : 27–35 kg/m2 ) , associated or not with a dietary motivational interview ( DMI ) during the follow-up , using a 2 × 2 factorial design . Main analysis was a per protocol analysis comparing patients attending BT to patients managed by UC , matched on sex , overweight or obese status , DMI r and omisation and a propensity score to attend BT or to be managed by UC . Results . From the 257 patients who completed the follow-up , 70 patients of each group could be matched . Mean BMI loss was 1.91 kg/m2 [ 95%CI : 1.46 ; 2.35 ] for the BT patients and 0.20 kg/m2 [ −0.24 ; 0.64 ] for the UC patients ( P was no significant effect of DMI and no interaction with BT or UC . No adverse reaction was observed for patients attending BT . Conclusion . A 3-week BT program provided a significant one-year benefit over the usual GP dietary advice for overweight and obese patients", "Background : Inhalation of thermal water ( TW ) is traditionally used as part of the treatment of chronic obstructive pulmonary disease ( COPD ) , but its benefit and mechanisms are controversial . We previously observed a reduced proportion of neutrophils in induced sputum after treatment with TW . Objectives : The aim of this study was to determine whether inhalation of TW in COPD patients is associated with biochemical changes of airway lining fluid , including a reduction in the neutrophil chemoattractant leukotriene B4 ( LTB4 ) . Methods : Thirteen COPD patients were r and omly assigned to receive a 2-week course of TW and normal saline inhalation in a cross-over , single-blind study design . Exhaled breath condensate ( EBC ) was collected before and after treatments . LTB4 concentrations in EBC were determined by ELISA , and EBC pH was measured before and after argon deaeration . Results : No significant differences in LTB4 concentrations in EBC were detected with either treatment . A significant decrease in pH of non-deaerated EBC was observed after a st and ard course of TW ( median 7.45 , interquartile range 6.93–7.66 , vs. median 6.99 , interquartile range 6.57–7.19 ; p = 0.05 ) , which disappeared after argon deaeration . Conclusions : There is no evidence that TW treatment affects LTB4 concentration in EBC . The results of EBC pH measurements suggest that TW inhalation induces an imbalance of volatile components of the buffer system in airway lining fluid", "Conclusions : In order to confirm these preliminary results , a prospect i ve double-blind study has been instituted in Padova University ENT Section to compare the efficacy of sulphurous-arsenical-ferruginous thermal water nasal irrigations vs isotonic sodium chloride solution nasal irrigations after functional endoscopic sinus surgery for chronic sinusitis . Objectives : Despite their widespread use , much uncertainty exists about the indications and therapeutic mechanisms of nasal thermal water inhalations in the treatment of sinonasal chronic disease . The aim of the present study was to evaluate the effects of sulphurous-arsenical-ferruginous thermal water inhalations on nasal respiratory flow , mucociliary transport , nasal cytology , and chemo-physics of nasal mucus in a group of consecutive patients with chronic sinonasal disease . Patients and methods : Thirty-seven patients with chronic sinonasal disease underwent a 12-day course of sulphurous-arsenical-ferruginous thermal water warm vapour inhalations ( 38 ° C ) followed by nasal aerosol of the same thermal water ( 7 microns micelle ) . Results : This preliminary study showed that a course of sulphurous-arsenical-ferruginous thermal water inhalations determined a significant improvement in nasal flow and reduction of nasal resistance ; a statistically significant reduction of mean mucociliary transport time , from pathologic to physiologic values , has also been shown . Statistical analysis of our data confirmed that the presence of nasal bacteria was significantly reduced by thermal water inhalations", "The effectiveness of spa therapy in the management of patients with Parkinson 's disease ( PD ) has never been evaluated . This is assessed in this pilot study . A prospect i ve , r and omized , cross-over , controlled study was conducted in 31 PD patients who underwent a 20-week spa period , including spa therapy for 3 weeks , and a 20-week non-spa period . Effectiveness was assessed using quality of life scales ( PDQ-39 and SF-36 ) , motor scale ( UPDRS ) and psychological question naire ( GHQ-28 ) , at baseline and at 4 ( T4 ) and at 20 weeks ( T20 ) . Direct medical costs ( radiological and laboratory tests , physician fees , drug therapy , and ancillary care ) were recorded over each 20-week period . At T4 , spa therapy improved significantly several dimensions of PDQ-39 and SF-36 , part IV of the UPDRS , and GHQ-28 . At T20 , no difference in any parameter was found . The mean direct medical cost over 20 weeks ( euro;1,328 + /- 167 ; pound 776 + /- 97 per patient ) in the spa period was slightly but significantly reduced in comparison with that of the non-spa period ( euro;1380 + /- 523 ; pound 807 + /- 306 per patient ) . This cost-effectiveness analysis suggests that spa therapy is more effective and less expensive than conventional treatment alone and could be beneficial in the management of PD", "The present study was performed in order to evaluate : ( 1 ) the influence of a bicarbonate-alkaline mineral water ( Uliveto ) on digestive symptoms in patients with functional dyspepsia ; ( 2 ) the effects of Uliveto on pre clinical models of gastric functions . Selected patients complained of dyspeptic symptoms in the absence of digestive lesions or Helicobacter pylori infection within the previous 3 months . They were treated with Uliveto water ( 1.5 l day(-1 ) ) for 30 days . Frequency and severity of symptoms were assessed at baseline and day 30 by a score system . Pre clinical experiments were carried out on rats , allowed to drink Uliveto or oligomineral water for 30 days . Animals then underwent pylorus ligation to evaluate gastric secretion of acid , pepsinogen , and mucus . In separate experiments , gastric emptying was assessed . Crenotherapy was associated with a relief of epigastric pain , retrosternal pyrosis , postpr and ial fullness and gastric distention . At pre clinical level , Uliveto water increased acid and pepsinogen secretions as well as gastric emptying , without changes in bound mucus . The enhancing actions of Uliveto on gastric secretions and emptying were prevented by L-365,260 , an antagonist of gastrin/CCK-2 receptors . These findings indicate that a regular intake of Uliveto favors an improvement of dyspeptic symptoms . The pre clinical study suggests that the clinical actions of Uliveto water depend mainly on its ability to enhance gastric motor and secretory functions", "INTRODUCTION The aim of this study was to evaluate the efficiency of sulphurous thermal water in the treatment of chronic rhinosinusitis ( CRS ) . METHODS Eighty patients with CRS were included and r and omly assigned into two groups . Patients underwent a 12-day course of warm vapour inhalations and nasal irrigations with sulphurous thermal water in group A , and a physiological solution in group B. RESULTS Compared with group B , in group A the results were as follows : serum concentration of IgE was significantly lower ( p 98.37±41.4 ) ; IgA titers were not significantly higher 12 days ( 231.09±120.3 mg/dl vs. 220.44 + 114.4 mg/dl ) and 3 months after the beginning of the treatment ( 235.44±118.5 mg/dl vs. 214.51±111.8 mg/dl ) ; VAS scores were significantly ( p ) ; NMIT was normal at 12 days ( 11.54±1.59 min vs. 17.38 + 1.83 min ) and 3 months after the beginning of the treatment ( 11.46 + 2.07 min vs. 17.43±2.01 min ) ; total nasal resistances were significantly ( p sulphurous thermal water in the treatment of CRS", "OBJECTIVE The psoriasis is chronic disease characterized from an acceleration of the kinetic of the cells of epidermis . To front of the empirical evidence of the benefits of the thermal therapy in the psoriasis , the experimentals-clinics studies is insufficient . The aim of research it has been that of quantify the benefits of the mud-bath therapy with mineral water in the psoriasis . PATIENT AND METHODS The study has been channel on a champion of 30 subjects of which 19 of male sex and 11 of female sex with middle equal age to 56 years + /- 5.3 affected from psoriasis . The subjects of the examined champion have been divided to r and om in 2 groups : A and B. The group A has been treated with drugs used for psoriasis for 12 days ; the B group has been treated , always for 12 consecutive days , with mud-bath therapy ( FBT ) with mineral water obtained from the mineral sources ( chlorinate-sulphureous-bicarbonate ) of the Spa of Stabia in Castellammare ( NA ) . To the beginning and at the end of the advised treatments has been valued the prurient symptomatology and the PASI ( Psoriasis and Severity Index ) . RESULTS The data highlight an significant ( P prurient symptomatology and of the PASI in both the groups considered . CONCLUSIONS The results of this first step of investigations seems to highlight that the FBT treatment , to the same way of the drugs anti-psoriasis , results useful in the ameliorate the quality of life of these patients", "OBJECTIVE The aim was to study the effect of climatotherapy and spa treatment on selected neuro- and immunomodulatory steroids known to affect well-being , and homocysteine , in a homogenous group of thyroidectomized women under st and ard substitution regime . METHODS Dehydroepi and rosterone , its precursors and metabolites , cortisol , major sex steroids , SHBG , and homocysteine were measured before and after three-weeks stay in a health resort Jeseník ( Graefenberg ) in Czech Republic . The studied group consisted of 21 women after total thyroidectomy which was performed at least 3 months before the admission to the spa resort . All patients received thyroid hormone substitution treatment which was not changed during their stay in that resort . RESULTS Out of the steroids investigated , five , namely dehydroepi and rosterone , and rostenedione , testosterone , 7beta-hydroxy-dehydroepi and rosterone and cortisol were changed significantly after treatment . The most considerable was the decrease of cortisol and of homocysteine ( p of thyroidectomized women substituted with thyroid hormones result ed in significant , mostly beneficial effects on steroid spectrum . This effect was achieved without any use of psychopharmacs", "OBJECTIVES Treatment of gynaecological disorders is a frequent , but only barely substantiated application of balneotherapy . This study investigated potential differences between the clinical symptoms , pelvic blood flow and specific laboratory parameters of patients undergoing balneotherapy with two different types of immersion : alum-containing and tap water . STUDY DESIGN The study population comprised 40 patients ( mean age : 39.4 years ) , r and omized into two groups . All subjects took 20 min baths in 38 degrees C water every other day , for 10 occasions altogether . Study parameters were : pain relief , reduction in tissue growth , hormone levels , psychic status , and pelvic blood flow . RESULTS Thermal water improved the clinical parameters of both groups significantly . In comparison with tap water , treatment with alum-containing water accomplished significantly greater progress , as reflected by the relief of pain elicited by h and ling the uterus and improvement of psychic status . Laboratory parameters ( FSH , LH , prolactin , oestradiol and beta-endorphin serum levels ) and the Doppler index did not change in either group . CONCLUSIONS As demonstrated by our results , 3-week balneotherapy is a potentially useful adjunct for the management of chronic pelvic inflammatory disease , but further , long-term studies are notwithst and ing necessary", "BACKGROUND Chronic heart failure is characterized by increased peripheral vascular resistance and reduced peripheral perfusion due to adrenergic and renin angiotensin activation and impaired endothelial function . Recent studies have shown that nonpharmacological peripheral vasodilation with thermal therapy by means of warm-water baths and sauna has beneficial effects in chronic heart failure . European hydrotherapy ( according to Kneipp ) additionally uses short cold water stimuli , which lead to prolonged vasodilation and adaptive responses . Studies on the efficacy of hydrotherapy in chronic heart failure are lacking . METHODS We studied 15 patients ( 5 men , 10 women , mean ( + /- SD ) age 64.3 + /- 1.8 years ) with mild chronic heart failure ( NYHA functional class II to III , ejection fraction 30%-40 % ) . Patients were r and omly assigned to 6 weeks of intensive home-based hydrotherapy or 6 weeks restriction in a crossover intervention trial . Quality of life and heart-failure -- related symptoms were assessed by means of a vali date d question naire ( PLC ) . Grade d bicycle exercise test with incremental workloads ( 0 , 50 , 75 , 100 watts ) was performed at the end of each treatment period . The hydrotherapeutic program consisted of a structured combination of daily home-based external warm- and cold-water applications . RESULTS Baseline characteristics were balanced between the groups . With hydrotherapy , a significant ( P quality of life ( mood , physical capacity , enjoyment ) and a significant reduction in heart-failure-related symptoms was found . Heart rates at rest and at 50-Watt workload were significantly reduced by hydrotherapy ; blood pressure decreased nonsignificantly at rest and during exercise . The hydrotherapeutic treatment was well accepted and no relevant adverse effects were observed . CONCLUSIONS A home-based hydrotherapeutic thermal treatment program improves quality of life , heart-failure-related symptoms and heart rate response to exercise in patients with mild chronic heart failure . The results of this investigation suggest a beneficial adaptive response to repeated brief cold stimuli in addition to enhanced peripheral perfusion due to thermal hydrotherapy in patients with chronic heart failure", "INTRODUCTION Preliminary studies have suggested that balneotherapy ( BT ) is an effective and well-tolerated treatment for generalized anxiety disorder ( GAD ) and psychotropic medication withdrawal syndrome . We carried out a study in 4 spa resorts to assess the efficacy of BT in GAD . METHOD We compared BT to paroxetine in terms of efficacy and safety in a r and omized multicentre study lasting 8 weeks . Patients meeting the diagnostic criteria of GAD ( DSM-IV ) were recruited . Assessment s were conducted using the Hamilton Rating Scale for Anxiety ( HAM-A ) and other scales , by a specifically trained and independent physician . The primary outcome measure was the change in the total HAM-A score between baseline and week 8 . RESULTS A total of 237 out patients were enrolled in four centres ; 117 were assigned r and omly to BT and 120 to paroxetine . The mean change in HAM-A scores showed an improvement in both groups with a significant advantage of BT compared to paroxetine ( -12.0 vs -8.7 ; p Remission and sustained response rates were also significantly higher in the BT group ( respectively 19 % vs 7 % and 51 % vs 28 % ) . CONCLUSION BT is an interesting way of treating GAD . Due to its safety profile it could also be tested in resistant forms of generalized anxiety and in patients who do not tolerate or are reluctant to use pharmacotherapies", "BACKGROUND Purpose of this study was to assess the effects of thermal hydrotherapy ( balneokinesis ) with a sulphurous water on clinical symptoms , quality of life and some functional parameters in patients with varicose veins . PATIENTS AND METHODS 70 patients with primary or secondary symptomatic varicosis were enrolled and su bmi tted to elastic compression therapy . Patients were then r and omized to receive ( 50 pts , group A ) or not receive ( 20 pts , group B ) balneokinetic treatment for 12 days \" on top \" of elastic compression . Clinical symptoms , quality of life and functional parameters obtained with light reflex plethysmography ( PPG ) and laser Doppler fluxmetry ( LDF ) were assessed after 3 and 6 months . RESULTS Scores for subjective symptoms as pain , edema , and venous claudication were decreased after 6 months in both groups , but more evidently in group A su bmi tted to balneokinesis . Some parameters related to quality of life evaluation as \" bodily pain \" and \" emotional role \" were improved only in patients undergoing balneokinesis . Regarding functional parameters , with PPG venous refilling time after foot exercise moderately increased in both groups . With LDF a significant improvement in the veno-arteriolar reflex was seen in the group treated with balneokinesis . CONCLUSIONS These results show additional benefits of balneokinetic treatment in patients with symptomatic varices su bmi tted to elastic compression . In fact , clinical and quality of life improvements were observed . The associated amelioration in the veno-arteriolar reflex may support these subjective benefits", "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", "A lot of studies show the efficacy of thermal therapy in psoriasis . The main indications concern all forms of psoriasis ( except for pustolosa and eritrodermic ) especially diffuse psoriasis , intensive itchy , artropatic psoriasis and gutted psoriasis child . Benefit effects of thermal water and muds , which are important parameters in psoriasis ' treatment , they are excellent to reduce inflammation , scaling , and erythema . In this study we evaluated the clinical efficacy of thermal bath plus muds in patients affected by psoriasis . 18 patients has been examined and r and omly divided in 3 group ( A-B-C ) . All the patients received thermal therapy for 4 weeks . To evaluate the behaviour of the disease we performed ( corneometry , sebometry , phmetry ) , as well as evaluation of P.A.S.I. At the end of the study , values of P.A.S.I. showed a reduction from 10 to 6 unites P.A.S.I. for patients belong to group A , more 12 to less 10 for patients belong to group C e no significant variations for group B ( because represent control group ) . Results obtained can be considered useful , considering that thermal treatment was used alone in the treatment of all patients", "OBJECTIVE To assess whether language of publication restrictions impact the estimates of an intervention 's effectiveness , whether such impact is similar for conventional medicine and complementary medicine interventions , and whether the results are influenced by publication bias and statistical heterogeneity . STUDY DESIGN AND SETTING We set out to examine the extent to which including reports of r and omized controlled trials ( RCTs ) in language s other than English ( LOE ) influences the results of systematic review s , using a broad data set of 42 language -inclusive systematic review s , involving 662 RCTs , including both conventional medicine ( CM ) and complementary and alternative medicine ( CAM ) interventions . RESULTS For CM interventions , language -restricted systematic review s , compared with language -inclusive ones , did not introduce biased results , in terms of estimates of intervention effectiveness ( r and om effects ration of odds rations ROR=1.02 ; 95 % CI=0.83 - 1.26 ) . For CAM interventions , however , language -restricted systematic review s result ed in a 63 % smaller protective effect estimate than language -inclusive review s ( r and om effects ROR=1.63 ; 95 % CI=1.03 - 2.60 ) . CONCLUSION Language restrictions do not change the results of CM systematic review s but do substantially alter the results of CAM systematic review s. These findings are robust even after sensitivity analyses , and do not appear to be influenced by statistical heterogeneity and publication bias", "BACKGROUND Lately , the number of systematic review s published has increased substantially . Many systematic review s exclude trials published in language s other than English . However , there is little empirical evidence to support this action . We looked for differences in the completeness of reporting between trials published in other language s and those published in English , to see whether the exclusion of trials published in other language s is justified . METHODS We compared completeness of reporting , design characteristics , and analytical approaches of 133 r and omised controlled trials ( RCTs ) published in English between 1989 and 1994 and 96 published in French , German , Italian , or Spanish during the same time . RCTs were identified by h and search ing of journals ( seven in English and six in the other language s ) . FINDINGS We found no significant differences between trials published in English and other- language trials for any single item in the completeness of reporting scale ( r and omisation , double-blinding , withdrawals ) , or for the overall score ( percentage of maximum possible score 51.0 % for trials in English , 46.2 % for trials in other language s ; 95 % CI for difference -1.1 to 10.5 ) . Other- language trials were more likely than English- language trials to have adult participants , to use two or more interventions , and to compare two or more active treatments without an untreated control group . Trials in other language s were less likely to report a clearly prespecified primary outcome or any rationale for sample size estimation . INTERPRETATION These results provide evidence for inclusion of all trial reports , irrespective of the language in which they are published , in systematic review s. Their inclusion is likely to increase precision and may reduce systematic errors . We hope that our findings will prove useful to those developing guidelines and policies for the conduct of reporting of systematic review", "OBJECTIVES The sulphur SPA inhalation therapy is useful in respiratory and otolaryngologic chronic inflammatory diseases in adult subjects and children . The therapeutic action relies on anti-inflammatory , mucolytic and trophic effects . Particularly in children , the sulphur SPA inhalation therapy , using endotympanic ventilation or Politzer method , would be suitable in the treatment of the rhinogenic deafness . Several reports have demonstrated the effectiveness of endotympanic ventilation while the results on the Politzer method are inconclusive . On the basis of these considerations , aim of our study was to analyze the effectiveness and the safety of the aerosol+Politzer with a sulphur mineral water in children affected by rhinogenic deafness or chronic inflammatory processes responsible for the onset or persistence of rhinogenic deafness . PATIENTS AND METHODS The study has been performed on 23 subjects in pediatric age ( 61 % women and 39 % males ; mean age : 6+/-2.4 years ; age range : 3 - 14 years ) affected by chronic catarrhalis otitis , chronic rhino-pharyngitis inflammations , chronic or recurrent adenoiditis with dysfunction of the Eustachian Tube . The investigated subjects underwent 12 consecutive days sulphur SPA inhalation therapy ( aerosol+Politzer ) at the Terme of Stabia in Castellammare ( Naples , Italy ) . At the beginning and at the end of the SPA cycle the functionality of the middle ear and the tolerability were evaluated . RESULTS The results have shown an increase of the impedance curves that correspond to the normal ventilation of the tympanic box ( type A ( 13 % before therapy and of 57 % post-therapy ) and a decrease of the pathological curves of type B and type C ( 87 % pre-therapy and of 43 % post-therapy ) ; a significant increase of compliance ( p 0.05 ) in pathological curves of type B and C. No adverse reaction to the SPA inhalation therapy has been reported during the study . CONCLUSIONS In concordance with the literature our data demonstrated that the sulphur SPA inhalation treatment induce a improvement of middle ear function of the subjects examined with good local and systemic tolerability", "OBJECTIVES Except for compression therapy , physical therapy has scarcely been evaluated in the treatment of chronic venous disorders ( CVD ) . Spa treatment is a popular way to administer physical therapy for CVD in France , but its efficacy has not been evaluated yet . This study aim ed to assess the efficacy of balneotherapy associated with patient education , as performed in the spa resort of La Léchère , in patients with advanced chronic venous insufficiency ( CEAP clinical classes C4/C5 ) . METHODS The study was a r and omized controlled trial , spa therapy being administered on top of the usual medical care . Evaluation was by a blinded independent investigator . Subjects were patients with primary or post-thrombotic CVD with skin changes but no active ulcer ( C4a , C4b , or C5 ) , living in Grenoble area , and willing to undergo a spa treatment course in La Léchère . The treated group had the three week spa treatment course in La Léchère , soon after r and omization ; the control group also had a spa treatment , but starting at day 365 . The treatment consisted of four balneology sessions per day , six days a week during three weeks , and three educational workshops . An independent follow-up was performed in Grenoble hospital every three months for 15 months . The main outcome criterion was the severity of the skin changes , as evaluated by means of malleolar chromametry . Quality of life , as measured by the Chronic Venous Insufficiency Question naire 2 scale , a visual analog scale ( VAS ) for leg symptoms , and the occurrence of leg ulcers were used as secondary criteria . The year after spa treatment in the treated group was compared with the year before spa treatment in the control group . RESULTS Fifty-nine subjects were enrolled ( 29 in the treatment group and 30 in the control group ) . No statistically significant difference between groups was found at study onset regarding age , sex , etiology , CEAP \" C \" class , and the outcome variables . After treatment , chromametry showed significantly decreased pigmentation and erythema in the treatment group compared with the controls ( P Quality of life ( P symptoms ( P spa therapy , associating balneotherapy and patient education , is able to improve significantly the skin trophic changes of the CVD patients and their CVD related quality of life and symptoms . This effect is of large magnitude and remains significant one year after the treatment course" ]

[ "BACKGROUND Atrial fibrillation ( AF ) and left ventricular systolic dysfunction ( LVSD ) frequently co-exist despite adequate rate control . Existing r and omized studies of AF and LVSD of varying etiologies have reported modest benefits with a rhythm control strategy . OBJECTIVES The goal of this study was to determine whether catheter ablation ( CA ) for AF could improve LVSD compared with medical rate control ( MRC ) where the etiology of the LVSD was unexplained , apart from the presence of AF . METHODS This multicenter , r and omized clinical trial enrolled patients with persistent AF and idiopathic cardiomyopathy ( left ventricular ejection fraction [ LVEF ] ≤45 % ) . After optimization of rate control , patients underwent cardiac magnetic resonance ( CMR ) to assess LVEF and late gadolinium enhancement , indicative of ventricular fibrosis , before r and omization to either CA or ongoing MRC . CA included pulmonary vein isolation and posterior wall isolation . AF burden post-CA was assessed by using an implanted loop recorder , and adequacy of MRC was assessed by using serial Holter monitoring . The primary endpoint was change in LVEF on repeat CMR at 6 months . RESULTS A total of 301 patients were screened ; 68 patients were enrolled between November 2013 and October 2016 and r and omized with 33 in each arm ( accounting for 2 dropouts ) . The average AF burden post-CA was 1.6 ± 5.0 % at 6 months . In the intention-to-treat analysis , absolute LVEF improved by 18 ± 13 % in the CA group compared with 4.4 ± 13 % in the MRC group ( p undergoing CA , the absence of late gadolinium enhancement predicted greater improvements in absolute LVEF ( 10.7 % ; p = 0.0069 ) and normalization at 6 months ( 73 % vs. 29 % ; p = 0.0093 ) . CONCLUSIONS AF is an underappreciated reversible cause of LVSD in this population despite adequate rate control . The restoration of sinus rhythm with CA results in significant improvements in ventricular function , particularly in the absence of ventricular fibrosis on CMR . This outcome challenges the current treatment paradigm that rate control is the appropriate strategy in patients with AF and LVSD . ( Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction [ CAMERA-MRI ] ; ACTRN12613000880741 )", "CONTEXT Treatment with antiarrhythmic drugs and anticoagulation is considered first-line therapy in patients with symptomatic atrial fibrillation ( AF ) . Pulmonary vein isolation ( PVI ) with radiofrequency ablation may cure AF , obviating the need for antiarrhythmic drugs and anticoagulation . OBJECTIVE To determine whether PVI is feasible as first-line therapy for treating patients with symptomatic AF . DESIGN , SETTING , AND PARTICIPANTS A multicenter prospect i ve r and omized study conducted from December 31 , 2001 , to July 1 , 2002 , of 70 patients aged 18 to 75 years who experienced monthly symptomatic AF episodes for at least 3 months and had not been treated with antiarrhythmic drugs . INTERVENTION Patients were r and omized to receive either PVI using radiofrequency ablation ( n=33 ) or antiarrhythmic drug treatment ( n=37 ) , with a 1-year follow-up . MAIN OUTCOME MEASURES Recurrence of AF , hospitalization , and quality of life assessment . RESULTS Two patients in the antiarrhythmic drug treatment group and 1 patient in the PVI group were lost to follow-up . At the end of 1-year follow-up , 22 ( 63 % ) of 35 patients who received antiarrhythmic drugs had at least 1 recurrence of symptomatic AF compared with 4 ( 13 % ) of 32 patients who received PVI ( P Hospitalization during 1-year follow-up occurred in 19 ( 54 % ) of 35 patients in the antiarrhythmic drug group compared with 3 ( 9 % ) of 32 in the PVI group ( P antiarrhythmic drug group , the mean ( SD ) number of AF episodes decreased from 12 ( 7 ) to 6 ( 4 ) , after initiating therapy ( P = .01 ) . At 6-month follow-up , the improvement in quality of life of patients in the PVI group was significantly better than the improvement in the antiarrhythmic drug group in 5 subclasses of the Short-Form 36 health survey . There were no thromboembolic events in either group . Asymptomatic mild or moderate pulmonary vein stenosis was documented in 2 ( 6 % ) of 32 patients in the PVI group . CONCLUSION Pulmonary vein isolation appears to be a feasible first-line approach for treating patients with symptomatic AF . Larger studies are needed to confirm its safety and efficacy", "Objective To determine whether or not radiofrequency ablation ( RFA ) for persistent atrial fibrillation in patients with advanced heart failure leads to improvements in cardiac function . Setting Patients were recruited from heart failure outpatient clinics in Scotl and . Design and intervention Patients with advanced heart failure and severe left ventricular dysfunction were r and omised to RFA ( rhythm control ) or continued medical treatment ( rate control ) . Patients were followed up for a minimum of 6 months . Main outcome measure Change in left ventricular ejection fraction ( LVEF ) measured by cardiovascular MRI . Results 22 patients were r and omised to RFA and 19 to medical treatment . In the RFA group , 50 % of patients were in sinus rhythm at the end of the study ( compared with none in the medical treatment group ) . The increase in cardiovascular magnetic resonance ( CMR ) LVEF in the RFA group was 4.5±11.1 % compared with 2.8±6.7 % in the medical treatment group ( p=0.6 ) . The RFA group had a greater increase in radionuclide LVEF ( a prespecified secondary end point ) than patients in the medical treatment group ( + 8.2±12.0 % vs + 1.4±5.9 % ; p=0.032 ) . RFA did not improve N-terminal pro-B-type natriuretic peptide , 6 min walk distance or quality of life . The rate of serious complications related to RFA was 15 % . Conclusions RFA result ed in long-term restoration of sinus rhythm in only 50 % of patients . RFA did not improve CMR LVEF compared with a strategy of rate control . RFA did improve radionuclide LVEF but did not improve other secondary outcomes and was associated with a significant rate of serious complications . Clinical trials registration number NCT00292162", "Background —Restoring sinus rhythm in patients with heart failure ( HF ) and atrial fibrillation ( AF ) may improve left ventricular ( LV ) function and HF symptoms . We sought to compare the effect of a catheter ablation strategy with that of a medical rate control strategy in patients with persistent AF and HF . Methods and Results — Patients with persistent AF , symptomatic HF , and LV ejection fraction catheter ablation or medical rate control . The primary end-point was the difference between groups in LV ejection fraction at 6 months . Baseline LV ejection fraction was 32±8 % in the ablation group and 34±12 % in the medical group . Twenty-six patients underwent catheter ablation , and 24 patients were rate controlled . Freedom from AF was achieved in 21/26 ( 81 % ) at 6 months off antiarrhythmic drugs . LV ejection fraction at 6 months in the ablation group was 40±12 % compared with 31±13 % in the rate control group ( P=0.015 ) . Ablation was associated with better peak oxygen consumption ( 22±6 versus 18±6 mL/kg per minute ; P=0.014 ) and Minnesota living with HF question naire score ( 24±22 versus 47±22 ; P=0.001 ) compared with rate control . Conclusions —Catheter ablation is effective in restoring sinus rhythm in selected patients with persistent AF and HF , and can improve LV function , functional capacity , and HF symptoms compared with rate control . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier :", "OBJECTIVES The aim of this study was to determine the independent hemodynamic effects of an irregular sequence of ventricular cycle lengths in patients with atrial fibrillation ( AF ) . BACKGROUND Atrial fibrillation may reduce cardiac output by several possible mechanisms , including loss of the atrial contribution to left ventricular filling , valvular regurgitation , increased ventricular rate or irregular RR intervals . This study was design ed to evaluate the effects of an irregular RR interval , independent of the average ventricular rate , on cardiac hemodynamic data during AF . METHODS Sixteen patients with AF were studied invasively . During intrinsically conducted AF ( mean rate 102 + /- 22 beats/ min ) , the right ventricular apex electrogram was recorded onto frequency-modulated ( FM ) tape . After atrioventricular node ablation , the right ventricular apex was stimulated in three pacing modes in r and omized sequence : 1 ) VVI at 60 beats/min ; 2 ) VVI at the same average rate as during intrinsically conducted AF ( 102 + /- 22 beats/min ) ; and 3 ) during VVT pacing in which the pacemaker was triggered by playback of the FM tape recording of the right ventricular apex electrogram previously recorded during intrinsically conducted AF ( VVT 102 + /- 22 beats/min ) . RESULTS Compared with VVI pacing at the same average rate , an irregular sequence of RR intervals decreased cardiac output ( 4.4 + /- 1.6 vs. 5.2 + /- 2.4 liters/min , p pulmonary capillary wedge pressure ( 17 + /- 7 vs. 14 + /- 6 mm Hg , p right atrial pressure ( 10 + /- 6 vs. 8 + /- 4 mm Hg , p hemodynamic consequences that are independent of heart rate", "BACKGROUND Pulmonary-vein isolation is increasingly being used to treat atrial fibrillation in patients with heart failure . METHODS In this prospect i ve , multicenter clinical trial , we r and omly assigned patients with symptomatic , drug-resistant atrial fibrillation , an ejection fraction of 40 % or less , and New York Heart Association class II or III heart failure to undergo either pulmonary-vein isolation or atrioventricular-node ablation with biventricular pacing . All patients completed the Minnesota Living with Heart Failure question naire ( scores range from 0 to 105 , with a higher score indicating a worse quality of life ) and underwent echocardiography and a 6-minute walk test ( the composite primary end point ) . Over a 6-month period , patients were monitored for both symptomatic and asymptomatic episodes of atrial fibrillation . RESULTS In all , 41 patients underwent pulmonary-vein isolation , and 40 underwent atrioventricular-node ablation with biventricular pacing ; none were lost to follow-up at 6 months . The composite primary end point favored the group that underwent pulmonary-vein isolation , with an improved question naire score at 6 months ( 60 , vs. 82 in the group that underwent atrioventricular-node ablation with biventricular pacing ; P 6-minute-walk distance ( 340 m vs. 297 m , P ejection fraction ( 35 % vs. 28 % , P underwent pulmonary-vein isolation , 88 % of patients receiving antiarrhythmic drugs and 71 % of those not receiving such drugs were free of atrial fibrillation at 6 months . In the group that underwent pulmonary-vein isolation , pulmonary-vein stenosis developed in two patients , pericardial effusion in one , and pulmonary edema in another ; in the group that underwent atrioventricular-node ablation with biventricular pacing , lead dislodgment was found in one patient and pneumothorax in another . CONCLUSIONS Pulmonary-vein isolation was superior to atrioventricular-node ablation with biventricular pacing in patients with heart failure who had drug-refractory atrial fibrillation . ( Clinical Trials.gov number , NCT00599976 .", "IMPORTANCE Atrial fibrillation ( AF ) is the most common rhythm disorder seen in clinical practice . Antiarrhythmic drugs are effective for reduction of recurrence in patients with symptomatic paroxysmal AF . Radiofrequency ablation is an accepted therapy in patients for whom antiarrhythmic drugs have failed ; however , its role as a first-line therapy needs further investigation . OBJECTIVE To compare radiofrequency ablation with antiarrhythmic drugs ( st and ard therapy ) in treating patients with paroxysmal AF as a first-line therapy . DESIGN , SETTING , AND PATIENTS A r and omized clinical trial involving 127 treatment-naive patients with paroxysmal AF were r and omized at 16 centers in Europe and North America to received either antiarrhythmic therapy or ablation . The first patient was enrolled July 27 , 2006 ; the last patient , January 29 , 2010 . The last follow-up was February 16 , 2012 . INTERVENTIONS Sixty-one patients in the antiarrhythmic drug group and 66 in the radiofrequency ablation group were followed up for 24 months . MAIN OUTCOMES AND MEASURES The time to the first documented atrial tachyarrhythmia of more than 30 seconds ( symptomatic or asymptomatic AF , atrial flutter , or atrial tachycardia ) , detected by either scheduled or unscheduled electrocardiogram , Holter , transtelephonic monitor , or rhythm strip , was the primary outcome . Secondary outcomes included symptomatic recurrences of atrial tachyarrhythmias and quality of life measures assessed by the EQ-5D tool . RESULTS Forty-four patients ( 72.1 % ) in the antiarrhythmic group and in 36 patients ( 54.5 % ) in the ablation group experienced the primary efficacy outcome ( hazard ratio [ HR ] , 0.56 [ 95 % CI , 0.35 - 0.90 ] ; P = .02 ) . For the secondary outcomes , 59 % in the drug group and 47 % in the ablation group experienced the first recurrence of symptomatic AF , atrial flutter , atrial tachycardia ( HR , 0.56 [ 95 % CI , 0.33 - 0.95 ] ; P = .03 ) . No deaths or strokes were reported in either group ; 4 cases of cardiac tamponade were reported in the ablation group . In the st and ard treatment group , 26 patients ( 43 % ) underwent ablation after 1-year . Quality of life was moderately impaired at baseline in both groups and improved at the 1 year follow-up . However , improvement was not significantly different among groups . CONCLUSIONS AND RELEVANCE Among patients with paroxysmal AF without previous antiarrhythmic drug treatment , radiofrequency ablation compared with antiarrhythmic drugs result ed in a lower rate of recurrent atrial tachyarrhythmias at 2 years . However , recurrence was frequent in both groups . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00392054", "BACKGROUND Up date d underst and ing of the risks of catheter ablation is important because techniques have evolved for procedures treating non-life-threatening as well as potentially lethal arrhythmias . OBJECTIVE This prospect i ve study sought to assess the incidence and predictors of major complications from contemporary catheter ablation procedures at a high-volume center . METHODS Over a 2-year period , 1,676 consecutive ablation procedures were prospect ively evaluated for major complications throughout 30 days postprocedure . Predictors of major complications were determined in a multivariate analysis adjusted for demographics , clinical variables , ablation type , and procedural factors . RESULTS Rates of major complications differed between procedure types , ranging from 0.8 % for supraventricular tachycardia , 3.4 % for idiopathic ventricular tachycardia ( VT ) , 5.2 % for atrial fibrillation ( AF ) , and 6.0 % for VT associated with structural heart disease ( SHD ) . Ablation type ( ablation for AF [ odds ratio ( OR ) 5.53 , 95 % confidence interval ( CI ) 1.81 to 16.83 ] , for VT with SHD [ OR 8.61 , 95 % CI 2.37 to 31.31 ] , or for idiopathic VT [ OR 5.93 , 95 % CI 1.40 to 25.05 ] all referenced to supraventricular tachycardia ablation ) , and serum creatinine level > 1.5 mg/dl ( OR 2.48 , 95 % CI 1.07 to 5.76 ) were associated with increased adjusted risk of major complications , whereas age , gender , body mass index , international normalized ratio level , hypertension , coronary artery disease , diabetes , and prior cerebrovascular accident were not associated with increased risk . CONCLUSION In a large cohort of contemporary catheter ablation , major complication rates ranged between 0.8 % and 6.0 % depending on the ablation procedure performed . Aside from ablation type , renal insufficiency was the only independent predictor of a major complication", "OBJECTIVES This study sought to compare catheter ablation with rate control for persistent atrial fibrillation ( AF ) in heart failure ( HF ) . BACKGROUND The optimal therapy for AF in HF is unclear . Drug-based rhythm control has not proved clinical ly beneficial . Catheter ablation improves cardiac function in patients with HF , but impact on physiological performance has not been formally evaluated in a r and omized trial . METHODS In a r and omized , open-label , blinded-endpoint clinical trial , adults with symptomatic HF , radionuclide left ventricular ejection fraction ( EF ) ≤35 % , and persistent AF were assigned to undergo catheter ablation or rate control . Primary outcome was 12-month change in peak oxygen consumption . Secondary endpoints were quality of life , B-type natriuretic peptide , 6-min walk distance , and EF . Results were analyzed by intention-to-treat . RESULTS Fifty-two patients ( age 63 ± 9 years , EF 24 ± 8 % ) were r and omized , 26 each to ablation and rate control . At 12 months , 88 % of ablation patients maintained sinus rhythm ( single-procedure success 68 % ) . Under rate control , rate criteria were achieved in 96 % . The primary endpoint , peak oxygen consumption , significantly increased in the ablation arm compared with rate control ( difference + 3.07 ml/kg/min , 95 % confidence interval : 0.56 to 5.59 , p = 0.018 ) . The change was not evident at 3 months ( + 0.79 ml/kg/min , 95 % confidence interval : -1.01 to 2.60 , p = 0.38 ) . Ablation improved Minnesota score ( p = 0.019 ) and B-type natriuretic peptide ( p = 0.045 ) and showed nonsignificant trends toward improved 6-min walk distance ( p = 0.095 ) and EF ( p = 0.055 ) . CONCLUSIONS This first r and omized trial of ablation versus rate control to focus on objective exercise performance in AF and HF shows significant benefit from ablation , a strategy that also improves symptoms and neurohormonal status . The effects develop over 12 months , consistent with progressive amelioration of the HF syndrome . ( A R and omised Trial to Assess Catheter Ablation Versus Rate Control in the Management of Persistent Atrial Fibrillation in Chronic Heart Failure ; NCT00878384 )", "OBJECTIVE This study undertook to determine if the presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular dysfunction was associated with increased mortality and , if so , whether the increase could be attributed to progressive heart failure or arrhythmic death . BACKGROUND Atrial fibrillation is a common condition in heart failure with the potential to impact hemodynamics and progression of left ventricular systolic dysfunction as well as the electrophysiologic substrate for arrhythmias . The available data do not conclusively define the effect of atrial fibrillation on prognosis in heart failure . METHODS A retrospective analysis of the Studies of Left Ventricular Dysfunction Prevention and Treatment Trials was conducted that compared patients with atrial fibrillation to those in sinus rhythm at baseline for the risk of all-cause mortality , progressive pump-failure death and arrhythmic death . RESULTS The patients with atrial fibrillation at baseline , compared to those in sinus rhythm , had greater all-cause mortality ( 34 % vs. 23 % , p death attributed to pump-failure ( 16.7 % vs. 9.4 % , p end point of death or hospitalization for heart failure ( 45 % vs. 33 % , p arrhythmic deaths . After multivariate analysis , atrial fibrillation remained significantly associated with all-cause mortality ( relative risk [ RR ] 1.34 , 95 % confidence interval [ CI ] 1.12 to 1.62 , p=0.002 ) , progressive pump-failure death ( RR 1.42 , 95 % CI 1.09 to 1.85 , p=0.01 ) , the composite end point of death or hospitalization for heart failure ( RR 1.26 , 95 % CI 1.03 to 1.42 , p=0.02 ) , but not arrhythmic death ( RR 1.13 ; 95 % CI 0.75 to 1.71 ; p=0.55 ) . CONCLUSIONS The presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular systolic dysfunction is associated with an increased risk for all-cause mortality , largely explained by an increased risk for pump-failure death . These data suggest that atrial fibrillation is associated with progression of left ventricular systolic dysfunction", "Background — Whether catheter ablation ( CA ) is superior to amiodarone ( AMIO ) for the treatment of persistent atrial fibrillation ( AF ) in patients with heart failure is unknown . Methods and Results — This was an open-label , r and omized , parallel-group , multicenter study . Patients with persistent AF , dual-chamber implantable cardioverter defibrillator or cardiac resynchronization therapy defibrillator , New York Heart Association II to III , and left ventricular ejection fraction ratio ) to undergo CA for AF ( group 1 , n=102 ) or receive AMIO ( group 2 , n=101 ) . Recurrence of AF was the primary end point . All-cause mortality and unplanned hospitalization were the secondary end points . Patients were followed up for a minimum of 24 months . At the end of follow-up , 71 ( 70 % ; 95 % confidence interval , 60%–78 % ) patients in group 1 were recurrence free after an average of 1.4±0.6 procedures in comparison with 34 ( 34 % ; 95 % confidence interval , 25%–44 % ) in group 2 ( log-rank P The success rate of CA in the different centers after a single procedure ranged from 29 % to 61 % . After adjusting for covariates in the multivariable model , AMIO therapy was found to be significantly more likely to fail ( hazard ratio , 2.5 ; 95 % confidence interval , 1.5–4.3 ; P than CA . Over the 2-year follow-up , the unplanned hospitalization rate was ( 32 [ 31 % ] in group 1 and 58 [ 57 % ] in group 2 ; P significantly lower mortality was observed in CA ( 8 [ 8 % ] versus AMIO ( 18 [ 18 % ] ; P=0.037 ) . Conclusions — This multicenter r and omized study shows that CA of AF is superior to AMIO in achieving freedom from AF at long-term follow-up and reducing unplanned hospitalization and mortality in patients with heart failure and persistent AF . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00729911" ]

[ "Context Is it cost-effective to screen older adults for abdominal aortic aneurysm ( AAA ) ? Contribution This 7-year follow-up report of a large r and omized trial in the United Kingdom found that men age 65 to 74 years who were invited to have ultrasonography and surveillance for AAA had lower mortality rates than did those who were not invited ( hazard ratio , 0.53 [ CI , 0.42 to 0.68 ] ) . Cost-effectiveness for AAA-related deaths , based on costs applied to the events experienced by the men , was estimated at $ 19500 ( CI , $ 12400 to $ 39800 ) per life-year gained . Caution s Only men were studied . Actual costs of screening and surveillance may vary substantially in different setting s. The Editors A fast-growing body of literature is providing evidence in favor of screening men for abdominal aortic aneurysm ( AAA ) . Several large , r and omized trials published in the past few years ( 14 ) have consistently shown that screening reduces AAA-related mortality . A few observational studies of programs under way in localized areas have established the feasibility of systematic screening and have explored its practical implementation ( 57 ) . In addition to the mortality benefit , evidence indicating that screening is highly cost-effective is increasing ( 811 ) . In light of this evidence , national screening programs are now being considered in many countries ( 1214 ) . However , there is little evidence regarding long-term outcomes after AAA screening ; almost all of the evidence from r and omized trials is limited to the first 4 years after screening ( 14 ) . Moreover , long-term cost-effectiveness has been estimated only through health economic modeling ( 10 ) . We describe cost-effectiveness based on 7-year follow-up from the largest of the 4 trials of AAA screeningthe Multicentre Aneurysm Screening Study ( MASS ) ( 2 ) . The trial r and omly assigned approximately 67800 men age 65 to 74 years to receive an invitation to screening or to not receive an invitation . At 4-year follow-up , the trial reported a substantial relative reduction of 42 % ( 95 % CI , 22 % to 58 % ) in AAA-related mortality and an incremental cost-effectiveness ratio of $ 44900 ( CI , $ 24000 to $ 231000 ) per life-year gained ( 9 ) , which is at the borderline of the commonly accepted threshold for interventions . All values are reported in U.S. dollars ( U.K. 1 = U.S. $ 1.58 ) ( 15 ) . The costs of AAA screening are primarily incurred at the start of the program , but benefits continue to accrue in terms of life-years gained in patients in whom AAA rupture is avoided through elective surgery . It is therefore expected that cost-effectiveness of screening will improve over time . The mid-term results of MASS provide reliable , trial-based information regarding clinical outcomes and cost-effectiveness over a longer period . Methods The details of the MASS protocol were described previously ( 2 ) , but a brief summary is provided ( Figure 1 ) . Between 1997 and 1999 , a population -based sample of 70495 men age 65 to 74 years from 4 centers in the United Kingdom was identified by obtaining records for every man in this age range who was registered with a family physician ( registered persons account for approximately 98 % of the population ) . Persons who were ineligible for the trial ( incorrect details , known AAA , previous AAA surgery , or terminal illness ) were excluded before r and omization . The remaining 67770 men were r and omly assigned to receive an invitation to ultrasonography for AAA or to not receive an invitation to ultrasonography . At screening , men with an aortic diameter of 3.0 cm or greater were defined as having an AAA and were subsequently invited for recall scans to monitor growth of the aneurysm . Men with an aortic diameter of 3.0 to 4.4 cm were rescreened every year , and those with an aortic diameter of 4.5 to 5.4 cm were rescreened every 3 months . Participants were considered for elective surgery when the aortic diameter reached 5.5 cm , aortic expansion was 1.0 cm or more in 1 year , or they experienced symptoms attributable to the aneurysm . Men with an aortic diameter less than 3.0 cm on the initial scan were not rescreened . Blood pressure was also measured ; although family physicians were informed of these measurements , no further intervention was provided through the screening program . We obtained approval from local ethics committees at each center , and all patients who had screening provided signed informed consent . Figure 1 . Study flow diagram . Additional data on follow-up scans and AAA surgeries were collected from hospital records . Deaths up to 31 March 2005 were confirmed by the U.K. Office of National Statistics after matching of the unique National Health Service number for each person . Follow-up ranged from 5.9 to 8.2 years ( mean , 7.1 years ) . The primary outcome of interest , AAA-related mortality , is defined as all deaths within 30 days of any AAA surgery ( elective or emergency ) plus all deaths with International Classification of Diseases , Ninth Revision , codes 441.3 ( ruptured abdominal aortic aneurysm ) , 441.4 ( abdominal aortic aneurysm without mention of rupture ) , 441.5 ( ruptured aortic aneurysm at unspecified site ) , or 441.6 ( aortic aneurysm at unspecified site without mention of rupture ) . The use of codes 441.5 and 441.6 may result in inclusion of some thoracic aortic aneurysm deaths . Investigation of the accuracy of cause-of-death coding on the death certificates was done by an independent mortality working party that was blinded to group allocation . The results of this analysis showed that inaccuracies in coding did not have an important impact on study outcomes ( 2 ) . Statistical Analysis All analyses were done by using Stata , version 9 ( Stata Corp. , College Station , Texas ) . Deaths related to AAA ( primary analysis ) and all-cause mortality ( secondary analysis ) were compared between the 2 r and omized groups by using unadjusted Cox regression by intention-to-treat analysis . Adjustment for age at baseline did not influence the results . The proportional hazards assumption was tested by using Schoenfeld residuals . An unbiased r and omization-based estimate of the benefit of screening was also obtained ( 16 ) . This estimate is calculated by subtracting from the control group a subgroup that is equivalent in terms of survival to the nonadherent subgroup in the invited group . Thus , the remaining controls are comparable to the group of invited patients who attended screening . Life-years gained are estimated as the area between the KaplanMeier curves for both groups ( 17 ) . The cost-effectiveness of screening is estimated from a health service perspective for follow-up truncated at 7 years , with adjustment for censoring ( 18 ) . Details of the costing exercise in the trial at 20002001 prices were reported previously ( 9 ) . The unit costs obtained ( U.K. 1 = U.S. $ 1.58 for the year 2000 [ 15 ] ) are inflated to the 20042005 financial-year level by using annual hospital and community health services pay and price inflation indices ( 19 ) . Costs are applied to the following events on the basis of individual re source use : invitation to screening ( $ 2.46 ) , reinvitation after nonresponse ( $ 2.42 ) , initial scan ( $ 35.95 ) , recall scan ( $ 86.74 ; done in the hospital rather than in the community and including costs for periodic routine meetings with a consultant ) , consultation for elective surgery ( $ 583.79 ) , elective AAA surgery ( $ 13015.74 ) , and emergency AAA surgery ( $ 21054.32 ) . Costs relating to scans of incidentally detected AAAs in the control group are not included ( data not available ) , but costs relating from result ant AAA repair surgery are included . Sensitivity analyses were done by using 1 ) costs retained at the 20002001 financial-year level for comparison with previous publications , 2 ) quality -adjusted life-years based on age-related reductions , 3 ) U.S.-based unit cost estimates for scans and surgeries , 4 ) an increase of 50 % in the cost of a consultation ( a U.S.-based estimate was not available , but this analysis reflects possible additional assessment s ) , 5 ) 3 and 4 combined . Quality -of-life adjustments are made only on the basis of age , with an adjustment of 0.78 for life-years gained between the ages 65 and 74 years and an adjustment of 0.75 for life-years gained at ages older than 75 years ( 20 ) . The U.S.-specific estimates for scans ( initial and recall ) are based on Medicare reimbursement for AAA screening at $ 90.95 ( Current Procedural Terminology code G0389 ) ( 21 ) , and U.S.-specific costs for surgeries are based on previously published estimates ( 22 , 23 ) that were inflated to 2004 prices ( 24 ) : $ 18160 for elective procedures and $ 31106 for emergency procedures . Discounting is applied at the current recommended values of 3 % per annum for costs and effects ( 25 ) . Estimates of AAA-related costs and effects take into account the rate of nonAAA-related deaths across both groups over time . The Fieller method is used to calculate bounds for the CI for cost-effectiveness ( 26 , 27 ) . Role of the Funding Source This study was funded by the Medical Research Council . The funding source had no role in the design , implementation , or analysis of the study . Results Figure 1 shows the flow of participants through the trial . Numbers differ slightly from earlier publications because of identification of a few duplicate records in the data base . Of 67770 r and omly assigned men , 33883 were invited to be screened : 27204 ( 80 % ) attended and 1334 ( 4.9 % ) AAAs were identified . The mean age at r and omization was 69.2 years in both groups . Loss to follow-up because of death was 2.1 % overall ( 2.2 % in the control group and 2.1 % in the invited group ) . Loss to clinical follow-up ( nonattendance at recall scans ) was 19 % at 4 years and 24 % at 7 years . The Appendix Table shows surgeries and deaths within 30 days in each of the r and omly assigned groups . A few endovascular operations are included in these figures6 in the control group and 14 in the invited group . As expected , the total number of elective procedures is greater in the invited group than in the control group", "BACKGROUND Opposing views have been published on the importance of ultrasound screening for abdominal aortic aneurysms . The Multicentre Aneurysm Screening Study was design ed to assess whether or not such screening is beneficial . METHODS A population -based sample of men ( n=67800 ) aged 65 - 74 years was enrolled , and each individual r and omly allocated to either receive an invitation for an abdominal ultrasound scan ( invited group , n=33839 ) or not ( control group , n=33961 ) . Men in whom abdominal aortic aneurysms ( > or =3 cm in diameter ) were detected were followed-up with repeat ultrasound scans for a mean of 4.1 years . Surgery was considered on specific criteria ( diameter > or = 5.5 cm , expansion > or = 1 cm per year , symptoms ) . Mortality data were obtained from the Office of National Statistics , and an intention-to-treat analysis was based on cause of death . Quality of life was assessed with four st and ardised scales . The primary outcome measure was mortality related to abdominal aortic aneurysm . FINDINGS 27147 of 33839 ( 80 % ) men in the invited group accepted the invitation to screening , and 1333 aneurysms were detected . There were 65 aneurysm-related deaths ( absolute risk 0.19 % ) in the invited group , and 113 ( 0.33 % ) in the control group ( risk reduction 42 % , 95 % CI 22 - 58 ; p=0.0002 ) , with a 53 % reduction ( 95 % CI 30 - 64 ) in those who attended screening . 30-day mortality was 6 % ( 24 of 414 ) after elective surgery for an aneurysm , and 37 % ( 30 of 81 ) after emergency surgery . INTERPRETATION Our results provide reliable evidence of benefit from screening for abdominal aortic aneurysms", "Objectives To compare attendance and prevalence of abdominal aortic aneurysm ( AAA ) in population based r and omised trials of sonographic screening in the United Kingdom , Western Australia , and Denmark . Methods 65 290 men were r and omised to screening in the four trials , and data were collected and analysed from 46 397 aortic scans for men aged between 64 and 83 years who attended one of four community screening programmes . Comparisons were made for age st and ardised population s ( 65–74 years ) . Results Age st and ardised attendance varied between 74 % and 81 % , and was highest in the United Kingdom and lowest in Western Australia . Age st and ardised prevalence of AAAs of 3.0 cm or more varied significantly between 4.5 % and 7.7 % , and was highest in the United Kingdom and lowest in Denmark . Conclusions Participation in the four programmes compares favourably with other reported screening studies . The possibility that variations may reflect the different recruitment methods used is discussed . The prevalence of AAA in central Denmark would appear to be significantly different from that in southern Engl and and Western Australia", "Objective : To improve compliance with computer-generated reminders to perform fecal occult blood testing ( FOBT ) , mammography , and cervical Papanicolaou ( Pap ) testing . Design : Six-month prospect i ve , r and omized , controlled trial . Setting : Academic primary care general internal medicine practice .Subjects : Thirty-one general internal medicine faculty , 145 residents , and 5,407 patients with scheduled visits who were eligible for any of the three cancer screening protocol s . Intervention : Primary care teams of internal medicine residents and faculty received either routine computer reminders ( control ) or the same reminders to which they were required to circle one of four responses : 1 ) “ done/order today , ” 2 ) “ not applicable to this patient , ” 3 ) “ patient refused , ” or 4 ) “ next visit . ” Results : Intervention physicians complied more frequently than control physicians with all reminders combined ( 46 % vs 38 % , respectively , p=0.002 ) and separately with reminders for FOBT ( 61 % vs 49 % , p=0.0007 ) and mammography ( 54 % vs 47 % , p=0.036 ) but not cervical Pap testing ( 21 % vs 18 % , p=0.2 ) . Intervention residents responded significantly more often than control residents to all reminders together and separately to reminders for FOBT and mammography but not Pap testing . There was no significant difference between intervention and control faculty , but the compliance rate for control faculty was significantly higher than the rate for control residents for all reminders together and separately for FOBT but not mammography or Pap testing . The intervention ’s effect was greatest for patients ≥70 years old , with significant results for all tests , together and singly , for residents but not faculty . Intervention physicians felt that the reminders were not applicable 21 % of the time ( due to inadequate data in patients ’ electronic medical records ) and stated that their patients refused 10 % of the time . Conclusions : Requiring physicians to respond to computer-generated reminders improved their compliance with preventive care protocol s , especially for elderly patients for whom control physicians ’ compliance was the lowest . However , 100 % compliance with cancer screening reminders will be unattainable due to incomplete data and patient refusal", "OBJECTIVE To assess the cost effectiveness of ultrasound screening for abdominal aortic aneurysms . DESIGN Primary analysis : four year cost effectiveness analysis based directly on results from a r and omised controlled trial in which patients were individually allocated to invitation to ultrasound screening ( intervention ) or to a control group not offered screening . Secondary analysis : projection of the data , based on conservative assumptions , to indicate likely cost effectiveness at 10 years . SETTING Four centres in the United Kingdom . Screening delivered in primary care setting s with follow up and surgery offered in the main hospitals Participants : Population based sample of 67 800 men aged 65 - 74 years . MAIN OUTCOME MEASURES Mortality from and costs ( screening , follow up , elective and emergency surgery ) related to abdominal aortic aneurysm ; cost per life year gained . RESULTS Over four years there were 47 fewer deaths related to abdominal aortic aneurysms in the screening group than in the control group , but the additional costs incurred were pound 2.2 m . After adjustment for censoring and discounted at 6 % the mean additional cost of the screening programme was pound 63.39 ( $ 97.77 , euro;100.48 ) ( 95 % confidence interval pound 53.31 to pound 73.48 ) per patient . The hazard ratio for abdominal aortic aneurysm was 0.58 ( 0.42 to 0.78 ) . Over four years the mean incremental cost effectiveness ratio for screening was pound 28 400 ( pound 15 000 to pound 146 000 ) per life year gained , equivalent to about pound 36 000 per quality adjusted life year . After 10 years this figure is estimated to fall to around pound 8000 per life year gained . CONCLUSIONS Even at four years the cost effectiveness of screening for abdominal aortic aneurysms is at the margin of acceptability according to current NHS thresholds . Over a longer period the cost effectiveness will improve substantially , the predicted ratio at 10 years falling to around a quarter of the four year figure", "BACKGROUND We previously reported the prevalence and associations of abdominal aortic aneurysm ( AAA ) in 73451 veterans aged 50 to 79 years who underwent ultrasound screening . OBJECTIVE To underst and the prevalence of and principal positive and negative risk factors for AAA , and to assess reproducibility of our previous findings . METHODS In the new cohort of veterans undergoing screening , 52 745 subjects aged 50 to 79 without history of AAA underwent successful ultrasound screening for AAA , after completing a question naire on demographics and potential risk factors . RESULTS We detected AAA of 4.0 cm or larger in 613 participants ( 1.2 % ; compared with 1.4 % in the earlier cohort ) . The direction and magnitude of the important associations reported in the first cohort were confirmed . Respective odds ratios for the major associations with AAA for the second and for the combined cohorts were as follows : 1.81 and 1.71 for age ( per 7 years ) , 0.12 and 0 . 18 for female sex , 0.59 and 0.53 for black race , 1.94 and 1.94 for family history of AAA , 4.45 and 5.07 for smoking , 0.50 and 0.52 for diabetes , and 1.60 and 1.66 for atherosclerotic diseases . The excess prevalence associated with smoking accounted for 75 % of all AAAs of 4.0 cm or larger in the total population of 126 196 . Associations for AAA of 3.0 to 3.9 cm were similar but tended to be somewhat weaker . CONCLUSIONS Our findings confirm our previous cohort findings . Age , smoking , family history of AAA , and atherosclerotic diseases remained the principal positive associations with AAA , and female sex , diabetes , and black race remained the principal negative associations", "BACKGROUND Preventive care is an important role for general practitioners , yet opportunities for prevention are often missed . METHOD We provided an automatic electronic record preventive care reminder system for 12 preventive care activities for one 10 doctor practice . All patients who attended were r and omised by the terminal digit of their record number . RESULTS The control uptake of opportunistic prevention was low ; ranging from 1.5 % ( tetanus immunisation ) to 27 % ( influenza immunisation ) . The reminders increased this by significant but small amounts for four out of 12 activities ( immunisation for tetanus and pneumococcus and recording of allergies and weight ) , insignificant increases for four ( mumps , measles and rubella immunisation , recording of smoking , and taking of cervical smears and of blood pressure ) , and insignificantly decreased influenza immunisation , and screening for diabetes and hyperlipidaemia . DISCUSSION Opportunistic electronic reminders have the potential to increase preventive care in general practice ", "BACKGROUND Based on r and omized , population -based screening protocol s , a single ultrasound examination reduces mortality from an abdominal aortic aneurysm ( AAA ) by facilitating elective surgical intervention before rupture . Ultrasound screening is accurate , noninvasive , inexpensive , and cost effective . By using a comprehensive electronic medical record , we inquired whether an age-prompted clinical reminder would facilitate the detection of AAA . METHODS The AAA risk screen was installed in May 2007 via a computerized patient record system prompt for male veterans ages 65 to 75 who ever smoked . This abbreviated ultrasound examination uses a 3.5- to 4-MHz scan head , measures anteroposterior and transverse planes , and reports the largest infrarenal aortic diameter . RESULTS Of 1437 examinations there were 73 AAAs of 3.0-cm diameter or larger ( 5.1 % ) ; 33 AAAs of 4.0-cm diameter or larger ( 2.3 % ) ; 15 AAAs of 5.0-cm diameter or larger ( 1.0 % ) ; and 11 AAAs of 5.5-cm diameter or larger ( .77 % ) . Fifty ( 68 % ) received counseling for abnormal findings . CONCLUSIONS Recognition of newly diagnosed AAA compared favorably with that of previous screening studies . Electronic clinical reminders identify undiagnosed , life-threatening AAAs before rupture . Immediate counseling is available in the vascular setting" ]

[ "This study extends findings on the effects of intensive applied behavior analytic treatment for children with autism who began treatment at a mean age of 5.5 years . The behavioral treatment group ( n = 13 , 8 boys ) was compared to an eclectic treatment group ( n = 12 , 11 boys ) . Assignment to groups was made independently based on the availability of qualified supervisors . Both behavioral and eclectic treatment took place in public kindergartens and elementary schools for typically developing children . At a mean age of 8 years , 2 months , the behavioral treatment group showed larger increases in IQ and adaptive functioning than did the eclectic group . The behavioral treatment group also displayed fewer aberrant behaviors and social problems at follow-up . Results suggest that behavioral treatment was effective for children with autism in the study", "This study reports results of a r and omized controlled trial aim ed at joint attention ( JA ) and symbolic play ( SP ) in preschool children with autism , with prediction to language outcome 12 months later . Participants were 58 children ( 46 boys ) with autism between 3 and 4 years of age . Children were r and omized to a JA intervention , an SP intervention , or control group . Interventions were conducted 30 min daily for 5 - 6 weeks . Assessment s of JA skills , SP skills , mother-child interactions , and language development were collected at 4 time points : pre- and postintervention and 6 and 12 months postintervention by independent testers . Results indicate that expressive language gains were greater for both treatment groups compared with the control group , and results could not be explained by differences in other interventions in which children participated . For children beginning treatment with the lowest language levels , the JA intervention improved language outcome significantly more than did the SP or control interventions . These findings suggest clinical ly significant benefits of actively treating JA and SP skills in young children with autism", "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", "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", "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 )", "BACKGROUND This prospect i ve study compared outcome for pre-school children with autism spectrum disorders ( ASD ) receiving autism-specific nursery provision or home-based Early Intensive Behavioural Interventions ( EIBI ) in a community setting . METHODS Forty-four 23- to 53-month-old children with ASD participated ( 28 in EIBI home-based programmes ; 16 in autism-specific nurseries ) . Cognitive , language , play , adaptive behaviour skills and severity of autism were assessed at intake and 2 years later . RESULTS Both groups showed improvements in age equivalent scores but st and ard scores changed little over time . At follow-up , there were no significant group differences in cognitive ability , language , play or severity of autism . The only difference approaching significance ( p = .06 ) , in favour of the EIBI group , was for Vinel and Daily Living Skills st and ard scores . However , there were large individual differences in progress , with intake IQ and language level best predicting overall progress . CONCLUSIONS Home-based EIBI , as implemented in the community , and autism-specific nursery provision produced comparable outcomes after two years of intervention", " An intervention group ( n=23 ) of preschool children with autism was identified on the basis of parent preference for early intensive behavioral intervention and a comparison group ( n=21 ) identified as receiving treatment as usual . Prospect i ve assessment was undertaken before treatment , after 1 year of treatment , and again after 2 years . Groups did not differ on assessment s at baseline but after 2 years , robust differences favoring intensive behavioral intervention were observed on measures of intelligence , language , daily living skills , positive social behavior , and a statistical measure of best outcome for individual children . Measures of parental well-being , obtained at the same three time points , produced no evidence that behavioral intervention created increased problems for either mothers or fathers of children receiving it", "ABSTRACT . Although previous studies have shown favorable results with early intensive behavioral treatment ( EIBT ) for children with autism , it remains important to replicate these findings , particularly in community setting s. The authors conducted a 3-year prospect i ve outcome study that compared 2 groups : ( 1 ) 21 children who received 35 to 40 hours per week of EIBT from a community agency that replicated Lovaas ' model of EIBT and ( 2 ) 21 age- and IQ-matched children in special education classes at local public schools . A quasi-experimental design was used , with assignment to groups based on parental preference . Assessment s were conducted by independent examiners for IQ ( Bayley Scales of Infant Development or Wechsler Preschool and Primary Scales of Intelligence ) , language ( Reynell Developmental Language Scales ) , nonverbal skill ( Merrill-Palmer Scale of Mental Tests ) , and adaptive behavior ( Vinel and Adaptive Behavior Scales ) . Analyses of covariance , with baseline scores as covariates and Year 1 - 3 assessment s as repeated measures , revealed that , with treatment , the EIBT group obtained significantly higher IQ ( F = 5.21 , p = .03 ) and adaptive behavior scores ( F = 7.84 , p = .01 ) than did the comparison group . No difference between groups was found in either language comprehension ( F = 3.82 , p = .06 ) or nonverbal skill . Six of the 21 EIBT children were fully included into regular education without assistance at Year 3 , and 11 others were included with support ; in contrast , only 1 comparison child was placed primarily in regular education . Although the study was limited by the nonr and om assignment to groups , it does provide evidence that EIBT can be successfully implemented in a community setting", "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", "Evidence from recent meta-analytic and narrative review suggests that early intensive behavioral intervention ( EIBI ) may improve life chances of preschool children with autism . Unfortunately , there are few data indicating whether early gains are maintained after intervention ceases . The purpose of the present study was to establish the 2-year follow-up outcome for children with autism ( N = 41 ) who had participated in an earlier 2-year controlled comparison of EIBI . Twenty-three children in the intervention group ( 100 % of original sample ) and 18 in the treatment-as-usual comparison group ( 86 % of original sample ) were located and retested . Group differences favoring intervention substantially diluted in this period but varied significantly between subgroups who had received university-supervised and parent-commissioned interventions , favoring the latter . These groups differed in terms of their baseline characteristics and intensity of intervention . Results strongly suggest a need for better characterization of those children who would benefit from more active maintenance programs" ]

[ "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 The effectiveness of mobile technology to improve medication adherence via customized Short Messaging Service ( SMS ) reminders for stroke has not been tested in re source poor areas . We design ed a r and omized controlled trial to test the effectiveness of SMS on improving medication adherence in stroke survivors in Pakistan . Methods This was a parallel group , assessor-blinded , r and omized , controlled , superiority trial . Participants were central ly r and omized in fixed block sizes . Adult participants on multiple medications with access to a cell phone and stroke at least 4 weeks from onset ( Onset as defined by last seen normal ) were eligible . The intervention group , in addition to usual care , received reminder SMS for 2 months that contained a ) Personalized , prescription tailored daily medication reminder(s ) b ) Twice weekly health information SMS . The Health Belief Model and Social Cognitive theory were used to design the language and content of messages . Frontline SMS software was used for SMS delivery . Medication adherence was self-reported and measured on the vali date d Urdu version of Morisky Medication Adherence Question naire . Multiple linear regression was used to model the outcome against intervention and other covariates . Analysis was conducted by intention-to-treat principle . Results Two hundred participants were enrolled . 38 participants were lost to follow-up . After 2 months , the mean medication score was 7.4 ( 95 % CI : 7.2–7.6 ) in the intervention group while 6.7 ( 95 % CI : 6.4–7.02 ) in the control group . The adjusted mean difference ( Δ ) was 0.54 ( 95 % CI : 0.22–0.85 ) . The mean diastolic blood pressure in the intervention group was 2.6 mmHg ( 95 % CI ; −5.5 to 0.15 ) lower compared to the usual care group . Conclusion A short intervention of customized SMS can improve medication adherence and effect stroke risk factors like diastolic blood pressure in stroke survivors with complex medication regimens living in re source poor areas .Trial registration Clinical trials.gov NCT01986023 last accessed at https:// clinical", "Background — We assessed the effect of automated treatment adherence support delivered via mobile phone short message system ( SMS ) text messages on blood pressure . Methods and Results — In this pragmatic , single-blind , 3-arm , r and omized trial ( SMS-Text Adherence Support [ StAR ] ) undertaken in South Africa , patients treated for high blood pressure were r and omly allocated in a 1:1:1 ratio to information only , interactive SMS text messaging , or usual care . The primary outcome was change in systolic blood pressure at 12 months from baseline measured with a vali date d oscillometric device . All trial staff were masked to treatment allocation . Analyses were intention to treat . Between June 26 , 2012 , and November 23 , 2012 , 1372 participants were r and omized to receive information-only SMS text messages ( n=457 ) , interactive SMS text messages ( n=458 ) , or usual care ( n=457 ) . Primary outcome data were available for 1256 participants ( 92 % ) . At 12 months , the mean adjusted change in systolic blood pressure compared with usual care was −2.2 mm Hg ( 95 % confidence interval , −4.4 to −0.04 ) with information-only SMS and −1.6 mm Hg ( 95 % confidence interval , −3.7 to 0.6 ) with interactive SMS . Odds ratios for the proportion of participants with a blood pressure general outpatient population of adults with high blood pressure , we found a small reduction in systolic blood pressure control compared with usual care at 12 months . There was no evidence that an interactive intervention increased this effect . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT02019823 . South African National Clinical Trials Register , number SANCTR DOH-27 - 1212 - 386 ; Pan Africa Trial Register , number PACTR201411000724141", "PURPOSE The present study evaluated whether an intervention using a short message service ( SMS ) by cellular phone and Internet would improve blood pressure , weight control , and serum lipids of obese patients with hypertension during 8 weeks . METHODS This is a quasi-experimental design with pre- and follow-up tests . Participants were recruited from the family medicine outpatient department of tertiary care hospital located in an urban city of South Korea . Twenty-eight patients were assigned to an intervention group and 21 to a control group . The goal of intervention was to bring blood pressure , body weight , and serum lipids levels close to normal ranges . Patients in the intervention group were requested to record their blood pressure and body weight in a weekly web based diary through the Internet or by cellular phones . The research ers sent optimal recommendations as an intervention to each patient , by both cellular phone and Internet weekly . The intervention was applied for 8 weeks . RESULTS Systolic ( SBP ) and diastolic blood pressures ( DBP ) significantly decreased by 9.1 and 7.2 mmHg respectively at 8 weeks from the baseline in the intervention group ( p SBP and DBP in the control group had not changed significantly . Yet , There were significant mean decreases in body weight and waist circumference by 1.6 kg ( p body weight and waist circumference ( p High density lipoprotein cholesterol ( HDL-C ) significantly increased , with a mean change of 3.7 mg/dl at 8 weeks from baseline in the intervention group ( p change of HDL-C in the control group was , however , not significant . CONCLUSION During 8 weeks using this web-based intervention by way of cellular phone and Internet SMS improved blood pressure , body weight , waist circumference , and HDL-C in patients with obese hypertension", "IMPORTANCE Cardiovascular disease prevention , including lifestyle modification , is important but underutilized . Mobile health strategies could address this gap but lack evidence of therapeutic benefit . OBJECTIVE To examine the effect of a lifestyle-focused semipersonalized support program delivered by mobile phone text message on cardiovascular risk factors . DESIGN AND SETTING The Tobacco , Exercise and Diet Messages ( TEXT ME ) trial was a parallel-group , single-blind , r and omized clinical trial that recruited 710 patients ( mean age , 58 [ SD , 9.2 ] years ; 82 % men ; 53 % current smokers ) with proven coronary heart disease ( prior myocardial infa rct ion or proven angiographically ) between September 2011 and November 2013 from a large tertiary hospital in Sydney , Australia . INTERVENTIONS Patients in the intervention group ( n = 352 ) received 4 text messages per week for 6 months in addition to usual care . Text messages provided advice , motivational reminders , and support to change lifestyle behaviors . Patients in the control group ( n=358 ) received usual care . Messages for each participant were selected from a bank of messages according to baseline characteristics ( eg , smoking ) and delivered via an automated computerized message management system . The program was not interactive . MAIN OUTCOMES AND MEASURES The primary end point was low-density lipoprotein cholesterol ( LDL-C ) level at 6 months . Secondary end points included systolic blood pressure , body mass index ( BMI ) , physical activity , and smoking status . RESULTS At 6 months , levels of LDL-C were significantly lower in intervention participants , with concurrent reductions in systolic blood pressure and BMI , significant increases in physical activity , and a significant reduction in smoking . The majority reported the text messages to be useful ( 91 % ) , easy to underst and ( 97 % ) , and appropriate in frequency ( 86 % ) . [ table : see text ] . CONCLUSIONS AND RELEVANCE Among patients with coronary heart disease , the use of a lifestyle-focused text messaging service compared with usual care result ed in a modest improvement in LDL-C level and greater improvement in other cardiovascular disease risk factors . The duration of these effects and hence whether they result in improved clinical outcomes remain to be determined . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12611000161921", "Background : Medication non-adherence leads to a vast range of negative outcomes in patients with coronary artery disease . An automated web-based system managing short message service ( SMS ) reminders is a telemedicine approach to optimise adherence among patients who frequently forget to take their medications or miss the timing . Aim : This paper sought to investigate the effect of automated SMS-based reminders on medication adherence in patients after hospital discharge following acute coronary syndrome ( ACS ) . Methods : An interventional study was conducted at a tertiary teaching hospital in Malaysia . A total of 62 patients with ACS were equally r and omised to receive either automated SMS reminders before every intake of cardiac medications or only usual care within eight weeks after discharge . The primary outcome was adherence to cardiac medications . Secondary outcomes were the heart functional status , and ACS-related hospital readmission and death rates . Results : There was a higher medication adherence level in the intervention group rather than the usual care group , ( χ2 (2)=18.614 , p of being low adherent among the control group was 4.09 times greater than the intervention group ( relative risk = 4.09 , 95 % confidence interval ( CI ) 1.82–9.18 ) . A meaningful difference was found in heart functional status between the two study groups with better results among patients who received SMS reminders , ( χ2 ( 1 ) = 16.957 , p automated SMS-based reminder system can potentially enhance medication adherence in ACS patients during the early post-discharge period", "Background : Self-care management has recently been suggested as an effective approach for secondary prevention of hypertension . This study was conducted to examine whether self-care behaviors could modulate blood pressure levels and also comparing the different training methods of self-care on patients ' adherence and controlling hypertension . Material s and Methods : This study was a prospect i ve r and omized controlled clinical trial , conducted on 180 hypertensive patients referring to four centers in Isfahan , Iran , between July and December 2013 . Block r and omization method were applied to divide eligible subjects into four equal groups , including group A in which the patients and their family were educated by cardiology resident about self-care behaviors through eight sessions , group B and group C were obtained self-care education through four pamphlets or eight short message services ( SMS ) , respectively and group D were obtained only usual care of hypertension without any training about self-care management . Results : Increasing vegetable intake and frequency of subject who took antihypertensive medication regularly and the reduction in the frequency of subjects who consumed high salt were significantly more in group A than the others ( P = 0.001 , P respectively ) . The systolic and diastolic blood pressure had significantly more reduction in the group A than the other groups ( −8.18 ± 18.3 and − 3.89 ± 4.1 ; P The self-care management education integration into the usual care along with using SMS and other educational material s may improve the efficient and effective adherence strategies ", "OBJECTIVE The impact of a text messaging-assisted lifestyle weight loss intervention on weight change among overweight adults in Beijing was examined . METHODS It was a 6-month r and omized two arm clinical trial . The control group received a brief advice session after r and omization . The intervention group received three group sessions , five coaching calls , and a daily text message prompting participants to follow predetermined lifestyle goals . RESULTS A total of 123 participants were r and omized . At 6 months , controls gained 0.24 ± 0.28 kg ( 0.21 % ± 0.38 % ) ( NS ) while intervention participants lost 1.6 ± 0.28 kg ( 2.31 % ± 0.38 % ) ( p decreased waist circumference ( WC ) ( -2.69 ± 0.43 cm , p ( % BF ) ( -0.66 % ± 0.19 % , p = 0.0007 ) , and systolic/diastolic blood pressure ( SBP/DBP ) significantly ( -1.71 ± 1.12/-3.24 ± 0.87 mmHg ) , while the controls had no change in WC and % BF and increased SBP/DBP by 2.43 ± 1.14/1.20 ± 0.88 mmHg ( between groups : p = 0.01/p = 0.0004 ) . CONCLUSIONS This text message-assisted lifestyle intervention was effective in reducing weight , WC , % BF , and improving BP . Coupled with the scalable feature of the intervention , this finding is intriguing in light of the potential reach of the intervention for countries like China where mobile phone penetration is high and the obesity rate continues to rise", "OBJECTIVE Pharmacologic treatment for secondary prevention of coronary heart disease ( CHD ) is critical to prevent adverse clinical outcomes . In a r and omized controlled trial , we compared antiplatelet and statin adherence among patients with CHD who received : ( 1 ) text messages ( TM ) for medication reminders and education , ( 2 ) educational TM only , or ( 3 ) No TM . METHODS A mobile health intervention delivered customized TM for 30 days . We assessed and analyzed medication adherence with electronic monitoring devices [ Medication Event Monitoring System ( MEMS ) ] by one-way ANOVA and Welch tests , two-way TM response rates by t-tests , and self-reported adherence ( Morisky Medication Adherence Scale ) by Repeated Measures ANOVA . RESULTS Among 90 patients ( 76 % male , mean age 59.2 years ) , MEMS revealed patients who received TM for antiplatelets had a higher percentage of correct doses taken ( p=0.02 ) , percentage number of doses taken ( p=0.01 ) , and percentage of prescribed doses taken on schedule ( p=0.01 ) . TM response rates were higher for antiplatelets than statins ( p=0.005 ) . Self-reported adherence revealed no significant differences among groups . CONCLUSION TM increased adherence to antiplatelet therapy demonstrated by MEMS and TM responses . PRACTICE IMPLICATION S Feasibility and high satisfaction were established . Mobile health interventions show promise in promoting medication adherence", "Background About one third of patients prescribed blood pressure or lipid-lowering drugs for the prevention of coronary heart disease and stroke do not take their medication as prescribed . We conducted a r and omized trial to evaluate text messaging as a means of improving adherence to cardiovascular disease preventive treatment . Methods 303 patients taking blood pressure and /or lipid-lowering medications were r and omly assigned to being sent text messages ( Text group , 151 ) or not being sent them ( No text group , 152 ) . Texts were sent daily for 2 weeks , alternate days for 2 weeks and weekly thereafter for 22 weeks ( 6 months overall ) , using an automated computer programme . Patients were asked to respond on whether they had taken their medication , whether the text reminded them to do so if they had forgotten , and if they had not taken their medication to determine if there was a reason for not doing so . At 6 months , use of medication was assessed . Results Two patients were lost to follow-up , providing data on 301 for analysis . In the No text group 38/151 ( 25 % ) took less than 80 % of the prescribed regimen ( ie . stopped medication completely or took it on fewer than 22 of the last 28 days of follow-up ) compared to 14/150 patients ( 9 % ) in the Text group – an improvement in adherence affecting 16 per 100 patients ( 95 % CI 7 to 24 ) , p take medication on at least one occasion and lead to 20/151 ( 13 % ) who stopped taking medication because of concern over efficacy or side-effects , resuming treatment . Conclusions In patients taking blood pressure or lipid-lowering treatment for the prevention of cardiovascular disease , text messaging improved medication adherence compared with no text messaging . Trial Registration Controlled-Trials.com IS RCT", "The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials" ]

[ "Background Little is known about preschool-aged children ’s levels of physical activity ( PA ) over the course of the day . Using time-stamped data , we describe the levels and patterns of PA in a population -based sample of four-year-old British children . Methods Within the Southampton Women ’s Survey the PA levels of 593 4-year-old children ( 51 % female ) were measured using ( Actiheart ) accelerometry for up to 7 days . Three outcome measures : minutes spent sedentary ( in light ( LPA : ≥20 – 399 cpm ) and in moderate-to-vigorous activity ( MVPA : ≥400 cpm ) were derived . Average daily activity levels were calculated and then segmented across the day ( morning , afternoon and evening ) . MVPA was log-transformed . Two-level r and om intercept models were used to analyse associations between activity level and temporal and demographic factors . Results Children were active for 67 % ( mean 568.5 SD 79.5 minutes ) of their daily registered time on average , with 88 % of active time spent in LPA . All children met current UK guidelines of 180 minutes of daily activity . There were no differences in children ’s average daily levels of sedentary activity and LPA by temporal and demographic factors : differences did emerge when activity was segmented across the day . Sex differences were largest in the morning , with girls being more sedentary , spending fewer minutes in LPA and 18 % less time in MVPA than boys . Children were more sedentary and less active ( LPA and MVPA ) in the morning if they attended childcare full-time compared to part-time , and on weekend mornings compared to weekdays . The reverse was true for weekend afternoons and evenings . Children with more educated mothers were less active in the evenings . Children were less sedentary and did more MVPA on summer evenings compared to winter evenings . Conclusions Preschool-aged children meet current physical activity guidelines , but with the majority of their active time spent in LPA , investigation of the importance of activity intensity in younger children is needed . Activity levels over the day differed by demographic and temporal factors , highlighting the need to consider temporality in future interventions . Increasing girls ’ morning activity and providing opportunities for daytime activity in winter months may be worthwhile", "Purpose Pattern recognition approaches to accelerometer data processing have emerged as viable alternatives to cut-point methods . However , few studies have explored the validity of pattern recognition approaches in preschoolers , and none have compared supervised learning algorithms trained on hip and wrist data . Purpose of this study was to develop , test , and compare activity class recognition algorithms trained on hip , wrist , and combined hip and wrist accelerometer data in preschoolers . Methods Eleven children 3–6 yr of age ( mean age , 4.8 ± 0.9 yr ) completed 12 developmentally appropriate physical activity ( PA ) trials while wearing an ActiGraph GT3X+ accelerometer on the right hip and nondominant wrist . PA trials were categorized as sedentary , light activity games , moderate-to-vigorous games , walking , and running . R and om forest ( RF ) and support vector machine ( SVM ) classifiers were trained using time and frequency domain features from the vector magnitude of the raw signal . Features were extracted from 15-s nonoverlapping windows . Classifier performance was evaluated using leave-one-out cross-validation . Results Cross-validation accuracy for the hip , wrist , and combined hip and wrist RF models was 0.80 ( 95 % confidence interval ( CI ) , 0.79–0.82 ) , 0.78 ( 95 % CI , 0.77–0.80 ) , and 0.82 ( 95 % CI , 0.80–0.83 ) , respectively . Accuracy for hip , wrist , and combined hip and wrist SVM models was 0.81 ( 95 % CI , 0.80–0.83 ) , 0.80 ( 95 % CI , 0.79–0.80 ) , and 0.85 ( 95 % CI , 0.84–0.86 ) , respectively . Recognition accuracy was consistently excellent for sedentary ( > 90 % ) ; moderate for light activity games , moderate-to-vigorous games , and running ( 69%–79 % ) ; and modest for walking ( 61%–71 % ) . Conclusions Machine learning algorithms such as RF and SVM are useful for predicting PA class from accelerometer data collected in preschool children . Although classifiers trained on hip or wrist data provided acceptable recognition accuracy , the combination of hip and wrist accelerometer delivered better performance ", "Background Identifying ways to promote physical activity and decrease sedentary time during childhood is a key public health issue . Research on the putative influences on preschool children ’s physical activity ( PA ) and sedentary behavior ( SB ) is limited and has yielded inconsistent results . Our aim was to identify correlates of PA and SB in preschool children . Methods Cross-sectional data were drawn from the Swiss Preschoolers ’ Health Study ( SPLASHY ) , a Swiss population -based cohort study . Of 476 two to six year old children , 394 ( 54 % boys ) had valid PA data assessed by accelerometry . Information on exposure data was directly measured or extracted from parental question naires . Multilevel linear regression modeling was used to separately assess associations between 35 potential correlates and total PA ( TPA ) , moderate-to-vigorous PA ( MVPA ) and SB . Results In total , 12 correlates from different domains were identified . TPA and MVPA were greater in boys than girls , increased with age and were positively associated with gross motor skills . Children from single parent families had a higher level of TPA and spent less time sedentary than those living with two parents . Time spent outdoors was positively associated with TPA and negatively with SB . The child ’s activity temperament was related all three outcomes , whereas parental sports club membership , living area per person and neighborhood safety were associated with SB only . Fixed and r and om factors in the final models accounted for 28 % , 32 % and 22 % of the total variance in TPA , MVPA and SB , respectively . Variance decomposition revealed that age , sex and activity temperament were the most influential correlates of both , TPA and MVPA , whereas the child ’s activity temperament , time outdoors and neighborhood safety were identified as the most important correlates of SB . Conclusions A multidimensional set of correlates of young children ’s activity behavior has been identified . Personal factors had the greatest influence on PA , whereas environmental-level factors had the greatest influence on SB . Moreover , we identified a number of previously unreported , potentially modifiable correlates of young children ’s PA and SB . These factors could serve to define target groups or become valuable targets for change in future interventions .Trial registration Current Controlled Trials IS RCT N41045021 ( date of registration : 21.03.14 )", "Aim To determine whether levels of daytime physical activity are associated with sleep duration and night waking in children assessed using accelerometry , and if these associations change over time . Methods 24-hour accelerometry data were obtained from 234 children at 3 , 5 and 7 years of age for at least 5 days at each time . Sleep duration was estimated using the Sadeh algorithm . Time spent in sedentary , light and moderate-vigorous ( MVPA ) activity was established using published cut-points . Appropriate statistical techniques were utilised to account for the closed nature of the data ( 24-hour periods ) . Results Time spent asleep was related more to sedentary or light activity and not to MVPA . The most active ( 95th percentile ) children spent 55–84 fewer minutes asleep and 16–19 more minutes awake at night compared to the least active ( 5th percentile ) children . Children with later bedtimes slept less at night ( 30–40 minutes ) and undertook more sedentary ( 10–15 minutes ) but also more light ( 18–23 minutes ) activity during the day . However , no differences in MVPA were apparent according to bedtime . Children slept slightly less on weekend nights ( 11 minutes ) compared with week-nights , but only at 3 years of age . Most relationships were broadly similar at 3 , 5 and 7 years of age . Conclusion Children who are more physically active during the day have shorter total sleep time and are more awake at night than less active children . The protective effect of sleep on obesity does not appear to be mediated by increased physical activity ", "OBJECTIVE To calibrate the Actigraph GT3X+ accelerometer for wrist-worn placement in young preschoolers by developing intensity thresholds for sedentary , low- and high-intensity physical activity . Furthermore , to cross-vali date the developed thresholds in young preschoolers . METHODS Actigraph GT3X+ was used to measure physical activity during structured activities and free play in 38 children ( 15 - 36 months ) . Activity was video recorded and scored into sedentary , low- and high-intensity physical activity based on Children 's Activity Rating Scale ( CARS ) and combined with accelerometer data using a 5 s epoch . Receiver operating characteristic analysis was used to develop intensity thresholds in 26 r and omly selected children . The remaining 12 children were used for cross-validation . RESULTS Intensity thresholds for sedentary were ≤89 vertical counts ( Y ) and ≤221 vector magnitude ( VM ) counts per 5 s and ≥440 Y counts and ≥730 VM counts per 5 s for high-intensity physical activity . Sensitivity and specificity were 60 - 100 % for the developed intensity thresholds . Strong correlations ( Spearman rank correlation 0.69 - 0.91 ) were found in the cross-validation sample between the developed thresholds for the accelerometer and CARS scoring time in all intensity categories . CONCLUSION The developed intensity thresholds appear valid to categorize sedentary behaviour and physical activity intensity categories in children 2 years of age", "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 Alcohol misuse is a key factor underlying the remarkable vulnerability to HIV infection among men and women in sub-Saharan Africa , especially within urban setting s. Its effects , however , vary by type of drinking , population group and are modified by socio-cultural co-factors . Methods We interviewed a r and om sample of 1465 men living in single-sex hostels and 1008 women in adjacent informal settlements in inner-city , Johannesburg , South Africa . Being drunk in the past week was used as an indicator of heavy episodic drinking , and frequency of drinking and number of alcohol units/week used as measures of volume . Associations between dimensions of alcohol use ( current drinking , volume of alcohol consumed and heavy episodic drinking patterns ) and sexual behaviours were assessed using multivariate logistic regression . Results Most participants were internal migrants from KwaZulu Natal province . About half of men were current drinkers , as were 13 % of women . Of current male drinkers , 18 % drank daily and 23 % were drunk in the past week ( women : 14 % and 29 % respectively ) . Among men , associations between heavy episodic drinking and sexual behaviour were especially pronounced . Compared with non-drinkers , episodic ones were 2.6 fold more likely to have transactional sex ( 95%CI = 1.7–4.1 ) and 2.2 fold more likely to have a concurrent partner ( 95%CI = 1.5–3.2 ) . Alcohol use in men , regardless of measure , was strongly associated with having used physical force to have sex . Overall effects of alcohol on sexual behaviour were larger in women than men , and associations were detected between all alcohol measures in women , and concurrency , transactional sex and having been forced to have sex . Conclusions Alcohol use and sexual behaviours are strongly linked among male and female migrant population s in inner-city Johannesburg . More rigorous interventions at both local and macro level are needed to alleviate alcohol harms and mitigate the alcohol-HIV nexus , especially among already vulnerable groups . These should target the specific dimensions of alcohol use that are harmful , assist women who drink to do so more safely and address the linkages between alcohol and sexual violence", "Background In the UK , thous and s of people with high cardiovascular risk are being identified by a national risk- assessment programme ( NHS Health Checks ) . Waste the Waist is an evidence -informed , theory-driven ( modified Health Action Process Approach ) , group-based intervention design ed to promote healthy eating and physical activity for people with high cardiovascular risk . This pilot r and omised controlled trial aim ed to assess the feasibility of delivering the Waste the Waist intervention in UK primary care and of conducting a full-scale r and omised controlled trial . We also conducted exploratory analyses of changes in weight . Methods Patients aged 40–74 with a Body Mass Index of 28 or more and high cardiovascular risk were identified from risk- assessment data or from practice data base search es . Participants were r and omised , using an online computerised r and omisation algorithm , to receive usual care and st and ardised information on cardiovascular risk and lifestyle ( Controls ) or nine sessions of the Waste the Waist programme ( Intervention ) . Group allocation was concealed until the point of r and omisation . Thereafter , the statistician , but not participants or data collectors were blinded to group allocation . Weight , physical activity ( accelerometry ) and cardiovascular risk markers ( blood tests ) were measured at 0 , 4 and 12 months . Results 108 participants ( 22 % of those approached ) were recruited ( 55 intervention , 53 controls ) from 6 practice s and 89 % provided data at both 4 and 12 months . Participants had a mean age of 65 and 70 % were male . Intervention participants attended 72 % of group sessions . Based on last observations carried forward , the intervention group did not lose significantly more weight than controls at 12 months , although the difference was significant when co- interventions and co-morbidities that could affect weight were taken into account ( Mean Diff 2.6Kg . 95%CI : −4.8 to −0.3 , p = 0.025 ) . No significant differences were found in physical activity . Conclusions The Waste the Waist intervention is deliverable in UK primary care , has acceptable recruitment and retention rates and produces promising preliminary weight loss results . Subject to refinement of the physical activity component , it is now ready for evaluation in a full-scale trial . Trial registration Current Controlled Trials IS RCT N10707899", "Objective Routine moderate-to-vigorous physical activity ( MVPA ) is associated with better health outcomes ; the purpose of this work was to evaluate healthy preschooler physical activity patterns with objective measurement . Methods and Procedures An objective prospect i ve study of fifty normally-developing children 3–5 years old who were ≥50th and Participants wore a tri-axial accelerometer for 7 continuous days . Outcome measures consisted of wear time examining four common MVPA patterns : isolated spurt ( IS ) , isolated sustained activity ( ISA ) , clustered spurt ( CS ) , and clustered sustained activity ( CSA ) . Results Participants were 4.3 years , 56 % female , 52 % African-American , and 26 % overweight . Forty-five children met wear time criteria . On average , children spent 14.5 % of wake-wear time in MVPA , requiring 11.3 hours to complete 90 % of their daily MVPA . Children spent the majority of MVPA in CS ( 62.1 % , followed by CSA ( 20.1 % ) . Remaining MVPA was spent in IS ( 15.5 % ) and ISA ( 2.3 % ) . Conclusion It takes most of the waking day for preschoolers to attain their PA . They engage in short spurts of small duration , in four common MVPA patterns . Utilizing this method could better characterize preschooler physical activity needs in practice and policy guidelines", "Background : Using a large population -based sample , this study aims to verify whether televiewing at 29 mo , a common early childhood pastime , is prospect ively associated with school readiness at 65 mo . Methods : Participants are a prospect i ve longitudinal cohort of 991 girls and 1,006 boys from the Quebec Longitudinal Study of Child Development with parent-reported data on weekly hours of televiewing at 29 mo of age . We conducted a series of ordinary least-squares regressions in which children ’s scores on direct child assessment s of vocabulary , mathematical knowledge , and motor skills , as well as kindergarten teacher reports of socioemotional functioning , were linearly regressed on early televiewing . Results : Every SD increase ( 1.2 h ) in daily televiewing at 29 mo predicted decreases in receptive vocabulary , number knowledge scores , classroom engagement , and gross motor locomotion scores , as well as increases in the frequency of victimization by classmates . Conclusion : Increases in total time watching television at 29 mo were associated with subsequent decreases in vocabulary and math skills , classroom engagement ( which is largely determined by attention skills ) , victimization by classmates , and physical prowess at kindergarten . These prospect i ve associations , independent of key potential confounders , suggest the need for better parental awareness and compliance with existing viewing recommendations put forth by the American Academy of Pediatrics ( AAP )", "Background : Using a birth cohort , this study aim ed to verify whether televiewing at 29 months , a common early childhood pastime , is prospect ively associated with self-reported victimization at age 12 . Methods : Participants are 991 girls and 1006 boys from the Quebec Longitudinal Study of Child Development . The main predictor comprised parent-reported daily televiewing by their children at 29 months . In the sixth grade , children reported how often they experienced victimization by classmates in the past year . The authors conducted multivariate linear regression , in which child self-reports of victimization were linearly regressed on early televiewing and potential confounders . Results : Every SD unit increase ( 0.88 hours ) in daily televiewing at 29 months predicted an 11 % SD unit increase in self-reported peer victimization by sixth grade classmates ( unst and ardized B = .031 , p Daily televiewing time at 29 months was associated with a subsequent increased risk of victimization by classmates at the end of sixth grade , a period which represents a critical developmental transition to middle school . Youth who experience peer victimization are at an increased risk of long-term mental health issues , such as depression , underachievement , and low self-esteem . This prospect i ve association , across a 10-year period , suggests the need for better parental awareness , acknowledgement , and compliance with existing recommendations put forth by the American Academy of Pediatrics", "BACKGROUND Young children depend on adult caregivers to provide opportunities for physical activity . Research has focused on barriers and facilitators to children 's physical activity while in childcare , but parental influences remain largely unknown . This study examines parent 's attitudes about preschoolers ' physical activity and outdoor time , compares them with those of childcare providers and determines the association between parental attitudes and preschoolers ' measured activity . METHODS Parents and childcare providers from 30 childcare centres were surveyed regarding attitudes towards preschoolers ' physical activity and outdoor time . Children 's moderate-to-vigorous physical activity was determined by using 24-h accelerometry . Parent and childcare providers ' responses were compared . Mixed-effect linear regression examined moderate-to-vigorous physical activity and sedentary time as outcomes with parental attitudes as predictors , family demographics as covariates and centre as a r and om effect . RESULTS Three hundred eighty-eight parents and 151 childcare providers participated . On average , children were 4.3 ( 0.7 ) years old . Parents and childcare providers both considered daily physical activity important for preschoolers , but providers rated the importance of daily outdoor time higher on a 10-point scale ( 8.9 vs. 7.6 , P children would get sick by playing outside in the cold ( 25 vs. 11 % , P comfortable with their child playing outside at childcare compared with outside at home ( 8.9 vs. 6.9 , P Lower income parents felt less comfortable than higher income parents with their child playing outside either near home or at childcare . Neither home nor total child activity levels were associated with most parental attitudes queried . CONCLUSIONS While parents and childcare providers value daily physical activity for children , some parents expressed discomfort about their young children engaging in outdoor play , especially around home and in cold weather . These findings highlight the importance of childcare-based interventions to promote preschoolers ' physical activity and outdoor play", "OBJECTIVE : The goal of this study was to examine activity pattern associations between Hispanic parents and their preschool-aged children . METHODS : We examined baseline data collected as part of a r and omized controlled trial . Self-defined Hispanic parents with children aged 3 to 5 years were r and omly assigned to either a weekly healthy lifestyle group ( intervention ) or a monthly school-readiness group ( control ) for 3 months . There were no weight eligibility criteria . All participants were instructed to wear an accelerometer for up to 7 consecutive days to measure physical activity . RESULTS : Of the 106 dyads enrolled in the study , 80 children and 85 parents provided useable actigraphy data . Mean percentage of time spent in sedentary behaviors was 82.0 % ( SD : 10.4 ) for parents and 69.8 % ( SD : 18.5 ) for preschool-aged children . Percentage of awake time per day spent in sedentary behavior was strongly correlated for parents and children ( r = 0.597 ; P activity level were large ( r = 0.895 and 0.739 for low and moderate activity levels , respectively ) , except for vigorous activity level , for which the parent-child correlation was nonsignificant ( P = .64 ) because of a near-0 level of vigorous parental activity . Child 's age ( P = .81 ) and gender ( P = .43 ) were nonsignificant predictors of child activity levels . CONCLUSIONS : These results suggest that parental activity levels are a powerful explanation of preschool-aged child activity levels , except for vigorous activity , which children do on their own without parental participation . Hispanic parents play a critical role in setting physical activity patterns in their children", "PURPOSE To test for relationships between objective ly measured habitual physical activity and fundamental movement skills in a relatively large and representative sample of preschool children . METHODS Physical activity was measured over 6 d using the Computer Science and Applications ( CSA ) accelerometer in 394 boys and girls ( mean age 4.2 , SD 0.5 yr ) . Children were scored on 15 fundamental movement skills , based on the Movement Assessment Battery , by a single observer . RESULTS Total physical activity ( r=0.10 , P percent time spent in moderate to vigorous physical activity ( MVPA ) ( r=0.18 , P total movement skills score . Time spent in light-intensity physical activity was not significantly correlated with motor skills score ( r=0.02 , P>0.05 ) . CONCLUSIONS In this sample and setting , fundamental movement skills were significantly associated with habitual physical activity , but the association between the two variables was weak . The present study questions whether the widely assumed relationships between motor skills and habitual physical activity actually exist in young children", "OBJECTIVE The impact of physical activity patterns and sleep duration on growth and body composition of preschool-aged children remains unresolved . Aims were ( 1 ) to delineate cross-sectional associations among physical activity components , sleep , total energy expenditure ( TEE ) , and body size and composition ; and ( 2 ) to determine whether physical activity components , sleep , and TEE predict 1-year changes in body size and composition in healthy preschool-aged children . METHODS Anthropometry , body composition , accelerometry , and TEE by doubly labeled water were measured at baseline ; anthropometry and body composition were repeated 1 year later ( n = 111 ) . RESULTS Cross-sectionally , positive associations between sedentary activity and weight and fat-free mass ( FFM ) ( P = 0.009 - 0.047 ) , and a negative association between moderate-vigorous physical activity ( MVPA ) and percent fat mass ( FM ) ( P = 0.015 ) were observed . TEE and activity energy expenditure ( AEE ) were positively associated with weight , body mass index ( BMI ) , FFM , and FM ( P = 0.0001 - 0.046 ) . Prospect ively , TEE , AEE , physical activity level , and MVPA , but not sedentary activity , were positively associated with changes in BMI ( P = 0.0001 - 0.051 ) and FFM ( P = 0.0001 - 0.037 ) , but not percent FM . Sleep duration inversely predicted changes in FM ( P = 0.005 ) and percent FM ( P = 0.006 ) . CONCLUSIONS Prospect ively , MVPA , TEE , AEE , and physical activity level promote normal growth and accretion of FFM , whereas sleep duration inversely predicts changes in adiposity in preschool-aged children" ]

[ "BACKGROUND A role for vitamin D deficiency in Parkinson disease ( PD ) has recently been proposed . OBJECTIVE To compare the prevalence of vitamin D deficiency in a research data base cohort of patients with PD with the prevalence in age-matched healthy controls and patients with Alzheimer disease ( AD ) . DESIGN Survey study and blinded comparison of plasma 25-hydroxyvitamin D ( 25[OH]D ) concentrations of stored sample s in a clinical research data base at Emory University School of Medicine . SETTING Referral center ( PD and AD patients ) , primary care clinics , and community setting ( controls ) . PARTICIPANTS Participants were recruited into the study between May 1992 and March 2007 . Every fifth consecutively enrolled PD patient was selected from the clinical research data base . Unrelated AD ( n = 97 ) and control ( n = 99 ) participants were r and omly selected from the data base after matching for age , sex , race , APOE genotype , and geographic location . MAIN OUTCOME MEASURES Prevalence of suboptimal vitamin D and mean 25(OH)D concentrations . RESULTS Significantly more patients with PD ( 55 % ) had insufficient vitamin D than did controls ( 36 % ) or patients with AD ( 41 % ; P = .02 , chi(2)test ) . The mean ( SD ) 25(OH)D concentration in the PD cohort was significantly lower than in the AD and control cohorts ( 31.9 [ 13.6 ] ng/mL vs 34.8 [ 15.4 ] ng/mL and 37.0 [ 14.5 ] ng/mL , respectively ; P = .03 ) . CONCLUSIONS This report of 25(OH)D concentrations in a predominantly white PD cohort demonstrates a significantly higher prevalence of hypovitaminosis in PD vs both healthy controls and patients with AD . These data support a possible role of vitamin D insufficiency in PD . Further studies are needed to determine the factors contributing to these differences and eluci date the potential role of vitamin D in pathogenesis and clinical course of PD", "Significant reduction in bone mineral density ( BMD ) occurs in patients with Parkinson 's disease ( PD ) , correlating with immobilization and with vitamin D deficiency , and increasing the risk of hip fracture , especially in elderly women . As a biological indicator of compromised vitamin K status , an increased serum concentration of undercarboxylated osteocalcin ( Oc ) has been associated with reduced BMD in the hip and an increased risk of fracture in otherwise healthy elderly women . We evaluated treatment with vitamin K(2 ) ( menatetrenone ; MK-4 ) in maintaining BMD and reducing the incidence of nonvertebral fractures in elderly female patients with PD . In a r and om and prospect i ve study of PD patients , 60 received 45 mg of MK-4 daily for 12 months , and the remaining 60 ( untreated group ) did not . At baseline , patients of both groups showed vitamin D and K(1 ) deficiencies , high serum levels of ionized calcium , and glutaminic residue ( Glu ) Oc , and low levels of parathyroid hormone ( PTH ) and 1,25-dihydroxyvitamin D [ 1,25-(OH)(2)D ] , indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1,25-(OH)(2)D and compensatory PTH secretion . BMD in the second metacarpals increased by 0.9 % in the treated group and decreased by 4.3 % in the untreated group ( p Vitamin K(2 ) level increased by 259.8 % in the treated group . Correspondingly , significant decreases in Glu Oc and calcium were observed in the treated group , in association with an increase in both PTH and 1,25-(OH)(2)D. Ten patients sustained fractures ( eight at the hip and two at other sites ) in the untreated group , and one hip fracture occurred among treated patients ( p = 0.0082 ; odds ratio = 11.5 ) . The treatment with MK-4 can increase the BMD of vitamin D- and K-deficient bone by increasing vitamin K concentration , and it can also decrease calcium levels through inhibition of bone resorption , result ing in an increase in 1,25-(OH)(2)D concentration" ]

[ "We investigated factors associated with falls in a community-based prospect i ve study of 761 subjects 70 years and older . The group experienced 507 falls during the year of monitoring . On entry to the study a number of variables had been assessed in each subject . Variables associated with an increased risk of falling differed in men and women . In men , decreased levels of physical activity , stroke , arthritis of the knees , impairment of gait , and increased body sway were associated with an increased risk of falls . In women , the total number of drugs , psychotropic drugs and drugs liable to cause postural hypotension , st and ing systolic blood pressure of less than 110 mmHg , and evidence of muscle weakness were also associated with an increased risk of falling . Most falls in elderly people are associated with multiple risk factors , many of which are potentially remediable . The possible implication s of this in diagnosis and prevention are discussed", "Objective : Comparison of two flooring types – carpet and vinyl – in the bed areas , and two modes of physiotherapy – conventional therapy and additional leg strengthening exercises – in avoiding falls . Design : R and omized 2 × 2 controlled trial . Setting : Elderly care rehabilitation ward in a community hospital . Subjects : Fifty-four consecutive patients referred for rehabilitation . Outcome measures : The incidence of falls , and the change in strength . Results : There were 10 falls on carpet , and only a single fall on vinyl floor covering ( relative risk 8.3 , 95 % confidence interval 0.95–73 , p = 0.05 ) . There were four falls in those receiving additional exercise , and seven falls in those receiving only conventional physiotherapy ( relative risk 0.21 , 95 % confidence interval 0.04–1.2 , p = 0.12 ) . Fifty-nine per cent of patients were able to complete strength measurements on admission and discharge . In these , h and grip strength improved more in those given additional exercise than conventional physiotherapy ( 2.1 kg versus – 0.3 kg , p preventing falls on a rehabilitation ward , but within this low-powered study , there was a strong trend towards vinyl being superior ", "Regular exercise has been recommended to improve balance , strength , and coordination in older persons . In this study , 44 persons , aged 50 to 75 years ( mean 62.4 yrs ) underwent assessment s of quadriceps strength , reaction time , neuromuscular control , and body sway on two occasions before beginning a 10-week exercise program . The subjects were retested for the same measures at the end of the program . The mean number of classes attended for the 40 subjects who were retested was 16.2 ( range 11 to 19 ) . On completion of the program , the subjects showed improved performance in the tests of quadriceps strength , reaction time , body sway on a firm surface with the eyes closed , and a compliant surface with the eyes open and closed . In contrast , a group of nonexercisers showed no improvements in any of the test measures . These results suggest that exercise may play a role in improving a number of sensorimotor systems that contribute to stability in older persons", "CONTEXT Hip fractures are common in the elderly , and despite st and ard rehabilitation , many patients fail to regain their prefracture ambulatory or functional status . OBJECTIVE To determine whether extended outpatient rehabilitation that includes progressive resistance training improves physical function and reduces disability compared with low-intensity home exercise among physically frail elderly patients with hip fracture . DESIGN , SETTING , AND PATIENTS R and omized controlled trial conducted between August 1998 and May 2003 among 90 community-dwelling women and men aged 65 years or older who had had surgical repair of a proximal femur fracture no more than 16 weeks prior and had completed st and ard physical therapy . INTERVENTION Participants were r and omly assigned to 6 months of either supervised physical therapy and exercise training ( n = 46 ) or home exercise ( control condition ; n = 44 ) . MAIN OUTCOME MEASURES Primary outcome measures were total scores on a modified Physical Performance Test ( PPT ) , the Functional Status Question naire physical function subscale ( FSQ ) , and activities of daily living scales . Secondary outcome measures were st and ardized measures of skeletal muscle strength , gait , balance , quality of life , and body composition . Participants were evaluated at baseline , 3 months , and 6 months . RESULTS Changes over time in the PPT and FSQ scores favored the physical therapy group ( P = .003 and P = .01 , respectively ) . Mean change ( SD ) in PPT score for physical therapy was + 6.5 ( 5.5 ) points ( 95 % confidence interval [ CI ] , 4.6 - 8.3 ) , and for the control condition was + 2.5 ( 3.7 ) points ( 95 % CI , 1.4 - 3.6 points ) . Mean change ( SD ) in FSQ score for physical therapy was + 5.2 ( 5.4 ) points ( 95 % CI , 3.5 - 6.9 ) and for the control condition was + 2.9 ( 3.8 ) points ( 95 % CI , 1.7 - 4.0 ) . Physical therapy also had significantly greater improvements than the control condition in measures of muscle strength , walking speed , balance , and perceived health but not bone mineral density or fat-free mass . CONCLUSION In community-dwelling frail elderly patients with hip fracture , 6 months of extended outpatient rehabilitation that includes progressive resistance training can improve physical function and quality of life and reduce disability compared with low-intensity home exercise", "BACKGROUND Muscle size and strength decrease with aging , and the result ant muscle weakness has been implicated in increased risk of falls in older adults . These falls have large economic and functional costs . METHODS The purpose of this r and omized , controlled study was to determine if an 8-week , 3-day per week intense ( 77.8 + /- 3.4 % of 1-repetition maximum [ 1RM ] ) strength training program could improve functional ability related to the risk of falling in subjects aged 61 - -87 years ( mean 72 , SD 6.3 ) . Twelve strength-training-naive subjects performed two sets of 10 repetitions for six lower body exercises while 12 subjects served as nonintervention controls . Subjects were tested pre- , mid- , and postintervention for strength gain and on three tests of functional ability . RESULTS Postintervention strength was significantly better ( p injuries were reported as a result of either training or 1RM testing . After controlling for preintervention differences , repeated measure analysis of covariance ( ANCOVA ) found a significant difference between experimental and nonintervention control subjects for postintervention maximal walking speed [ F(1,19 ) = 5.03 , p 1-leg blind balance time or 5-repetition sit-to-st and performance [ F(1,19 ) = .082 ; F(1,19 ) = .068 , respectively , p > .05 ] . CONCLUSIONS These findings suggest that strength training alone does not appear to enhance st and ing balance or sit-to-st and performance in active , community-dwelling older adults but that it may improve maximal walking speed . The relationship between strength gain and risk of falls remains unclear . The data do reinforce the notion that intense strength training is a safe and effective way to increase muscle strength in this population", "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", "OBJECTIVE To determine whether a 12-month program of regular exercise can improve dynamic postural stability in older women . DESIGN R and omized controlled trial of 12 months ' duration . SETTING Conducted as part of the R and wick Falls and Fractures Study , in Sydney , Australia . PARTICIPANTS One hundred and twelve community-dwelling women aged 60 to 85 years ( mean age 71.2 , SD = 5.4 ) . OUTCOME MEASURES Quantitative measures of dynamic postural stability : maximal balance range and coordinated stability . MAIN RESULTS Exercise and control subjects were tested before , midway through , and at the end of the trial . The stability measures had good test-retest reliability , and test performances were significantly associated with measures of lower limb muscle strength , reaction time , neuromuscular control , and body sway . At initial testing , exercisers and controls performed similarly in the two stability measures . The mean number of classes attended for the 48 exercise subjects who completed the program was 58.4 ( range 26 - 77 ) . At the end of the trial , the exercise subjects showed significantly improved performance in both the maximal balance range and coordinated stability tests , with no improvement evident in the controls . Improvements in coordinated stability were associated with corresponding improvements in ankle dorsiflexion , hip extension , and hip flexion strength . CONCLUSION These findings show that exercise can significantly improve dynamic postural stability in older persons and eluci date some possible mechanisms by which such improvements may be mediated", "OBJECTIVE To determine whether a 12-month program of regular exercise can improve balance , reaction time , neuromuscular control , and muscle strength and reduce the rate of falling in older women . DESIGN A r and omized , controlled trial of 12 months duration . SETTING Conducted as part of the R and wick Falls and Fractures Study in Sydney , Australia . PARTICIPANTS One hundred ninety-seven women aged 60 to 85 years ( mean age 71.6 , SD = 5.4 ) who were r and omly recruited from the community . OUTCOME MEASURES Accidental falls , postural sway , reaction time , neuromuscular control , and lower limb muscle strength . MAIN RESULTS Exercise and control subjects were tested before , midway through , and at the end of the trial . At initial testing , exercisers and controls performed similarly in all tests and were well matched in relevant health and lifestyle factors . The mean number of classes attended for the 75 exercise subjects who completed the program was 60.0 ( range 26 - 82 ) . At the end of the trial , the exercise subjects showed improved performance in all five strength measures , in reaction time , neuromuscular control , body sway on a firm surface with the eyes open , and body sway on a compliant surface with the eyes open and closed . In contrast , there were no significant improvements in any of the test measures in the controls . In one test measure , hip flexion strength , the exercisers showed continued improvement throughout the study year . There was no significant difference in the proportion of fallers between the exercise and control subjects . Interesting trends were evident , however , between falls frequency and adherence to the exercise program . CONCLUSIONS These findings show that exercise can produce long-term benefits with regard to improving sensorimotor function in older persons . The findings also suggest that high compliance to an exercise program may reduce falls frequency , although further studies are required to conclusively demonstrate that exercise offers an effective means of preventing falls", "BACKGROUND Age-related decline in muscle power may be an early indicator of balance deficits and fall risk , even in nonfrail adults . This study examined the dose-dependent effect of power training on balance performance in healthy older adults . METHODS One hundred twelve community-dwelling healthy older adults ( 69 + /- 6 years ) were r and omized to 8 - 12 weeks of power training at 20 % ( LOW ) , 50 % ( MED ) , or 80 % ( HIGH ) of maximal strength , or a nontraining control ( CON ) group . Participants trained twice weekly ( five exercises ; three sets of eight rapid concentric/slow eccentric repetitions ) using pneumatic resistance machines . Balance , muscle performance ( strength , power , endurance , contraction velocity ) , and body composition were measured . RESULTS Power training significantly improved balance performance ( p = .006 ) in participants who underwent power training compared to controls . Low intensity power training produced the greatest improvement in balance performance ( p = .048 ) . Average contraction velocity at low load ( 40 % one repetition maximum [ 1RM ] ) at baseline independently predicted improvement in balance following training ( r = -.29 , p = .004 ) . CONCLUSIONS Power training improves balance , particularly using a low load , high velocity regimen , in older adults with initial lower muscle power and slower contraction . Further studies are warranted to define the mechanisms underlying this adaptation , as well as the optimum power training intensity for a range of physiological and clinical outcomes in older adults with varying levels of health status and functional independence", "OBJECTIVES To determine whether a 12-month program of group exercise can improve physical functioning and reduce the rate of falling in frail older people . DESIGN Cluster r and omized , controlled trial of 12 months duration . SETTING Retirement villages in Sydney and Wollongong , Australia . PARTICIPANTS Five hundred fifty-one people aged 62 to 95 ( mean+/-st and ard deviation=79.5+/-6.4 ) who were living in self- and intermediate-care retirement villages . MEASUREMENTS Accidental falls , choice stepping reaction time , 6-minute walk distance postural sway , leaning balance , simple reaction time , and lower-limb muscle strength . RESULTS Two hundred eighty subjects were r and omized to the weight-bearing group exercise ( GE ) intervention that was design ed to improve the ability of subjects to undertake activities for daily living . Subjects r and omized to the control arm ( n=271 ) attended flexibility and relaxation ( FR ) classes ( n=90 ) or did not participate in a group activity ( n=181 ) . In spite of the reduced precision of cluster r and omization , there were few differences in the baseline characteristics of the GE and combined control ( CC ) subjects , although the mean age of the GE group was higher than that of the CC group , and there were fewer men in the GE group . The mean number of classes attended was 39.4+/-28.7 for the GE subjects and 31.5+/-25.2 for the FR subjects . After adjusting for age and sex , there were 22 % fewer falls during the trial in the GE group than in the CC group ( incident rate ratio=0.78 , 95 % confidence interval (CI)=0.62 - 0.99 ) , and 31 % fewer falls in the 173 subjects who had fallen in the past year ( incident rate ratio=0.69 , 95 % CI=0.48 - 0.99 ) . At 6-month retest , the GE group performed significantly better than the CC group in tests of choice stepping reaction time , 6-minute walking distance , and simple reaction time requiring a h and press . The groups did not differ at retest in tests of strength , sway , or leaning balance . CONCLUSION These findings show that group exercise can prevent falls and maintain physical functioning in frail older people", "OBJECTIVE The purpose of this pilot was to determine whether a strength and flexibility program in frail long-term care facility ( LTC ) residents would result in improved function . DESIGN A prospect i ve , r and omized , controlled , semicrossover trial was design ed with participants assigned either to group exercise ( EX ) or recreational therapy ( C ) . In the EX group , the intervention continued for 1 year . In the C group , recreation continued for 6 months ; these controls were then crossed over to the same exercise intervention as the EX group and followed for an additional 6 months . Functional outcomes were measured at baseline and 3 , 6 , 9 , and 12 months for both groups . SETTING A LTC facility , which included both assisted living ( AL ) and nursing home ( NH ) residents . PARTICIPANTS Twenty frail residents ( 5 from NH , 15 from AL ) aged 75 to 99 years at one LTC facility . INTERVENTION After r and om group assignment , the EX group met 1 hour three times per week . An exercise physiologist and LTC staff conducted sessions which included seated range of motion ( ROM ) exercises and strength training using simple equipment such as elastic resistance b and s ( therab and s ) and soft weights . The C group met three times per week and participated in activities such as painting during the first 6 months , before crossing over to exercise . MEASUREMENTS AND METHODS Objective measures of physical and cognitive function were obtained at baseline and 3 , 6 , 9 , and 12 months using the timed get-up- and -go test ( TUG ) , Berg balance scale , physical performance test ( PPT ) , and mini-mental status exam ( MMSE ) . Because we were interested in the impact of exercise on multiple endpoints and to protect the type I error rate , a global hypothesis test was used . RESULTS There was a significant overall impact across the four measures of the exercise intervention ( P = 0.013 ) . Exercise benefit as indicated by the difference between exercise and control conditions showed exercise decreased TUG by 18 seconds , which represents an effect size ( in st and ard deviation units ) of 0.50 , increased PPT scores by 1.3 , with effect size = 0.40 , increased Berg scores by 4.8 , with effect size of 0.32 , and increased MMSE by 3.1 , with effect size = 0.54 . Except for the Berg , 90 % confidence intervals on these exercise effects excluded 0 . CONCLUSION Frail elderly in a LTC facility were able to participate and benefit from a strength training program . The program was delivered with low-cost equipment by an exercise physiologist and LTC staff . The advantage of such a program is that it provides recreational and therapeutic benefits ", "Elderly participants experiencing difficulty in chair rising and with a maximum knee-extensor torque below 87.5 N . m were r and omized to different versions of a strength-training program for the knee-extensors : to a high-guidance group ( HG ; two group sessions supervised by a physical therapist and one unsupervised home session per week , n = 17 ) , a medium-guidance group ( MG ; one supervised group session and two unsupervised home sessions per week , n = 16 ) , or a control group ( C ; no exercise , n = 16 ) . Maximal isometric knee strength increased more in HG than in C ( p = .03 ) and with increasing guidance ( p = .03 ) . The effect was mainly the result of participants with low initial strength . Walking speed increased more for HG than for C ( p = .02 ) and than for MG ( p = .06 ) . No statistically significant improvements were seen on other functional tests . In summary , the study shows a trend toward better results with more supervision , but more and larger studies are needed to confirm this", "The purpose of this study was to evaluate the effects of a 24-month moderate-intensity resistive-training intervention on strength and function in older adults . A repeated- measures experimental research design was employed as a sample of 55 apparently healthy , older , community-dwelling volunteers ( 30 exercisers- 25 women and 5 men ; 25 comparisons- 16 women and 9 men ) were evaluated for strength of 5 muscle groups that influence lower extremity movement and physical function . Strength and function were evaluated at 6-month intervals . The findings from this study indicate that a moderate-intensity resistive-training program increases strength in older adults and that the strength benefits are retained for the duration of the intervention . Furthermore , a long-term strength-training program can increase independent-function skills in older adults and might therefore aid in prolonging functional independence" ]

[ "UNLABELLED Chronic diseases of the musculoskeletal system rank first as causes of early retirement in Germany . Therefore orthopaedic rehabilitation has to identify patients with work-related problems and to promote return to work through differential treatment and vocational counselling . In the framework of the IopKo-Project such measures were developed and evaluated . These measures encompass : ( 1 ) an intensive and multiprofessional diagnostic pathway which allows early detection and treatment of mental disorders and job related problems ; ( 2 ) homogeneous treatment groups based on multiprofessional diagnostics ; ( 3 ) differential treatments , among these a multidisciplinary programme for patients with chronic low back pain or high risk of chronification ( Rückenfit ) ; ( 4 ) interactive training modules which mediate principles of performance and disability expertise , the legal bases of retirement pensioning , and measures to support occupational rehabilitation ; and ( 5 ) a work hardening training programme . METHOD To evaluate the effects of these measures in comparison to a control group with usual care , a prospect i ve longitudinal study was conducted . A total of 307 patients were assigned to the multidisciplinary in-patient treatment programme , whereas 176 patients in the control group had a st and ard rehabilitation programme . RESULTS The results show positive moderate and strong effects in the intervention group concerning function , pain , psychic strains as well as the number of sick days and return to work rates 10 months after discharge . The effects in the intervention group exceeded the effects achieved in the control group . PATIENTS WITH HIGH RISK OF CHRONIFICATION : Beside the full sample , a subgroup of patients with chronic pain or high risk of chronification was analyzed , who had received a multidisciplinary functional restoration treatment . Also for this subgroup we found moderate and strong effects of treatment for function , psychic strains and sick days superior to those in the control group . CONCLUSION By this study we were able to show that orthopedic rehabilitation in a multimodal and multidisciplinary setting with a focus on activating and motivating therapy can have sustainable positive effects on pain , function and psychic well-being as well as on economic parameters . We interpret these persistent and superior effects in the treatment group ( 1 ) as a result of multiprofessional diagnosis and assignment which helps to subdivide the inhomogeneous group of patients with unspecific back pain into more homogeneous and thus more effective subgroups , ( 2 ) as a result of increased motivation by closed treatment groups , ( 3 ) as a result of intense and multilevel counselling of work related problems , ( 4 ) as a result of work hardening modules , and ( 5 ) as a result of direct and efficient treatment of psychic strains . The results also demonstrate the significance of inpatient rehabilitation , which will be efficient if differential treatment - adequate to the problems of the patient - is offered", "BACKGROUND Breast cancer may adversely affect work experience . We assessed whether there was evidence of discrimination at work , defined as negative or involuntary changes in employment situation ( including changes in position , wages , and other conditions ) , associated with a breast cancer diagnosis in a population -based retrospective cohort study conducted in Quebec , Canada . METHODS The study was based on the consecutive series of women aged less then 60 years when first treated for breast cancer ( identified through the Quebec Tumor Registry ) and a r and om sample of frequency-matched women living in Quebec ( identified from provincial health care files ) who had never been diagnosed with cancer . Eligibility for the study was restricted to women who were employed at the time of diagnosis ( for breast cancer survivors ) or the same calendar period ( for women in the comparison group ) . We conducted telephone interviews of eligible women 3 years after diagnosis for 646 survivors or after the matched calendar period for 890 women in the comparison group . Binomial regression was used to evaluate the relationship between having breast cancer and work situation . All statistical tests were two-sided . RESULTS Working conditions were similar between the two groups at the beginning of follow-up . After 3 years , slightly more survivors ( 21 % ) than women in the comparison group ( 15 % ) were unemployed ( adjusted relative risk for being unemployed = 1.29 , 95 % confidence interval = 1.05 to 1.59 ) , although most women who were not working ( 84 % of unemployed survivors and 76 % of unemployed women in the comparison group ) said that the decision to stop working was their own . Among women still employed , no deterioration in working conditions was observed in either group . CONCLUSION We found little evidence that women diagnosed with breast cancer experience discrimination at work . This information may be helpful for working women concerned about employment after breast cancer", "Objective To evaluate the effectiveness of an integrated care programme , combining a patient directed and a workplace directed intervention , for patients with chronic low back pain . Design Population based r and omised controlled trial . Setting Primary care ( 10 physiotherapy practice s , one occupational health service , one occupational therapy practice ) and secondary care ( five hospitals ) . Participants 134 adults aged 18 - 65 sick listed for at least 12 weeks owing to low back pain . Intervention Patients were r and omly assigned to usual care ( n=68 ) or integrated care ( n=66 ) . Integrated care consisted of a workplace intervention based on participatory ergonomics , involving a supervisor , and a grade d activity programme based on cognitive behavioural principles . Main outcome measures The primary outcome was the duration of time off work ( work disability ) due to low back pain until full sustainable return to work . Secondary outcome measures were intensity of pain and functional status . Results The median duration until sustainable return to work was 88 days in the integrated care group compared with 208 days in the usual care group ( P=0.003 ) . Integrated care was effective on return to work ( hazard ratio 1.9 , 95 % confidence interval 1.2 to 2.8 , P=0.004 ) . After 12 months , patients in the integrated care group improved significantly more on functional status compared with patients in the usual care group ( P=0.01 ) . Improvement of pain between the groups did not differ significantly . Conclusion The integrated care programme substantially reduced disability due to chronic low back pain in private and working life . Trial registration Current Controlled Trials IS RCT N28478651", "Study Design . R and omized parallel-group comparative trial with a 6-month follow-up period . Objective . To compare , in chronic low back pain patients , the effectiveness of a functional restoration program , including intensive physical training , occupational therapy , and psychological support to an active individual therapy consisting of 3 hours physical therapy per week during 5 weeks . Summary of Background Data . Controlled studies conducted in the United States showed a benefit of functional restoration in patients with low back pain , especially on return to work . R and omized Canadian and European trials had less favorable results . In France , there has been up to now no r and omized study . Controlled studies suggested a positive effect of functional restoration programs . Methods . Eighty-six patients with low back pain were r and omized to either the functional restoration ( 44 patients ) or the active individual therapy ( 42 patients ) program . One person in each group never started the program . Two patients did not complete the functional restoration program , and one was lost to follow-up at 6 months . The mean number of sick-leave days in the 2 previous years was 6 months . Results . After adjustment on the variable ≪ workplace enrolled in an ergonomic program ≫ , the mean number of sick-leave days was significantly lower in the functional restoration group . Physical criteria and treatment appreciation were also better . There was no significant difference in the intensity of pain , the quality of life and functional indexes , the psychological characteristics , the number of contacts with the medical system , and the drug intake . Conclusions . This study demonstrates the effectiveness of a functional restoration program on important outcome measures , such as sick leave , in a country that has a social system that protects people facing difficultiesat work", "Background The causes of prolonged disability due to back pain are multiply determined , involving medical , social , and environmental factors . Possible solutions to the problem of prolonged back pain disability have emerged from recent research but few efforts have been made to transfer evidence -based programs to large community setting s. Objective This article describes three phases of the process of transfer of evidence from rehabilitation research to community practice in the province of Quebec . Methods and Results Phase A : Based on literature review and expert knowledge , the Sherbrooke model was developed and assessed through a population -based , r and omized clinical trial . Results at 1-year follow-up showed quicker return to regular work and improvement of quality of life ; the 6-year follow-up showed the cost-effectiveness of the method .Phase B : Based on the Sherbrooke model experience and recent evidence , a new program addressing the disability paradigm was developed and implemented in the province of Quebec ( Canada ) . Results at 1- and 3-year follow-ups showed that only 24 % of workers were not working owing to their musculoskeletal disorder . The program is presently being tested through a population -based , r and omized clinical trial in a population of construction workers . Phase C : To implement the program at a provincial level , a network for management , research and education in work rehabilitation was developed . An external assessment is presently planned to evaluate return to work and economic outcomes and quality of implementation of the program in various setting", "BACKGROUND Major depression has far-reaching consequences for work functioning and absenteeism . In most cases depression is treated by medication and clinical management . The addition of occupational therapy ( OT ) might improve outcome . We determined the cost-effectiveness of the addition of OT to treatment as usual ( TAU ) . METHOD Sixty-two adults with major depression and a mean absenteeism of 242 days were r and omized to TAU ( out-patient psychiatric treatment ) or TAU+OT [ 6 months , including ( i ) diagnostic phase with occupational history and work reintegration plan , and ( ii ) therapeutic phase with individual sessions and group sessions ] . Main outcome domains were depression , work resumption , work stress and costs . Assessment s were at baseline and at 3 , 6 , 12 and 42 months . RESULTS The addition of OT to TAU : ( i ) did not improve depression outcome , ( ii ) result ed in a reduction in work-loss days during the first 18 months , ( iii ) did not increase work stress , and ( iv ) had a 75.5 % probability of being more cost-effective than TAU alone . CONCLUSION Addition of OT to good clinical practice does not improve depression outcome , improves productivity without increasing work stress and is superior to TAU in terms of cost-effectiveness", "Coronary catheter revascularisation is less costly than bypass surgery due to lower direct ( medical ) and indirect costs ( loss of work ) . Many studies show that the time patients stay out of work following coronary intervention is much longer than necessary . This leads to a considerable increase of indirect costs , which can far exceed the medical costs of the treatment . This prospect i ve r and omised study was done to determine whether specific information to patient and family doctor results in an earlier return to work . After catheter revascularisation 100 working patients ( mean age 52.4 years ) were r and omised either to the intervention group ( information to patient and family doctor ) or to the control group ( no specific information about return to work ) . Four months later 81 patients had returned to their previous jobs ( mean sick leave 18.9 + /- 24.8 days ) while 19 were still out of work . In the control group , the rate was 79 % and the mean sick leave was 16.4 + /- 22.0 days ( median 7 ) ; in the intervention group 83 % had returned to work after a mean of 21.5 + /- 27.4 days ( median 10 ) . There was no significant difference between the two groups , neither according to the rate of returned workers nor to the duration of sick leave . In the subgroup of patients with a private insurance ( 23 % of all ) 96 % started to work again ( mean sick leave 5.7 + /- 5.1 days median 3.5 ) , while the rate was 77 % in the group of panel patients ( mean sick leave 23.7 + /- 27.4 days , median 11 ) . The difference in sick leave between these two groups was highly significant ( p = 0.0003 ) . Specific information to the patient and family doctor has no effect on the time patients stay out of work following catheter revascularisation . It seems that the observed delay depends on social and psychological factors that can not be influenced directly", "OBJECTIVES --The aim was to combat occurrence of chronic occupational back pain . METHODS --A multidisciplinary model to manage back pain that includes both clinical and ergonomic approaches has been developed . Early detection , early clinical and ergonomic evaluations , and early active treatment make up the cornerstone of management . Detection of cases starts after four weeks of absence from work . An ergonomic intervention is implemented at six weeks . A medical specialist is involved at eight weeks . If return to work is not possible after 12 weeks , a functional recovery therapy followed by a therapeutic return to work is implemented . A multidisciplinary team decides if return to original or modified work is possible or if vocational rehabilitation is necessary . This model has been implemented by the investigators in the Sherbrooke ( Quebec , Canada ) area , and is presently being evaluated through a r and omised trial in 31 industrial settlements ( about 20,000 workers ) . A cluster r and omisation of industries and workers will allow separate testing of ergonomic and clinical interventions . RESULTS --One year after implementation , 31 of 35 of the eligible industrial sites participated in the study and 79 of 88 of the eligible workers affected by recent back pain had agreed to participate . Ergonomic and clinical interventions have been implemented as planned . Only three workers dropped out . Hence this global clinical and ergonomic management programme has been shown to be feasible in a general population . CONCLUSION --A global management programme of back pain joining ergonomic and clinical intervention with a multidisciplinary approach has not been tested yet . Linking these two strategies in a same multidisciplinary team represents a systemic approach to this multifactorial ailment . During the first year of this trial we did not find any conflict between these two interventions from the employer 's or worker 's point of view", "In a pilot trial in Rhinel and -Palatinate two instruments for optimizing medical and occupational rehabilitation of myocardial infa rct ion patients were tested : ( 1 ) A regional cardiology working group was founded which selected measures to accelerate the rehabilitation process in model region hospitals . ( 2 ) At the pilot rehabilitation clinic a counselling service for patients under a case management trial scheme was established . The evaluation showed that three weeks after the heart attack , exercise ECGs were carried out in 77.1 % of pilot trial patients ( case group ) as opposed to only 54.5 % of patients receiving st and ard treatment ( control group ) . During in-patient rehabilitation , a higher proportion of case patients discussed their return to work with their employers . After rehabilitation , the occupational future still was uncertain in 13.2 % of the case group , in contrast with 29.5 % of the control group . 91.8 % of case group patients ( 64 % of controls ) had been briefed about support possibilities facilitating a stepwise return to work according to section 74 SGB V ; half a year following the beginning of rehabilitation , case group patients were reentergrated into working life in 56.3 % ( 50 % of controls )", "OBJECTIVES To determine the relative efficacy of 2 different acute traumatic brain injury ( TBI ) rehabilitation approaches : cognitive didactic versus functional-experiential , and secondarily to determine relative efficacy for different patient sub population s. DESIGN R and omized , controlled , intent-to-treat trial comparing 2 alternative TBI treatment approaches . SETTING Four Veterans Administration acute inpatient TBI rehabilitation programs . PARTICIPANTS Adult veterans or active duty military service members ( N=360 ) with moderate to severe TBI . INTERVENTIONS One and a half to 2.5 hours of protocol -specific cognitive-didactic versus functional-experiential rehabilitation therapy integrated into interdisciplinary acute Commission for Accreditation of Rehabilitation Facilities-accredited inpatient TBI rehabilitation programs with another 2 to 2.5 hours daily of occupational and physical therapy . Duration of protocol treatment varied from 20 to 60 days depending on the clinical needs and progress of each participant . MAIN OUTCOME MEASURES The 2 primary outcome measures were functional independence in living and return to work and /or school assessed by independent evaluators at 1-year follow-up . Secondary outcome measures consisted of the FIM , Disability Rating Scale score , and items from the Present State Exam , Apathy Evaluation Scale , and Neurobehavioral Rating Scale . RESULTS The cognitive-didactic and functional-experiential treatments did not result in overall group differences in the broad 1-year primary outcomes . However , analysis of secondary outcomes found differentially better immediate posttreatment cognitive function ( mean+/-SD cognitive FIM ) in participants r and omized to cognitive-didactic treatment ( 27.3+/-6.2 ) than to functional treatment ( 25.6+/-6.0 , t332=2.56 , P=.01 ) . Exploratory subgroup analyses found that younger participants in the cognitive arm had a higher rate of returning to work or school than younger patients in the functional arm , whereas participants older than 30 years and those with more years of education in the functional arm had higher rates of independent living status at 1 year posttreatment than similar patients in the cognitive arm . CONCLUSIONS Results from this large multicenter r and omized controlled trial comparing cognitive-didactic and functional-experiential approaches to brain injury rehabilitation indicated improved but similar long-term global functional outcome . Participants in the cognitive treatment arm achieved better short-term functional cognitive performance than patients in the functional treatment arm . The current increase in war-related brain injuries provides added urgency for rigorous study of rehabilitation treatments . ( http:// Clinical Trials.gov ID # NCT00540020 . )" ]

[ "While weight-management interventions are effective in attenuating antipsychotic-induced weight , there is no available evidence on their long-term effectiveness . This study sought to investigate the 2-year effects of an early behavioural intervention ( EBI ) design ed to prevent antipsychotic-induced weight gain in first-episode psychosis ( FEP ) patients . Sixty-one FEP patients were r and omized to receive either EBI or treatment-as-usual . Intention-to-treat and observed-cases analysis showed that patients in the EBI group gained significantly less weight than those allocated to routine care at intervention completion ( 3-month follow-up ) with treatment effects maintained over 3months . Differences between groups were no longer significant by 12months . Weight-management interventions may need to be offered for longer periods to maintain preventative effects . Alternatively , booster sessions may need to be regularly delivered after intervention completion", "Obesity and diabetes have caused problems for individuals with schizophrenia long before atypical antipsychotic agents . The prevalence of obesity , insulin resistance , impaired glucose tolerance , type 2 diabetes mellitus , dyslipidemia , and the Metabolic Syndrome has increased in people with schizophrenia as compared to the general population . Risk reduction studies for persons with obesity , diabetes , and cardiovascular disease indicate that cognitive/behavioral interventions that promote motivation and provide strategies to overcome the barriers in adherence to diet and activity modification are effective interventions for weight management and risk reduction . In the l and mark multi-center r and omized-controlled trial study , the Diabetes Prevention Project ( DPP ) , a cognitive/behavioral intervention , was more successful in producing weight loss and preventing diabetes than the drugs metformin , troglitazone or placebo . This pilot study examined the effectiveness of a cognitive/behavioral group intervention , modified after the DPP program , in individuals with schizophrenia or schizoaffective disorder taking atypical antipsychotics in a large urban public mental health system . Outcome measures included body weight , body mass index , waist-hip ratios , and fasting glucose levels . Both groups demonstrated elevated fasting glucose levels and were obese with a mean BMI of 33 . The group that received the cognitive/behavioral group intervention lost more weight than the treatment as usual group . The CB group participants lost an average of 5.4 lb or 2.9 % of body weight , and those in the control group lost 1.3 lb or 0.6 % body weight . The range of weight loss for the treatment group was from 1 to 20 lb . This pilot study has demonstrated that weight loss is possible with cognitive/behavioral interventions in a population with a psychotic disorder", "Background Weight gain is common for people with schizophrenia and this has serious implication s for health and well being . Objectives To determine the effects of both pharmacological ( excluding medication switching ) and non pharmacological strategies for reducing or preventing weight gain in people with schizophrenia . Search methods We search ed key data bases and the Cochrane Schizophrenia Group 's trials register ( April 2006 ) , reference sections within relevant papers , h and search ed key journals , and contacted the first author of each relevant study and other experts to collect further information . Selection criteria We included all clinical r and omised controlled trials comparing any pharmacological or non pharmacological intervention for weight gain ( diet and exercise counselling ) with st and ard care or other treatments for people with schizophrenia or schizophrenia-like illnesses . Data collection and analysis We reliably selected , quality assessed and extracted data from studies . As weight is a continuous outcome measurement , weighted mean differences ( WMD ) of the change from baseline were calculated . The primary outcome measure was weight loss . Main results Twenty-three r and omised controlled trials met the inclusion criteria for this review . Five trials assessed a cognitive/behavioural intervention and eighteen assessed a pharmacological adjunct . In terms of prevention , two cognitive/behavioural trials showed significant treatment effect ( mean weight change ) at end of treatment ( n=104 , 2 RCTs , WMD -3.38 kg CI -4.2 to -2.0 ) . Pharmacological adjunct treatments were significant with a modest prevention of weight gain ( n=274 , 6 RCTs , WMD - 1.16 kg CI -1.9 to -0.4 ) . In terms of treatments for weight loss , we found significantly greater weight reduction in the cognitive behavioural intervention group ( n=129 , 3 RCTs , WMD -1.69 kg CI -2.8 to -0.6 ) compared with st and ard care . Authors ' conclusions Modest weight loss can be achieved with selective pharmacological and non pharmacological interventions . However , interpretation is limited by the small number of studies , small sample size , short study duration and by variability of the interventions themselves , their intensity and duration . Future studies adequately powered , with longer treatment duration and rigorous methodology will be needed in further evaluating the efficacy and safety of weight loss interventions for moderating weight gain . At this stage , there is insufficient evidence to support the general use of pharmacological interventions for weight management in people with schizophrenia", "BACKGROUND The main objective was to assess the efficacy of a weight management program design ed for out patients taking olanzapine for schizophrenia or schizoaffective disorder and to compare these patients with a r and omized control group . The effects of the weight management program were also assessed with regard to safety and quality of life . METHOD Forty-eight patients were enrolled in a 12-week , r and omized , multicenter weight management study . Thirty-three patients were r and omly allocated to an intervention group in which they received olanzapine within a weight management program . Fifteen patients were allocated to a control group in which they were given olanzapine treatment as usual out patients . Weight , body mass index ( BMI ) , and measurements of safety and quality of life were evaluated . The study was conducted from January 7 , 2003 , to September 16 , 2003 . RESULTS Thirty-six patients ( 75 % ) completed this study . We found significant differences in weight ( -3.94 + /- 3.63 kg vs. -1.48 + /- 1.88 kg , p = .006 ) and BMI ( -1.50 + /- 1.34 vs. -0.59 + /- 0.73 , p = .007 ) change from baseline to endpoint between the intervention and control groups , respectively . Significant differences in weight reduction were initially observed at week 8 ( p = .040 ) . No significant differences were found with regard to the safety outcomes . When the ratio of low-density lipoproteins to high-density lipoproteins was calculated , change from baseline was greater in the intervention group than the control group ( -0.19 vs. -0.04 ) , but the difference was not statistically significant ( p = .556 ) . After the completion of the weight management program , there was a trend toward statistical difference in the physical health score changes between the weight management and control groups ( 1.12 in the intervention group vs. -0.93 in the control group , p = .067 ) . CONCLUSION The weight management program was effective in terms of weight reduction in patients with schizophrenia or schizoaffective disorder taking olanzapine and was also found to be safe in terms of psychiatric symptoms , vital signs , and laboratory data . In addition , such a weight management program might improve quality of life in patients with schizophrenia or schizoaffective disorder with respect to their physical well-being", "Background : Increasing numbers of reports have raised concerns about significant increases in weight and adiposity over both short- and long-term treatment in patients treated with antipsychotics ( APs ) . The management of overweight and obesity in patients treated with APs has included pharmacological interventions , dietary suggestions , and behavioral strategies . Nevertheless , current evidence does not support the use of pharmacological management of this specific type of obesity , and only a limited number of studies have been published regarding prevention and treatment of weight gain with other strategies . Objective : The aim of this study was to evaluate the effectiveness of an educational intervention ( EI ) that combines low-calorie diet with increased physical activity to prevent and treat weight gain in patients treated with APs . Method : Data were from 53 subjects whose body mass index ( BMI ) had increased by more than 7 % after starting an AP therapy and who consented to participate in a 12-week educational intervention study aim ed at preventing further weight gain and , when possible , at inducing a weight loss . Weight and BMI were measured at baseline ( at each of the monthly follow-up visits ) and at study completion 12 weeks from entry in the study . Results : Twenty-six patients completed the 12-week program . Completers showed a significant mean body weight decrease of 3.15 kg , with a mean BMI reduction of 1.2 ( kg/m2 ) at the end of the 3-month period . Conclusions : Educational intervention can be an important tool for the management of weight increase in patients treated with APs . A larger prospect i ve and controlled study is now needed to confirm our findings", "The objective was to explore the impact on physical health of a lifestyle programme among persons with psychiatric disabilities , and their caregivers . Their satisfaction with the intervention was also assessed . Somatic comorbidity and an increased mortality related to the lifestyle among persons with psychiatric disabilities are well known . Few r and omized controlled trials have been aim ed specifically at lifestyle issues among persons with a psychiatric disability . This trial includes clients with psychiatric disabilities living in supported housing and their staff . Forty-one persons with a DSM-?V diagnosis of severe mental illness from psychiatric disability from 10 supported housing facilities and 41 of their caregivers participated in this 12-month study during 2005–2006 in Sweden . The supported housing facilities with residents and staff were r and omly assigned to either a health intervention programme or a control programme with an aesthetic content . The presence of metabolic syndrome and changes in the mean of physiological parameters such as Hba1c , P-glucose , P-insulin , lipids , blood pressure , physical working capacity , body mass index , Heart Score were investigated and participants ’ satisfaction assessed . There was a significant reduction in the mean of metabolic syndrome criteria in the intervention group compared with the control group at the follow-up . The participants expressed satisfaction with the programme . The results indicate that health interventions on lifestyle issues when involving carers are appreciated , feasible and could be successful in reducing some health-related risk factors among persons with psychiatric disabilities", "BACKGROUND Obesity is common in persons with schizophrenia . Besides its adverse health effects , obesity reduces quality of life and contributes to the social stigma of schizophrenia . METHOD This 14-week , multicenter , open-label , rater-blinded , r and omized study evaluated the effects of a group-based behavioral treatment ( BT ) for weight loss in overweight and obese stable patients with DSM-IV schizophrenia or schizoaffective disorder who had been switched from olanzapine to risperidone . Participants were r and omly assigned to receive BT or usual clinical care ( UC ) . BT included 20 sessions during which patients were taught to reduce caloric intake . In UC , patients were encouraged to lose weight but received no special advice about weight reduction . The primary outcome measure was change in body weight . RESULTS Seventy-two patients were enrolled . The mean + /- SD weight loss at endpoint was significant in both groups ( p or = 5 % of their body weight at endpoint ( 26.5 % [ 9/34 ] and 10.8 % [ 4/37 ] , respectively ; p = .082 ) . A post hoc analysis of patients attending at least 1 BT session showed that significantly more patients in the BT than the UC group had lost > or = 5 % of their body weight at endpoint ( 32.1 % [ 9/28 ] vs. 10.8 % [ 4/37 ] , respectively , p = .038 ) and at week 14 ( complete population ; 40.9 % [ 9/22 ] and 14.3 % [ 4/28 ] , respectively , p = .027 ) . CONCLUSION BT may be an effective method for weight reduction in patients with chronic psychotic illness", "OBJECTIVE Patients with schizophrenia treated with clozapine often gain weight . This study evaluated the effects of dietary control and physical activity among obese in patients with schizophrenia being treated with clozapine . METHODS Fifty-three clozapine-treated obese patients with schizophrenia in a veterans hospital in eastern Taiwan who had a body mass index greater than 27 ( weight divided by height in meters squared ) and who were taking clozapine were r and omly assigned to a study group of 28 or a control group of 25 . The study group was placed on a diet that reduced calorie intake by 200 to 300 kcal per day ( to 1,300 to 1,500 kcal per day for women and to 1,600 to 1,800 kcal per day for men ) and a six-month regimen of regular physical activity in which participants used approximately 600 to 750 kcal per week ( level walking and walking on stairs for 60 minutes three days per week ) . Anthropometric , metabolic , and hormonal parameters were measured after three and six months by using anthropometry , an enzyme autoanalyzer , immunoassay , and enzyme-linked immunosorbent assay . RESULTS Compared with the control group , the study group showed a significant decrease in body weight , body mass index ( 5.4 % reduction ) , waist circumference ( 3.3 cm ) , and hip circumference ( 3.3 cm ) after three months and after six months . Triglyceride and insulin-like growth factor-binding protein-3 ( IGFBP-3 ) decreased significantly only after six months . CONCLUSIONS A program of dietary control and regular physical activity can significantly reduce body weight and improve metabolic profiles of insulin , triglyceride , and IGFBP-3 among obese in patients taking clozapine for the treatment of schizophrenia", "BACKGROUND Overweight and obesity are common concerns in individuals with severe mental disorders . In particular , antipsychotic drugs ( AP ) frequently induce weight gain . This phenomenon lacks current management and no previous controlled studies seem to use cognitive therapy to modify eating and weight-related cognitions . Moreover , none of these studies considered binge eating or eating and weight-related cognitions as possible outcomes . AIM The main aim of this study is to assess the effectivity of cognitive and behavioural treatment ( CBT ) on eating and weight-related cognitions , binge eating symptomatology and weight loss in patients who reported weight gain during AP treatment . METHOD A r and omized controlled study ( 12-week CBT vs. Brief Nutritional Education ) was carried out on 61 patients treated with an antipsychotic drug who reported weight gain following treatment . Binge eating symptomatology , eating and weight-related cognitions , as well as weight and body mass index were assessed before treatment , at 12 weeks and at 24 weeks . RESULTS The CBT group showed some improvement with respect to binge eating symptomatology and weight-related cognitions , whereas the control group did not . Weight loss occurred more progressively and was greater in the CBT group at 24 weeks . CONCLUSION The proposed CBT treatment is particularly interesting for patients suffering from weight gain associated with antipsychotic treatment", "BACKGROUND The purpose of this study was to compare an early behavioral intervention ( EBI ) with nonstructured st and ard physical care ( routine care intervention [ RCI ] ) in preventing antipsychotic-induced weight gain in drug-naive first-episode psychosis patients . METHOD Sixty-one patients with a DSM-IV-diagnosed psychotic disorder were first r and omly assigned to 3 different antipsychotic treatments ( risperidone [ N = 23 ] , olanzapine [ N = 18 ] , and haloperidol [ N = 21 ] ) and subsequently r and omly assigned to the intervention condition ( EBI , N = 35 ) or RCI ( N = 27 ) . EBI was specifically design ed to teach strategies to enhance control over factors associated with antipsychotic-induced weight gain and consisted of 8 flexible intervention modules that incorporated behavioral interventions , nutrition , and exercise . In the RCI group , patients were informed about potential weight gain and advised to increase their exercise and limit food intake . Body weight and body mass index were measured at baseline and then weekly for 3 months . In addition to change in weight and body mass index , a third outcome measure was the proportion of patients who had gained more than 7 % of their body weight at 3 months . Participating patients were referred between August 2002 and September 2004 . RESULTS All 61 participants completed the study . Patients in the EBI group gained significantly less weight ( mean = 4.1 kg , SD = 4.0 ) than those allocated to the RCI group ( mean = 6.9 kg , SD = 4.5 ) ( p body mass index , which was significantly less in the EBI group than in the RCI group ( 1.40 vs. 2.39 kg/m2 ) ( p their baseline weight by more than 7 % , the cutoff for clinical ly meaningful weight gain . CONCLUSIONS EBI was effective in attenuating antipsychotic-induced weight gain in a drug-naive first-episode psychosis cohort . Patients displayed good adherence to this type of preventive intervention", "Obesity is a serious medical problem that disproportionately affects people with severe mental illness . Behavioral strategies aim ed at lifestyle modification have proven effective for weight loss in general population but have not been studied adequately among persons with schizophrenia . We have conducted a r and omized controlled pilot trial of an established weight loss program , modified for this specific population , and supplemented with a novel food replacement program , as well as practical , community based teaching of shopping and preparing healthy food . The program not only arrested weight gain , and produced meaningful weight loss , but also weight loss continued 6 months after the intervention is completed . Cognitive impairment had no bearing to the extent a participant benefited from the program . As a conclusion , well design ed simple behavioral programs can produce lasting weight loss for patients with schizophrenia and comorbid obesity , improve metabolic indices , and possibly decrease significant medical risks associated with obesity", "PURPOSE To assess the effect of an educational intervention on antipsychotic-induced weight gain among patients with schizophrenia . DESIGN AND METHODS Quasi-experimental . Seventy patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder entered this 6-month study condicted in the United States . All participants began receiving olanzapine treatment when they entered the study . The patients were then r and omly assigned to an intervention group or a st and ard care group . Over the next 4-months , the intervention group participated in weekly psychoeducation classes focused on nutrition , exercise , and living a healthy lifestyle . Patients were followed for an additional 2 months to assess weight change . FINDINGS A statistically significant difference in weight change between the two groups was observed post-treatment and at endpoint . At endpoint , the mean weight change of the intervention group was -.06 pounds , while the mean weight change in the st and ard care group was 9.57 pounds . In both groups , men gained significantly more weight than did women . CONCLUSIONS The results indicate that a structured educational intervention might have a positive effect on antipsychotic-induced weight gain among patients with schizophrenia", "OBJECTIVE Olanzapine is the most commonly prescribed atypical antipsychotic medication in Australia . Research reports an average weight gain of between 4.5 and 7 kg in the 3 months following its commencement . Trying to minimize this weight gain in a population with an already high prevalence of obesity , mortality and morbidity is of clinical and social importance . This r and omized controlled trial investigated the impact of individual nutrition education provided by a dietitian on weight gain in the 3 and 6 months following the commencement of olanzapine . METHOD Fifty-one individuals ( 29 females , 22 males ) who had started on olanzapine in the previous 3 months ( mean length of 27 days + /- 20 ) were recruited through Peninsula Health Psychiatric Services and were r and omly assigned to either the intervention ( n = 29 ) or the control group ( n = 22 ) . Individuals in the intervention group received six 1 hour nutrition education sessions over a 3-month period . Weight , waist circumference , body mass index ( BMI ) and qualitative measures of exercise levels , quality of life , health and body image were collected at baseline at 3 and 6 months . RESULTS After 3 months , the control group had gained significantly more weight than the treatment group ( 6.0 kg vs 2.0 kg , p Weight gain of more than 7 % of initial weight occurred in 64 % of the control group compared to 13 % of the treatment group . The control group 's BMI increased significantly more than the treatment group 's ( 2 kg/m(2)vs 0.7 kg/m(2 ) , p moderate exercise levels , quality of life , health and body image compared to the controls . At 6 months , the control group continued to show significantly more weight gain since baseline than the treatment group ( 9.9 kg vs 2.0 kg , p BMI ( 3.2 kg/m(2)vs 0.8 kg/m(2 ) , p Individual nutritional intervention provided by a dietitian is highly successful at preventing olanzapine-induced weight gain", "The purpose of this study was to determine the effects a health education and exercise program would have in limiting weight gain and in improving fitness and psychological parameters in adults with mood or psychotic disorders . Thirty volunteers were r and omly assigned to the healthy lifestyle group ( HL ) or a control group . The HL group engaged in exercise for 12 weeks . Pre- and post-exercise testing was conducted to assess body fat , lipid profile , and cardiovascular fitness . Educational seminars were held weekly . The intervention group evidence d greater weight loss than the control group , although not statistically significant . Significant differences were observed in ratings of general health ( p empowerment ( p exercise interventions may encourage weight loss , particularly if barriers to full participation can be addressed . Additionally , such interventions may contribute to \" perceived \" well-being even among those with sub clinical participation" ]

[ "PURPOSE The Comparison of Ophthalmic Medications for Tolerability ( COMTOL ) question naire was developed for use in clinical trials to compare the tolerability of topical ophthalmic medications used in the treatment of glaucoma . The question naire captures the frequency and bother of common side effects ( i.e. , ocular and other local effects , and effects on visual function ) of topical therapy for lowering intraocular pressure . In addition , the question naire measures the extent to which these side effects and any associated limitations in routine living activities interfere with health-related quality of life , medication compliance , and patient satisfaction with the medication . This study was design ed to assess the measurement characteristics of the COMTOL question naire . METHODS The internal consistency , reliability , reproducibility , construct validity , discriminant validity , and responsiveness of the question naire were assessed in 70 adult patients with glaucoma in a clinical trial comparing timolol and pilocarpine . RESULTS The question naire showed good-to-excellent internal consistency ( 0.73 to 0.98 ) , reliability ( 0.76 to 0.94 ) , and reproducibility ( 0.75 to 0.93 ) . In general , there was a strong correlation in the expected direction between the frequency and bother of side effects and patient-perceived global measures . The question naire discriminated between patients receiving timolol and patients receiving pilocarpine . The question naire demonstrated significant responsiveness to change . CONCLUSIONS The COMTOL question naire showed acceptable measurement characteristics for inclusion as a tolerability measure to supplement spontaneous adverse event reporting in clinical trials of topical ophthalmic therapy", "Purpose To provide initial validation of the Treatment Satisfaction Survey-Intraocular Pressure ( TSS-IOP ) quality -of-life survey that analyses specific issues related to side effects , patient satisfaction , and compliance . Methods A prospect i ve , observational cohort of 250 consecutive patients with primary open-angle glaucoma or ocular hypertension was administered the TSS-IOP survey . Results Factors that correlated with patient satisfaction included perceived effectiveness of the medicine ( F=7.47 , P ocular irritation ( F=6.06 , P conjunctival hyperaemia ( F=4.40 , P ease of use ( F=8.52 , P convenience of use ( F=6.90 , P Patient compliance , acceptance of their illness , and knowledge of glaucoma were also related to perceived effectiveness of the medicine ( P ease of use ( P convenience ( P Physician ratings of patient pressure control , side effects , and instillation problems also were significantly correlated to patient satisfaction ( R=0.13–0.26 , P=0.05–0.001 ) . The physician ratings of patient compliance , however , were not significantly related to any dimension of patient satisfaction ( P>0.05 ) . Among monotherapy prostagl and in treatments , latanoprost demonstrated statistically greater satisfaction than bimatoprost or travoprost regarding conjunctival hyperaemia ( P eye irritation ( P compliance , perceived effectiveness of treatment , adverse side effects , ease and convenience of use , acceptance of illness , and knowledge of glaucoma ", "PURPOSE To verify the quality of life in a Brazilian glaucoma population and the influence of possible modifiers ( e.g. , visual acuity , visual field impairment ) . METHODS Forty-five consecutive patients from CEROF - Federal University of Goiás , Brazil were included prospect ively in the study . The quality of life was assessed using the Portuguese version of the VFQ . Possible modifiers were evaluated , initially separately with the Spearman 's Correlation and then together in a regression model . RESULTS The mean age was 59.6 ± 12.4 years . The mean quality of life score was 79 ± 15 ( range 45 - 100 ) . Age ( r = −0.402 , p = 0.006 ) , visual acuity in the better eye ( r = −0.497 , p = 0.001 ) and in the worse eye ( r = −0.608 , p ) , Hodapp-Parrish- And erson visual field grading scale in the better ( r = −0.353 , p = 0.01 ) and worse eye ( r = −0.387 , p = 0.009 ) , visual field Mean Deviation ( MD ) in the better ( r = 0.355 , p = 0.01 ) and worse eye ( r = 0.320 , p = 0.04 ) and ability to perform a visual field test in both eyes ( r = −0.397 , p = 0.007 ) were significantly correlated with the quality of life scores . However , only age ( younger , better quality of life , p = 0.008 ) and visual acuity in the better eye ( direct relation , p = 0.04 ) were significant in the regression model ( r = 0.633 , r2 = 0.401 ) . CONCLUSIONS The VFQ may be a useful tool to assess the quality of life in glaucoma patients . The preliminary results indicate that age and visual acuity in the better eye are the main factors related to the quality of life in these patients", "PURPOSE To evaluate the relationship between visual disability and the remaining visual field in glaucoma patients . DESIGN Prospect i ve noncomparative survey . PARTICIPANTS One hundred forty-seven Japanese patients with glaucoma were examined . METHODS Using a previously developed question naire , we assessed the relationship between visual disability indices and both the visual field examined using program 30 - 2 of the Humphrey Field Analyzer and visual acuity . MAIN OUTCOME MEASURES Pearson 's correlation coefficients between visual disability indices and the 22 visual field and 2 visual acuity measurements were calculated . Multiple regression analysis with stepwise variable selection identified factors significantly contributing to visual disability . RESULTS We identified a significant correlation between visual disability and both the visual field and visual acuity measurements collected . Of the factors examined , retinal sensitivity in the lower hemifield within 5 degrees of the fixation and visual acuity in the better eye significantly contributed to all the item and total disability indices ( DIs ) , measurements of the degree of visual disability as evaluated by the question naire ; visual acuity in the worse eye contributed to two of the seven item DIs , as well as the total DI . The R value for total DI ( R = 0.87 , P visual disability could be explained by these factors . CONCLUSIONS The Japanese glaucoma patients ' visual disability is explained primarily by retinal sensitivity in the lower hemifield within 5 degrees of the fixation and visual acuity in the better eye and secondarily by visual acuity in the worse eye", "PURPOSE To evaluate the effect of treatment , visual function , and other factors on vision-targeted health-related quality of life ( HRQOL ) of patients with early glaucoma . DESIGN R and omized clinical trial . PARTICIPANTS Two hundred fifty-five patients with newly detected open-angle glaucoma and repeatable early visual field ( VF ) defects , 50 to 80 years old ( 66 % female ) . METHODS Patients were r and omized to receive either betaxolol plus laser trabeculoplasty in eligible eye(s ) or no initial treatment and had ophthalmologic examinations every 3 months . A Swedish translation of the 25-item National Eye Institute Visual Function Question naire ( NEI VFQ-25 ) was self-administered at 2 follow-up visits ( 3 and 6 years after r and omization ) . MAIN OUTCOME Multiple linear regression analyses determined the effect of treatment and other factors on ( 1 ) VFQ-25 composite scores at the first administration and ( 2 ) change in scores between administrations . RESULTS Two hundred thirty-three patients had 1 NEI VFQ-25 administration and 167 patients had 2 administrations . Internal consistency reliability was high for the composite VFQ-25 score ( Cronbach alpha = 0.88 ) and satisfactory ( alpha > or = 0.76 ) for most subscale scores . At the first administration , the composite score was high ( 88.8+/-11.7 ) . Mean subscale scores were also generally high ( 98.0 - 58.3 ) and were similar for each study group when analyzed separately . Most lower subscale scores were modestly but significantly related to worse visual acuity ( VA ) or mean deviation ( MD ) ( better eye , r = 0.15 - 0.35 ) . Composite scores were similar for treated and untreated patients . Lower composite scores were associated with low VA in the better eye ( worse than 0.70 ) and worse perimetric MD ( nuclear lens opacities ( Lens Opacities Classification System II grade > or = 2 ) , but not with age , gender , VF progression , intraocular pressure , cardiovascular disease , or hypertension . Between VFQ-25 administrations , larger decreases in the composite score were associated with larger decreases in VA ( P HRQOL . CONCLUSIONS Results suggest that absence or delay of treatment did not influence vision-targeted HRQOL in these newly diagnosed glaucoma patients . However , visual function affected vision-targeted quality of life up to 6 years after Early Manifest Glaucoma Trial enrollment", "The final development of the Sickness Impact Profile ( SIP ) , a behaviorally based measure of health status , is presented . A large field trial on a r and om sample of prepaid group practice enrollees and smaller trials on sample s of patients with hyperthyroidism , rheumatoid arthritis and hip replacements were undertaken to assess reliability and validity of the SIP and provide data for category and item analyses . Test-retest reliability ( r = 0.92 ) and internal consistency ( r = 0.94 ) were high . Convergent and discriminant validity was evaluated using the multitrait – multi method technique . Clinical validity was assessed by determining the relationship between clinical measures of disease and the SIP scores . The relationship between the SIP and criterion measures were moderate to high and in the direction hypotheszed . A technique for describing and assessing similarities and differences among groups was developed using profile and pattern analysis . The final SIP contains 136 items in 12 categories . Overall , category , and dimension scores may be calculated", "PURPOSE The Tube Versus Trabeculectomy ( TVT ) Study will compare the safety and efficacy of nonvalved tube shunt surgery to trabeculectomy with mitomycin C in patients with previous intraocular surgery . DESIGN Multicenter r and omized clinical trial . METHODS SETTING 17 Clinical Centers . STUDY POPULATION Patients 18 to 85 years of age who have undergone previous trabeculectomy , cataract extraction with intraocular lens implantation , or both and have inadequately controlled glaucoma with intraocular pressure ( IOP ) > or=18 mm Hg and INTERVENTIONS Study patients were r and omized to undergo placement of a 350-mm(2 ) Baerveldt glaucoma implant or trabeculectomy with mitomycin C ( 0.4 mg/ml for 4 minutes ) . MAIN OUTCOME MEASURES IOP , complication rates , visual acuity , visual field , quality of life , reoperations for glaucoma , and need for supplemental medical therapy . RESULTS A total of 212 patients were enrolled between October 1999 and April 2004 . The age of the study population was 71.0 + /- 10.4 years ( mean + /- SD ) , and 53 % were women . The baseline IOP was 25.3 + /- 5.3 mm Hg ( mean + /- SD ) . There were no significant differences in the demographic and ocular characteristics between the 2 treatment groups . CONCLUSIONS Practice patterns vary in the surgical management of glaucoma , and there are differing opinions among glaucoma surgeons regarding the preferred surgical approach in patients who have undergone previous cataract extraction and /or failed filtering surgery . Forthcoming data from the TVT Study should provide valuable information comparing two surgical procedures commonly used in this patient population", "This 3-month multicenter , open-label study of 89 geriatric patients with glaucoma evaluated the substitution of brimonidine twice daily for topical beta blockers that had been used for at least 6 months . The primary outcome measures were reduction in intraocular pressure ( IOP ) from baseline at 2 hours postdose , change in cardiac and respiratory function , quality of life , and patient satisfaction . Patients were queried about adverse events at each visit and completed a quality -of-life question naire at the final evaluation . In this cohort with a mean age of 75.4 years , the average duration of topical beta-blocker therapy was 5 years . Brimonidine twice daily produced an additional mean reduction in IOP of 8.2 % ( 1.4 mm Hg;P as satisfied with brimonidine as with their previous beta-blocker regimen , and 46 % ( 31/68 ) reported greater satisfaction with brimonidine . Additionally , 40 % of patients ( 27/68 ) noted increased energy after the switch , and 43 % ( 29/68 ) described brimonidine as more soothing than topical beta blockers . In this elderly population , the replacement of topical beta blockers with brimonidine twice daily significantly decreased IOP , improved quality of life , and enhanced patient satisfaction", "A multicenter open-label study investigated the clinical effectiveness and economic feasibility of switching 142 patients from dual therapy to twice-daily monotherapy with brimonidine for glaucoma or ocular hypertension . Evaluations were performed at baseline and 2 ( visit 2 ) and 8 ( visit 3 ) weeks after the switch . Patients completed a question naire that rated medication-related visual function and satisfaction ( comfort , convenience , vision , ease of remembering to use drops ) at each visit . At visit 3 , investigators , taking into account IOP measurements , safety , and responses on the question naire , recommended whether the patient should remain on brimonidine . A pharmacoeconomic analysis , including the number of visits , cost of medication , and success rates , compared the cost of dual therapy with that of switching to brimonidine monotherapy . Of the 131 patients who completed the study , 77 ( 59 % ) had no change or a decrease in IOP from baseline , and 53 ( 41 % ) had an increase . Investigators recommended that 77 % of the study completers continue to take brimonidine monotherapy . Extending treatment with brimonidine for 12 months would achieve a significant cost savings of 16 % . Brimonidine monotherapy is an efficacious and cost-effective alternative to dual therapy for glaucoma and ocular hypertension . Appropriate monotherapy may be as effective as dual therapy for many patients , and a clinical ly relevant trial such as this may be economically advantageous for testing a switch", "OBJECTIVE The Collaborative Initial Glaucoma Treatment Study ( CIGTS ) was design ed to determine whether patients with newly diagnosed open-angle glaucoma are better treated initially by medicine or immediate filtering surgery . This paper describes the quality -of-life ( QOL ) measurement approach , instruments included , and the CIGTS participants ' QOL findings at the time of diagnosis . DESIGN Baseline results from a r and omized , controlled clinical trial . PARTICIPANTS Six hundred seven patients from 14 clinical centers were enrolled . INTERVENTION Patients r and omized to initial medication received a stepped medical regimen ( n = 307 ) . Those r and omized to initial surgery underwent a trabeculectomy ( n = 300 ) . The baseline interview was conducted before treatment initiation . All baseline and posttreatment QOL assessment s were conducted by telephone from a central ized interviewing center . MAIN OUTCOME MEASURES The primary outcome measure described in this paper was QOL . The QOL instrument is multidimensional and incorporates both disease-specific and generic measures , including the Visual Activities Question naire , Sickness Impact Profile , and a Symptom and Health Problem CHECKLIST : RESULTS The correlations between QOL measures and clinical outcomes were in the expected direction , but relatively weak . At initial diagnosis , difficulty with bright lights and with light and dark adaptation were the most frequently reported symptoms related to visual function , whereas visual distortion was the most bothersome . Approximately half of the patients reported at least some worry or concern about the possibility of blindness . Within the Visual Activities Question naire , higher scores on the Peripheral Vision subscale were associated with more field loss ( P visual field loss was significantly associated with higher dysfunction among five disease-specific QOL measures ( P Newly diagnosed glaucoma patients reported experiencing some visual function symptoms at the time of diagnosis that would not be intuitively expected based on clinical testing . Some discussion about the association between clinical presentation and worry about blindness may reduce unnecessary concern . These results provide the basis for long-term comparisons of the QOL effects of initial medical and surgical treatment for open-angle glaucoma", "Purpose To evaluate efficacy , safety and quality of life in ocular hypertensive or open-angle glaucoma patients changed to latanoprost from previous therapy . Methods A prospect i ve , multicenter , active-controlled design in which qualified patients had their previous therapy substituted for latanoprost and were followed for at least thee months . Results In 1068 patients , latanoprost was continued 92 % throughout the 36-month observation period . Latanoprost treatment reduced the intraocular pressure (IOP)(p alpha-antagonists ( -3.9 ± 3.0 mmHg , 14 % ) , miotics ( -3.8 ± 3.5 mmHg , 2 % ) , or carbonic anhydrase inhibitors ( CAI ) ( -3.8 ± 3.6 mmHg , n = 16 % ) , and adjunctive therapy including : beta-blocker and CAI ( -3.7 ± 3.1 mmHg , n = 12 % ) , alpha-agonist ( -3.7 ± 3.4 mmHg , n = 5 % ) , or pilocarpine ( -3.4 ± 3.7 mmHg , n = 6 % ) , or CAI and alpha-agonist ( -4.6 ± 6.4 mm Hg , n = 2%)(p was ocular allergy ( 1.5 % incidence ) . Patients showed a preference for latanoprost for many systemic and ocular quality of life measures on a non-vali date d question naire ( p experience reduced IOP , deceased side effects and increased quality of life measures ", "OBJECTIVE To test the reliability and validity of the 51-item Field Test Version of the National Eye Institute Visual Function Question naire ( NEI-VFQ ) across 5 common chronic eye conditions . DESIGN Prospect i ve observational cohort study of persons with 1 of 5 chronic eye diseases who were scheduled for nonurgent visits in ophthalmology practice s or had low vision from any cause , and a reference sample of persons without eye disease . SETTING Six university-based ophthalmology practice s and the National Eye Institute Clinical Center , Bethesda , Md. PATIENTS Eligible participants had to have 1 of the following eye conditions : age-related cataracts , age-related macular degeneration , diabetic retinopathy , primary open-angle glaucoma , cytomegalovirus retinitis , or low vision from any cause . Each of the 7 sites also enrolled persons in a reference sample . Reference sample participants had no evidence of underlying eye disease but were scheduled for either screening eye examinations or correction of refractive error . All eligible persons had to be aged 21 years or older , English speaking , and cognitively able to give informed consent and participate in a health status interview . MEASUREMENTS AND MAIN RESULTS To provide the data needed to assess the reliability and validity of the 51-item NEI-VFQ , all subjects completed an interview that consisted of the 51-item NEI-VFQ , the Medical Outcomes Study 36-Item Short-Form Health Survey , and at least 1 measure of vision-targeted functional status . Estimates of internal consistency and test-retest reproducibility indicate that the 51-item NEI-VFQ is reliable . Tests of association with other scales and clinical variables support the construct validity of the survey . CONCLUSIONS In this cross-sectional study , the 51-item NEI-VFQ seems to be reliable and valid and should be a useful tool for group-level comparisons of vision-targeted , health-related quality of life in clinical research . Additionally , the psychometric properties of the NEI-VFQ were not influenced by the type or severity of the underlying eye disease , suggesting that the measure will provide reproducible and valid data when used across multiple eye conditions", "Purpose To determine the effectiveness and safety of brimonidine when used in combination with one or more glaucoma medications in patients with glaucoma or ocular hypertension . Methods Post hoc analysis of a multicenter , 2-month , open-label , prospect i ve , clinical trial in which 2,335 patients received brimonidine as monotherapy , replacement therapy , or combination therapy . Patients who received brimonidine as combination therapy ( n = 554 ) were examined in the current analysis . Efficacy was determined by the reduction in intraocular pressure ( IOP ) from baseline before the addition of brimonidine . Safety and tolerability parameters included adverse events and quality -of-life measures ( e.g. , ocular comfort , energy level , breathing ability , night vision ) . Results Addition of brimonidine to preexisting regimens result ed in an overall mean additional reduction in IOP of 17.9 % ( 4.26 mm Hg ) at month 2 ( P additional IOP lowering was provided by brimonidine in combination with each preexisting regimen evaluated ( P ≤ 0.061 ) . When brimonidine was added to monotherapy with a nonselective & bgr;-blocker , the mean additional IOP reduction was 15.5 % ( 3.61 mm Hg , P brimonidine to latanoprost monotherapy provided a 32.2 % ( 5.89 mm Hg ) mean additional IOP reduction ( P brimonidine to combination regimens that included latanoprost provided additional mean decreases in IOP ranging from 15.5 % ( 3.63 mm Hg , P All quality -of-life parameters remained high or improved during the study . Mild to moderate adverse events were reported in 5.23 % of patients ( 29 of 552 ) ; 98.1 % of physicians rated brimonidine adjunctive therapy as good or excellent . Conclusions Brimonidine , when added to existing glaucoma regimens , safely and effectively lowered IOP in this community-based trial", "In this study , we examined the relation between spontaneously reported adverse experiences and responses given on the comparison of ophthalmic medications for tolerability ( COMTOL ) checklist question naire which queries the frequency and bother of specific side-effects known to be associated with topical ophthalmic agents used to treat ocular hypertension or open-angle glaucoma , and the impact that the side-effects have on health-related quality of life . The study was a 4-week , r and omized , open-label , two-period cross-over clinical trial comparing dorzolamide and pilocarpine in 92 patients who were also receiving timolol for the treatment of ocular hypertension or open-angle glaucoma . Patients completed the COMTOL question naire at baseline and at the end of each period and spontaneous reports of adverse experiences ( AEs ) were collected throughout the study by the investigator . Since there were only 3 spontaneously reported AEs related to drug treatment while patients received dorzolamide and since COMTOL scores indicated a low level of side-effects , the analyses were limited to pilocarpine treatment periods . We discovered that during the pilocarpine treatment periods , a large percentage ( 94 % ) of the 47 patients , who failed to spontaneously report any adverse experiences , indicated on the COMTOL that they had experienced side-effects . These discrepancies between the methods of spontaneous reports and a checklist question naire are similar to those previously reported in the literature for other drugs . Unlike previous literature , we went beyond identifying discrepancies with the two reporting methods and we looked for possible explanations for why the discrepancies existed . We discovered that patients who spontaneously reported AEs expressed more bother from these specific side-effects on the question naire than patients who did not spontaneously report AEs . As well , patients who spontaneously reported AEs and discontinued drug as a result of the AEs expressed on the COMTOL the greatest bother from side-effects . This trend of increasing negative impact ( as patients reported AEs and discontinued ) was also observed with COMTOL global question scores on the impact of side-effects on health-related quality of life , the impact of activity limitations on quality of life , satisfaction with medication and compliance with medication . Therefore , spontaneous reporting of side-effects appears to be detecting the most clinical ly meaningful side-effects", "Objective To test the Italian adaptation of the 25-item National Eye Institute Visual Function Question naire ( NEI-VFQ 25 ) and to investigate its validity and reliability . Methods This prospect i ve observational study enrolled nonhospitalized patients with 1 of 5 chronic eye diseases , and a reference sample of subjects without eye diseases . Eligible participants had to be cognitively able to respond to a health status interview and be affected by 1 of the following eye conditions : senile cataract , age-related macular degeneration , glaucoma , diabetic retinopathy , and cytomegalovirus retinitis or low vision . A control group was composed of subjects with no evidence of underlying eye diseases . The Italian self-administered versions of Medical Outcomes Study Short Form and of the NEI-VFQ 25 were administered to all participants . Reliability and validity of the Italian translation of the NEI-VFQ 25 were tested using statistical methods . Results Statistical analysis points out that the Italian version of the NEI-VFQ 25 has good validity , discriminatory power , internal consistency , and reliability . Conclusions This Italian version of the NEI-VFQ 25 shows psychometric properties comparable to those of the American version , and thus can be used in clinical research as a specific measure of quality of life in patients with chronic eye diseases", "BACKGROUND Patients with glaucoma or ocular hypertension may have inadequately controlled intraocular pressure ( IOP ) or experience adverse effects with their current medication regimens . OBJECTIVE This post hoc re analysis determined the effectiveness and tolerability of brimonidine used as replacement therapy in a real-life clinical practice setting . METHODS In this multicenter , open-label , observational , 2-month study , 460 patients received brimonidine 0.2 % as a 1:1 replacement for another antiglaucoma medication in their current regimen . Effectiveness was assessed by calculating the mean additional reduction in IOP from the treated baseline measurement ( before the switch to brimonidine ) to 2 months postbaseline , and by determining physicians ' opinions of treatment effectiveness . Tolerability was determined based on quality -of-life assessment s and recorded adverse events . RESULTS Overall , brimonidine replacement significantly reduced mean ( + /- SEM ) IOP by an additional 2.33 + /- 0.17 mm Hg ( 9.8 % + /- 0.9 % ; P reductions in IOP were seen when brimonidine replaced an agent used either as monotherapy or adjunctive therapy , regardless of the drug class of the agent replaced . However , particularly good hypotensive effectiveness and additional lowering of IOP were observed when brimonidine replaced certain medications , including latanoprost ( 12.44 % ; P betaxolol ( 13.56 % ; P latanoprost ( 16.08 % ; P therapy . The effectiveness of brimonidine was rated as good or excellent by 92.4 % of physicians . All quality -of-life variables remained favorable or improved throughout the study , and brimonidine treatment was well tolerated . CONCLUSIONS Brimonidine 0.2 % used as a 1:1 replacement for monotherapy or adjunctive therapy with other antiglaucoma drugs significantly lowered IOP from that produced by previous therapy and was well tolerated . Brimonidine offers a useful treatment option in patients who require replacement therapy", "Abstract Objective : Physicians need reliable , valid and sensitive question naires to assess QOL related to glaucoma or ocular hypertension . This article presents the psychometric properties of the French version of the National Eye Institute Visual Function Question naire — 25 ( NEI VFQ-25 ) . Methods : A mail survey was sent to 20 000 households . The survey identified 581 residents with glaucoma or ocular hypertension . Of these a r and om sample ( n = 204 ) took part in a telephone survey during which the NEI VFQ-25 was completed by eligible patients ( those taking at least one topical treatment for glaucoma or ocular hypertension on the day of the interview ) . Multi-trait analysis was performed to assess the construct validity of the question naire . Internal consistency reliability was assessed using Cronbach ’s α and the average inter-item correlation . Known groups validity was assessed by comparing patients grouped by duration of glaucoma , adjusted for age and gender . Results : One hundred and seventy-three patients participated in the survey . Analysis of convergent validity showed that all of the items in each scale correlated above 0.40 with their own scale except for the ‘ driving ’ scale . The success rate of the discriminant validity ranged from 57.1 % to 100 % except for the ‘ driving ’ scale , which was 7.1 % . Cronbach ’s α coefficients were all above 0.70 except the ‘ driving ’ score . Participants with glaucoma for less than 20 years consistently had better ‘ global ’ , ‘ near vision ’ , ‘ distant vision ’ , ‘ driving ’ , ’ social function ’ and ‘ peripheral vision ’ scores than those with disease of 20 + years duration , indicating better QOL in patients with a shorter disease duration . Conclusion : The NEI VFQ-25 is a vali date d instrument to measure vision-targeted QOL in French population s with glaucoma", "Purpose : To compare two gel-forming timolol maleate ophthalmic solutions , Timoptol XE ® and Lizmon TG ® , in regard to efficacy and tolerability in patients with glaucoma or ocular hypertension by means of a patient-masked prospect i ve r and omized crossover study . Subjects and Methods : A total of 37 patients with glaucoma or ocular hypertension under treatment with antiglaucoma ophthalmic solutions including 0.5 % twice-daily timolol maleate participated in this study . Only timolol maleate was withdrawn and either Timoptol XE or Lizmon TG was r and omly allocated . After instillation for 1 month , the other ophthalmic solution was subsequently instilled for another month . Routine ophthalmic examination including slit-lamp examination and intraocular pressure ( IOP ) monitoring was conducted before instillation of gel-forming ophthalmic solutions and just after completing the instillation of each ophthalmic solution . Patient question naire surveys were also performed just after completing the instillation of each ophthalmic solution . Results : Mean IOP , just before the withdrawal of timolol ophthalmic solution , was 16.4 ± 2.9 mm Hg . At the end of Timoptol XE or Lizmon TG instillation , mean IOPs were 16.3 ± 2.5 or 16.3 ± 3.0 mm Hg , respectively . The results of the question naire survey showed no significant difference between Timoptol XE and Lizmon TG in regard to all survey items . Twenty-nine patients ( 78.4 % ) preferred to use gel-forming timolol solutions rather than twice-daily timolol ophthalmic solution . The presence of concurrently used ophthalmic solutions did not effect the incidences of subjective symptoms . The incidences of objective adverse effects were not significantly different between two gel-forming timolol ophthalmic solutions . Conclusion : Both gel-forming timolol ophthalmic solutions could be good choices for glaucoma treatment", "OBJECTIVES The Early Manifest Glaucoma Trial ( EMGT ) will evaluate the effectiveness of reducing intraocular pressure ( IOP ) in early , previously untreated open-angle glaucoma . Its secondary aims are to explore factors related to glaucoma progression and to study the natural history of the disease . This article describes the EMGT design and presents baseline data . DESIGN R and omized , clinical trial . PARTICIPANTS Newly diagnosed patients 50 to 80 years of age with early glaucomatous visual field defects were mainly identified from a population -based screening of more than 44,000 residents of Malmö and Helsingborg , Sweden . Exclusion criteria were advanced visual field loss ; mean IOP greater than 30 mmHg or any IOP greater than 35 mmHg ; visual acuity less than 0.5 ; and inability to complete follow-up protocol s. INTERVENTIONS After informed consent , patients were r and omized to treatment or no initial treatment with close follow-up . Treated patients had laser trabeculoplasty and started receiving topical betaxolol twice daily in eligible eyes . Follow-up visits include computerized perimetry and tonometry every 3 months and fundus photography every 6 months . Decisions to change or begin treatment are made jointly with the patient when EMGT progression occurs and also later if clinical ly needed . MAIN OUTCOME MEASURES The EMGT progression is defined by sustained increases of visual field loss in three consecutive C30 - 2 Humphrey tests , as determined from computer-based analyses , or by optic disc changes , as determined from flicker chronoscopy and side-by-side comparisons of fundus photographs performed by masked , independent grade rs . RESULTS A total of 255 patients were r and omized between 1993 and 1997 and will be followed for at least 4 years . All had generally good health status ; mean age was 68.1 years , and 66 % were women . At baseline , mean IOP was 20.6 mmHg and 80 % of eyes had IOP less than 25 mmHg . CONCLUSIONS The Early Manifest Glaucoma Trial is the first large r and omized , clinical trial to evaluate the role of immediate pressure reduction , as compared to no initial reduction , in patients with early glaucoma and normal or moderately elevated IOP . Its results will have implication s for : ( 1 ) the clinical management of glaucoma ; ( 2 ) underst and ing the role of IOP and the natural history of glaucoma ; and ( 3 ) evaluating the rationale for glaucoma screening" ]

[ "The purpose s of this study were to : 1 ) describe the patterns of screen-based sedentary behaviors , and 2 ) examine the association between screen-based sedentary behavior and cardiovascular disease ( CVD ) risk factors in representative Korean children and adolescents , aged 12 to 18 yr , in the Korean National Health and Nutrition Examination Survey . Screen-based sedentary behavior was measured using self-report question naires that included items for time spent watching TV and playing PC/video games . Physical activity was measured using items for frequency and duration of moderate-to-vigorous physical activity ( MVPA ) . CVD risk factors such as body mass index ( BMI ) , waist circumference , LDL cholesterol , HDL cholesterol , total cholesterol , triglycerides , glucose , systolic blood pressure , and diastolic blood pressure were measured . Boys spent more time playing PC/video games , and girls spent more time watching TV . After adjusting for age , gender , annual household income , and MVPA , an additional hour of watching TV was significantly associated with the risk of overweight ( OR 1.17 [ 95 % CI 1.03 - 1.33 ] ) , high abdominal adiposity ( OR 1.27 [ 1.06 - 1.51 ] ) , and low HDL cholesterol ( OR 1.27 [ 1.10 - 1.47 ] ) . An additional hour spent playing PC/video games also increased the risk of high abdominal adiposity ( OR 1.20 [ 1.03 - 1.40 ] ) . Prospect i ve observations and interventions are needed to determine causal relationships between screen-based sedentary behavior and CVD risk profiles in Korean youth", "PURPOSE The objectives of this study were to describe longitudinal trends in adolescent physical activity in a sample of U.S. adolescents and to assess the effect of multiple individual , parental , and environmental factors on initial level and rates of change in adolescent physical activity . METHODS Study subjects were 12,812 boys and girls 10 to 18 years of age who were participating in the Growing Up Today Study and their mothers . We used accelerated longitudinal analysis to describe trajectories of physical activity from 1997 - 1999 , and r and om effects linear mixed models to determine which factors were independently associated with baseline physical activity and changes in physical activity over time . RESULTS Mean hours of physical activity ranged from 7.3 - 11.6 hours per week in boys and from 8.0 - 11.2 hours per week in girls . Physical activity was best modeled as a quadratic function of age , increasing until early adolescence and declining after age 13 in boys and girls . Multivariable modeling demonstrated that variables associated with physical activity level at baseline in boys and girls were age , body mass index , psychosocial variables , personal attitudes about body shape , perceived peer attitudes about body shape/fitness , parental attitudes about physical activity , parental physical activity , and environmental barriers to physical activity . Age was the only factor that predicted change in physical activity over time . CONCLUSIONS Interventions to increase physical activity in adolescents should begin before adolescence . Interventions may be more effective if they are multimodal and focus on modifiable individual , parental , and environmental factors", "Observational longitudinal research is particularly useful for assessing etiology and prognosis and for providing evidence for clinical decision making . However , there are no structured reporting requirements for studies of this design to assist authors , editors , and readers . The authors developed and tested a checklist of criteria related to threats to the internal and external validity of observational longitudinal studies . The checklist criteria concerned recruitment , data collection , biases , and data analysis and descriptive issues relevant to study rationale , study population , and generalizability . Two raters independently assessed 49 r and omly selected articles describing stroke research published from 1999 to 2003 in six journals : American Journal of Epidemiology , Journal of Epidemiology and Community Health , Stroke , Annals of Neurology , Archives of Physical Medicine and Rehabilitation , and American Journal of Physical Medicine and Rehabilitation . On average , 17 of the 33 checklist criteria were reported . Criteria describing the study design were better reported than those related to internal validity . No relation was found between study type ( etiologic or prognostic ) or word count and quality of reporting . A flow diagram for summarizing participant flow through a study was developed . Editors and authors should consider using a checklist and flow diagram when reporting on observational longitudinal research", "To cite this article : Vahlkvist S , Inman MD , Pedersen S. Effect of asthma treatment on fitness , daily activity and body composition in children with asthma . Allergy 2010 ; 65 : 1464–1471", "AIMS Girls with Type 1 diabetes often gain excessive weight during puberty . The aims of this study were to compare objective ly assessed physical activity and energy intake in girls with Type 1 diabetes with those in healthy age-matched controls . METHODS This prospect i ve cohort study comprised 26 girls with Type 1 diabetes and 49 control girls . The mean age of the diabetic girls was 15.7 + /- 2.1 years and that of the control girls 15.8 + /- 2.1 years . In the diabetic group , mean haemoglobin A1c was 7.6 + /- 1.4 % and daily insulin dosage was 1.1 + /- 0.3 U/kg . Physical activity was measured during 7 consecutive days with a uniaxial accelerometer , and energy intake was assessed concurrently with a 7-day food diary . RESULTS There was a tendency towards lower total amount of physical activity in the diabetes group but the difference between the study groups did not reach statistical significance ( Diabetes : 464 + /- 123 counts/min/day ; CONTROLS 523 + /- 138 counts/min/day ; P = 0.06 ) . No difference was found between the groups regarding total energy intake ( Diabetes : 8.5 + /- 1.8 MJ/day ; CONTROLS 8.4 + /- 2.6 MJ/day ) . The carbohydrate intake was lower and the protein and fibre intakes were higher in girls with diabetes . No association was observed between physical activity , energy intake and HbA1c . CONCLUSIONS In this prospect i ve cohort study , we found a tendency towards lower physical activity but no differences in energy intake between girls with Type 1 diabetes and age-matched controls . Larger studies are needed to further explore the importance of the total amount of physical activity for excessive weight gain in adolescent girls with Type 1 diabetes", "OBJECTIVE To compare objective ly assessed physical activity levels , between asthmatic children and non-asthmatic controls . METHODS From a r and om community sample of 794 children aged 8 - 9 years , in a case-control design , 104 children with ever doctor 's diagnosis of asthma and 99 non-asthmatic controls were recruited and had assessment of physical activity with biaxial accelerometers for 7 days . RESULTS Children with active ( also reporting at least one episode of wheezing in the last 12 months ) and inactive ( no wheezing in past 12 months ) asthma appeared to have similar physical activity and sedentary activity levels compared to non-asthmatic children . However , girls with active asthma had significantly lower moderate-to-vigorous physical activity ( MVPA ) levels than their peers with adjusted geometric mean ratio of 0.59 ( 95 % CI : 0.369 , 0.929 , P-value = 0.024 ) . No difference in physical and sedentary activity levels was observed between asthmatic and non-asthmatic boys . The difference between genders in the comparison of MVPA levels in asthmatics and controls was statistically significant ( P-value of likelihood ratio test [ LRT ] for effect modification by gender = 0.034 ) . CONCLUSIONS Unlike boys , girls with active asthma appear to be less active than their healthy peers , and this gender difference might explain the inconsistent evidence from previous reports on physical activity levels in asthmatic children . Further studies are needed to confirm the gender interaction in the childhood asthma-physical activity relation and the implication s on current guidelines for physical exercise prescriptions in asthmatic children", "PURPOSE We established accelerometer count ranges for the Computer Science and Applications , Inc. ( CSA ) activity monitor corresponding to commonly employed MET categories . METHODS Data were obtained from 50 adults ( 25 males , 25 females ) during treadmill exercise at three different speeds ( 4.8 , 6.4 , and 9.7 km x h(-1 ) ) . RESULTS Activity counts and steady-state oxygen consumption were highly correlated ( r = 0.88 ) , and count ranges corresponding to light , moderate , hard , and very hard intensity levels were or = 9499 cnts x min(-1 ) , respectively . A model to predict energy expenditure from activity counts and body mass was developed using data from a r and om sample of 35 subjects ( r2 = 0.82 , SEE = 1.40 kcal x min(-1 ) ) . Cross validation with data from the remaining 15 subjects revealed no significant differences between actual and predicted energy expenditure at any treadmill speed ( SEE = 0.50 - 1.40 kcal x min(-1 ) ) . CONCLUSIONS These data provide a template on which patterns of activity can be classified into intensity levels using the CSA accelerometer", "BACKGROUND Patients with type 1 diabetes mellitus ( T1DM ) may experience poor muscle health as a result of chronic hyperglycemia . Despite this , muscle function in children with T1DM with good or poor glycemic control has yet to be examined in detail . OBJECTIVE To assess differences in muscle-related fitness variables in children with T1DM with good glycemic control ( T1DM-G ) , as well as those with poor glycemic control ( T1DM-P ) , and non-diabetic , healthy controls . SUBJECTS Eight children with T1DM-G [ glycosylated hemoglobin ( HbA1c ) ≤ 7.5 % for 9 months ] , eight children with T1DM-P ( HbA1c ≥ 9.0 % for 9 months ) , and eight healthy controls completed one exercise session . METHODS Anaerobic and aerobic muscle functions were assessed with a maximal isometric grip strength test , a Wingate test , and an incremental continuous cycling test until exhaustion . Blood sample s were collected at rest to determine HbA1c at the time of testing . Physical activity was monitored over 7 d using accelerometry . RESULTS Children with T1DM-P displayed lower peak oxygen consumption ( VO2peak ) values ( mL/kg/min ) compared to healthy controls ( T1DM-P : 33.2 ± 5.6 , controls : 43.5 ± 6.3 , p between VO2peak and HbA1c% ( r = -0.54 , p all other fitness variables . There were no group differences in physical activity variables . CONCLUSION Children with T1DM-G did not display signs of impaired muscle function , while children with T1DM-P have signs of altered aerobic muscle capacity " ]

[ "OBJECTIVE To determine geographical variation in the prevalence of rheumatoid arthritis ( RA ) and spondyloarthropathies ( SpA ) in France . METHODS The survey sample was drawn from 7 areas of France . Households were r and omly selected using the national telephone directory , and an individual within each household was r and omly chosen by the next-birthday method . All cases of suspected RA and SpA were confirmed by the patient 's rheumatologist or by clinical examination . St and ardized estimates of prevalence were compared between regions and groups of regions . RESULTS In total 15,219 anonymous telephone numbers were selected . An average response rate of 64 % led to a total of 9395 respondents included in the study . The highest regional rates of RA were observed in the south ( range 0.59 - 0.66 % ) , and the lowest in the north ( range 0.14 - 0.24 % ) , with a national rate of 0.31 % ( 95 % CI 0.18 - 0.48 % ) . Regional heterogeneity was observed for SpA , with the highest rates in Bretagne ( 0.47 % ) and the Sud-Est ( 0.53 % ) and a national rate of 0.30 % ( 95 % CI 0.17 - 0.46 % ) . CONCLUSION This study is the largest of its kind conducted in France . It shows inter-regional variations , mainly in RA , with a higher prevalence in the south of the country . The many potential reasons for the heterogeneity observed , including genetic and environmental factors , warrant further research", "BACKGROUND It is 40 yr since the last age- and sex-specific estimates of the prevalence of rheumatoid arthritis ( RA ) for the UK were published . Since then the classification criteria for RA have been revised and there has been evidence of a fall in the incidence of RA , especially in women . OBJECTIVES To estimate the age- and sex-specific point prevalence of RA ( defined as fulfilment of a modification of the 1987 ACR classification criteria for RA on the day of assessment ) . The estimate was made in the primary care setting in Norfolk , UK . METHODS A stratified r and om sample was drawn from seven age and gender b and s. The 7050 individuals selected were mailed a screening question naire . Positive responders were invited to attend for a clinical examination . The sample was matched against the names in the Norfolk Arthritis Register ( NOAR ) , a register of incident cases of inflammatory polyarthritis which has been in existence since 1990 . RESULTS The overall response rate was 82 % . Sixty-six cases of RA were identified . Extrapolated to the population of the UK , the overall minimum prevalence of RA is 1.16 % in women and 0.44 % in men . A number of incident cases of RA previously notified to NOAR were not identified as cases in the survey because they had entered into treatment-induced remission . In addition , some cases who failed to attend for examination had significant disability . These prevalence figures are therefore an underestimate . CONCLUSIONS The prevalence of RA in women , but not in men , in the UK may have fallen since the 1950s", "Background —Rheumatoid arthritis may be associated with an increased risk of cardiovascular disease . We compared the incidence rates of myocardial infa rct ion and stroke in subjects with and without rheumatoid arthritis . Methods and Results —A prospect i ve cohort study was conducted among the 114 342 women participating in the Nurses ’ Health Study who were free of cardiovascular disease and rheumatoid arthritis at baseline in 1976 . All self-reported cases of rheumatoid arthritis were confirmed by medical record review . Fatal and nonfatal myocardial infa rct ions and strokes were similarly confirmed . Multivariate pooled logistic regression was used to adjust for potential cardiovascular risk factors . Five hundred twenty-seven incident cases of rheumatoid arthritis and 3622 myocardial infa rct ions and strokes were confirmed during 2.4 million person-years of follow-up . The adjusted relative risk of myocardial infa rct ion in women with rheumatoid arthritis compared with those without was 2.0 ( 95 % confidence interval [ CI ] , 1.23 to 3.29 ) . For stroke , the adjusted relative risk was 1.48 ( 95 % CI , 0.70 to 3.12 ) . Women who had rheumatoid arthritis for at least 10 years had a risk for myocardial infa rct ion of 3.10 ( 95 % CI , 1.64 to 5.87 ) . Conclusion —In this large prospect i ve cohort of women , participants with rheumatoid arthritis had a significantly increased risk of myocardial infa rct ion but not stroke compared with those without rheumatoid arthritis . If these data are confirmed , aggressive coronary heart disease prevention strategies should be tested for persons with rheumatoid arthritis", "OBJECTIVES To investigate the maintenance of physical activity 12 months after two 1-year Internet-based physical activity interventions in patients with RA . METHODS This follow-up study was a r and omized comparison of an Internet-based individualized training ( IT ) and a general training ( GT ) programme in sedentary RA patients . Outcome measures included physical activity ( meeting public health recommendations for moderate physical activity , i.e. 30 min for at least 5 days/week ; or vigorous physical activity , i.e. 20 min for at least 3 days/week ) , functional ability and quality of life ( QoL ) . RESULTS Of the 152 RA patients who completed the initial study , 110 ( 72 % ) were available at follow-up . At 24 months , the proportions of patients meeting public health recommendations for moderate intensity physical activity were significantly higher compared with baseline in both the IT and GT groups ( 19 and 24 % , respectively , P meeting the recommendation for vigorous activity was only significantly higher compared with baseline in the IT group ( P proportions of patients meeting moderate or vigorous physical activity recommendations at 24 months . Apart from a significantly higher RAQoL score in the IT group at 24 months compared with baseline , there were no significant differences within or between the programmes regarding functional ability or QoL. CONCLUSION In RA patients , the effectiveness of both an individualized and a general 1-year Internet-based physical activity programme is sustained with respect to moderate intensity physical activity up to 12 months after the interventions", "OBJECTIVE To evaluate the impact of a 2-year program of strength training on muscle strength , bone mineral density ( BMD ) , physical function , joint damage , and disease activity in patients with recent-onset ( METHODS In this prospect i ve trial , 70 RA patients were r and omly assigned to perform either strength training ( all major muscle groups of the lower and upper extremities and trunk , with loads of 50 - 70 % of repetition maximum ) or range of motion exercises ( without resistance ) twice a week ; all were encouraged to engage in recreational activities 2 - 3 times a week . All patients completed training diaries ( evaluated bi-monthly ) and were examined at 6-month intervals . All were treated with medications to achieve disease remission . Maximum strength of the knee extensors , trunk flexors and extensors , and grip strength was measured with dynamometers . BMD was measured at the femoral neck and lumbar spine by dual x-ray densitometry . Disease activity was determined by the Disease Activity Score , the extent of joint damage by the Larsen score , and functional capacity by the Health Assessment Question naire ( HAQ ) ; walking speed was also measured . RESULTS Sixty-two patients ( 31 per group ) completed the study . Strength training compliance averaged 1.4 - 1.5 times/week . The maximum strength of all muscle groups examined increased significantly ( 19 - 59 % ) in the strength-training group , with statistically significant improvements in clinical disease activity parameters , HAQ scores , and walking speed . While muscle strength , disease activity parameters , and physical function also improved significantly in the control group , the changes were not as great as those in the strength-training group . BMD in the femoral neck and spine increased by a mean + /- SD of 0.51 + /- 1.64 % and by 1.17 + /- 5.34 % , respectively , in the strength-training group , but decreased by 0.70 + /- 2.25 % and 0.91 + /- 4.07 % in the controls . Femoral neck BMD in the 17 patients with high initial disease activity ( and subsequent use of oral glucocorticoids ) remained constantly at a statistically significantly lower level than that in the other 45 patients . CONCLUSION Regular dynamic strength training combined with endurance-type physical activities improves muscle strength and physical function , but not BMD , in patients with early RA , without detrimental effects on disease activity", "OBJECTIVES Cardiovascular disease ( CVD ) is responsible for 50 % of the excess mortality for patients with RA . This study aim ed to evaluate a novel 8-week cognitive behavioural patient education intervention design ed to effect behavioural change with regard to modifiable CVD risk factors in people with RA . METHODS This was a non-blinded r and omized controlled trial with a delayed intervention arm . Participants were r and omly assigned to receive the cognitive behavioural education intervention or a control information leaflet at a ratio of 1:1 . The primary outcome measure was patient 's knowledge of CVD in RA ; secondary measures were psychological measures relating to effecting behaviour change , actual behaviour changes and clinical risk factors . Data were collected at baseline , 2 and 6 months . RESULTS A total of 110 participants consented ( 52 in the intervention group and 58 in the control group ) to participate in the study . At 6 months , those in the intervention group had significantly higher knowledge scores ( P improved behavioural intentions to increase exercise ( P eat a low-fat diet ( P = 0.01 ) and lose weight ( P = 0.06 ) ; and lower mean diastolic blood pressure by 3.7 mmHg , whereas the control group 's mean diastolic blood pressure increased by 0.8 mmHg . There was no difference between the groups on actual behaviours . CONCLUSIONS Patient education has a significant role to play in CVD risk factor modification for patients with RA , and the detailed development of this programme probably contributed to its successful results . It is disappointing that behaviours , as we measured them , did not change . The challenge , as always , is how to translate behavioural intentions into action . Larger studies , powered specifically to look at behavioural changes , are required . Trial registration . National Institute for Health Research , UKCRN 4566", "The purpose of this study is to evaluate the effects of targeting both the motivation and action phases of behaviour change in a 5-week intervention to increase physical activity ( PA ) among patients with rheumatoid arthritis ( RA ) not meeting current PA recommendations . In a r and omised controlled trial , a control group — which received a group-based patient education session led by a physical therapist — was compared to a treatment group which received the education session plus a motivational interview from a physical therapist and two self-regulation coaching sessions from a rheumatology nurse . Outcomes included leisure-time PA , days per week with at least 30 min of moderate-intensity PA , self-efficacy and autonomous motivation ( cognitions which predict PA initiation and maintenance ) , disease activity , functional status , depressive symptoms and fatigue . Effects were assessed using mixed models repeated measures . Of the 78 patients r and omised , 76 and 67 completed the post-treatment and follow-up assessment s , respectively . Significant treatment effects were found for leisure-time PA ( p = 0.022 ) , active days/week ( p = 0.016 ) , self-efficacy ( p = 0.008 ) and autonomous motivation ( p = 0.001 ) . At post-treatment and 6-months follow-up , significantly more treated patients than controls met current PA recommendations . No significant effects were found for disease activity , functional status , depressive symptoms or fatigue . Combining motivation- and action-focused intervention approaches improved PA-related cognitions and led to improved uptake and maintenance of leisure-time PA . However , further research is necessary to identify ways of helping patients with RA transition to— and maintain — more intensive forms of PA which are more likely to improve disease activity and functional status", "OBJECTIVE To examine the reliability , validity , and responsiveness of a continuous ambulatory activity monitor in patients with rheumatoid arthritis ( RA ) . METHODS Forty-one patients with RA , participating in a r and omized controlled trial examining the effect of an intensive exercise program , were assessed by means of the Dynaport ADL ( activities of daily living ) monitor ( AM ) . The time spent on activities ( locomotion , st and ing , and active sitting ) during 24 hours and the intensity of trunk movement during these activities were recorded . To determine test-retest reliability 20 patients were reassessed with the AM one week after the first assessment . Construct validity of the AM was determined by comparing the AM results with physical fitness measures ( muscle strength , endurance , joint mobility ) , disease activity , and functional status . As well , 37 patients were assessed 18 months after the first assessment to determine responsiveness . RESULTS All AM measurements showed satisfactory test-retest reliability ( ICC 0.63 - 0.76 ) . AM measures were significantly associated with physical fitness , functional status , and disease activity , indicating construct validity of the AM . The AM could discriminate between patients with improvement and deterioration in physical fitness , indicating sufficient responsiveness of AM variables . CONCLUSION This study shows the value of an ambulatory activity monitor to quantify both the amount and intensity of physical activity of patients with RA during a day in their own environment . The ambulatory activity monitor seems to be a promising instrument for research into rehabilitation of patients with RA", "OBJECTIVE To determine the effect of education on the exercise habits of patients with rheumatoid arthritis ( RA ) after 6 and 12 months . METHODS We studied 208 out patients recruited between June 2001 and December 2002 . This was a prospect i ve controlled r and omized trial . The active group received a multidisciplinary education program , including training in home-based exercises and guidelines for leisure physical activity ( PA ) . The control group received a booklet added to usual medical care . Compliance with home-based exercises was defined as a practice rate > or= 30 % of the prescribed training . Compliance with leisure PA was defined as > or= 20 % increase in Baecke question naire score . Additional assessment s involved possible predictors of compliance and changes with regard to the compliance . RESULTS At 6-month followup , home-based exercise and leisure PA compliance were significantly higher [ 13.5 % vs 1 % , respectively ( p = 0.001 ) ; and 28.2 % vs 13.8 % ( p = 0.02 ) ] , but were not at 12 months . Predictors of leisure PA compliance at 6 months included participating in the active group ( odds ratio 2.74 , 95 % CI 1.17 to 6.38 ) and previous low leisure PA ( OR 6.01 , 95 % CI 2.47 to 14.61 ) , with decreased fatigue ( FACIT-F mean -2.94 + /- 8.04 vs -0.1 + /- 7.25 for noncompliant subjects ; p = 0.04 ) and improved psychological status ( Arthritis Impact Measurement Scale mean -1.25 + /- 3.12 vs 0.11 + /- 3.39 ; p = 0.03 ) . CONCLUSION Education of patients with RA may increase compliance especially with leisure PA , particularly when it is poor at baseline , but these effects are limited and short-term", "OBJECTIVE To investigate the effect of a 1-year coaching program for healthy physical activity on perceived health status , body function , and activity limitation in patients with early rheumatoid arthritis . METHODS A total of 228 patients ( 169 women , 59 men , mean age 55 years , mean time since diagnosis 21 months ) were r and omized to 2 groups after assessment s with the EuroQol visual analog scale ( VAS ) , Grippit , Timed-St and s Test , Escola Paulista de Medicina Range of Motion scale , walking in a figure-of-8 , a visual analog scale for pain , the Health Assessment Question naire disability index , a self-reported physical activity question naire , and the Disease Activity Score in 28 joints . All patients were regularly seen by rheumatologists and underwent rehabilitation as prescribed . Those in the intervention group were further individually coached by a physical therapist to reach or maintain healthy physical activity ( > or = 30 minutes , moderately intensive activity , most days of the week ) . RESULTS The retention rates after 1 year were 82 % in the intervention group and 85 % in the control group . The percentages of individuals in the intervention and control groups fulfilling the requirements for healthy physical activity were similar before ( 47 % versus 51 % ; P > 0.05 ) and after ( 54 % versus 44 % ; P > 0.05 ) the intervention . Analyses of outcome variables indicated improvements in the intervention group over the control group in the EuroQol VAS ( P = 0.025 ) and muscle strength ( Timed-St and s Test ; P = 0.000 ) ( Grippit ; P = 0.003 ) , but not in any other variables assessed . CONCLUSION A 1-year coaching program for healthy physical activity result ed in improved perceived health status and muscle strength , but the mechanisms remain unclear , as self-reported physical activity at healthy level did not change", "OBJECTIVES To investigate the long-term effects on perceived general health , disease activity , pain , activity limitation and cognitive behavioural factors of a one-year coaching programme performed in ordinary physical therapy practice to promote the adoption of health-enhancing physical activity in patients with early rheumatoid arthritis ( RA ) . METHODS A total of 228 patients with early RA , from 10 rheumatology clinics in Sweden , were r and omly assigned to an intervention group ( IG ; n = 94 ) or a control group ( CG ; n = 134 ) . The IG was coached by physical therapists during the first year to adopt health-enhancing levels of physical activity ( 30 minutes/day , moderately intensive , ≥ 4 days/week ) . No coaching was given during the subsequent year between post-intervention and follow-up . Follow-up assessment consisted of a postal question naire on physical activity and of visual analogue scales for ratings of general health perception and pain . The Health Assessment Question naire Disability Index ( HAQ ) and the Disease Activity Score in 28 joints ( DAS 28 ) were collected at regular medical check-ups . RESULTS Sixty-five ( 69 % ) participants in the IG and 92 ( 69 % ) in the CG completed the entire study period by filling in the follow-up question naire on physical activity two years after baseline . The intervention seemed to lack any significant influence on long-term outcome . However , different patterns of change in physical activity behaviour were observed in the two groups . CONCLUSIONS No long-term improvement in perceived general health or other outcomes were found in the follow-up . This may partly be because the intervention lacked several important behavioural elements for physical activity maintenance", "OBJECTIVE To compare the effectiveness of 2 Internet-based physical activity interventions for patients with rheumatoid arthritis ( RA ) . METHODS A total of 160 physically inactive patients with RA who had a computer with Internet access were r and omly assigned to an Internet-based physical activity program with individual guidance , a bicycle ergometer , and group contacts ( individualized training [ IT ] group ; n = 82 ) or to an Internet-based program providing only general information on exercises and physical activity ( general training [ GT ] group ; n = 78 ) . Outcome measures included quantity of physical activity ( question naire and activity monitor ) , functional ability , quality of life , and disease activity ( baseline , 3 , 6 , 9 , and 12 months ) . RESULTS The proportion of physically active patients was significantly greater in the IT than in the GT group at 6 ( 38 % versus 22 % ) and 9 months ( 35 % versus 11 % ; both P in physical activity as measured with an activity monitor , functional ability , quality of life , or disease activity . CONCLUSION An Internet-based physical activity intervention with individually tailored supervision , exercise equipment , and group contacts is more effective with respect to the proportion of patients who report meeting physical activity recommendations than an Internet-based program without these additional elements in patients with RA . No differences were found regarding the total amount of physical activity measured with an activity monitor", "ABSTRACT Cardiorespiratory function and exercise tolerance appear very limited in persons with rheumatoid arthritis ( RA ) . Many studies have demonstrated that aerobic exercise training is beneficial to prevent physical deconditioning without inducing adverse effects on an individual 's joints and general health . The present study was conducted to demonstrate that a dance-based exercise program is a safe and efficient activity to improve physical fitness and psychological state in persons with RA . A group of 19 persons ( mean age , 49.3 ± 13 yr ) participated in a 12-wk exercise program ( twice weekly ) , whereas 10 persons ( mean age , 49.4 ± 12 yr ) served as controls . Health status , use of medication , joint pain and swelling , physical fitness , activity of daily living and psychological state were assessed at baseline , after the 12-wk training program and 6 mo after the end of the program . Exercise training induced a mean improvement of 13 % in aerobic power , with the highest values reaching 40 % . No significant changes were observed in joint status , even though the count of painful joints tended to decrease in the exercise group . Positive changes in depression , anxiety , fatigue and tension were observed after the 12-wk exercise program . These findings provide some evidence s in favor of aerobic exercise in individuals with RA . Furthermore , it is of primary interest to note that a weight-bearing activity with limited ground impacts do not provoke short-term adverse effects on joint status . Further studies , however , are required to determine the long-term effect of weight-bearing exercise on the health status of individuals with RA", "OBJECTIVE To evaluate the functional , clinical , radiological and quality of life outcomes of a 4-week dynamic exercise programme ( DEP ) in RA . METHODS Patients matched on the principal medico-social parameters were r and omly assigned to either the DEP or the conventional joint rehabilitation group . Primary end point for judging effectiveness was functional status assessed by HAQ . Secondary outcomes included Nottingham Health Profile ( NHP ) , Arthritis Impact Measurement Scale 2-Short Form ( AIMS 2-SF ) and radiological worsening measured by Simple Narrowing Erosion Score ( SENS ) . Clinical evaluation consisted of disease activity score ( DAS 28 ) , cycling aerobic fitness and dexterity . Dexterity was measured using Sequential Occupational Dexterity Assessment ( SODA ) and Duruoz H and Index ( DHI ) . Data were collected at baseline 1 , 6 and 12 months . RESULTS Fifty patients were enrolled . HAQ improved throughout the length of the trial in the DEP group . This improvement was greater in DEP than in the st and ard joint rehabilitation group at 1 month ( -0.2 vs no variation from baseline , P = 0.04 ) , but not at 6 months ( -0.2 vs -0.1 in control group , P = 0.25 ) or 12 months ( -0.1 vs no variation in control group , P = 0.51 ) . DEP improved NHP ( -23 vs + 7 % in control group , P = 0.01 ) and aerobic fitness ( + 0.3 vs + 0.1 km per 5 min in control group , P = 0.02 ) at 1 month but the progress was not statistically significant thereafter . DEP also improved DHI , SODA , DAS 28 and AIMS 2-SF , although not significantly . CONCLUSION DEP was effective on functional status assessed by HAQ , quality of life and aerobic fitness at 1 month" ]

[ "BACKGROUND Autologous bone graft is the so-called gold st and ard for reconstruction of bone defects and nonunions . The most frequent complication is donor site pain . The iliac crest is a common source for autologous bone graft . The purpose of this study was to determine whether a continuous infusion of 0.5 % bupivacaine into the iliac crest harvest site provides pain relief that is superior to the relief provided by systemic narcotic pain medication alone in patients undergoing reconstructive orthopaedic trauma procedures . METHODS A prospect i ve , double-blind r and omized study of patients over eighteen years of age who were undergoing harvesting of iliac crest bone graft was conducted . The patients were r and omized to the treatment arm ( bupivacaine infusion pump ) or the placebo arm . Postoperatively , all study patients received morphine sulfate with use of a patient-controlled analgesia pump . The patients recorded the pain at the donor and recipient sites with use of a scale ranging from 0 to 10 . The use of systemic narcotic medication was recorded . Independent- sample s t tests were used to assess differences in perceived pain relief between the treatment and control groups at zero , eight , sixteen , twenty-four , thirty-two , forty , and forty-eight hours after surgery . Pain was also assessed at two and six weeks postoperatively . RESULTS Sixty patients were enrolled . Across all data points , except pain at the recipient site at twenty-four hours , no significant differences in the perception of pain were found between the bupivacaine group and the placebo group . On the average , patients in the treatment group reported more pain than those in the control group . No significant difference was found between the two groups with regard to the amount of narcotic medication used . CONCLUSIONS No difference in perceived pain was found between the groups . The results of this small , unstratified study indicate that continuous infusion of bupivacaine at iliac crest bone-graft sites during the postoperative period is not an effective pain-control measure in hospitalized patients receiving systemic narcotic medication", "In r and omized controlled trials , no single definition of response is ideal for all purpose s. We propose a method to present in a simple fashion the likelihood of response over a full range of response levels , which will facilitate a better underst and ing of clinical trial data . We present the technique called the cumulative proportion of responders analysis ( CPRA ) and its application to four pain clinical trial data sets as examples . The CPRA can be used to present the proportion of responders over the entire range of possible cut-off points as a graph . This allows the reader to compare treatment groups at any responder level that is valid for their patient population . Whether as a primary or secondary approach to a clinical trial of pain therapy , the display of data in a CPRA format may be useful in the underst and ing of results and applicability to patient care", "Although nonsteroidal antiinflammatory drugs ( NSAIDs ) improve postoperative pain relief after cesarean delivery , they carry potential side effects ( e.g. , bleeding ) . Perioperative cyclooxygenase (COX)-2 inhibitors show similar analgesic efficacy to nonsteroidal antiinflammatory drugs in many surgical models but have not been studied after cesarean delivery . We design ed this r and omized double-blind study to determine the analgesic efficacy and opioid-sparing effects of valdecoxib after cesarean delivery . Healthy patients undergoing elective cesarean delivery under spinal anesthesia were r and omized to receive oral valdecoxib 20 mg or placebo every 12 h for 72 h postoperatively . As a result of cyclooxygenase-2 inhibitors safety concerns that became apparent during this study , the study was terminated early after evaluating 48 patients . We found no differences in total analgesic consumption between the valdecoxib and placebo groups ( 121 ± 70 versus 143 ± 77 morphine mg-equivalents , respectively ; P = 0.26 ) . Pain at rest and during activity were similar between the groups despite adequate post hoc power to have detected a clinical ly significant difference . There were also no differences in IV morphine requirements , time to first analgesic request , patient satisfaction , side effects , breast-feeding success , or functional activity . Postoperative pain was generally well controlled . Adding valdecoxib after cesarean delivery under spinal anesthesia with intrathecal morphine is not supported at this time", "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", "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", "Background : Ketamine potentiates intravenous or epidural morphine analgesia . The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain . Methods : Forty-nine patients scheduled to undergo open thoracotomy were r and omly assigned to receive one of two anesthesia regimens : continuous epidural infusion of ropivacaine and morphine , along with intravenous infusion of ketamine ( 0.05 mg · kg−1 · h−1 [ approximately 3 mg/h ] , ketamine group , n = 24 ) or placebo ( saline , control group , n = 25 ) . Epidural analgesia was continued for 2 days after surgery , and infusion of ketamine or placebo was continued for 3 days . Pain was assessed at 6 , 12 , 24 , and 48 h after surgery . Patients were asked about their pain , abnormal sensation on the wound , and inconvenience in daily life at 7 days and 1 , 3 , and 6 months after surgery . Results : The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group ( pain at rest , 9 ± 11 vs. 25 ± 20 and 9 ± 11 vs. 18 ± 13 ; pain on coughing , 26 ± 16 vs. 50 ± 17 and 30 ± 18 vs. 43 ± 18 , mean ± SD ; P = 0.002 and P = 0.01 , P . The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group ( 0.5 [ 0–4 ] vs. 2 [ 0–5 ] and 0 [ 0–5 ] vs. 1.5 [ 0–6 ] , median [ range ] , respectively ; P = 0.02 ) . Three months after surgery , a higher number of control patients were taking pain medication ( 2 vs. 9 ; P = 0.03 ) . Conclusions : Very-low-dose ketamine ( 0.05 mg · kg−1 · h−1 ) potentiated morphine-ropivacaine analgesia and reduced postthoracotomy pain ", "Although clonidine has been shown to increase the duration of local anesthetic action and prolong postoperative analgesia when included in single-injection nerve blocks , the only controlled investigation of the efficacy of this practice to improve analgesia for continuous perineural local anesthetic infusion failed to discern any clinical ly relevant benefits . For this study , we used a larger dose of clonidine in an attempt to improve analgesia . Patients ( n = 20 ) undergoing moderately painful orthopedic surgery of the shoulder received an interscalene brachial plexus block ( 40 mL of mepivacaine 1.5 % , epinephrine 2.5 & mgr;g/mL , and clonidine 50 & mgr;g ) and a perineural catheter before surgery . After surgery , ropivacaine 0.2 % or ropivacaine 0.2 % plus clonidine 2 & mgr;g/mL was delivered via the catheter for 3 days ( basal rate , 5 mL/h ; patient-controlled bolus , 5 mL ; lockout , 1 h ) . Investigators and patients were blind to r and om group assignment . The primary outcome variable was design ated as the most intense pain during the day after surgery . Secondary end-points included additional pain scores , patient-controlled bolus doses , oral analgesic use , sleep quality , and catheter- or infusion-related complications . There were no statistically significant differences between groups for any of the variables investigated . We conclude that adding clonidine 2 & mgr;g/mL to a ropivacaine interscalene perineural infusion does not decrease breakthrough pain intensity the day after surgery . For the additional end-points , our negative findings are only suggestive of a lack of effect and require further study for verification", "Background : Neuropathic pain in spinal cord injury is a common challenging therapeutic condition . The current study examines the analgesic effect of the sodium channel blocker lidocaine on neuropathic pain in patients with spinal cord injury and the predictive role of concomitant evoked pain on pain relief with lidocaine . Methods : Twenty-four spinal cord injury patients with neuropathic pain at or below the level of injury were r and omized and completed a double-blind crossover trial of 5 mg/kg lidocaine and placebo infused over 30 min . Twelve patients reported evoked pain , and 12 patients had no evoked pain . Spontaneous and evoked pains were assessed using a visual analog scale and quantitative sensory testing . Results : Lidocaine significantly reduced spontaneous pain in all patients ( P Lidocaine significantly relieved both at-level and below-level neuropathic pain and decreased brush-evoked dysesthesia but not cold allodynia , pinprick hyperalgesia , or pain evoked by repetitive pinprick . Conclusions : Lidocaine reduced neuropathic pain at and below the level of injury irrespective of the presence or absence of evoked pain . Results are consistent with a central -acting effect of sodium channel blockers acting on neuronal hyperexcitability . Agents ( such as anticonvulsants or antiarrhythmics ) with sodium channel – blocking properties may be a treatment option for spinal cord injury pain", "BACKGROUND : Gabapentin , an oral non-opioid analgesic , has been used to decrease pain after a variety of surgical procedures . We hypothesized that premedication with gabapentin would minimize tourniquet-related pain in patients receiving IV regional anesthesia ( IVRA ) . METHODS : Patients undergoing elective h and surgery with IVRA were r and omly assigned to one of two study groups using a double-blind study design . The control group ( n = 20 ) received placebo capsules 1 h before the surgery , and the gabapentin group ( n = 20 ) received gabapentin 1.2 g p.o . before the operation . IVRA was achieved in all patients with lidocaine , 3 mg/kg , diluted with saline to a total volume of 40 mL. Fentanyl , 0.5 & mgr;g/kg IV , was administered as a rescue analgesic during surgery . Sensory and motor block onset and recovery times , tourniquet pain , and quality of anesthesia were assessed at specific time intervals during the perioperative period . Visual analog scale pain scores ( 0–10 ) were recorded during the 24 h follow-up period , and patients received diclofenac , 75 mg IM , if their pain score was > 4 . RESULTS : The onset of the sensory and motor block did not differ between the two study groups . However , tourniquet pain scores at 30 , 40 , 50 , and 60 min after cuff inflation were lower in the gabapentin group ( P The time to intraoperative analgesic rescue was prolonged in the gabapentin group ( 35 ± 10 min vs 21 ± 13 min , P The quality of anesthesia , as independently assessed by the anesthesiologist and the surgeon , was significantly better in the gabapentin ( versus control ) group . In the gabapentin group , the time to requesting a rescue analgesic after surgery was prolonged ( 135 ± 25 min vs 85 ± 19 min , P and postoperative pain scores at 60 min ( 3.8 ± 0.9 vs 2.2 ± 0.5 ) and 120 min ( 3.2 ± 1.4 vs 1.8 ± 0.8 ) , as well as diclofenac consumption ( 30 ± 38 mg vs 60 ± 63 mg ) , were reduced after surgery . CONCLUSIONS : Premedication with oral gabapentin ( 1.2 g ) decreased tourniquet-related pain and improved the quality of anesthesia during h and surgery under IVRA . Gabapentin also reduced pain scores in the early postoperative period", "BACKGROUND Lateral epicondylitis is a common condition for which botulinum toxin has been reported to have a therapeutic role in uncontrolled studies . OBJECTIVE To determine if an injection of botulinum toxin is more effective than placebo for reducing pain in adults with lateral epicondylitis . DESIGN R and omized , double-blind , placebo-controlled trial conducted from September 2002 to December 2004 . SETTING Outpatient clinics at a university hospital and a district hospital in Hong Kong . PARTICIPANTS 60 patients with lateral epicondylitis . MEASUREMENTS The primary outcome was change in subjective pain as measured by a 100-mm visual analogue scale ( VAS ) ranging from 0 ( no pain ) to 10 ( worst pain ever ) at 4 weeks and 12 weeks . All patients completed post-treatment follow-up . INTERVENTIONS A single injection of 60 units of botulinum toxin type A or normal saline placebo . RESULTS Mean VAS scores for the botulinum group at baseline and at 4 weeks were 65.5 mm and 25.3 mm , respectively ; respective scores for the placebo group were 66.2 mm and 50.5 mm ( between-group difference of changes , 24.4 mm [ 95 % CI , 13.0 to 35.8 mm ] ; P mean VAS scores were 23.5 mm for the botulinum group and 43.5 mm for the placebo group ( between-group difference of changes , 19.3 mm [ CI , 5.6 to 32.9 mm ] ; P = 0.006 ) . Grip strength was not statistically significantly different between groups at any time . Mild paresis of the fingers occurred in 4 patients in the botulinum group at 4 weeks . One patient 's symptoms persisted until week 12 , whereas none of the patients receiving placebo had the same complaint . At 4 weeks , 10 patients in the botulinum group and 6 patients in the placebo group experienced weak finger extension on the same side as the injection site . LIMITATIONS The trial was small , and most participants were women . The blinding protocol may have been ineffective because the 4 participants who experienced paresis of the fingers could have correctly assumed that they received an active treatment . CONCLUSIONS Botulinum toxin injection may improve pain over a 3-month period in some patients with lateral epicondylitis , but injections may be associated with digit paresis and weakness of finger extension", "There is experimental evidence that nimodipine , an L-type dihydropiridine calcium channel blocker with relatively high blood-brain barrier penetration , enhances the antinociceptive properties of morphine . We tested the hypothesis that oral nimodipine taken preoperatively and 6 hourly for 48 h postoperatively would reduce visual analog scale pain scores and morphine consumption in morphine-naive patients with acute postoperative pain . Forty patients undergoing total knee replacement surgery ( age 70 ± 7 yr , 28 male ) were r and omized by computer-generated numbers to receive capsules containing either nimodipine 30 mg or placebo in a double-blind study design . All patients received 3 capsules ( nimodipine 90 mg or placebo ) 1–2 h before induction of anesthesia followed by oral nimodipine 30 mg or placebo 6 hourly for 48 hours postoperatively . Spinal anesthesia was induced with hyperbaric bupivacaine 0.5 % ( 2.4–3.0 mL ) and fluids and ephedrine were given at the discretion of the anesthesiologist . Morphine patient-controlled analgesia ( PCA , bolus 1 mg , lockout 5 min ) was given for postoperative analgesia . Primary outcome measures were visual analog pain scores at rest and on moving ( sitting forward ) and PCA morphine consumption . Morphine consumption was significantly larger in nimodipine patients at 12 h ( 39 ± 18 versus 29 ± 15 ; P = 0.04 ) , 24 h ( 62 ± 23 versus 45 ± 24 ; P = 0.02 ) , and 48 h ( 88 ± 34 versus 61 ± 27 ; P = 0.01 ) . There were no significant differences in pain scores at rest or moving or in time to first use of morphine analgesia . This study has demonstrated increased morphine consumption after 12 h in postoperative patients receiving nimodipine , suggesting that , in patients undergoing knee replacement surgery , it has no adjunctive analgesic effect and may actually inhibit the analgesic effect of morphine", "& 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 and Purpose Aquatic physical therapy is frequently used in the management of patients with hip and knee osteoarthritis ( OA ) , yet there is little research establishing its efficacy for this population . The purpose of this study was to evaluate the effects of aquatic physical therapy on hip or knee OA . Subjects A total of 71 volunteers with symptomatic hip OA or knee OA participated in this study . Methods The study was design ed as a r and omized controlled trial in which participants r and omly received 6 weeks of aquatic physical therapy or no aquatic physical therapy . Outcome measures included pain , physical function , physical activity levels , quality of life , and muscle strength . Results The intervention result ed in less pain and joint stiffness and greater physical function , quality of life , and hip muscle strength . Totals of 72 % and 75 % of participants reported improvements in pain and function , respectively , compared with only 17 % ( each ) of control participants . Benefits were maintained 6 weeks after the completion of physical therapy , with 84 % of participants continuing independently . Discussion and Conclusion Compared with no intervention , a 6-week program of aquatic physical therapy result ed in significantly less pain and improved physical function , strength , and quality of life . It is unclear whether the benefits were attributable to intervention effects or a placebo response", "Babcock MS , Foster L , Pasquina P , Jabbari B : Treatment of pain attributed to plantar fasciitis with botulinum toxin A : A short-term , r and omized , placebo-controlled , double-blind study . Am J Phys Med Rebabil 2005;84:649–654 . Objective : To investigate the effect of botulinum toxin A on associated pain and functional impairment of refractory plantar fasciitis . Design : This is a r and omized , double-blind , placebo-controlled study of 27 patients ( 43 feet ) with plantar fasciitis . Block r and omization was performed using computer software . In patients with bilateral symptoms of comparable severity , botulinum toxin A was injected in one foot and saline in the other foot . The treatment group received a total of 70 units of botulinum toxin A divided into two sites per foot . One of the two sites was the tender area in the medial aspect of the heel close to the calcaneal tuberosity ( 40 units ) , and the other was in the arch of the foot between an inch anterior to the heel and middle of the foot ( 30 units ) . The placebo group received the same volume of normal saline . Main outcome measures included : Pain Visual Analog Scale , Maryl and Foot Score , Pain Relief Visual Analog Scale , and pressure algometry response . Patients were assessed before injection , at 3 wks , and at 8 wks . Results : The study revealed statistically significant changes in the treatment group . Compared with placebo injections , the botulinum toxin A group improved in all measures : Pain Visual Analog Scale ( P Maryl and Foot Score ( P = 0.001 ) , Pain Relief Visual Analog Scale ( P pressure algometry response ( P = 0.003 ) . No side effects were noted . Conclusions : Botulinum toxin A injection for plantar fasciitis yields significant improvements in pain relief and overall foot function at both 3 and 8 wks after treatment", "The purpose of this study was to vali date the changes in acute pain measurement scales that are most strongly associated with a patient-determined indicator of clinical importance . Measures of pain intensity and pain relief are commonly used outcomes in therapeutic clinical trials . Recent studies of the properties of acute pain measures have provided data defining the cut-off points that are best associated with clinical ly important differences . Validation of these findings in another clinical trial data set is important . Data were obtained from the titration phase of a recently conducted r and omized controlled clinical trial of oral transmucosal fentanyl citrate ( OTFC ) , which compared OTFC to immediate release morphine sulfate ( MSIR ) for the treatment of cancer-related acute breakthrough pain . Changes in pain intensity and pain relief were recorded every 15 minutes for 60 minutes and global medication performance recorded at the end of each study pain episode . At any titration step , if the patient felt that the first dose of the study medication did not provide adequate relief within 30 minutes , an additional rescue medication could be taken . To find the level of each pain scale best associated with this measure of the adequacy of pain relief , the calculated sensitivity , specificity , and accuracy for different cut-off points of the measured pain scales were compared to whether or not the patient needed rescue medication . The overall ability of the pain measures to discriminate episodes for which a rescue was not needed was calculated using area under the receiver operating characteristics ( ROC ) curves . Data were analyzed from 134 OTFC-naive patients who collected data on 1307 episodes of breakthrough pain . Using the criteria of a balanced sensitivity and specificity , the best cut-off points were determined to be : 33 % for the percent pain intensity difference ; > or = 2 for the raw pain intensity difference on a 0 - 10 numeric rating scale ; > or = 2 ( i.e. , moderate or better ) for pain relief ; > or = 33 % for the percent maximum total pain relief ; and > or = 2 ( good or better ) for global medication performance . ROC area under the curve ranged from 0.839 to 0.862 for each of the pain measures listed above , calculated at 60 minutes . These data indicate that the pain scale cut-off points that are best associated with a patient-derived measure of a clinical ly important difference closely approximate those found in an earlier study . ROC analysis provided evidence that the overall pain measures were strongly associated with not requiring an \" additional dose of rescue medication . \" Thus , the cut-off points determined for these pain scales provide a good surrogate measure of a patient-determined clinical ly important response . This provides support for the usefulness of these values in future clinical trials of pain therapy", "OBJECTIVE To evaluate the effectiveness of intrauterine lignocaine as an anaesthetic during endometrial sampling . DESIGN Prospect i ve , r and omised , double-blind , placebo-controlled trial . SETTING Outpatient gynaecological minor operation unit in a public hospital . POPULATION Two hundred premenopausal women scheduled for endometrial sampling because of abnormal uterine bleeding . METHODS Transcervical intrauterine instillation of 5 mL of 2 % lignocaine or 5 mL of normal saline before performing endometrial sampling with vacuum aspirator . MAIN OUTCOME MEASURES Evaluation of pain associated with the procedure using a visual analogue scale . RESULTS The use of intrauterine lignocaine reduced pain during suction curettage in endometrial sampling . CONCLUSIONS Transcervical instillation of lignocaine reduced pain during endometrial sampling", "PURPOSE The aim of this study was to compare the analgesic efficacy of single-dose preoperative intravenous versus oral tramadol for preventing pain after third molar surgery . PATIENTS AND METHODS Seventy-two patients undergoing elective third molar surgery were r and omized to receive either intravenous ( n = 36 ) or oral ( n = 36 ) tramadol 50 mg . The intravenous group received an oral placebo capsule followed by intravenous tramadol 50 mg preoperatively . The oral tramadol group received a 50-mg oral tramadol capsule followed by intravenous placebo saline preoperatively . In both groups , a st and ard intravenous sedation technique was administered and the impacted third molars were removed under local anesthesia . The difference in postoperative pain was assessed by 4 primary end points : hourly pain intensity as measured by a 100-mm visual analog scale for 8 hours , time to rescue analgesic , postoperative acetaminophen consumption , and a 5-point global assessment scale ( 0 = poor , 1 = fair , 2 = good , 3 = very good , and 4 = excellent ) . RESULTS Throughout the 8-hour investigation period , patients reported significantly lower pain intensity scores in the intravenous versus oral group ( 15.9 + /- 9.6 mm versus 36.9 + /- 17.2 mm , P = .03 ) . Patients also reported significantly longer time to rescue analgesic ( 7.0 hours versus 3.5 hours , P = .00001 ) , lesser postoperative acetaminophen consumption ( 1,823 + /- 1,266 mg versus 3,558 + /- 1,418 mg , P = .000006 ) , and better global assessment ( 2.6 + /- 0.9 versus 1.1 + /- 0.8 , P = .01 ) for the intravenous versus oral group . CONCLUSIONS We conclude that preoperative intravenous tramadol is superior to oral tramadol for preventing postoperative pain following third molar surgery . However , it should be noted that there is a difference in the bioavailability between the 2 formulations of up to 30 % , which may explain the findings", "We conducted this study to evaluate the effects of magnesium , when added to lidocaine for IV regional anesthesia ( IVRA ) , on tourniquet pain . Thirty patients undergoing elective h and surgery during IVRA were r and omly assigned to two groups . IVRA was achieved with 10 mL of saline plus 3 mg/kg lidocaine 0.5 % diluted with saline to a total of 40 mL in group C or with 10 mL of 15 % magnesium sulfate ( 12.4 mmol ) plus 3 mg/kg lidocaine 0.5 % diluted with saline to a total of 40 mL in group M. Injection pain , sensory and motor block onset and recovery time , tourniquet pain , and anesthesia quality were noted . Patients were instructed to receive 75 mg of IM diclofenac when the visual analog scale ( VAS ) score was > 4 , and analgesic requirements were recorded . Sensory and motor block onset times were shorter and recovery times were prolonged in group M ( P 0.05 ) . VAS scores of tourniquet pain were lower in group M at 15 , 20 , 30 , 40 , and 50 min ( P 0.001 ) . Anesthesia quality , as determined by the anesthesiologist and surgeon , was better in group M ( P ) . Time to the first postoperative analgesic request in group C was 95 ± 29 min and in group M was 155 ± 38 min ( P were higher for the first postoperative 6 h in group C ( P 0.05 ) . Diclofenac consumption was significantly less in group M ( 50 ± 35 mg ) when compared with group C ( 130 + 55 mg ) ( P lidocaine improves the quality of anesthesia and analgesia in IVRA", "Chae J , Yu DT , Walker ME , Kirsteins A , Elovic EP , Flanagan SR , Harvey RL , Zorowitz RD , Frost FS , Grill JH , Fang ZP : Intramuscular electrical stimulation for hemiplegic shoulder pain : A 12-month follow-up of a multiple-center , r and omized clinical trial . Am J Phys Med Rehabil 2005;84:832–842 . Objective : Assess the effectiveness of intramuscular electrical stimulation in reducing hemiplegic shoulder pain at 12 mos posttreatment . Design : A total of 61 chronic stroke survivors with shoulder pain and subluxation participated in this multiple-center , single-blinded , r and omized clinical trial . Treatment subjects received intramuscular electrical stimulation to the supraspinatus , posterior deltoid , middle deltoid , and upper trapezius for 6 hrs/day for 6 wks . Control subjects were treated with a cuff-type sling for 6 wks . Brief Pain Inventory question 12 , an 11-point numeric rating scale was administered in a blinded manner at baseline , end of treatment , and at 3 , 6 , and 12 mos posttreatment . Treatment success was defined as a minimum 2-point reduction in Brief Pain Inventory question 12 at all posttreatment assessment s. Secondary measures included pain-related quality of life ( Brief Pain Inventory question 23 ) , subluxation , motor impairment , range of motion , spasticity , and activity limitation . Results : The electrical stimulation group exhibited a significantly higher success rate than controls ( 63 % vs. 21 % , P = 0.001 ) . Repeated-measure analysis of variance revealed significant treatment effects on posttreatment Brief Pain Inventory question 12 ( F = 21.2 , P and Brief Pain Inventory question 23 ( F = 8.3 , P < 0.001 ) . Treatment effects on other secondary measures were not significant . Conclusions : Intramuscular electrical stimulation reduces hemiplegic shoulder pain , and the effect is maintained for ≥12 mos posttreatment", "Background : Pain after amputation is common but difficult to treat . Therefore , the authors examined whether postoperative treatment with gabapentin could reduce postamputation stump and phantom pain . Methods : Forty-six patients scheduled to undergo lower limb amputation were r and omly assigned to receive oral gabapentin or placebo . Treatment was started on the first postoperative day and continued for 30 days . The daily dose of gabapentin or placebo was gradually increased to 2,400 mg/day . The intensity of stump and phantom pain was recorded every day on a numeric rating scale ( 0–10 ) during the 30-day treatment period . Five interviews were performed after 7 , 14 , and 30 days and after 3 and 6 months . Results : Results from 41 patients were included in the data analysis . The risk of phantom pain ( gabapentin vs. placebo ) was 55.0 % versus 52.6 % ( risk difference , 2.4 % ; 95 % confidence interval , −28.9 to 33.7 % ; P = 0.88 ; 30 days ) and 58.8 % versus 50.0 % ( risk difference , 8.8 % ; 95 % confidence interval , −23.3 to 40.9 % ; P = 0.59 ; 6 months ) . The median intensity of phantom pain ( gabapentin vs. placebo ) was 1.5 ( range , 0–9.0 ) versus 1.2 ( range , 0–6.6 ) ( P = 0.60 ; 30 days ) and 1.0 ( range , 0–6.0 ) versus 0.5 ( range , 0–5.0 ) ( P = 0.77 ; 6 months ) . The median intensity of stump pain was 0.85 ( range , 0–8.2 ) versus 1.0 ( range , 0–5.4 ) ( P = 0.68 ; 30 days ) and 0 ( range , 0–8.0 ) versus 0 ( range , 0–5.0 ) ( P = 0.58 ; 6 months ) . Conclusion : Gabapentin administered in the first 30 postoperative days after amputation does not reduce the incidence or intensity of postamputation pain", "OBJECTIVE Although common treatments for osteoarthritis ( OA ) pain , such as nonsteroidal antiinflammatory drugs ( NSAIDs ) , simple analgesics , and weak opioids , provide relief in some cases , they fail to control pain or are poorly tolerated in many cases . Strong opioids have been used to successfully treat several types of noncancer pain but have rarely been tested in controlled studies . Therefore , we tested the effects of transdermal fentanyl ( TDF ) in patients with moderate-to-severe OA pain , in a placebo-controlled study . METHODS The cohort comprised patients with radiologically confirmed OA of the hip or knee ( meeting the American College of Rheumatology criteria ) requiring joint replacement and with moderate-to-severe pain that had been inadequately controlled by weak opioids . The patients were r and omized to receive TDF or placebo for 6 weeks after a 1-week pretreatment run-in phase . During study treatment , previously prescribed NSAIDs and simple analgesics were continued , but weak opioids were discontinued . All patients had access to paracetamol and metoclopramide . Pain was recorded on a visual analog scale ( VAS ) , and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . RESULTS Data were available for 399 patients ( 202 receiving TDF , 197 receiving placebo ) , of whom 199 ( 50 % ) completed the study . TDF provided significantly better pain relief than placebo , as demonstrated by the primary outcome measure ( area under the curve for VAS scores -20 in the TDF group versus -14.6 in the placebo group ; P = 0.007 ) . TDF was also associated with significantly better overall WOMAC scores and pain scores . The most common adverse events were nausea , vomiting , and somnolence , and these occurred more often in the TDF group . CONCLUSION TDF can reduce pain and improve function in patients with knee or hip OA", "OBJECTIVE : To study the effects of a 4 % intrauterine lidocaine infusion on perceived patient pain in first-trimester abortions . METHODS : A r and omized , double-blind , placebo-controlled trial of 80 women receiving either a 5-mL 4 % lidocaine ( n = 40 ) or saline ( n = 40 ) intrauterine infusion and a st and ard paracervical block before first-trimester abortion . Women completed a series of 100-mm visual analog scales ( anchors : 0 = none , 100 mm = worst imaginable ) to measure their perceived pain ( anticipated pain , after speculum insertion , after intrauterine infusion , after cervical dilation , after suction aspiration , and 30 minutes postprocedure ) . Eight women volunteered for serum lidocaine levels after the lidocaine infusion . RESULTS : Groups were similar in respect to age , parity , prior abortion , ethnicity , gestational age , and level of dysmenorrhea . Pain scores demonstrated a significant difference between groups during cervical dilation ( saline 55 mm ± 26 , lidocaine 35 mm ± 30 , P The lidocaine group reported significantly more symptoms ( ie , oral numbness and tingling ) than the saline group ( saline 0/39 , lidocaine 16/38 , 42 % , P highest serum lidocaine level recorded was 4.0 & mgr;g/mL ( lidocaine group ) . There was no difference in overall satisfaction between the 2 groups . CONCLUSION : Compared with paracervical block alone , the addition of a 4 % intrauterine lidocaine infusion result ed in a significant reduction in patient perception of pain during first-trimester abortion . Although subjective symptoms of systemic lidocaine effect were common , no subjects demonstrated serum levels consistent with lidocaine toxicity . However , further studies to determine safety are needed . LEVEL OF EVIDENCE :", "OBJECTIVE The purpose of this study was to compare Monsel 's paste with fulguration with ball electrode for hemostasis after loop electrosurgical excision procedure . STUDY DESIGN One hundred healthy women were assigned r and omly by computer-generated r and om numbers to ball electrode or thickened Monsel 's paste for hemostasis after loop electrosurgical excision procedure . Patients rated pain during hemostasis using a visual analog scale . At 2 weeks , postprocedural vaginal discharge was rated on a Likert scale . Pathology was review ed for dysplasia grade and margin status . Recurrent dysplasia on repeat Papanicolaou tests was noted . RESULTS Six patients ( 2 Monsel 's and 4 fulguration ) required an alternate method of hemostasis . Patient demographics , postprocedural discharge , and recurrent dysplasia were comparable between the 2 groups . Visual analog scale scores and hemostasis time were significantly higher in the fulguration group . Estimated blood loss , although higher in the fulguration group , was not significant between groups . CONCLUSION Monsel 's paste and fulguration with ball electrode appear be equally effective as hemostatic agents after loop electrosurgical excision procedure", "BACKGROUND Postherpetic neuralgia is the most frequent complication of herpes zoster . Treatment of this neuropathic pain syndrome is difficult and often disappointing . We assessed the effectiveness of a single epidural injection of steroids and local anaesthetics for prevention of postherpetic neuralgia in older patients with herpes zoster . METHODS We r and omly assigned 598 patients older than 50 years , with acute herpes zoster ( rash , to receive either st and ard therapy ( oral antivirals and analgesics ) or st and ard therapy with one additional epidural injection of 80 mg methylprednisolone acetate and 10 mg bupivacaine . The primary endpoint was the proportion of patients with zoster-associated pain 1 month after inclusion . Analyses were by intention-to-treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N32866390 . FINDINGS At 1 month , 137 ( 48 % ) patients in the epidural group reported pain compared with 164 ( 58 % ) in the control group ( relative risk [ RR ] 0.83 , 95 % CI 0.71 - 0.97 , p=0.02 ) . After 3 months these values were 58 ( 21 % ) and 63 ( 24 % ) respectively ( 0.89 , 0.65 - 1.21 , p=0.47 ) and , at 6 months , 39 ( 15 % ) and 44 ( 17 % ; 0.85 , 0.57 - 1.13 , p=0.43 ) . We detected no subgroups in which the relative risk for pain 1 month after inclusion substantially differed from the overall estimate . No patient had major adverse events related to epidural injection . INTERPRETATION A single epidural injection of steroids and local anaesthetics in the acute phase of herpes zoster has a modest effect in reducing zoster-associated pain for 1 month . This treatment is not effective for prevention of long-term postherpetic neuralgia", "OBJECTIVE : To estimate whether botulinum toxin type A is more effective than placebo at reducing pain and pelvic floor pressure in women with chronic pelvic pain and pelvic floor muscle spasm . METHODS : This study was a double-blinded , r and omized , placebo-controlled trial . All participants presented with chronic pelvic pain of more than 2 years duration and evidence of pelvic floor muscle spasm . Thirty women had 80 units of botulinum toxin type A injected into the pelvic floor muscles , and 30 women received saline . Dysmenorrhea , dyspareunia , dyschezia , and nonmenstrual pelvic pain were assessed by visual analog scale ( VAS ) at baseline and then monthly for 6 months . Pelvic floor pressures were measured by vaginal manometry . RESULTS : There was significant change from baseline in the botulinum toxin type A group for dyspareunia ( VAS score 66 versus 12 ; χ2=25.78 , P and nonmenstrual pelvic pain ( VAS score 51 versus 22 ; χ2=16.98 , P=.009 ) . In the placebo group only dyspareunia was significantly reduced from baseline ( 64 versus 27 ; χ2=2.98 , P=.043 ) . There was a significant reduction in pelvic floor pressure ( centimeters of H2O ) in the botulinum toxin type A group from baseline ( 49 versus 32 ; χ2=39.53 , P the placebo group also having lower pelvic floor muscle pressures ( 44 versus 39 ; χ2=19.85 , P=.003 ) . CONCLUSION : Objective reduction of pelvic floor spasm reduces some types of pelvic pain . Botulinum toxin type A reduces pressure in the pelvic floor muscles more than placebo . Botulinum toxin type A may be a useful agent in women with pelvic floor muscle spasm and chronic pelvic pain who do not respond to conservative physical therapy . Clinical Trial Registration : Australian Clinical Trials Registry , http://www.actr.org.au/ , ACTRN012605000515695 LEVEL OF EVIDENCE :", "Background : Meta-analyses report similar numbers needed to treat for nonsteroidal antiinflammatory drugs ( NSAIDs ) and opioids . Differences in baseline pain intensity among the studies from which these numbers needed to treat were derived may have confounded the results . NSAIDs have an opioid-sparing effect , but the importance of this effect is unclear . Therefore , the authors sought to compare the proportions of subjects who obtain pain relief with ketorolac versus morphine after surgery and to determine whether the opioid-sparing effect of an NSAID reduces the magnitude of opioid side effects . Methods : The study was a double-blind , r and omized controlled trial . The authors r and omly assigned 1,003 adult patients to receive 30 mg ketorolac or 0.1 mg/kg morphine intravenously . They calculated the proportion of subjects who achieved at least 50 % reduction in pain intensity 30 min after analgesic administration . Further , so long as pain intensity 30 min after analgesic administration was 5 or more out of 10 , patients received 2.5 mg morphine every 10 min until pain intensity was 4 or less out of 10 . The authors assessed the presence of opioid-related side effects . Results : Five hundred patients received morphine and 503 received ketorolac . Fifty percent of patients in the morphine group achieved pain relief , compared with 31 % in the ketorolac group ( difference , 19 % ; 95 % confidence interval , 13–25 % ) . The ketorolac – morphine group required less morphine ( difference , 6.5 mg ; 95 % confidence interval , −5.8 to −7.2 ) and had a lower incidence of side effects ( difference , 11 % ; 95 % confidence interval , 5–16 % ) than the morphine group . Conclusions : Opioids are more efficacious analgesics than NSAIDs , although historic data for these two drugs yield similar numbers needed to treat . Adding NSAIDs to the opioid treatment reduces morphine requirements and opioid-related side effects in the early postoperative period", "THE R AND OMIZED controlled trial ( RCT ) , more than any other methodology , can have a powerful and immediate impact on patient care . Ideally , the report of such an evaluation needs to convey to the reader relevant information concerning the design , conduct , analysis , and generalizability of the trial . This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial . Accurate and complete reporting also benefits editors and review ers in their deliberations regarding su bmi tted manuscripts . For RCTs to ultimately benefit patients , the published report should be of the highest possible st and ard", "OBJECTIVE To compare the clinical effectiveness of aerobic exercise in the water with walking/jogging for women with fibromyalgia ( FM ) . METHODS Sixty sedentary women with FM , ages 18 - 60 years , were r and omly assigned to either deep water running ( DWR ) or l and -based exercises ( LBE ) . Patients were trained for 15 weeks at their anaerobic threshold . Visual analog scale of pain , Fibromyalgia Impact Question naire ( FIQ ) , Beck Depression Inventory , Short Form 36 Health Survey ( SF-36 ) , and a patient 's global assessment of response to therapy ( PGART ) were measured at baseline , week 8 , and week 15 . Statistical analysis included all patients . RESULTS Four patients dropped out from each group . Both groups improved significantly at week 15 compared with baseline , with an average 36 % reduction in pain intensity . For PGART , 40 % of the DWR group and 30 % of the LBE group answered \" much better \" at posttreatment . FIQ total score and FIQ depression improvements in the DWR group were faster ( week 8) than the LBE group and kept improving ( week 15 ; P improvements in SF-36 role emotional ( P = 0.006 ) . No significant between-group differences were observed for peak oxygen uptake and other outcomes . CONCLUSION DWR is a safe exercise that has been shown to be as effective as LBE regarding pain . However , it has been shown to bring more advantages related to emotional aspects . Aerobic gain was similar for both groups , regardless of symptom improvement . Therefore , DWR could be studied as an exercise option for patients with FM who have problems adapting to LBE or lower limbs limitations", "OBJECTIVE To determine the most appropriate means to assess the response to treatment in terms of pain and functional impairment in a chronic rheumatic condition ( knee osteoarthritis [ OA ] ) and an acute rheumatic condition ( rotator cuff syndrome [ RCS ] ) . METHODS Two prospect i ve studies were conducted consisting of 1,019 out patients with knee OA and 271 patients with acute RCS . The minimal clinical ly important improvement and the patient acceptable symptom state were determined for knee OA pain using a visual analog scale , and for knee OA function using the Western Ontario and McMaster Universities Osteoarthritis Index function subscale ; for acute RCS pain , a numeral rating scale was used , and the Neer function subscale was used for RCS function . RESULTS The minimal clinical ly important improvement was shown to be the change required to achieve the patient acceptable symptom state , whatever the baseline level of symptom , the outcome ( pain or function ) , or type of condition ( chronic or acute ) . This acceptable state for pain was higher for chronic ( 27.0 - 36.4 across the baseline score ) than acute ( 16.7 - 24.1 ) conditions . The level of functional impairment considered satisfactory by patients with knee OA was higher for more disabled patients ( 43.1 ) than for less disabled patients ( 20.4 ) . CONCLUSION Patients consider that they experienced an important improvement only if this improvement allowed them to achieve a state they consider satisfactory . The most appropriate means to assess the response to therapy seems to be to assess whether patients feel good ( i.e. , achieve the patient acceptable symptom state )", "PURPOSE Prostate biopsy for diagnosing cancer can be painful . Tramadol is a central ly acting analgesic used to treat many pain disorders . We determined whether administering oral tramadol and acetaminophen combined with 1 % lidocaine induced periprostatic nerve block would significantly decrease the pain experienced by patients during st and ard 10-core transrectal ultrasound guided needle biopsy of the prostate . MATERIAL S AND METHODS A total of 60 men who presented for diagnostic prostate biopsy were r and omized to receive placebo plus periprostatic 1 % lidocaine as the control group of 30 or 75 mg tramadol/650 mg acetaminophen orally plus periprostatic 1 % lidocaine as the experimental group of 30 before undergoing biopsy . Immediately after biopsy each patient was asked to rate the pain on a linear 10-point scale and a st and ard 6-point faces pain scale . Complications of pain medication administration in each group were noted and compared . RESULTS Pain medication administration was well tolerated by each study group except for lightheadedness/dizziness and itching in 1 patient each in the experimental group , and lightheadedness/dizziness in 1 patient in the control group . Overall patients in the experimental group reported a mean decrease + /- SD in the pain score of 2.3 + /- 2.4 on the scale of 1 to 10 ( p = 0.0008 ) and 1.11 + /- 1.25 on the scale of 0 to 5 compared with scores in controls ( p = 0.0009 ) . CONCLUSIONS Administering 75 mg tramadol/650 mg acetaminophen orally with periprostatic 1 % lidocaine before transrectal ultrasound guided prostate biopsy is a safe , easy and effective method of controlling pain during the biopsy procedure", "BACKGROUND In clinical trials , at the group level , results are usually reported as mean and st and ard deviation of the change in score , which is not meaningful for most readers . OBJECTIVE To determine the minimal clinical ly important improvement ( MCII ) of pain , patient 's global assessment of disease activity , and functional impairment in patients with knee and hip osteoarthritis ( OA ) . METHODS A prospect i ve multicentre 4 week cohort study involving 1362 out patients with knee or hip OA was carried out . Data on assessment of pain and patient 's global assessment , measured on visual analogue scales , and functional impairment , measured on the Western Ontario McMaster Universities Osteoarthritis Index ( WOMAC ) function subscale , were collected at baseline and final visits . Patients assessed their response to treatment on a five point Likert scale at the final visit . An anchoring method based on the patient 's opinion was used . The MCII was estimated in a subgroup of 814 patients ( 603 with knee OA , 211 with hip OA ) . RESULTS For knee and hip OA , MCII for absolute ( and relative ) changes were , respectively , ( a ) -19.9 mm ( -40.8 % ) and -15.3 mm ( -32.0 % ) for pain ; ( b ) -18.3 mm ( -39.0 % ) and -15.2 mm ( -32.6 % ) for patient 's global assessment ; ( c ) -9.1 ( -26.0 % ) and -7.9 ( -21.1 % ) for WOMAC function subscale score . The MCII is affected by the initial degree of severity of the symptoms but not by age , disease duration , or sex . CONCLUSION Using criteria such as MCII in clinical trials would provide meaningful information which would help in interpreting the results by expressing them as a proportion of improved patients", "BACKGROUND : Spinal fusion surgery causes severe postoperative pain , hampering reconvalescense . We investigated the efficacy of patient-controlled epidural analgesia ( PCEA ) in a prospect i ve , double-blind , r and omized , controlled comparison with patient-controlled IV analgesia ( PCIA ) . METHODS : After lumbar anterior-posterior fusion receiving an epidural catheter intraoperatively , 72 patients were given either PCEA ( ropivacaine 0.125 % and sufentanil 1.0 & mgr;g/mL at 14 mL/h ; bolus : 5 mL ; lockout time : 15 min ) and IV placebo or PCIA ( morphine 2.0 mg/mL ; bolus : 3 mg ; lockout time : 15 min ) and epidural placebo . Pain levels ( visual analog scale 0 - 10 ) , functional capabilities ( turning in bed , st and ing , and walking ) , analgesic consumption , and side effects were evaluated until 72 h after surgery . RESULTS : Fourteen patients were excluded by predetermined criteria , leaving 58 patients for data analysis . Pain levels at rest and during mobilization were significantly lower in the PCEA when compared with that in the PCIA group throughout the study period ( P Time until able to turn in bed was achieved earlier in the PCEA group ( P PCEA group were significantly more satisfied with pain therapy ( P PCEA with ropivacaine and sufentanil , using intraoperatively placed epidural catheters , provides superior analgesia and higher patient satisfaction when compared with PCIA after spinal fusion surgery", " This r and omized , double-blind , placebo-controlled crossover study measured the effect of a single dose of oral gabapentin ( 900 mg ) on pain and allodynia associated with herpes zoster . Pain severity decreased by 66 % with gabapentin compared to 33 % with placebo . Reductions in allodynia area and severity , and overall pain relief , were also greater with gabapentin", "Objective : To study the effectiveness of intrauterine anesthesia for pain relief during fractional curettage . Methods : A double-blinded , r and omized , placebo-controlled trial was conducted in 66 patients with abnormal uterine bleeding undergoing fractional curettage under paracervical block , using 10-mL 1 % lidocaine plus intrauterine 5-mL 2 % lidocaine ( n = 33 ) or saline ( n = 33 ) . The primary outcome was the maximum pain score measured with a 10-cm visual analog scale . Other outcomes measured included pain profile , number of patients with pain score more than 4 , each patient 's global satisfaction index , adverse events , and serum lidocaine profile . Results : The 2 groups were comparable in age , body mass index , education , socioeconomic status , menopausal status , and parity . Compared with the saline group , the lidocaine group had a significantly lower median value for the maximum pain score ( 2.3 versus 4.7 , P = .022 ) and fewer patients with a pain score more than 4 ( 33.3 % versus 60.6 % , P = .026 ) . The pain scores were lower at the endocervical curettage and the uterine curettage steps . There was no difference between the 2 groups in other outcomes . The number needed to treat to prevent a case with a pain score more than 4 was 3.7 ( 95 % confidence interval 2.4–38.5 ) . Conclusion : The addition of intrauterine anesthesia to paracervical block can further reduce pain during fractional curettage without increasing adverse effects . Level of Evidence :", "Abstract Heat induced pain has been shown to follow a positively accelerating power function for groups of subjects , yet the extent to which this applies to individual subjects is unknown . Statistical methods were developed for assessing the goodness of fit and reliability of the power function for data from individual subjects with the aim of using such functions for characterizing individual differences in heat‐pain sensitivity . 175 subjects rated ascending and r and om series of contact heat stimuli with visual analogue scales for pain intensity ( VAS‐I ) and unpleasantness ( VAS‐A ) . Curve fitting showed excellent model fit . Substitution of model estimates in place of observed VAS scores produced minimal bias in group means , about 0.3 VAS units in the ascending series and 1.0 in the r and om series , on a 0–100 scale . Individual power function exponents were considerably higher for the ascending than for the r and om series and somewhat higher for VAS‐A than for VAS‐I ( means : ascending VAS‐I=9.04 , VAS‐A=9.80 ; r and om VAS‐I=4.95 , VAS‐A=5.67 ) . The reliability of VAS estimates was high ( ≧.93 ) , and for the ascending series it remained so when extrapolating 4 ° C beyond the empirical range . Exponent reliability was high for the ascending series ( VAS‐I=.92 ; VAS‐A=.91 ) , but considerably lower for the r and om series ( VAS‐I=.69 ; VAS‐A=.71 ) . Individual differences constituted 60 % of the total variance in pain ratings , whereas stimulus temperature accounted for only 40 % . This finding underscores the importance of taking individual differences into account when performing pain studies", "STUDY OBJECTIVE We compare a st and ard weight-based dose of intravenous hydromorphone ( Dilaudid ) to a st and ard weight-based dose of intravenous morphine in adults presenting to the ED with acute severe pain . METHODS This was a prospect i ve , r and omized , double-blind , clinical trial conducted in an academic medical center . Of the 198 adult patients presenting to the ED with acute severe pain who were r and omized to receive either intravenous hydromorphone at 0.015 mg/kg or intravenous morphine at 0.1 mg/kg , 191 patients had sufficient data for analysis . The main outcome measure was the difference between the 2 groups in pain reduction at 30 minutes as measured on a vali date d numeric rating scale . Adverse effects , pain reduction at 5 minutes and 2 hours postbaseline , and additional analgesics and antiemetics were tracked as secondary outcome measures . RESULTS The mean change of pain from baseline to 30 minutes postbaseline in patients allocated to intravenous hydromorphone was -5.5 numeric rating scale units versus -4.1 in patients allocated to intravenous morphine ( difference -1.3 ; 95 % confidence interval -2.2 to -0.5 ) . Adverse effects were similar in both groups , with the exception of pruritus , which did not occur in patients receiving hydromorphone ( 0 % versus 6 % [ difference -6 % ; 95 % confidence interval -11 % to -1 % ] ) . No patient required naloxone . CONCLUSION For the treatment of acute , severe pain in the emergency department , intravenous hydromorphone at 0.015 mg/kg represents a feasible alternative to intravenous morphine at 0.1 mg/kg" ]

[ "The aim of this study of the present experiment was to study the marginal periimplant tissues at intentionally non-submerged ( 1-stage implants ) and initially submerged and subsequently exposed implants ( 2-stage implants ) . 5 beagle dogs , about 1-year-old , were used , 3 months after the extraction of the m and ibular premolars , fixtures of the Astra Tech Implants Dental System , the Brånemark System and the Bonefit -- ITI system were installed . In each m and ibular quadrant , 1 fixture of each implant system was installed in a r and omised order . The installation procedure followed the recommendations given in the manuals for each system . Thus , following installation , the bone crest coincided with the fixture margin of the Astra Tech Implants Dental System and the Brånemark System , whereas the border between the plasma sprayed and the machined surface of the Bonefit-ITI implant system was positioned at the level of the bone crest . Following a healing period of 3 months , abutment connection was carried out in the 2-stage systems ( the Astra Tech Implants Dental System and the Brånemark system ) . A 6-month period of plaque control was initiated . The animals were sacrificed and biopsies representing each important region dissected . The tissue sample s were prepared for light microscopy and exposed to histometric and morphometric measurements . The mucosal barrier which formed to the titanium surface following 1-stage and 2-stage implant installations comprised an epithelial and a connective tissue component , which for that 3 systems studied , had similar dimensions and composition . The amount of lamellar bone contained in the periimplant region close to the fixture part of the 3-implant systems was almost identical . It is suggested that correctly performed implant installation may ensure proper conditions for both and hard tissue healing , and that the geometry of the titanium implant seems to be of limited importance", "This paper describes the 5-year results of a comparative study between Astra Tech and Brånemark system implants . The aim was to compare the systems primarily with regard to bone level changes , and also with regard to other variables of interest . Sixty-six patients with edentulous jaws were included in the study . R and omisation schedules were used to allocate the patients to the two implant systems . 184 Astra Tech implants with a titanium-blasted surface and 187 Brånemark implants with a turned surface were used . The implants were inserted with a two-stage technique and the insertion followed the routines for the respective implant system . All patients were provided with full-arch fixed bridges . All patients were followed up with clinical and radiographic examinations from fixture insertion to the 5-year follow-up . The total mean bone level change in the upper jaw between fixture insertion and the 5-year examination was -1.74+/-0.45 mm at the Astra implants and -1.98+/-0.21 at the Brånemark implants . The corresponding values for the lower jaw were -1.06+/-0.19 for Astra and -1.38+/-0.17 for Brånemark . The major postoperative changes of the marginal bone level took place between fixture insertion and baseline . During this period , there was also a different pattern of bone remodelling between the implant systems . Between baseline ( prosthesis connection ) and the 5-year examination , the marginal bone level changes were small , with no difference between the implant systems . The implant stability was examined with the supraconstructions removed . At the 5-year examination , the survival rate for Astra Tech implants was 98.4 % and for the Brånemark implants it was 94.6 % . The difference was not statistically significant", "Previous papers in this series on evidence -based dentistry have discussed the first 2 steps in seeking answers to clinical problems formulating a clear question and strategically search ing for evidence . The next step , critical appraisal of the evidence , is made easier if one underst and s the basic concepts of clinical research design . The strongest design , especially for questions related to therapeutic or preventive interventions , is the r and omized , controlled trial . Questions relating to diagnosis , prognosis and causation are often studied with observational , rather than experimental , research design s. The strongest study design should be used whenever possible . Rules have been established to grade research evidence . This paper , the fourth in the series , presents an overview of research methodology most commonly used in the dental literature", "The purpose of the investigation was to gain more underst and ing of marginal inflammatory reactions around osseointegrated implants . The significance of the lacking periodontal ligament of implants was examined in the initial breakdown phase of supporting tissues by comparing clinical and radiographic manifestations of ligature-induced marginal inflammation related to osseointegrated implants with those around ankylosed and normal control teeth in 8 cynomolgus monkeys ( Macaca fascicularis ) . Bilateral extraction of the first and second m and ibular molars was carried out initially , and 12 weeks later 2 implants were placed in each side . Ankylosis of the second maxillary molars was established by extracting and replanting the teeth after a drying period . When ankylosis and osseointegration were established , ligature-induced marginal inflammation was induced in the right or left side at r and om around implants , ankylosed teeth and normal control teeth ( second maxillary premolar ) for 7 weeks . Although the clinical manifestations as expressed by plaque score , gingival score , probing depth and attachment loss were quite similar , the radiographic features differed . Significant loss of bone height was limited to implants and ankylosed teeth and did not occur in relation to normal control teeth . Furthermore , the bone loss around implants was significantly greater than the loss around ankylosed teeth . Bone loss was limited to implants and ankylosed teeth ; the study therefore suggests that the presence of marginal inflammation around implants and ankylosed teeth may have more serious implication s than does marginal inflammation around teeth with a periodontal ligament . However , variations in microbiota and susceptibility of different jaw positions to periodontal breakdown may influence the results of this study", "The aim of the present experiment was to study the location and composition of plaque associated lesions in the mucosa adjacent to implant systems that differed with respect to both geometry and dimension . At day 0 extraction of the m and ibular premolars were performed . After a healing period of 3 months , fixtures of the Astra Tech Implants , Dental System , the Brånemark System and the ITI Dental Implant System were installed . In each m and ibular quadrant 1 fixture of each implant system was installed in a r and omized order . A period of plaque control was initiated . Following another 3 months of healing , abutment connection was performed in the 2-stage systems ( the Astra Tech Implants , Dental System and the Brånemark System ) . After 1 month , the plaque control measures were ab and oned and plaque formation was allowed for 5 months . The animals were killed and biopsies representing each implant region obtained . The tissue sample s were prepared for light microscopy and exposed to histometric and morphometric measurements . The present study demonstrated that plaque formation result ed in the establishment of an ICT lateral to a pocket epithelium . The lesion was found to be similar regarding extension and composition in the peri-implant mucosa of the 3 implant systems tested . The vertical extension of the ICT was in all systems within 91 - 99 % of the vertical dimension of the junctional epithelium . The marginal bone level , measured from the abutment/fixture ( PS ) border , did not differ between the three systems", "This investigation is the result of a multicenter research project between the Catholic University of Leuven and the University of Madrid with the purpose of study ing histometrically and ultrastructurally periimplant marginal tissue reactions in mendium-term Brånemark implants . 12 patients were selected and distributed according to predefined clinical and radiological parameters into a periimplant infection group ( A ) and a non-periimplant infection group ( B ) . Biopsies were taken from these patients and analyzed by means of microscopy ( LM ) , histometry ( HM ) and transmission electron microscopy ( TEM ) . With LM group A showed pathological features consistent with an advanced gingivitis lesion , while group B showed signs of healthy gingiva in the connective tissue and vauolae formation in the epithelium . With HM , group A showed significantly higher transmigration of inflammatory cells in the epithelium than group B. In the connective tissue , group A showed a higher % of inflammatory infiltrate with significantly higher numbers of plasma cells and mononuclear cells than group B. With TEM , group A showed an ultrastructural picture consistent with plaque-induced periodontitis , while group B showed a rather healthy connective tissue and vacuolae formation in the epithelium . These results suggest that supracrestal marginal tissues around osseointegrated implants react to plaque bacteria similarly to periodontal tissues around teeth by chronic inflammation", "BACKGROUND Progressive peri-implant bone losses , which are accompanied by inflammatory lesions in the soft tissues , are referred to as peri-implantitis . The aim of this study was to compare the effects of photodynamic therapy ( PDT ) and conventional technique on microbial reduction in ligature-induced peri-implantitis in dogs . METHODS Eighteen third premolars from nine Labrador retriever dogs were extracted and the implants were submerged . After osseointegration , peri-implantitis was induced . After 4 months , ligature was removed and natural bacterial plaque was allowed to form for another 4 months . The animals were then r and omly divided into two groups . In the conventional group , they were treated using mucoperiosteal flaps for scaling the implant surface and chlorexidine ( conventional ) irrigation . In the PDT group , only mucoperiosteal scaling was carried out before photodynamic therapy . Inside the peri-implant pocket , a paste-based azulene photosensitizer was placed and then a GaAlAs low-power laser ( lambda=660 nm , P=40 mW , E=7.2 J for 3 minutes ) was used . Microbiological sample s were obtained before and immediately after treatment . Before treatment , one implant was removed and analyzed by scanning electron microscopy to vali date the contamination . RESULTS The results of this study showed that Prevotella sp. , Fusobacterium sp. , and S. Beta-haemolyticus were significantly reduced for both groups . After treatment , no significant differences were observed between the groups . CONCLUSION These findings suggest that photodynamic therapy is a non-invasive method that could be used to reduce microorganisms in peri-implantitis", " After 3 years , 82 of the original 92 patients remain in this prospect i ve multicenter study of single-tooth restorations supported by Brånemark implants . Since the 1-year follow-up , 6 more patients have been lost , but no additional implants have failed in those patients examined at the 3-year follow-up visit . After 1 year of function , 97.2 % of the implants survived in 88 patients , and between the 1- and 3-year follow-up , 100 % survived in 82 patients , giving a 3-year cumulative success rate of 97.2 % . No changes were observed in the status of gingivitis , pocket depth , periodontal pocket bleeding index , and tooth and implant mobility from those reported after 1 year . Marginal bone resorption remained at a low level -- less than 0.1 mm annually during the second and third years . Abutment screw loosening continued , but at a significantly reduced rate from that reported after 1 year . When used , gold rather than titanium abutment screws remained secure", "BACKGROUND Today , implants are placed using both non-submerged and submerged approaches , and in 1- and 2-piece configurations . Previous work has demonstrated that peri-implant crestal bone reactions differ radiographically under such conditions and are dependent on a rough/smooth implant border in 1-piece implants and on the location of the interface ( microgap ) between the implant and abutment/restoration in 2-piece configurations . The purpose of this investigation was to examine histometrically crestal bone changes around unloaded non-submerged and submerged 1- and 2-piece titanium implants in a side-by-side comparison . METHODS A total of 59 titanium implants were r and omly placed in edentulous m and ibular areas of 5 foxhounds , forming 6 different implant subgroups ( types A-F ) . In general , all implants had a relatively smooth , machined coronal portion as well as a rough , s and blasted and acid-etched ( SLA ) apical portion . Implant types A-C were placed in a non-submerged approach , while types D-F were inserted in a submerged fashion . Type A and B implants were 1-piece implants with the rough/smooth border ( r/s ) at the alveolar crest ( type A ) or 1.0 mm below ( type B ) . Type C implants had an abutment placed at the time of surgery with the interface located at the bone crest level . In the submerged group , types D-F , the interface was located either at the bone crest level ( type D ) , 1 mm above ( type E ) , or 1 mm below ( type F ) . Three months after implant placement , abutment connection was performed in the submerged implant groups . At 6 months , all animals were sacrificed . Non-decalcified histology was analyzed by evaluating peri-implant crestal bone levels . RESULTS For types A and B , mean crestal bone levels were located adjacent ( within 0.20 mm ) to the rough/smooth border ( r/s ) . For type C implants , the mean distance ( + /- st and ard deviation ) between the interface and the crestal bone level was 1.68 mm ( + /- 0.19 mm ) with an r/s border to first bone-to-implant contact ( fBIC ) of 0.39 mm ( + /- 0.23 mm ) ; for type D , 1.57 mm ( + /- 0.22 mm ) with an r/s border to fBIC of 0.28 mm ( + /- 0.21 mm ) ; for type E , 2.64 mm ( + /- 0.24 mm ) with an r/s border to fBIC of 0.06 mm ( + /- 0.27 mm ) ; and for type F , 1.25 mm ( + /- 0.40 mm ) with an r/s border to fBIC of 0.89 mm ( + /- 0.41 mm ) . CONCLUSIONS The location of a rough/smooth border on the surface of non-submerged 1-piece implants placed at the bone crest level or 1 mm below , respectively , determines the level of the fBIC . In all 2-piece implants , however , the location of the interface ( microgap ) , when located at or below the alveolar crest , determines the amount of crestal bone resorption . If the same interface is located 1 mm coronal to the alveolar crest , the fBIC is located at the r/s border . These findings , as evaluated by non-decalcified histology under unloaded conditions , demonstrate that crestal bone changes occur during the early phase of healing after implant placement . Furthermore , these changes are dependent on the surface characteristics of the implant and the presence/absence as well as the location of an interface ( microgap ) . Crestal bone changes were not dependent on the surgical technique ( submerged or non-submerged )", "BACKGROUND Endosseous implants can be placed according to a non-submerged or submerged approach and in 1- or 2-piece configurations . Recently , it was shown that peri-implant crestal bone changes differ significantly under such conditions and are dependent on a rough/smooth implant border in 1-piece implants and on the location of an interface ( microgap ) between the implant and abutment/restoration in 2-piece configurations . Several factors may influence the result ant level of the crestal bone under these conditions , including movements between implant components and the size of the microgap ( interface ) between the implant and abutment . However , no data are available on the impact of possible movements between these components or the impact of the size of the microgap ( interface ) . The purpose of this study was to histometrically evaluate crestal bone changes around unloaded , 2-piece non-submerged titanium implants with 3 different microgap ( interface ) dimensions and between implants with components welded together or held together by a transocclusal screw . METHODS A total of 60 titanium implants were r and omly placed in edentulous m and ibular areas of 5 hounds forming 6 different implant subgroups ( A through F ) . In general , all implants had a relatively smooth , machined suprabony portion 1 mm long , as well as a rough , s and blasted , and acid-etched ( SLA ) endosseous portion , all placed with their interface ( microgap ) 1 mm above the bone crest level and having abutments connected at the time of first-stage surgery . Implant types A , B , and C had a microgap of animals were sacrificed . Non-decalcified histology was analyzed histometrically by evaluating peri-implant crestal bone changes . RESULTS For implants in the laser-welded group ( A , B , and C ) , mean crestal bone levels were located at a distance from the interface ( IF ; microgap ) to the first bone-to-implant contact ( fBIC ) of 1.06 + /- 0.46 mm ( st and ard deviation ) for type A , 1.28 + /- 0.47 mm for type B , and 1.17 + /- 0.51 mm for type C. All implants of the non-welded group ( D , E , and F ) had significantly increased amounts of crestal bone loss , with 1.72 + /- 0.49 mm for type D ( P canine m and ible , that crestal bone changes around 2-piece , non-submerged titanium implants are significantly influenced by possible movements between implants and abutments , but not by the size of the microgap ( interface ) . Thus , significant crestal bone loss occurs in 2-piece implant configurations even with the smallest-sized microgaps ( < 10 microns ) in combination with possible movements between implant components", "The reader of oral and maxillofacial implant literature is challenged to be cognizant of the quality of clinical research data . The large variety of possible study design s utilized by clinical research ers requires the reader to have a fundamental awareness of the advantages , disadvantages , and limitations of commonly utilized study design s. This article aims to provide the reader with information to make an informed decision regarding the quality of a clinical research paper , so that he or she can judge whether the information presented in any given manuscript was obtained in a manner that truly minimizes bias , in the form of systematic or r and om errors , and whether it warrants serious consideration for clinical decision making . Special consideration is given to scientific literature pertaining to the use of oral and maxillofacial implants . In addition , the reader is presented with a method for placing any single manuscript within a \" hierarchy of evidence \" enabling an \" estimate of confidence \" in a particular therapy . By utilizing such methods to appraise the quality of research data , clinicians and patients will be better informed when making treatment-planning decisions", "The successful maintenance of crestal bone surrounding dental implants is imperative for long-term implant success . Crestal bone loss is reportedly related to stress . However , early perforation and partial exposure of the implant ’s covering device are a focus for plaque accumulation , which , if left untreated , may result in inflammation . The objective of this study was to evaluate the crestal bone levels adjacent to submerged and exposed unloaded dental implants during the initial healing phase . In addition , the microbiota around exposed implants were studied . Bilateral implants were placed in the m and ible of 10 patients . In one quadrant , the implants were covered by the flap . In the other quadrant , the flap was sutured , leaving the cover screws completely exposed . St and ardized periapical radiographs were obtained at implant placement and 4 months later . Radiographs were digitalized , aligned , and analyzed with a computer-assisted method . Cultures were obtained from exposed implant sites . All patients showed more crestal bone loss around exposed dental implants compared to submerged implants . Prevotella sp. , Streptococcus beta-hemoliticus , and Fusobacterium sp. were the microorganisms identified in most of the sites . The exposure of the implant covering device created foci for bacterial plaque accumulation , which may have facilitated periimplant crestal bone loss . The initial healing phase follow-up may be critical for implant success", "This interim report presents the data from a prospect i ve study of BioHorizons , a bone quality -based implant system , with four implant design s. The surgical survival of 975 implants was 99.4 % , with the survival 100 % for D4 bone . Three critical phases of crestal bone loss have been identified : bone remodeling from stage I to stage II surgery ; stage II uncovery to prosthesis delivery ( transition period ) ; and prosthesis delivery up to the first year of loading ( early loading bone loss ) . The stage I to stage II uncovery crestal bone remodeling result ed in a mean vertical bone loss of 0.21 mm to 0.36 mm ( SD = 0.90 mm ) , dependent on whether the implant became exposed in the oral cavity during osseous healing . No statistically significant difference was found among the four implant design s , diameter , bone density , or location . The stage II to prosthesis delivery mean vertical bone loss ranged from 0.12 mm to 0.20 mm . One hundred three consecutive patients ( partially and totally edentulous ) were restored , with 360 implants and 105 prostheses in function for a period of 12 to 26 months . No early loading implant failure occurred , and all patients with implants are in satisfactory to optimum health according to the Misch Implant Quality Scale . The mean early loading bone loss was 0.29 mm ( SD = 0.99 mm ) . Past clinical reports in the literature indicate most failures or crestal bone loss occur by the first year of loading . This study suggests the bone quality based dental implant design minimizes overall implant failure and crestal bone loss , regardless of bone density", "PURPOSE The aim of the present study was to evaluate the periimplant conditions and the maintenance requirements for implant-supported overdentures in the m and ible retained with ball or bar attachments during a 5-year period . MATERIAL S AND METHODS Twenty-six completely edentulous patients had two Astra Tech dental implants placed in the anterior part of the m and ible . The denture attachment system for the patients was chosen r and omly by drawing lots . Eleven patients drew the bar attachment system and fifteen patients drew the ball attachment system . Plaque Index , Gingival Index , and probing pocket depth were assessed around each implant . Periotest values were recorded , and periodically identical intraoral radiographs were obtained with a specially design ed film-holding device . RESULTS No implants were lost from baseline to the 5-year registration . The periimplant conditions were very healthy after 5 years . No significant differences of the periimplant variables were recorded between the bar and the ball groups . During the first year of function , significantly more complications/repairs were registered in the bar group than in the ball group . In the following years , no significant differences were registered . The mean frequency of complications/repairs per patient per year was 1.0 in the bar group and 0.6 in the ball group during the 5-year observation period . CONCLUSION Two implants with ball or bar attachment supported an overdenture in the m and ible for 5 years with a 100 % survival rate . No differences in marginal bone loss or health of the periimplant mucosa were observed between bar and ball attachment , but the frequency of technical complications/repairs per patient was higher around bar than ball attachments", "BACKGROUND Following connection to the oral cavity , osseointegrated dental implants and surrounding tissues are exposed to microbiologic and biomechanical challenges . The establishment of a firm functional periimplant soft tissue barrier ( PSTB ) is considered to be important to protect the implant 's interface from invasion of bacteria . The current knowledge on the histologic architecture of the PSTB is mainly based on animal experiments . PURPOSE The aim of this study was to histologically characterize the PSTB formed in humans around experimental one-piece mini-implants with different surface topography . MATERIAL S AND METHODS Five patients received a total of 12 experimental titanium , one-piece mini-implants with an oxidized ( n = 4 ) , an acid-etched ( n = 4 ) , or a machined ( n = 4 ) surface distal to therapeutic implants . Following transmucosal healing of 8 weeks and at abutment connection of the regular implants , the mini-implants were harvested with a layer of surrounding hard and soft tissue . The specimens were fixed and processed for histologic sectioning according to st and ard procedures . The most central bucco-oral section cut in the long axis was used for morphologic analyses of the PSTB . The vertical soft tissue morphology was quantified using histometric measurements . RESULTS The overall height of the soft tissue , that is , the biologic width , was around 4 to 4.5 mm and consisted of an epithelial and a supracrestal connective tissue barrier . The junctional epithelium established the attachment to the implant surface , whereas the collagen fibers and fibroblasts of the connective tissue seal were oriented parallel to the implant . The epithelial attachment was shorter at the oxidized and acid-etched surfaces compared with the machined surfaces . Accordingly , the oxidized and acid-etched mini-implants exhibited a longer zone of connective tissue seal . CONCLUSION The periimplant soft tissue formed at the experimental one-piece mini-implants in humans was of a character similar to that described in animal studies . The oxidized and acid-etched implants revealed less epithelial downgrowth and longer connective tissue seal than machined implants", "In order to achieve esthetically more satisfying results , it has been proposed to place ITI implants with their border between the rough and smooth surfaces below the level of the alveolar crest , thereby obtaining a submucosally located implant shoulder following healing . The aim of the present experimental study was to clinical ly and radiographically evaluate the tissue response to the placement of one-stage transmucosal implants with the border between the rough and the smooth surfaces sunk by 1 mm into a subcrestal location . 11 patients underwent comprehensive dental care including the placement of 2 implants of the ITI Dental Implant System in the same quadrant ( test and control ) . R and omly assigned control implants were placed according to the manufacturer 's instructions , i.e. the border between the rough titanium plasma-sprayed and the smooth polished surfaces precisely at the alveolar crest . At the test implant the apical border of the polished surface was placed approximately 1 mm below the alveolar crest . Probing bone levels were assessed at implant placement ( baseline ) , 4 and 12 months later . Modified plaque and modified gingival indices were recorded at 1 , 2 , 3 , 4 and 12 months . Clinical probing depth and \" attachment \" levels were measured at 4 and 12 months . All parameters were assessed at 6 sites around each implant . The mean for each implant was calculated and used for analysis . The Wilcoxon matched pairs signed rank test and the Student t-test were applied to detect differences over time and between the test and control implants . At baseline , a mean difference in probing bone level of -0.86 mm ( SD 0.43 mm , p clinical bone height during the first 4 months ( test 1.16 mm , p significantly lost clinical bone height from 4 - 12 months ( test 1.04 mm , p bone height during the first year of service . On the average , the test implants demonstrated a bone level of 0.38 mm lower than the controls at 12 months . Except for the modified gingival index at 4 months ( mean difference 0.21 , SD 0.19 , p < 0.05 ) , no clinical parameters yielded significant differences between test and control implants at any time . It is concluded that in addition to the crestal bone resorption occurring at implants placed under st and ard conditions , the bone adjacent to the polished surface of more deeply placed ITI implants is also lost over time . From a biological point of view , the placement of the border between the rough and the smooth surfaces into a subcrestal location should not be recommended", "STATEMENT OF THE PROBLEM It is not known if healing abutments replaced subsequently with permanent abutments adversely affect the soft tissues and marginal bone levels around dental implants . PURPOSE This study evaluated the mucosal condition and marginal bone levels 3 years after placement of healing abutments in patients provided with fixed prostheses supported by Brånemark implants . MATERIAL AND METHODS Data were analyzed retrospectively from 117 patients treated at five centers in which 318 healing abutments were placed on maxillary and 112 on m and ibular implants . A prospect i ve 3-year appraisal with a specific protocol assessed the response of mucosal cuffs and marginal bone levels surrounding surviving implants . RESULTS Exchange of abutments did not affect expected survival rates of implants ( 94 % maxilla , 99 % m and ible ) or produce mean levels of marginal bone loss greater than anticipated for the system . Mean marginal bone levels correlated significantly with the jaw . Most patients achieved good oral hygiene and favorable peri-implant soft tissue health . CONCLUSION No evidence was found to suggest abutment exchange adversely affects outcome of implant treatment" ]

[ "There is increased global recognition of attention deficit hyperactivity disorder ( ADHD ) as a serious medical condition with long-term consequences . Although originally conceived of as a childhood disorder , ADHD is being increasingly recognized in adults . Individual geographic regions may have specific interests and objectives for the study of ADHD . A systematic review of long-term outcomes ( LTOs ) in ADHD was conducted to evaluate research on ADHD LTOs on a global scale . Studies that were at least 2 years in duration were examined . A total of 351 studies were identified in the final analysis . We identified nine outcomes of interest and classified studies by specific geographical regions , age groups studied and study design by region and over time . Published studies of LTOs in ADHD have increased in all geographical regions over the past three decades , with a peak number of 42 publications in 2008 . This rise in publications on ADHD LTOs may reflect a rise in global interest and recognition of consequences and impairment associated with ADHD . Although many world regions have published on ADHD LTOs , the majority of studies have emerged from the US and Canada , followed by Europe . While investigators in the US and Canada were predominantly interested in drug addiction as a LTO , European research ers were more interested in antisocial behavior , and Eastern Asian investigators focused on both of these LTOs as well as self-esteem . Geographical differences in the focus of ADHD LTO studies may reflect regional variations in cultural values . Proportionally fewer prospect i ve longitudinal studies and proportionally more retrospective and cross-sectional studies have been published in more recent decades . Finally , more studies focusing on ADHD in adolescents and adults have been conducted in recent years , and particularly adolescents in Eastern Asia . These changes in basic study design may reflect an increase in the recognition that ADHD is a lifetime chronic disorder . This systematic review analysis of publication trends in ADHD LTOs reflects geographically based interests that change over time", "OBJECTIVE In the intent-to-treat analysis of the Multimodal Treatment Study of Children With ADHD ( MTA ) , the effects of medication management ( MedMgt ) , behavior therapy ( Beh ) , their combination ( Comb ) , and usual community care ( CC ) differed at 14 and 24 months due to superiority of treatments that used the MTA medication algorithm ( Comb+MedMgt ) over those that did not ( Beh+CC ) . This report examines 36-month outcomes , 2 years after treatment by the study ended . METHOD For primary outcome measures ( attention-deficit/hyperactivity disorder [ ADHD ] and oppositional defiant disorder [ ODD ] symptoms , social skills , reading scores , impairment , and diagnostic status ) , mixed-effects regression models and orthogonal contrasts examined 36-month outcomes . RESULTS At 3 years , 485 of the original 579 subjects ( 83.8 % ) participated in the follow-up , now at ages 10 to 13 years , ( mean 11.9 years ) . In contrast to the significant advantage of MedMgt+Comb over Beh+CC for ADHD symptoms at 14 and 24 months , treatment groups did not differ significantly on any measure at 36 months . The percentage of children taking medication > 50 % of the time changed between 14 and 36 months across the initial treatment groups : Beh significantly increased ( 14 % to 45 % ) , MedMed+Comb significantly decreased ( 91 % to 71 % ) , and CC remained constant ( 60%-62 % ) . Regardless of their treatment use changes , all of the groups showed symptom improvement over baseline . Notably , initial symptom severity , sex ( male ) , comorbidity , public assistance , and parental psychopathology ( ADHD ) did not moderate children 's 36-month treatment responses , but these factors predicted worse outcomes over 36 months , regardless of original treatment assignment . CONCLUSIONS By 36 months , the earlier advantage of having had 14 months of the medication algorithm was no longer apparent , possibly due to age-related decline in ADHD symptoms , changes in medication management intensity , starting or stopping medications altogether , or other factors not yet evaluated", "We report a prospect i ve longitudinal study of 101 male adolescents ( ages 16 to 23 years ) who had been diagnosed hyperactive in childhood ( ages 6 to 12 years ) , compared with 100 normal controls . The DSM-III diagnoses were made blind to group membership . Information was obtained for 98 % of the original cohort . The full attention deficit disorder with hyperactivity ( ADDH ) syndrome persisted in 31 % of the prob and s vs in 3 % of the controls . The only other two conditions that distinguished the groups significantly were conduct and substance use disorders . These disorders aggregated significantly among the prob and s with continued ADDH . The results indicate that the greatest risk factor for the development of antisocial behavior and drug abuse is the maintenance of ADDH symptoms . Substance use disorders followed the onset of conduct disorder in the overwhelming majority of the cases", "Treatment with psychostimulant medication has been shown to improve scholastic functioning in children with attention-deficit/hyperactivity disorder ( ADHD ) . However , the extent to which long-term academic gains are apparent in those having received such treatment remains elusive . This study examined prospect ively the relationship of childhood stimulant treatment to academic functioning during adolescence . Children ( n = 169 ) were initially recruited and diagnosed with ADHD when they were 7 - 11 years old . A sub sample of those with childhood ADHD ( n = 90 ) was reevaluated on average 9.13 ( SD = 1.5 ) years later . Prob and s who did and did not receive treatment with stimulant medication were compared to each other and to a never-ADHD comparison group ( n = 80 ) on three subtests from the Wechsler Individual Achievement Test-II ( WIAT-II ) , as well as high school grade point average ( GPA ) and number of retentions in school as derived from school records . Analyses of covariance controlling for severity of childhood ADHD symptoms indicated that prob and s treated with psychostimulant medication achieved better academic outcomes , as measured by WIAT-II subtests and high school GPA , than those not treated with psychostimulants ( p Psychostimulant treatment for children with ADHD may benefit long-term adolescent academic performance , although the extent of improvement is likely to vary as a function of multiple factors", "OBJECTIVES To determine any long-term effects , 6 and 8 years after childhood enrollment , of the r and omly assigned 14-month treatments in the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder ( MTA ; N = 436 ) ; to test whether attention-deficit/hyperactivity disorder ( ADHD ) symptom trajectory through 3 years predicts outcome in subsequent years ; and to examine functioning level of the MTA adolescents relative to their non-ADHD peers ( local normative comparison group ; N = 261 ) . METHOD Mixed-effects regression models with planned contrasts at 6 and 8 years tested a wide range of symptom and impairment variables assessed by parent , teacher , and youth report . RESULTS In nearly every analysis , the originally r and omized treatment groups did not differ significantly on repeated measures or newly analyzed variables ( e.g. , grade s earned in school , arrests , psychiatric hospitalizations , other clinical ly relevant outcomes ) . Medication use decreased by 62 % after the 14-month controlled trial , but adjusting for this did not change the results . ADHD symptom trajectory in the first 3 years predicted 55 % of the outcomes . The MTA participants fared worse than the local normative comparison group on 91 % of the variables tested . CONCLUSIONS Type or intensity of 14 months of treatment for ADHD in childhood ( at age 7.0 - 9.9 years ) does not predict functioning 6 to 8 years later . Rather , early ADHD symptom trajectory regardless of treatment type is prognostic . This finding implies that children with behavioral and sociodemographic advantage , with the best response to any treatment , will have the best long-term prognosis . As a group , however , despite initial symptom improvement during treatment that is largely maintained after treatment , children with combined-type ADHD exhibit significant impairment in adolescence . Innovative treatment approaches targeting specific areas of adolescent impairment are needed", "BACKGROUND Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder ( ADHD ) , but no longer-term ( i.e. , > 4 months ) investigations have compared these 2 treatments or their combination . METHODS A group of 579 children with ADHD Combined Type , aged 7 to 9.9 years , were assigned to 14 months of medication management ( titration followed by monthly visits ) ; intensive behavioral treatment ( parent , school , and child components , with therapist involvement gradually reduced over time ) ; the two combined ; or st and ard community care ( treatments by community providers ) . Outcomes were assessed in multiple domains before and during treatment and at treatment end point ( with the combined treatment and medication management groups continuing medication at all assessment points ) . Data were analyzed through intent-to-treat r and om-effects regression procedures . RESULTS All 4 groups showed sizable reductions in symptoms over time , with significant differences among them in degrees of change . For most ADHD symptoms , children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care . Combined and medication management treatments did not differ significantly on any direct comparisons , but in several instances ( oppositional/aggressive symptoms , internalizing symptoms , teacher-rated social skills , parent-child relations , and reading achievement ) combined treatment proved superior to intensive behavioral treatment and /or community care while medication management did not . Study medication strategies were superior to community care treatments , despite the fact that two thirds of community-treated subjects received medication during the study period . CONCLUSIONS For ADHD symptoms , our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication . Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms , but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes", "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 compare delinquent behavior and early substance use between the children in the Multimodal Treatment Study of Children With ADHD ( MTA ; N = 487 ) and those in a local normative comparison group ( n = 272 ) at 24 and 36 months postr and omization and to test whether these outcomes were predicted by the r and omly assigned treatments and subsequent self-selected prescribed medications . METHOD Most MTA children were 11 to 13 years old by 36 months . Delinquency seriousness was coded ordinally from multiple measures /reporters ; child-reported substance use was binary . RESULTS Relative to local normative comparison group , MTA children had significantly higher rates of delinquency ( e.g. , 27.1 % vs. 7.4 % at 36 months ; p = .000 ) and substance use ( e.g. , 17.4 % vs. 7.8 % at 36 months ; p = .001 ) . Children r and omized to intensive behavior therapy reported less 24-month substance use than other MTA children ( p = .02 ) . R and om effects ordinal growth models revealed no other effects of initial treatment assignment on delinquency seriousness or substance use . By 24 and 36 months , more days of prescribed medication were associated with more serious delinquency but not substance use . CONCLUSIONS Cause- and -effect relationships between medication treatment and delinquency are unclear ; the absence of associations between medication treatment and substance use needs to be re-evaluated at older ages . Findings underscore the need for continuous monitoring of these outcomes as children with attention-deficit/hyperactivity disorder enter adolescence ", "OBJECTIVE To evaluate the predictors of persistence and the timing of remission of attention-deficit hyperactivity disorder ( ADHD ) . METHOD Subjects were 6- to 17-year old Caucasian , non-Hispanic boys with and without ADHD . DSM-III-R structured diagnostic interviews and blind raters were used to examine psychiatric diagnoses , cognitive achievement , social , school , and family functioning at a 4-year follow-up assessment . RESULTS At the 4-year follow-up assessment , 85 % of children with ADHD continued to have the disorder and 15 % remitted . Of those who remitted , half did so in childhood and the other half in adolescence . Predictors of persistence were familiality of ADHD , psychosocial adversity , and comorbidity with conduct , mood , and anxiety disorders . CONCLUSIONS The findings prospect ively confirm that the majority of children with ADHD will continue to express the disorder 4 years later . For a minority of children , ADHD was a transient disorder that remits early in development . In addition , we have shown that persistence of ADHD is predictable . Familiality , adversity , and psychiatric comorbidity may be clinical ly useful predictors of which children with ADHD are at risk for a persistent disorder", "The height of young adults who were treated with methylpheni date hydrochloride in childhood because of hyperactivity ( average daily dose , 45 mg ; duration of treatment , six months to five years ) was studied . There was no significant difference in height between the treated patients ( n = 61 ) and controls ( n = 99 ) ; both groups were at the national US norm in stature . The findings indicated that methylpheni date therapy does not compromise final height , even when it has an adverse impact on children 's growth rate during the active treatment phase . A compensatory growth rate , or growth rebound , appears to occur following discontinuation of stimulant therapy", "OBJECTIVE Despite the existence of several follow-up studies of children with ADHD followed up into adulthood , there is limited information on whether patterns of persistence and remission in ADHD can be predicted over the long term . The main aim of this study was to evaluate predictors of persistence of ADHD in a large sample of boys with and without ADHD followed prospect ively for 11 years into young adulthood . METHOD Subjects were Caucasian , non-Hispanic boys with ( N = 110 ) and without ( N = 105 ) ADHD who were 6 - 17 years old at the baseline assessment ( mean age 11 years ) and 15 to 31 years old at the follow-up assessment ( mean age 22 years ) . Subjects were comprehensively and blindly assessed with structured diagnostic interviews and assessment s of cognitive , social , school , and family functioning . RESULTS At the 11-year follow-up , 78 % of children with ADHD continued to have a full ( 35 % ) or a partial persistence ( subsyndromal ( 22 % ) , impaired functioning ( 15 % ) , or remitted but treated ( 6 % ) ) . Predictors of persistence were severe impairment of ADHD , psychiatric comorbidity , and exposure to maternal psychopathology at baseline . CONCLUSIONS These findings prospect ively confirm that persistence of ADHD over the long term is predictable from psychosocial adversity and psychiatric comorbidity ascertained 11 years earlier", "OBJECTIVE Intent-to-treat analyses of the Multimodal Treatment Study of ADHD ( MTA ) revealed group differences on attention-deficit/hyperactivity disorder symptoms ratings , with better outcome in groups of participants who were assigned the medication algorithm-medication alone ( MedMgt ) and combined (Comb)--than in those who were not-behavior modification ( Beh ) alone and community comparison ( CC ) . However , the effect size was reduced by 50 % from the end of treatment to the first follow-up . The convergence of outcomes suggests differential changes by treatment group beween 14 and 24 months , which this report explores , both for benefits of treatment and for side effects on growth . METHODS We documented reported medication use at 14- and 24-month assessment s and formed 4 naturalistic subgroups ( Med/Med , Med/NoMed , NoMed/Med , and NoMed/NoMed ) . Then we performed exploratory mediator analyses to evaluate effects of changes in medication use on 14- to 24-month change scores of effectiveness ( symptom ratings ) and growth ( height and weight measures ) . RESULTS The r and omly assigned groups with the greatest improvement at the end of the treatment phase ( Comb and MedMgt ) deteriorated during the follow-up phase , but the other 2 groups ( Beh and CC ) did not . There were no significant differences in the 14- to 24-month growth rates among the r and omly assigned groups , in contrast to significant growth suppression in the Comb and MedMgt at the end of the treatment phase . Changes in medication use mediated the 14- to 24-month change in attention-deficit/hyperactivity disorder symptom ratings : the subgroup that reported stopping medication ( Med/NoMed ) showed the largest deterioration , the subgroup that consistently reported ( Med/Med ) or never reported ( NoMed/NoMed ) medication use showed modest deterioration , and the subgroup that reported starting medication ( NoMed/Med ) showed improvement . Changes in medication use also mediated growth effects : the subgroup that consistently reported medication use ( Med/Med ) showed reduced height gain compared with the subgroup that never reported medication use ( NoMed/NoMed ) , which actually grew faster than predicted by population norms . CONCLUSION In the MTA follow-up , exploratory naturalistic analyses suggest that consistent use of stimulant medication was associated with maintenance of effectiveness but continued mild growth suppression", "OBJECTIVE In the Multimodal Treatment Study of ADHD ( MTA ) , the effects of medication management ( MedMgt ) and behavior modification therapy ( Beh ) and their combination ( Comb ) and usual community comparison ( CC ) in the treatment of attention-deficit/hyperactivity disorder ( ADHD ) differed at the 14-month assessment as a result of superiority of the MTA MedMgt strategy ( Comb or MedMgt ) over Beh and CC and modest additional benefits of Comb over MedMgt alone . Here we evaluate the persistence of these beneficial effects 10 months beyond the 14 months of intensive intervention . METHODS Of 579 children who entered the study , 540 ( 93 % ) participated in the first follow-up 10 months after the end of treatment . Mixed-effects regression models explored possible persisting effects of the MTA medication strategy , the incremental benefits of Comb over MedMgt alone , and the possible superiority of Beh over CC on 5 effectiveness and 4 service use domains . RESULTS The MTA medication strategy showed persisting significant superiority over Beh and CC for ADHD and oppositional-defiant symptoms at 24 months , although not as great as at 14 months . Significant additional benefits of Comb over MedMgt and of Beh over CC were not found . The groups differed significantly in mean dose ( methylpheni date equivalents 30.4 , 37.5 , 25.7 , and 24.0 mg/day , respectively ) . Continuing medication use partly mediated the persisting superiority of Comb and MedMgt . CONCLUSION The benefits of intensive MedMgt for ADHD extend 10 months beyond the intensive treatment phase only in symptom domains and diminish over time", "A form of the hyperkinetic syndrome , assumed to be a juvenile condition , has been found in an adult with a previously undiagnosed condition . The pathognomonic paradoxical calming of the hyperkinetic by amphetamine was shown in a 22-year-old man and further eluci date d by quantitative self-estimation of mood following doubleblind administrations of dextroamphetamine sulfate and placebo . Compared to his response to placebo , he not only showed externally visible calming and depression , but also subjectively reported decreased anxiety , increased depression , and increased concentration , with no change in self-esteem", "OBJECTIVE To evaluate the magnitude and clinical significance of methylpheni date ( MPH ) effects on the classroom behavior and academic performance of 76 children with attention deficit disorder/hyperactivity ( ADDH ) . METHOD A double-blind , placebo controlled , within-subject ( crossover ) experimental design was used to evaluate acute MPH effects at four dose levels ( 5 mg , 10 mg , 15 mg , and 20 mg ) on children 's attention , academic functioning , and behavior in regular classroom setting s. Results were contrasted with a normal control sample . RESULTS St and ard statistical analysis revealed MPH effects on classroom functioning that were primarily linear . Analysis of the clinical significance of effects indicated that large proportions of treated children exhibited significantly improved or normalized classroom functioning ; however , a large subset of them failed to show improved academic functioning . Overall , children failing to respond at lower dose levels have a high probability of improving or becoming normalized as a function of increasing dose . CONCLUSIONS For a majority of children with ADDH , MPH results in significantly improved or normalized attention and classroom behavior . A significant subset , however , fail to realize gains in their academic functioning and will require supplemental interventions", "The present study reports on st and ardized behavioral ratings received by a large sample of hyperactive children meeting research diagnostic criteria ( n=108 ) and a community control sample of normal children ( n=61 ) who were followed prospect ively over 8 years into adolescence . On some parentreport measures both groups declined in the severity of their behavior problems across time , while on other measures only the hyperactive group declined , but the hyperactives always remained more deviant than the controls at followup . The hyperactives and controls also differed on most teacher and selfreport ratings at followup . The greatest degree of agreement between raters at adolescence was between parent and youth ratings . These results are consistent with previous research demonstrating more deviant scores for hyperactive children than controls on various rating scales at adolescent followup . They also are consistent with research showing significant longitudinal continuity of both internalizing and externalizing behavioral pathology", "OBJECTIVE The paucity of data concerning the long-term natural history of attention-deficit hyperactivity disorder ( ADHD ) , a common childhood psychiatric disorder , prompted a longitudinal study to investigate the adult sequelae of the childhood disorder . DESIGN Prospect i ve study , follow-up intervals ranging from 13 to 19 years ( mean , 16 years ) , with blind systematic clinical assessment s. SUBJECTS Ninety-one white males ( mean age , 26 years ) , representing 88 % of a cohort systematic ally diagnosed as hyperactive in childhood , and 95 ( 95 % ) of comparison cases of similar race , gender , age , whose teachers had voiced no complaints about their school behavior in childhood . RESULTS Prob and s had significantly higher rates than comparisons of ADHD symptoms ( 11 % vs 1 % ) , antisocial personality disorders ( 18 % vs 2 % ) , and drug abuse disorders ( 16 % vs 4 % ) . Significant comorbidity occurred between antisocial and drug disorders . Educational and occupational achievements were significantly compromised in the prob and s. These disadvantages were independent of psychiatric status . We did not find increased rates of affective or anxiety disorders in the prob and s. CONCLUSIONS Childhood ADHD predicts specific adult psychiatric disorders , namely antisocial and drug abuse disorders . In the adolescent outcome of this cohort , we found that these disturbances were dependent on the continuation of ADHD symptoms . In contrast , in adulthood , antisocial and drug disorders appeared , in part , independent of sustained ADHD . In addition , regardless of psychiatric status , ADHD placed children at relative risk for educational and vocational disadvantage . The results do not support a relationship between childhood ADHD and adult mood or anxiety disorders", " Prospect i ve young adult outcomes ( mean age 21.8 years ) of children who had been diagnosed as having attention deficit disorder with hyperactivity and who had been treated with methylpheni date for at least 3 years were compared with those of a matched normal control group and a group of hyperactive young adults who had not received any stimulant treatment . Results suggest that in many areas , e.g. , school , work , and personality disorders , stimulant-treated hyperactives function significantly worse than matched normal controls but similar to untreated hyperactives . In some areas , e.g. , less car accidents , more positive view of childhood , later delinquency , and better social skills and self-esteem , stimulant-treated hyperactives did better than their untreated counterparts . Thus stimulant treatment for hyperactive children may not eliminate educational work or life difficulties , but may result in less social ostracism and improved feelings toward themselves and others" ]

[ "OBJECTIVE Impairments associated with attention-deficit/hyperactivity disorder ( ADHD ) and noncompliance are prevalent in children with autism spectrum disorder ( ASD ) . However , ADHD response to stimulants is well below rates in typically developing children , with frequent side effects . Group studies of treatments for noncompliance are rare in ASD . We examined individual and combined-effectiveness of atomoxetine ( ATX ) and parent training ( PT ) for ADHD symptoms and noncompliance . METHOD In a 3-site , 10-week , double-blind , 2 × 2 trial of ATX and PT , 128 children ( ages 5 - 14 years ) with ASD and ADHD symptoms were r and omized to ATX , ATX+PT , placebo+PT , or placebo . ATX was adjusted to optimal dose ( capped at 1.8 mg/kg/day ) over 6 weeks and maintained for 4 additional weeks . Nine PT sessions were provided . Primary outcome measures were the parent-rated DSM ADHD symptoms on the Swanson , Nolan and Pelham ( SNAP ) scale and Home Situations Question naire ( HSQ ) . RESULTS On the SNAP , ATX , ATX+PT and placebo+PT were each superior to placebo ( effect sizes 0.57 - 0.98 ; p values of .0005 , .0004 , and .025 , respectively ) . For noncompliance , ATX and ATX+PT were superior to placebo ( effect sizes 0.47 - 0.64 ; p values .03 and .0028 , respectively ) . ATX was associated with decreased appetite but was otherwise well tolerated . CONCLUSION Both ATX and PT result ed in significant improvement on ADHD symptoms , whereas ATX ( both alone and combined with PT ) was associated with significant decreases on measures of noncompliance . ATX appears to have a better side effects profile than psychostimulants in the population with ASD . CLINICAL TRIAL REGISTRATION INFORMATION Atomoxetine , Placebo and Parent Management Training in Autism ; http:// clinical trials.gov/ ; NCT00844753", "BACKGROUND Risperidone is a second generation antipsychotic agent , with potent serotonin 5-HT2A and dopamine D2 receptor blocking effects . Specifically , risperidone possesses a unique balance of serotonin and dopamine antagonism , namely that its affinity for 5-HT2A receptors is significantly greater than its affinity for D2 receptors . Risperidone is well-established medication , with the proven effects on positive and negative symptoms of schizophrenia . The aim of research was to establish the effectiveness and safety of risperidone in patients with schizophrenia . SUBJECTS AND METHODS The sample consisted of 60 subjects , age ranged was between 18 - 60 years , both genders , who met the criteria for the diagnosis various types of schizophrenia , according to ICD-10 ( International Statistical Classification of Diseases ) . They were enrolled in the study as outpatient and inpatient setting . All subjects signed informed consent before entering into this study which had been conducted at the Psychiatric Clinic , University Clinical Center Sarajevo . Study was design ed for 8-week , open-label , flexible-dose observational study . The subjects had to have a total score > -40 on Positive and Negative scale -two parts of the Positive and Negative Syndrome Scale ( PANSS ) , and to be able to discontinue current antipsychotic medications . The primary efficacy parameter was the percent of score difference between baseline and week 8 of therapy on two above-mentioned PANSS subscales . The difference was considered as significant improvement if decrease from the baseline was 20 % or more . The secondary efficacy parameter was subjective clinical evaluation of efficacy with five possible answers : very good , good , moderate , not satisfactory , not possible to evaluate . It was measured at the end of observational period by the investigator . RESULTS All 60 enrolled patients completed the study . After the 8 weeks of treatment , 54/60 patients ( 90 % ) had clinical ly significant improvement of 20 % or more decreased total PANSS score ( Positive and Negative subscale ) . In 6/60 patients ( 10 % ) clinical improvement was also reported with less of 20 % decreased total PANSS score . The side effects were registered in 8/60 patients ( 13.32 % ) . The mild extrapyramidal symptoms registered in 1/60 ( 11.66 % ) patients , whom dose of risperidone was reduced . Increase of prolactine in 7/60 ( 11.66 % ) , patients , whose dose of risperidone also were reduced . Average weight gain was 0.84 kg . CONCLUSION In this study Risperidone has shown very good effectiveness and safety", "Some open-label studies suggest that risperidone can be useful in the treatment of certain target symptoms in children with autism . We aim ed to study whether the use of risperidone in comparison with placebo improved functioning in children with autism with regard to behavior ( aggressiveness , hyperactivity , irritability ) , social and emotional responsiveness , and communication skills . We conducted a r and omized , double-blind , placebo-controlled trial with 40 consecutive children with autism , whose ages ranged from 2 to 9 years , who were receiving either risperidone or placebo given orally at a dose of 1 mg/day for 6 months . Autism symptoms were monitored periodically . The outcome variables were total scores on the Childhood Autism Rating Scale ( CARS ) and the Children 's Global Assessment Scale ( CGAS ) after 6 months . Of the 40 children enrolled , 39 completed the trial over a period of 18 months ; 19 received risperidone , and 20 received placebo . In the risperidone group , 12 of 19 children showed improvement in the total Childhood Autism Rating Scale score and 17 of 19 children in the Children 's Global Assessment Scale score compared with 0 of 20 children for the Childhood Autism Rating Scale score and 2 of 20 children for the Children 's Global Assessment Scale score in the placebo group ( P social responsiveness and nonverbal communication and reduced the symptoms of hyperactivity and aggression . Risperidone was associated with increased appetite and a mild weight gain , mild sedation in 20 % , and transient dyskinesias in three children . Risperidone improved global functioning and social responsiveness while reducing hyperactivity and aggression in children with autism and was well tolerated . ( J Child Neurol 2006;21:450—455 ; DOI 10.2310/7010.2006.00099 )", "OBJECTIVE Many children with pervasive developmental disorders ( PDDs ) have serious , functionally impairing behavioral problems . We tested whether combined treatment ( COMB ) with risperidone and parent training ( PT ) in behavior management is superior to medication alone ( MED ) in improving severe behavioral problems in children with PDDs . METHOD This 24-week , three-site , r and omized , parallel-groups clinical trial enrolled 124 children , aged 4 through 13 years , with PDDs , accompanied by frequent tantrums , self-injury , and aggression . The children were r and omized 3:2 to COMB ( n = 75 ) or MED ( n = 49 ) . The participants received risperidone monotherapy from 0.5 to 3.5 mg/day ( with switch to aripiprazole if risperidone was ineffective ) . Parents in the COMB group ( n = 75 ; 60.5 % ) received a mean of 10.9 PT sessions . The primary measure of compliance was the Home Situations Question naire ( HSQ ) score . RESULTS Primary : intent-to-treat r and om effects regression showed that COMB was superior to MED on HSQ ( p = .006 ) [ effect size at week 24 ( d ) = 0.34 ] . The HSQ score declined from 4.31 ( ± 1.67 ) to 1.23 ( ± 1.36 ) for COMB compared with 4.16 ( ± 1.47 ) to 1.68 ( ± 1.36 ) for MED . Secondary : groups did not differ on Clinical Global Impressions-Improvement scores at endpoint ; compared with MED , COMB showed significant reductions on Aberrant Behavior Checklist Irritability ( d = 0.48 ; p = .01 ) , Stereotypic Behavior ( d = 0.23 ; p = .04 ) , and Hyperactivity/Noncompliance subscales ( d = 0.55 ; p = .04 ) . Final risperidone mean dose for MED was 2.26 mg/day ( 0.071 mg/kg ) , compared with 1.98 mg/day for COMB ( 0.066 mg/kg ) ( p = .04 ) . CONCLUSIONS Medication plus PT result ed in greater reduction of serious maladaptive behavior than MED in children with PDDs , with a lower risperidone dose", "INTRODUCTION Early intervention in autism spectrum disorders ( ASDs ) appears promising and may represent a window of opportunity for more effective treatment . Whereas the safety and efficacy of risperidone have been established for children aged 5 and older , they has not been adequately tested in preschool children . METHODS A r and omized placebo-controlled study of risperidone in preschool children was conducted in a sample of young children , most of whom were also undergoing intensive behavioral treatment . RESULTS Preschool children tolerated low-dose risperidone well with no serious adverse effects observed over a 6-month treatment period . Weight gain and hypersalivation were the most common side effects reported , and hyperprolactinemia without lactation or related signs was observed . Significant differences between groups found at baseline complicated the analyses ; however , controlling for some of these differences revealed that preschoolers on risperidone demonstrated greater improvements in autism severity . The change in autism severity scores from baseline to 6-month follow up for the risperidone group was 8 % compared to 3 % for the placebo group . Notably , both groups significantly improved over the 6-month treatment period . CONCLUSIONS Study findings suggest that risperidone is well tolerated in preschoolers over a 6-month period , but that only minimally greater improvement in target symptoms was evident in the risperidone group , possibly due to the differences between groups at baseline or due to the small sample size . Although these findings are not sufficient to direct treatment , they suggest that larger-scale , double-blind , placebo-controlled investigations of risperidone in preschoolers with ASDs should now be conducted", "Objective . To investigate the efficacy and safety of risperidone for the treatment of disruptive behavioral symptoms in children with autism and other pervasive developmental disorders ( PDD ) . Methods . In this 8-week , r and omized , double-blind , placebo-controlled trial , risperidone/placebo solution ( 0.01–0.06 mg/kg/day ) was administered to 79 children who were aged 5 to 12 years and had PDD . Behavioral symptoms were assessed using the Aberrant Behavior Checklist ( ABC ) , Nisonger Child Behavior Rating Form , and Clinical Global Impression-Change . Safety assessment s included vital signs , electrocardiogram , extrapyramidal symptoms , adverse events , and laboratory tests . Results . Subjects who were taking risperidone ( mean dosage : 0.04 mg/kg/day ; 1.17 mg/day ) experienced a significantly greater mean decrease on the irritability subscale of the ABC ( primary endpoint ) compared with those who were taking placebo . By study endpoint , risperidone-treated subjects exhibited a 64 % improvement over baseline in the irritability score almost double that of placebo-treated subjects ( 31 % ) . Risperidone-treated subjects also exhibited significantly greater decreases on the other 4 subscales of the ABC ; on the conduct problem , insecure/anxious , hyperactive , and overly sensitive subscales of the Nisonger Child Behavior Rating Form ( parent version ) ; and on the Visual Analog Scale of the most troublesome symptom . More risperidone-treated subjects ( 87 % ) showed global improvement in their condition compared with the placebo group ( 40 % ) . Somnolence , the most frequently reported adverse event , was noted in 72.5 % versus 7.7 % of subjects ( risperidone vs placebo ) and seemed manageable with dose/dose-schedule modification . Risperidone-treated subjects experienced statistically significantly greater increases in weight ( 2.7 vs 1.0 kg ) , pulse rate , and systolic blood pressure . Extrapyramidal symptoms scores were comparable between groups . Conclusions . Risperidone was well tolerated and efficacious in treating behavioral symptoms associated with PDD in children", "BACKGROUND Atypical antipsychotic agents , which block postsynaptic dopamine and serotonin receptors , have advantages over traditional antipsychotic medications in the treatment of adults with schizophrenia and may be beneficial in children with autistic disorder who have serious behavioral disturbances . However , data on the safety and efficacy of atypical antipsychotic agents in children are limited . METHODS We conducted a multisite , r and omized , double-blind trial of risperidone as compared with placebo for the treatment of autistic disorder accompanied by severe tantrums , aggression , or self-injurious behavior in children 5 to 17 years old . The primary outcome measures were the score on the Irritability subscale of the Aberrant Behavior Checklist and the rating on the Clinical Global Impressions - Improvement ( CGI-I ) scale at eight weeks . RESULTS A total of 101 children ( 82 boys and 19 girls ; mean [ + /-SD ] age , 8.8+/-2.7 years ) were r and omly assigned to receive risperidone ( 49 children ) or placebo ( 52 ) . Treatment with risperidone for eight weeks ( dose range , 0.5 to 3.5 mg per day ) result ed in a 56.9 percent reduction in the Irritability score , as compared with a 14.1 percent decrease in the placebo group ( P Irritability score and a rating of much improved or very much improved on the CGI-I scale , was 69 percent in the risperidone group ( 34 of 49 children had a positive response ) and 12 percent in the placebo group ( 6 of 52 , P Risperidone therapy was associated with an average weight gain of 2.7+/-2.9 kg , as compared with 0.8+/-2.2 kg with placebo ( P Increased appetite , fatigue , drowsiness , dizziness , and drooling were more common in the risperidone group than in the placebo group ( P Risperidone was effective and well tolerated for the treatment of tantrums , aggression , or self-injurious behavior in children with autistic disorder . The short period of this trial limits inferences about adverse effects such as tardive dyskinesia", "OBJECTIVE Risperidone is effective for short-term treatment of aggression , temper outbursts , and self-injurious behavior in children with autism . Because these behaviors may be chronic , there is a need to establish the efficacy and safety of longer-term treatment with this agent . METHOD The authors conducted a multisite , two-part study of risperidone in children ages 5 to 17 years with autism accompanied by severe tantrums , aggression , and /or self-injurious behavior who showed a positive response in an earlier 8-week trial . Part I consisted of 4-month open-label treatment with risperidone , starting at the established optimal dose ; part II was an 8-week r and omized , double-blind , placebo-substitution study of risperidone withdrawal . Primary outcome measures were the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression improvement scale . RESULTS Part I included 63 children . The mean risperidone dose was 1.96 mg/day at entry and remained stable over 16 weeks of open treatment . The change on the Aberrant Behavior Checklist irritability subscale was small and clinical ly insignificant . Reasons for discontinuation of part I included loss of efficacy ( N=5 ) and adverse effects ( N=1 ) . The subjects gained an average of 5.1 kg . Part II included 32 patients . The relapse rates were 62.5 % for gradual placebo substitution and 12.5 % for continued risperidone ; this difference was statistically significant . CONCLUSIONS Risperidone showed persistent efficacy and good tolerability for intermediate-length treatment of children with autism characterized by tantrums , aggression , and /or self-injurious behavior . Discontinuation after 6 months was associated with a rapid return of disruptive and aggressive behavior in most subjects", "OBJECTIVE The objective of this research was to explore the effects of risperidone on cognitive processes in children with autism and irritable behavior . METHOD Thirty-eight children , ages 5 - 17 years with autism and severe behavioral disturbance , were r and omly assigned to risperidone ( 0.5 to 3.5 mg/day ) or placebo for 8 weeks . This sample of 38 was a subset of 101 subjects who participated in the clinical trial ; 63 were unable to perform the cognitive tasks . A double-blind placebo-controlled parallel groups design was used . Dependent measures included tests of sustained attention , verbal learning , h and -eye coordination , and spatial memory assessed before , during , and after the 8-week treatment . Changes in performance were compared by repeated measures ANOVA . RESULTS Twenty-nine boys and 9 girls with autism and severe behavioral disturbance and a mental age > or=18 months completed the cognitive part of the study . No decline in performance occurred with risperidone . Performance on a cancellation task ( number of correct detections ) and a verbal learning task ( word recognition ) was better on risperidone than on placebo ( without correction for multiplicity ) . Equivocal improvement also occurred on a spatial memory task . There were no significant differences between treatment conditions on the Purdue Pegboard ( h and -eye coordination ) task or the Analog Classroom Task ( timed math test ) . CONCLUSION Risperidone given to children with autism at doses up to 3.5 mg for up to 8 weeks appears to have no detrimental effect on cognitive performance", "OBJECTIVE Risperidone has been found efficacious for decreasing severe tantrums , aggression , and self-injurious behavior in children and adolescents with autistic disorder ( autism ) . The authors report on whether risperidone improves the core symptoms of autism , social and communication impairment and repetitive and stereotyped behavior . METHOD The data base from an 8-week double-blind , placebo-controlled trial ( N=101 ) and 16-week open-label continuation study ( N=63 ) of risperidone for children and adolescents with autism was used to test for drug effects on secondary outcome measures : scores on the Ritvo-Freeman Real Life Rating Scale , the Children 's Yale-Brown Obsessive Compulsive Scale , and the maladaptive behavior domain of the Vinel and Adaptive Behavior Scales . RESULTS Compared to placebo , risperidone led to a significantly greater reduction in the overall score on the Ritvo-Freeman Real Life Rating Scale , as well as the scores on the subscales for sensory motor behaviors ( subscale I ) , affectual reactions ( subscale III ) , and sensory responses ( subscale IV ) . No statistically significant difference was observed , however , on the subscale for social relatedness ( subscale II ) or language ( subscale V ) . Risperidone also result ed in significantly greater reductions in scores on the Children 's Yale-Brown Obsessive Compulsive Scale and Vinel and maladaptive behavior domain . This pattern of treatment response was maintained for 6 months . CONCLUSIONS Risperidone led to significant improvements in the restricted , repetitive , and stereotyped patterns of behavior , interests , and activities of autistic children but did not significantly change their deficit in social interaction and communication . Further research is necessary to develop effective treatments for the core social and communicative impairments of autism", "Objective The aim of the study was to compare safety , efficacy and tolerability of risperidone with haloperidol in the treatment of Autistic Disorder ( AD ) . Method This study was design ed as a double-blind , prospect i ve , for a 12-week period . A total of 30 subjects , between the ages of 8 and 18 with AD based on DSM IV criteria , were included in the study . Behavioral Rating Scales were performed by the investigators and the parents . Safety assessment included vital signs , electrocardiogram , electroencephalogram , adverse events , laboratory tests , extrapyramidal symptoms and the side effects . Both treatments were applied in a once daily dosage regimen of 0.01–0.08 mg/kg/day . Results The reduction from baseline in Ritvo – Freeman Real Life Rating Scale ( RF-RLRS ) , sensory motor ( subscale I ) and language ( subscale V ) scores were significant in risperidone group ( P haloperidol , risperidone led to a significantly greater reduction in the Aberrant Behavior Checklist ( ABC ) and Turgay DSM-IV Pervasive Developmental Disorder ( PDD ) scale scores ( P prolactin in the risperidone group , while alanine amino transferase ( ALT ) had further increased in the haloperidol group . Sensory motor behaviors ( subscale I ) and language at the end of the 12th week , RF-RLRS sensory motor and language subscale scores decreased in the risperidone group further than the other group ( P Risperidone was found to be more effective than haloperidol in the treatment of behavioral symptoms , impulsivity , language skills , and impaired social relations in children with AD . These results demonstrated that both drugs were safe and well tolerated in the treatment of AD", "In this double-blind , placebo-controlled study the administration of haloperidol result ed in significant decreases in behavioral symptoms and in general clinical improvement in 40 autistic children ages 2.33 to 6.92 years . Haloperidol also produced greater facilitation and retention of discrimination learning in the laboratory . No adverse effects were observed at therapeutic doses , which ranged from 0.5 to 3.0 mg/day or 0.019 to 0.217 mg/kg per day", "BACKGROUND Neurobiological research has implicated the dopamine and serotonin systems in the pathogenesis of autism . Open-label reports suggest that the serotonin2A-dopamine D2 antagonist risperidone may be safe and effective in reducing the interfering symptoms of patients with autism . METHODS Thirty-one adults ( age [ mean+/-SD ] , 28.1+/-7.3 years ) with autistic disorder ( n=17 ) or pervasive developmental disorder not otherwise specified ( n=14 ) participated in a 12-week double-blind , placebo-controlled trial of risperidone . Patients treated with placebo subsequently received a 12-week open-label trial of risperidone . RESULTS For persons completing the study , 8 ( 57 % ) of 14 patients treated with risperidone were categorized as responders ( daily dose [ mean+/-SD ] , 2.9+/-1.4 mg ) compared with none of 16 in the placebo group ( P Risperidone was superior to placebo in reducing repetitive behavior ( P aggression ( P anxiety or nervousness ( P depression ( P irritability ( P overall behavioral symptoms of autism ( P social behavior and language did not occur . Nine ( 60 % ) of 15 patients who received treatment with open-label risperidone following the double-blind placebo phase responded . Other than mild , transient sedation , risperidone was well tolerated , with no evidence of extrapyramidal effects , cardiac events , or seizures . CONCLUSION Risperidone is more effective than placebo in the short-term treatment of symptoms of autism in adults", "BACKGROUND The aim of the study was to investigate safety , efficacy and tolerability of risperidone in comparison with haloperidol in the long-term treatment of autistic disorder . METHODS This was an open-label continuation study of the r and omized , double-blind , controlled trial of risperidone and haloperidol study for 12 week in autistic children and adolescents . A total of 28 subjects between 8 and 18 ages with autistic disorder were enrolled to the open label phase of the study . Behavioral rating scales ( Clinical Global Impression Scale [ CGI-I ] , Ritvo-Freeman Real Life Rating Scale [ RF-RLRS ] ) , Aberrant Behavior Checklist [ ABC ] , Turgay DSM-IV Pervasive Developmental Disorder Rating Scale [ TPDDRS ] ) and safety assessment scales ( Extrapyramidal Symptoms Rating Scale [ ESRS ] , UKU-Side Effect Rating Scale ) were performed at 12 , 16 , 20 and 24 weeks , following the 12 week double-blind phase . Risperidone and haloperidol treatments were applied with a once daily dosage regimen as 0.01 - 0.08 mg/kg/day . RESULTS Risperidone led to a significant greater reduction on CGI scale . There was significant improvement on RF-RLRS sensory motor and language subscale and ABC scores in risperidone group . Weight gain was observed more frequently in the haloperidol group at week 24 . CONCLUSIONS These results demonstrate that risperidone is more efficacious and well tolerated than haloperidol in the long-term maintenance treatment of autistic disorder", "The effects of haloperidol on behavioral symptoms and learning were critically assessed in autistic children in an ongoing double-blind placebo-controlled clinical trial . Children were r and omly assigned to haloperidol-placebo-haloperidol or placebo-haloperidol-placebo treatment sequences . Statistically , haloperidol was significantly superior to placebo in reducing behavioral symptoms . In discrimination learning paradigm , children receiving haloperidol learned the discrimination while those on placebo did not . Discrimination attained on haloperidol was retained when the children were switched to placebo", "IMPORTANCE Disruptive behavior is common in children with autism spectrum disorder . Behavioral interventions are used to treat disruptive behavior but have not been evaluated in large-scale r and omized trials . OBJECTIVE To evaluate the efficacy of parent training for children with autism spectrum disorder and disruptive behavior . DESIGN , SETTING , AND PARTICIPANTS This 24-week r and omized trial compared parent training ( n = 89 ) to parent education ( n = 91 ) at 6 centers ( Emory University , Indiana University , Ohio State University , University of Pittsburgh , University of Rochester , Yale University ) . We screened 267 children ; 180 children ( aged 3 - 7 years ) with autism spectrum disorder and disruptive behaviors were r and omly assigned ( 86 % white , 88 % male ) between September 2010 and February 2014 . INTERVENTIONS Parent training ( 11 core , 2 optional sessions ; 2 telephone boosters ; 2 home visits ) provided specific strategies to manage disruptive behavior . Parent education ( 12 core sessions , 1 home visit ) provided information about autism but no behavior management strategies . MAIN OUTCOMES AND MEASURES Parents rated disruptive behavior and noncompliance on co- primary outcomes : the Aberrant Behavior Checklist-Irritability subscale ( range , 0 - 45 ) and the Home Situations Question naire-Autism Spectrum Disorder ( range , 0 - 9 ) . On both measures , higher scores indicate greater severity and a 25 % reduction indicates clinical improvement . A clinician blind to treatment assignment rated the Improvement scale of the Clinical Global Impression ( range , 1 - 7 ) , a secondary outcome , with a positive response less than 3 . RESULTS At week 24 , the Aberrant Behavior Checklist-Irritability subscale declined 47.7 % in parent training ( from 23.7 to 12.4 ) compared with 31.8 % for parent education ( 23.9 to 16.3 ) ( treatment effect , -3.9 ; 95 % CI , -6.2 to -1.7 ; P 0.62 ) . The Home Situations Question naire-Autism Spectrum Disorder declined 55 % ( from 4.0 to 1.8 ) compared with 34.2 % in parent education ( 3.8 to 2.5 ) ( treatment effect , -0.7 ; 95 % CI , -1.1 to -0.3 ; P with a positive response on the Clinical Global Impression-Improvement scale were 68.5 % for parent training vs 39.6 % for parent education ( P For children with autism spectrum disorder , a 24-week parent training program was superior to parent education for reducing disruptive behavior on parent-reported outcomes , although the clinical significance of the improvement is unclear . The rate of positive response judged by a blinded clinician was greater for parent training vs parent education . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01233414", "BACKGROUND Recent evidence indicates that atypical antipsychotics represent a promising option for the treatment of autistic disorder . In particular , risperidone appears to be effective in treating aggressiveness , hyperactivity , irritability , stereotypies , social withdrawal , and lack of interests . OBJECTIVE The aim of the present study was to evaluate the effectiveness and tolerability of risperidone in children with autistic disorder and to examine the correlation between plasma levels of risperidone and its active metabolite 9-hydroxyrisperidone ( 9-OH-risperidone ) and the clinical response . METHODS The effect of treatment with risperidone ( 0.75 - 2 mg/day ; mean + /- SD dose = 1.26 + /- 0.42 mg/day ) was studied for 24 weeks in 20 children ( 14 boys , 6 girls ) ages 3 to 10 years ( mean age 6.0 + /- 2.4 years ) , diagnosed with autistic disorder . Fourteen items selected from the Children 's Psychiatric Rating Scale ( CPRS-14 ) and Clinical Global Impression ( CGI ) were used for behavioral evaluation . Patients were classified as responders if they showed a 25 % or greater decrease on CPRS-14 total score at final evaluation compared with baseline and a final CGI rating of 1 or 2 . Patients were rated for extrapyramidal side effects on the Abnormal Involuntary Movement Scale ( AIMS ) . Other side effects , including the expected side effects of atypical antipsychotics drugs , were assessed by a checklist . Blood sample s for determination of risperidone and its active metabolite 9-OH-risperidone were obtained after 12 weeks , and serum prolactin levels were measured on admission and at weeks 12 and 24 . RESULTS The psychopathological state , as assessed by CPRS , improved significantly over the duration of treatment . The mean CPRS-14 scores decreased significantly from 63.7 + /- 10.0 at baseline to 52.9 + /- 14.3 at week 12 ( p serum prolactin levels increased significantly ( p risperidone treatment . Weight gain and increased appetite were the most common unwanted effects . A mean increase of 3.7 + /- 1.7 kg in body weight was observed at final evaluation as compared with baseline . There was no significant correlation between percent improvement in total CPRS score and the plasma level of risperidone 's active fractions ( the sum of the risperidone and 9-OH-risperidone plasma concentration ) . CONCLUSIONS This study provides further evidence of the beneficial effects of risperidone in children diagnosed with autistic disorder . However , the potential advantages of risperidone should be weighed against the risk of unwanted effects , such as an increase in serum prolactin levels and weight gain . No relation was observed between total plasma risperidone and 9-OH-risperidone concentrations and clinical response", "OBJECTIVE To report results from a long-term prospect i ve study of safety of haloperidol treatment and prevalence of haloperidol-related dyskinesias . METHOD Subjects were children with autism requiring pharmacotherapy for target symptoms . After baseline assessment s , children received haloperidol treatment ; responders requiring further treatment were considered for enrollment into the present study . Six-month haloperidol treatment periods were followed by a 4-week placebo period . The procedure was repeated if further haloperidol treatment was required . At specified times children were evaluated by using multiple instruments . RESULTS Between 1979 and 1994 , 118 children aged 2.3 to 8.2 years participated in the study . The mean dose of haloperidol was 1.75 mg/day . Mainly withdrawal dyskinesias ( WD ) developed in 40 ( 33.9 % ) children ; 20 had more than one dyskinetic episode . A subgroup that remained significantly longer in the study and had a significantly higher cumulative dose of haloperidol evidence d a significantly higher incidence of WD . Occurrence rates of tardive dyskinesia ( TD ) and multiple episodes of TD/WD were higher among girls . CONCLUSION Female gender and pre- and perinatal complications may be involved in susceptibility to dyskinesias ; greater cumulative haloperidol dose and /or longer exposure to haloperidol may increase the risk", "Abstract Aripiprazole and risperidone are the only FDA approved medications for treating irritability in autistic disorder , however there are no head-to-head data comparing these agents . This is the first prospect i ve r and omized clinical trial comparing the safety and efficacy of these two medications in patients with autism spectrum disorders . Fifty nine children and adolescents with autism spectrum disorders were r and omized to receive either aripiprazole or risperidone for 2 months . The primary outcome measure was change in Aberrant Behavior Checklist ( ABC ) scores . Adverse events were assessed . Aripiprazole as well as risperidone lowered ABC scores during 2 months . The rates of adverse effects were not significantly different between the two groups . The safety and efficacy of aripiprazole ( mean dose 5.5 mg/day ) and risperidone ( mean dose 1.12 mg/day ) were comparable . The choice between these two medications should be on the basis of clinical equipoise considering the patient ’s preference and clinical profile", "OBJECTIVE To evaluate the short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder . METHOD Two hundred eighteen children and adolescents ( aged 6 - 17 years ) with a diagnosis of autistic disorder , and with behaviors such as tantrums , aggression , self-injurious behavior , or a combination of these symptoms , were r and omized 1:1:1:1 to aripiprazole ( 5 , 10 , or 15 mg/day ) or placebo in this 8-week double-blind , r and omized , placebo-controlled , parallel-group study . Efficacy was evaluated using the caregiver-rated Aberrant Behavior Checklist Irritability subscale ( primary efficacy measure ) and the clinician-rated Clinical Global Impressions-Improvement score . Safety and tolerability were also assessed . RESULTS At week 8 , all aripiprazole doses produced significantly greater improvement than placebo in mean Aberrant Behavior Checklist Irritability subscale scores ( 5 mg/day , -12.4 ; 10 mg/day , -13.2 ; 15 mg/day , -14.4 ; versus placebo , -8.4 ; all p aripiprazole doses demonstrated significantly greater improvements in mean Clinical Global Impressions-Improvement score than placebo at week 8 . Discontinuation rates due to adverse events were as follows : placebo 7.7 % , aripiprazole 5 mg/day 9.4 % , 10 mg/day 13.6 % , and 15 mg/day 7.4 % . The most common adverse event leading to discontinuation was sedation . There were two serious adverse events : presyncope ( 5 mg/day ) and aggression ( 10 mg/day ) . At week 8 , mean weight change ( last observation carried forward ) was as follows : placebo + 0.3 kg , aripiprazole 5 mg/day + 1.3 kg , 10 mg/day + 1.3 kg , and 15 mg/day + 1.5 kg ; all p Aripiprazole was efficacious and generally safe and well tolerated in the treatment of children and adolescents with irritability associated with autistic disorder", "This double-blind and placebo-controlled clinical trial in autistic children had three objectives : ( a ) to replicate earlier findings that haloperidol administration is associated with a significant reduction of behavioral symptoms ; ( b ) to further assess its safety when given on a short-term basis : and ( c ) to assess whether it has an effect on discrimination learning . Forty-five children , 2.02 to 7.58 years old ( M=4.49 ) , completed this crossover design , with r and om assignment to treatment sequences . Haloperidol was shown to be a powerful therapeutic agent when administered for 4 weeks and free of side effects ; at doses ranging from 0.25 to 4.0 mg/day ( M=0.844 ) , there was a clinical ly and statistically significant reduction of a variety of symptoms . Under the given conditions , the children failed to learn on either haloperidol or placebo" ]

[ "BACKGROUND Iron-deficiency anemia in non-dialysis-dependent chronic kidney disease ( NDD-CKD ) frequently requires parenteral iron replacement , but existing therapies often require multiple administrations . We evaluated the efficacy and cardiovascular safety of ferric carboxymaltose ( FCM ) , a non-dextran parenteral iron permitting large single-dose infusions , versus iron sucrose in patients with iron-deficiency anemia and NDD-CKD . METHODS A total of 2584 participants were r and omized to two doses of FCM 750 mg in one week , or iron sucrose 200 mg administered in up to five infusions in 14 days . The primary efficacy endpoint was the mean change to highest hemoglobin from baseline to Day 56 . The primary composite safety endpoint included all-cause mortality , nonfatal myocardial infa rct ion , nonfatal stroke , unstable angina , congestive heart failure , arrhythmias and hyper- and hypotensive events . RESULTS The mean hemoglobin increase was 1.13 g/dL in the FCM group and 0.92 g/dL in the iron sucrose group ( 95 % CI , 0.13 - 0.28 ) . Similar results were observed across all subgroups , except Stage 2 CKD . More subjects in the FCM group achieved a hemoglobin increase of ≥ 1.0 g/dL between baseline and Day 56 ( 48.6 versus 41.0 % ; 95 % CI , 3.6 - 11.6 % ) . There was no significant difference between FCM and iron sucrose recipients with respect to the primary composite safety endpoint , including the major adverse cardiac events of death , myocardial infa rct ion , or stroke . A significant difference in the number of protocol -defined , predominantly transient hypertensive episodes was observed in the FCM group . CONCLUSIONS Two 750-mg infusions of FCM are a safe and effective alternative to multiple lower dose iron sucrose infusions in NDD-CKD patients with iron-deficiency anemia", "Background . Iron deficiency is a common cause of anaemia and hyporesponsiveness to erythropoiesis-stimulating agents ( ESAs ) in non-dialysis-dependent chronic kidney disease ( ND-CKD ) patients . Current intravenous iron agents can not be administered in a single high dose because of adverse effects . Ferric carboxymaltose , a non-dextran parenteral iron preparation , can be rapidly administered in high doses . Methods . This open-label trial r and omized 255 subjects with glomerular filtration rates ≤ 45 mL/min/1.73 m2 , haemoglobin ≤ 11 g/dL , transferrin saturation ≤ 25 % , ferritin ≤ 300 ng/mL , and stable ESA dose to either intravenous ferric carboxymaltose 1000 mg over 15 min ( with up to two additional doses of 500 mg at 2-week intervals ) or oral ferrous sulphate 325 mg thrice daily for a total of 195 mg elemental iron daily for 56 days . Results . In the modified intent-to-treat population , the proportion of subjects achieving a haemoglobin increase ≥ 1 g/dL at any time was 60.4 % with ferric carboxymaltose and 34.7 % with oral iron ( P 42 , mean increase in haemoglobin was 0.95 ± 1.12 vs 0.50 ± 1.23 g/dL ( P = 0.005 ) , mean increase in ferritin was 432 ± 189 ng/mL vs 18 ± 45 ng/mL ( P ) and mean increase in transferrin saturation was 13.6 ± 11.9 % vs 6.1 ± 8.1 % ( P events were significantly fewer with ferric carboxymaltose than with oral iron ( 2.7 % and 26.2 % , respectively ; P 1000 mg ferric carboxymaltose can be rapidly administered , is more effective and is better tolerated than oral iron for treatment of iron deficiency in ND-CKD patients", "This is the first study to investigate the efficacy of intravenous iron in treating fatigue in nonanemic patients with low serum ferritin concentration . In a r and omized , double-blinded , placebo-controlled study , 90 premenopausal women presenting with fatigue , serum ferritin ≤ 50 ng/mL , and hemoglobin ≥ 120 g/L were r and omized to receive either 800 mg of intravenous iron (III)-hydroxide sucrose or intravenous placebo . Fatigue and serum iron status were assessed at baseline and after 6 and 12 weeks . Median fatigue at baseline was 4.5 ( on a 0 - 10 scale ) . Fatigue decreased during the initial 6 weeks by 1.1 in the iron group compared with 0.7 in the placebo group ( P = .07 ) . Efficacy of iron was bound to depleted iron stores : In patients with baseline serum ferritin ≤ 15 ng/mL , fatigue decreased by 1.8 in the iron group compared with 0.4 in the placebo group ( P = .005 ) , and 82 % of iron-treated compared with 47 % of placebo-treated patients reported improved fatigue ( P = .03 ) . Drug-associated adverse events were observed in 21 % of iron-treated patients and in 7 % of placebo-treated patients ( P = .05 ) ; none of these events was serious . Intravenous administration of iron improved fatigue in iron-deficient , nonanemic women with a good safety and tolerability profile . The efficacy of intravenous iron was bound to a serum ferritin concentration ≤ 15 ng/mL. This study was registered at the International St and ard R and omized Controlled Trial Number Register ( www.is rct n.org ) as IS RCT N78430425", "Background Unexplained fatigue is often left untreated or treated with antidepressants . This r and omized , placebo-controlled , single-blinded study evaluated the efficacy and tolerability of single-dose intravenous ferric carboxymaltose ( FCM ) in iron-deficient , premenopausal women with symptomatic , unexplained fatigue . Methods Fatigued women ( Piper Fatigue Scale [ PFS ] score ≥5 ) with iron deficiency ( ferritin and , blinded to the study drug and r and omized ( computer-generated r and omization sequence ) to a single FCM ( 1000 mg iron ) or saline ( placebo ) infusion . Primary endpoint was the proportion of patients with reduced fatigue ( ≥1 point decrease in PFS score from baseline to Day 56 ) . Results The full analysis included 290 women ( FCM 144 , placebo 146 ) . Fatigue was reduced in 65.3 % ( FCM ) and 52.7 % ( placebo ) of patients ( OR 1.68 , 95%CI 1.05–2.70 ; p = 0.03 ) . A 50 % reduction of PFS score was achieved in 33.3 % FCM- vs. 16.4 % placebo-treated patients ( p had hemoglobin levels ≥120 g/L ( vs. 87 % at baseline ) ; with placebo , the proportion decreased from 86 % to 81 % . Mental quality -of-life ( SF-12 ) and the cognitive function scores improved better with FCM . ‘ Power of attention ’ improved better in FCM-treated patients with ferritin µg/L. Treatment-emergent adverse events ( placebo 114 , FCM 209 ; most frequently headache , nasopharyngitis , pyrexia and nausea ) were mainly mild or moderate . Conclusion A single infusion of FCM improved fatigue , mental quality -of-life , cognitive function and erythropoiesis in iron-deficient women with normal or borderline hemoglobin . Although more side effects were reported compared to placebo , FCM can be an effective alternative in patients who can not tolerate or use oral iron , the common treatment of iron deficiency . Overall , the results support the hypothesis that iron deficiency can affect women ’s health , and a normal iron status should be maintained independent of hemoglobin levels . Trial Registration Clinical Trials.gov", "Background : Secondary thrombocytosis is a common clinical feature . In patients with cancer , it is a risk factor for venous thromboembolic events . In inflammatory bowel disease ( IBD ) , thrombocytosis is so far considered a marker of active disease and may contribute to the increased thromboembolic risk in this population . Observed effects of iron therapy on normalization of platelet counts led us to hypothesize that iron itself may regulate megakaryopoiesis . Here , we want to test the effect of iron replacement on platelet count and activity in IBD-associated thrombocytosis . Methods : We performed a r and omized , single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose ( FCM ) in patients with IBD with secondary thrombocytosis ( platelets > 450 G/L ) . Changes in platelet counts , hemoglobin , iron parameters , disease activity , megakaryopoietic growth factors , erythropoietin , and platelet activity were assessed . Patients received placebo or up to 1500 mg iron as FCM . Endpoints were evaluated at week 6 . Results : A total of 26 patients were included in the study , 15 patients were available for the per protocol analysis . A drop in platelets > 25 % ( primary endpoint ) was observed in 4 of 8 ( 50 % , iron group ) and 1 of 7 patients ( 14 % , placebo group , P = 0.143 ) . Mean platelet counts dropped on FCM but not on placebo ( 536 G/L to 411 G/L versus 580 G/L to 559 G/L ; P = 0.002 ) . Disease activity and megakaryopoietic growth factors remained unchanged and hemoglobin and iron parameters increased on FCM . The normalization of platelet counts was associated with a decrease in platelet aggregation and P-selectin expression . Conclusion : FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis", "Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed", "Abstract Objective : Iron deficiency is a common but treatable comorbidity in chronic heart failure ( CHF ) that is associated with impaired health-related quality -of-life ( HRQoL ) . This study evaluates the cost-effectiveness of the intravenous iron preparation ferric carboxymaltose ( FCM ) for the treatment of iron deficiency in CHF from a Swedish healthcare perspective . Methods : A cost-effectiveness analysis with a time horizon of 24 weeks was performed to compare FCM treatment with placebo . Data on health outcomes and medical re source use were mainly taken from the FAIR-HF trial and combined with Swedish cost data . An incremental cost-effectiveness ratio ( ICER ) was calculated as well as the change in per-patient costs for primary care and hospital care . Results : In the FCM group compared with placebo , quality -adjusted life years ( QALYs ) are higher ( difference = 0.037 QALYs ) , but so are per-patient costs [ ( difference = SEK 2789 ( € 303 ) ] . Primary care and hospital care equally share the additional costs , but within hospitals there is a major shift of costs from inpatient care to outpatient care . The ICER is SEK 75,389 ( € 8194 ) per QALY . The robustness of the result is supported by sensitivity analyses . Conclusions : Treatment of iron deficiency in CHF with FCM compared with placebo is estimated to be cost-effective . The ICER in the base case scenario is twice as high as previously thought , but noticeably below SEK 500,000 ( € 54,300 ) per QALY , an informal average reference value used by the Swedish Dental and Pharmaceutical Benefits Agency . Increased HRQoL and fewer hospitalizations are the key drivers of this result", "OBJECTIVE The aim of this study was to ascertain whether high-dose intravenous ( IV ) iron sucrose could improve symptoms and change brain iron concentrations in idiopathic RLS . METHODS The study was a r and omized , parallel-group double-blind study of 1000 mg iron sucrose given IV versus placebo . Primary measures of the clinical status were global rating scale ( GRS ) and periodic leg movements of sleep ( PLMS ) . Primary measures of brain iron status were CSF ferritin and MRI-determined iron in the substantia nigra . RESULTS At the time of the interim analysis there were 7 placebo and 11 iron-treated subjects . At 2-weeks post-treatment , iron treatment result ed in a small but significant increase in CSF ferritin and a decrease in RLS severity ( GRS ) but did not change PLMS or MRI iron index . None of the secondary outcomes changed with treatment . There was no single case of clear treatment benefit in any of the patients . This interim analysis revealed an effect size that was too small to allow for adequate power to find significant differences with the planed 36-subject enrollment for either the primary objective outcome of PLMS or any of the secondary outcomes . The study was stopped at this planned break-point given the lack of both adequate power and any indication for clinical ly significant benefit . CONCLUSIONS High-dose IV iron failed to demonstrate the robust changes reported in three prior open-label studies . Differences in iron formulation , dosing regiment , and peripheral iron status may explain some of the discrepancies between this and previous IV iron treatment studies", "There is limited safety information about ferric carboxymaltose ( FCM ) , a new intravenous iron preparation . This r and omized , crossover study compared the safety and tolerability of double‐blinded intravenous doses of FCM or placebo in patients with iron deficiency anemia . Subjects ( 559 ) with iron deficiency anemia received a dose of either FCM ( 15 mg/kg , maximum 1000 mg ) over 15 minutes or placebo on day 0 . On day 7 , subjects received the other agent . Safety evaluations were performed on days 7 and 14 . The primary endpoint was the incidence of treatment‐emergent adverse events during each 7‐day study period . During the first 24 hours and during the 7‐day treatment period , at least one treatment‐emergent adverse event was experienced by 15.0 % and 29.3 % of subjects after FCM and 11.4 % and 19.7 % after placebo , respectively . Most were classified as Grade 1 or 2 . Six subjects had Grade 3 treatment‐emergent adverse events after FCM and 9 subjects after placebo . One subject had a Grade 4 , and 1 subject had a Grade 5 treatment‐emergent adverse event , but neither was considered study drug‐related . During the first 24 hours of the treatment period , drug‐related adverse events were reported in 9.3 % of subjects receiving FCM and 4.8 % receiving placebo . Of drug‐related Grade 3 events , 4 subjects received FCM and 5 subjects received placebo . Administration of FCM ( 15 mg/kg , maximum of 1000 mg ) over 15 minutes was well tolerated and associated with minimal risk of adverse reactions in patients with iron deficiency anemia", "OBJECTIVES To compare the safety and efficacy of iron carboxymaltose with ferrous sulfate to treat iron deficiency anemia in the post partum . METHODS Patients were r and omized ( 2:1 ratio ) to receive iron carboxymaltose ( up to 3 weekly doses of 1000 mg maximum , applied in 15 min ; n=227 ) or ferrous sulfate ( 100 mg twice daily , 12 weeks ; n=117 ) . Changes in hemoglobin and iron stores up to week 12 were analyzed . RESULTS Iron carboxymaltose was as effective as oral iron sulfate in changing hemoglobin , despite the much shorter treatment period ( 2 weeks vs 12 weeks ) . Ferritin levels were significantly higher . Except for injection site burning , iron carboxymaltose was better tolerated than ferrous sulfate , mainly concerning gastrointestinal side effects . There were no safety concerns identified in breast-fed infants . CONCLUSION Parenteral iron carboxymaltose is a safe and effective treatment option for postpartum anemia , with advantages of a shorter treatment period , better compliance , rapid normalization of iron storages , and lower incidence of gastrointestinal side effects", "BACKGROUND AIMS : Anemia is a common complication of inflammatory bowel diseases ( IBD ) This multicenter study tested the noninferiority and safety of a new intravenous iron preparation , ferric carboxymaltose ( FeCarb ) , in comparison with oral ferrous sulfate ( FeSulf ) in reducing iron deficiency anemia ( IDA ) in IBD . METHODS : Two hundred patients were r and omized in a 2:1 ratio ( 137 FeCarb:63 FeSulf ) to receive FeCarb ( maximum 1,000 mg iron per infusion ) at 1-wk intervals until the patients ' calculated total iron deficit was reached or FeSulf ( 100 mg b.i.d . ) for 12 wk . The primary end point was change in hemoglobin ( Hb ) from baseline to week 12 . RESULTS : The median Hb improved from 8.7 to 12.3 g/dL in the FeCarb group and from 9.1 to 12.1 g/dL in the FeSulf group , demonstrating noninferiority ( P = 0.6967 ) . Response ( defined as Hb increase of > 2.0 g/dL ) was higher for FeCarb at week 2 ( P = 0.0051 ) and week 4 ( P = 0.0346 ) . Median ferritin increased from 5.0 to 323.5 μg/L at week 2 , followed by a continuous decrease in the FeCarb group ( 43.5 μg/L at week 12 ) . In the FeSulf group , a moderate increase from 6.5 to 28.5 μg/L at week 12 was observed . Treatment-related adverse events ( AEs ) occurred in 28.5 % of the FeCarb and 22.2 % of the FeSulf groups , with discontinuation of study medication due to AEs in 1.5 % and 7.9 % , respectively . CONCLUSIONS : FeCarb is effective and safe in IBD-associated anemia . It is noninferior to FeSulf in terms of Hb change over 12 wk , and provides a fast Hb increase and a sufficient refill of iron stores", "BACKGROUND & AIMS Iron-deficiency anemia is the most common systemic complication of inflammatory bowel diseases ( IBD ) . Iron-deficiency anemia recurs frequently and rapidly after iron-replacement therapy in patients with IBD . We performed a r and omized , placebo-controlled trial to determine if administration of ferric carboxymaltose ( FCM ) prevents anemia in patients with IBD and low levels of serum ferritin . METHODS We performed a single-blind , multicenter study of nonanemic patients who had completed the FERGIcor study . Serum levels of ferritin were assessed every second month , and patients were given FCM ( total iron dose , 1181 ± 662 mg ; n = 105 ) or placebo ( n = 99 ) when levels decreased to less than 100 μg/L. The primary end point was time to recurrence of anemia within 8 months . Secondary end points included changes of quality of life , disease activity , results from laboratory tests , and adverse events . RESULTS Anemia recurred in 26.7 % of subjects given FCM and in 39.4 % given placebo . The time to anemia recurrence was longer in the FCM group ( hazard ratio , 0.62 ; 95 % confidence interval , 0.38 - 1.00 ; P = .049 ) . Markers of body levels of iron increased or remained at normal levels in subjects given FCM ( ferritin increased by 30.3 μg/L , transferrin saturation increased by 0.6 % ) but decreased in the group given placebo ( ferritin decreased by 36.1 μg/L , transferrin saturation decreased by 4.0 % ) . Changes in quality of life and disease activity were comparable between groups . Adverse events were reported in 59.0 % of the FCM group and 50.5 % of the placebo group , and serious adverse events were reported in 6.7 % and 8.1 % , respectively . CONCLUSIONS FCM prevents recurrence of anemia in patients with IBD , compared with placebo . Nevertheless , the high rate of anemia recurrence warrants optimization of the frequency and requirements for FCM treatment", "OBJECTIVE : To estimate efficacy of rapid , large-dose intravenous ( IV ) administration of ferric carboxymaltose compared with oral iron therapy in anemic postpartum women . METHODS : In a r and omized , controlled trial , we assigned anemic women ( hemoglobin [ Hb ] less than or equal to 10 g/dL ) within 10 days postpartum to receive either IV ferric carboxymaltose ( less than or equal to1,000 mg over 15 minutes , repeated weekly to achieve a total calculated replacement dose ) or ferrous sulfate ( FeSO4 ) 325 mg orally thrice daily for 6 weeks . RESULTS : One hundred seventy-four patients received 350 IV doses of ferric carboxymaltose ( mean total dose 1,403.1 mg ) in 3 , 2 , or 1 injection ( 10.9 % , 79.3 % , or 9.8 % of patients , respectively ) ; 178 received FeSO4 . Patients assigned to IV ferric carboxymaltose compared with those assigned to oral iron achieved a Hb rise greater than or equal to 2.0 g/dL earlier ( 7.0 compared with 14.0 days , P Hb rise greater than or equal to 3.0 g/dL at any time ( 86.3 % compared with 60.4 % , P Hb greater than 12.0 g/dL ( 90.5 % compared with 68.6 % , P Hb rise greater than or equal to 2.0 g/dL ( 96.4 % compared with 94.1 % , IV compared with oral , P=.443 ) . There were no serious adverse drug reactions . CONCLUSION : Large-dose IV ferric carboxymaltose administration is a new iron agent that is effective for the treatment of postpartum anemia . When compared with oral ferrous sulfate , IV ferric carboxymaltose is better tolerated , prompts a more rapid Hb response , and corrects anemia more reliably . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00396292 LEVEL OF EVIDENCE :", "Background : It is unknown whether intravenous iron or oral iron repletion alone can correct anemia associated with chronic kidney disease ( CKD ) . We conducted a r and omized multicenter controlled trial in adult anemic , iron-deficient non-dialysis CKD ( ND-CKD ) patients ( ≧stage 3 ) not receiving erythropoiesis-stimulating agents ( ESAs ) . Methods : The participants were r and omized to receive either a sodium ferric gluconate complex ( intravenous iron ) 250 mg i.v . weekly × 4 or ferrous sulfate ( oral iron ) 325 mg t.i.d . × 42 days . Hemoglobin ( Hgb ) , ferritin and transferrin saturation ( TSAT ) were measured serially , and the Kidney Disease Quality of Life ( KDQoL ) question naire was administered on days 1 and 43 . The primary outcome variable was change from baseline ( CFB ) to endpoint in Hgb values . Results : Seventy-five patients were analyzed ( intravenous iron n = 36 , oral iron n = 39 ) . CFB in Hgb was similar in the two groups ( intravenous iron 0.4 g/dl vs. oral iron 0.2 g/dl , p = n.s . ) . However , the increase in Hgb was only significant with intravenous iron ( p greater improvements in ferritin ( 232.0 ± 160.8 vs. 55.9 ± 236.2 ng/ml , p ) and TSAT ( 8.3 ± 7.5 vs. 2.9 ± 8.8 % , p = 0.007 ) . Intravenous iron caused greater improvements in KDQoL scores than oral iron ( p with intravenous iron was hypotension , while constipation was more common with oral iron . Conclusions : Oral and intravenous iron similarly increase Hgb in anemic iron-depleted ND-CKD patients not receiving ESAs . Although in comparison to oral iron , intravenous iron may result in a more rapid repletion of iron stores and greater improvement in quality of life , it exposes the patients to a greater risk of adverse effects and increases inconvenience and cost ", "OBJECTIVE The objective of the study was to evaluate the efficacy , safety , and tolerability of intravenous ferric carboxymaltose , compared with oral ferrous sulfate in women with postpartum anemia . STUDY DESIGN In a multicenter , r and omized , controlled study , 291 women less than 10 days after delivery with hemoglobin 10 g/dL or less were r and omized to receive ferric carboxymaltose ( n = 143 ) 1000 mg or less intravenously over 15 minutes or less , repeated weekly to a calculated replacement dose ( maximum 2500 mg ) or ferrous sulfate ( n = 148 ) 325 mg orally thrice daily for 6 weeks . RESULTS Ferric carboxymaltose-treated subjects were significantly more likely to : ( 1 ) achieve a hemoglobin greater than 12 g/dL in a shorter time period with a sustained hemoglobin greater than 12 g/dL at day 42 , ( 2 ) achieve hemoglobin rise 3 g/dL or greater more quickly , and ( 3 ) attain higher serum transferrin saturation and ferritin levels . Drug-related adverse events occurred less frequently with ferric carboxymaltose . CONCLUSION Intravenous ferric carboxymaltose was safe and well tolerated with an efficacy superior to oral ferrous sulfate in the treatment of postpartum iron deficiency anemia", "BACKGROUND The objective was to evaluate efficacy and safety of rapid , large-dose intravenous ( IV ) administration of ferric carboxymaltose compared to oral iron in correcting iron deficiency anemia due to heavy uterine bleeding . STUDY DESIGN AND METHODS In a r and omized , controlled trial , 477 women with anemia , iron deficiency , and heavy uterine bleeding were assigned to receive either IV ferric carboxymaltose ( of ferrous sulfate ( 65 mg elemental iron ) prescribed orally thrice daily for 6 weeks . RESULTS Compared to those assigned to ferrous sulfate , more patients assigned to ferric carboxymaltose responded with a hemoglobin ( Hb ) increase of 2.0 g/dL or more ( 82 % vs. 62 % , 95 % confidence interval for treatment difference 12.2 - 28.3 , p 3.0 g/dL or more increase ( 53 % vs. 36 % , p or= 12 g/dL ) of anemia ( 73 % vs. 50 % , p ferric carboxymaltose compared to those prescribed ferrous sulfate reported greater gains in vitality and physical function and experienced greater improvement in symptoms of fatigue ( p serious adverse drug events . CONCLUSIONS In patients with iron deficiency anemia due to heavy uterine bleeding , rapid IV administration of large doses of a new iron agent , ferric carboxymaltose , is more effective than oral iron therapy in correcting anemia , replenishing iron stores , and improving quality of life", "OBJECTIVES Our objective was to evaluate in a double-blind , r and omized , placebo-controlled study possible modifications in NT-pro-brain natriuretic peptide ( NT-proBNP ) and C-reactive protein ( CRP ) levels together with clinical and functional parameters , in a group of anemic patients with chronic heart failure ( CHF ) and chronic renal failure ( CRF ) receiving intravenous iron therapy , without recombinant human erythropoietin ( rhEPO ) , versus placebo . BACKGROUND Chronic heart failure and CRF associated with absolute or relative iron deficiency anemia is a common problem . This situation is linked with a variable inflammatory status . Both NT-proBNP and CRP are recognized markers for left ventricular dysfunction and inflammatory status , respectively . In this double-blind , r and omized , placebo-controlled study , modifications in NT-proBNP and CRP level and clinical and functional parameters , in anemic patients with CHF and CRF receiving intravenous iron therapy , without rhEPO , versus placebo were evaluated . METHODS Forty patients with hemoglobin ( Hb ) into 2 groups ( n = 20 for each ) . For 5 weeks , group A received isotonic saline solution and group B received iron sucrose complex , 200 mg weekly . Minnesota Living with Heart Failure Question naire ( MLHFQ ) and 6-min walk ( 6MW ) test were performed . NT-pro brain natriuretic peptide and CRP were evaluated throughout the study . No patients received erythroprotein any time . RESULTS After 6 months follow-up , group B showed better hematology values and CrCl ( p NT-proBNP ( 117.5 + /- 87.4 pg/ml vs. 450.9 + /- 248.8 pg/ml , p CRP ( 2.3 + /- 0.8 mg/l vs. 6.5 + /- 3.7 mg/l , p Hb and NT-proBNP ( group A : r = -0.94 and group B : r = -0.81 ) and after 6 months only in group A : r = -0.80 . Similar correlations were observed with Hb and CRP . Left ventricular ejection fraction percentage ( 35.7 + /- 4.7 vs. 28.8 + /- 2.4 ) , MLHFQ score , and 6MW test were all improved in group B ( p hospitalizations : 0 of 20 versus group A , 5 of 20 ( p Intravenous iron therapy without rhEPO substantially reduced NT-proBNP and inflammatory status in anemic patients with CHF and moderate CRF . This situation was associated with an improvement in LVEF , NYHA functional class , exercise capacity , renal function , and better quality of life", "BACKGROUND & AIMS Iron deficiency anemia ( IDA ) is common in chronic diseases and intravenous iron is an effective and recommended treatment . However , dose calculations and inconvenient administration may affect compliance and efficacy . We compared the efficacy and safety of a novel fixed-dose ferric carboxymaltose regimen ( FCM ) with individually calculated iron sucrose ( IS ) doses in patients with inflammatory bowel disease ( IBD ) and IDA . METHODS This r and omized , controlled , open-label , multicenter study included 485 patients with IDA ( ferritin Patients received either FCM in a maximum of 3 infusions of 1000 or 500 mg iron , or Ganzoni-calculated IS dosages in up to 11 infusions of 200 mg iron . Primary end point was Hb response ( Hb increase ≥ 2 g/dL ) ; secondary end points included anemia resolution and iron status normalization by week 12 . RESULTS The results of 240 FCM-treated and 235 IS-treated patients were analyzed . More patients with FCM than IS achieved Hb response ( 150 [ 65.8 % ] vs 118 [ 53.6 % ] ; 12.2 % difference , P = .004 ) or Hb normalization ( 166 [ 72.8 % ] vs 136 [ 61.8 % ] ; 11.0 % difference , P = .015 ) . Both treatments improved quality of life scores by week 12 . Study drugs were well tolerated and drug-related adverse events were in line with drug-specific clinical experience . Deviations from scheduled total iron dosages were more frequent in the IS group . CONCLUSIONS The simpler FCM-based dosing regimen showed better efficacy and compliance , as well as a good safety profile , compared with the Ganzoni-calculated IS dose regimen", "OBJECTIVES There is evidence of iron deficiency ( ID ) in patients treated with lipoprotein apheresis . Aim of this study was to assess ID in apheresis patients and to study its management comparing safety and efficacy of two approved intravenous ( i.v . ) iron formulations . METHODS Inclusion criteria were defined as a ) serum ferritin b ) ferritin Other causes for anemia were ruled out by thorough history-taking and examination/blood tests . Patients were treated with six different lipoprotein apheresis methods : DALI , Liposorber D , TheraSorb LDL , HELP , MONET and Lipidfiltration . 50 patients were r and omized to either ferric carboxymaltose ( FCM , 500 - 1000 mg as single shot infusion over 20 min ) or ferric gluconate ( FG , 62.5 mg once weekly ) . RESULTS 50 of 67 patients of our Lipoprotein Apheresis Center showed iron deficiency . Both i.v . iron formulations studied were equally safe ( no serious adverse events ( SAEs ) , 6 patients /group showed adverse events ( AEs ) ) and both effective ( clinical ly and with respect to laboratory data ) in lipoprotein apheresis patients , however FCM led to a more rapid and steeper rise of iron parameters . CONCLUSIONS ID and IDA are common findings in lipoprotein apheresis patients . The pathogenesis remains yet poorly understood and is probably multifactorial . Differential diagnosis of ID/IDA is as essential as differential therapy . H and led with care , older i.v . iron preparations like FG appear to be safe and effective in lipoprotein apheresis patients . However , novel formulations like FCM can be administered rapidly at higher doses due to high complex stability , allowing faster filling of iron stores . Newer laboratory parameters ( Reticulocyte-He , low/medium/high fluorescence reticulocytes ( LFR/MFR/HFR ) ) assessing iron status may be helpful in early detection of ID and in monitoring iron replacement therapy", "Levels of hepcidin , a major regulator of iron homeostasis , may identify patients with iron deficiency anemia ( IDA ) who will not respond to oral iron therapy . In this study , IDA patients underwent a 14‐day trial ( run‐in ) course of ferrous sulfate therapy . Nonresponders ( Hgb increase r and omized to IV ferric carboxymaltose ( FCM ; two injections of 750 mg ) or further oral iron for 14 days . Screening hepcidin levels were 38.4 versus 11.3 ng/mL , P = 0.0002 in nonresponders versus responders to a trial of oral iron . Hepcidin of > 20 ng/mL , showed sensitivity of 41.3 % , specificity of 84.4 % , and positive predictive value of 81.6 % for predicting nonresponsiveness to oral iron . PPVs for ferritin > 30 ng/mL or transferrin saturation (TSAT)>15 % were 59.2 and 55 % , respectively . Negative predictive values for hepcidin , ferritin , and TSAT were 46.3 , 22.7 , and 19.7 , respectively . FCM versus oral iron showed Hgb increases of ≥1 gm/dL in 65.3 % versus 20.8 % ( P predicts nonresponsiveness to oral iron in patients with IDA and is superior to TSAT or ferritin for this purpose . Nonresponse to oral iron therapy does not rule out IDA , since two‐thirds of patients subsequently responded to intravenous iron . Am . J. Hematol . 88:97–101 , 2013 . © 2012 Wiley Periodicals ,", "BACKGROUND Iron dextran administration is associated with a high incidence of adverse reactions including anaphylaxis and death . Although dextran , rather than iron , is believed to be the cause of these reactions , it is not known whether iron dextran-sensitive patients can be safely administered another form of parenteral iron , sodium ferric gluconate in sucrose ( SFGC ) . METHODS In a 69 center , prospect i ve , double-blind , controlled trial of safety and tolerability of SFGC , the rate of reactions to SFGC and placebo in 144 iron dextran-sensitive patients was compared with 2194 patients who were previously tolerant to iron dextran preparations . Serum tryptase levels , a marker of mast cell degranulation , also were measured . RESULTS Among 143 iron dextran-sensitive patients exposed to SFGC , three ( 2.1 % ) were intolerant . All three had suspected allergic events to SFGC , including one patient with a serious reaction ( 0.7 % ) . One dextran-sensitive patient ( 0.7 % ) had a suspected allergic reaction after placebo . In contrast , among 2194 iron dextran-tolerant patients , reactions to SFGC were significantly less common , with SFGC intolerance seen in seven patients ( 0.3 % ; P = 0.020 ) , including five ( 0.2 % ) who had suspected allergic events ( P = 0.010 ) , but none who had serious events ( 0.0 % ; P = 0.061 ) . Two iron dextran-tolerant patients ( 0.09 % ) had allergic-like reactions following placebo injections . Two of the three suspected allergic events in the iron dextran-sensitive group were confirmed as mast cell dependent by a 100 % increase in serum tryptase , while there were no confirmed allergic events in the iron dextran-tolerant group . Long-term exposure to SFGC in iron dextran-sensitive patients result ed in intolerance in only one additional patient and no serious adverse events . CONCLUSIONS Patients with a history of iron dextran sensitivity had approximately sevenfold higher rates of reaction to both placebo and SFGC compared to iron dextran tolerant patients . However , logistic regression analysis , performed to account for the higher reaction rate to placebo , suggests that this increased reactivity was not drug-specific nor immunologically mediated , but represented host idiosyncrasy . These results support the conclusions that reactions to SFGC can be attributed to pseudoallergy , and that SFGC is not a true allergen" ]

[ "OBJECTIVE The aim of this study was to evaluate the levels of adipose tissue related hormones , cytokines , and antioxidative substances in obese women before and after intervention with diet alone or with diet plus an inhibitor of gastrointestinental lipase-orlistat . DESIGN Seventy-one obese women of childbearing age were included in the study and were r and omly assigned into two groups according to the type of intervention : group A1 ( n=35 ) included women who received orlistat as well as a hypocaloric diet , and group A2 ( n=36 ) included women who were only on hypocaloric diet . The intervention period lasted 6 months . Anthropometric parameters , such as Body Weight ( BW ) , Body Mass Index ( BMI ) , Waist Circumference ( WC ) , and % Body fat ( BF ) were recorded . Insulin , leptin , resistin , interleukin-6 ( IL-6 ) , insulin like growth factor 1 ( IGF-1 ) , tumor necrosis factor alpha ( TNFalpha ) , adiponectin , hsC-reactive protein ( CRP ) , glutathione peroxidase , and isoprostane were determined by appropriate methodology prior to and following the 6-month intervention period . Insulin resistance was measured using the homeostasis model assessment index ( HOMA-IR ) . All participants had normal glucose tolerance . RESULTS In both groups B MI values were lower after intervention and all measured parameters were ameliorated . A statistically significant difference was found between group A1 ( orlistat plus diet ) and group A2 ( diet only ) with regard to the levels of triglycerides , CRP , TNF-alpha , IGF-1 , and isoprostane , even after correcting for weight loss . CONCLUSION Hypocaloric diet plus orlistat in obese women is superior to diet alone with regard to the changes observed in adipokines , CRP , TNFalpha , triglycerides , IGF-1 , and oxidative stress following intervention", "The aim of this study was to determine if orlistat , an inhibitor of fat absorption , combined with caloric restriction in overweight subjects with nonalcoholic steatohepatitis results in weight loss and improved liver histology . Fifty overweight subjects ( body mass index = > or=27 ) with biopsy proven nonalcoholic steatohepatitis were r and omized to receive a 1,400 Kcal/day diet plus vitamin E ( 800 IU ) daily with or without orlistat ( 120 mg three times a day ) for 36 weeks . Liver biopsies were repeated at week 36 . Twenty-three subjects in the orlistat/diet/vitamin E group and 18 in the diet/vitamin E group completed the study . The mean age was 47 + /- 9.0 ( st and ard deviation ) years and mean body mass index was 36.4 + /- 6.3 kg/m(2 ) . Four subjects were diabetic . The orlistat group lost a mean of 8.3 % body weight compared to 6.0 % in the diet plus vitamin E group ( not significant ) . Both groups also had similarly improved serum aminotransferases , hepatic steatosis , necroinflammation , ballooning , and nonalcoholic fatty liver disease activity scores . Stratified according to weight loss instead of treatment group , a loss of > or=5 % body weight ( n = 24 ) compared to insulin sensitivity ( P = 0.001 ) and steatosis ( P = 0.015 ) . Comparing subjects who lost > or=9 % of body weight ( n = 16 ) , to those that did not ( n = 25 ) , improved insulin sensitivity ( P adiponectin ( P = 0.03 ) , steatosis ( P = 0.005 ) , ballooning ( P = 0.04 ) , inflammation ( P = 0.045 ) , and nonalcoholic fatty liver disease activity score ( P = 0.009 ) were seen . Increases in adiponectin strongly correlated with improved ballooning and nonalcoholic fatty liver disease activity score ( P = 0.03 ) . Orlistat did not enhance weight loss or improve liver enzymes , measures of insulin resistance , and histopathology . However , subjects who lost > or=5 % of body weight over 9 months improved insulin resistance and steatosis , and those subjects who lost > or=9 % also achieved improved hepatic histologic changes", "We investigated the effects of different weight loss protocol s on leptin levels in obese females with the aim of addressing the leptin resistance which has been found to be an aggravating factor in obesity . Twenty-four obese females enrolled to one of three 12-week weight loss protocol s : orlistat-induced weight loss ( OWL , n=8 ) , exercise-induced weight loss ( EWL , n=8 ) and orlistat plus exercise-induced weight loss ( OEWL , n=8 ) . Serum leptin levels were measured in duplicate by radioimmunoassay . There were significant reductions ( P body weight and fat mass after the 12 week period in all groups : -11.4+/-0.5 kg and -9.8+/-0.5 kg ( OEWL ) , -8.3+/-0.8 kg and -5.7+/-0.9 kg ( OWL ) , -8.9+/-1.2 kg and -7.4+/-1.2 kg ( EWL ) , respectively . Serum leptin levels were also decreased markedly in all groups : -59.2 % ( OEWL1 ) , -37.8 % ( OWL ) and -48.6 % ( EWL ) ( P leptin levels for each kilogram of fat mass after the 12 week period : -48.2+/-7.2 % ( OEWL ) , -27.8+/-4.8 % ( OWL ) and -39.3+/-4.3 % ( EWL ) ( P serum leptin levels expressed per kilogram of fat mass were significantly higher in the OEWL group compared to the OWL group ( P=0.03 ) . Consequently , an exercise training program in adjunct to pharmacotherapy provides higher weight reduction and fat mass loss in obesity treatment . It also seems to have further beneficial effects on leptin resistance , as indicated by decreases in leptin levels expressed per kilogram of fat mass", "OBJECTIVE To assess the impact of weight reduction on serum adipocytokines , C-reactive protein ( CRP ) , and insulin sensitivity in hypertensive female patients with central obesity . METHODS This study was performed using the data base and stored serum sample s of female patients who had participated in an intervention study focused on weight loss . Thirty hypertensive women aged 18 to 65 , body mass index ( BMI ) > 27 kg/m2 , and central obesity were selected . They were r and omly assigned to receive either a low-calorie diet plus orlistat 120 mg three times daily or a low-calorie diet alone for 16 weeks . Patients who experienced weight loss greater than 5 % ( n = 24 ) were assessed for blood pressure , anthropometric parameters , visceral fat , insulin resistance ( HOMA-R - homeostasis model assessment of insulin resistance ) and sensitivity ( ISI - Insulin Sensitivity Index ) indices , plus serum lipids , adipocytokines ( adiponectin , leptin , IL-6 , and TNF-alpha ) and CRP levels . RESULTS After BMI had been reduced by approximately 5 % in both groups , visceral fat , fasting glucose , triglycerides , and TNF-alpha decreased . Only the orlistat group , which was more insulin resistant at baseline , showed a significant reduction in blood glucose after oral glucose load , in addition to increased insulin sensitivity . CONCLUSION This study 's findings indicate that a weight loss greater than 5 % is associated with improved inflammatory status and decreased insulin resistance , regardless of changes in adiponectin and TNF-a levels . The greatest improvements in insulin sensitivity experienced by the orlistat-treated patients could not be attributed to the use of this drug because of the higher number of insulin-resistant subjects in this group", "BACKGROUND Orlistat has been shown to increase adiponectin and reduce progression to type 2 diabetes in obese Caucasians . Some effects of orlistat are thought to be independent of weight loss by altering gut flora and the production of endotoxin lipopolysaccharide ( LPS ) . We studied the effect of dietary treatment with and without orlistat in South Asian individuals with impaired glucose tolerance ( IGT ) on adiponectin and inflammatory markers including LPS . METHODS South Asian individuals were r and omised to either dietary treatment with orlistat or dietary treatment alone . At the end of 12 months , a comparison was made between the two groups for differences in anthropomorphic measurements and serum markers . RESULTS Three hundred and five individuals underwent oral glucose tolerance test of whom 40 had IGT . Complete baseline and 1-year data was available for 31 patients . After 1 year , patients in the orlistat group demonstrated a greater but insignificant decrease in weight ( 4.5 + /- 0.1 kg ) , and a significant increase in adiponectin ( 6.73 + /- 3.2 microg/ml ) and decrease in LPS ( 4.55 + /- 1.98 EU/ml ) compared with- the diet-alone group . In the orlistat group the reduction in LPS was correlated with the increase in adiponectin ( p orlistat group would suggest that orlistat may reduce the progression to type 2 diabetes in South Asian individuals by raising serum adiponectin . The finding that LPS levels are also reduced by orlistat and that this reduction correlates with the increase in adiponectin raises the possibility that the increase in adiponectin may be mediated via an effect on LPS levels", "Aim : To evaluate the effects of 1-year treatment with orlistat compared with placebo on different inflammatory parameters in type 2 obese diabetic patients . Material s and methods : Two hundred and fifty-four type 2 diabetic patients were r and omized to take orlistat 120 mg three times a day or placebo for 12 months . We evaluated at baseline and after 3 , 6 , 9 and 12 months : leptin , tumor necrosis factor (TNF)-α , adiponectin ( ADN ) , vaspin and high-sensitivity C-reactive protein ( HS-CRP ) , body weight , waist circumference , body mass index ( BMI ) , lipid profile , glycemic profile , fasting plasma insulin ( FPI ) and homeostasis model assessment insulin resistance index ( HOMA-IR ) . Results : Regarding inflammatory parameters , there was a significant improvement of ADN and TNF-α , and a faster decrease of leptin and HS-CRP in the orlistat group compared with the control group . We also recorded a significant reduction of body weight and BMI with orlistat , but not with placebo . A faster improvement of glycemic profile and FPI was obtained with orlistat compared with the controls . Also , there was a significant reduction of lipid profile with orlistat , not reached with placebo . Conclusions : Orlistat was more effective than placebo in ameliorating inflammatory parameters such as ADN and TNF-α , and anthropometric parameters ", "To evaluate the effects of 1-year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight , glycemic and lipid control , and inflammatory parameters in obese type 2 diabetic patients . Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus ( T2DM ) [ glycated hemoglobin ( HbA(1c ) ) > 8.0 % ] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and r and omized to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day . We evaluated the following parameters at baseline and after 3 , 6 , 9 , and 12 months : body weight , body mass index ( BMI ) , glycated hemoglobin ( HbA(1c ) ) , fasting plasma glucose ( FPG ) , postpr and ial plasma glucose ( PPG ) , fasting plasma insulin ( FPI ) , homeostasis model assessment insulin resistance index ( HOMA-IR ) , total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , triglycerides ( Tg ) , adiponectin ( ADN ) , leptin , tumor necrosis factor-α ( TNF-α ) , vaspin , and high-sensitivity C-reactive protein ( Hs-CRP ) . We observed a better decrease in body weight , glycemic profile , HOMA-IR , LDL-C , and ADN and a faster improvement in FPI , TC , Tg , leptin , TNF-α , Hs-CRP with orlistat plus L-carnitine compared to orlistat alone . We also recorded an improvement in vaspin with orlistat plus l-carnitine not reached with orlistat alone . Orlistat plus L-carnitine gave a better improvement in body weight , glycemic and lipid profile compared to orlistat alone ; furthermore , a faster and better improvement in inflammatory parameters was observed with orlistat plus L-carnitine compared to orlistat alone", "BACKGROUND Leptin is likely to be involved in the homeostasis of body weight . Insulin is suggested to regulate both short-term and long-term circulating leptin levels . The present study aims to assess the relation between insulin and leptin levels in obese humans . METHODS Some 53 obese subjects ( body mass index 35.1 + /- 3.9 kg m-2 ( mean + /- SD ) ) were prescribed a hypocaloric diet and r and omized to either a placebo or the intestinal lipase inhibitor orlistat for 2 years . Serum leptin and insulin levels were determined repeatedly during these 2 years ( 5 times in the fasting condition and twice after an oral glucose load ) . RESULTS Leptin concentrations appeared to be regulated at a specific level for each individual throughout the weight-loss period . The BMI explained 39.7 % of the total variance in leptin levels , the body-fat distribution 17.2 % , individual characteristics 30.3 % ; and the fasting serum insulin concentration 1.0 % . After a mean weight loss of 7.7 + /- 4.9 kg , the time-integrated insulin response to an oral glucose load was significantly lower but the leptin response remained unchanged . CONCLUSIONS The BMI is the main determinant of the circulating leptin concentration in obese humans . Individual characteristics seem to determine the leptin level , given the BMI . In a short-term observational study in obese humans , changes of insulin levels do not appear to be correlated to changes in leptin levels", "OBJECTIVE To investigate the effects of : I ) short- ( 8 weeks ) , II ) long-term ( 3 years ) weight loss , and III ) the degree of weight loss on circulating levels of adiponectin , high sensitive-C reactive protein ( hs-CRP ) , and fibrinogen in obese subjects . Moreover , to evaluate the effect of the lipase inhibitor , orlistat , on these parameters . DESIGN Weight loss induced in 93 obese subjects ( mean weight : 108.9+/-15.8 kg ) through 8-week very-low-energy diet ( VLED , 800 kcal/day ) followed by r and omization to orlistat or placebo together with lifestyle intervention for further 3 years . Adiponectin and hs-CRP were measured at baseline , after 8 weeks of VLED and 6 , 12 , and 36 months after the VLED by flowmetric xMAP technology ( Luminex Multi-Analyte Profiling System , Luminex Corp. , Austin , TX , USA ) . Fibrinogen was measured in a coagulation assay . RESULTS Weight loss after VLED treatment was 14.3+/-4.5 kg and after 3 years 7.7+/-8.7 kg . Orlistat-treated subjects regained 3.9 kg less than placebo-treated from the end of the VLED to 3 years ( P=0.01 ) . No differences were detected between the two groups regarding changes in adiponectin , hs-CRP , or fibrinogen . Accordingly , the groups were combined for further analyses . Serum adiponectin increased by 22 % ( P weight losses needed to be in excess of 10 % ( approximately 12 kg ) in order to increase adiponectin levels significantly . Weight loss was associated with a significant decrease in hs-CRP . Fibrinogen decreased by 12 % ( P obese subjects , weight loss was associated with an increase in serum adiponectin and a decrease in hs-CRP and plasma fibrinogen . Long-term weight loss ( 3 years ) must exceed 10 % to induce a combined significant improvement in these inflammatory markers", "OBJECTIVE Ghrelin is postulated to be an orexigenic signal that promotes weight regain after weight loss ( WL ) . However , it is not known whether this putative effect of ghrelin is sustained after weight stabilization . The objective of this study was to investigate the relationship of plasma ghrelin concentrations to active WL and weight maintenance in obese subjects . RESEARCH METHODS AND PROCEDURES This study was a r and omized clinical trial , with a 12-month follow-up period . Obese Mexican-American women matched for age and BMI were r and omized to a 12-month WL program ( n = 25 ) or no intervention ( controls , n = 23 ) . Interventions included diet , exercise , and orlistat . Body weight and fasting ghrelin , leptin , insulin , and glucose concentrations were measured at baseline and 6 and 12 months . RESULTS The WL group lost 8.5 % of body weight after 6 months and maintained the new weight for the next 6 months . Ghrelin concentrations increased significantly at 6 months but returned to baseline at 12 months . Baseline ghrelin concentrations were directly related to the degree of WL achieved after 12 months . Controls experienced no change in BMI or ghrelin levels . There were no associations between plasma ghrelin and leptin or insulin concentrations . DISCUSSION Consistent with previous results , ghrelin rises in response to WL , perhaps as a counterregulatory mechanism . However , the present results indicate that ghrelin concentrations return to baseline with sustained weight maintenance , suggesting that its effects are unlikely to regulate long-term energy balance . Baseline ghrelin concentrations are related to the degree of WL that can be achieved by active weight reduction", "BACKGROUND The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established . METHODS We enrolled in our study 10,744 overweight or obese subjects , 55 years of age or older , with preexisting cardiovascular disease , type 2 diabetes mellitus , or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events . All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week , single-blind , lead-in period , after which 9804 subjects underwent r and om assignment in a double-blind fashion to sibutramine ( 4906 subjects ) or placebo ( 4898 subjects ) . The primary end point was the time from r and omization to the first occurrence of a primary outcome event ( nonfatal myocardial infa rct ion , nonfatal stroke , resuscitation after cardiac arrest , or cardiovascular death ) . RESULTS The mean duration of treatment was 3.4 years . The mean weight loss during the lead-in period was 2.6 kg ; after r and omization , the subjects in the sibutramine group achieved and maintained further weight reduction ( mean , 1.7 kg ) . The mean blood pressure decreased in both groups , with greater reductions in the placebo group than in the sibutramine group ( mean difference , 1.2/1.4 mm Hg ) . The risk of a primary outcome event was 11.4 % in the sibutramine group as compared with 10.0 % in the placebo group ( hazard ratio , 1.16 ; 95 % confidence interval [ CI ] , 1.03 to 1.31 ; P=0.02 ) . The rates of nonfatal myocardial infa rct ion and nonfatal stroke were 4.1 % and 2.6 % in the sibutramine group and 3.2 % and 1.9 % in the placebo group , respectively ( hazard ratio for nonfatal myocardial infa rct ion , 1.28 ; 95 % CI , 1.04 to 1.57 ; P=0.02 ; hazard ratio for nonfatal stroke , 1.36 ; 95 % CI , 1.04 to 1.77 ; P=0.03 ) . The rates of cardiovascular death and death from any cause were not increased . CONCLUSIONS Subjects with preexisting cardiovascular conditions who were receiving long-term sibutramine treatment had an increased risk of nonfatal myocardial infa rct ion and nonfatal stroke but not of cardiovascular death or death from any cause . ( Funded by Abbott ; Clinical Trials.gov number , NCT00234832 .", "BACKGROUND Leptin , which has been identified as an antiobesity hormone , regulates body weight by controlling food intake and energy expenditure via the hypothalamic-pituitary-gonadal axis . It appears that leptin may be an important factor in obesity management . Orlistat , a pancreatic lipase inhibitor , could reduce fat absorption and promote weight loss due to leptin metabolism . OBJECTIVE The purpose of this study was to investigate the effects of orlistat therapy on serum leptin levels . METHODS Obese women ( body mass index [ BMI ] , 30 kg/m(2 ) ) aged 18 to 50 years were r and omly assigned to receive 12 weeks of oral treatment with diet-orlistat ( 120 mg TID ) ( DO group ) or diet-placebo ( DP group ) . During the treatment period , patients were asked to eat a balanced diet of -1200 to 1600 kcal/d . Body composition was determined by bioelectrical impedance . Serum leptin levels were measured using radioimmunoassay at baseline and at study end . RESULTS A total of 24 patients entered the study ; 14 patients ( mean [ SE ] BMI , 37.7 [ 1.1 ] kg/m(2 ) ) received orlistat and 10 patients ( mean [ SE ] BMI , 39.4 [ 1.3 ] kg/m(2 ) ) received placebo . Compared with baseline , mean percentages of loss of body weight and fat mass after 12 weeks of treatment were significant in the DO group ( 9.1 % and 14.8 % , respectively ; both P = 0.001 ) and in the DP group ( 9.5 % and 17.6 % ; both P = 0.005 ) . The between-group differences were not statistically significant . Mean ( SE ) serum leptin levels also decreased significantly after treatment in the DO group ( 16.2 [ 1.2 ] vs 9.0 [ 1.0 ] ng/mL ; P = 0.001 ) and in the DP group ( 19.3 [ 2.1 ] vs 9.7 [ 1.4 ] ng/mL ; P = 0.005 ) . The between-group difference was not statistically significant . CONCLUSIONS In this study of obese women , orlistat treatment was associated with a similar decrease in body weight , fat mass , and serum leptin levels as placebo over a 12-week period . In this regard , short-term orlistat therapy may not provide an additional effect on serum leptin levels , and reduction in leptin levels were closely related to the decrease in fat mass", "Orlistat lowers lipids and improves insulin sensitivity , but its effect on other metabolic syndrome related parameters is not known . To assess its influence on adiponectin , high sensitive C-reactive protein ( hs-CRP ) and other metabolic syndrome related parameters , this study enrolled 106 participants in a weight-reduction program and categorized them into a group of 51 who had been treated with orlistat 360 mg/day for one year and a group of 55 age and sex and body mass index ( BMI ) matched controls . The orlistat group had greater changes in BMI , % body fat ( % BF ) , waist circumference , and insulin resistance , hs-CRP , leptin and adiponectin levels after one year on the program than the controls . After adjusting for % BF and waist circumference , change of serum leptin and adiponectin levels remained significantly different . It was found that orlistat could effectively manage obesity related co-morbidities , especially insulin resistance and atherosclerosis risk . It decreases leptin and increases adiponectin independent of % BF and waist circumference . Therefore , orlistat appears to have anti-diabetic and anti-atherogenic properties and may help prevent metabolic syndrome in the overweight people", "WHAT IS KNOWN AND OBJECTIVE The behavioural approach is usually slow and not always sufficient to achieve optimal targets in weight and metabolic control in obese diabetic patients , and a pharmacological treatment is often necessary . The aim of this study was to compare the effects of orlistat and placebo on body weight , glycaemic and lipid profile and insulin resistance in patients with type 2 diabetes . METHODS Two hundred and fifty-four obese , diabetic patients were enrolled in this study and r and omized to take orlistat 360 mg or placebo for 1year . We evaluated at baseline and after 3 , 6 , 9 and 12months body weight , waist circumference ( WC ) , body mass index ( BMI ) , glycated haemoglobin ( HbA(1c ) ) , fasting plasma glucose ( FPG ) , post-pr and ial plasma glucose ( PPG ) , fasting plasma insulin ( FPI ) , homeostasis model assessment insulin resistance index ( HOMA-IR ) , lipid profile , retinol-binding protein-4 ( RBP-4 ) , resistin , visfatin and high-sensitivity C-reactive protein ( Hs-CRP ) . RESULTS AND DISCUSSION We observed a significant reduction in body weight , WC , BMI , lipid profile , RBP-4 and visfatin in the orlistat group but not in control group . Faster improvements in HbA(1c ) , PPG , FPI , HOMA-IR , resistin and Hs-CRP were recorded with orlistat than with placebo . A similar decrease in FPG was seen in the two groups . Significant predictors of change in insulin resistance ( HOMA-IR ) were RBP-4 and resistin concentration in the orlistat group ( r=-0·53 , P of orlistat on insulin resistance and markers of inflammation . Orlistat improved lipid profile and led to faster glycaemic control and insulin resistance parameters than the control , without any serious adverse event . Orlistat also improved RBP-4 and visfatin , effects not observed with placebo ", "Our study wants to evaluate the effects of one year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight , glycemic and lipid control , and insulin resistance state in type 2 diabetic patients . Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus ( T2DM ) [ glycated hemoglobin ( HbA(1c ) ) > 8.0 % ] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and r and omised to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day . We evaluated at baseline , and after 3 , 6 , 9 , and 12 months these parameters : body weight , body mass index ( BMI ) , HbA(1c ) , fasting plasma glucose ( FPG ) , post-pr and ial plasma glucose ( PPG ) , fasting plasma insulin ( FPI ) , homeostasis model assessment insulin resistance index ( HOMA-IR ) , total cholesterol ( TC ) , low density lipoprotein-cholesterol ( LDL-C ) , high density lipoprotein-cholesterol ( HDL-C ) , triglycerides ( Tg ) , retinol binding protein-4 ( RBP-4 ) , resistin , visfatin , high sensitivity-C reactive protein ( Hs-CRP ) . We observed a faster , and better decrease of body weight , HbA(1c ) , FPG , PPG , LDL-C , HOMA-IR with orlistat plus L-carnitine compared to orlistat . A faster improvement of TC , Tg , FPI , resistin , RBP-4 , visfatin , and Hs-CRP was reached with orlistat plus L-carnitine compared to orlistat . We can safely conclude that the association of orlistat plus L-carnitine was better than orlistat in improving body weight , glycemic and lipid profile , insulin resistance , and inflammatory parameters and no significant adverse events were recorded", "The aim of this study was to evaluate the effect of an oral glucose tolerance test ( OGTT ) on the level of endothelial dysfunction and vascular inflammation markers in healthy subjects ( H ) and diabetic overweight patients ( D ) . We enrolled 256 healthy subjects and 274 type 2 diabetic patients . We evaluated blood glucose ( BG ) , soluble intercellular adhesion molecule-1 ( sICAM-1 ) , interleukin-6 ( IL-6 ) , high-sensitivity C reactive protein ( hsCRP ) , soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) , soluble E-selectin ( sE-selectin ) , and tumor necrosis factor-alpha ( TNF-alpha ) at baseline and after OGTT . We observed that BG , sICAM-1 , IL-6 , hs-CRP , sVCAM-1 , sE-selectin , and TNF-alpha values were higher in D group than in H group . In a large sample of adult healthy subjects and type 2 diabetics we observed that both answer to an OGTT with a significant increase in biomarkers of systemic low- grade inflammation and endothelial dysfunction such as hsCRP , IL-6 , TNF-alpha , sICAM-1 , sVCAM-1 , and sE-selectin . Type 2 diabetics experienced , however , a more significant increase in TNF-alpha , and sE-selectin" ]

[ "Background Late infection is the second most frequent early complication after total hip arthroplasty ( THA ) and the most frequent after hemiarthroplasty . Known risk factors for infection after THA include posttraumatic osteoarthritis , previous surgery , chronic liver disease , corticoid therapy , and excessive surgical time . However , risk factors for hemiarthroplasty are not clearly established . Questions / purpose sWe therefore determined the preoperative and intraoperative risk factors for late infection ( more than 3 months after surgery ) in patients with hemiarthroplasties and THAs . Methods We retrospectively compared 47 patients with a hip arthroplasty ( 23 hemiarthroplasties , 24 total hip arthroplasties ) and late infection with 200 r and omly-selected patients with primary arthroplasty ( 100 hemiarthroplasties , 100 total hip arthroplasties ) during the same time period of time without any infection during followup . Potential risk factors were identified from medical records . Minimum followup was 12 months ( mean , 27 months ; range , 12–112 months ) for the study group and 18 months ( mean , 84 months ; range , 18–144 months ) for the control group . Results The following factors were more frequent in late infected hemiarthroplasties : female gender ; previous surgery ; obesity ( body mass index greater than 30 kg/m2 ) ; glucocorticoid and immunosuppressant treatments ; prolonged surgical time ; inadequate antibiotic prophylaxis ; prolonged wound drainage ; hematoma ; dislocation ; and cutaneous , urinary , and /or abdominal infections . The following were more frequent in infected total hip arthroplasties : posttraumatic osteoarthritis ; previous surgery ; glucocorticoids ; chronic liver disease ; alcohol and intravenous drug abuse ; prolonged surgical time ; prolonged wound drainage ; dislocation ; subsequent surgery ; and cutaneous , urinary , respiratory and abdominal infections . Diabetes did not appear to be a risk factor . Conclusions Our data suggest there are specific risk factors for infection in hemiarthroplasties . The major risk factors for late infection in hip arthroplasty must be recognized so they can be minimized or controlled if not possible to employ prophylactic measures .Level of Evidence Level III , prognostic study . See Guidelines for Authors for a complete description of levels of evidence", "Background The benefits of robotic techniques for implanting femoral components during THA are still controversial . Questions / Purpose sThe purpose of this study was to prospect ively compare the results and complications of robotic-assisted and h and -rasping stem implantation techniques . Method The minimum followup was 5 years ( mean , 67 months ; range , 60–85 months ) . One hundred forty-six primary THAs on 130 patients were included in this study . Robot-assisted primary THA was performed on 75 hips and a h and -rasping technique was used on 71 hips . Results At 2 and 3 years postoperatively , the Japanese Orthopaedic Association ( JOA ) clinical score was slightly better in the robotic-assisted group . At 5 years followup , however , the differences were not significant . Postoperative limb lengths of the robotic-milling group had significantly less variance than the h and -rasping group . At 2 years postoperatively , there was significantly more stress shielding of the proximal femur in the h and -rasping group ; this difference was more significant 5 years postoperatively . Conclusions Substantially more precise implant positioning seems to have led to less variance in limb-length ine quality and less stress shielding of the proximal femur 5 years postoperatively . Level of Evidence Level II , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence", "The ROBODOC ® system was design ed to address potential human errors in performing cementless total hip replacement . The system consists of a preoperative planning computer workstation ( called ORTHODOC ) and a five-axis robotic arm with a high speed milling device as an end effector . The combined experience of the United States Food and Drug Administration multicenter trial and the German postmarket use of the system are reported . The United States study is controlled and r and omized with 136 hip replacements performed at three centers ( 65 ROBODOC ® and 62 control ) . Followup was 1 year on 127 hip replacements and 2 years on 93 hip replacements . No differences were found in the Harris hip scores or the Short Form Health Survey outcomes question naire . Length of stay also was not different , but the surgical time and blood loss were greater in the ROBODOC ® group . This was attributed to a learning curve at each center . Radiographs were evaluated by an independent bone radiologist and showed statistically better fit and positioning of the femoral component in the ROBODOC ® group . Complications were not different , except for three cases of intraoperative femoral fracture in the control group and none in the ROBODOC ® group . The German study reports on 858 patients , 42 with bilateral hip replacements and this includes 30 revision cases for a total of 900 hip replacements . The Harris hip score rose from 43.7 to 91.5 . In these cases the surgical time declined quickly from 240 minutes for the first case to 90 minutes . No intraoperative femoral fractures occurred in 900 cases . Other complications were comparable with total hip replacements performed using conventional techniques . The ROBODOC ® system is thought to be safe and effective in producing radiographically superior implant fit and positioning while eliminating femoral fractures", "AIM Robotic assisted total hip arthroplasty remains controversial , since wider exposure of the proximal femur and placement of the leg in maximal hip adduction and external rotation using a rigid leg-holder apparatus may impair significantly the hip abductors . Consequently , it is the purpose of this study to analyse and report both clinical outcome and hip abductor function following robotic assisted versus conventional total hip arthroplasty . MATERIAL AND METHODS 36 robotic-assisted ( CASPAR , Orto-Maquet , Rastatt , Germany ) and 35 conventional cementless total hip arthroplasties were followed on average for 18 months regarding incidence of complications , Harris hip score , the scoring system according to Merle d'Aubigné and Postel , hip abductor function ( using a spring-balance ) , and incidence of Trendelenburg 's sign ( according to the Kuhfuss-classification ) . Statistical analysis was performed in case of continuous data using the t test and the Mann-Whitney test , respectively , and in case of categorical data using Fisher 's exact test and the chi-squared test , respectively . The level of significance was set as p Average duration of surgery ( CASPAR : 100.6 min ; conventional : 51.5 min ; p average loss of haemoglobin ( CASPAR : 4.5 mg/dL ; conventional : 3.3 mg/dL ; p = 0.0002 ) differed significantly , whereas the incidence of complications ( CASPAR : two dislocations , one sciatic paresis , one deep infection ; conventional : one dislocation , two fissures ) , revision rate ( CASPAR : 5.6 % ; conventional : 2.9 % ) , and incidence of heterotopic ossifications ( CASPAR : 30.6 % ; conventional : 17.1 % ) was comparable following both procedures ( p > 0.05 ) . Improvement of the Harris hip score also was comparable in both groups ( CASPAR : 40.9 to 86.1 points ; conventional : 39.5 to 88.0 points ; p = 0.21 ) , whereas improvement of the score according to Merle d'Aubigné and Postel was significantly greater following the manual procedure ( CASPAR : 10.1 to 16.0 points ; conventional : 8.3 to 16.6 points ; p regarding hip abductor function ( CASPAR : 76.1 % ; conventional : 93.8 % of the contralateral hip ; p incidence of Trendelenburg 's sign ( CASPAR : 61.1 % ; conventional : 25.7 % ; p = 0.0014 ) . CONCLUSION The significant functional impairment following robotic assisted THA should be taken critically into consideration prior to initiating such procedure", "The ROBODOC system has provided better fit and fill of the stem and less destruction of the bony architecture than with manual surgery . These benefits might affect femoral periprosthetic bone remodeling . We evaluated the effects of robotic milling in cementless total hip arthroplasty ( THA ) in a longitudinal 24-month follow-up study using dual energy X-ray absorptiometry ( DEXA ) and plain radiographs of 29 patients ( 31 hips ) after ROBODOC THA and 24 patients ( 27 hips ) after manual THA with the same stem design . To minimize the influence of other factors on bone remodeling , only female osteoarthritis patients , who had no drugs that might affect bone metabolism were enrolled . Significantly less bone loss occurred at the proximal periprosthetic areas in the ROBODOC group . In zone 1 , the decrease was 15.5 versus 29.9 % using conventional rasping ; in zone 7 , the loss was 17.0 % with ROBODOC compared to 30.5 % with conventional rasping ( p endosteal spot welds in the proximal medial portion were more pronounced in the ROBODOC group ( 48 vs. 11 % in the conventional group , p milling is effective in facilitating proximal load transfer around the femoral component and minimizing bone loss after cementless THA", "We performed a prospect i ve , r and omised controlled trial of unicompartmental knee arthroplasty comparing the performance of the Acrobot system with conventional surgery . A total of 27 patients ( 28 knees ) awaiting unicompartmental knee arthroplasty were r and omly allocated to have the operation performed conventionally or with the assistance of the Acrobot . The primary outcome measurement was the angle of tibiofemoral alignment in the coronal plane , measured by CT . Other secondary parameters were evaluated and are reported . All of the Acrobot group had tibiofemoral alignment in the coronal plane within 2 degrees of the planned position , while only 40 % of the conventional group achieved this level of accuracy . While the operations took longer , no adverse effects were noted , and there was a trend towards improvement in performance with increasing accuracy based on the Western Ontario and McMaster Universities Osteoarthritis Index and American Knee Society scores at six weeks and three months . The Acrobot device allows the surgeon to reproduce a pre-operative plan more reliably than is possible using conventional techniques which may have clinical advantages", "Abstract Restoration of femoral offset and acetabular inclination may have an effect on polyethylene ( PE ) wear in THA . We therefore assessed the effect of femoral offset and acetabular inclination ( angle ) on acetabular conventional ( not highly cross-linked ) PE wear in uncemented THA . We prospect ively followed 43 uncemented THAs for a minimum of 49 months ( mean , 64 months ; range , 49–88 months ) . Radiographs were assessed for femoral offset , acetabular inclination , and conventional PE wear . The mean ( ± st and ard deviation ) linear wear rate in all THAs was 0.14 mm/year ( ± 0.01 mm/year ) and the mean volumetric wear rate was 53.1 mm3/year ( ± 5.5 mm3/year ) . In THAs with an acetabular angle less than 45 ° , the mean wear was 0.12 mm/year ( ± 0.01 mm/year ) compared with 0.18 mm/year ( ± 0.02 mm/year ) in those with a reconstructed acetabular angle greater than 45 ° . Reproduction of a reconstructed femoral offset to within 5 mm of the native femoral offset was associated with a reduction in conventional PE wear ( 0.12 mm/year versus 0.16 mm/year ) . Careful placement of the acetabular component to ensure an acetabular angle less than 45 ° in the reconstructed hip allows for reduced conventional PE wear . Level of Evidence : Level II , prospect i ve study . See Guidelines for Authors for a complete description of levels of evidence", "Background Improper acetabular component orientation in THA has been associated with increased dislocation rates , component impingement , bearing surface wear , and a greater likelihood of revision . Therefore , any reasonable steps to improve acetabular component orientation should be considered and explored . Questions / purpose sWe therefore sought to compare THA with a robotic-assisted posterior approach with manual alignment techniques through a posterior approach , using a matched-pair controlled study design , to assess whether the use of the robot made it more likely for the acetabular cup to be positioned in the safe zones described by Lewinnek et al. and Callanan et al. Methods Between September 2008 and September 2012 , 160 THAs were performed by the senior surgeon . Sixty-two patients ( 38.8 % ) underwent THA using a conventional posterior approach , 69 ( 43.1 % ) underwent robotic-assisted THA using the posterior approach , and 29 ( 18.1 % ) underwent radiographic-guided anterior-approach THAs . From September 2008 to June 2011 , all patients were offered anterior or posterior approaches regardless of BMI and anatomy . Since introduction of the robot in June 2011 , all THAs were performed using the robotic technique through the posterior approach , unless a patient specifically requested otherwise . The radiographic cup positioning of the robotic-assisted THAs was compared with a matched-pair control group of conventional THAs performed by the same surgeon through the same posterior approach . The safe zone ( inclination , 30 ° –50 ° ; anteversion , 5 ° –25 ° ) described by Lewinnek et al. and the modified safe zone ( inclination , 30 ° –45 ° ; anteversion , 5 ° –25 ° ) of Callanan et al. were used for cup placement assessment . Matching criteria were gender , age ± 5 years , and ( BMI ) ± 7 units . After exclusions , a total of 50 THAs were included in each group . Strong interobserver and intraobserver correlations were found for all radiographic measurements ( r > 0.82 ; p the robotic-assisted THAs were within the safe zone described by Lewinnek et al. compared with 80 % ( 40/50 ) of the conventional THAs ( p = 0.001 ) . Ninety-two percent ( 46/50 ) of robotic-assisted THAs were within the modified safe zone described by Callanan et al. compared with 62 % ( 31/50 ) of conventional THAs p ( p = 0.001 ) . The odds ratios for an implanted cup out of the safe zones of Lewinnek et al. and Callanan et al. were zero and 0.142 , respectively ( 95 % CI , 0.044 , 0.457 ) . Conclusions Use of the robot allowed for improvement in placement of the cup in both safe zones , an important parameter that plays a significant role in long-term success of THA . However , whether the radiographic improvements we observed will translate into clinical benefits for patients —such as reductions in component impingement , acetabular wear , and prosthetic dislocations , or in terms of improved longevity — remains unproven . Level of Evidence Level III , therapeutic study . See the Instructions for Authors for a complete description of levels of evidence", "BACKGROUND Robotic-assisted total hip replacement has become a common method of implantation , especially in Europe . It frequently has been postulated that robotic reaming would result in an improved clinical outcome due to the better fit of the prosthesis , but that has never been demonstrated in a prospect i ve study , to our knowledge . The purpose of this study was to compare robotic-assisted implantation of a total hip replacement with conventional manual implantation . METHODS One hundred and fifty-four patients scheduled for total hip replacement were r and omly assigned to undergo either conventional manual implantation of an S-ROM prosthesis ( eighty patients ) or robotic-assisted implantation of such a prosthesis ( seventy-four patients ) . The five-axis ROBODOC was used for the robotic-assisted procedures . Preoperatively as well as at three , six , twelve , and twenty-four months after surgery , the scores according to the Harris and Merle d'Aubigné systems and the Mayo clinical score were determined . Radiographs made at these intervals were analyzed for evidence of loosening , prosthetic alignment , and heterotopic ossification . RESULTS Thirteen ( 18 % ) of the seventy-four attempted robotic implantations had to be converted to manual implantations as a result of failure of the system . The duration of the robotic procedures was longer than that of the manual procedures ( mean and st and ard deviation,107.1 + /- 29.1 compared with 82.4 + /- 23.4 minutes , p Limb-length e quality ( mean discrepancy , 0.18 + /- 0.30 compared with 0.96 + /- 0.93 cm , p varus-valgus orientation of the stem ( mean angle between the femur and the shaft of the prosthesis , 0.34 degrees + /- 0.67 degrees compared with 0.84 degrees + /- 1.23 degrees , p robotic procedures . At six months , slightly more heterotopic ossification was seen in the group treated with robotic implantation . The group treated with robotic implantation had a better Mayo clinical score at six and twelve months and a better Harris score at twelve months ; however , by twenty-four months , no difference was found between the groups with regard to any of the three scores . Dislocation was more frequent in the group treated with robotic implantation : it occurred in eleven of the sixty-one patients in that group compared with three of eighty in the other group ( p . Recurrent dislocation and pronounced limping were indications for revision surgery in eight of the sixty-one patients treated with robotic implantation compared with none of the seventy-eight ( excluding two with revision for infection ) treated with manual insertion ( p Rupture of the gluteus medius tendon was observed during all of the revision operations . CONCLUSIONS The robotic-assisted technology had advantages in terms of preoperative planning and the accuracy of the intraoperative procedure . Disadvantages were the high revision rate ; the amount of muscle damage , which we believe was responsible for the higher dislocation rate ; and the longer duration of surgery . This technology must be further developed before its widespread usage can be justified", "Total knee replacement ( TKR ) is a common procedure for treatment of severe gonarthrosis , but the outcome may be unsatisfactory due to primary malalignment of the prosthetic components . In order to improve precision and accuracy of this surgical procedure , a commercial robotic surgical system ( CASPAR ) has been adapted to assist the surgeon in the preoperative planning and intraoperative execution of TKR . So far , 70 patients with idiopathic gonarthrosis were successfully treated with a robot-assisted technique in our institution . No major adverse events related to the use of the robotic system have been observed . The mean difference between preoperatively planned and postoperatively achieved tibiofemoral alignment was 0.8 degrees ( 0 - 4.1 degrees ) in the robotic group vs. 2.6 degrees ( 0 - 7 degrees ) in a manually operated historical control group of 50 patients . A clear advantage of robot-assisted TKR seems to be the ability to execute a highly precise preoperative plan based on computed tomography ( CT ) scans . Due to better alignment of the prosthetic components and improved bone-implant fit , implant loosening is anticipated to be diminished which may be most evident in non-cemented prostheses . Current disadvantages such as the need for placement of fiducial markers , increased operating times and higher overall costs have to be resolved in the future", "Abstract Background : Recently , two topical issues in total hip arthroplasty ( THA ) have been robot-assisted surgery and use of a short stem . The purpose of this study was to evaluate the effects of robotic milling on the accuracy of short femoral stem positioning and on the short-term clinical outcome in THA using a prospect i ve , r and omized design . Methods : We r and omized 54 patients into two groups , either robotic milling group or manual rasping group . The patients were assessed clinical ly and radiographically at 8 weeks , 5 months , 12 months , and 24 months . Results : Robotic milling group had a significantly longer operation time , requiring on average 8.9 min for registration and 11.2 min for milling . On the other h and , robotic milling group showed superior results in terms of stem alignment and leg length e quality . Two intraoperative femoral fractures occurred only in manual rasping group . Harris hip scores and WOMAC scores at 24 months postoperatively were similar in both groups . No complications including stem loosening , infection , nerve palsy , or dislocation were encountered in either group during the follow-up period . Conclusions : The present study suggested that robot-assisted short stem THA could increase the accuracy of stem alignment , improve leg length e quality , and help reduce the risk of intraoperative femoral fracture as compared with manual rasping . However , the clinical outcome scores did not differ between the two groups at the time of short-term follow-up . Long-term follow-up is needed to determine whether there will be a long-term clinical relevance of robot-assisted implantation of short femoral stems in THA" ]

[ "The natural history of mitochondrial diseases is poorly understood , limiting our ability to offer prognostic advice to patients or to evaluate therapy . One major obstacle to improving our underst and ing is the lack of a clinical rating scale to monitor the extensive clinical spectrum of mitochondrial disease . In this article , the authors describe the development and validation of a practical and semiquantitative rating scale , the Newcastle Mitochondrial Disease Adult Scale .", "Objective : To develop a reliable and valid new rating scale for measuring the functional impact of muscular dystrophy . Design : Prospect i ve and longitudinal investigation . Setting : Three academic medical centres in Taiwan and the Muscular Dystrophy Association of Taiwan . Measures : The Brooke Scale , the Vignos Scale , the Barthel Index , muscular strength , contracture severity , and predicted forced vital capacity ( FVC% ) . Methods : Scale development was in three stages . In stage I , a preliminary pool of 53 items was generated from patient interviews ( n-/25 ) , literature review , existing functional rating scales and expert opinion . In stage II , these items were administered to 85 patients with muscular dystrophy . The result ing data were analysed to construct a rating scale ( the Muscular Dystrophy Functional Rating Scale , MDFRS ) that encompassed four unidimensional constructs : mobility , basic activities of daily living , arm function and impairment . In stage III , the measurement properties of this rating scale were assessed in 121 muscular dystrophy patients different from those examined with the preliminary instrument . Results : Internal consistency reliability was excellent for all domains of the final 33-item scale , with values of Cronbach ’s alpha ranging from 0.84 to 0.97 . Intraclass correlation coefficients for test-retest and inter-rater reliability were 0.99 for all domains of the MDFRS . The MDFRS showed moderate to high correlations with a range of functional rating scales measuring similar aspects and impairment parameters ( Spearman ’s rho=0.65 - 0.91 ; P floor and ceiling effects in the study sample s. Sensitivity to change was confirmed by large st and ardized response means for the MDFRS total score . Conclusions : The MDFRS is a reliable and valid disease-specific measure of functional status for patients with muscular dystrophy", "INTRODUCTION The Motor Function Measure ( MFM ) is widely used to assess severity and progression of neuromuscular diseases . Validity was established in a group of patients aged 6 - 60 years with suspected or confirmed diagnosis of neuromuscular diseases , Duchenne Muscular Dystrophy being the most frequent diagnosis in the population tested . OBJECTIVES Our aim was to check the validity of the MFM in a hospital department specialized in neuromuscular diseases in the follow-up of adult out- patients presenting a myopathy , such population being very different from the MFM validation group in terms of age and sub-groups of myopathy . METHODS One hundred patients were r and omly selected in the Reference Center for Neuromuscular Diseases of Nice ( France ) between 2005 and 2007 . Were collected : the MFM score , manual muscular testing ( MMT ) of lower and upper limb , face and spine , Brooke and Vignos scores . MFM and its three dimensions D1 ( st and ing position and transfers ) , D2 ( axial and proximal limb motor function ) and D3 ( distal motor function ) were compared to the other scores with the Spearman Correlation Coefficient and the Principal Component Analysis . RESULTS Patients were aged 18 - 78 years . The most frequent diagnoses were Steinert 's Muscular Dystrophy ( DM1 ) and Facio-ScapuloHumeral Dystrophy ( FSHD ) ( 30 % and 29 % ) . MFM was significantly correlated to all other scores except for Face MMT . However , Face MMT was correlated to D1 and D2 in DM1 patients and to D2 in FSHD patients . DISCUSSION Our results confirm the validity of the MFM in adult patients with muscular diseases . However , the MFM global score and its three dimensions D1 , D2 and D3 are variously correlated with the facial and axial muscle testing . Therefore , we recommend using separately the three dimensions D1 , D2 , D3 ( rather than the global score ) and , if more accuracy is required , the facial and axial muscle testing", "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", "STUDY OBJECTIVES The purpose was to investigate a possible relationship between different parameters of physical function , spirometric measurements , and the approaching need for mechanical ventilation . DESIGN A nonr and omized , prospect i ve , descriptive study of 11 patients with spinal muscular atrophy type II ( SMA-II ) and 14 patients with Duchenne muscular dystrophy ( DMD ) . At a home visit , the anthropometric indices of age , height , and weight were recorded , the degree of disability was scored , and measurement of the strength of eight muscle groups and spirometry was performed . The interdependence of the variables was analyzed and the intergroup differences evaluated . Eighteen months later , it was found that one of the authors ( B.J. ) , who was blind to the results of the first examination had instituted home mechanical ventilation on seven of the patients . The data were analyzed retrospectively for their predictive value as indicators of approaching ventilator dependency . RESULTS The seven patients who needed mechanical ventilation were the patients with DMD with the highest disability score ( Egen Klassifikation [ EK ] sum > 20 ) and the smallest values for FVC FVC% and the EK sum at the first examination and between the FVC% and the time until treatment with mechanical ventilation was instituted ( p = 0.023 ) . Although 7 of the 11 patients with SMA type II had FVC below 1.2 L and some of them had an EK sum score higher ( indicating more disability ) than some patients with DMD who needed mechanical ventilation , none of them required mechanical ventilation . CONCLUSION In this investigation , a combination of EK sum and FVC% provided a better indication of the approaching need for mechanical ventilation in the patients with DMD than the variables separately", "Therapeutic trials in muscular dystrophy have often been inconclusive . A protocol has been design ed which selects patients with Duchenne muscular dystrophy and permits accurate measurement of their status . An integral part of the protocol is a system for checking on the consistency of the data obtained using a computer program", "Abstract Sporadic inclusion body myositis ( s-IBM ) is an acquired inflammatory muscle disease of unknown cause . In general , s-IBM presents with slowly progressive , asymmetric weakness , and atrophy of skeletal muscle . There is a mild transitory or nil responsiveness to st and ard immunosuppressive treatment . A controlled cross-over study of ¶22 s-IBM patients over 3 months showed a partial improvement in those treated with high-dose intravenous immunoglobulin therapy ( IVIG ) versus placebo . The present study included 22 patients aged 32–75 years and with a mean duration of disease of 5.2 ± 3.6 years . They were r and omized by a double-blind , placebo-controlled , cross-over design to monthly infusions of ¶2 g/kg bodyweight IVIG or to placebo for 6 months each , followed by the alternative treatment . After 6 and 12 months the response to treatment was evaluated , using a modified Medical Research Council scale , Neuromuscular Symptom Score ( NSS ) , the patient ’s own assessment of improvement , arm outstretched time , and electromyography . No serious side effects were seen , in particular no viral infection and no major cardiac or neurological complications . Overall there was no progression of the disease in 90 % of patients , unlike that which might have been expected in untreated patients . A mild and significant improvement ( 11 % ) in clinical symptoms was found using NSS , but not with other test procedures . There was a trend to mild improvement in treated patients when using other tests . Individual responses to treatment was heterogeneous . The validity of this study may be reduced by mismatch of groups with regard to age at onset and variability in disease expression . The findings of this study largely confirm those of a previous IVIG trial . Treatment with IVIG may be mildly effective in s-IBM by preventing disease progression or inducing mild improvement . Long-term studies are needed to evaluate further the benefit of IVIG therapy in s-IBM", "A multiclinic , collaborative study has been design ed to assess the natural progression and efficacy of treatment of Duchenne muscular dystrophy . This article describes the protocol for the evaluation technique and the method used to establish within ( intraobserver ) and between ( interobserver ) reliability of the protocol evaluation procedures . St and ardized patient evaluations were used , and consistency of evaluation was monitored by a computer . The reliability of the measures was analyzed 1 ) within observers by comparing the results of each of the first three tests done by each evaluator for all patients and 2 ) between observers by comparing , at multicenter group meetings , the results of each of the four evaluators ' tests of the same patient . We have demonstrated reliability for an evaluation method that will provide an objective foundation on which to cl aim a drug or therapeutic procedure does or does not have an effect in treating Duchenne muscular dystrophy", "Case reports and open-label studies suggest that coenzyme Q(10 ) ( CoQ(10 ) ) treatment may have beneficial effects in mitochondrial disease patients ; however , controlled trials are warranted to clinical ly prove its effectiveness . Thirty patients with mitochondrial cytopathy received 1200 mg/day CoQ(10 ) for 60 days in a r and omized , double-blind , cross-over trial . Blood lactate , urinary markers of oxidative stress , body composition , activities of daily living , quality of life , forearm h and grip strength and oxygen desaturation , cycle exercise cardiorespiratory variables , and brain metabolites were measured . CoQ(10 ) treatment attenuated the rise in lactate after cycle ergometry , increased ( ∽1.93 ml ) VO(2)/kg lean mass after 5 minutes of cycling ( P 0.005 ) , and decreased gray matter choline-containing compounds ( P CoQ(10 ) treatment had minor effects on cycle exercise aerobic capacity and post-exercise lactate but did not affect other clinical ly relevant variables such as strength or resting lactate", "Fatigue in patients with mitochondrial cytopathies is associated with decreased basal and postactivity muscle phosphocreatine ( PCr ) . Creatine monohydrate supplementation has been shown to increase muscle PCr and high-intensity power output in healthy subjects . We studied the effects of creatine monohydrate administration ( 5 g PO b.i.d . x 14 days -- > 2 g PO b.i.d . x 7 days ) in 7 mitochondrial cytopathy patients using a r and omized , crossover design . Measurements included : activities of daily living ( visual analog scale ) ; ischemic isometric h and grip strength ( 1 min ) ; basal and postischemic exercise lactate ; evoked and voluntary contraction strength of the dorsiflexors ; nonischemic , isometric , dorsiflexion torque ( NIDFT , 2 min ) ; and aerobic cycle ergometry with pre- and post-lactate measurements . Creatine treatment result ed in significantly ( P h and grip strength , NIDFT , and postexercise lactate , with no changes in the other measured variables . We concluded that creatine monohydrate increased the strength of high-intensity anaerobic and aerobic type activities in patients with mitochondrial cytopathies but had no apparent effects upon lower intensity aerobic activities", "OBJECTIVE Polymyositis is a rare inflammatory muscular disease of unknown cause . Corticosteroids and immunosuppressive drugs are the first choice of therapy but are not always effective and may cause serious side effects . Many studies have shown that polyvalent intravenous immunoglobulin ( IVIG ) may be of interest for the treatment of dermatomyositis . We carried out an open , prospect i ve study to evaluate the efficacy of IVIG in subjects with polymyositis that was refractory to traditional treatments , and we evaluated the benefits of this therapy over a long-term period of followup . METHODS Thirty-five adult white patients ( 20 female , 15 male , mean age 43.5 years [ SD 16.8 ] ) with chronic , refractory polymyositis were treated with high doses of IVIG , after the patients had received the following traditional treatments : prednisone ( n = 35 ) , methotrexate ( n = 24 ) , azathioprine ( n = 13 ) , cyclophosphamide ( n = 4 ) , cyclosporine ( n = 7 ) , chlorambucil ( n = 1 ) , plasmapheresis ( n = 8) , lymphopheresis ( n = 1 ) , and total body irradiation ( n = 1 ) . There had been no changes in the patients ' treatment in the 2 months before the initiation of IVIG therapy , and doses were not increased during IVIG treatment . We used preparations of polyvalent human IVIG with increased concentrations of intact IgG. The patients received 1 gm/kg/day for 2 consecutive days per month . The mean course of treatment was 4 - 6 months . The clinical assessment involved the evaluation of proximal muscle power , muscle disability scale score , and esophageal disorders . The biochemical evaluations carried out before each treatment period were compared by Student 's t-test and nonparametric Wilcoxon test . Results were considered to be significant at P = 0.05 . RESULTS In the short-term , significant clinical improvement was noted in 25 of the 35 patients ( 71.4 % ) . Mean muscle power was estimated before and after IVIG therapy and was found to be significantly improved ( P Mean creatine kinase levels during IVIG therapy decreased significantly before the fourth IVIG perfusion ( P Side effects , usually minor , were noted in 6 patients . This benefit allowed the initial prednisone dose to be reduced by > 50 % in all patients . The mean ( + /- SD ) followup time for the 25 patients who responded favorably to IVIG treatment was 51.4 + /- 13.1 months . Twelve of these 25 patients remained in full remission following their initial course of IVIG , result ing in complete stoppage of medication in 5 patients or low doses of steroids in 7 patients . The condition of 6 patients remained improved and no other drugs were prescribed , but the patients remained dependent on IVIG infusions . Seven of the 25 patients who responded well to IVIG treatment relapsed at an average of 17.1 months ( range 4 - 23 months ) after the discontinuation of IVIG . CONCLUSION IVIG is an interesting therapy for the treatment of polymyositis , with results showing that the condition of approximately 70 % of the patients tested improved . After the discontinuation of the IVIG therapy , the efficacy remained stable in 50 % of the patients , with a followup of over 3 years" ]

[ "Astronauts experience spine deconditioning during exposure to microgravity due to the lack of axial loads on the spine . Treadmill exercise in a lower body negative pressure ( LBNP ) chamber provides axial loads on the lumbar spine . We hypothesize that daily supine LBNP exercise helps counteract lumbar spine deconditioning during 28 days of microgravity simulated by bed rest . Twelve sets of healthy , identical twins underwent 6 degrees head-down-tilt bed rest for 28 days . One subject from each set of twins was r and omly assigned to the exercise ( Ex ) group , whereas their sibling served as a nonexercise control ( Con ) . The Ex group exercised in supine posture within a LBNP chamber for 45 min/day , 6 days/wk . All subjects underwent magnetic resonance imaging of their lumbar spine before and at the end of bed rest . Lumbar spinal length increased 3.7 + /- 0.5 mm in the Con group over 28-day bed rest , whereas , in the Ex group , lumbar spinal length increased significantly less ( 2.3 + /- 0.4 mm , P = 0.01 ) . All lumbar intervertebral disk heights ( L5-S1 , L4 - 5 , L3 - 4 , L2 - 3 , and L1 - 2 ) in the Con group increased significantly over the 28-day bed rest ( P L5-S1 and L4 - 5 disk heights . Lumbar lordosis decreased significantly by 3.3 + /- 1.2 degrees during bed rest in the Con group ( P = 0.02 ) , but it did not decrease significantly in the Ex group . Our results suggest that supine LBNP treadmill exercise partially counteracts lumbar spine lengthening and deconditioning associated with simulated microgravity", "The purpose of this study was to determine whether lower body negative pressure ( LBNP ) treadmill exercise maintains lumbar spinal compressive properties , curvature , and back muscle strength after 28 days of 6 degrees head-down tilt ( HDT ) bed rest ( BR ) . We hypothesize that LBNP treadmill exercise will maintain lumbar spine compressibility , lumbar lordosis and back muscle strength after 28 days of 6 degrees HDT bed rest . Fifteen healthy identical twin pairs ( 14 women and 16 men ) participated in this study . One identical twin was r and omly assigned to the nonexercise control ( Con ) group , and their sibling was assigned to the exercise ( Ex ) group . The lumbar spine was significantly more compressible Post-BR compared with Pre-BR in the Con ( P=0.01 ) . Lumbar spine compressibility Post-BR was not significantly different compared with Pre-BR in the Ex group ( P=0.89 ) . In both the Con and Ex groups , there were no significant changes Post-BR in lumbar lordosis compared with Pre-BR . Back muscle strength significantly decreased in the Con group Post-BR ( P=0.002 ) , whereas in the Ex group back muscle strength was not significantly different from Pre-BR values . A significant increase in lumbar spine compressibility in the Con group suggests that spinal deconditioning to gravity occurs during 28-day bed rest . Changes in the mechanical properties of the lumbar spine may be an early indicator of lumbar intervertebral disk degeneration . Supine LBNP treadmill exercise provides axial loads to the lumbar spine and may prevent lumbar spine deconditioning associated with HDT bed rest", "BACKGROUND CONTEXT Loss of functional weightbearing during spaceflight or extended bed rest ( BR ) causes swelling of the lumbar intervertebral discs ( IVDs ) , elongates the spine , and increases the incidence of low back pain ( LBP ) . Effective interventions for the negative effects of unloading are critical but not yet available . PURPOSE To test the hypothesis that high-frequency , low-magnitude mechanical signals ( LMMS ) can attenuate the detrimental morphologic changes in the lumbar IVDs . STUDY DESIGN / SETTING Volunteers were subjected to 90d of BR and 7d of reambulation . While retaining this supine position , 18 r and om subjects received LMMS ( 30Hz ) for 10min/d , at peak-to-peak acceleration magnitudes of either 0.3 g ( n=12 ) or 0.5 g ( n=6 ) . The remaining subjects served as controls ( CTRs ) . PATIENT SAMPLE Eighteen males and 11 female ( 33+/-7y ) healthy subjects of astronaut age ( 35+/-7y , 18 males , 11 females ) and without a history of back pain participated in this study . OUTCOME MEASURES A combination of magnetic resonance imaging and computed tomography scans of the lumbar spine of all subjects were taken at baseline , 60d , 90d , and 7d post-BR . Back pain was self-reported . METHODS IVD morphology , spine length , and back pain were compared between CTR and LMMS subjects . RESULTS Compared with untreated CTRs , LMMS attenuated mean IVD swelling by 41 % ( p disc volume of the CTR group was still 8 % ( p LMMS group returned the disc volume to baseline levels . In contrast to BR alone , LMMS also retained disc convexity at all time points and reduced the incidence of LBP by 46 % ( p LMMS can mitigate the detrimental changes in disc morphology , which arise during nonweightbearing , and provides preliminary support for a novel means of addressing spinal deterioration both on earth and in space", "The purpose of this investigation was to study the effects of a 17-day spaceflight on the contractile properties of individual fast- and slow-twitch fibers isolated from biopsies of the fast-twitch gastrocnemius muscle of four male astronauts . Single chemically skinned fibers were studied during maximal Ca2 + -activated contractions with fiber myosin heavy chain ( MHC ) isoform expression subsequently determined by SDS gel electrophoresis . Spaceflight had no significant effect on the mean diameter or specific force of single fibers expressing type I , IIa , or IIa/IIx MHC , although a small reduction in average absolute force ( P(o ) ) was observed for the type I fibers ( 0.68 + /- 0.02 vs. 0.64 + /- 0.02 mN , P fiber diameter and P(o ) where significantly reduced for the type I and IIa fibers obtained from one astronaut and for the type IIa fibers from another astronaut . Average unloaded shortening velocity [ V(o ) , in fiber lengths (FL)/s ] was greater after the flight for both type I ( 0.60 + /- 0.03 vs. 0.76 + /- 0.02 FL/s ) and IIa fibers ( 2.33 + /- 0.25 vs. 3.10 + /- 0.16 FL/s ) . Postflight peak power of the type I and IIa fibers was significantly reduced only for the astronaut experiencing the greatest fiber atrophy and loss of P(o ) . These results demonstrate that 1 ) slow and fast gastrocnemius fibers show little atrophy and loss of P(o ) but increased V(o ) after a typical 17-day spaceflight , 2 ) there is , however , considerable intersubject variation in these responses , possibly due to intersubject differences in in-flight physical activity , and 3 ) in these four astronauts , fiber atrophy and reductions in P(o ) were less for slow and fast fibers obtained from the phasic fast-twitch gastrocnemius muscle compared with slow and fast fibers obtained from the slow antigravity soleus [ J. J. Widrick , S. K. Knuth , K. M. Norenberg , J. G. Romatowski , J. L. W. Bain , D. A. Riley , M. Karhanek , S. W. Trappe , T. A. Trappe , D. L. Costill , and R. H. Fitts . J Physiol ( Lond ) 516 : 915 - 930 , 1999 ]", "Study Design . Prospect i ve longitudinal study . Objective . To investigate , using magnetic resonance imaging ( MRI ) , the influence of bed rest on the lumbopelvic musculature . Summary of Background Data . Reduced gravitational loading and inactivity ( bed rest ) are known to result in significant change in musculoskeletal function , although little is known about its effects on specific muscles of the lumbopelvic region . Methods . Ten healthy male subjects underwent 8 weeks of bed rest with 6 months of follow-up . MRI of the lumbopelvic region was conducted at regular time-points during and after bed rest . Using uniplanar images at L4 , cross-sectional areas ( CSAs ) of the multifidus , lumbar erector spinae , quadratus lumborum , psoas , anterolateral abdominal , and rectus abdominis muscles were measured . Results . Multifidus CSA decreased by day 14 of bed rest ( F = 7.4 , P = 0.04 ) . The lumbar erector spinae and quadratus lumborum CSA showed no statistically significant difference to baseline across the time of bed rest ( P > 0.05 ) . The anterolateral abdominal , rectus abdominis , and psoas CSA all increased over this time . Psoas CSA increased by day 14 ( F = 6.9 , P = 0.047 ) and remained so until day 56 , whereas the anterolateral abdominal CSA ( F = 29.4 , P = 0.003 ) and rectus abdominis CSA ( F = 8.9 , P = 0.03 ) were not statistically larger than baseline until day 56 . On reambulation after completion of the bed rest phase , multifidus , anterolateral abdominal , and rectus abdominis CSA returned to baseline levels ( P > 0.05 ) by day 4 of follow-up , whereas psoas CSA returned to baseline level after day 28 of the follow-up period . Conclusions . Bed rest result ed in selective atrophy of the multifidus muscle . An increased CSA of the trunk flexor musculature ( increases in psoas , anterolateral abdominal , and rectus abdominis muscles ) may reflect muscle shortening or possible overactivity during bed rest . Some of the changes resemble those seen in low back pain and may in part explain the negative effects of bed rest seen in low back pain sufferers", "Study Design . R and omized controlled trial . Objective . Determine the effectiveness a resistive exercise countermeasure with whole-body vibration in relation to lumbo-pelvic muscle and spinal morphology changes during simulated spaceflight ( bed-rest ) . Summary of Background Data . Spinal lengthening , flattening of the spinal curves , increases in disc size , and muscle atrophy are commonly seen in spaceflight simulation . This may represent a risk for low back injury . Consideration of exercise counter measures against these changes is critical for success of long-term spaceflight missions . Methods . Twenty healthy male subjects underwent 8-weeks of bed-rest with 6-months follow-up and were r and omly allocated to an inactive control or countermeasure exercise group . Magnetic resonance imaging of the lumbo-pelvic region was conducted at regular time-points during and after bed-rest . Using uniplanar images at L4 , cross-sectional areas of the multifidus , lumbar erector spinae , quadratus lumborum , psoas , anterolateral abdominal , and rectus abdominis muscles were measured . Sagittal scans were used to assess lumbar spine morphology ( length , sagittal disc area and height , and intervertebral angles ) . Results . The countermeasure group exhibited less multifidus muscle atrophy ( P = 0.024 ) and its atrophy did not persist long-term as in the control group ( up to 3-months ; P Spinal lengthening ( P = 0.03 ) and increases in disc area ( P = 0.041 ) were also reduced . Significant partial correlations ( P spinal morphology and muscle cross-sectional area changes . Conclusion . The resistive vibration exercise countermeasure reduced , but did not entirely prevent , multifidus muscle atrophy and passive spinal tissue deconditioning during bed-rest . Atrophy of the multifidus muscles was persistent long-term in the inactive subjects . Future work could consider closer attention to spinal posture during exercise and optimizing exercise dose", "Study Design . A report on plenary presentations and discussion s of an expert panel and workshop ( “ Exercise as a treatment for subacute low back pain ” ) that was held at the Amsterdam Forum VIII on Low Back Pain Research in Primary Care . Objective . To highlight important issues regarding the design , conduct , and reporting of exercise trials and to provide suggestions for improvement in each domain . Summary of Background Data . Despite improvements in the method ologic quality of r and omized clinical trials on low back pain ( LBP ) , current trials on exercise therapy still show method ologic flaws in the design and reporting of studies . Methods . Important issues in the design , conduct , and reporting of exercise trials for LBP were introduced by 4 presenters , and this was followed by a group discussion among 40 attendees . Conclusions and recommendations were extracted by the workshop panelists and summarized in this paper . Results . Workshop discussion led to the following recommendations : ( 1 ) specify a theoretical framework for exercise therapy for design ing the intervention and selecting appropriate treatment efficacy measures ; ( 2 ) to overcome blinding problems in exercise trials , include sham interventions and assess the success of blinding ; ( 3 ) evaluate the role of patient-provider interactions through the use of self-report or observational measures ; ( 4 ) to assure quality of treatment , use exercise interventions that reference existing exercise guidelines ; ( 5 ) use subgroup analyses to identify subgroups of patients most likely to benefit ; ( 6 ) in reporting exercise trials , include an extensive description of the study population , a detailed exercise protocol , and some measure of patient compliance ; ( 7 ) further categorization of exercise interventions is needed , in terms of concept , mode , intensity , duration , frequency , and length ; and ( 8) trial;1 > registration and publication of detailed study protocol s may help to strengthen the evidence -based concerning exercise therapy for LBP . Conclusion . By paying proper attention to issues concerning the design and reporting of exercise protocol s when conducting future exercise trials , research may provide a stronger evidence basis for recommending or not recommending various exercise therapies for LBP" ]

[ "BACKGROUND Many PROMs used for evaluation of ankle osteoarthritis are not vali date d for this purpose . We hypothesize that frequently used PROMs have an early ceiling or floor effect . METHODS We prospect ively collected data from patients with ankle osteoarthritis between 2011 and 2013 . At baseline visit patients completed the Foot and Ankle Outcome Score , the Ankle Osteoarthritis Score , the American Orthopaedic Foot and Ankle Society scale , a visual analogue scale for pain and quality of life . Outcomes were analyzed for floor or ceiling effects . RESULTS 197 patients were included in the study . A floor effect was present for the AOFAS and VAS for pain in all groups . Floor and ceiling effect are absent for the FAOS outcome measure for all groups . CONCLUSIONS Physicians should be aware of floor or ceiling effects when evaluating treatment using patient reported outcome measures . The FAOS outcome measure lacks early ceiling or floor effects", "Responsiveness , the ability to detect meaningful clinical change , is a critical attribute of instruments used to evaluate outcomes of treatments . The authors hypothesized that self-administered symptom severity and functional status question naires are more responsive to clinical improvement after carpal tunnel release than traditional physical examination measures of strength and sensibility . Data were obtained from a r and omized clinical trial of endoscopic versus open carpal tunnel release conducted in four university medical centers . Patients were evaluated before surgery and 3 months after surgery . Seventy-four patients indicating that they were more than 80 % satisfied with the results of surgery were assumed to have clinical ly meaningful improvement and were the focus of the analysis . Evaluations included question naires assessing symptom severity , functional status , and activities of daily living as well as measurement of grip , pinch , and abductor pollicus brevis strength , and 2-point discrimination and Semmes-Weinstein pressure sensibility . Responsiveness was calculated with the st and ardized response mean ( mean change/st and ard deviation of change ) as well as the effect size ( mean change/st and ard deviation of baseline values ) . The symptom severity scale was four times as responsive , and the functional status and activities of daily living scales were twice as responsive , as the measures of strength and sensibility . Self-administered symptom severity and functional status scales are much more responsive to clinical improvement than measures of neuromuscular impairment and should serve as primary outcomes in clinical studies of therapy for carpal tunnel syndrome", "OBJECTIVES The authors evaluated the relative responsiveness to change of generic versus disease-specific and unweighted versus weighted health status measures in carpal tunnel syndrome ( CTS ) . METHODS Data were obtained from 196 subjects followed in a prospect i ve community-based cohort study in Maine who underwent carpal tunnel release ( The Maine Carpal Tunnel Syndrome Study ) . Patients were evaluated before and 6 months after surgery . The disease-specific , unweighted severity score was derived from the vali date d Carpal Tunnel Syndrome Assessment Question naire . Patients were asked to rate the importance of each symptom included in the severity score . Each severity question was weighted by its importance , creating a disease-specific weighted score . Generic instruments were the SF-36 , SF-12 , and a Quality of Life Rating Scale . Sensitivity to change was calculated with the st and ardized response mean ( SRM , mean change/st and ard deviation of change ) as well as the effect size ( ES , mean change/st and ard deviation of baseline values ) . The ability of the instruments to distinguish clinical ly important differences was assessed by correlating the changes in scores with global ratings on satisfaction and perceived improvement as external criteria . RESULTS The disease-specific weighted score ( SRM : 1.56 , ES : 1.99 ) was more responsive than the unweighted score ( SRM : 1.36 , ES : 1.57 ) . The Quality of Life Rating Scale , SF-36 , and SF-12 subscales were less sensitive to change , with st and ardized response means and effect sizes that ranged from -0.23 to 0.88 . The ability to distinguish clinical ly important differences was higher for the two disease-specific scales . The coefficients of correlation with the external criteria ranged from 0.50 to 0.56 for the unweighted score and 0.56 to 0.62 for the weighted score and were significantly stronger than the correlations between external measures and the most responsive subscale of the SF-36 ( Bodily Pain subscale , r = 0.36 ) . The SF-12 health survey performed as well as the SF-36 in term of responsiveness and ability to distinguish clinical ly important change . CONCLUSIONS Disease-specific measures were superior to generic measures in capturing clinical change after carpal tunnel release , and a weighted score was slightly more responsive than the unweighted score . The SF-12 showed comparable psychometric properties compared with the longer 36-item Short-Form Survey", "Background : The increasing use of computerized adaptive tests ( CATs ) to generate outcome measures during rehabilitation has prompted questions concerning score interpretation . Objective : The purpose of this study was to describe meaningful interpretations of functional status ( FS ) outcome measures estimated with a body part – specific CAT developed from the Lower-Extremity Functional Scale ( LEFS ) . Design : This investigation was a prospect i ve cohort study of 8,714 people who had hip impairments and were receiving physical therapy in 257 outpatient clinics in 31 states ( United States ) between January 2005 and June 2007 . Methods : Four approaches were used to clinical ly interpret outcome data . First , the st and ard error of the estimate was used to construct the 90 % confidence interval for each CAT-generated score estimate . Second , percentile ranks were applied to FS scores . Third , 2 threshold approaches were used to define individual subject – level change : statistically reliable change and clinical ly important change . The fourth approach was a functional staging method . Results : The precision of a single score was estimated from the FS score ±4 . On the basis of the score distribution , 25th , 50th , and 75th percentile ranks corresponded to intake FS scores of 40 , 48 , and 59 and discharge FS scores of 50 , 61 , and 75 , respectively . The reliable change index supported the conclusion that changes in FS scores of 7 or more units represented statistically reliable change , and receiver operating characteristic analyses supported the conclusion that changes in FS scores of 6 or more units represented minimal clinical ly important improvement . Participants were classified into 5 hierarchical levels of FS using a functional staging method . Limitations : Because this study was a secondary analysis of prospect ively collected data via a proprietary data base management company , generalizability of results may be limited to participating clinics . Conclusions : The results demonstrated how outcome measures generated from the hip LEFS CAT can be interpreted to improve clinical meaning . This finding might facilitate the use of patient-reported outcomes by clinicians during rehabilitation services", "Background : The use of patient-reported outcomes continues to exp and beyond the scope of clinical research to involve st and ard of care assessment s across orthopedic practice s. It is currently unclear how to interpret and apply this information in the daily care of patients in a foot and ankle clinic . We prospect ively examined the relationship between preoperative patient-reported outcomes ( PROMIS Physical Function , Pain Interference and Depression scores ) , determined minimal clinical important differences for these values , and assessed if these preoperative values were predictors of improvement after operative intervention . Methods : Prospect i ve collection of all consecutive patient visits to a multisurgeon tertiary foot and ankle clinic was obtained between February 2015 and April 2016 . This consisted of 16 023 unique visits across 7996 patients , with 3611 new patients . Patients undergoing elective operative intervention were identified by ICD-9 and CPT code . PROMIS physical function , pain interference , and depression scores were assessed at initial and follow-up visits . Minimum clinical ly important differences ( MCIDs ) were calculated using a distribution-based method . Receiver operating characteristic ( ROC ) curves were calculated to determine whether preoperative PROMIS scores were predictive of achieving MCID . Cutoff values for PROMIS scores that would predict achieving MCID and not achieving MCID with 95 % specificity were determined . Prognostic pre- and posttest probabilities based off these cutoffs were calculated . Patients with a minimum of 7-month follow-up ( mean 9.9 ) who completed all PROMIS domains were included , result ing in 61 patients . Results : ROC curves demonstrated that preoperative physical function scores were predictive of postoperative improvement in physical function ( area under the curve [ AUC ] 0.83 ) . Similarly , preoperative pain interference scores were predictive of postoperative pain improvement ( AUC 0.73 ) and preoperative depression scores were also predictive of postoperative depression improvement ( AUC 0.74 ) . Patients with preoperative physical function T score below 29.7 had an 83 % probability of achieving a clinical ly meaningful improvement in function as defined by MCID . Patients with preoperative physical function T score above 42 had a 94 % probability of failing to achieve MCID . Patients with preoperative pain above 67.2 had a 66 % probability of achieving MCID , whereas patients with preoperative pain below 55 had a 95 % probability of failing to achieve MCID . Patients with preoperative depression below 41.5 had a 90 % probability of failing to achieve MCID . Conclusion : Patient-reported outcomes ( PROMIS ) scores obtained preoperatively predicted improvement in foot and ankle surgery . Threshold levels in physical function , pain interference , and depression can be shared with patients as they decide whether surgery is a good option and helps place a numerical value on patient expectations . Physical function scores below 29.7 were likely to improve with surgery , whereas those patients with scores above 42 were unlikely to make gains in function . Patients with pain scores less than 55 were similarly unlikely to improve , whereas those with scores above 67 had clinical ly significant pain reduction postoperatively . Reported prognostic cutoff values help to provide guidance to both the surgeon and the patient and can aid in shared decision making for treatment . Level of Evidence : Level II , prognostic study", "The patient-reported outcomes measurement information system ( PROMIS ) physical function item bank v1 ( PPFIB ) contains 124 item response theory ( IRT ) calibrated items ( Rose et al. 2008 . J Clin Epidemiol 61:17–33).We report the psychometric properties of these items within an outpatient , orthopaedic patient population . In particular , we investigated whether a single unidimensional IRT scale can adequately define physical function of patients presenting with primarily upper or lower extremity orthopaedic complaints . We conducted a prospect i ve study at an orthopaedic outpatient clinic to collect data from 865 adult patients with all 124 PROMIS physical function items and seven demographic items . Items were evaluated by a Rasch model . Total variance ( 60.6 % ) across the 124 items was explained by a single Rasch dimension . The variance explained by the second dimension was 7.7 % , reflecting differential item functioning in the upper and lower extremity patients . The upper extremity physical function items had a pronounced ceiling effect . A single physical function dimension accounts for most of the item variance in the PPFIB , suggesting that the items are measuring predominantly one single construct . Separate subscales for lower versus upper extremities , especially with additional items at the upper trait level of the upper extremity subscale , may further enhance evaluation of physical function in orthopaedic patients", "The use of retrospectively acquired preoperative AOFAS rating scores in clinical research to assess the outcomes of elective foot and ankle surgery has not been vali date d. The data obtained utilizing this methodology may misrepresent the results and lead to spurious conclusions . This investigation compared preoperative AOFAS Ankle-Hindfoot scores obtained before and after surgery from patients who had undergone elective surgery to determine if retrospectively acquired scores match those collected prospect ively . Only two out of 47 patients ( 4 % ) recalled identical AOFAS scores . The mean difference between the preoperative scores ( preoperative score obtained after surgery minus preoperative score obtained before surgery ) was −5.3 points . Fifteen patients ( 32 % ) had preoperative scores that differed by 20 points or more . Kappa statistics found little agreement among the five elements that comprised the two preoperative scores when responses obtained before and after surgery were compared to one another . The results suggest that preoperative clinical rating scores obtained after elective surgery are a poor predictor of the patient 's preoperative condition and that studies which employ retrospectively acquired preoperative AOFAS clinical rating scores may overestimate the benefit of surgery", "Abstract Of the various methods for measuring pain the visual analogue scale seems to be the most sensitive . For assessing response to treatment a pain-relief scale has advantages over a pain scale . Pain can not be said to have been relieved unless pain or pain relief has been directly measured", "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", "The assessment of a measure of chronic pain , should be reliable , valid and sensitive to change . Our study evaluated the reliability of 3 pain scales , visual analogue scale ( VAS ) , numerical rating scale ( NRS ) and verbal rating scale ( VRS ) in literate and illiterate patients with rheumatoid arthritis ( RA ) . Patients with RA attending an outpatient rheumatology clinic were interviewed and asked to score their pain levels on the 3 pain scales . The scales were presented in r and om order , twice , before and just after a regular medical consultation . Ninety-one patients were studied ( 25 illiterate and 66 literate ) . The Pearson product moment correlation between first and second assessment was 0.937 for VAS , 0.963 for NRS and 0.901 for VRS in the literate patient group and 0.712 for VAS , 0.947 for NRS and 0.820 for VRS in the illiterate patient group . These results indicate that the NRS has the higher reliability in both groups of patients", "STUDY DESIGN Prospect i ve cohort study of 10 287 patients with foot/ankle impairments receiving outpatient physical therapy . OBJECTIVES To describe meaningful interpretations of functional status ( FS ) outcomes measures , estimated using a body-part-specific computerized adaptive test ( CAT ) . BACKGROUND Increased use of CATs to generate outcome measures in rehabilitation has stimulated questions concerning score interpretation . Identifying meaningful intra-individual change and reporting clinical interpretation of those generated outcomes are essential to advance the quality of rehabilitation practice . METHODS We performed 4 approaches to clinical ly interpret outcomes data . First , we used the st and ard error of the estimate to construct a 90 % confidence interval for each CAT estimated score . Second , we presented the percentile rank of FS scores . Third , we used 2 threshold approaches to define individual-patient-level change : statistically reliable change and clinical ly important change . Last , we illustrated a functional staging method . RESULTS Precision of a single score was estimated by an FS score of + /-4 . Based on score distribution , percentile ranks at 25th , 50th , and 75th percentiles corresponded to intake FS scores of 38 , 47 , and 57 , and discharge FS scores of 52 , 64 , and 77 , respectively . Minimal detectable change supported 7 or more FS change units out of 100 represented statistically reliable change , and ROC analyses supported 8 or more FS change units represented minimal clinical ly important improvement . Using a functional staging system , we established 5 hierarchical functional status levels . CONCLUSION CAT-generated outcome measures can be interpreted to improve clinical interpretation and to assist clinicians in using patient-reported outcomes during therapy practice" ]

[ "BACKGROUND Impaired motor development can significantly affect a child 's life and may result in an increased risk of a range of physical and psychological disorders . Active video game ( AVG ) interventions have been demonstrated to enhance motor skills in children with Developmental Coordination Disorder ( DCD ) ; however a home-based intervention has not been assessed . OBJECTIVES The primary aim of this study was to compare the changes in motor coordination between a 16 week period of AVG use , with 16 weeks of normal activities ( NAG ) . The secondary aim was to compare the child and parent perceptions of their physical performance between the AVG and NAG conditions . METHODS Twenty-one 9 - 12 year olds ( 10 males ) were confirmed to be at risk of DCD ( ⩽ 16th percentile Movement Assessment Battery for Children-2nd edition ( MABC-2 ) and ⩽ 15th percentile Developmental Coordination Disorder Question naire ( DCDQ ) ) and participated in this crossover r and omised and controlled trial . Data was collected at study entry , after the first 16 week condition and following the final 16 week condition , including ; ( 1 ) the MABC-2 , ( 2 ) three-dimensional motion analysis of single leg balance and finger-nose tasks , and ( 3 ) parent perception of physical skills . Participant perception of physical skills was collected only after the first and second conditions . RESULTS There was no significant difference between AVG and NAG for any of the primary variables including the MABC-2 , balance centre-of-mass path distance and finger-nose path distance . There was no significant intervention effect for secondary measures of motor coordination ; however the children perceived their motor skills to be significantly enhanced as a result of the AVG intervention in comparison to the period of no intervention . CONCLUSION A 16 week home based AVG intervention did not enhance motor skills in children with DCD , although they perceived their physical skills to be significantly improved . TRIAL REGISTRATION Australia and New Zeal and Clinical trials Registry ( ACTRN 12611000400965 )", "[ Purpose ] The purpose of the study was to evaluate the effects of conventional neurological treatment and a virtual reality training program on eye-h and coordination in children with cerebral palsy . [ Subjects ] Sixteen children ( 9 males , 7 females ) with spastic diplegic cerebral palsy were recruited and r and omly assigned to the conventional neurological physical therapy group ( CG ) and virtual reality training group ( VRG ) . [ Methods ] Eight children in the control group performed 45 minutes of therapeutic exercise twice a week for eight weeks . In the experimental group , the other eight children performed 30 minutes of therapeutic exercise and 15 minutes of a training program using virtual reality twice a week during the experimental period . [ Results ] After eight weeks of the training program , there were significant differences in eye-h and coordination and visual motor speed in the comparison of the virtual reality training group with the conventional neurological physical therapy group . [ Conclusion ] We conclude that a well- design ed training program using virtual reality can improve eye-h and coordination in children with cerebral palsy", "The purpose of this study was to investigate the effects of training with the Wii-balance board on balance and balance-related skills of children with poor motor performance . Twenty-nine children ( 23 boys , 6 girls ; aged 7 - 12 years ) participated in this study and were r and omly assigned to an experimental and control group . All children scored below the 16th percentile on a st and ardized test of motor ability and balance skills ( Movement Assessment Battery for children ( M-ABC-2 ) ) . Before and after a six-week Wii-intervention ( M=8h , 22 min , SD=53 min ) , the balance skills of the experimental group and control group were measured with the M-ABC-2 and the Bruininks-Oseretsky test of motor proficiency ( BOT-2 ) . Both groups improved on all tests . The M-ABC-2 and the BOT-2 total balance-scores of the experimental group improved significantly from pre to post intervention , whereas those of the control group showed no significant progress . This result ed in significant interaction-effects , favoring the experimental children . No transfer-effects of the intervention on balance-related skills were demonstrated . Our findings showed that the Wii-balance board is an effective intervention for children with poor balance control . Further development and investigation of the intervention could be directed toward the implementation of the newly acquired balance-skills in daily life", "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", "The aim of the present study was to determine the user satisfaction of the EyeToy for the training of the upper limb in children with cerebral palsy ( CP ) . User satisfaction was measured in 12 children with CP , using a postexperience question naire , primarily based on a presence question naire . In general , children with CP were satisfied with and motivated by the EyeToy training . In addition , a first evaluation study was performed to determine the effect of this training method on the upper limb function . Ten children with CP were r and omly assigned to the intervention ( mean age 11 years , 9 months ; SD 2,3 ) and the control group ( mean age 12 years , 3 months ; SD 3,2 ) . After a treatment period of 6 weeks , the intervention group completed a user satisfaction question naire . Functional outcome was measured using the Melbourne Assessment scores . Percentage scores of the Melbourne Assessment of 7 of the 10 children were the same or changed only 1 % to 2 % from baseline to followup . However , in the experimental group , two children improved more , 9 % and 13 % respectively . In conclusion , it can be said that the EyeToy is a motivational training tool for the training of children with CP and has the potential to improve upper extremity function", "BACKGROUND / PURPOSE Improvement in mobility function has been the primary goal in the rehabilitation of children with cerebral palsy . Few studies have examined the effectiveness of task-oriented strength training for children with cerebral palsy . The purpose of this study was to examine the effects of task-oriented strength training on mobility function in children with cerebral palsy . STUDY DESIGN A single-blind , r and omized controlled trial with pre-training and post-training evaluations . MATERIAL S AND METHODS Ten children with cerebral palsy ( GMFCS levels I-III ) were r and omly assigned to an experimental group ( N = 5 ) or control group ( N = 5 ) . Mobility function was assessed using the Gross Motor Function Measure ( GMFM ) and the Timed \" Up and Go \" ( TUG ) test . Participants in the control group received conventional physical therapy focused on improving walking and balance through facilitation and normalization of movement patterns . Participants in the experiment group received task-oriented strength training focused on strengthening the lower extremities and practicing functional tasks similar to those the child performs during daily activities . RESULTS After the 5-week training period there were significant improvements in the experimental group for dimension D ( p = 0.009 ) , and dimension E ( p = 0.009 ) of the GMFM . The experimental group significantly reduced the time taken to complete the TUG ( p = 0.017 ) . CONCLUSION / SIGNIFICANCE This study supports the efficacy of task-oriented strength training for improving mobility function in children with cerebral palsy . The findings demonstrate that the application of a task-oriented strength training program is linked to positive functional outcomes . The results suggest that children with cerebral palsy may benefit from a task-oriented strength training program . Further studies with a larger r and omized sample and longer post-intervention follow-up are necessary to document the long-term effects of participation in task-oriented strength training programs in the cerebral palsy population", "[ Purpose ] Motor control and muscle strength impairments are the prime reasons for motor behavior disorders in children with spastic cerebral palsy . These impairments lead to histological changes in muscle growth and the learning of motor skills . Therefore , such children experience reduced muscle force generation and decreased muscle flexibility . We investigated the effect of training with Nintendo Wii Fit games on motor performance in children with spastic cerebral palsy . [ Subjects and Methods ] Forty children with cerebral palsy spastic diplegia aged 6–10 years diagnosed with level-3 functional capabilities according to the Gross Motor Classification System ( GMFCS ) were enrolled . Participants were divided r and omly into equal groups : group ( A ) that practice d with the Nintendo Wii Fit game for at least 20 minutes/day for 12 weeks and group ( B ) that underwent no training ( control group ) . The Movement Assessment Battery for Children-2 ( mABC-2 ) was used to assess motor performance , because it mainly involves motor tasks very similar to those involved in playing Nintendo Wii Fit games , e.g. , goal -directed arm movements , balancing , and jumping . [ Results ] There were significant improvements in the subscales of the motor performance test of those who practice d with the Nintendo Wii , while the control group showed no significant changes . [ Conclusion ] Using motion interactive games in home rehabilitation is feasible for children with cerebral palsy", "INTRODUCTION This study aim ed to evaluate if use of an activity promoting computer game , used in the home ( Nintendo Wii Fit ; Nintendo Co Ltd , Japan ) , could influence balance related outcome measures in children with cerebral palsy . METHOD Eighteen children with hemiplegic or diplegic cerebral palsy were recruited for the study . A r and omised cross-over design was used with children tested at baseline , after five weeks of playing Wii Fit games and after five weeks without any intervention . Outcome measures of interest included : performance on the modified sensory organisation test , reactive balance test and rhythmic weight shift test . RESULTS No significant difference was observed between testing occasions for any of the balance measures investigated ( p > 0.05 ) . CONCLUSION Our results suggest that use of a Nintendo Wii balance board and Wii Fit software for a minimum of thirty minutes per day in the patient 's own home , over a five week period , is not effective as a balance training tool in children with cerebral palsy", "Neuromotor Task Training ( NTT ) and Nintendo Wii Fit Training ( Wii training ) are both task-based interventions used to improve performance in children with motor coordination problems . The aim of this study was to compare the efficacy of these two interventions on the motor performance , isometric strength and cardiorespiratory fitness ( aerobic and anaerobic capacity ) of children with Developmental Coordination Disorder ( DCD ) attending mainstream schools in a low-income setting . A pragmatic , quasi-experimental study design was utilized . Children between the ages of 6 - 10 years , who scored at or below the 16th percentile on the Movement Assessment Battery for Children-2 ( MABC-2 ) and whose teacher reported a functional motor problem , were allocated to either NTT ( n=37 ) or Wii training ( n=19 ) groups depending on school of attendance . The MABC-2 , a h and -held dynamometer , the Functional Strength Measure , the Muscle Power Sprint Test and the 20 m Shuttle Run Test were used to assess performance at baseline and after the intervention . The main findings show that the mean motor performance scores of both groups improved over the study period . However , significant differences in improvement were detected between groups , with the NTT group showing greater improvement in motor performance , functional strength and cardiorespiratory fitness . No improvements in isometric strength were seen in either group . The Wii training group showed significant improvement in anaerobic performance . This study provides evidence to support the use of both the Wii Training and NTT for children with DCD . However , in comparison to Wii training , the NTT approach yields superior results across measures of motor proficiency , cardiorespiratory fitness and functional strength . The decision to use either approach may be influenced by re sources and time constraints", "This quasi-experimental study compared the effect of st and ard occupational therapy ( SOT ) and virtual reality using Wii gaming technology ( VRWii ) on children with Down syndrome ( DS ) . Children ( n = 105 ) were r and omly assigned to intervention with either SOT or VRWii , while another 50 served as controls . All children were assessed with measures of sensorimotor functions . At post-intervention , the treatment groups significantly outperformed the control group on all measures . Participants in the VRWii group had a greater pre-post change on motor proficiency , visual-integrative abilities , and sensory integrative functioning . Virtual reality using Wii gaming technology demonstrated benefit in improving sensorimotor functions among children with DS . It could be used as adjuvant therapy to other proven successful rehabilitative interventions in treating children with DS", "Purpose : To evaluate the effectiveness of the Nintendo Wii compared to traditional balance therapy in improving balance , motivation , and functional ability in children undergoing acute rehabilitation after brain injury . Methods : A non-concurrent , r and omized multiple baseline single-subject research design was used with three participants . Data were analyzed by visual inspection of trend lines . Results : Daily Wii balance training was equally motivating to traditional balance therapy for two participants and more motivating for one participant . While improvements in dynamic balance were observed , the results for static balance remain inconclusive . All participants demonstrated improvements in functional ability . Conclusion : Wii balance therapy is a safe , feasible , and motivating intervention for children undergoing acute rehabilitation after an acquired brain injury . Further research to examine the effectiveness of Wii balance therapy in this population is warranted", "The aim of this article is to present a set of evidence levels , accompanied by 14 quality or rigor questions , to foster a critical review of published single‐subject research articles . In developing these guidelines , we review ed levels of evidence and quality /rigor criteria that are in wide use for group research design s , e.g. r and omized controlled trials , such as those developed by the Treatment Outcomes Committee of the American Academy for Cerebral Palsy and Developmental Medicine . We also review ed method ological articles on how to conduct and critically evaluate single‐subject research design s ( SSRDs ) . We then subjected the quality questions to interrater agreement testing and refined them until acceptable agreement was reached . We recommend that these guidelines be implemented by clinical research ers who plan to conduct single‐subject research or who incorporate SSRD studies into systematic review s , and by clinicians who aim to practise evidence ‐based medicine and who wish to critically review pediatric single‐subject research", "OBJECTIVES Physical and occupational therapists have started to use the Nintendo Wii ™ gaming system with adults and children as part of their regular treatment . Despite the growing use of the Wii and trend towards evidence -based practice , limited evidence is available on the effectiveness of virtual reality using the Wii for children with developmental delay . The purpose of this study was to determine the feasibility and preliminary effectiveness of a low-cost gaming system for young children with developmental delay . STUDY DESIGN Single-blind , r and omised controlled trial . PARTICIPANTS AND SETTING Forty children with developmental delay ( age 39 to 58 months ) who attended a segregated or integrated preschool participated in this study . All children 's parents read and signed an informed consent form approved by the institutional review board . Children were assigned at r and om to an experimental ( Wii ) group ( n=20 ) or a control group ( n=20 ) . INTERVENTION Two weekly sessions for 10 weeks using Nintendo Wii Sports ™ and Nintendo Wii Fit ™ , including balance , strength training and aerobics games . MAIN OUTCOME MEASURES Participants were evaluated 1 week before and 1 week after the programme by a blinded investigator . Primary outcomes were gait speed , timed up and go test , single leg stance test , five-times-sit-to-st and test , timed up and down stairs test , 2-minute walk test and grip strength . The Gross Motor Function Measure ( GMFM ) was used to assess gross motor skills . RESULTS The two groups were homogenous regarding all parameters at baseline . The Wii training was feasible and enjoyable for those in the experimental group . There were no adverse effects or injuries reported over 267 training sessions . Comparison of groups following the intervention indicated that the experimental group showed significant improvements compared with the control group in single leg stance test { mean difference 1.03 [ st and ard deviation ( SD ) 1.7 ] , 95 % confidence interval ( CI ) 0.2 to 1.9 ; P=0.017 } , right grip strength [ mean difference 1.11 ( SD 1.84 ) , 95 % CI 0.15 to 2.06 ; P=0.024 ] and left grip strength [ mean difference 0.90 ( SD 1.67 ) , 95 % CI 0.03 to 1.77 ; P=0.043 ] . Although changes in other outcome measures were not significant between the study groups , there were trends towards greater improvements in the experimental group compared with the control group . CONCLUSION This study supports use of the Wii as a feasible , safe and potentially effective therapeutic tool to augment the rehabilitation of young children with developmental delay . The potential application of the Wii to increase the intensity of therapy or as a rehabilitation tool in children 's homes and rural setting s is an area worthy of investigation . The promising results of this study suggest that further studies are warranted to vali date the potential benefits of a low-cost commercially available gaming system as a treatment strategy to supplement rehabilitation of children with disabilities", "BACKGROUND Children with Developmental Co-ordination Disorder ( DCD ) experience poor motor and psychosocial outcomes . Interventions are often limited within the healthcare system , and little is known about how technology might be used within schools or homes to promote the motor skills and /or psychosocial development of these children . This study aim ed to evaluate whether short , regular school-based sessions of movement experience using a commercially available home video game console ( Nintendo 's Wii Fit ) would lead to benefits in both motor and psychosocial domains in children with DCD . METHODS A r and omized crossover controlled trial of children with movement difficulties/DCD was conducted . Children were r and omly assigned to an intervention ( n = 10 ) or comparison ( n = 8) group . The intervention group spent 10 min thrice weekly for 1 month using Wii Fit during the lunch break , while the comparison group took part in their regular Jump Ahead programme . Pre- and post-intervention assessment s considered motor proficiency , self-perceived ability and satisfaction and parental assessment of emotional and behavioural problems . RESULTS Significant gains were seen in motor proficiency , the child 's perception of his/her motor ability and reported emotional well-being for many , but not all children . CONCLUSIONS This study provides preliminary evidence to support the use of the Wii Fit within therapeutic programmes for children with movement difficulties . This simple , popular intervention represents a plausible method to support children 's motor and psychosocial development . It is not possible from our data to say which children are most likely to benefit from such a programme and particularly what the dose and duration should be . Further research is required to inform across these and other questions regarding the implementation of virtual reality technologies in therapeutic services for children with movement difficulties", "Objective : To investigate whether Wii Sports Resort ™ training is effective and if any benefits are maintained . Design : R and omized , single-blind trial . Participants : Sixty-two hemiplegic children with cerebral palsy ( 6–13 years ) . Intervention : Experimental group undertook six weeks of home-based Wii Sports Resort ™ training plus usual therapy , while the control group received usual therapy . Main measures : Outcomes were coordination , strength , h and function , and carers ’ perception of h and function , measured at baseline , six , and 12 weeks by a blinded assessor . Results : There was a trend of mean difference ( MD ) for the experimental group to have more grip strength by six ( MD 4.0 N , 95 % confidence interval ( CI ) −0.8 to 8.8 , p = 0.10 ) and 12 ( MD 4.1 N , 95 % CI −2.1 to 10.3 , p = 0.19 ) weeks , and to have a higher quantity of h and function according to carers ’ perception by six ( MD 4.5 N , 95 % CI −0.7 to 9.7 , p = 0.09 ) and strengthened by 12 ( MD 6.4 , 95 % CI 0.6 to 12.3 , p = 0.03 ) weeks than the control group . There was no difference between groups in coordination and h and function by six or 12 weeks . Conclusion : Wii ™ training did not improve coordination , strength , or h and function . Beyond the intervention , carers perceived that the children used their h and s more" ]

[ "Background Selective serotonin reuptake inhibitors ( SSRIs ) are typically thought to have a delay of several weeks in the onset of their clinical effects . However , recent reports suggest they may have a much earlier therapeutic onset . A reduction in amygdala responsivity has been implicated in the therapeutic action of SSRIs . Aims To investigate the effect of a single dose of an SSRI on the amygdala response to emotional faces . Method Twenty-six healthy volunteers were r and omised to receive a single oral dose of citalopram ( 20 mg ) or placebo . Effects on the processing of facial expressions were assessed 3 h later using functional magnetic resonance imaging . Results Volunteers treated with citalopram displayed a significantly reduced amygdala response to fearful facial expressions compared with placebo . Conclusions Such an immediate effect of an SSRI on amygdala responses to threat supports the idea that antidepressants have an earlier onset of therapeutically relevant effects than conventionally thought", "BACKGROUND Patients with schizophrenia often suffer from cognitive deficits and negative symptoms that are poorly responsive to antipsychotics including clozapine . Clozapine-induced sedation can worsen cognition and impair social and occupational functioning . OBJECTIVES To evaluate the efficacy , tolerability , and safety of modafinil for negative symptoms , cognition , and wakefulness/fatigue in DSM-IV-diagnosed schizophrenia patients treated with clozapine . METHOD A double-blind , placebo-controlled , flexible-dosed 8-week pilot trial was conducted between September 2003 and September 2007 , adding modafinil up to 300 mg/d to stabilized schizophrenia out patients receiving clozapine . Psychopathology , cognition , and wakefulness/fatigue were assessed with st and ard rating scales . RESULTS Thirty-five patients were r and omly assigned to treatment with study drug and included in the analysis . Modafinil did not reduce negative symptoms or wakefulness/fatigue or improve cognition compared to placebo . Modafinil was well tolerated and did not worsen psychosis . CONCLUSIONS Results of this pilot trial do not support routine use of modafinil to treat negative symptoms , cognitive deficits , or wakefulness/fatigue in patients on clozapine . However , given our limited power to detect a treatment effect and the clear possibility of a type II error , larger trials are needed to resolve or refute a potential therapeutic effect of uncertain magnitude . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00573417", "Rationale Cognitive impairments are important determinants of functional outcome in psychosis , which are inadequately treated by antipsychotic medication . Modafinil is a wake-promoting drug that has been shown to improve attention , memory and executive function in the healthy population and in patients with schizophrenia . Objectives We aim ed to establish modafinil ’s role in the adjunctive treatment of cognitive impairments in the first episode of psychosis , a time when symptoms may be more malleable than at chronic stages of the disease . Methods Forty patients with a first episode of psychosis participated in a r and omised , double-blind , placebo-controlled crossover design study assessing the effects of a single dose of 200 mg modafinil on measures of executive functioning , memory , learning , impulsivity and attention . Results Modafinil improved verbal working memory ( d = 0.24 , p = 0.04 ) , spatial working memory errors ( d = 0.30 , p = 0.0004 ) and strategy use ( d = 0.23 , p = 0.03 ) . It also reduced discrimination errors in a task testing impulsivity . Modafinil showed no effect on impulsivity measures , sustained attention , attentional set-shifting , learning or fluency . Conclusions Modafinil selectively enhances working memory in first episode psychosis patients , which could have downstream effects on patients ’ social and occupational functioning", "Abstract : In a double-blind , parallel groups study , 60 healthy student volunteers ( 29 men and 31 women , aged 19 - 22 years ) were r and omly allocated to receive placebo , 100 or 200 mg modafinil . Two hours later , in the early evening , they completed an extensive cognitive battery . The 3 groups did not differ in self-ratings of sleepiness or tiredness before the testing session , and there were no treatment-associated changes in these or in mood ratings during the tests . Modafinil was without effect in several tests of reaction time and attention , but the 200-mg group was faster at simple color naming of dots and performed better than placebo in the Rapid Visual Information Processing test of sustained attention . Modafinil was without effect on spatial working memory , but the 100-mg group performed better in the backward part of the digit span test . Modafinil was without effect on verbal short-term memory ( story recall ) , but 100 mg improved digit span forward , and both doses improved pattern recognition , although this was accompanied by a slowing of response latency in the 200-mg group . There were no significant effects of modafinil compared with placebo in tests of long-term memory , executive function , visuospatial and constructional ability , or category fluency . These results suggest that the benefits of modafinil are not clearly dose-related , and those from 100 mg are limited to the span of immediate verbal recall and short-term visual recognition memory , which is insufficient for it to be considered as a cognitive enhancer in non-sleep-deprived individuals", "Abstract Rationale . Modafinil , a novel wake-promoting agent , has been shown to have a similar clinical profile to that of conventional stimulants such as methylpheni date . We were therefore interested in assessing whether modafinil , with its unique pharmacological mode of action , might offer similar potential as a cognitive enhancer , without the side effects commonly experienced with amphetamine-like drugs . Objectives . The main aim of this study was to evaluate the cognitive enhancing potential of this novel agent using a comprehensive battery of neuropsychological tests . Methods . Sixty healthy young adult male volunteers received either a single oral dose of placebo , or 100 mg or 200 mg modafinil prior to performing a variety of tasks design ed to test memory and attention . A r and omised double-blind , between-subjects design was used . Results . Modafinil significantly enhanced performance on tests of digit span , visual pattern recognition memory , spatial planning and stop-signal reaction time . These performance improvements were complemented by a slowing in latency on three tests : delayed matching to sample , a decision-making task and the spatial planning task . Subjects reported feeling more alert , attentive and energetic on drug . The effects were not clearly dose dependent , except for those seen with the stop-signal paradigm . In contrast to previous findings with methylpheni date , there were no significant effects of drug on spatial memory span , spatial working memory , rapid visual information processing or attentional set-shifting . Additionally , no effects on paired associates learning were identified . Conclusions . These data indicate that modafinil selectively improves neuropsychological task performance . This improvement may be attributable to an enhanced ability to inhibit pre-potent responses . This effect appears to reduce impulsive responding , suggesting that modafinil may be of benefit in the treatment of attention deficit hyperactivity disorder", "OBJECTIVE Antidepressants that inhibit the reuptake of serotonin ( SSRIs ) or norepinephrine ( SNRIs ) are effective in the treatment of disorders such as depression and anxiety . Cognitive psychological theories emphasize the importance of correcting negative biases of information processing in the nonpharmacological treatment of these disorders , but it is not known whether antidepressant drugs can directly modulate the neural processing of affective information . The present study therefore assessed the actions of repeated antidepressant administration on perception and memory for positive and negative emotional information in healthy volunteers . METHOD Forty-two male and female volunteers were r and omly assigned to 7 days of double-blind intervention with the SSRI citalopram ( 20 mg/day ) , the SNRI reboxetine ( 8 mg/day ) , or placebo . On the final day , facial expression recognition , emotion-potentiated startle response , and memory for affect-laden words were assessed . Question naires monitoring mood , hostility , and anxiety were given before and after treatment . RESULTS In the facial expression recognition task , citalopram and reboxetine reduced the identification of the negative facial expressions of anger and fear . Citalopram also abolished the increased startle response found in the context of negative affective images . Both antidepressants increased the relative recall of positive ( versus negative ) emotional material . These changes in emotional processing occurred in the absence of significant differences in ratings of mood and anxiety . However , reboxetine decreased subjective ratings of hostility and elevated energy . CONCLUSIONS Short-term administration of two different antidepressant types had similar effects on emotion-related tasks in healthy volunteers , reducing the processing of negative relative to positive emotional material . Such effects of antidepressants may ameliorate the negative biases in information processing that characterize mood and anxiety disorders . They also suggest a mechanism of action potentially compatible with cognitive theories of anxiety and depression", "Modafinil , a novel cognitive enhancer , selectively improves neuropsychological task performance in healthy volunteers and adult patients with attention deficit hyperactivity disorder ( ADHD ) . It has been argued that persistent cognitive deficits in patients with schizophrenia are responsible for the failure of many patients to rehabilitate socially even when psychotic symptoms are in remission . The present study examined the potential of modafinil as a cognitive enhancer in schizophrenia . Twenty chronic patients with a diagnosis of schizophrenia were entered into a double-blind , r and omized , placebo-controlled crossover study using a 200 mg dose of modafinil . Modafinil had some cognitive enhancing properties in schizophrenia similar to those observed in healthy adults and adult patients with ADHD . Improvement was seen on short-term verbal memory span , with trends towards improved visual memory and spatial planning . This was accompanied by slowed response latency on the spatial planning task . No effect on stop-signal performance was seen . Importantly , significant improvement in attentional set shifting was seen , despite no effect of modafinil on this task being seen in healthy volunteers or ADHD patients . Modafinil may have potential as an important therapy for cognitive impairment in patients with schizophrenia , particularly because of its beneficial effects on attentional set shifting", "Methamphetamine (MA)-dependent individuals exhibit deficits in cognition and prefrontal cortical function . Therefore , medications that improve cognition in these subjects may improve the success of therapy for their addiction , especially when cognitive behavioral therapies are used . Modafinil has been shown to improve cognitive performance in neuropsychiatric patients and healthy volunteers . We therefore conducted a r and omized , double-blind , placebo-controlled , cross-over study , using functional magnetic resonance imaging , to examine the effects of modafinil on learning and neural activity related to cognitive function in abstinent , MA-dependent , and healthy control participants . Modafinil ( 200 mg ) and placebo were administered orally ( one single dose each ) , in counterbalanced fashion , 2 h before each of two testing sessions . Under placebo conditions , MA-dependent participants showed worse learning performance than control participants . Modafinil boosted learning in MA-dependent participants , bringing them to the same performance level as control subjects ; the control group did not show changes in performance with modafinil . After controlling for performance differences , MA-dependent participants showed a greater effect of modafinil on brain activation in bilateral insula/ventrolateral prefrontal cortex and anterior cingulate cortices than control participants . The findings suggest that modafinil improves learning in MA-dependent participants , possibly by enhancing neural function in regions important for learning and cognitive control . These results suggest that modafinil may be a suitable pharmacological adjunct for enhancing the efficiency of cognitive-based therapies for MA dependence", "Changes in serotonin neurotransmission have also been implicated in the etiology and treatment of impulse control disorders , depression , and anxiety . We have investigated the effect of enhancing serotonin function on fundamental brain processes that we have proposed are abnormal in these disorders . In all , 12 male volunteers received citalopram ( 7.5 mg intravenously ) and placebo pretreatment in a single-blind crossover design before undertaking Go/No-go , Loss/No-loss , and covert ( aversive ) face emotion recognition tasks during functional magnetic resonance imaging ( fMRI ) . Blood oxygenation level dependent responses were analyzed using Statistical Parametric Mapping ( SPM2 ) . The tasks activated prefrontal and subcortical regions generally consistent with literature with lateral orbitofrontal cortex ( BA47 ) common to the three tasks . Citalopram pretreatment enhanced the right BA47 responses to the No-go condition , but attenuated this response to aversive faces . Attenuations were seen following citalopram in the medial orbitofrontal ( BA11 ) responses to the No-go and No-loss ( ie relative reward compared with Loss ) conditions . The right amygdala response to aversive faces was attenuated by citalopram . These results support the involvement of serotonin in modulating basic processes involved in psychiatric disorders but argue for a process-specific , rather than general effect . The technique of combining drug challenge with fMRI ( pharmacoMRI ) has promise for investigating human psychiatric disorders", "OBJECTIVES Modafinil has recently been approved for the treatment of shift work sleep disorder , making it potentially available for shift-working emergency physicians . The authors ' objectives were to determine whether modafinil improved cognitive performance of emergency physicians following overnight shifts and to record symptoms and subjective evaluations of the effect of modafinil on the participants . METHODS This was a r and omized , double-blind , placebo-controlled crossover study that followed CONSORT guidelines . Participants were assigned to one of two study groups , with study sessions occurring at least seven weeks apart , and received either modafinil or placebo depending on their r and om allocation . Testing after night shifts included a coding task and an AX version of the Continuous Performance Task , both of which test cognitive function . Participants also completed visual analog scales for three subjective outcomes , and symptoms were elicited . RESULTS Modafinil facilitated performance on long interstimulus-interval AX trials ( F [ 1 , 23 ] = 6.65 , p = 0.1 ) and marginally reduced errors on AY trials in the Continuous Performance Task ( F [ 1 , 23 ] = 3.59 , p = 0.07 ) , suggesting facilitation of sustained attention , cognitive control , and working memory . Additionally , modafinil , compared with placebo , facilitated performance on the coding task at the first session . Subjective data from visual analog scales confirmed that modafinil increased perceived alertness during the simulated patient care sessions but worsened sleep onset when opportunities for sleep arose . CONCLUSIONS Modafinil increased certain aspects of cognitive function and subjectively improved participants ' ability to attend post-night-shift didactic sessions but made it more difficult for participants to fall asleep when opportunities for sleep arose", "Objectives : A modafinil daily dosing strategy promotes wakefulness in narcolepsy patients experiencing excessive daytime sleepiness ; however , some patients may continue to experience late-day sleepiness . Excessive sleepiness in narcolepsy is associated with cognitive impairment . Modafinil has improved executive function in other models of excessive sleepiness . This study evaluated the effects of once-daily vs. split doses of modafinil on wakefulness and of combined doses on executive function in narcolepsy patients experiencing late-day sleepiness despite satisfactory modafinil treatment earlier in the day . Methods : After a 2-week washout , 24 patients received 3 weeks of double-blind treatment with modafinil 400-mg once daily ( 7 AM ) plus placebo ( noon ) or modafinil 600-mg split dose ( 400 mg , 7 AM ; 200 mg , noon ) . Assessment s included a Maintenance of Wakefulness Test ( MWT ) for individual regimens and the Wisconsin Card Sort Test ( WCST ) for treatments combined . Results : Modafinil 600-mg split dose was significantly more effective than modafinil 400-mg once daily in improving late-day MWT scores ( 5 PM–7 PM ; P total number of errors and 5.9 ± 1.9 in total percent of errors ( P tolerated ; adverse events included headache ( n = 1 ) , emotional lability ( n = 1 ) , bronchitis ( n = 1 ) , and accidental injury ( n = 2 ) , with no reports of insomnia . Conclusions : For patients with residual late-day sleepiness associated with narcolepsy , an additional 200-mg dose of modafinil taken at midday was effective in sustaining wakefulness throughout the entire waking day . Treatment with modafinil also significantly improved executive function", "OBJECTIVE Negative symptoms are core features of schizophrenia that are functionally debilitating , associated with poor outcomes , and resistant to existing pharmacotherapies . We performed a r and omized , double-blind , placebo-controlled study of modafinil , a medication approved for the treatment of excessive daytime sleepiness , to explore its efficacy as an adjunctive therapy for negative symptoms in schizophrenia . METHOD Twenty subjects with DSM-IV schizophrenia or schizoaffective disorder were r and omly assigned to double-blind treatment with modafinil or placebo for 8 weeks . The study ran from March 2002 through March 2006 . Outcome measures included the Scale for the Assessment of Negative Symptoms ( SANS ) , Brief Psychiatric Rating Scale ( BPRS ) , Clinical Global Impressions ( CGI ) scale , Quality of Life Interview , neurocognitive assessment s ( California Verbal Learning Test , De grade d Performance-Continuous Performance Test , Trail-Making Test B ) , and somatic measures ( sleep , weight , side effects ) . RESULTS Modafinil treatment was associated with a greater rate ( CGI-Improvement [ CGI-I ] score global negative symptoms as measured by the total SANS or SANS individual global items . Modafinil did not significantly worsen psycho-pathology ( according to the BPRS ) , compared with placebo , and was well tolerated . CONCLUSIONS Although no effect on negative symptoms was found , adjunctive therapy with modafinil may result in global improvements in patients with schizophrenia who have prominent negative symptoms", "Modafinil differs from other arousal-enhancing agents in chemical structure , neurochemical profile , and behavioral effects . Most functional neuroimaging studies to date examined the effect of modafinil only on information processing underlying executive cognition , but cognitive enhancers in general have been shown to have pronounced effects on emotional behavior , too . We examined the effect of modafinil on neural circuits underlying affective processing and cognitive functions . Healthy volunteers were enrolled in this double-blinded placebo-controlled trial ( 100 mg/day for 7 days ) . They underwent BOLD fMRI while performing an emotion information-processing task that activates the amygdala and two prefrontally dependent cognitive tasks — a working memory ( WM ) task and a variable attentional control ( VAC ) task . A clinical assessment that included measurement of blood pressure , heart rate , the Hamilton anxiety scale , and the profile of mood state ( POMS ) question naire was also performed on each test day . BOLD fMRI revealed significantly decreased amygdala reactivity to fearful stimuli on modafinil compared with the placebo condition . During executive cognition tasks , a WM task and a VAC task , modafinil reduced BOLD signal in the prefrontal cortex and anterior cingulate . Although not statistically significant , there were trends for reduced anxiety , for decreased fatigue-inertia and increased vigor-activity , as well as decreased anger-hostility on modafinil . Modafinil in low doses has a unique physiologic profile compared with stimulant drugs : it enhances the efficiency of prefrontal cortical cognitive information processing , while dampening reactivity to threatening stimuli in the amygdala , a brain region implicated in anxiety", "This study was undertaken to investigate regional metabolic abnormalities and to determine the effects of modafinil in narcoleptics on cerebral glucose metabolism using [ (18)F ] fluorodeoxyglucose positron emission tomography ( FDG PET ) . Eight narcoleptic patients participated in the study . Two [ (18)F ] FDG PET scans were obtained before and after 2 weeks of modafinil treatment . To identify the effect of modafinil on regional cerebral abnormalities in narcoleptics , pre- and post-treatment PET scans were compared using paired t-statistics with voxel-wised manner . In narcolepsy patients , significant decreases in cerebral glucose metabolism were observed in the midbrain and upper pons , bilateral hypothalamus , posterior thalamus , hippocampus and right parahippocampus as compared with healthy subjects . After treatment , a significant increase in glucose metabolism in the left hippocampus was found in comparison with pre-treatment scan . This study demonstrated that modafinil activates the hippocampus which receives the afferents from hypothalamus , the center of sleep-wake rhythm", "OBJECTIVE We evaluated the effects of modafinil , a wake-promoting agent , on patient functioning , health-related quality of life , and nighttime and daytime sleep in patients with excessive sleepiness associated with shift work sleep disorder ( SWSD ) . METHOD A 12-week , r and omized , double-blind , placebo-controlled study was performed at 31 centers in the United States between February 2001 and March 2002 . Adults ( N = 278 ) with excessive sleepiness associated with chronic SWSD ( International Classification of Sleep Disorders criteria ) were r and omly assigned to receive modafinil 200 or 300 mg or placebo , 30 to 60 minutes before each night shift . Effects on patient functioning and quality of life were assessed using the Functional Outcomes of Sleep Question naire ( FOSQ ) and the 36-item Short Form Health Survey ( SF-36 ) , respectively . Daily patient diaries were used as a sleep log . RESULTS Modafinil 300 mg significantly improved mean FOSQ total score relative to placebo ( 2.3-point increase from baseline vs. 1.6 for placebo ; p mean SF-36 mental component scores relative to placebo ( mean changes from baseline of 3.2 , 3.7 , and 0.7 points in the modafinil 300-mg , modafinil 200-mg , and placebo groups , respectively ; p ) . Modafinil did not adversely affect sleep when sleep was desired or caffeine use . Modafinil was well tolerated . Headache ( 21.5 % ) and nausea ( 12.4 % ) were the most common adverse events in modafinil-treated patients . Differences between modafinil and placebo for vital sign measurements , physical examination findings , or electrocardiography results were not clinical ly meaningful . CONCLUSIONS Modafinil significantly improves functioning and quality of life in patients with SWSD . Modafinil is an effective treatment for excessive sleepiness associated with SWSD", "Common complaints among shift workers are sleep disruptions and increased sleepiness while working , which may contribute to shift workers being more susceptible to diminished performance and work-related accidents . The purpose of this double-blind , within-participant study was to examine the effects of the alerting agent modafinil on cognitive/psychomotor performance , mood , and measures of sleep during simulated shift work . In all , 11 participants completed this 23-day residential laboratory study . They received a single oral modafinil dose ( 0 , 200 , 400 mg ) 1 h after waking for three consecutive days under two shift conditions : day shift and night shift . Shifts alternated three times during the study , and shift conditions were separated by an ‘ off ’ day . When participants received placebo , cognitive performance and subjective ratings of mood were disrupted during the night shift , relative to the day shift . Objective and subjective measures of sleep were also disrupted , but to a lesser extent . Modafinil reversed disruptions in cognitive performance and mood during the night shift . While modafinil produced few effects on sleep measures during the night shift , the largest dose produced several sleep alterations during the day shift . These data demonstrate that abrupt shift changes produced cognitive performance impairments and mood disruptions during night shift work . Therapeutic doses of modafinil attenuated night-shift-associated disruptions , but the larger dose produced some sleep impairments when administered during day-shift work", "Deficits in the ability to perceive facial and vocal emotion expression are common in schizophrenia . However , relatively little is known about how such deficits might affect functional outcomes . This prospect i ve study examined cross-sectional and longitudinal relationships between perception of emotion and aspects of psychosocial functioning , including family relationships , social relationships , work functioning , and independent living/self-care in 94 clinical ly stabilized schizophrenia out patients from five community-based rehabilitation programs . Emotion perception ( facial emotion , voice emotion , and affect perception ) and psychosocial outcome ( Strauss and Carpenter Outcome Scale and Role Functioning Scale ) were assessed at baseline and after 12 months of psychosocial rehabilitation . Significant associations were found between perception of emotion and work functioning/independent living both cross-sectionally and prospect ively over the 12 months . Causal explanatory models suggested that perception of emotion might cause work functioning/independent living outcome over 1 year . The results remained significant when conceptual disorganization was statistically controlled . We did not find differences between men and women in the correlations between emotion perception and work functioning/independent living . Associations between social functioning/family relationships and perception of emotion were not significant . These findings suggest that emotion processing is a key determinant of work functioning/independent living for individuals with serious mental illness", "BACKGROUND Schizophrenia is associated with widespread cognitive deficits that have an impact on social function . Modafinil promotes wakefulness and is reported to enhance cognition . AIMS To study the acute effects of modafinil administration upon brain activity and cognitive performance in people with chronic schizophrenia . METHOD In a r and omised double-blind placebo-controlled crossover design , 19 patients received either modafinil ( 100 mg ) or placebo prior to undertaking a working memory task with functional magnetic resonance imaging . RESULTS Seventeen patients completed the study and another underwent acute relapse 4 days post-drug . Modafinil administration was associated with significantly greater activation in the anterior cingulate cortex during the working memory task . The anterior cingulate cortex signal correlated with cognitive performance , although only a subset of patients exhibited ' enhancement ' . CONCLUSIONS Modafinil modulates anterior cingulate cortex function in chronic schizophrenia but its beneficial cognitive effects may be restricted to a subset of patients requiring further characterisation", "RationalIn recent years , evidence suggests that modafinil may be useful for certain symptom domains of schizophrenia , especially for the negative and cognitive symptoms . However , the results are not consistent . Objective This study was design ed to investigate the effect of modafinil added to risperidone in patients with chronic schizophrenia in a double blind and r and omized clinical trial . Methods Participants were in patients males ( 35 ) and females ( 11 ) , ages 20–49 years at two teaching psychiatric hospital in Iran . All patients were in the active phase of the illness and met DSM-IV-TR criteria for schizophrenia . Patients were allocated in a r and om fashion 23 patients to risperidone 6 mg/day plus modafinil 200 mg/day and 23 patients to risperidone 6 mg/day plus placebo . The principal measure of outcome was the positive and negative syndrome scale ( PANSS ) . Patients were assessed by a psychiatrist at baseline and after 2 , 4 , 6 and 8 weeks after the start of medication . Results The modafinil group had significantly greater improvement in the negative symptoms as well as PANSS total scores over the 8-week trial . Therapy with 200 mg/day of modafinil was well tolerated and no clinical ly important side effects were observed . Conclusion The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms . Nevertheless , results of larger-controlled trials are needed before recommendation for broad clinical application can be made . This trial is registered with the Iranian Clinical Trials Registry ( I RCT 138903131556N16 )", "STUDY OBJECTIVES To assess the effect of 200 mg of modafinil compared to placebo on alertness , neurobehavioral performance , and executive function during 4 consecutive simulated night shifts . DESIGN Double-blind , r and omized , parallel groups . SETTING Sleep research facility . PARTICIPANTS 32 male and female volunteers between the ages of 18 and 55 years . INTERVENTIONS 200 mg of modafinil or placebo given nightly on the 4 consecutive simulated night shifts . MEASUREMENTS AND RESULTS Subjects were r and omly assigned to 1 of the 2 treatment conditions , following medical , psychiatric , and polysomnographic screening . On 4 consecutive nights , subjects took study drug at 2200 , and then from about 2300 to 0730 participated in a simulated night shift that included the Maintenance of Wakefulness Test , Psychomotor Vigilance Test , Digit Symbol Substitution Test , measures of subjective alertness , and multiple executive-function measures . At 0800 , daytime sleep periods were recorded polysomnographically for 6 to 8 hours . Alertness -- as measured by the MWT , vigilance and reaction time as indexed by Psychomotor Vigilance Test lapses , and slowest 10 % of reaction times-- and 3 executive-function tasks showed significant enhancement with modafinil versus placebo . Subjective sleepiness at night and some performance measures did not show consistent treatment differences . Daytime sleep showed minimal differences between conditions . CONCLUSIONS The physiologic sleepiness and neurobehavioral deficits that occurred during the hours of a typical night shift were clearly attenuated by modafinil . Modafinil also had beneficial effects on some measures of executive function", "STUDY OBJECTIVES Sleep loss consistently impairs performance on measures of alertness , vigilance , and response speed , but its effects on higher-order executive functions are not well delineated . Similarly , whereas deficits in arousal and vigilance can be temporarily countered by the use of several different stimulant medications , it is not clear how these compounds affect complex cognitive processes in sleep-deprived individuals . DESIGN We evaluated the effects of double-blind administration of 3 stimulant medications or placebo on the ability to appreciate humor in visual ( cartoons ) or verbal ( headlines ) stimuli presented on a computer screen following 49.5 hours of sleep deprivation . SETTING In-residence sleep-laboratory facility at the Walter Reed Army Institute of Research . PARTICIPANTS Fifty-four healthy adults ( 29 men , 24 women ) , ranging in age from 18 to 36 years . INTERVENTIONS Each participant was r and omly assigned to 1 of 3 stimulant medication groups , including caffeine , 600 mg , n = 12 ; modafinil , 400 mg , n = 11 ; dextroamphetamine , 20 mg , n = 16 ; or placebo , n = 14 . MEASUREMENTS AND RESULTS Humor appreciation for cartoon stimuli was enhanced by modafinil relative to both placebo and caffeine , but there was no effect of any stimulant medication on the appreciation of verbal humor during sleep loss . In contrast , all 3 stimulants improved psychomotor response speed , whereas only caffeine and dextroamphetamine improved ratings of subjective sleepiness . CONCLUSIONS Findings suggest that , despite similar alerting and vigilance-promoting effects , these 3 compounds have significantly different effects on those highly complex cognitive abilities mediated by the pre-frontal cortex", "Introduction In addition to excessive sleepiness , patients with narcolepsy often have significant fatigue , depressed mood , and decreased quality of life . Objective To determine whether treatment with modafinil for excessive sleepiness improves fatigue , mood , and health-related quality of life ( HRQOL ) in patients with narcolepsy . Material s and methods Out patients with narcolepsy underwent a 14-day washout of psychostimulants and then were enrolled in this 6-week , open-label , multicenter study . Patients received modafinil starting at 200 mg once daily for week 1 , and then 200 or 400 mg daily for weeks 2 through 6 . Efficacy was evaluated using the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) and the Profile of Mood States ( POMS ) . Safety was assessed by monitoring adverse events ( AE ) . Results At baseline , 151 patients had moderate to severe excessive sleepiness ( mean Epworth Sleepiness Scale score=17.8±4.4 ) . Most patients ( ≥70 % of 123 who completed the study ) received 400 mg modafinil once daily during weeks 2 through 6 . Modafinil significantly improved HRQOL , based on SF-36 measures of mental and physical component summary scores and subdomain scores of role-physical , social functioning , and vitality ( each P ) . Modafinil treatment was also associated with significantly reduced fatigue and significantly improved vigor and cognition as assessed by the POMS ( each P with modafinil treatment were headache , nausea , and insomnia ; most AE were mild or moderate in nature . Only seven patients ( 5 % ) withdrew from the study because of AE . Conclusion In narcolepsy patients who were switched from psychostimulants , modafinil therapy improved HRQOL and subjective feelings of vigor and cognitive functioning and reduced fatigue ", "Avolition affects quality of life in chronic schizophrenia . We investigated the effect of modafinil upon unconstrained motor activity in 18 male patients . In a r and omised crossover design study , wrist-worn actigraphic monitors were used to objective ly record motor activity over a 20 h period . Patients ' total activity was significantly greater when given the drug . These data suggest that modafinil increases quantifiable motor behaviour in schizophrenia and may have an impact on avolition", "Abstract . Rationale : The performance and alertness effects of modafinil were evaluated to determine whether modafinil should replace caffeine for restoring performance and alertness during total sleep deprivation in otherwise healthy adults . Objectives : Study objectives were to determine ( a ) the relative efficacy of three doses of modafinil versus an active control dose of caffeine 600 mg ; ( b ) whether modafinil effects are dose-dependent ; and ( c ) the extent to which both agents maintain performance and alertness during the circadian trough . Methods : Fifty healthy young adults remained awake for 54.5 h ( from 6:30 a.m. day 1 to 1:00 p.m. on day 3 ) and performance and alertness tests were administered bi-hourly from 8:00 a.m. day 1 until 10:00 p.m. day 2 . At 11:55 p.m. on day 2 ( after 41.5 h awake ) , subjects received double blind administration of one of five drug doses : placebo ; modafinil 100 , 200 , or 400 mg ; or caffeine 600 mg ( n=10 per group ) , followed by hourly testing from midnight through 12:00 p.m. on day 3 . Results : Performance and alertness were significantly improved by modafinil 200 and 400 mg relative to placebo , and effects were comparable to those obtained with caffeine 600 mg . Although a trend toward better performance at higher modafinil doses suggested a dose-dependent effect , differences between modafinil doses were not significant . Performance enhancing effects were especially salient during the circadian nadir ( 6:00 a.m. through 10:00 a.m. ) . Few instances of adverse subjective side effects ( nausea , heart pounding ) were reported . Conclusions : Like caffeine , modafinil maintained performance and alertness during the early morning hours , when the combined effects of sleep loss and the circadian trough of performance and alertness trough were manifest . Thus , equivalent performance- and alertness-enhancing effects were obtained with drugs possessing different mechanisms of action . However , modafinil does not appear to offer advantages over caffeine ( which is more readily available and less expensive ) for improving performance and alertness during sleep loss in otherwise normal , healthy adults", "OBJECTIVE Individuals who are methamphetamine dependent exhibit higher rates of cognitive dysfunction than healthy people who do not use methamphetamine , and this dysfunction may have a negative effect on the success of behavioral treatments for the disorder . Therefore , a medication that improves cognition , such as modafinil ( Provigil ) , may serve as a useful adjunct to behavioral treatments for methamphetamine dependence . Although cognitive-enhancing effects of modafinil have been reported in several population s , little is known about the effects of modafinil in methamphetamine-dependent individuals . We thus sought to evaluate the effects of modafinil on the cognitive performance of methamphetamine-dependent and healthy individuals . METHOD Seventeen healthy subjects and 24 methamphetamine- dependent subjects participated in this r and omized , double-blind , placebo-controlled , crossover study . Effects of modafinil ( 200 mg , single oral dose ) were assessed on participants ' performance on tests of inhibitory control , working memory , and processing speed/attention . RESULTS Across subjects , modafinil improved performance on a test of sustained attention , with no significant improvement on any other cognitive tests . However , within the methamphetamine-dependent group only , participants with a high baseline frequency of methamphetamine use demonstrated a greater effect of modafinil on tests of inhibitory control and processing speed than those participants with low baseline use of methamphetamine . CONCLUSIONS Although modafinil produced limited effects across all participants , methamphetamine-dependent participants with a high baseline use of methamphetamine demonstrated significant cognitive improvement on modafinil relative to those with low baseline methamphetamine use . These results add to the findings from a clinical trial that suggested that modafinil may be particularly useful in methamphetamine-dependent subjects who use the drug frequently", "Patients with schizophrenia experience cognitive impairments associated with hypofunctioning of the frontal cortex . Modafinil , a novel wake-promoting agent , works through the sleep – wake centers of the brain to activate the cortex . This 4-week , open-label , pilot study evaluated adjunct modafinil in patients with schizophrenia or schizoaffective disorder . Eleven patients received once-daily oral doses of modafinil ( 100 mg/day , days 1–14 ; 100 or 200 mg/day , days 15–28 ) in addition to antipsychotic therapy . Modafinil significantly improved patients ' global functioning as assessed by a blinded clinician ( week 2 , P = 0.026 ; week 4 , P = 0.012 ) and the investigator ( week 3 , P = 0.035 ) . Modafinil significantly improved overall clinical condition , with 64 % and 82 % of patients rated as clinical ly improved at week 4 by a blinded clinician and the investigator respectively . Eighty-nine percent of patients considered themselves to be clinical ly improved . Modafinil significantly improved fatigue ( P = 0.025 , week 3 ) and tended to improve cognitive functioning scores . Control of positive symptoms was well maintained . Treatment-emergent adverse events included dry mouth ( n = 2 ) and hallucinations ( n = 2 ) . One patient discontinued the study because of hallucinations that were considered to be possibly related to inadequate antipsychotic therapy . Although preliminary , these results suggest modafinil may be an effective and well-tolerated adjunct treatment that improves global functioning and clinical condition , and reduces fatigue in patients with schizophrenia or schizoaffective disorder . Additional controlled studies are warranted", "Modafinil is a selective wakefulness-promoting agent with beneficial effects in narcolepsy and conditions of sleep deprivation . In a double-blind study we examined its effects in 30 healthy , non sleep-deprived students ( 19 men and 11 women , aged 19 - 23 years ) , who were r and omly allocated to placebo , 100 or 200 mg modafinil and 3 h later completed 100 mm visual analogue scales relating to mood and bodily symptoms , before and after an extensive battery of cognitive tests ( pen and paper and CANTAB ) . There were no significant differences between the three treatment groups on any of the cognitive tests used in this study . There was a significant post-treatment change in the factor measuring ' somatic anxiety ' and in individual ratings of ' shaking ' , ' palpitations ' , ' dizziness ' , ' restlessness ' , ' muscular tension ' , ' physical tiredness ' and ' irritability ' , which was mainly due to significantly higher ratings of somatic anxiety in the 100 mg group compared with the other two groups . Further changes in mood were revealed after the stress of cognitive testing , with the 100 mg group showing greater increases in the ' psychological anxiety ' and the ' aggressive mood ' factors ( as measured from the Bond and Lader scales )", "Cognitive abilities such as vigilance , attention , memory , and executive functioning can be de grade d significantly following extended periods of wakefulness . Although much evidence suggests that sleep-loss induced deficits in alertness and vigilance can be reversed or mitigated by stimulants such as caffeine , it is not clear how these compounds may affect other higher level cognitive processes such as emotional perception and judgment . Following 47 h of sleep deprivation , the study examined the effect of three stimulant medications ( modafinil 400 mg , dextroamphetamine 20 mg , caffeine 600 mg ) or placebo on the ability of 54 healthy participants to discriminate and label simple emotional expressions versus complex affect blends ( created by morphing photographs of two different affective facial expressions ) . For simple affective faces , neither sleep loss nor stimulant medications made any difference on the accuracy of judgments . In contrast , for complex emotion blends , all three stimulant medications significantly improved the ability to discriminate subtle aspects of emotion correctly relative to placebo , but did not differ from one another . These findings suggest that all three stimulant medications are effective at restoring some aspects of subtle affective perception", "To investigate the effects of a wake-promoting drug , modafinil on regional cerebral blood flow ( rCBF ) in healthy volunteers , we performed (99m)Tc-ethylcysteinate dimer single photon emission computed tomography ( SPECT ) before and after modafinil or placebo administration . Twenty-one healthy subjects received single doses of 400 mg modafinil or placebo in a double blind r and omized crossover study design . Administrations of modafinil or placebo in a subject were separated by a 2-week washout . Brain SPECT was performed twice before and 3 h after modafinil or placebo administration . For statistical parametric mapping analysis , all SPECT images were spatially normalized to the st and ard SPECT template and then smoothed using a 12-mm full width at half-maximum Gaussian kernel . The paired t-test was used to compare pre- versus post-modafinil and pre- versus post-placebo SPECT images . Differences in rCBF between post-modafinil and post-placebo conditions were also tested . Modafinil decreased Epworth and Stanford sleepiness scales whereas placebo did not . The post-modafinil condition was associated with increased rCBF in bilateral thalami and dorsal pons , whereas the post-placebo condition showed increased rCBF in a smaller area of the dorsal pons when compared with the drug naïve baseline condition . Compared with the post-placebo condition , the post-modafinil condition showed higher rCBF in bilateral frontopolar , orbitofrontal , superior frontal , middle frontal gyri , short insular gyri , left cingulate gyrus , left middle/inferior temporal gyri , left parahippocampal gyrus , and left pons . In healthy volunteers , modafinil increased wakefulness and rCBF in the arousal-related systems and in brain areas related to emotion and executive function", "Objectives : To investigate the effect of modafinil 200 mg on the performance of a cohort of healthy male doctors after 1 night of supervised sleep deprivation . Summary Background Data : Sleep-deprived and fatigued doctors pose a safety risk to themselves and their patients . Yet , because of the around-the-clock nature of medical practice , doctors frequently care for patients after periods of extended wakefulness or during circadian troughs . Studies suggest that a group of substances may be capable of safely and effectively reversing the effects of fatigue . However , little work has been done to investigate their role within our profession . Methods : We conducted a parallel , double-blind , r and omized , and placebo-controlled study to investigate the effect of pharmacological enhancement on performance doctors . Thirty-nine healthy male resident doctors received either lactose placebo ( n = 19 ) or modafinil 200 mg ( n = 20 ) after 1 night of sleep deprivation . A selection of CANTAB neuropsychological tests was used to assess higher cognitive function . Clinical psychomotor performance was assessed using the Minimally Invasive Surgical Trainer Virtual Reality . Assessment s were carried out between 6.00 AM and approximately 8.00 AM . Results : Modafinil improved performance on tests of higher cognitive function ; participants in the modafinil group worked more efficiently when solving working memory ( F 1,38 = 5.24 , P = 0.028 ) and planning ( F 1,38 = 4.34 , P = 0.04 ) problems , were less-impulsive decision makers ( F 1,37 = 6.76 , P = 0.01 ) , and were more able to flexibly redirect their attention ( F 1,38 = 4.64 , P = 0.038 ) . In contrast , no improvement was seen in tests of clinical psychomotor performance . Conclusions : Our results suggest that fatigued doctors might benefit from pharmacological enhancement in situations that require efficient information processing , flexible thinking , and decision making under time pressure . However , no improvement is likely to be seen in the performance of basic procedural tasks", "OBJECTIVE To examine the effect of once-daily dosing of modafinil , a stimulant that has a long duration of action , on clinical features of attention-deficit/hyperactivity disorder ( ADHD ) in children . METHOD An open-label design was used to compare the Conners Parent and Teacher Rating Scale-Revised ( L ) ( CPRS , CTRS ) , the ADHD Rating Scale-IV , and the Test of Variables of Attention ( TOVA ) , without and with medication , in children with ADHD . Eleven children with ADHD , ranging in age from 5 to 15 years , took modafinil for an average of 4.6 weeks . RESULTS Average TOVA ADHD scores improved by 2.43 SD ( p = .0009 ) . CTRS and CPRS ADHD index T scores improved by an average of 14.1 ( p = .0009 ) and 17.7 points ( p = .001 ) , respectively . The mean ADHD Rating Scale-IV scores improved from the 88th percentile to the 75th percentile ( p = .047 ) . One subject withdrew from the study because of an adverse event that was resolved completely with medication withdrawal . Other side effects were mild and responded to dose adjustment . No subjects required more than one dose per day . CONCLUSIONS Modafinil may be a useful once-daily treatment for children with ADHD . Further study using a double-blind , placebo-controlled design is needed", "Previous clinical evidence suggested that modafinil may improve clinical features of children with attention-deficit hyperactivity disorder . To test this hypothesis , a r and omized , double-blind , placebo-controlled study design was used . Of 24 children initially r and omized into the study , 11 control subjects and 11 treatment patients completed the study , with evaluation before medication and after 5 to 6 weeks . The average Test of Variables of Attention attention-deficit hyperactivity disorder z score improved by 2.53 S.D.s for the modafinil group compared with a decline of 1.02 for control patients ( P Conners Rating Scales ADHD total t scores for the modafinil group improved from 76.6 to 68.2 compared with improvement from 77.7 to 76.0 for control subjects ( P = 0.04 ) . Ten of 11 treatment patients were reported as \" significantly \" improved , whereas eight of 11 control subjects were reported as manifesting \" no \" or \" slight \" improvement ( P Adverse effects were few and manageable , with no anorexia . Modafinil may be a useful treatment for children with ADHD , particularly when anorexia limits use of stimulants", "There is good evidence that clozapine is more efficacious than first-generation antipsychotic drugs in resistant schizophrenia . It is less clear if clozapine is more effective than the other second-generation antipsychotic ( SGA ) drugs . A noncommercially funded , pragmatic , open , multisite , r and omized controlled trial was conducted in the United Kingdom National Health Service ( NHS ) . Participants were 136 people aged 18 - 65 with DSM-IV schizophrenia and related disorders whose medication was being changed because of poor clinical response to 2 or more previous antipsychotic drugs . Participants were r and omly allocated to clozapine or to one of the class of other SGA drugs ( risperidone , olanzapine , quetiapine , amisulpride ) as selected by the managing clinician . Outcomes were assessed blind to treatment allocation . One-year assessment s were carried out in 87 % of the sample . The intent to treat comparison showed no statistically significant advantage for commencing clozapine in Quality of Life score ( 3.63 points ; CI : 0.46 - 7.71 ; p = .08 ) but did show an advantage in Positive and Negative Syndrome Scale ( PANSS ) total score that was statistically significant ( -4.93 points ; CI : -8.82 to -1.05 ; p = .013 ) during follow-up . Clozapine showed a trend toward having fewer total extrapyramidal side effects . At 12 weeks participants who were receiving clozapine reported that their mental health was significantly better compared with those receiving other SGA drugs . In conclusion , in people with schizophrenia with poor treatment response to 2 or more antipsychotic drugs , there is an advantage to commencing clozapine rather than other SGA drugs in terms of symptom improvement over 1 year", "OBJECTIVE To assess the effects of modafinil on fatigue , symptoms , attention , working memory , and executive functioning in schizophrenia patients treated with psychotropic medications . METHOD Twenty-four patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder ( 10 men and 14 women ) were r and omly assigned to modafinil up to 200 mg a day ( N = 13 ) or placebo ( N = 11 ) as an adjunct therapy in an 8-week , double-blind , placebo-controlled study . Data were collected from May 18 , 2001 to September 11 , 2003 . RESULTS Four subjects terminated the study early , including one because of worsening of psychosis during the first week taking modafinil . In the modafinil ( N = 10 ) and placebo ( N = 10 ) groups , fatigue improved significantly over time ( p fatigue , positive and negative symptoms , or cognition . CONCLUSION Fatigue improved in both groups , and there were no differences between groups on changes in fatigue , symptoms , attention , working memory , or executive functioning . Lack of differences between groups may be due to small sample size or possible regression to the mean in the placebo group", "Modafinil , a medication for the excessive sleepiness associated with narcolepsy , has been hypothesized to improve not just alertness but mood as well . The purpose of this study was to determine how treatment with modafinil affects mood in healthy volunteers . Normal healthy volunteers ( n = 12 , 10 men and 2 women ; 30 - 44 years ) underwent a 3-day , counterbalanced , r and omized , crossover , inpatient trial of modafinil ( 400 mg daily ) versus placebo with 4-day washout period between 2 treatments . Mood was assessed daily using both the Positive and Negative Affect Schedule and a general mood scale , which consisted of 10 bipolar adjective ratings based on a severity scale ranging from 1 to 10 . Modafinil increased general mood and Negative Affect scales relative to placebo and had a significant effect on Positive Affect scales . These results suggest that modafinil may have general mood-elevating effects accompanied by increased negative affect ( anxiety ) . The findings may have implication s for clinical practice , in particular for the adjunctive use of modafinil in treatment-resistant depression", "OBJECTIVE To evaluate the efficacy and tolerability of modafinil in children and adolescents , ages 7 to 17 , with attention-deficit/hyperactivity disorder ( ADHD ) . METHOD In this 9-week , double-blind , flexible-dose study , patients were r and omized to once-daily modafinil ( 170 - 425 mg ) or placebo . Assessment s included ADHD Rating Scale-IV ( ADHD-RS-IV ) School and Home Versions and Clinical Global Impression of Improvement ( CGI-I ) scale . RESULTS Two hundred patients were r and omized . Modafinil produced significant reductions in ADHD-RS-IV total scores at school ( n = 128 ; mean change + /- SD : -17.5 + /- 13.1 points ) compared with placebo ( n = 66 ; -9.7 + /- 10.3 points ; p ADHD-RS-IV total scores at home compared with placebo ( -17.6 + /- 13.3 versus -7.5 + /- 11.8 points ; p placebo met pre study criteria for responder on the CGI-I ( p insomnia , headache , decreased appetite , and weight loss than r and omization to placebo , but discontinuation attributed to adverse events did not differ statistically between treatment groups ( modafinil , 5 % ; placebo , 6 % ) . CONCLUSION Modafinil was well tolerated and reduced ADHD symptoms at school and home compared with placebo ", "UNLABELLED SUBJECT OBJECTIVES : To assess the effect of the wake-promoting drug modafinil on working memory and brain activation in the executive network , following a single night of sleep deprivation . DESIGN R and omized , placebo-controlled , 4-arm , double-blind evaluation of a single 200-mg dose of modafinil on working memory ( 1- , 2- , and 3-back)-related functional brain activation and performance following overnight sleep deprivation . SETTING General Clinical Research Center , Biomedical Imaging Center . SUBJECTS Eight medication-free men , aged 21 to 35 years . INTERVENTIONS Overnight sleep deprivation , single-dose 200-mg modafinil , functional magnetic resonance imaging MEASUREMENTS AND RESULTS Brain activation patterns and regional signal intensity based on the blood-oxygen level-dependent signal were assessed . The following reaction times were used as measures of performance : ( 1 ) attention in the scanner before functional scanning , ( 2 ) \" back \" responses during the active-task block , and ( 3 ) attention during the baseline task block . Contrast of activation maps among conditions revealed sleep-deprivation and drug effects , and their interactions . Performance in the deprived state was enhanced by modafinil only at an intermediate ( 2-back ) level of task difficulty and was associated with the recruitment of increased cortical activation volumes . Strong and consistent individual differences in performance were noted on the working memory tasks . CONCLUSIONS Modafinil effectively counters the adverse effects of overnight sleep deprivation on working memory but only when task difficulty is moderate , recruiting extensive areas in the executive network to do so . Interindividual differences in working-memory performance are stable trait characteristics", "OBJECTIVE Modafinil is approved by the U.S. Food and Drug Administration for improving wakefulness in patients with excessive sleepiness associated with narcolepsy , obstructive sleep apnea , and shift-work sleep disorder . This study was conducted to evaluate the efficacy and safety of adjunctive modafinil in bipolar depression , which is often characterized by excessive sleepiness and fatigue . METHOD Eighty-five patients with bipolar depression that was inadequately responsive to a mood stabilizer with or without concomitant antidepressant therapy were r and omly assigned to receive adjunctive modafinil ( N=41 ) or placebo ( N=44 ) for 6 weeks . The primary outcome measure was baseline-to-endpoint change in score on the Inventory of Depressive Symptoms -- Clinician Rated ( IDS ) . RESULTS The baseline-to-endpoint change in IDS score was significantly greater in the modafinil group ( mean dose , 177 mg/day ) compared with the placebo group . Improvement in depressive symptoms was significantly greater in the modafinil group by week 2 , and this greater improvement was maintained at weeks 4 , 5 , and 6 . Both the response and remission rates were significantly higher in the modafinil group ( 44 % and 39 % ) compared with the placebo group ( 23 % and 18 % ) . During the 6-week study period , there was no difference between groups in treatment-emergent hypomania or mania ( six patients in the modafinil group and five in the placebo group ) or hospitalization for mania ( one in each group ) . CONCLUSIONS These data suggest that adjunctive modafinil at doses of 100 - 200 mg a day may improve depressive symptoms in patients with bipolar disorder", "BACKGROUND Modafinil , a novel cognitive enhancer , has a clinical profile similar to conventional stimulants such as methylpheni date , despite a seemingly different mechanism of action . Modafinil selectively improves neuropsychological task performance in healthy volunteers , possibly through improved inhibitory control . We examined whether modafinil induced similar improvements in adults with attention-deficit/hyperactivity disorder . METHODS Twenty patients with a DSM-IV diagnosis of attention-deficit/hyperactivity disorder were entered into a double-blind , r and omized , placebo-controlled crossover study using a single 200 mg dose of modafinil . RESULTS Modafinil produced a similar pattern of cognitive enhancement to that observed in healthy adults , with improvements on tests of short-term memory span , visual memory , spatial planning , and stop-signal motor inhibition . On several measures , increased accuracy was accompanied by slowed response latency . This alteration in the speed-accuracy trade-off may indicate that modafinil increases the ability to \" reflect \" on problems coupled with decreased impulsive responding . Improvements were also seen in sustained attention , which was unaffected in healthy subjects . CONCLUSIONS If these benefits are shown to be maintained with chronic administration , modafinil may have potential as an important therapy for attention-deficit/hyperactivity disorder with a similar effect to stimulants such as methylpheni date in improving stop-signal response inhibition but without the side effects commonly experienced with amphetamine-like drugs", "BACKGROUND Emotional impairments are important determinants of functional outcome in psychosis , and current treatments are not particularly effective . Modafinil is a wake-promoting drug that has been shown to improve emotion discrimination in healthy individuals and attention and executive function in schizophrenia . We aim ed to establish whether modafinil might have a role in the adjuvant treatment of emotional impairments in the first episode of psychosis , when therapeutic endeavor is arguably most vital . METHODS Forty patients with a first episode of psychosis participated in a r and omized , double-blind , placebo-controlled crossover design study testing the effects of a single dose of 200 mg modafinil on neuropsychological performance . Emotional functions were evaluated with the emotional face recognition test , the affective go-no go task , and the reward and punishment learning test . Visual analogue scales were used throughout the study to assess subjective mood changes . RESULTS Modafinil significantly improved the recognition of sad facial expressions ( z = 2.98 , p = .003 ) . In contrast , there was no effect of modafinil on subjective mood ratings , on tasks measuring emotional sensitivity to reward or punishment , or on interference of emotional valence on cognitive function , as measured by the affective go-no go task . CONCLUSIONS Modafinil improves the analysis of emotional face expressions . This might enhance social function in people with a first episode of psychosis" ]